Habbema, J.D.F.

Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening (Article)

2013-05-01T00:00:00Z

Objective The sensitivity and specificity of a single faecal immunochemical test (FIT) are limited. The performance of FIT screening can be improved by increasing the screening frequency or by providing more than one sample in each screening round. This study aimed to evaluate if two-sample FIT screening is cost-effective compared with one-sample FIT. Design The MISCANecolon microsimulation model was used to estimate costs and benefits of strategies with either one or two-sample FIT screening. The FIT cut-off level varied between 50 and 200 ng haemoglobin/ml, and the screening schedule was varied with respect to age range and interval. In addition, different definitions for positivity of the two-sample FIT were considered: at least one positive sample, two positive samples, or the mean of both samples being positive. Results Within an exemplary screening strategy, biennial FIT from the age of 55-75 years, one-sample FIT provided 76.0-97.0 life-years gained (LYG) per 1000 individuals, at a cost of $259000-264000 (range reflects different FIT cut-off levels). Two-sample FIT screening with at least one sample being positive provided 7.3-12.4 additional LYG compared with one-sample FIT at an extra cost of $50000-59 000. However, when all screening intervals and age ranges were considered, intensifying screening with one-sample FIT provided equal or more LYG at lower costs compared with two-sample FIT. Conclusion If attendance to screening does not differ between strategies it is recommended to increase the number of screening rounds with one-sample FIT screening, before considering increasing the number of FIT samples provided per screening round.

Fecal occult blood testing when colonoscopy capacity is limited (Article)

2011-12-07T00:00:00Z

Background Fecal occult blood testing (FOBT) can be adapted to a limited colonoscopy capacity by narrowing the age range or extending the screening interval, by using a more specific test or hemoglobin cutoff level for referral to colonoscopy, and by restricting surveillance colonoscopy. Which of these options is most clinically effective and cost-effective has yet to be established. Methods We used the validated MISCAN-Colon microsimulation model to estimate the number of colonoscopies, costs, and health effects of different screening strategies using guaiac FOBT or fecal immunochemical test (FIT) at various hemoglobin cutoff levels between 50 and 200 ng hemoglobin per mL, different surveillance strategies, and various age ranges. We optimized the allocation of a limited number of colonoscopies on the basis of incremental cost-effectiveness. Results When colonoscopy capacity was unlimited, the optimal screening strategy was to administer an annual FIT with a 50 ng/mL hemoglobin cutoff level in individuals aged 45-80 years and to offer colonoscopy surveillance to all individuals with adenomas. When colonoscopy capacity was decreasing, the optimal screening adaptation was to first increase the FIT hemoglobin cutoff value to 200 ng hemoglobin per mL and narrow the age range to 50-75 years, to restrict colonoscopy surveillance, and finally to further decrease the number of screening rounds. FIT screening was always more cost-effective compared with guaiac FOBT. Doubling colonoscopy capacity increased the benefits of FIT screening up to 100%. Conclusions FIT should be used at higher hemoglobin cutoff levels when colonoscopy capacity is limited compared with unlimited and is more effective in terms of health outcomes and cost compared with guaiac FOBT at all colonoscopy capacity levels. Increasing the colonoscopy capacity substantially increases the health benefits of FIT screening.

The impact of mobility on HIV control: A modelling study (Article)

2011-12-01T00:00:00Z

Mobility is associated with HIV due to more risky sexual behaviour of mobile groups such as travellers and migrants. Limited participation of such groups may reduce the effectiveness of HIV interventions disproportionally. The established STDSIM model, which simulates transmission and control of HIV and STD, was extended to simulate mobility patterns based on data from Tanzania. We explored the impact of non-participation of mobile groups (travellers and recent migrants) on the effectiveness of two interventions: condom promotion and health education aiming at partner reduction. If mobile groups do not participate, the effectiveness of both interventions could be reduced by 40%. The impact of targeting travellers with a combined HIV campaign is close to that of a general population intervention. In conclusion, it is important to account for possible non-participation of migrants and travellers. If non-participation is substantial, impact of interventions can be greatly improved by actively approaching these people.

Practical implications of differential discounting of costs and health effects in cost-effectiveness analysis (Article)

2011-12-01T00:00:00Z

Informed choice on Pap smear still limited by lack of knowledge on the meaning of false-positive or false-negative test results (Article)

2011-11-01T00:00:00Z

Objective: Screening for cervical cancer may have favourable or unfavourable effects at the individual level. This study assesses whether invitees in the Netherlands made an informed choice about screen uptake. Methods: Attached to the invitation letter and the information leaflet, screen invitees were sent a questionnaire. An informed decision was defined as based on decision-relevant knowledge, while the woman's attitude was consistent with her actual screening behaviour. Results: Of all cervical screen participants, 60% (924/1551) responded to the questionnaire. Decision-relevant knowledge was sufficient in 595 women. Especially knowledge about false-positive and false-negative test results was limited. The attitude towards cervical screening was mainly positive (99%). Requirements for informed decision making were met in 571 (68%) women and in 91% when an alternative cut-off point of sufficient decision-relevant knowledge was applied. Most frequently reported main reasons to attend were early detection of abnormalities (67%) and reassurance in case of a normal smear (22%). Conclusion: Insufficient decision-relevant knowledge was the main cause of uninformed attendance. Practice implication: Adequate strategies to provide invitees with sufficient decision-relevant information are still needed, especially regarding false-positive and false-negative test results.

Cost-effectiveness analysis of a quantitative immunochemical test for colorectal cancer screening (Article)

2011-11-01T00:00:00Z

Background & Aims: Two European randomized trials (N = 30,000) compared guaiac fecal occult blood testing with quantitative fecal immunochemical testing (FIT) and showed better attendance rates and test characteristics for FIT. We aimed to identify the most cost-effective FIT cutoff level for referral to colonoscopy based on data from these trials and allowing for differences in screening ages. Methods: We used the validated MIcrosimulation SCreening ANalysis (MISCAN)-Colon microsimulation model to estimate costs and effects of different screening strategies for FIT cutoff levels of 50, 75, 100, 150, and 200 ng/mL hemoglobin. For each cutoff level, screening strategies were assessed with various age ranges and screening intervals. We assumed sufficient colonoscopy capacity for all strategies. Results: At all cost levels, FIT screening was most effective with the 50 ng/mL cutoff level. The incremental cost-effectiveness ratio of biennial screening between ages 55 and 75 years using FIT at 50 ng/mL, for example, was 3900 euro per life year gained. Annual screening had an incremental cost-effectiveness ratio of 14,900 euro per life year gained, in combination with a wider age range (between ages 45 and 80 years). In the sensitivity analysis, 50 ng/mL remained the preferred cutoff level. Conclusions: FIT screening is more cost-effective at a cutoff level of 50 ng/mL than at higher cutoff levels. This supports the recommendation to use FIT at a cutoff level of 50 ng/mL, which is considerably lower than the values used in current practice.

Postpartum fepression after mild and severe preeclampsia (Article)

2011-10-01T00:00:00Z

Objective: To describe the prevalence of postpartum depressive symptoms after preeclampsia, to assess the extent to which the prevalence of postpartum depressive symptoms differs after mild and severe preeclampsia, and to investigate which factors contribute to such differences. Methods: Women diagnosed with preeclampsia (n=161) completed the Edinburgh Postnatal Depression Scale (EPDS) at 6, 12, or 26 weeks postpartum. Multiple logistic regression analysis was used to investigate the association between severity of preeclampsia, contributing factors and postpartum depression (PPD) (1) at any time during the first 26 weeks postpartum and (2) accounting for longitudinal observations at three time points. Results: After mild preeclampsia, 23% reported postpartum depressive symptoms at any time up to 26 weeks postpartum compared to 44% after severe preeclampsia (unadjusted odds ratio [OR] 2.65, 95% confidence interval [CI] 1.16-6.05) for depression at any time up to 26 weeks postpartum (unadjusted OR 2.57, 95% CI, 1.14-5.76) while accounting for longitudinal observations. Admission to the neonatal intensive care unit (NICU) (adjusted OR 3.19, 95% CI 1.15-8.89) and perinatal death (adjusted OR 2.96, 95% CI 1.09-8.03) contributed to this difference. Conclusions: It appears that not the severity of preeclampsia itself but rather the consequences of the severity of the disease (especially admission to the NICU and perinatal death) cause postpartum depressive symptoms. Obstetricians should be aware of the high risk of postpartum depressive symptoms after severe preeclampsia, particularly among women whose infant has been admitted to the NICU or has died.

Effect of micronutrient and probiotic fortified yogurt on immune-function of anti-retroviral therapy naive HIV patients (Article)

2011-10-01T00:00:00Z

Background: Micronutrient supplementation has been shown to reduce the progression of HIV but does not have an effect on the intestinal barrier or the intestinal microbiota of HIV patients. Studies have suggested that probiotics could potentially complement micronutrients in preserving the immune-function of HIV patients. Objective: Assess the impact of micronutrient supplemented probiotic yogurt on the immune function of HIV patients. Design: We performed a randomized, double blind, controlled trial with CD4 count as primary outcome among HIV patients naïve to anti-retroviral treatment. Secondary outcomes included hematological parameters, incidence of diarrhea and clinical symptoms. A total of 112 HIV patients were randomized to receive a micronutrient fortified yogurt with (n = 55) or without additional probiotic Lactobacillus rhamnosus GR-1 (n = 57) for four weeks. Results: An average decline in CD4 count of -70 cells/μL (95% CI: -154 to -15) was observed in the micronutrient, probiotic group versus a decrease of -63 cells/μL (95% CI: -157 to -30) in the micronutrient control group (p = 0.9). Additional probiotic supplementation was well tolerated and not associated with adverse events. No difference between groups was detected in incidence of diarrhea or clinical symptoms. An improvement of hemoglobin levels was observed for all subjects,based upon a mean difference from baseline of 1.4 g/L (SD = 6) (p = 0.02). Conclusion: The addition of probiotics to a micronutrient fortified yogurt was well tolerated by HIV patients but was not associated with a further increase in CD4 count after one month.

How much colonoscopy screening should be recommended to individuals with various degrees of family history of colorectal cancer? (Article)

2011-09-15T00:00:00Z

BACKGROUND: Individuals with a family history of colorectal cancer (CRC) are at increased risk for CRC. Current screening recommendations for these individuals are based on expert opinion. The authors investigated optimal screening strategies for individuals with various degrees of family history of CRC based on a cost-effectiveness analysis. METHODS: The MISCAN-Colon microsimulation model was used to estimate costs and effects of CRC screening strategies, varying by the age at which screening was started and stopped and by screening interval. The authors defined 4 risk groups, characterized by the number of affected first-degree relatives and their age at CRC diagnosis. For all risk groups, the optimal screening strategy had an incremental cost-effectiveness ratio of approximately $50,000 per life-year gained. RESULTS: The optimal screening strategy for individuals with 1 first-degree relative diagnosed after age 50 years was 6 colonoscopies every 5 years starting at age 50 years, compared with 4 colonoscopies every 7 years starting at age 50 years for average risk individuals. The optimal strategy had 10 colonoscopies every 4 years for individuals with 1 first-degree relative diagnosed before age 50 years, 13 colonoscopies every 3 years for individuals with 2 or more first-degree relatives diagnosed after age 50 years, and 15 colonoscopies every 3 years for individuals with 2 or more first-degree relatives of whom at least 1 was diagnosed before age 50 years. CONCLUSIONS: The optimal screening strategy varies considerably with the number of affected first-degree relatives and their age of diagnosis. Shorter screening intervals than the currently recommended 5 years may be appropriate for the highest risk individuals.

The long term effect of current and new interventions on the new case detection of leprosy: A modeling study (Article)

2011-09-01T00:00:00Z

Background: Although the number of newly detected leprosy cases has decreased globally, a quarter of a million new cases are detected annually and eradication remains far away. Current options for leprosy prevention are contact tracing and BCG vaccination of infants. Future options may include chemoprophylaxis and early diagnosis of subclinical infections. This study compared the predicted trends in leprosy case detection of future intervention strategies. Methods: Seven leprosy intervention scenarios were investigated with a microsimulation model (SIMCOLEP) to predict future leprosy trends. The baseline scenario consisted of passive case detection, multidrug therapy, contact tracing, and BCG vaccination of infants. The other six scenarios were modifications of the baseline, as follows: no contact tracing; with chemoprophylaxis; with early diagnosis of subclinical infections; replacement of the BCG vaccine with a new tuberculosis vaccine ineffective against Mycobacterium leprae ("no BCG"); no BCG with chemoprophylaxis; and no BCG with early diagnosis. Findings: Without contact tracing, the model predicted an initial drop in the new case detection rate due to a delay in detecting clinical cases among contacts. Eventually, this scenario would lead to new case detection rates higher than the baseline program. Both chemoprophylaxis and early diagnosis would prevent new cases due to a reduction of the infectious period of subclinical cases by detection and cure of these cases. Also, replacing BCG would increase the new case detection rate of leprosy, but this effect could be offset with either chemoprophylaxis or early diagnosis. Conclusions: This study showed that the leprosy incidence would be reduced substantially by good BCG vaccine coverage and the combined strategies of contact tracing, early diagnosis, and treatment of infection and/or chemoprophylaxis among household contacts. To effectively interrupt the transmission of M. leprae, it is crucial to continue developing immuno- and chemoprophylaxis strategies and an effective test for diagnosing subclinical infections.

Clarifying differences in natural history between models of screening: The case of colorectal cancer (Article)

2011-07-01T00:00:00Z

Background. Microsimulation models are important decision support tools for screening. However, their complexity makes them difficult to understand and limits realization of their full potential. Therefore, it is important to develop documentation that clarifies their structure and assumptions. The authors demonstrate this problem and explore a solution for natural history using 3 independently developed colorectal cancer screening models. Methods. The authors first project effectiveness and cost-effectiveness of colonoscopy screening for the 3 models (CRC-SPIN, SimCRC, and MISCAN). Next, they provide a conventional presentation of each model, including information on structure and parameter values. Finally, they report the simulated reduction in clinical cancer incidence following a one-time complete removal of adenomas and preclinical cancers for each model. They call this new measure the maximum clinical incidence reduction (MCLIR). Results. Projected effectiveness varies widely across models. For example, estimated mortality reduction for colonoscopy screening every 10 years from age 50 to 80 years, with surveillance in adenoma patients, ranges from 65% to 92%. Given only conventional information, it is difficult to explain these differences, largely because differences in structure make parameter values incomparable. In contrast, the MCLIR clearly shows the impact of model differences on the key feature of natural history, the dwell time of preclinical disease. Dwell times vary from 8 to 25 years across models and help explain differences in projected screening effectiveness. Conclusions. The authors propose a new measure, the MCLIR, which summarizes the implications for predicted screening effectiveness of differences in natural history assumptions. Including the MCLIR in the standard description of a screening model would improve the transparency of these models.

Advance notification letters increase adherence in colorectal cancer screening: A population-based randomized trial (Article)

2011-06-01T00:00:00Z

Objective: The population benefit of screening depends not only on the effectiveness of the test, but also on adherence, which, for colorectal cancer (CRC) screening remains low. An advance notification letter may increase adherence, however, no population-based randomized trials have been conducted to provide evidence of this. Method: In 2008, a representative sample of the Dutch population (aged 50-74. years) was randomized. All 2493 invitees in group A were sent an advance notification letter, followed two weeks later by a standard invitation. The 2507 invitees in group B only received the standard invitation. Non-respondents in both groups were sent a reminder 6. weeks after the invitation. Results: The advance notification letters resulted in a significantly higher adherence (64.4% versus 61.1%, p-value 0.019). Multivariate logistic regression analysis showed no significant interactions between group and age, sex, or socio-economic status. Cost analysis showed that the incremental cost per additional detected advanced neoplasia due to sending an advance notification letter was €957. Conclusion: This population-based randomized trial demonstrates that sending an advance notification letter significantly increases adherence by 3.3%. The incremental cost per additional detected advanced neoplasia is acceptable. We therefore recommend that such letters are incorporated within the standard CRC-screening invitation process.

Practical implications of differential discounting in cost-effectiveness analyses with varying numbers of cohorts (Article)

2011-06-01T00:00:00Z

Objective: To call attention to the influence of the number of birth-cohorts used in cost-effectiveness analysis (CEA) models on incremental cost-effectiveness ratios (ICERs) under differential discounting. Methods: The consequences of increasing the number of birth-cohorts are demonstrated using a CEA of cervical cancer prevention as an example. The cost-effectiveness of vaccinating 12-year-old girls against the human papillomavirus is estimated with the MISCAN microsimulation screening analysis model for 1, 10, 20, and 30 birth-cohorts. Costs and health effects are discounted with equal rates of 4% and alternatively with differential rates of 4% and 1.5% respectively. The effects of increasing the number of cohorts are shown by comparing the ICERs under equal and differential discounting. Results: The ICER decreases as the number of cohorts increases under differential discounting, but not under equal discounting. Conclusions: The variation of ICERs with the number of cohorts under differential discounting prompts questions regarding the appropriate specification of CEA models and interpretation of their results. In particular, it raises concerns that arbitrary variation in study specification leads to arbitrary variation in results. Such variations could lead to erroneous policy decisions. These findings are relevant to CEA guidance authorities, CEA practitioners, and decision makers. Our results do not imply a problem with differential discounting per se, yet they highlight the need for practical guidance for its use. Copyright

Diagnostic Yield Improves With Collection of 2 Samples in Fecal Immunochemical Test Screening Without Affecting Attendance (Article)

2011-04-01T00:00:00Z

Background & Aims: The fecal immunochemical test (FIT) is superior to the guaiac-based fecal occult blood test in detecting neoplasia. There are not much data on the optimal number of FITs to perform. We conducted a population-based trial to determine attendance and diagnostic yield of 1- and 2-sample FIT screening. Methods: The study included 2 randomly selected groups of subjects aged 50-74 years (1-sample FIT, n = 5007; 2-sample FIT, n = 3197). The 2-sample group was instructed to collect fecal samples on 2 consecutive days. Subjects were referred for colonoscopy when at least 1 sample tested positive (≥50 ng hemoglobin/mL). Results: Attendance was 61.5% in the 1-sample group (2979 of 4845; 95% confidence interval, 60.1%-62.9%) and 61.3% in the 2-sample group (1875 of 3061; 95% confidence interval, 59.6%-63.0%; P = .84). In the 1-sample group 8.1% tested positive, and in the 2-sample group 12.8% had at least 1 positive test outcome and 5.0% had 2 positive test outcomes (P < .05). When the mean from both test results in the 2-sample group was used, 10.1% had a positive test outcome (P < .05). The detection rates for advanced neoplasia were 3.1% in the 1-sample group, 4.1% in the 2-sample group with at least 1 positive test outcome, 2.5% when both test results were positive, and 3.7% among subjects with the mean from both test results being positive. Conclusions: There is no difference in attendance for subjects offered 1- or 2-sample FIT screening. The results allow for the development of efficient FIT screening strategies that can be adapted for local colonoscopy capacities, rather than varying the cut-off value in a 1-sample strategy.

Randomized controlled trial of screening for type 2 diabetes mellitus in obese subjects (Internal Report)

2011-03-25T00:00:00Z

Role of semen analysis in subfertile couples (Article)

2011-03-01T00:00:00Z

Objective: To evaluate the associations between the results of the male partner's semen analysis (classified according to the World Health Organization [WHO] criteria) and fathering a child without any treatment. Design: Prospective multicenter cohort study. Setting: Twenty subfertility centers in The Netherlands. Patient(s): A total of 3,345 consecutive couples presenting for subfertility. Intervention(s): None. Main Outcome Measure(s): Associations between the results of the male partner's semen analysis, classified according to the WHO criteria, and fathering a child without any treatment within a time horizon of 1 year. Subsequently, we redefined semen quality criteria and reevaluated the associations. Result(s): Follow-up data of 3,129 couples (94%) were available, of which 517 (17%) had a healthy pregnancy without treatment. The 1-year pregnancy rate in men with WHO normozoospermia did not differ significantly from that in men with WHO impaired semen (24% vs. 23%). In contrast, we observed lower chances of fathering a child for sperm concentrations <40 Ã 106/mL, total sperm count <200 Ã 106, and sperm morphology <20% normal forms. With a multivariable regression model based on the redefined male semen subfertility criteria we were able to make a finer differentiation between subfertile men, with probabilities of fathering a child ranging from 7% to 41%. Conclusion(s): The current WHO criteria for semen quality do not discriminate between fertile and subfertile men. Our redefined and graded semen criteria have strong predictive value. If interpreted correctly, the fast and inexpensive semen analysis remains the gold standard for defining a man's role in subfertility.

Role of semen analysis in subfertile couples (Article)

2011-03-01T00:00:00Z

Would the effect of HPV vaccination on non-cervical HPV-positive cancers make the difference for its cost-effectiveness? (Article)

2011-02-01T00:00:00Z

Besides cervical cancer, the human papillomavirus (HPV) is found in other cancers and may be preventable with HPV vaccination. However, these other cancers are often not accounted for in cost-effectiveness analyses of HPV vaccination. This study estimates the potential maximum effect on the cost-effectiveness ratio (CER) of HPV vaccination in preventing non-cervical HPV-positive cancers. For the Dutch situation, a mathematical equation was used to estimate the maximum impact if all cancer cases of the penis, vulva/vagina, anus, oral cavity and oro-pharynx with HPV16/18 are prevented, in terms of number of life years gained, savings and improvement in the CER of the vaccination. For other countries and for future developments, we show how the impact on the CER varies depending on the incidence of cervical/non-cervical HPV 16/18-positive cancers, vaccine costs and clinical costs. If in the Netherlands all HPV 16/18-positive cancers are prevented by vaccination in women only, compared to if only HPV 16/18-positive cervical cancer is prevented, the life years gained increase with 14%, the savings increase with 18%, and the CER decreases with 13%. If vaccination prevents HPV-positive cancers in both men and women, these figures increase to 25%, 26% and 21%, respectively. In conclusion, if HPV vaccination fully prevents all non-cervical HPV-positive cancers, this would substantially increase its cost-effectiveness. The impact of the vaccination varies depending on the incidence of cervical/non-cervical HPV16/18-positive cancers, the vaccine costs and clinical costs. Observed combinations of these parameters in different countries show a decrease in the CER between 10% and 31%.

Uptake of faecal immunochemical test screening among non-participants in a flexible sigmoidoscopy screening programme (Article)

2011-01-01T00:00:00Z

Different mechanisms for heterogeneity in leprosy susceptibility can explain disease clustering within households (Article)

2010-12-03T00:00:00Z

The epidemiology of leprosy is characterized by heterogeneity in susceptibility and clustering of disease within households. We aim to assess the extent to which different mechanisms for heterogeneity in leprosy susceptibility can explain household clustering as observed in a large study among contacts of leprosy patients. We used a microsimulation model, parameterizing it with data from over 20,000 contacts of leprosy patients in Bangladesh. We simulated six mechanisms producing heterogeneity in susceptibility: (1) susceptibility was allocated at random to persons (i.e. no additional mechanism), (2) a household factor, (3, 4) a genetic factor (dominant or recessive), or (5, 6) half a household factor and half genetic. We further assumed that a fraction of 5%, 10%, and 20% of the population was susceptible, leading to a total of 18 scenarios to be fitted to the data. We obtained an acceptable fit for each of the six mechanisms, thereby excluding none of the possible underlying mechanisms for heterogeneity of susceptibility to leprosy. However, the distribution of leprosy among contacts did differ between mechanisms, and predicted trends in the declining leprosy case detection were dependent on the assumed mechanism, with genetic-based susceptibility showing the slowest decline. Clustering of leprosy within households is partially caused by an increased transmission within households independent of the leprosy susceptibility mechanism. Even a large and detailed data set on contacts of leprosy patients could not unequivocally reveal the mechanism most likely responsible for heterogeneity in leprosy susceptibility.

Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 to prevent or cure bacterial vaginosis among women with HIV (Article)

2010-12-01T00:00:00Z

Objective: To assess, among women with HIV, whether long-term oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 supplementation can prevent bacterial vaginosis (BV) and enhance the cure rate of metronidazole among those with BV. Methods: A randomized, double-blind, placebo-controlled trial conducted among 65 HIV-infected women with an aberrant microbiota (Nugent score 4-10) who were randomized to receive daily probiotics or placebo for 6 months. Those with BV (Nugent score 7-10) additionally received metronidazole for 10 days (400 mg twice daily). Results: We did not find an enhanced cure rate of BV among women with HIV treated with adjuvant probiotics to metronidazole treatment. Among women with an intermediate vaginal flora, probiotics tended to increase the probability of a normal vaginal flora (odds ratio 2.4; P = 0.1) and significantly increased the probability of a beneficial vaginal pH (odds ratio 3.8; P = 0.02) at follow-up. Conclusion: Supplementation of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 did not enhance the cure of BV among women living with HIV, but may prevent the condition among this population. Trial registration: NCT00536848.

Increased risk of adenomas in individuals with a family history of colorectal cancer: results of a meta-analysis (Article)

2010-12-01T00:00:00Z

Objective: It is unclear to what extent the increased risk of colorectal cancer in individuals with a family history of colorectal cancer and no known genetic disorders is associated with a higher adenoma prevalence. Our aim is to estimate the relative difference in adenoma prevalence and its age-pattern in individuals with a family history of colorectal cancer compared to those without. Methods: We performed a literature search to identify colonoscopy studies reporting the adenoma prevalence by age. Using multilevel logistic regression, we examined how the adenoma prevalence by age differed between individuals with and without a family history of colorectal cancer. We excluded members of families with a known genetic disorder. Results: Thirteen colonoscopy studies were identified. The adenoma prevalence was significantly higher in individuals with a family history than in those without (OR 1.7, 95% CI 1.4-3.5). The adenoma prevalence increased with age (OR per year of age 1.06, 95% CI 1.05-1.07). The age trend did not differ significantly between the two groups. Conclusion: Individuals with a family history of colorectal cancer have a considerably higher prevalence of adenomas compared to individuals without a family history. This is consistent with their increased risk of colorectal cancer.

Health seeking behaviour and utilization of health facilities for schistosomiasis-related symptoms in ghana (Article)

2010-11-01T00:00:00Z

Background: Schistosomiasis causes long-term illness and significant economic burden. Morbidity control through integration within existing health care delivery systems is considered a potentially sustainable and cost-effective approach, but there is paucity of information about health-seeking behaviour. Methods: A questionnaire-based study involving 2,002 subjects was conducted in three regions of Ghana to investigate health-seeking behaviour and utilization of health facilities for symptoms related to urinary (blood in urine and painful urination) and intestinal schistosomiasis (diarrhea, blood in stool, swollen abdomen and abdominal pain). Fever (for malaria) was included for comparison. Results: Only 40% of patients with urinary symptoms sought care compared to.70% with intestinal symptoms and.90% with fever. Overall, about 20% of schistosomiasis-related symptoms were reported to a health facility (hospital or clinic), compared to about 30% for fever. Allopathic self-medication was commonly practiced as alternative action. Health-care seeking was relatively lower for patients with chronic symptoms, but if they took action, they were more likely to visit a health facility. In a multivariate logistic regression analysis, perceived severity was the main predictor for seeking health care or visiting a health facility. Age, socio-economic status, somebody else paying for health care, and time for hospital visit occasionally showed a significant impact, but no clear trend. The effect of geographic location was less marked, although people in the central region, and to a lesser extent the north, were usually less inclined to seek health care than people in the south. Perceived quality of health facility did not demonstrate impact. Conclusion: Perceived severity of the disease is the most important determinant of seeking health care or visiting a health facility in Ghana. Schistosomiasis control by passive case-finding within the regular health care delivery looks promising, but the number not visiting a health facility is large and calls for supplementary control options.

Effect of postpartum lifestyle interventions on weight loss, smoking cessation, and prevention of smoking relapse: A systematic review (Article)

2010-10-01T00:00:00Z

Postpartum lifestyle interventions are recommended for women after pregnancies complicated by preeclampsia, intrauterine growth restriction, and/or gestational diabetes, since they are at increased cardiovascular risk. To identify potential intervention strategies to reduce this risk, a systematic review of the literature is presented on the effectiveness of postpartum lifestyle interventions aimed at weight loss, smoking cessation, and smoking relapse prevention. The main characteristics of these postpartum lifestyle interventions are briefly described. The PubMed, Embase, Web of Science, PsychInfo, and Cinahl databases were searched for studies on the effects of postpartum lifestyle interventions on weight loss, and smoking cessation or prevention of smoking relapse, initiated for up to 1 year postpartum. No studies on the effectiveness of postpartum lifestyle interventions after the aforementioned specific pregnancy complications were found. However, 21 studies are included that describe existing postpartum lifestyle interventions, which were applied to unselected (on the basis of pregnancy complications) postpartum women. Copyright

Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV/AIDS (Article)

2010-10-01T00:00:00Z

Aim: To evaluate the long term effect of yogurt supplemented with Lactobacillus rhamnosus Fiti on the immune function (CD4 count) of people living with HIV/AIDS. Background: Gastrointestinal infections and the leakage of microbial products from the gut have a profound impact on the deterioration of the immune system among people living with HIV/AIDS. Among persons not infected with the virus, probiotics can prevent gastrointestinal infections and restore an effective gut barrier, suggesting they might have a beneficial effect on the immune function of people living with HIV/AIDS. Study: We carried out an observational retrospective study over a period of 3 years, with longitudinal comparison of the CD4 count within participants (n=68) before and during probiotic yogurt consumption, and compared with a control group of participants not consuming the yogurt (n=82). Results: Among the yogurt consumers before use and the nonconsumers, an average increase in CD4 count was seen of 0.13 cells/μL/day (95% CI; 0.07-0.20, P=<0.001). After commencing consumption, yogurt consumers experienced an additional increase of 0.28 cells/μL/day (95% CI; 0.10-0.46, P=0.003). When adjusting for length of time using antiretroviral medication, the additional increase explained by yogurt consumption remained 0.17 cells/μL/day (95% CI; 0.01-0.34, P=0.04). Treatment with antiretroviral medication was associated with an increase of 0.27 cells/μL/day (95% CI; 0.17-0.38, P=<0.001). CONCLUSION: The introduction of probiotic yogurt, made by local women in a low-income community in Tanzania, was significantly associated with an increase in CD4 count among consumers living with HIV.

Anaplasma phagocytophilum in livestock and small rodents (Article)

2010-08-01T00:00:00Z

To identify the prevalence of Anaplasma phagocytophilum in both wild rodents and domestic animals and to make clear the genetic characteristics of the agents from different animals in China, a total of 105 livestock and 159 small rodents were analyzed by real-time-PCR and sequence analysis. The prevalence rate was 6.7% (7/105) and 14.5% (23/159), respectively. The nucleotide sequences of 16S rRNA (rrs) from the positive livestock and rodents were identical to each other. The phylogenetic analysis based on partial A. phagocytophilum p44ESup1 gene revealed that A. phagocytophilum identified in this study was placed on a separate clade distinct from those in other continents. These findings indicated A. phagocytophilum in rodents might be able to infect livestock and intensified the threats of anaplasmosis to livestock in the area. Further studies on public health significance of the agent are worth investigation in future.

Screening for colorectal cancer: Comparison of perceived test burden of guaiac-based faecal occult blood test, faecal immunochemical test and flexible sigmoidoscopy (Article)

2010-07-01T00:00:00Z

Background: Perceived burden of colorectal cancer (CRC) screening is an important determinant of participation in subsequent screening rounds and therefore crucial for the effectiveness of a screening programme. This study determined differences in perceived burden and willingness to return for a second screening round among participants of a randomised population-based trial comparing a guaiac-based faecal occult blood test (gFOBT), a faecal immunochemical test (FIT) and flexible sigmoidoscopy (FS) screening. Methods: A representative sample of the Dutch population (aged 50-74 years) was randomised to be invited for gFOBT, FIT and FS screening. A random sample of participants of each group was asked to complete a questionnaire about test burden and willingness to return for CRC screening. Results: In total 402/481 (84%) gFOBT, 530/659 (80%) FIT and 852/1124 (76%) FS screenees returned the questionnaire. The test was reported as burdensome by 2.5% of gFOBT, 1.4% of FIT and 12.9% of FS screenees (comparing gFOBT versus FIT p = 0.05; versus FS p < 0.001). In total 94.1% of gFOBT, 94.0% of FIT and 83.8% of FS screenees were willing to attend successive screening rounds (comparing gFOBT versus FIT p = 0.84; versus FS p < 0.001). Women reported more burden during FS screening than men (18.2% versus 7.7%; p < 0.001). Conclusions: FIT slightly outperforms gFOBT with a lower level of reported discomfort and overall burden. Both FOBTs are better accepted than FS screening. All three tests have a high level of acceptance, which may affect uptake of subsequent screening rounds and should be taken into consideration before implementing a CRC screening programme.

Is human fecundity declining in Western countries? (Article)

2010-06-01T00:00:00Z

Since Carlsen and co-workers reported in 1992 that sperm counts have decreased during the second half of the last century in Western societies, there has been widespread anxiety about the adverse effects of environmental pollutants on human fecundity. The Carlsen report was followed by several re-analyses of their data set and by many studies on time trends in sperm quality and on secular trends in fecundity. However, the Results of these studies were diverse, complex, difficult to interpret and, therefore, less straightforward than the Carlsen report suggested. The claims that population fecundity is declining and that environmental pollutants are involved, can neither be confirmed nor rejected, in our opinion. However, it is of great importance to find out because the possible influence of widespread environmental pollution, which would adversely affect human reproduction, should be a matter of great concern triggering large-scale studies into its causes and possibilities for prevention. The fundamental reason we still do not know whether population fecundity is declining is the lack of an appropriate surveillance system. Is such a system possible? In our opinion, determining total sperm counts (as a measure of male reproductive health) in combination with time to pregnancy (as a measure of couple fecundity) in carefully selected populations is a feasible option for such a monitoring system. If we want to find out whether or not population fecundity will be declining within the following 20-30 years, we must start monitoring now.

A randomised controlled trial on the effectiveness of bracing patients with idiopathic scoliosis: Failure to include patients and lessons to be learnt (Article)

2010-05-01T00:00:00Z

Trials often do not succeed in including as many patients as anticipated beforehand. The aim of this paper was to describe why we were not able to include more than a few patients in our randomized controlled treatment trial on the effectiveness of bracing patients with idiopathic scoliosis, and to describe which lessons can be learnt. A pilot study on the willingness to participate in such a trial was conducted amongst 21 patients and their parents. A description of how we prepared and designed this trial, the problems we faced and how we tried to improve the inclusion are given. A total of four patients were included, and 14 refused to participate in an 18-month period. There were a lot less eligible patients than anticipated (40 instead of 100 per year), and the patients' participation rate was much lower than we had found in our pilot study (21% instead of 70%). The trial failed to include more than a few patients because of an overestimation of the number of eligible patients and because a lot less eligible patients were willing to participate compared to our pilot study. One reason for a low participation rate could be that this trial evaluated a frequently used existing treatment instead of a new treatment, and patients and parents might be afraid of not being treated (despite an intensive secure system for the control arm).

Preferences for colorectal cancer screening strategies: a discrete choice experiment (Article)

2010-03-01T00:00:00Z

Background:Guidelines underline the role of individual preferences in the selection of a screening test, as insufficient evidence is available to recommend one screening test over another. We conducted a study to determine the preferences of individuals and to predict uptake for colorectal cancer (CRC) screening programmes using various screening tests. Methods:A discrete choice experiment (DCE) questionnaire was distributed among naive subjects, yet to be screened, and previously screened subjects, aged 50-75 years. Subjects were asked to choose between scenarios on the basis of faecal occult blood test (FOBT), flexible sigmoidoscopy (FS), total colonoscopy (TC) with various test-specific screening intervals and mortality reductions, and no screening (opt-out). Results:In total, 489 out of 1498 (33%) screening-naïve subjects (52% male; mean age±s.d. 61±7 years) and 545 out of 769 (71%) previously screened subjects (52% male; mean age±s.d. 61±6 years) returned the questionnaire. The type of screening test, screening interval, and risk reduction of CRC-related mortality influenced subjects' preferences (all P<0.05). Screening-naive and previously screened subjects equally preferred 5-yearly FS and 10-yearly TC (P=0.24; P=0.11), but favoured both strategies to annual FOBT screening (all P-values <0.001) if, based on the literature, realistic risk reduction of CRC-related mortality was applied. Screening-naive and previously screened subjects were willing to undergo a 10-yearly TC instead of a 5-yearly FS to obtain an additional risk reduction of CRC-related mortality of 45% (P<0.001). Conclusion:These data provide insight into the extent by which interval and risk reduction of CRC-related mortality affect preferences for CRC screening tests. Assuming realistic test characteristics, subjects in the target population preferred endoscopic screening over FOBT screening, partly, due to the more favourable risk reduction of CRC-related mortality by endoscopy screening. Increasing the knowledge of potential screenees regarding risk reduction by different screening strategies is, therefore, warranted to prevent unrealistic expectations and to optimise informed choice.British Journal of Cancer advance online publication, 2 March 2010; doi:10.1038/sj.bjc.6605566 www.bjcancer.com.

Labeled versus unlabeled discrete choice experiments in health economics: An application to colorectal cancer screening (Article)

2010-03-01T00:00:00Z

Objectives: Discrete choice experiments (DCEs) in health economics commonly present choice sets in an unlabeled form. Labeled choice sets are less abstract and may increase the validity of the results. We empirically compared the feasibility, respondents' trading behavior, and convergent validity between a labeled and an unlabeled DCE for colorectal cancer (CRC) screening programs in The Netherlands. Methods: A labeled DCE version presented CRC screening test alternatives as "fecal occult blood test," "sigmoidoscopy," and "colonoscopy," whereas the unlabeled DCE version presented them as "screening test A" and "screening test B." Questionnaires were sent to participants and nonparticipants in CRC screening. Results: Total response rate was 276 (39%) out of 712 and 1033 (46%) out of 2267 for unlabeled and labeled DCEs, respectively (P < 0.001). The labels played a significant role in individual choices; approximately 22% of subjects had dominant preferences for screening test labels. The convergent validity was modest to low (participants in CRC screening: r = 0.54; P = 0.01; nonparticipants: r = 0.17; P = 0.45) largely because of different preferences for screening frequency. Conclusion: This study provides important insights in the feasibility and difference in results from labeled and unlabeled DCEs. The inclusion of labels appeared to play a significant role in individual choices but reduced the attention respondents give to the attributes. As a result, unlabeled DCEs may be more suitable to investigate trade-offs between attributes and for respondents who do not have familiarity with the alternative labels, whereas labeled DCEs may be more suitable to explain real-life choices such as uptake of cancer screening.

Response (Article)

2010-03-01T00:00:00Z

Response Re: Cost-effectiveness analysis of human papillomavirus vaccination in the Netherlands. (Article)

2010-03-01T00:00:00Z

What determines individuals' preferences for colorectal cancer screening programmes? A discrete choice experiment. (Article)

2010-01-01T00:00:00Z

INTRODUCTION: In many countries uptake of colorectal cancer (CRC) screening remains low. AIM: To assess how procedural characteristics of CRC screening programmes determine preferences for participation and how individuals weigh these against the perceived benefits from participation in CRC screening. METHODS: A discrete choice experiment was conducted among subjects in the age group of 50-75 years, including both screening-naive subjects and participants of a CRC screening programme. Subjects were asked on their preferences for aspects of CRC screening programmes using scenarios based on pain, risk of complications, screening location, preparation, duration of procedure, screening interval and risk reduction of CRC-related death. RESULTS: The response was 31% (156/500) for screening-naive and 57% (124/210) for CRC screening participants. All aspects proved to significantly influence the respondents' preferences. For both groups combined, respondents required an additional relative risk reduction of CRC-related death by a screening programme of 1% for every additional 10 min of duration, 5% in order to expose themselves to a small risk of complications, 10% to accept mild pain, 10% to undergo preparation with an enema, 12% to use 0.75l of oral preparation combined with 12h fasting and 32% to use an extensive bowel preparation. Screening intervals shorter than 10 years were significantly preferred to a 10-year screening interval. CONCLUSION: This study shows that especially type of bowel preparation, risk reduction of CRC related death and length of screening interval influence CRC screening preferences. Furthermore, improving awareness on CRC mortality reduction by CRC screening may increase uptake.

What determines individuals' preferences for colorectal cancer screening programmes? A discrete choice experiment. (Article)

2010-01-01T00:00:00Z

Screening for colorectal cancer: Randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy (Article)

2010-01-01T00:00:00Z

Background: Screening for colorectal cancer (CRC) is widely accepted, but there is no consensus on the preferred strategy. We conducted a randomised trial comparing participation and detection rates (DR) per screenee of guaiac-based faecal occult blood test (gFOBT), immunochemical FOBT (FIT), and flexible sigmoidoscopy (FS) for CRC screening. Methods: A representative sample of the Dutch population (n=15 011), aged 50-74 years, was 1:1:1 randomised prior to invitation to one of the three screening strategies. Colonoscopy was indicated for screenees with a positive gFOBT or FIT, and for those in whom FS revealed a polyp with a diameter >10 mm; adenoma with >25% villous component or high grade dysplasia; serrated adenoma; >3 adenomas; >20 hyperplastic polyps; or CRC. Results: The participation rate was 49.5% (95% confidence interval (CI) 48.1 to 50.9%) for gFOBT, 61.5% (CI, 60.1 to 62.9%) for FIT and 32.4% (CI, 31.1 to 33.7%) for FS screening. gFOBT was positive in 2.8%, FIT in 4.8% and FS in 10.2%. The DR of advanced neoplasia was significantly higher in the FIT (2.4%; OR, 2.0; CI, 1.3 to 3.1) and the FS arm (8.0%; OR, 7.0; CI, 4.6 to 10.7) than the gFOBT arm (1.1%). FS demonstrated a higher diagnostic yield of advanced neoplasia per 100 invitees (2.4; CI, 2.0 to 2.8) than gFOBT (0.6; CI, 0.4 to 0.8) or FIT (1.5; CI, 1.2 to 1.9) screening. Conclusion: This randomised population-based CRCscreening trial demonstrated superior participation and detection rates for FIT compared to gFOBT screening. FIT screening should therefore be strongly preferred over gFOBT screening. FS screening demonstrated a higher diagnostic yield per 100 invitees than both FOBTs.

Can differences in IVF success rates between centres be explained by patient characteristics and sample size? (Article)

2010-01-01T00:00:00Z

BACKGROUND: Pregnancy rates cannot be used reliably for comparison of IVF clinic performance because of differences in patients between clinics. We investigate if differences in pregnancy chance between IVF centres remain after adjustment for patient mix. METHODS: We prospectively collected IVF and ICSI treatment data from 11 out of 13 IVF centres in the Netherlands, between 2002 and 2004. Adjustment for sampling variation was made using a random effects model. A prognostic index for subfertility-related factors was used to adjust for differences in patient mix. The remaining variability between centres was split into random variation and true differences. RESULTS: The crude 1-year ongoing pregnancy chance per centre differed by nearly a factor 3 between centres, with hazard ratios (HRs) of 0.48 (95% CI: 0.34-0.69) to 1.34 (95% CI: 1.18-1.51) compared with the mean 1-year ongoing pregnancy chance of all centres. After accounting for sampling variation, the difference shrank since HRs became 0.66 (95% CI: 0.51-0.85) to 1.28 (95% CI: 1.13-1.44). After adjustment for patient mix, the difference narrowed somewhat further to HRs of 0.74 (95% CI: 0.57-0.94) to 1.33 (95% CI: 1.20-1.48) and 17 of the variation between centres could be explained by patient mix. The 1-year cumulative ongoing pregnancy rate in the two most extreme centres was 36% and 55%. CONCLUSION: SOnly a minor part of the differences in pregnancy chance between IVF centres is explained by patient mix. Further research is needed to elucidate the causes of the remaining differences.

Tick-borne agents in rodents, China, 2004-2006 (Article)

2009-12-01T00:00:00Z

A total of 705 rodents from 6 provinces and autonomous regions of mainland People's Republic of China were tested by PCRs for tick-borne agents (Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, spotted fever group rickettsiae, and Francisella tularensis). Infection rates were 5.5%, 6.7%, 9.1% and 5.0%, respectively. Eighteen (2.6%) rodents of 10 species were positive for 2 or 3 agents. Sequence analysis of PCR products confirmed the presence and genotypes of detected agents. These findings demonstrate that these tick-borne agents cocirculate and that a variety of rodent species may be involved in their enzootic maintenance.

Mathematical modelling of SARS and other infectious diseases in China: A review (Article)

2009-11-09T00:00:00Z

Objective To give an overview of the recent history of publications on mathematical modelling of infectious diseases in the Chinese literature, and a more detailed review of the models on severe acute respiratory syndrome (SARS). Method Literature review through the Chinese CAJ full-text database. Results The number of Chinese publications on mathematical modelling has at least quadrupled since the SARS epidemic in 2003. This increase not only included papers on SARS, but also on various other infectious diseases, indicating a substantial expansion of modelling experience in China. Typical problems of most studies were poor availability of data and lack of involvement of disease experts and decision-makers rendering the studies less useful for policies on control. Conclusions We expect that the recent experience on modelling and current better access to and exchange of epidemiological data have paved the way for a more substantial role of this discipline during possible future outbreaks of infectious diseases. By making Chinese modelling initiatives more visible to non-Chinese readers, we hope to attract more international collaborators.

Letter to the Editor of Human Reproduction Update (Article)

2009-10-01T00:00:00Z

Response to the letter to the editor by Hassan et al.: The diminutive lesion versus the advanced adenoma: Which is the real target of CT colonography screening? (Article)

2009-09-01T00:00:00Z

Incidence of cervical cancer after several negative smear results by age 50: prospective observational study (Article)

2009-08-17T00:00:00Z

OBJECTIVE: To determine the incidence of cervical cancer after several negative cervical smear tests at different ages. DESIGN: Prospective observational study of incidence of cervical cancer after the third consecutive negative result based on individual level data in a national registry of histopathology and cytopathology (PALGA). SETTING: Netherlands, national data. Population 218,847 women aged 45-54 and 445,382 aged 30-44 at the time of the third negative smear test. MAIN OUTCOME MEASURES: 10 year cumulative incidence of interval cervical cancer. RESULTS: 105 women developed cervical cancer within 2 595,964 woman years at risk after the third negative result at age 30-44 and 42 within 1,278,532 woman years at risk after age 45-54. During follow-up, both age groups had similar levels of screening. After 10 years of follow-up, the cumulative incidence rate of cervical cancer was similar: 41/100,000 (95% confidence interval 33 to 51) in the younger group and 36/100,000 (24 to 52) in the older group (P=0.48). The cumulative incidence rate of cervical intraepithelial neoplasia grade I+ was twice as high in the younger than in the older group (P<0.001). CONCLUSIONS: The risk for cervical cancer after several negative smear results by age 50 is similar to the risk at younger ages. Even after several negative smear results, age is not a good discriminative factor for early cessation of cervical cancer screening.

Cost-effectiveness analysis of human papillomavirus vaccination in the Netherlands (Article)

2009-08-01T00:00:00Z

BackgroundIn the Netherlands, low cervical cancer incidence and mortality rates might limit the cost-effectiveness of vaccination against the human papillomavirus (HPV). We examined the effect on cervical cancer incidence and mortality of adding HPV vaccination to the current Dutch cervical cancer screening situation and calculated the cost-effectiveness.MethodsCosts and effects were estimated under favorable assumptions (ie, that HPV vaccination provides lifelong protection against 70% of all cervical cancers, has no side effects, and is administered to all women regardless of their risk of cervical cancer) by using the microsimulation screening analysis (MISCAN) model. The impact of changes in the price of vaccination, number of booster vaccinations, vaccination attendance rate, vaccination efficacy, cervical cancer incidence level, and quality-of-life assumptions was investigated in sensitivity analyses.ResultsUsing the current price of €118 per vaccine dose and with discounting of costs and effects at an annual rate of 3%, adding HPV vaccination to the current Dutch screening situation had a cost-effectiveness ratio of €53500 per quality-adjusted life-year (QALY) gained. The threshold price per vaccine dose at which the cost-effectiveness of vaccination would correspond to an acceptability threshold of €20000 per QALY gained was €40. With the addition of one or more (up to four) booster vaccinations during a lifetime, this threshold price decreased to €33 for one booster (to €16 for four boosters). With a doubling of the cervical cancer incidence level, the cost-effectiveness ratio was €24400 per QALY gained and the maximum price per dose at threshold of €20000 was €97. All threshold prices were lower under less favorable effectiveness assumptions.ConclusionsIn the Netherlands, HPV vaccination is not cost-effective even under favorable assumptions. To become cost-effective, the vaccine price would have to be decreased considerably, depending on the effectiveness of the vaccine.

Individualizing colonoscopy screening by sex and race (Article)

2009-07-01T00:00:00Z

Background: There is increasing discussion whether colorectal cancer (CRC) screening guidelines should be individualized by sex and race. Objectives: To determine individualized colonoscopic screening guidelines by sex and race for the average-risk population and to compare the cost-effectiveness of this approach with that of uniform guidelines for all. Design: We used the MISCAN-Colon microsimulation model to estimate life expectancy and lifetime CRC screening and treatment costs in a U.S. cohort of black and white men and women at average risk for CRC. We compared the base-case strategy of no screening and 3 competing colonoscopy strategies: (1) the currently recommended "uniform 10-yearly colonoscopy from age 50 years," (2) a shorter interval "uniform 8-yearly colonoscopy from age 51 years," and (3) "individualized screening according to sex and race.". Results: The base-case strategy of no screening was the least expensive, yet least effective. The uniform 10-yearly colonoscopy strategy was dominated. The uniform 8-yearly colonoscopy and individualized strategies both increased life expectancy by 0.0433 to 0.0435 years per individual, at a cost of $15,565 to $15,837 per life-year gained. In the individualized strategy, blacks began screening 6 years earlier, with a 1-year shorter interval compared with whites. The individualized policies were essentially the same for men and women, because the higher CRC risk in men was offset by their shorter life expectancy. The results were robust for changes in model assumptions. Conclusions: The improvements in costs and effects of individualizing CRC screening on a population level were only marginal. Individualized guidelines, however, could contribute to decreasing disparities between blacks and whites. The acceptability and feasibility of individualized guidelines, therefore, should be explored.

A novel hypothesis on the sensitivity of the fecal occult blood test: Results of a joint analysis of 3 randomized controlled trials (Article)

2009-06-26T00:00:00Z

BACKGROUND: Estimates of the fecal occult blood test (FOBT) (Hemoccult II) sensitivity differed widely between screening trials and led to divergent conclusions on the effects of FOBT screening. We used microsimulation modeling to estimate a preclinical colorectal cancer (CRC) duration and sensitivity for unrehydrated FOBT from the data of 3 randomized controlled trials of Minnesota, Nottingham, and Funen. In addition to 2 usual hypotheses on the sensitivity of FOBT, we tested a novel hypothesis where sensitivity is linked to the stage of clinical diagnosis in the situation without screening. METHODS: We used the MISCAN-Colon microsimulation model to estimate sensitivity and duration, accounting for differences between the trials in demography, background incidence, and trial design. We tested 3 hypotheses for FOBT sensitivity: sensitivity is the same for all preclinical CRC stages, sensitivity increases with each stage, and sensitivity is higher for the stage in which the cancer would have been diagnosed in the absence of screening than for earlier stages. Goodness-of-fit was evaluated by comparing expected and observed rates of screen-detected and interval CRC. RESULTS: The hypothesis with a higher sensitivity in the stage of clinical diagnosis gave the best fit. Under this hypothesis, sensitivity of FOBT was 51% in the stage of clinical diagnosis and 19% in earlier stages. The average duration of preclinical CRC was estimated at 6.7 years. CONCLUSIONS: Our analysis corroborated a long duration of preclinical CRC, with FOBT most sensitive in the stage of clinical diagnosis.

What Is the Evidence on Efficacy of Spinal Cord Stimulation in (Subgroups of) Patients With Critical Limb Ischemia? (Article)

2009-05-01T00:00:00Z

The use of spinal cord stimulation (SCS) has been advocated for the management of ischemic pain and the prevention of amputations in patients with inoperable critical limb ischemia (CLI), although data on benefit are conflicting. Several reports described apparently differential treatment effects in subgroups. The purpose of this study was to analyze the data on the efficacy of SCS and to clarify preselection issues. Five randomized trials have been performed with a total number of 332 patients. Primary outcome measures were mortality and limb survival. In the largest multicenter randomized trial (n = 120), which compared SCS treatment and best medical treatment alone in patients with inoperable CLI, we determined the incidence of amputation and its relation to various predefined risk factors. We used Kaplan-Meier and Cox regression analyses to quantify prognostic effects and differential treatment effects. Meta-analysis yielded a relative risk for amputation of 0.79 and a risk difference of -0.07 (p = 0.15). The risk factor analysis clearly showed that patients with ischemic skin lesions (ulcerations or gangrene) had a worse prognosis (i.e., higher risk of amputation) (relative risk 2.30, p = 0.01). We did not observe significant interactions between this prognostic factor (or any other) and the effect of SCS. The analysis did not indicate a subgroup of patients who might specifically be helped by SCS. Meta-analysis including all randomized data shows insufficient evidence for higher efficacy of SCS treatment compared with best medical treatment alone. Although some factors provide prognostic information as to the risk of amputation in patients with CLI, there are no data supporting a more favorable treatment effect in any group.

The impact of healthcare costs in the last year of life and in all life years gained on the cost-effectiveness of cancer screening (Article)

2009-04-21T00:00:00Z

It is under debate whether healthcare costs related to death and in life years gained (LysG) due to life saving interventions should be included in economic evaluations. We estimated the impact of including these costs on cost-effectiveness of cancer screening. We obtained health insurance, home care, nursing homes, and mortality data for 2.1 million inhabitants in the Netherlands in 1998-1999. Costs related to death were approximated by the healthcare costs in the last year of life (LastYL), by cause and age of death. Costs in LYsG were estimated by calculating the healthcare costs in any life year. We calculated the change in cost-effectiveness ratios (CERs) if unrelated healthcare costs in the LastYL or in LYsG would be included. Costs in the LastYL were on average 33% higher for persons dying from cancer than from any cause. Including costs in LysG increased the CER by \\[euro]4040 in women, and by \\[euro]4100 in men. Of these, \\[euro]660 in women, and \\[euro]890 in men, were costs in the LastYL. Including unrelated healthcare costs in the LastYL or in LYsG will change the comparative cost-effectiveness of healthcare programmes. The CERs of cancer screening programmes will clearly increase, with approximately \\[euro]4000. However, because of the favourable CER's, including unrelated healthcare costs will in general have limited policy implications.

Screening for colorectal cancer: Random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels (Article)

2009-04-07T00:00:00Z

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n10 011), aged 50-74 years, was 1: 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml 1, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2-9.1%) and 3.5% (95% CI: 2.9-4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6-3.9%) and 2.1% (95% CI: 1.6-2.6%), and the specificity ranged between 95.5% (95% CI: 94.5-96.3%) and 98.8% (95% CI: 98.4-99.0%). At a cut-off value of 75 ng ml 1, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml 1 provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.

At what costs will screening with CT colonography be competitive? A cost-effectiveness approach (Article)

2009-03-01T00:00:00Z

The costs of computed tomographic colonography (CTC) are not yet established for screening use. In our study, we estimated the threshold costs for which CTC screening would be a cost-effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population. We used the MISCAN-colon microsi-mulation model to estimate the costs and life-years gained of screening persons aged 50-80 years for 4 screening strategies: (i) optical colonoscopy; and CTC with referral to optical colonoscopy of (ii) any suspected polyp; (iii) a suspected polyp ≥6 mm and (iv) a suspected polyp ≥ 10 mm. For each of the 4 strategies, screen intervals of 5, 10, 15 and 20 years were considered. Subsequently, for each CTC strategy and interval, the threshold costs of CTC were calculated. We performed a sensitivity analysis to assess the effect of uncertain model parameters on the threshold costs. With equal costs ($662), optical colonoscopy dominated CTC screening. For CTC to gain similar life-years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps ≥6 mm. For this strategy to be as cost-effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39-47%). With 25% higher adherence than colonoscopy, CTC threshold costs could be 71% of colonoscopy costs. Our estimate of 43% is considerably lower than previous estimates in literature, because previous studies only compared CTC screening to 10-yearly colonoscopy, where we compared to different intervals of colonoscopy screening.

Absence from work and emotional stress in women undergoing IVF or ICSI: An analysis of IVF-related absence from work in women and the contribution of general and emotional factors (Article)

2008-11-28T00:00:00Z

Objective. To assess productivity losses due to absence from work during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and to describe the pattern of IVF-related absence from work. Additionally, the influence of general and psychological variables on IVF-related absence from work was analyzed. Design. Prospective cohort study. Setting. Eight IVF hospitals participated in the study. Sample. Women undergoing their first treatment with IVF/ICSI. Methods. The Health and Labour Questionnaire (HLQ) was used to estimate the costs of IVF-related absence from work (n=384). Diaries were used to collect background information and reasons for IVF-related absence. Psychological data were derived using the Spielberger State and Trait Anxiety Inventory (STAI), the Beck Depression Inventory for Primary Care (BDI-PC) and the Inventory Social Relations and the Illness Cognition Questionnaire. Regression analyses were performed using two models, one without and one with psychological data, to assess the impact of the different variables on IVF-related absence from work. Main outcome measure. IVF-related absence from work and the costs of productivity losses due to IVF/ICSI per treatment. Results. Overall absence from work during IVF/ICSI treatment was on average 33 hours, of which 23 hours were attributed to IVF/ICSI. Costs of productivity losses due to IVF/ICSI were €596 per woman. Significant predictors of IVF-related absence from work were the number of hours of paid work, age and self-reported physical and/or emotional problems due to IFV treatment. Conclusions. Women experiencing emotional complaints and women with physical complaints due to IVF/ICSI reported significantly more IVF-related absence from work.

LYMFASIM, a simulation model for predicting the impact of lymphatic filariasis control: quantification for African villages. (Article)

2008-11-23T00:00:00Z

LYMFASIM is a simulation model for lymphatic filariasis transmission and control. We quantified its parameters to simulate Wuchereria bancrofti transmission by Anopheles mosquitoes in African villages, using a wide variety of reported data. The developed model captures the general epidemiological patterns, but also the differences between communities. It was calibrated to represent the relationship between mosquito biting rate and the prevalence of microfilariae (mf) in the human population, the age-pattern in mf prevalence, and the relation between mf prevalence and geometric mean mf intensity. Explorative simulations suggest that the impact of mass treatment depends strongly on the mosquito biting rate and on the assumed coverage, compliance and efficacy. Our sensitivity analysis showed that some biological parameters strongly influence the predicted equilibrium pre-treatment mf prevalence (e.g. the lifespan of adult worms and mf). Other parameters primarily affect the post-treatment trends (e.g. severity of density dependence in the mosquito uptake of infection from the human blood, between-person variability in exposure to mosquito bites). The longitudinal data, which are being collected for evaluation of ongoing elimination programmes, can help to further validate the model. The model can help to assess when ongoing elimination activities in African populations can be stopped and to design surveillance schemes. It can be a valuable tool for decision making in the Global Programme to Eliminate Lymphatic Filariasis.

No increased risk for cervical cancer after a broader definition of a negative pap smear (Article)

2008-11-08T00:00:00Z

The definition of minimal relevant Pap smear abnormality is crucial for balancing the beneficial effects of screening (prevented mortality) with negative side-effects (the high positivity rate). After inflammation ceased to be defined as a borderline abnormal smear outcome in The Netherlands in 1996, the proportion of these smears dropped from 10% to less than 2%. Because this may have caused a loss in smear sensitivity, we analysed the changes in the incidence of cervical cancer after a negative Pap smear. All negative smears made at ages 30-64 in 1990-1995 (n = 1,546,252) and 1998-2006 (n = 3,552,716), registered in the national registry of histo- and cytopathology (PALGA), were followed for up to 9 years. During follow-up of the 1990-1995 smears, 377 women developed cervical cancer within 5,232,959 woman-years at risk, while during the follow-up of the 1998-2006 smears, 619 women developed cervical cancer within 11,210,675 woman-years at risk. The cumulative incidence after the definition change was not significantly higher than before: e.g. at 6 years, the cumulative incidence for smears made in 1990-1995 was 46 per 100,000 (95% CI: 41-52), and for smears in 1998-2006 was 48 per 100,000 (95% CI: 43-54), p = 0.59. The hazard ratio for 1998-2006 compared to 1990-1995 adjusted for age, number of previous negative smears and history of abnormalities was 0.90 (95% CI: 0.78-1.03). In The Netherlands, a setting with high-quality cytological screening, treating smears with only signs of inflammation as negative leads to a considerably lower positivity rate without increasing the risk for cervical cancer after a negative smear.

Male circumcision for HIV prevention in sub-Saharan Africa: Who, what and when? (Article)

2008-09-12T00:00:00Z

BACKGROUND AND OBJECTIVE: Male circumcision (circumcision) reduces HIV incidence in men by 50-60%. The United Nations Joint Programme on HIV/AIDS (UNAIDS) recommends the provision of safe circumcision services in countries with high HIV and low circumcision prevalence, prioritizing 12-30 years old HIV-uninfected men. We explore how the population-level impact of circumcision varies by target age group, coverage, time-to-scale-up, level of risk compensation and circumcision of HIV-infected men. DESIGN AND METHODS: An individual-based model was fitted to the characteristics of a typical high-HIV-prevalence population in sub-Saharan Africa and three scenarios of individual-level impact corresponding to the central and the 95% confidence level estimates from the Kenyan circumcision trial. The simulated intervention increased the prevalence of circumcision from 25 to 75% over 5 years in targeted age groups. The impact and cost-effectiveness of the intervention were calculated over 2-50 years. Future costs and effects were discounted and compared with the present value of lifetime HIV treatment costs (US$ 4043). RESULTS: Initially, targeting men older than the United Nations Joint Programme on HIV/AIDS recommended age group may be the most cost-effective strategy, but targeting any adult age group will be cost-saving. Substantial risk compensation could negate impact, particularly if already circumcised men compensate. If circumcision prevalence in HIV-uninfected men increases less because HIV-infected men are also circumcised, this will reduce impact in men but would have little effect on population-level impact in women. CONCLUSION: Circumcision is a cost-saving intervention in a wide range of scenarios of HIV and initial circumcision prevalence but the United Nations Joint Programme on HIV/AIDS/WHO recommended target age group should be widened to include older HIV-uninfected men and counselling should be targeted at both newly and already circumcised men to minimize risk compensation. To maximize infections-averted, circumcision must be scaled up rapidly while maintaining quality.

Can assisted reproductive technologies help to offset population ageing? (Article)

2008-09-01T00:00:00Z

Predictive value of pregnancy history in subfertile couples: results from a nationwide cohort study in the Netherlands (Article)

2008-09-01T00:00:00Z

Objective: To assess whether pregnancy history can predict the occurrence of a spontaneous ongoing pregnancy in subfertile couples. Design: Prospective cohort study. Setting: Thirty fertility centers in the Netherlands. Patient(s): Subfertile, ovulatory women with at least one patent tube and male partners without severely impaired semen quality. Intervention(s): Fertility work-up, including a detailed pregnancy history. Main Outcome Measure(s): Spontaneous ongoing pregnancy. Result(s): We included 4445 couples, of whom 793 (18%) had a spontaneous ongoing pregnancy within 1 year of follow-up. Previous live birth and miscarriage in current partnership were both associated with higher fecundity as compared with primary infertility (hazard rate ratios for spontaneous pregnancy [HR] 1.4; 95% CI, 1.2-1.7 and 1.3; 95% CI, 1.0-1.5, respectively). Pregnancies in a woman's previous partnerships did not affect the fecundity of the couple. A pregnancy in a previous partnership of the male partner was associated with lower fecundity (HR 0.76; 95% CI, 0.58-0.99). A previous pregnancy after fertility treatment also was associated with lower fecundity (HR 0.52; 95% CI, 0.30-0.90). Conclusion(s): Accurate prediction of the future fertility of a couple requires an exact assessment of the fertility history of both partners.

MUSIDH, multiple use of simulated demographic histories, a novel method to reduce computation time in microsimulation models of infectious diseases (Article)

2008-09-01T00:00:00Z

Microsimulation of infectious diseases requires simulation of many life histories of interacting individuals. In particular, relatively rare infections such as leprosy need to be studied in very large populations. Computation time increases disproportionally with the size of the simulated population. We present a novel method, MUSIDH, an acronym for multiple use of simulated demographic histories, to reduce computation time. Demographic history refers to the processes of birth, death and all other demographic events that should be unrelated to the natural course of an infection, thus non-fatal infections. MUSIDH attaches a fixed number of infection histories to each demographic history, and these infection histories interact as if being the infection history of separate individuals. With two examples, mumps and leprosy, we show that the method can give a factor 50 reduction in computation time at the cost of a small loss in precision. The largest reductions are obtained for rare infections with complex demographic histories.

Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics (Article)

2008-08-07T00:00:00Z

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability. A reliable prediction of outcome on admission is of great clinical relevance. We aimed to develop prognostic models with readily available traditional and novel predictors. METHODS & FINDINGS: Prospectively collected individual patient data were analyzed from 11 studies. We considered predictors available at admission in logistic regression models to predict mortality and unfavorable outcome according to the Glasgow Outcome Scale at 6 months after injury. Prognostic models were developed in 8509 patients with severe or moderate TBI, with cross-validation by omitting each of the 11 studies in turn. External validation was on 6681 patients from the recent MRC CRASH trial. We found that the strongest predictors were age, motor score, pupillary reactivity and CT characteristics including the presence of traumatic subarachnoid hemorrhage. A prognostic model that combined age, motor score, and pupillary reactivity had an area under the receiver operating characteristic curve (AUC) between 0.66 and 0.84 at cross-validation. This performance could be improved (AUC increase approximately 0.05) by considering CT characteristics, secondary insults (hypotension, hypoxia), and laboratory parameters (glucose and hemoglobin). External validation confirmed the adequate discriminative ability (AUC 0.80). Outcomes were systematically worse than predicted, but less so in 1588 patients from high income countries in the CRASH trial. CONCLUSIONS: Prognostic models using baseline characteristics provide adequate discrimination between patients with good and poor 6 month outcomes after TBI, especially if CT and laboratory findings are considered in addition to traditional predictors. The model predictions may support clinical practice and research, including the design and analysis of randomised controlled trials.

Is affordable and cost-effective assisted reproductive technology in low-income countries possible? What should we know to answer the question? (Article)

2008-07-01T00:00:00Z

Decision making on infertility treatment in low-income countries (LIC) assumes answers to quite a few questions: how should the infertility problem be defined? How often does infertility occur? What is the burden-of-disease of infertility? What is the income in LIC, and what can be spend on health care? How cheap should IVF be in order to be accessible to a considerable part of the population? With what alternative health interventions should infertility treatment be compared? How cost-effective should IVF be in order to compete with those other interventions? These questions will be discussed. The emphasis is on the situation in Sub-Saharan Africa (SSA). It is concluded that a place for ART in a health care package is not straightforward. Many of the questions are not or only partially answered. Moreover, cheap and effective ART has yet to be developed and tested. From the limited evidence available for each of the questions, it could be calculated that an IVF cycle should cost between 50 and 75 dollar in order to be a candidate for the inclusion in a health package in SSA. This estimate can easily change considerably when in the future the calculations will be based on thorough research. Thus, a targeted research programme for answering the open questions, especially on quality-of-life implications of infertility in different societies, is the preferred option for facilitating the future evaluation of ART in LIC.

A newly discovered Anaplasma phagocytophilum variant in rodents from southeastern China (Article)

2008-06-01T00:00:00Z

Anaplasma phagocytophilum was detected by polymerase chain reaction in 13 (14.1%) of 92 rodents captured from a mountainous area of Zhejiang Province in southeastern China. The nucleotide sequences of 1442-bp, nearly entire 16S rRNA gene amplified from these rodents, had 100% identity, but varied from all known corresponding sequences of A. phagocytophilum deposited in GenBank. To further identify and classify the variant, fragments of 357-bp partial citrate synthase gene (gltA), 849-bp major surface protein 4 gene (msp4), and 443-bp groESL heat-shock operon gene, were amplified and analyzed. The nucleotide sequences of the partial gltA gene amplified from the rodents were identical to each other, but distinct from previously reported A. phagocytophilum sequences, as were msp4 and groESL. These findings indicate that the newly discovered agent represents a novel A. phagocytophilum variant.

A decision-analytic approach to define poor prognosis patients: A case study for non-seminomatous germ cell cancer patients (Article)

2008-05-16T00:00:00Z

Background. Classification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks a formal basis. We propose a decision analytic approach to weigh benefits and harms explicitly to define the treatment threshold for more aggressive treatment. This approach is illustrated by a case study in advanced testicular cancer, where patients with a high risk of mortality under standard treatment may be eligible for high-dose chemotherapy with stem cell support, which is currently defined by the IGCC classification. Methods. We used published literature to estimate the benefit and harm of high-dose chemotherapy (HD-CT) versus standard-dose chemotherapy (SD-CT) for patients with advanced non-seminomatous germ cell cancer. Benefit and harm were defined as the reduction and increase in absolute risk of mortality due to HD-CT respectively. Harm included early and late treatment related death, and treatment related morbidity (weighted by 'utility'). Results. We considered a conservative and an optimistic benefit of 30 and 40% risk reduction respectively. We estimated the excess treatment related mortality at 2%. When treatment related morbidity was taken into account, the harm of HD-CT increased to 5%. With a relative benefit of 30% and harm of 2 or 5%, HD-CT might be beneficial for patients with over 7 or 17% risk of cancer specific mortality with SD chemotherapy, while with a relative benefit of 40% HD-CT was beneficial over 5 and 12.5% risk respectively. Compared to the IGCC classification 14% of the patients would receive more aggressive treatment, and 2% less intensive treatment. Conclusion. Benefit and harm can be used to define 'poor prognosis' explicitly for non-seminomatous germ cell cancer patients who are considered for high-dose chemotherapy. This approach can readily be adapted to new results and extended to other cancers to define candidates for more aggressive treatments.

The impact of pre-exposure prophylaxis (PrEP) on HIV epidemics in Africa and India: A simulation study (Article)

2008-05-07T00:00:00Z

Background: Pre-exposure prophylaxis (PrEP) is a promising new HIV prevention method, especially for women. An urgent demand for implementation of PrEP is expected at the moment efficacy has been demonstrated in clinical trials. We explored the long-term impact of PrEP on HIV transmission in different HIV epidemics. Methodology/Principal Findings: We used a mathematical model that distinguishes the general population, sex workers and their clients. PrEP scenarios varying in effectiveness, coverage and target group were modeled in the epidemiological settings of Botswana, Nyanza Province in Kenya, and Southern India. We also studied the effect of condom addition or condom substitution during PrEP use. Main outcome was number of HIV infections averted over ten years of PrEP use. PrEP strategies with high effectiveness and high coverage can have a substantial impact in African settings. In Southern India, by contrast, the number of averted HIV infections in different PrEP scenarios would be much lower. The impact of PrEP may be strongly diminished or even reversed by behavioral disinhibition, especially in scenarios with low coverage and low effectiveness. However, additional condom use during low coverage and low effective PrEP doubled the amount of averted HIV infections. Conclusions/Significance: The public health impact of PrEP can be substantial. However, this impact may be diminished, or even reversed, by changes in risk behavior. Implementation of PrEP strategies should therefore come on top of current condom campaigns, not as a substitution.

Treating curable sexually transmitted infections to prevent HIV in Africa: Still an effective control strategy? (Article)

2008-03-01T00:00:00Z

BACKGROUND: Evidence regarding the effectiveness of sexually transmitted infection (STI) treatment for HIV prevention in Africa is equivocal, leading some policy makers to question whether it should continue to be promoted for HIV control. We explore whether treating curable STIs remains a cost-effective HIV control strategy in Africa. METHODS: The model STDSIM was fitted to the characteristics of 4 populations in East and West Africa. Over the simulated HIV epidemics, the population-attributable fractions (PAFs) of incident HIV attributable to STIs, the impact of syndromic STI management on HIV incidence, and the cost per HIV infection averted were evaluated and compared with an estimate of lifetime HIV treatment costs (US $3500). RESULTS: Throughout the HIV epidemics in all cities, the total PAF for all STIs remained high, with ≥50% of HIV transmission attributed to STIs. The PAF for herpes simplex virus type 2 increased during the epidemics, whereas the PAF for curable STIs and the relative impact of syndromic management decreased. The models showed that the absolute impact of syndromic management remains high in generalized epidemics, and it remained cost-saving in 3 of the 4 populations in which the cost per HIV infection averted ranged between US $321 and $1665. CONCLUSION: Curable STI interventions may remain cost-saving in populations with generalized HIV epidemics, particularly in populations with high-risk behaviors or low male circumcision rates.

A detailed cost analysis of in vitro fertilization and intracytoplasmic sperm injection treatment (Article)

2008-02-01T00:00:00Z

Objective: To provide detailed information about costs of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment stages and to estimate the cost per IVF and ICSI treatment cycle and ongoing pregnancy. Design: Descriptive micro-costing study. Setting: Four Dutch IVF centers. Patient(s): Women undergoing their first treatment cycle with IVF or ICSI. Intervention(s): IVF or ICSI. Main Outcome Measure(s): Costs per treatment stage, per cycle started, and for ongoing pregnancy. Result(s): Average costs of IVF and ICSI hormonal stimulation were €1630 and €1585; the costs of oocyte retrieval were €500 and €725, respectively. The cost of embryo transfer was €185. Costs per IVF and ICSI cycle started were €2381 and €2578, respectively. Costs per ongoing pregnancy were €10,482 and €10,036, respectively. Conclusion(s): Hormonal stimulation covered the main part of the costs per cycle (on average 68% and 61% for IVF and ICSI, respectively) due to the relatively high cost of medication. The costs of medication increased with increasing age of the women, irrespective of the type of treatment (IVF or ICSI). Fertilization costs (IVF laboratory) constituted 12% and 20% of the total costs of IVF and ICSI. The total cost per ICSI cycle was 8.3% higher than IVF.

Cost-effectiveness of a mild compared with a standard strategy for IVF: A randomized comparison using cumulative term live birth as the primary endpoint (Article)

2008-02-01T00:00:00Z

BACKGROUND: Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. METHODS: Four hundred and four patients were randomly assigned to undergo either mild ovarian stimulation/GnRH antagonist co-treatment combined with single embryo transfer, or standard stimulation/GnRH agonist long protocol and the transfer of two embryos. The main outcome measures are total costs of treatment within a 12 months period after randomization, and the relationship between total costs and proportion of cumulative pregnancies resulting in term live birth within 1 year of randomization. RESULTS: Despite a significantly increased average number of IVF cycles (2.3 versus 1.7; P < 0.001), lower average total costs over a 12-month period (8333 versus €10 745; P = 0.006) were observed using the mild strategy. This was mainly due to higher costs of the obstetric and post-natal period for the standard strategy, related to multiple pregnancies. The costs per pregnancy leading to term live birth were €19 156 in the mild strategy and €24 038 in the standard. The incremental cost-effectiveness ratio of the standard strategy compared with the mild strategy was €185 000 per extra pregnancy leading to term live birth. CONCLUSIONS: Despite an increased mean number of IVF cycles within 1 year, from an economic perspective, the mild treatment strategy is more advantageous per term live birth. It is unlikely, over a wide range of society's willingness-to-pay, that the standard treatment strategy is cost-effective, compared with the mild strategy.

Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women (Article)

2008-02-01T00:00:00Z

BACKGROUND: Obesity is increasing rapidly among women all over the world. Obesity is a known risk factor for subfertility due to anovulation, but it is unknown whether obesity also affects spontaneous pregnancy chances in subfertile, ovulatory women. METHODS: We evaluated whether obesity affected the chance of a spontaneous pregnancy in a prospectively assembled cohort of 3029 consecutive subfertile couples. Women had to be ovulatory and had to have at least one patent tube, whereas men had to have a normal semen analysis. Time to spontaneous ongoing pregnancy within 12 months was the primary endpoint. RESULTS: The probability of a spontaneous pregnancy declined linearly with a body mass index (BMI) over 29 kg/m2. Corrected for possible related factors, women with a high BMI had a 4% lower pregnancy rate per kg/m2increase [hazard ratio: 0.96 (95% CI 0.91-0.99)]. CONCLUSIONS: These results indicate that obesity is associated with lower pregnancy rates in subfertile ovulatory women.

Separation of spouses due to travel and living apart raises HIV risk in Tanzanian couples. (Article)

2008-01-01T00:00:00Z

BACKGROUND: Persons with absent partners may be more vulnerable to risky sexual behavior and therefore HIV. Partner absence can be due to traveling (e.g., family visits or funerals) or to living apart (e.g., work-related or in polygamous marriages). We investigated to what extent partner absence leads to more risky sexual behavior in Tanzanian couples. METHODS: We compared 95 men and 85 women living apart with 283 men and 331 women living together. Only persons who were still married were included, either living apart or cohabiting at the time of the interview. Subjects were classified into 4 groups: coresidents being either nonmobile or mobile, and people living apart either frequently or infrequently seeing each other. RESULTS: Most people living apart were polygamously married. Men living apart did not report more extramarital sex than coresident men. However, among coresident men, extramarital sex was reported by 35% of those being mobile compared with 15% of those nonmobile. Among women, those living apart reported extramarital sex more often than coresidents (14% vs. 7%), and this was mainly due to women living apart who infrequently saw their husbands. CONCLUSIONS: Risky sexual behavior occurs more often in mobile coresident men, and in women living apart infrequently seeing their spouses. These groups are relatively easy to identify and need extra attention in HIV prevention campaigns.

Prueba de la eficacia de la estimulación de la médula espinal en pacientes con isquemia crítica (Article)

2008-01-01T00:00:00Z

Se ha recomendado el uso de estimulación de la médula espinal (EME) para el tratamiento del dolor isquémico y la prevención de las amputaciones en pacientes con isquemia crítica de la extremidad (ICE) inoperable, aunque los datos sobre sus beneficios son conflictivos. En diversos artículos publicados, se han descrito efectos aparentemente diferentes del tratamiento en distintos subgrupos. El objetivo del presente estudio fue analizar los datos existentes sobre eficacia de la EME y clarificar los criterios de preselección. Se han identificado cinco ensayos aleatorizados con un número total de 332 pacientes. Las variables primarias analizadas fueron la mortalidad y la supervivencia de la extremidad. En el ensayo multicéntrico aleatorizado a mayor escala (n = 120), que comparó el tratamiento EME con el mejor tratamiento médico solo en pacientes con ICE inoperable, determinamos la incidencia de amputación y su relación con diversos factores de riesgo predefinidos. Utilizamos un análisis de Kaplan-Meier y una regresión de Cox para cuantificar los efectos pronósticos y los efectos diferenciales del tratamiento. El metaanálisis deparó un riesgo relativo de amputación de 0,79 y una diferencia de riesgo de -0,07 (p = 0,15). El análisis de factores de riesgo reveló claramente que los pacientes con lesiones cutáneas isquémicas (ulceraciones o gangrena) tuvieron un peor pronóstico (es decir, mayor riesgo de amputación) (riesgo relativo 2,30, p = 0,01). No observamos interacciones significativas entre este factor pronóstico (o cualquier otro) y el efecto de la EME. El análisis no indicó que un subgrupo de pacientes pudiera beneficiarse específicamente de la EME. El metaanálisis, que incluyó todos los datos aleatorizados, muestra pruebas insuficientes de una mayor eficacia del tratamiento EME comparado con el mejor tratamiento médico solo. Aunque algunos factores proporcionan información pronóstica, por lo que respecta al riesgo de amputación en pacientes con ICE, no se dispone de datos suficientes que respalden un efecto más favorable del tratamiento en ningún grupo.

Methodological quality and publication bias in observational studies on risk of rupture of unruptured intracranial aneurysms (Letter To Editor)

2008-01-01T00:00:00Z

To the Editor: We would like to comment on some aspects of the very interesting updated meta-analysis on risk of rupture of unruptured intracranial aneurysms by Wermer and colleagues.1 First, with regard to the assessment of methodological quality of the included studies, the authors have rated studies as “good” when they fulfilled 3 criteria with regard to design, completeness of follow-up and certainty of diagnosis of subarachnoid hemorrhage. ...

Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial (Article)

2007-12-01T00:00:00Z

After randomization of subfertile couples with an isolated cervical factor to intrauterine insemination for 6 months or expectant management for 6 months, 26 women (51%) vs. 16 women (33%) conceived, respectively. Of these pregnancies, 22 (43%) vs. 13 (27%) were ongoing (relative risk, 1.6; 95% confidence interval, 0.91 to 2.8). There was one multiple pregnancy in the group that was allocated to intrauterine insemination. This trial suggests a beneficial effect of IUI in couples with an isolated cervical factor.

The additional value of ovarian hyperstimulation in intrauterine insemination for couples with an abnormal postcoital test and a poor prognosis: a randomized clinical trial (Article)

2007-12-01T00:00:00Z

Objective: To assess the effectiveness of controlled ovarian hyperstimulation (COH) in intrauterine insemination (IUI) for subfertile couples with an abnormal postcoital test and a poor prognosis. Design: Randomized clinical trial. Setting: Twenty-four fertility centers in the Netherlands. Patient(s): Subfertile couples with a well-timed nonprogressive PCT and additional factors that reduce fertility. Intervention(s): Couples were randomly allocated to three cycles of IUI with COH or three cycles of IUI without COH. Main Outcome Measure(s): Ongoing pregnancy within three IUI cycles. Result(s): We randomly allocated 132 couples to IUI with COH, and 133, to IUI without COH. We observed 33 pregnancies (25%) in the couples allocated to IUI with COH, of which 28 were ongoing (21%), vs. 28 pregnancies (21%) in the couples allocated to IUI without COH, of which 23 were ongoing (17%; relative risk of an ongoing pregnancy, 1.2; 95% confidence interval, 0.75 to 2.0). Two multiple pregnancies occurred in the IUI with COH group, and one, in the IUI without COH group. Conclusion(s): In couples with an abnormal PCT and a poor prognosis, IUI with COH leads to pregnancy rates comparable to those for IUI without COH. We propose to perform IUI without COH in couples with an abnormal PCT.

Human papillomavirus triage of women with persistent borderline or mildly dyskaryotic smears: Comparison of costs and side effects of three alternative strategies (Article)

2007-10-01T00:00:00Z

The conventional direct referral to colposcopy of persistent borderline or mildly dyskaryotic (BMD) smears in cervical cancer screening leads to considerable unnecessary referrals and associated anxiety and costs. This may be improved by including testing for oncogenic human papillomavirus (HPV) in the triage. We assessed costs and side effects (referrals, treatments and time in follow-up) for 3 possible HPV triage strategies (immediate HPV testing, a 6-month delay in HPV testing, a 2-stage combination of both) and compared them with the conventional strategy. The assessments are based on recent Dutch data from various national databases and trials. We estimated that the referral rate could be reduced by 49, 58 and 58% with immediate, delayed and 2-stage HPV testing, respectively. As a consequence, the average length of follow-up, as well as average costs, also decrease. Therefore, we advocate including HPV testing before referring to colposcopy. Among the 3 HPV strategies, analysis of additional aspects favors implementation of immediate HPV testing.

Predicting ongoing pregnancy chances after IVF and ICSI: A national prospective study (Article)

2007-09-01T00:00:00Z

Background: The Dutch IVF guideline suggests triage of patients for IVF based on diagnostic category, duration of infertility and female age. There is no evidence for the effectiveness of these criteria. We evaluated the predictive value of patient characteristics that are used in the Dutch IVF guideline and developed a model that predicts the IVF ongoing pregnancy chance within 12 months. Methods: In a national prospective cohort study, pregnancy chances after IVF and ICSI treatment were assessed. Couples eligible for IVF or ICSI were followed during 12 months, using the databases of 11 IVF centres and 20 transport IVF clinics. Kaplan-Meier analysis was performed to estimate the cumulative probability of an ongoing pregnancy, and Cox regression was used for assessing the effects of predictors of pregnancy. Results: 4928 couples starting IVF/ICSI treatment were prospectively followed. On average, couples had 1.8 cycles in 12 months for both IVF and ICSI. The 1-year probability of ongoing pregnancy was 44.8% (95% CI 42.1-47.5%). ICSI for severe oligospermia had a significantly higher ongoing pregnancy rate than IVF indicated treatments, with a multivariate Hazard ratio (HR) of 1.22 (95% CI 1.07-1.39). The success rates were comparable for all diagnostic categories of IVF. The highest success rate is at age 30, with a slight decline towards younger women and women up to 35 and a sharp drop after 35. Primary subfertility with a HR of 0.90 (95% CI 0.83-0.99) and duration of subfertility with a HR of 0.97 (95% CI 0.95-0.99) per year significantly affected the pregnancy chance. Conclusions: The most important predictors of the pregnancy chance after IVF and ICSI are women's age and ICSI. The diagnostic category is of no consequence. Duration of subfertility and pregnancy history are of limited prognostic value.

Reply: Pregnancy is predictable: A large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples [2] (Article)

2007-08-01T00:00:00Z

Proportion of new HIV infections attributable to herpes simplex 2 increases over time: Simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics (Article)

2007-08-01T00:00:00Z

Objective: To understand the changing impact of herpes simplex 2 (HSV-2) and other sexually transmitted infections (STIs) on HIV incidence over time in four sub-Saharan African cities, using simulation models. Methods: An individual-based stochastic model was fitted to demographic, behavioural and epidemiological data from cross-sectional population-based surveys in four African cities (Kisumu, Kenya; Ndola, Zambia; Yaoundé, Cameroon; and Cotonou, Benin) in 1997. To estimate the proportion of new HIV infections attributable to HSV-2 and other STIs over time, HIV incidence in the fitted model was compared with that in model scenarios in which the cofactor effect of the STIs on HIV susceptibility and infectivity were removed 5, 10, 15, 20 and 25 years into the simulated HIV epidemics. Results: The proportion of incident HIV attributable to HSV-2 infection (the model estimated population attributable fraction (PAFM)) increased with maturity of the HIV epidemic. In the different cities, the PAFMwas 8-31% 5 years into the epidemic, but rose to 35-48% 15 years after the introduction of HIV. In contrast, the proportion of incident HIV attributable to chancroid decreased over time with strongest effects five years after HIV introduction, falling to no effect 15 years after. Sensitivity analyses showed that, in the model, recurrent HSV-2 ulcers had more of an impact on HIV incidence than did primary HSV-2 ulcers, and that the effect of HSV-2 on HIV infectivity may be more important for HIV spread than the effect on HIV susceptibility, assuming that HSV-2 has similar cofactor effects on HIV susceptibility and infectivity. The overall impact of other curable STIs on HIV spread (syphilis, gonorrhoea and chlamydia) remained relatively constant over time. Conclusions: Although HSV-2 appears to have a limited impact on HIV incidence in the early stages of sub-Saharan African HIV epidemics when the epidemic is concentrated in core groups, it has an increasingly large impact as the epidemic progresses. In generalised HIV epidemics where control programmes for curable STIs are already in place, interventions against HSV-2 may have a key role in HIV prevention.

Feasibility study of adjustment for contamination and non-compliance in a prostate cancer screening trial (Article)

2007-07-01T00:00:00Z

BACKGROUND. The use of PSA as a screening test has become increasingly prevalent in the general population and therefore also in the control arm of the European Randomized study of Screening for Prostate Cancer (ERSPC). We present a feasibility study and impact simulation of a secondary analysis, which imitates a situation where all participants in the study are managed according to their random assignment. METHODS. The results of the Rotterdam section of the ERSPC were adjusted for contamination and non-compliance according to Cuzick et al. [Stat Med 1997; 16:1017-1029]. Endpoints of this analysis were simulated reductions in prostate cancer mortality. RESULTS. Of the men allocated to the screen arm, 27.1% were non-compliant. In the control arm 30.7% had their PSA-level measured by a general practitioner (GP) (i.e., contamination). For a scenario in which the intention-to-screen analysis was assumed to give a decrease in the mortality in the men randomized to screening of 6.7%, the secondary analysis resulted in a decrease of 16.1% for those actually screened. CONCLUSION. Although the definition of contamination as "PSA ever tested" gives an indication of the proportion of contamination, it will be important to differentiate the screening use of PSA from its diagnostic use. For the rest, adjustment for non-compliance and contamination was shown to be feasible in this prostate cancer screening trial. It can therefore be used to carry out a secondary analysis on the definitive outcome of the ERSPC and will provide accurate information for those men who are in fact screened.

A case study of the applicability of a prediction model for the selection of patients undergoing in vitro fertilization for single embryo transfer in another center (Article)

2007-06-01T00:00:00Z

Objective: To evaluate the application in a different fertility clinic of a prediction model for selecting IVF patients for elective single embryo transfer. Design: Retrospective analysis of a large database obtained from a tertiary infertility center. Setting: University medical center. Patient(s): The model, derived at the "development center" was applied in 494 consecutive first IVF cycles carried out at the "application center.". Intervention(s): After adjustment of embryo scoring system to be compatible with that used by the prediction model, it was applied to the development center data. A score chart for predicting the probability of singleton or twin pregnancy was constructed. Main Outcome Measure(s): The area under the receiver operator curve (ROC) was determined to measure the ability of the model to discriminate between ongoing pregnancy and twin pregnancy. Calibration plots were made to assess agreement between predicted and observed pregnancy rates (PR). Results: The areas under the ROC for predicting ongoing pregnancy and twin pregnancy were 0.63 and 0.66, respectively. Insertion of a correction factor equivalent to the difference in odds ratios for ongoing PR between the two centers was required to improve the calibration of the model. Conclusion(s): After adaptation, the model performed well in the application center.

Predictive value and clinical impact of basal follicle-stimulating hormone in subfertile, ovulatory women (Article)

2007-06-01T00:00:00Z

Context: Basal FSH is a marker for ovarian reserve. Objectives: The objective of the study was to investigate the predictive value of basal FSH on spontaneous ongoing pregnancy in subfertile ovulatory women. Design: This was a prospective cohort study. Setting: The study was conducted in 19 fertility centers in The Netherlands. Participants: Subfertile ovulatory women without two-sided tubal pathology and in whom the man had normal sperm parameters (total motile count ≥ 3 × 106) participated in the study. Interventions: Interventions included a fertility work-up, including a basal FSH measurement on cycle d 3. Main Outcome Measures: Spontaneous ongoing pregnancy was measured. Results: We included 3519 consecutive couples of which 562 (16%) had a spontaneous ongoing pregnancy within 1 yr. Basal FSH levels of 8 IU/liter or higher were associated with a decreased probability of spontaneous ongoing pregnancy [hazard ratio (HR) 0.93/IU·liter (95% confidence interval [CI] 0.87-0.98)]. In a multivariable analysis, female age (HR 0.97/yr, 95% CI 0.95-0.99), cycle length (HR 0.96/d, 95% CI 0.93-1.0), and FSH levels 8 IU/liter or greater (HR 0.93/IU·liter, 95% CI 0.87-0.99) were strong negative predictors for spontaneous ongoing pregnancy. Addition of FSH to a prediction model based on female age, duration of subfertility, previous pregnancy, referral status, and semen analysis changed the probability to conceive spontaneously from 30% or greater to less than 30% in 97 of 3219 couples (3.0%). Conclusions: In ovulatory women, a basal FSH level of 8 IU/liter or higher is associated with decreasing fecundity, independent of female age and cycle length. Because the number of couples in whom the FSH level alters management decisions is low, we do not recommend routine testing of basal FSH in subfertile couples. Copyright

Knowledge and understanding of disease process, risk factors and treatment modalities in patients with a recent TIA or minor ischemic stroke (Article)

2007-05-01T00:00:00Z

Background: Patients with acute stroke often have a striking lack of knowledge of causes, warning signs, and risk factors. Lack of knowledge may lead to inappropriate secondary prevention behavior. We investigated the knowledge of patients with a TIA or minor stroke about specific aspects of their disease 3 months after the event. Methods: Patients with a TIA or minor stroke who participated in a randomized controlled trial of the effect of health education by an individualized multimedia computer program (IMCP) were included. All patients received information about their disease from their treating neurologist and half of the patients received extra information through the IMCP. The patients' knowledge was tested after 3 months by means of a questionnaire that contained items on pathogenesis, warning signs, vascular diseases, risk factors, lifestyle and treatment. The highest possible score was 71 points. Results: The 57 patients had a mean total score of 41.2 points (SD 10.4) of the maximum 71. Only 15 (26%) correctly identified the brain as the affected organ in stroke and TIA, and only 21 (37%) could give a correct description of a TIA or stroke. In contrast, 80-90% of the patients identified hypertension and/or obesity as vascular risk factors. Knowledge of various treatment modalities of hypertension, hypercholesterolemia and obesity was moderate to high (40-91% adequate responses). Conclusion: The vast majority of patients with TIA or stroke lack specific knowledge about their disease, but they do have a reasonable knowledge of general vascular risk factors and treatment. This suggests that counseling by neurologists of patients with a TIA or stroke can be improved. Copyright

Side-effects of treatment for localized prostate cancer: Are they valued differently by patients and healthy controls? (Article)

2007-04-01T00:00:00Z

OBJECTIVES: To determine how men treated for localized prostate cancer and who had permanent side-effects, and healthy controls, would value five descriptions of health states associated with side-effects of treatment for localized prostate cancer, hypothesising that patients would value the health states as less detrimental than men with no prostate cancer. PATIENTS, SUBJECTS AND METHODS: In previous research, patients with prostate cancer reported high generic quality-of-life scores after primary treatment, despite side-effects; it was suggested that these patients accepted the side-effects, i.e. urinary, bowel and sexual dysfunction, as 'part of the bargain' because they felt they were saved from a life-threatening disease. Thus, we asked 54 men who had been treated for localized prostate cancer and had permanent side-effects, and 53 healthy controls, to value five descriptions of health states. All respondents valued all descriptions using two valuation methods, a visual analogue scale (VAS, range 0-100) and time trade-off (TTO, range 0-1). The respondent functioning was assessed using the EuroQol-5D, completed with items on urinary, bowel and sexual function. RESULTS: Patients and healthy controls had similar valuations for nine of the 10 comparisons (five health states by two methods). Valuations in both groups resulted in the same ranking order of states on the TTO and one exchange in rank order on the VAS. CONCLUSIONS: When asked to value five health states associated with side-effects of treatment for localized prostate cancer, there was no difference in the valuation of erectile, urinary and bowel dysfunction between patients with permanent side-effects after treatment and healthy controls. More likely explanations for the high generic quality-of-life scores after primary treatment for prostate cancer are a response shift and insensitivity of generic health-related quality-of-life measures.

Prostate Cancer in the Swedish Section of ERSPC-Evidence for Less Metastases at Diagnosis but not for Mortality Reduction (Article)

2007-03-01T00:00:00Z

A Swedish randomized screening study, which is a part of European Randomized Study of Screening for Prostate Cancer (ERSPC), reported the risks involved in diagnosing prostate cancer among men. The study included the effectiveness of intention-to-screen analysis program in terms of reducing metastatic disease at the time of diagnosis. The study found a total of 48% and 70% of different control group prostate cancers. The ERSPC study also found that the metastatic disease and the avoidance of metastatic disease are important end points of the study, and the proportion of men with metastatic disease are predicted to die of prostate cancer depending on the the diagnosis of the disease. The death rates in different cancer control arms change with mortality follow-up during the years after the 8-10 yr period. The results of ERSPC study show that over 10-yr period, the incidence of metastatic disease in men can be reduced by almost 50%.

Risk-based selection from the general population in a screening trial: Selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON) (Article)

2007-02-15T00:00:00Z

A method to obtain the optimal selection criteria, taking into account available resources and capacity and the impact on power, is presented for the Dutch-Belgian randomised lung cancer screening trial (NELSON). NELSON investigates whether 16-detector multi-slice computed tomography screening will decrease lung cancer mortality compared to no screening. A questionnaire was sent to 335,441 (mainly) men, aged 50-75. Smoking exposure (years smoked, cigarettes/day, years quit) was determined, and expected lung cancer mortality was estimated for different selection scenarios for the 106,931 respondents, using lung cancer mortality data by level of smoking exposure (US Cancer Prevention Study I and II). Selection criteria were chosen so that the required response among eligible subjects to reach sufficient sample size was minimised and the required sample size was within our capacity. Inviting current and former smokers (quit ≤ 10 years ago) who smoked >15 cigarettes/day during >25 years or >10 cigarettes/day during >30 years was most optimal. With a power of 80%, 17,300-27,900 participants are needed to show a 20-25% lung cancer mortality reduction 10 years after randomisation. Until October 18, 2005 11,103 (first recruitment round) and 4,325 (second recruitment round) (total = 15,428) participants have been randomised. Selecting participants for lung cancer screening trials based on risk estimates is feasible and helpful to minimize sample size and costs. When pooling with Danish trial data (n = ±4,000) NELSON is the only trial without screening in controls that is expected to have 80% power to show a lung cancer mortality reduction of at least 25% 10 years after randomisation.

Pregnancy is predictable: A large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples (Article)

2007-02-01T00:00:00Z

Background: Prediction models for spontaneous pregnancy may be useful tools to select subfertile couples that have good fertility prospects and should therefore be counselled for expectant management. We assessed the accuracy of a recently published prediction model for spontaneous pregnancy in a large prospective validation study. Methods: In 38 centres, we studied a consecutive cohort of subfertile couples, referred for an infertility work-up. Patients had a regular menstrual cycle, patent tubes and a total motile sperm count (TMC) >3 × 106. After the infertility work-up had been completed, we used a prediction model to calculate the chance of a spontaneous ongoing pregnancy (www.freya.nl/probability.php). The primary end-point was time until the occurrence of a spontaneous ongoing pregnancy within 1 year. The performance of the pregnancy prediction model was assessed with calibration, which is the comparison of predicted and observed ongoing pregnancy rates for groups of patients and discrimination. Results: We included 3021 couples of whom 543 (18%) had a spontaneous ongoing pregnancy, 57 (2%) a non-successful pregnancy, 1316 (44%) started treatment, 825 (27%) neither started treatment nor became pregnant and 280 (9%) were lost to follow-up. Calibration of the prediction model was almost perfect. In the 977 couples (32%) with a calculated probability between 30 and 40%, the observed cumulative pregnancy rate at 12 months was 30%, and in 611 couples (20%) with a probability of ≥40%, this was 46%. The discriminative capacity was similar to the one in which the model was developed (c-statistic 0.59). Conclusions: As the chance of a spontaneous ongoing pregnancy among subfertile couples can be accurately calculated, this prediction model can be used as an essential tool for clinical decision-making and in counselling patients. The use of the prediction model may help to prevent unnecessary treatment.

Female sex workers and unsafe sex in urban and rural Nyanza, Kenya: Regular partners may contribute more to HIV transmission than clients (Article)

2007-02-01T00:00:00Z

Objectives: To compare the sexual behaviour of female sex workers in urban and rural areas in Nyanza province in Kenya, and to compare their unsafe sex with clients and with regular partners. Methods: In a cross-sectional study among 64 sex workers (32/32 in urban/rural areas), sex workers kept a sexual diary for 14 days after being interviewed face-to-face. Results: Most sex workers were separated/divorced and had one or two regular partners, who were mostly married to someone else. Sex workers in Kisumu town were younger, had started sex work at an earlier age, and had more clients in the past 14 days than rural women (6.6 vs. 2.4). Both groups had an equal number of sex contacts with regular partners (4.7). With clients, condom use was fairly frequent (75%) but with regular partners, it was rather infrequent (<40%). For both urban and rural areas, the mean number of sex acts in which no condom was used was greater for regular partners (3.2 and 2.8 respectively) than for clients (1.9 and 1.0 respectively). Conclusions: Sex workers in urban and rural areas of Nyanza province practise more unsafe sex with regular partners than with clients. Interventions for sex workers should also focus on condom use in regular partnerships.

Effects of an individualized multimedia computer program for health education in patients with a recent minor stroke or transient ischemic attack - A randomized controlled trial (Article)

2007-01-01T00:00:00Z

Background - Transient ischemic attack (TIA) and stroke patients often show a striking lack of knowledge about their disease. We developed a computer program that provided health education fitting the educational level, risk profile and symptoms of patients and evaluated it in a randomized controlled trial. Methods - Transient ischemic attack or minor stroke patients were allocated to health education by a physician (n = 32) or to a combination of education by a physician and the computer program (n = 33). Knowledge was tested by means of a questionnaire at 1 and 12 weeks after inclusion. The maximum possible score was 71 points. Results - Overall knowledge was low - the mean score was 43.6 at 1 week and 42.0 points at 12 weeks for both the groups. The intervention group had slightly better scores at 1 week after using the computer program, 45.4 vs 41.5 (P = 0.09), with the difference increasing to 4.3 points after (post-hoc) adjustment for age and level of education (P = 0.06). After 12 weeks, the score in the intervention group dropped significantly to 42.0 points (P = 0.05), and was no longer different from the standard group Conclusion - This study did not show a lasting effect of health education by an individualized computer program on the knowledge of TIA and minor stroke patients.

Predicting Retroperitoneal Histology in Postchemotherapy Testicular Germ Cell Cancer: A Model Update and Multicentre Validation with More Than 1000 Patients (Article)

2006-07-14T00:00:00Z

Objectives: Surgical resection of postchemotherapy retroperitoneal lymph nodes is often performed in patients with advanced nonseminomatous testicular germ cell cancer. We previously developed a model to predict the probability that the lymph nodes contain only necrotic or fibrotic (benign) tissue versus mature teratoma and viable cancer (tumour) to identify patients who actually need resection. The present study used an updated model with new patient data and studied the validity of the updated model across various settings. Methods: We combined data of 544 patients from the original model with data of 550 new patients and performed a new logistic regression analysis, which included the same six predictors: histology of the primary tumour, prechemotherapy serum levels of a-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase, residual mass size measured on computed tomography, and change in mass size. The validity of the updated model was studied in individual centres. Calibration of the predicted probabilities was assessed graphically and with the Hosmer-Lemeshow test. Discrimination was studied with the concordance (c)-statistic. Results: The updated model had slightly different, although more precise, regression coefficients. Statistically nonsignificant Hosmer-Lemeshow tests confirmed good calibration in most centres. The c-statistic for all centres except one exceeded 0.80. The updated model was valid over the complete range of predicted probabilities across a broad spectrum of centres. Conclusions: This finding gives confidence in the applicability of the model to select patients for resection, particularly patients with small residual masses and low predicted probabilities of benign tissue (i.e., substantial predicted risks of residual tumour).

No difference in HIV incidence and sexual behaviour between out-migrants and residents in rural Manicaland, Zimbabwe (Article)

2006-05-01T00:00:00Z

objectives Migration is associated with HIV infection, but the relationship has been mostly assessed in cross-sectional studies. In a prospective study, we investigated whether out-migrants are a selection of high-risk individuals and whether rural-to-urban migration results in risky sexual behaviour for HIV incidence. methods A population cohort was enrolled in a stratified household census in four different community types in Manicaland, east Zimbabwe, between July 1998 and February 2000, and followed-up after 3 years. Out-migrants to the national capital (Harare), the provincial capital (Mutare) and other study areas were followed-up. A structured questionnaire was administered and an HIV test was conducted at each interview. HIV prevalence and sexual risk behaviour at baseline, and HIV incidence and sexual behaviour during follow-up were compared for out-migrants and residents. results At baseline, future migrants were significantly younger, better educated and more likely to be single than residents. For males, migration was highest from subsistence farming areas and roadside trading centres and lowest from estates. After adjusting for age, education, marital status and location, there were no differences in HIV prevalence and sexual risk behaviour between future migrants and residents at baseline, for either sex. No significant differences in HIV incidence or sexual behaviour during follow-up were detected between rural-to-urban out-migrants and residents. conclusions Out-migrants from rural Zimbabwe did not have higher levels of HIV infection or sexual risk behaviour than residents either before or after they moved. These findings may be related to the mature stage of the HIV epidemic and the social and living conditions of migrants in Zimbabwean cities.

Advances and challenges in predicting the impact of lymphatic filariasis elimination programmes by mathematical modelling. (Article)

2006-03-28T00:00:00Z

Mathematical simulation models for transmission and control of lymphatic filariasis are useful tools for studying the prospects of lymphatic filariasis elimination. Two simulation models are currently being used. The first, EPIFIL, is a population-based, deterministic model that simulates average trends in infection intensity over time. The second, LYMFASIM, is an individual-based, stochastic model that simulates acquisition and loss of infection for each individual in the simulated population, taking account of individual characteristics. For settings like Pondicherry (India), where Wuchereria bancrofti infection is transmitted by Culex quinquefasciatus, the models give similar predictions of the coverage and number of treatment rounds required to bring microfilaraemia prevalence below a level of 0.5%. Nevertheless, published estimates of the duration of mass treatment required for elimination differed, due to the use of different indicators for elimination (EPIFIL: microfilaraemia prevalence < 0.5% after the last treatment; LYMFASIM: reduction of microfilaraemia prevalence to zero, within 40 years after the start of mass treatment). The two main challenges for future modelling work are: 1) quantification and validation of the models for other regions, for investigation of elimination prospects in situations with other vector-parasite combinations and endemicity levels than in Pondicherry; 2) application of the models to address a range of programmatic issues related to the monitoring and evaluation of ongoing control programmes. The models' usefulness could be enhanced by several extensions; inclusion of different diagnostic tests and natural history of disease in the models is of particular relevance.

Mobility and HIV in Tanzanian couples: both mobile persons and their partners show increased risk (Article)

2006-02-01T00:00:00Z

Objective: To investigate how mobility is related to sexual risk behavior and HIV infection, with special reference to partners staying behind in mobile couples. Methods: HIV status, sexual behavior and demographic data of 2800 couples were collected in a longitudinal study in Kisesa, rural Tanzania. People were considered short-term mobile if they had slept outside the household at least once the night before one of the five demographic interviews, and long-term mobile if they were living elsewhere at least once at the time of a demographic round. Results: Overall, while long-term mobile men did not report more risk behavior than resident men, short-term mobile men reported significantly more often two or more sex partners in the last year (47.8% vs 40.0%, p=0.006). In contrast, long-term mobile women reported more often multiple sex partners than resident women (6.8% vs 2.4%, p=0.001), and also had a higher HIV prevalence (7.7% vs 2.7%, p=0.02). In couples, men and women who were resident and had a long-term mobile partner both reported more sexual risk behavior and also showed higher HIV prevalence than people with resident/short-term mobile partners. Remarkably, risk behavior of men increased more when their wives moved than when they were mobile themselves. Conclusions: More sexual risk behavior and an increased risk of HIV infection was not only seen in mobile persons, but also in partners staying behind. Interventions aiming at reducing risk behavior due to mobility should therefore include partners staying behind.

Two new prediction rules for spontaneous pregnancy leading to live birth among subfertile couples, based on the synthesis of three previous models. (Article)

2004-09-01T00:00:00Z

BACKGROUND: Several models have been published for the prediction of spontaneous pregnancy among subfertile patients. The aim of this study was to broaden the empirical basis for these predictions by making a synthesis of three previously published models. METHODS: We used the original data from the studies of Eimers et al. (1994), Collins et al. (1995) and Snick et al. (1997) on couples consulting for various forms of subfertility. We developed a so-called three-sample synthesis model for predicting spontaneous conception leading to live birth within 1 year after intake based on the three data sets. The predictors used are duration of subfertility, women's age, primary or secondary infertility, percentage of motile sperm, and whether the couple was referred by a general practitioner or by a gynaecologist (referral status). The performance of this model was assessed according to a 'jack-knife' analysis. Because the post-coital test (PCT) was not assessed in one of the samples, a synthesis model including the PCT was based on two samples only. RESULTS: The ability of the synthesis models to distinguish between women who became pregnant and those who did not was comparable to the ability of the one-sample models when applied in the other samples. The reliability of the predictions by the three-sample synthesis model was somewhat better. Predictions improved considerably by including the PCT. CONCLUSIONS: The synthesis models performed better and had a broader empirical basis than the original models. They are therefore better suitable for application in other centres.

Identifying subgroups among poor prognosis patients with nonseminomatous germ cell cancer by tree modelling: a validation study. (Article)

2004-09-01T00:00:00Z

BACKGROUND: In order to target intensive treatment strategies for poor prognosis patients with non-seminomatous germ cell cancer, those with the poorest prognosis should be identified. These patients might profit most from more intensive treatment strategies. For this purpose, a regression tree was previously developed on 332 patients. We aimed to evaluate the performance and structure of this tree. PATIENTS AND METHODS: The previously developed tree was applied to 456 patients with a poor prognosis as defined by the International Germ Cell Cancer Collaborative Group (IGCCCG). Next, we developed a new tree to evaluate whether a similar structure to the previous tree was found. We assessed the internal validity of the new tree, and compared the 2-year survival estimates of each subgroup together with the discriminative ability for both the previously developed and the new tree. Discriminative ability was measured by a concordance (c) statistic, which varies between 0.5 (no discrimination) and 1.0 (perfect discrimination). RESULTS: The 2-year survival estimates in the IGCCCG data ranged from 33% to 63%. The ordering of the subgroups was different and discriminative ability was lower than originally found (c = 0.56 in the IGCCCG data versus 0.63 originally). The new tree differed considerably from the original tree, and identified poor prognosis subgroups with 2-year survival estimates from 38% to 73%. Internal validation showed similar discriminative ability for the new tree and the original tree (c = 0.59 versus 0.56). CONCLUSIONS: The previously developed tree showed poor validity with respect to discriminative ability and the stability of its structure. The performance of the new tree was also unsatisfactory. Given the low proportion of patients categorised as poor prognosis, it seems that the potential to identify further subgroups with the currently available patient characteristics is limited.

Towards less confusing terminology in reproductive medicine: a proposal. (Article)

2004-07-01T00:00:00Z

The use of the term "infertility" and related terms in reproductive medicine is reviewed. Current terminology is found to be ambiguous, confusing and misleading. We recommend that the fertility investigation report of a couple should consist of statements concerning description, diagnosis and prognosis. The description concerns the duration of non-pregnancy before consulting the clinician. A system for prognostic grading is proposed. The fertility investigation report forms the basis for further action, including the possibility of waiting with treatment in case of almost normal or only slightly reduced fertility. The use of the terms infertility, subfertility and fecundity is not necessary, and it is recommended to avoid them.

Should the post-coital test (PCT) be part of the routine fertility work-up? (Article)

2004-06-01T00:00:00Z

BACKGROUND: This study aimed to determine whether medical history and semen analysis can predict the result of the post-coital test (PCT). METHODS: A previously reported data set of Dutch patients collected between 1985 and 1993 was used. Our study was limited to just patients with an ovulatory cycle. Data were complete for medical history, semen analysis and PCT. We performed logistic regression analysis to evaluate whether these factors could predict the result of the PCT (PCT model). Furthermore, we evaluated the additional contribution of the PCT in the prediction of treatment-independent pregnancy (pregnancy model). RESULTS: Thirty-four percent (179 out of 522) had an abnormal PCT. The PCT model contained previous pregnancy [odds ratio (OR) 2.1; 95% confidence interval (CI) 1.3-3.5], semen volume (OR 0.88; 95% CI 0.77-0.99), sperm concentration (OR 0.96; 95% CI 0.94-0.97), sperm motility (OR 0.97; 95% CI 0.96-0.98) and sperm morphology (OR 2.7; 95% CI 1.2-6.8). The area under the ROC curve of the model was 0.81. In the pregnancy model, the result of the actual PCT could be replaced by the predicted result of the PCT model in about half of the couples, without compromising its predictive capacity. CONCLUSION: The medical history and semen analysis can predict the result of the PCT in approximately 50% of the subfertile couples with a regular cycle, without compromising its potential to predict pregnancy.

Comparison of outcomes after aortic valve replacement with a mechanical valve or a bioprosthesis using microsimulation (Article)

2004-01-01T00:00:00Z

BACKGROUND: Mechanical valves and bioprostheses are widely used for aortic valve replacement. Though previous randomised studies indicate that there is no important difference in outcome after implantation with either type of valve, knowledge of outcomes after aortic valve replacement is incomplete. OBJECTIVE: To predict age and sex specific outcomes of patients after aortic valve replacement with bileaflet mechanical valves and stented porcine bioprostheses, and to provide evidence based support for the choice of prosthesis. METHODS: Meta-analysis of published results of primary aortic valve replacement with bileaflet mechanical prostheses (nine reports, 4274 patients, and 25,726 patient-years) and stented porcine bioprostheses (13 reports, 9007 patients, and 54,151 patient-years) was used to estimate the annual risks of postoperative valve related events and their outcomes. These estimates were entered into a microsimulation model, which was employed to calculate age and sex specific outcomes after aortic valve replacement. RESULTS: Life expectancy (LE) and event-free life expectancy (EFLE) for a 65 year old man after implantation with a mechanical valve or a bioprosthesis were 10.4 and 10.7 years and 7.7 and 8.4 years, respectively. The lifetime risk of at least one valve related event for a mechanical valve was 48%, and for a bioprosthesis, 44%. For LE and EFLE, the age crossover point between the two valve types was 59 and 60 years, respectively. CONCLUSIONS: Meta-analysis based microsimulation provides insight into the long term outcome after aortic valve replacement and suggests that the currently recommended age threshold for implanting a bioprosthesis could be lowered further.

Impact of ivermectin on onchocerciasis transmission: assessing the empirical evidence that repeated ivermectin mass treatments may lead to elimination/eradication in West-Africa (Article)

2003-01-01T00:00:00Z

BACKGROUND: The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the question whether elimination of infection or eradication of onchocerciasis can be achieved using this strategy of critical importance. This study was undertaken to explore this issue. METHODS: An empirical approach was adopted in which a comprehensive analysis was undertaken of available data on the impact of more than a decade of ivermectin treatment on onchocerciasis infection and transmission. Relevant entomological and epidemiological data from 14 river basins in the OCP and one basin in Cameroon were reviewed. Areas were distinguished by frequency of treatment (6-monthly or annually), endemicity level and additional control measures such as vector control. Assessment of results were in terms of epidemiological and entomological parameters, and as a measure of inputs, therapeutic and geographical coverage rates were used. RESULTS: In all of the river basins studied, ivermectin treatment sharply reduced prevalence and intensity of infection. Significant transmission, however, is still ongoing in some basins after 10-12 years of ivermectin treatment. In other basins, transmission may have been interrupted, but this needs to be confirmed by in-depth evaluations. In one mesoendemic basin, where 20 rounds of four-monthly treatment reduced prevalence of infection to levels as low as 2-3%, there was significant recrudescence of infection within a few years after interruption of treatment. CONCLUSIONS: Ivermectin treatment has been very successful in eliminating onchocerciasis as a public health problem. However, the results presented in this paper make it almost certain that repeated ivermectin mass treatment will not lead to the elimination of transmission of onchocerciasis from West Africa. Data on 6-monthly treatments are not sufficient to draw definitive conclusions.

High singleton live birth rate following classical ovulation induction in normogonadotrophic anovulatory infertility (WHO 2) (Article)

2003-01-01T00:00:00Z

BACKGROUND: Medical induction of ovulation using clomiphene citrate (CC) as first line and exogenous gonadotrophins as second line forms the classical treatment algorithm in normogonadotrophic anovulatory infertility. Because the chances of success following classical ovulation induction are not well established, a shift in first-line therapy can be observed towards alternative treatment. The study aim was to: (i) reliably assess the probability of singleton live birth following classical induction of ovulation; and (ii) construct a prediction model, based on individual patient characteristics assessed upon standardized initial screening, to help identify patients with poor chances of success. METHODS: A total of 240 consecutive women visiting a specialist academic fertility unit with a history of infertility, oligomenorrhoea or amenorrhoea, and normal FSH and estradiol serum concentrations (WHO group 2) was prospectively followed. The women had not been previously treated with ovulation-inducing agents. All patients commenced with CC. Patients who did not ovulate within three treatment cycles of incremental daily doses up to 150 mg for 5 consecutive days or ovulatory CC patients who did not conceive within six cycles, subsequently underwent gonadotrophin induction of ovulation applying a step-down dose regimen. The main outcome measure was pregnancy resulting in singleton live birth. Cox regression was used to construct a multivariable prediction model. RESULTS: Overall, there were 134 pregnancies ending in a singleton live birth (56% of women). The cumulative pregnancy rate after 12 and 24 months of follow-up was 50% and 71% respectively. Polycystic ovary syndrome (PCOS) patients (49%), clearly non-PCOS patients (13%) and the in-between group did not differ in prognosis (P = 0.9). The multivariable Cox regression model contained the woman's age, the insulin:glucose ratio and duration of infertility. With a cut-off value of 30% for low chance, the model predicted probabilities at 12 months lower than this cut-off for 25 out of 240 patients (10.4%). CONCLUSIONS: Classical ovulation induction produces very good results in normogonadotrophic anovulatory infertility. Alternative treatment options may not be indicated as first-line therapy in these patients, except for subgroups with poor prognosis. These women can be identified by older age, longer duration of infertility and higher insulin:glucose ratio.

Disappearance of leprosy from Norway: an exploration of critical factors using an epidemiological modelling approach (Article)

2002-01-01T00:00:00Z

BACKGROUND: By the middle of the 19th century, leprosy was a serious public health problem in Norway. By 1920, new cases only rarely occurred. This study aims to explain the disappearance of leprosy from Norway. METHODS: Data from the National Leprosy Registry of Norway and population censuses were used. The patient data include year of birth, onset of disease, registration, hospital admission, death, and emigration. The Norwegian data were analysed using epidemiological models of disease transmission and control. RESULTS: The time trend in leprosy new case detection in Norway can be reproduced adequately. The shift in new case detection towards older ages which occurred over time is accounted for by assuming that infected individuals may have a very long incubation period. The decline cannot be explained fully by the Norwegian policy of isolation of patients: an autonomous decrease in transmission, reflecting improvements in for instance living conditions, must also be assumed. The estimated contribution of the isolation policy to the decline in new case detection very much depends on assumptions made on build-up of contagiousness during the incubation period and waning of transmission opportunities due to rapid transmission to close contacts. CONCLUSION: The impact of isolation on interruption of transmission remains uncertain. This uncertainty also applies to contemporary leprosy control that mainly relies on chemotherapy treatment. Further research is needed to establish the impact of leprosy interventions on transmission.

Cost-effectiveness of cervical cancer screening: comparison of screening policies (Article)

2002-01-01T00:00:00Z

BACKGROUND: Recommended screening policies for cervical cancer differ widely among countries with respect to targeted age range, screening interval, and total number of scheduled screening examinations (i.e., Pap smears). We compared the efficiency of cervical cancer-screening programs by performing a cost-effectiveness analysis of cervical cancer-screening policies from high-income countries. METHODS: We used the microsimulation screening analysis (MISCAN) program to model and determine the costs and effects of almost 500 screening policies, some fictitious and some actual (i.e., recommended by national guidelines). The costs (in U.S. dollars) and effects (in years of life gained) were compared for each policy to identify the most efficient policies. RESULTS: There were 15 efficient screening policies (i.e., no alternative policy exists that results in more life-years gained for lower costs). For these policies, which considered two to 40 total scheduled examinations, the age range expanded gradually from 40-52 years to 20-80 years as the screening interval decreased from 12 to 1.5 years. For the efficient policies, the predicted gain in life expectancy ranged from 11.6 to 32.4 days, compared with a gain of 46 days if cervical cancer mortality were eliminated entirely. The average cost-effectiveness ratios increased from $6700 (for the longest screening interval) to $23 900 per life-year gained. For some countries, the recommended screening policies were close to efficient, but the cost-effectiveness could be improved by reducing the number of scheduled examinations, starting them at later ages, or lengthening the screening interval. CONCLUSIONS: The basis for the diversity in the screening policies among high-income countries does not appear to relate to the screening policies' cost-effectiveness ratios, which are highly sensitive to the number of Pap smears offered during a lifetime.

The effect of HIV, behavioural change, and STD syndromic management on STD epidemiology in sub-Saharan Africa: simulations of Uganda (Article)

2002-01-01T00:00:00Z

An assessment was made of how the HIV epidemic may have influenced sexually transmitted disease (STD) epidemiology in Uganda, and how HIV would affect the effectiveness of syndromic STD treatment programmes during different stages of the epidemic. The dynamic transmission model STDSIM was used to simulate the spread of HIV and four bacterial and one viral STD. Model parameters were quantified using demographic, behavioural, and epidemiological data from rural Rakai and other Ugandan populations. The findings suggest that severe HIV epidemics can markedly alter STD epidemiology, especially if accompanied by a behavioural response. Likely declines in bacterial causes of genital ulcers should be considered in defining policies on syndromic STD management in severe HIV epidemics.

Antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease: a cost effectiveness analysis (Article)

2001-01-01T00:00:00Z

OBJECTIVE: To assess the cost effectiveness of antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease. METHODS: In a decision analysis, data from a prospective study on bacterial arthritis in 4907 patients with joint disease were combined with literature data to assess risks and benefits of antibiotic prophylaxis. Effectiveness and cost effectiveness calculations were performed on antibiotic prophylaxis for various patient groups. Grouping was based on (a) type of event leading to transient bacteraemia-that is, infections (dermal, respiratory/urinary tract) and invasive medical procedures-and (b) the patient's susceptibility to bacterial arthritis which was increased in the presence of rheumatoid arthritis, large joint prostheses, comorbidity, and old age. RESULTS: Of the patients with joint disease, 59% had no characteristics that increased susceptibility to bacterial arthritis, and 31% had one. For dermal infections, the effectiveness of antibiotic prophylaxis was maximally 35 quality adjusted life days (QALDs) and the cost effectiveness maximally $52 000 per quality adjusted life year (QALY). For other infections, the effectiveness of prophylaxis was lower and the cost effectiveness higher. Prophylaxis for invasive medical procedures seemed to be acceptable only in patients with high susceptibility: 1 QALD at a cost of $1300/QALY; however, the results were influenced substantially when the level of efficacy of the prophylaxis or cost of prophylactic antibiotics was changed. CONCLUSION: Prophylaxis seems to be indicated only for dermal infections, and for infections of the urinary and respiratory tract in patients with increased susceptibility to bacterial arthritis. Prophylaxis for invasive medical procedures, such as dental treatment, may only be indicated for patients with joint disease who are highly susceptible.

Prognosis after aortic valve replacement with a bioprosthesis: predictions based on meta-analysis and microsimulation (Article)

2001-01-01T00:00:00Z

BACKGROUND: Bioprostheses are widely used as an aortic valve substitute, but knowledge about prognosis is still incomplete. The purpose of this study was to provide insight into the age-related life expectancy and actual risks of reoperation and valve-related events of patients after aortic valve replacement with a porcine bioprosthesis. METHODS AND RESULTS: We conducted a meta-analysis of 9 selected reports on stented porcine bioprostheses, including 5837 patients with a total follow-up of 31 874 patient-years. The annual rates of valve thrombosis, thromboembolism, hemorrhage, and nonstructural dysfunction were 0.03%, 0.87%, 0.38%, and 0.38%, respectively. The annual rate of endocarditis was estimated at 0.68% for >6 months of implantation and was 5 times as high during the first 6 months. Structural valve deterioration was described with a Weibull model that incorporated lower risks for older patients. These estimates were used to parameterize, calibrate, and validate a mathematical microsimulation model. The model was used to predict life expectancy and actual risks of reoperation and valve-related events after implantation for patients of different ages. For a 65-year-old male, these figures were 11.3 years, 28%, and 47%, respectively. CONCLUSIONS: The combination of meta-analysis with microsimulation enabled a detailed insight into the prognosis after aortic valve replacement with a bioprosthesis for patients of different ages. This information will be useful for patient counseling and clinical decision making. It also could serve as a baseline for the evaluation of newer valve types.

Adaptive extensions of the Nelder and Mead Simplex Method for optimization of stochastic simulation models (Research Paper)

2000-05-25T00:00:00Z

We consider the Nelder and Mead Simplex Method for the optimization of stochastic simulation models. Existing and new adaptive extensions of the Nelder and Mead simplex method designed to improve the accuracy and consistency of the observed best point are studied. We compare the performance of the extensions on a small microsimulation model, as well as on five test functions. We found that gradually decreasing the noise during an optimization run is the most preferred approach for stochastic objective functions. The amount of computation effort needed for successful optimization is very sensitive to the timing of noise reduction and to the rate of decrease of the noise. Restarting the algorithm during the optimization run, in the sense that the algorithm applies a fresh simplex at certain iterations during an optimization run, has adverse effects in our tests for the microsimulation model and for most test functions.

Endoscopic colorectal cancer screening: a cost-saving analysis (Article)

2000-01-01T00:00:00Z

BACKGROUND: Comprehensive analyses have shown that screening for cancer usually induces net costs. In this study, the possible costs and savings of endoscopic colorectal cancer screening are explored to investigate whether the induced savings may compensate for the costs of screening. METHODS: A simulation model for evaluation of colorectal cancer screening, MISCAN-COLON, is used to predict costs and savings for the U.S. population, assuming that screening is performed during a period of 30 years. Plausible baseline parameter values of epidemiology, natural history, screening test characteristics, and unit costs are based on available data and expert opinion. Important parameters are varied to extreme but plausible values. RESULTS: Given the expert opinion-based assumptions, a program based on every 5-year sigmoidoscopy screenings could result in a net savings of direct health care costs due to prevention of cancer treatment costs that compensate for the costs of screening, diagnostic follow-up, and surveillance. This result persists when costs and health effects are discounted at 3%. The "break-even" point, the time required before savings exceed costs, is 35 years for a screening program that terminates after 30 years and 44 years for a screening program that continues on indefinitely. However, net savings increase or turn into net costs when alternative assumptions about natural history of colorectal cancer, costs of screening, surveillance, and diagnostics are considered. CONCLUSIONS: Given the present, limited knowledge of the disease process of colorectal cancer, test characteristics, and costs, it may well be that the induced savings by endoscopic colorectal cancer screening completely compensate for the costs.

Retroperitoneal metastases in testicular cancer: role of CT measurements of residual masses in decision making for resection after chemotherapy (Article)

2000-01-01T00:00:00Z

PURPOSE: To determine the relative importance of computed tomographic (CT) measurements for the prediction of histologic findings in residual masses in patients with nonseminomatous testicular cancer. MATERIALS AND METHODS: Measurements of the maximum transverse size of retroperitoneal metastases before and after chemotherapy were available in 641 patients who underwent resection after chemotherapy while their levels of tumor markers were normal. Radiologic measurements of mass size and clinical characteristics (histologic findings in primary tumor and levels of alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase before chemotherapy) were related to histologic findings in the residual mass with logistic regression analysis. RESULTS: At resection, 302 patients had benign tissue, and 339 had residual tumor (mature teratomas or cancer). Tumor was more frequent in larger masses after chemotherapy but was unrelated to mass size before chemotherapy. Inclusion of the reduction in size significantly improved the logistic regression model, which included mass size after chemotherapy. This model was further improved with the addition of clinical characteristics. Areas under the receiver operating characteristic curves increased from 0.74 to 0.77 and 0.83 with these models. CONCLUSION: A small retroperitoneal mass after chemotherapy is an important predictor of benign histologic findings in residual masses in patients with nonseminomatous testicular cancer. However, better predictions can be made when the reduction in size and clinical characteristics are considered as well. Decisions regarding resection should be based on the combination of these characteristics rather than on only mass size after chemotherapy.

Continuous ST-segment monitoring associated with infarct size and left ventricular function in the GUSTO-I trial (Article)

1999-09-21T00:00:00Z

Background: The aim of this study was to evaluate whether in patients with myocardial infarction, the intensity and duration of myocardial ischemia as measured by continuous ST monitoring are associated with infarct size and residual left ventricular function. Methods and Results: The analyses included patients with myocardial infarction, receiving thrombolytic therapy, who were enrolled in the electrocardiographic substudy of GUSTO-I, monitored by a vector-derived 12-lead electrocardiographic recording system, and in whom either infarct size (defined as cumulative release of α-hydroxybutyrate dehydrogenase activity per liter of plasma over a 72-hour period [Q(72)]) or left ventricular ejection fraction (LVEF) was determined. With the use of linear regression analysis, we investigated the association of various ST- trend characteristics with Q(72) (206 patients) and with LVEF (180 patients). A higher area under the ST trend since thrombolysis until 50% ST recovery and a higher area under recurrent ischemic episodes (ST reelevations) were significantly associated with a higher Q(72), whereas only a higher area under recurrent ischemic episodes was significantly associated with a lower LVEF. These associations remained after adjusting for other patient characteristics such as age, sex, infarct location, and time to treatment. Conclusions: These findings support the physiologic hypothesis that both the intensity and duration of myocardial ischemia (both reflected by the estimated areas under the ST-trend curve) determine myocardial damage and thus are associated with infarct size and ejection fraction in patients with acute myocardial infarction who receive thrombolytic therapy.

Correlations in uncertainty analysis for medical decision making: an application to heart valve replacement. (Article)

1999-09-01T00:00:00Z

A Monte Carlo uncertainty analysis with correlations between parameters is applied to a Markov-chain model that is used to support the choice of a replacement heart-valve. The objective is to quantify the effects of uncertainty in and of correlations between probabilities of valve-related events on the life expectancies of four valve types. The uncertainty in the logit- and log-transformed parameters—mostly representing proba bilities and durations—is modeled as a multivariate normal distribution. The univariate distributions are obtained through values for the median and the 0.975 quantile of each parameter. Correlations between parameters are difficult to quantify. A sensitivity anal ysis is suggested to study their influences on the uncertainty in valve preference prior to further elicitation efforts. The results of the uncertainty analysis strengthen the con clusions from a preceding study, which did not include uncertainty in the model param eters, where the homograft turned out to be the best choice. It is concluded that the influence of correlations is limited in most cases. Preference statements become more certain when the correlation between valve types increases.

Comparison of response surface methodology and the Nelder and Mead simplex method for optimization in microsimulation models (Research Paper)

1999-07-28T00:00:00Z

Microsimulation models are increasingly used in the evaluation of cancer screening. Latent parameters of such models can be estimated by optimization of the goodness-of-fit. We compared the efficiency and accuracy of the Response Surface Methodology and the Nelder and Mead Simplex Method for optimization of microsimulation models. To this end, we tested several automated versions of both methods on a small microsimulation model, as well as on a standard set of test functions. With respect to accuracy, Response Surface Methodology performed better in case of optimization of the microsimulation model, whereas the results for the test functions were rather variable. The Nelder and Mead Simplex Method performed more efficiently than Response Surface Methodology, both for the microsimulation model and the test functions.

Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility (Article)

1999-01-01T00:00:00Z

The present prospective follow-up study was designed to identify whether clinical, endocrine, or ultrasound characteristics assessed by standardized initial screening of normogonadotropic oligo/amenorrheic infertile patients could predict conception in 160 women who reached ovulation after clomiphene citrate (CC) medication. Additional inclusion criteria were total motile sperm count of the partner above 1 million and a negative history for any tubal disease. Daily CC doses of 50 mg (increasing up to 150 mg in case of absent ovarian response) from cycle days 3-7 were used. First conception (defined as a positive urinary pregnancy test) was the end point for this study. A cumulative conception rate of 73% was reached within 9 CC-induced ovulatory cycles. Patients who did conceive presented more frequently with lower age (P < 0.0001) and amenorrhea (P < 0.05) upon initial screening. In a univariate analysis, patients with elevated initial serum LH concentrations (>7.0 IU/L) had a higher probability of conceiving (P < 0.01). In a multivariate analysis, age and cycle history (oligomenorrhea vs. amenorrhea) were identified as the only significant parameters for prediction of conception. These observations suggest that there is more to be gained from CC ovulation induction in younger women presenting with profound oligomenorrhea or amenorrhea. Screening characteristics involved in the prediction of ovulation after CC medication in normogonadotropic oligo/amenorrheic patients (body weight and hyperandrogenemia, as shown previously) are distinctly different from predictors of conception in ovulatory CC patients (age and the severity of cycle abnormality). This disparity suggests that the FSH threshold (magnitude of FSH required for stimulation of ongoing follicle growth and ovulation) and oocyte quality (chances for conception in ovulatory cycles) may be differentially regulated.

Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility (Article)

1998-01-01T00:00:00Z

The diagnostic criteria used to identify patients suffering from polycystic ovary syndrome remain controversial. The present prospective longitudinal follow-up study was designed to identify whether certain criteria assessed during standardized initial screening could predict the response to ovulation induction with clomiphene citrate (CC) in 201 patients presenting with oligomenorrhea or amenorrhea and infertility. Serum FSH levels were within the normal range (1-10 IU/L), and all patients underwent spontaneous or progestin-induced withdrawal bleeding. Initial CC doses were 50 mg daily for 5 days starting on cycle day 3. In the case of an absent response, doses were increased to 100 and 150 mg daily in subsequent cycles. First ovulation with CC was used as the end point. After a complete follow-up (in the case of a nonresponse, at least 3 treatment cycles with daily CC doses up to 150 mg), 156 patients (78%) ovulated. The free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), body mass index (BMI), cycle history (oligomenorrhea vs. amenorrhea), serum androgen (testosterone and/or androstenedione) levels, and mean ovarian volume assessed by transvaginal sonography were all significantly different (P < 0.01) in responders from those in nonresponders. FAI was chosen to be the best predictor in univariate analysis. The area under the receiver operating characteristics curve in a multivariate prediction model including FAI, BMI, cycle history, and mean ovarian volume was 0.82. Patients whose ovaries are less likely to respond to stimulation by FSH due to CC treatment can be predicted on the basis of initial screening characteristics, such as FAI, BMI, cycle history (oligomenorrhea or amenorrhea), and mean ovarian volume. These observations may add to ongoing discussion regarding etiological factors involved in ovarian dysfunction in these patients and classification of normogonadotropic anovulatory infertile women.

Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrences (Article)

1998-01-01T00:00:00Z

OBJECTIVES: Febrile seizures recur frequently. Factors increasing the risk of febrile seizure recurrence include young age at onset, family history of febrile seizures, previous recurrent febrile seizures, time lapse since previous seizure <6 months, relative low temperature at the initial seizure, multiple type initial seizure, and frequent febrile illnesses. Prevention of seizure recurrences serves two useful purposes: meeting parental fear of recurrent febrile seizures in general and reducing the (small) risk of a long-lasting and eventually injurious recurrent seizure. In daily practice, children with febrile seizures often are treated with antipyretics during fever to prevent febrile seizure recurrences. Thus far, no randomized placebo-controlled trial has been performed to assess the efficacy of intermittent antipyretic treatment in the prevention of seizure recurrence. METHODS: We performed a randomized, double-blind, placebo-controlled trial. Children 1 to 4 years of age who had had at least one risk factor for febrile seizure recurrence were enrolled. They were randomly assigned to either ibuprofen syrup, 20 mg/mL, 0.25 mL (= 5 mg) per kilogram of body weight per dose, or matching placebo, to be administered every 6 hours during fever (temperature, >/=38.5 degrees C). Parents were instructed to take the child's rectal temperature immediately when the child seemed ill or feverish and to promptly administer the study medication when the temperature was >/=38.5 degrees C. Doses were to be administered every 6 hours until the child was afebrile for 24 hours. The parents were instructed not to administer any other antipyretic drug to the child. For measuring rectal temperature, a Philips HP5316 digital thermometer (Philips, Eindhoven, The Netherlands) was distributed. During subsequent treatment of the fever episode, parents had to call the investigator at least once each day to notify the investigator in case of febrile seizure recurrence. The investigator could be contacted by parents 24 hours per day. The primary outcome was the first recurrence of a febrile seizure. Kaplan-Meier curves and Cox regression were used for the statistical analysis. The treatment effect on the course of the temperature was assessed using analysis of covariance, with temperature at fever onset as covariate. Two analyses were performed. In an intention-to-treat analysis, all first recurrences were considered regardless of study medication compliance. A per-protocol analysis was limited to those recurrences that occurred in the context of study medication compliance. RESULTS: Between October 1, 1994, and April 1, 1996, 230 children were randomly assigned to ibuprofen syrup (111 children) or placebo (119 children). Median follow-up time was 1.04 years (25th-75th percentiles; 0.7-1.8 years) in the ibuprofen group and 0.98 years (0.7-1.6 years) in the placebo group. Of all children, 67 had a first febrile seizure recurrence, with 31 in the ibuprofen group and 36 in the placebo group. The 2-year recurrence probabilities were 32% and 39%, respectively. The recurrence risk in the ibuprofen group was 0.9 (95% confidence interval: 0.6-1.5) times the recurrence risk in the placebo group (intention to treat). Adjustment for baseline characteristics did not affect the risk-reduction estimate. Of the 67 recurrences, 30 occurred in the context of study medication compliance (13 ibuprofen, 17 placebo). The per-protocol analysis, which was limited to these events, showed similar results. A significant reduction in temperature (0.7 degrees C) after fever onset in the ibuprofen group compared with the placebo group was demonstrated if all 555 fever episodes were considered. In the fever episodes with a seizure recurrence, a similar temperature increase was shown in both groups, with no significant difference between the intention-to-treat and the per-protocol analysis. DISCUSSION: (ABSTRACT TRUNCATED)

Costs, effects, and savings of screening for cystic fibrosis gene carriers (Article)

1998-01-01T00:00:00Z

STUDY OBJECTIVE: Evaluating the costs, effects, and savings of several strategies for cystic fibrosis (CF) gene carrier screening. DESIGN: A general model for evaluating prenatal, preconceptional, school, and neonatal carrier screening was constructed. For prenatal and preconceptional screening, two strategies were evaluated: single entry and double entry two step couple screening. Firstly, the Dutch situation was evaluated prospectively; subsequently the results were generalised to other carrier frequencies. SETTING: Prospective simulation model. MAIN RESULTS: Of all screening strategies, neonatal carrier screening gives most carrier couples an informed choice concerning reproduction. If the parents of carrier newborns would not be tested however, prenatal screening detects most carrier couples. Prenatal and single entry preconceptional screening programmes have a favourable cost-savings balance in the Netherlands under a wide range of assumptions. For double entry preconceptional screening and neonatal screening, high enough values of uptake of screening, prenatal diagnosis, and induced abortion are necessary. School carrier screening does not have a favourable cost-savings balance. CONCLUSIONS: If a CF screening programme is judged to be useful on individual and social grounds, costs considerations are no obstacle for prenatal and single entry preconceptional screening.

Blood transfusions for severe malaria-related anemia in Africa: a decision analysis (Article)

1998-01-01T00:00:00Z

Severe childhood malarial anemia is commonly treated using blood transfusion. Although transfusion may decrease short-term mortality, the risk of human immunodeficiency virus (HIV) transmission is considerable in Africa. We constructed a decision tree to weigh the short-term mortality benefit of transfusion against HIV infection risk. Probability estimates were derived from published studies. The base-case was a two-year-old child with a 13.5% mortality risk to be transfused with screened or unscreened blood (1% or 13% HIV contamination risk, respectively), with reduction of mortality to 5.5% by transfusion (odds ratio=2.7), and a 2.4% risk of fatal transfusion complications. A sensitivity analysis was performed to assess the influence of variation in these estimates. If a child developed acquired immunodeficiency syndrome, survival was weighed as one-tenth of normal survival. For the base-case, we found that transfusion with screened blood provided a survival benefit of 5%. In contrast, transfusion with unscreened blood decreased survival by 2%. Patients with a mortality risk < 5% derived no benefit from a transfusion with screened blood. Other important factors for the benefit of transfusion were the effectiveness of transfusion in reducing mortality and the risk of blood contamination. A blood transfusion was clearly beneficial if the mortality risk was high and the risk of contamination was low. Our findings can be used as a basis for a clinical transfusion policy that limits transfusions to situations in which they are likely to be beneficial. This will in turn optimize child survival and prevent unnecessary exposure of low risk children to the transfusion risks.

A behavioral rating scale as a predictor for survival of demented nursing home patients (Article)

1994-05-17T00:00:00Z

As part of a study towards determinants of survival in nursing home patients with dementia, the prognostic value of a behavioral rating scale for nursing home patients is assessed in an 8-year follow-up study. The 2-year survival rate for the entire cohort (n = 569) was 56%. Women (n = 459) had a 2-year survival rate of 62%, and men (n = 110) had a 2-year survival rate of 40%. Items indicating physical impairment, dependency and apathy had most prognostic value. Items measuring aggressive or depressive behavior, and cognitive impairment were less predictive. These results were confirmed in a multivariate proportional hazards analysis. A prognostic model with age, gender and five behavioral items (needs help when walking, occupied in useful activity, restless at night, utters physical complaints, and socializes with other patients) substantially differentiated in survival chances in patients with dementia. The model gives a predicted 2-year survival chance of less than 20% or more than 80% in 80 of the 569 patients. When adjusted for the variables in the model, previous residence had no prognostic value anymore. Possibilities for further work in this area of research are discussed.

Kwantitatieve methoden bij besluitvorming in de geneeskunde (Inaugural Lecture)

1988-12-01T00:00:00Z