Bossuyt, P.M.M.

Informed decision-making in colorectal cancer screening using colonoscopy or CT-colonography (Article)

2013-06-01T00:00:00Z

Objective: To evaluate the level of informed decision making in a randomized controlled trial comparing colonoscopy and CT-colonography for colorectal cancer screening. Methods: 8844 citizens aged 50-75 were randomly invited to colonoscopy (. n=. 5924) or CT-colonography (. n=. 2920) screening. All invitees received an information leaflet. Screenees received a questionnaire within 4 weeks before the planned examination, non-screenees 4 weeks after the invitation. A decision was categorized as informed when characterized by sufficient decision-relevant knowledge and consistent with personal attitudes toward participation in screening. Results: Knowledge and attitude items were completed by 1032/1276 colonoscopy screenees (81%), by 698/4648 colonoscopy non-screenees (15%), by 824/982 CT-colonography screenees (84%) and by 192/1938 CT-colonography non-screenees (10%). 1027 colonoscopy screenees (>99%) and 815 CT-colonography screenees (99%) had adequate knowledge; 915 (89%) and 742 (90%) had a positive attitude. 675 non-screenees invited to colonoscopy (97%) and 182 invited to CT-colonography (95%) had adequate knowledge; 344 (49%) and 94 (49%) expressed a negative attitude. Conclusion: A large majority of screenees made an informed decision on participation. Almost half of responding non-screenees, made an uninformed decision, suggesting additional barriers to participation. Practice implications: Efforts to understand the additional barriers will create opportunities to facilitate informed participation to colorectal cancer screening.

Inter-clinic variation in the chances of natural conception of subfertile couples (Article)

2013-05-01T00:00:00Z

Study Questio: NAre there differences between clinics in the chances of natural conception of couples? Summary Answer: We found significant differences between clinics in the couples' natural conception chances, which could not be explained by differences in characteristics of the patients or the clinics. What Is Known Already: In pooled data from multiple centers the synthesis prediction model for natural conception was found to be valid, yet the outcome of interest (i.e. natural conception) might differ between centers. Possible differences between clinics in natural conception rates, as well as the validity of the prediction model in each individual clinic are addressed in this paper.STUDY Design: , SIZE AND DURATIONA secondary data-analysis of a prospective cohort study among 3020 subfertile couples recruited in 38 clinics in the Netherlands between January 2002 and December 2004. Clinics with less than 20 couples were excluded from the analyses, resulting in 21 clinics with 2916 couples. Participants/Materials, Setting, Methods: Inclusion of 2916 subfertile couples who underwent a basic fertility work-up. Couples were excluded who had a fertility disorder (one or two-sided tubal pathology, ovulation disorder, total motile sperm count <3 × 106). Included couples were counseled for expectant management for at least six months or followed until the first day of treatment. Follow-up began at the completion of the fertility work-up. Couples lost to follow-up were censored at the last day of contact. Kaplan-Meier survival curves and a log-rank statistic were estimated. Crude and adjusted hazard ratios were determined, adjusted for patient characteristics and the type of clinic (university hospitals with an assisted conception unit (ACU), non-university hospitals with an ACU and non-university hospitals without an ACU). Hazard ratios were also ascertained with empirical Bayes (EB) estimates. Validation of the prediction model per clinic was performed through calibration. Main Results and the Role of Chance: We found significant differences between clinics in the chance of ongoing pregnancy (P < 0.001); even after adjustment for female age, duration of subfertility, percentage of progressive motile sperm, primary/secondary subfertility and post-coital test (P < 0.001). Adjusted hazard ratios and EB estimates ranged from 0.50 to 2.21 and 0.58 to 1.53, respectively. Among the 21 clinics, there were 4 university hospitals, 10 non-university hospitals with an ACU and 7 non-university hospitals without an ACU. In the multivariable analysis, the type of clinic was not significant (P = 0.11). Calibration gave an average intercept of-0.25 (95% range:-1.04-0.53) and average slope of 0.81 (95% range: 0.03-1.60). Six clinics had a negative intercept that differed significantly from zero and three clinics had a negative or positive slope that differed significantly from one. Limitations, Reasons For Cautiona: more extensive model including more predictors could give less variation in the differences between the clinics. Variation in work-up protocol between clinics could also have played a role. In fertility prediction research the Cox proportional hazards regression is the most widely used statistical model, but as the underlying assumptions have rarely been evaluated, this model could lead to biased outcomes. Wider Implications of the Findings: Our findings suggest that the synthesis model to predict natural conception is useful overall in clinical practice but in a minority of clinics the model is not well calibrated. Updating the synthesis model to include a center-specific baseline chance might improve the synthesis model for certain clinics. Study Funding/Competing Interest: (S)The study (on which this secondary data-analysis was based) was supported by grant 945/12/002 from ZonMW, the Netherlands Organization for Health Research and Development, The Hague, the Netherlands. © 2013 The Author.

Burden of colonoscopy compared to non-cathartic CT-colonography in a colorectal cancer screening programme: Randomised controlled trial (Article)

2012-11-01T00:00:00Z

Objective: CT-colonography has been suggested to be less burdensome for primary colorectal cancer (CRC) screening than colonoscopy. To compare the expected and perceived burden of both in a randomised trial. Design: 8844 Dutch citizens aged 50-74 years were randomly invited for CRC screening with colonoscopy (n=5924) or CT-colonography (n=2920). Colonoscopy was performed after full colon lavage, or CT-colonography after limited bowel preparation (non-cathartic). All invitees were asked to complete the expected burden questionnaire before the procedure. All participants were invited to complete the perceived burden questionnaire 14 days later. Mean scores were calculated on 5-point scales. Results: Expected burden: 2111 (36%) colonoscopy and 1199 (41%) CT-colonography invitees completed the expected burden questionnaire. Colonoscopy invitees expected the bowel preparation and screening procedure to be more burdensome than CT-colonography invitees: mean scores 3.0±1.1 vs 2.3±0.9 (p<0.001) and 3.1±1.1 vs 2.2±0.9 (p<0.001). Perceived burden: 1009/1276 (79%) colonoscopy and 801/982 (82%) CT-colonography participants completed the perceived burden questionnaire. The full screening procedure was reported as more burdensome in CT-colonography than in colonoscopy: 1.8±0.9 vs 2.0±0.9 (p<0.001). Drinking the bowel preparation resulted in a higher burden score in colonoscopy (3.0±1.3 vs 1.7±1.0, p<0.001) while related bowel movements were scored more burdensome in CT-colonography (2.0±1.0 vs 2.2±1.1, p<0.001). Most participants would probably or definitely take part in a next screening round: 96% for colonoscopy and 93% for CT-colonography (p=0.99). Conclusion: In a CRC screening programme, colonoscopy invitees expected the screening procedure and bowel preparation to be more burdensome than CT-colonography invitees. In participants, CT-colonography was scored as more burdensome than colonoscopy. Intended participation in a next screening round was comparable.

Authors' response (Article)

2012-10-01T00:00:00Z

Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: A randomised controlled trial (Article)

2012-01-01T00:00:00Z

Background: Screening for colorectal cancer is widely recommended, but the preferred strategy remains unidentified. We aimed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography. Methods: Members of the general population, aged 50-75 years, and living in the regions of Amsterdam or Rotterdam, identified via the registries of the regional municipal administration, were randomly allocated (2:1) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography. Randomisation was done per household with a minimisation algorithm based on age, sex, and socioeconomic status. Invitations were sent between June 8, 2009, and Aug 16, 2010. Participants assigned to CT colonography who were found to have one or more large lesions (≥10 mm) were offered colonoscopy; those with 6-9 mm lesions were offered surveillance CT colonography. The primary outcome was the participation rate, defined as number of invitees undergoing the examination relative to the total number of invitees. Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees. Invitees and screening centre employees were not masked to allocation. This trial is registered in the Dutch trial register, number NTR1829. Findings: 1276 (22%) of 5924 colonoscopy invitees participated, compared with 982 (34%) of 2920 CT colonography invitees (relative risk [RR] 1·56, 95% CI 1·46-1·68; p<0·0001). Of the participants in the colonoscopy group, 111 (9%) had advanced neoplasia of whom seven (<1%) had a carcinoma. Of CT colonography participants, 84 (9%) were offered colonoscopy, of whom 60 (6%) had advanced neoplasia of whom five (<1%) had a carcinoma; 82 (8%) were offered surveillance. The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography (RR 1·46, 95% CI 1·06-2·03; p=0·02) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography (RR 0·91, 0·66-2·03; p=0·56). The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography, respectively (RR 0·74, 95% CI 0·53-1·03; p=0·07). Serious adverse events related to the screening procedure were post-polypectomy bleedings: two in the colonoscopy group and three in the CT colonography group. Interpretation: Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography. The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies, indicating that both techniques can be used for population-based screening for colorectal cancer. Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable. Funding: Netherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation.

Accuracy and reproducibility of 3D-CT measurements for early response assessment of chemoradiotherapy in patients with oesophageal cancer (Article)

2011-12-01T00:00:00Z

Background: Chemoradiotherapy is increasingly applied in patients with oesophageal cancer. The aim of the present study was to determine whether 3D-CT volumetry is able to differentiate between responding and non-responding oesophageal tumours early in the course of neoadjuvant chemoradiotherapy. Patients and methods: Serial CT before and after two weeks of neoadjuvant chemoradiotherapy was performed in the multimodality treatment arm of a randomised trial including patients with oesophageal carcinoma. CT response was measured with the change in tumour volume between baseline and after 14 days of neoadjuvant therapy. Receiver Operating Characteristic (ROC) analysis was used to evaluate the ability of 3D-CT as an early imaging marker of response. Results: CT response analysis was performed in 39 patients, of whom 26 patients were histopathological responders. Median tumour volume increased between baseline and after 14 days of chemoradiotherapy in histopathological responders as well as in non-responders, though changes were not statistically significant. The area under the ROC curve was 0.71. Conclusion: Tumour volume changes after 14 days of neoadjuvant chemoradiotherapy as measured by 3D-CT were not associated with histopathological tumour response. CT volumetry should not be used for early response assessment in patients with potentially curable oesophageal cancer treated with neoadjuvant chemoradiotherapy.

Chlamydia trachomatis IgG seropositivity is associated with lower natural conception rates in ovulatory subfertile women without visible tubal pathology (Article)

2011-11-01T00:00:00Z

Background The relation between Chlamydia trachomatis infection and subsequent tubal damage is widely recognized. As such, C. trachomatis antibody (CAT) testing can be used to triage women for immediate tubal testing with hysterosalpingography (HSG) or laparoscopy. However, once invasive tubal testing has ruled out tubal pathology, CAT serology status is ignored, as its clinical significance is currently unknown. This study aimed to determine whether positive CAT serology is associated with lower spontaneous pregnancy rates in women in whom HSG and/or diagnostic laparoscopy showed no visible tubal pathology. Methods We studied ovulatory women in whom HSG or laparoscopy showed patent tubes. Women were tested for C. trachomatis immunoglobulin G (IgG) antibodies with either micro-immunofluorescence (MIF) or an ELISA. CAT serology was positive if the MIF titre was <1:32 or if the ELISA index was >1.1. The proportion of couples pregnant without treatment was estimated at 12 months of follow-up. Time to pregnancy was considered censored at the date of the last contact when the woman was not pregnant or at the start of treatment. The association between CAT positivity and an ongoing pregnancy was evaluated with Cox regression analyses. Results Of the 1882 included women without visible tubal pathology, 338 (18) had a treatment-independent pregnancy within 1 year [estimated cumulative pregnancy rate 31; 95 confidence interval (CI): 2735]. Because of differential censoring after 9 months of follow-up, regression analyses were limited to the first 9 months after tubal testing. Positive C. trachomatis IgG serology was associated with a statistically significant 33 lower probability of an ongoing pregnancy [adjusted fecundity rate ratio 0.66 (95 CI 0.490.89)]. Conclusions Even after HSG or laparoscopy has shown no visible tubal pathology, subfertile women with a positive CAT have lower pregnancy chances than CAT negative women. After external validation, this finding could be incorporated into existing prognostic models.

Preventing preterm birth with progesterone: Costs and effects of screening low risk women with a singleton pregnancy for short cervical length, the Triple P study (Article)

2011-10-24T00:00:00Z

Background: Women with a short cervical length in mid-trimester pregnancy have a higher risk of preterm birth and therefore a higher rate of neonatal mortality and morbidity. Progesterone can potentially decrease the number of preterm births and lower neonatal mortality and morbidity. Previous studies showed good results of progesterone in women with either a history of preterm birth or a short cervix. However, it is unknown whether screening for a short cervix and subsequent treatment in mid trimester pregnancy is effective in low risk women.Methods/Design: We plan a combined screen and treat study among women with a singleton pregnancy without a previous preterm birth. In these women, we will measure cervical length at the standard anomaly scan performed between 18 and 22 weeks. Women with cervical length ≤ 30 mm at two independent measurements will be randomly allocated to receive either vaginal progesterone tablets or placebo between 22 and 34 weeks. The primary outcome of this trial is adverse neonatal condition, defined as a composite outcome of neonatal mortality and severe morbidity. Secondary outcomes are time to delivery, preterm birth rate before 32, 34 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We will assess growth, physical condition and neurodevelopmental outcome of the children at two years of age.Discussion: This study will provide evidence for the usefulness and cost-effectiveness of screening for short cervical length at the 18-22 weeks and subsequent progesterone treatment among low risk women.Trial registration: Netherlands Trial Register (NTR): NTR207.

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

Evaluation of a standardized CT colonography training program for novice readers (Article)

2011-02-01T00:00:00Z

Purpose: To determine how many computed tomographic (CT) colonography training studies have to be evaluated by novice readers to obtain an adequate level of competence in polyp detection. Materials and Methods: The study was approved by the Institutional Review Board. Informed consent was obtained from all participants. Six physicians (one radiologist, three radiology residents, two researchers) and three technicians completed a CT colonography training program. Two hundred CT colonographic examinations with colonoscopic verification were selected from a research database, with 100 CT colonographic examinations with at least one polyp 6 mm or larger. After a lecture session and short individual hands-on training, CT colonography training was done individually with immediate feedback of colonoscopy outcome. Per-polyp sensitivity was calculated for four sets of 50 CT colonographic examinations for lesions 6 mm or larger. By using logistic regression analyses, the number of CT colonographic examinations to reach 90% sensitivity for lesions 6 mm or larger was estimated. Reading times were registered. Results: The average per-polyp sensitivity for lesions 6 mm or larger was 76% (207 of 270) in the first set of 50 CT colonographic examinations, 77% (262 of 342) in the second (P = .96 vs first set), 80% (310 of 387) in the third(P = .67 vs first set), and 91% (261 of 288) in the fourth(P = .018). The estimated number of CT colonographic examinations for a sufficient sensitivity was 164. Six of nine readers reached this level of competence within 175 CT colonographic examinations. Reading times decreased significantly from the first to the second set of 50 CT colonographic examinations for six readers. Conclusion: Novice CT colonography readers obtained sensitivity equal to that of experienced readers after practicing on average 164 CT colonographic studies.

Fluorodeoxyglucose positron emission tomography for evaluating early response during neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer (Article)

2011-01-01T00:00:00Z

Background: Neoadjuvant chemoradiotherapy before surgery can improve survival in patients with potentially curable esophageal cancer, but not all patients respond. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been proposed to identify nonresponders early during neoadjuvant chemoradiotherapy. The aim of the present study was to determine whether FDG-PET could differentiate between responding and nonresponding esophageal tumors early in the course of neoadjuvant chemoradiotherapy. Methods: This clinical trial comprised serial FDG-PET before and 14 days after start of chemoradiotherapy in patients with potentially curable esophageal carcinoma. Histopathologic responders were defined as patients with no or less than 10% viable tumor cells (Mandard score on resection specimen). PET response was measured using the standardized uptake value (SUV). Receiver operating characteristic analysis was used to evaluate the ability of SUV in distinguishing between histopathologic responders and nonresponders. Results: In 100 included patients, 64 were histopathologic responders. The median SUV decrease 14 days after the start of therapy was 30.9% for histopathologic responders and 1.7% for nonresponders (P = 0.001). In receiver operating characteristic analysis, the area under the curve was 0.71 (95% CI = 0.60-0.82). Using a 0% SUV decrease cutoff value, PET correctly identified 58 of 64 responders (sensitivity 91%) and 18 of 36 nonresponders (specificity 50%). The corresponding positive and negative predictive values were 76% and 75%, respectively. Background: SUV decrease 14 days after the start of chemoradiotherapy was significantly associated with histopathologic tumor response, but its accuracy in detecting nonresponders was too low to justify the clinical use of FDG-PET for early discontinuation of neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer.

CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population (Article)

2010-12-01T00:00:00Z

Purpose: Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population. Methods: In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas. Results: In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma ≥ 10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88-96) vs. 96% (95% CI: 93-99) for colonoscopy (P = 0.26). For adenomas and carcinomas ≥ 10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89-97) vs. 97% (95% CI: 94-99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas ≥ 10 mm was 95% (95% CI: 91-99) for CTC vs. 99% (95% CI: 98-100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86-95) and 96% (95% CI: 94-99), respectively (P < 0.001). Conclusion: CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions.

Therapeutic delay and survival after surgery for cancer of the pancreatic head with or without preoperative biliary drainage (Article)

2010-11-01T00:00:00Z

Objective: To evaluate the relation between delay in surgery because of preoperative biliary drainage (PBD) and survival in patients scheduled for surgery for pancreatic head cancer. Background: Patients with obstructive jaundice due to pancreatic head cancer can undergo PBD. The associated delay of surgery can lead to more advanced cancer stages at surgical exploration, affecting resection rate and survival. Methods: We conducted a multicenter, randomized controlled clinical trial to compare PBD with early surgery (ES) for pancreatic head cancer for complications. We obtained Kaplan-Meier estimates of overall survival for patients with pathology-proven malignancy and compared survival functions of ES and PBD groups using log-rank test statistics. Multivariable Cox regression analyses were performed to evaluate the prognostic role of time to surgery for overall survival. Results: Mean times from randomization to surgery were 1.2 (0.9-1.5) and 5.1 (4.8-5.5) weeks in the ES and PBD groups, respectively (P < 0.001). In the ES group, 60 (67%) of 89 patients underwent resection, versus 53 (58%) of 91 patients in the PBD group (P = 0.20). Median survival after randomization was 12.2 (9.1-15.4) months in the ES group versus 12.7 (8.9-16.6) months in the PBD group (P = 0.91). A longer time to surgery was significantly associated with slightly lower mortality rate after surgery (hazard ratio = 0.90, 95% CI, 0.83-0.97), when taking into account resection, bilirubin, complications, pancreatic adenocarcinoma, tumor-positive lymph nodes, and microscopically residual disease. Conclusions: In patients with pancreatic head cancer, the delay in surgery associated with PBD does not impair or benefit survival rate. Copyright

Clinical decision rule and D-dimer have lower clinical utility to exclude pulmonary embolism in cancer patients: Explanations and potential ameliorations (Article)

2010-10-01T00:00:00Z

Patients with malignancy frequently present with clinically suspected pulmonary embolism (PE). However, the safe and efficient combination of a clinical decision rule (CDR) and D-dimer test to rule out PE performs less well in patients with malignancy. We examined potential explanations and analysed whether elevating the D-dimer cut-off could improve the clinical utility. We used data on consecutive patients with suspected PE included in a multicenter management study. The performance of the Wells CDR and the D-dimer test was compared between patients with and without malignancy and multivariable analysis was used to compare the weights of the CDR variables. Furthermore, we combined the CDR (cut-off ≤4) with different D-dimer cut-off levels for the exclusion of PE. Of 3,306 patients with suspected PE, 475 (14%) had cancer. The Wells rule variables were less diagnostic in cancer patients. Increasing the D-dimer cut-off level to 700 μg/l for all ages or using an age-dependent cut-off resulted in an increase in the proportion of patients in whom PE could be excluded from 8.4% to 13% and 12%, respectively. The corresponding false-negative rates were 1.6% (95% confidence interval 0.3-8.7%) and 0.0% (0.0-6.3%). The Wells CDR and D-dimer perform less well in patients with suspected PE if they have cancer. Individual variables in the Wells rule are less diagnostic in cancer patients than in non-cancer patients with suspected PE. A CDR combined with an age-dependent D-dimer cut-off shows a modest improvement of the strategy in cancer patients.

Time to pregnancy after a previous miscarriage in subfertile couples (Article)

2010-07-01T00:00:00Z

Objective: To assess the time to spontaneous ongoing pregnancy after a previous miscarriage in subfertile couples. Design: A prospective cohort study. Setting: The study was conducted in 38 fertility centers in the Netherlands. Patient(s): Subfertile couples who miscarried after completing their basic fertility work-up. Intervention(s): Expectant management after a miscarriage. Main Outcome Measure(s): Spontaneous ongoing pregnancy. Result(s): We included 5,663 subfertile couples, of which 1,098 (19%) conceived spontaneously. Among these 1,098 couples, 199 (18%) miscarried and these couples were included in the present study. Follow-up was completed for 171 couples, of which 95 conceived again within 24 months of follow-up. Of these 95 pregnancies, 86 (91%) were ongoing. The cumulative spontaneous ongoing pregnancy rate (PR) after 24 months was 70% (95% confidence interval [CI] 59%-81%). Conclusion(s): Subfertile couples, who experience a treatment-independent pregnancy resulting in a miscarriage, have very good prospects of a spontaneous ongoing pregnancy in the near future. This information is useful in counseling couples who had a miscarriage after a previous period of subfertility.

Study protocol: Population screening for colorectal cancer by colonoscopy or CT colonography: A randomized controlled trial (Article)

2010-05-19T00:00:00Z

Background: Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives.Methods and design: 7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After providing informed consent, participants will be scheduled for the screening procedure. The primary outcome measure of this study is the participation rate. Secondary outcomes are the diagnostic yield, the expected and perceived burden of the screening test, level of informed choice and cost-effectiveness of both screening methods.Discussion: This study will provide further evidence to enable decision making in population screening for colorectal cancer.Trial registration: Dutch trial register: NTR1829.

Preoperative biliary drainage for cancer of the head of the pancreas (Article)

2010-01-14T00:00:00Z

BACKGROUND: The benefits of preoperative biliary drainage, which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head, are unclear. METHODS: In this multicenter, randomized trial, we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head. Patients with obstructive jaundice and a bilirubin level of 40 to 250 μmol per liter (2.3 to 14.6 mg per deciliter) were randomly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks, followed by surgery, or surgery alone within 1 week after diagnosis. Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retrograde cholangiopancreatography. The primary outcome was the rate of serious complications within 120 days after randomization. RESULTS: We enrolled 202 patients; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage; 6 patients were excluded from the analysis. The rates of serious complications were 39% (37 patients) in the early-surgery group and 74% (75 patients) in the biliary-drainage group (relative risk in the early-surgery group, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). Preoperative biliary drainage was successful in 96 patients (94%) after one or more attempts, with complications in 47 patients (46%). Surgery-related complications occurred in 35 patients (37%) in the early-surgery group and in 48 patients (47%) in the biliary-drainage group (relative risk, 0.79; 95% CI, 0.57 to 1.11; P = 0.14). Mortality and the length of hospital stay did not differ significantly between the two groups. CONCLUSIONS: Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications. (Current Controlled Trials number, ISRCTN31939699.) Copyright

Using CT colonography as a triage technique after a positive faecal occult blood test in colorectal cancer screening (Article)

2009-09-01T00:00:00Z

Objective: The purpose of this study was to evaluate the effectiveness of CT colonography (CTC) as a triage technique in faecal occult blood test (FOBT)-positive screening participants. Methods: Consecutive guaiac (G-FOBT) and immunochemical (I-FOBT) FOBT-positive patients scheduled for colonoscopy underwent CTC with iodine tagging bowel preparation. Each CTC was read independently by two experienced observers. Per patient sensitivity, specificity and positive and negative predictive values (PPV and NPV) were calculated based on double reading with different CTC cut-off lesion sizes using segmental unblinded colonoscopy as the reference standard. The acceptability of the technique to patients was evaluated with questionnaires. Results: 302 FOBT-positive patients were included (54 G-FOBT and 248 I-FOBT). 22 FOBT-positive patients (7%) had a colorectal carcinoma and 211 (70%) had a lesion ≥6 mm. Participants considered colonoscopy more burdensome than CTC (p<0.05). Using a 6 mm CTC size cut-off, per patient sensitivity for CTC was 91% (95% CI 85% to 91%) and specificity was 69% (95% CI 60% to 89%) for the detection of colonoscopy lesions ≥6 mm. The PPV of CTC was 87% (95% CI 80% to 93%) and NPV 77% (95% CI 69% to 85%). Using CTC as a triage technique in 100 FOBT-positive patients would mean that colonoscopy could be prevented in 28 patients while missing ≥10 mm lesions in 2 patients. Conclusion: CTC with limited bowel preparation has reasonable predictive values in an FOBT-positive population and a higher acceptability to patients than colonoscopy. However, due to the high prevalence of clinically relevant lesions in FOBT-positive patients, CTC is unlikely to be an efficient triage technique in a first round FOBT population screening programme.

Prediction models in reproductive medicine: A critical appraisal (Article)

2009-08-27T00:00:00Z

Background: Prediction models have been developed in reproductive medicine to help assess the chances of a treatment-(in)dependent pregnancy. Careful evaluation is needed before these models can be implemented in clinical practice. Methods: We systematically searched the literature for papers reporting prediction models in reproductive medicine for three strategies: expectant management, intrauterine insemination (IUI) or in vitro fertilization (IVF). We evaluated which phases of development these models had passed, distinguishing between (i) model derivation, (ii) internal and/or external validation, and (iii) impact analysis. We summarized their performance at external validation in terms of discrimination and calibration. Results: We identified 36 papers reporting on 29 prediction models. There were 9 models for the prediction of treatment-independent pregnancy, 3 for the prediction of pregnancy after IUI and 17 for the prediction of pregnancy after IVF. All of the models had completed the phase of model derivation. For six models, the validity of the model was assessed only in the population in which it was developed (internal validation). For eight models, the validity was assessed in populations other than the one in which the model was developed (external validation), and only three of these showed good performance. One model had reached the phase of impact analysis. Conclusions: Currently, there are three models with good predictive performance. These models can be used reliably as a guide for making decisions about fertility treatment, in patients similar to the development population. The effects of using these models in patient care have to be further investigated.

Diagnostic strategies for pre-treatment staging of patients with oesophageal cancer (Article)

2009-05-01T00:00:00Z

Background/Aims: Current guidelines for staging oesophageal cancer recommend a series of preoperative investigations. There is no consensus on the recommended order for these investigations or whether all investigations are necessary in all patients. Our aim was to determine an efficient strategy for pre-treatment staging of patients with oesophageal cancer. Methods: We retrospectively compared 15 staging strategies, based on all possible orders of all possible subsets of three staging modalities (computed tomography, endoscopic ultrasonography and external ultrasonography of the neck). We assumed that if distant metastases or local irresectability were found and confirmed, no further investigations would be performed. Main outcome was the minimal number of investigations needed to detect all patients with incurable disease. Results: Using all three investigations in all 412 patients would lead to performance of 1,236 investigations. Both strategies starting with computed tomography or endoscopic ultrasonography and ending with external ultrasonography were most efficient, using a total of 1,112 investigations. Conclusion: The use of a conditional staging strategy with a specific order of imaging can reduce the number of tests necessary to identify incurable patients with oesophageal cancer by 10%. In our opinion, this is not enough to recommend implementation of a logistically more complex diagnostic system. Copyright

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: A randomized multicenter trial (LIR!C-trial) (Article)

2008-09-19T00:00:00Z

Background. With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction. The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. Methods/design. The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. Discussion. The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. Trial registration. Nederlands Trial Register NTR1150.

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.

Can the outcome of pelvic-floor rehabilitation in patients with fecal incontinence be predicted? (Article)

2008-05-01T00:00:00Z

Purpose: Pelvic-floor rehabilitation does not provide the same degree of relief in all fecal incontinent patients. We aimed at studying prospectively the ability of tests to predict the outcome of pelvic-floor rehabilitation in patients with fecal incontinence. Materials and methods: Two hundred fifty consecutive patients (228 women) underwent medical history and a standardized series of tests, including physical examination, anal manometry, pudendal nerve latency testing, anal sensitivity testing, rectal capacity measurement, defecography, endoanal sonography, and endoanal magnetic resonance imaging. Subsequently, patients were referred for pelvic-floor rehabilitation. Outcome of pelvic-floor rehabilitation was quantified by the Vaizey incontinence score. Linear regression analyses were used to identify candidate predictors and to construct a multivariable prediction model for the posttreatment Vaizey score. Results: After pelvic-floor rehabilitation, the mean baseline Vaizey score (18, SD±3) was reduced with 3.2 points (p<0.001). In addition to the baseline Vaizey score, three elements from medical history were significantly associated with the posttreatment Vaizey score (presence of passive incontinence, thin stool consistency, primary repair of a rupture after vaginal delivery at childbed) (R2, 0.18). The predictive value was significantly but marginally improved by adding the following test results: perineal and/or perianal scar tissue (physical examination), and maximal squeeze pressure (anal manometry; R2, 0.20; p=0.05). Conclusion: Additional tests have a limited role in predicting success of pelvic-floor rehabilitation in patients with fecal incontinence.

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.

Further validation and simplification of the Wells clinical decision rule in pulmonary embolism (Article)

2008-01-01T00:00:00Z

The Wells rule is a widely applied clinical decision rule in the diagnostic work-up of patients with suspected pulmonary embolism (PE).The objective of this study was to replicate, validate and possibly simplify this rule.We used data collected in 3,306 consecutive patients with clinically suspected PE to recalculate the odds ratios for the variables in the rule, to calculate the proportion of patients with PE in the probability categories,the area under the ROC curve and the incidence of venous thromboembolism during follow-up. We compared these measures with those for a modified and a simplified version of the decision rule. In the replication, the odds ratios in the logistic regression model were found to be lower for each of the seven individual variables (p=0.02) but the proportion of patients with PE in the probability categories in our study group were comparable to those in the original derivation and validation groups.The area under the ROC of the original, modified and simplified decision rule was similar: 0.74 (p=0.99; p=0.07).The venous thromboembolism incidence at three months in the group of patients with a Wells score ≤ 4 and a normal D-climer was 0.5%, versus 0.3% with a modified rule and 0.5% with a simplified rule.The proportion of patients safely excluded for PE was 32%, versus 31 % and 30%, respectively.This study further validates the diagnostic utility of the Wells rule and indicates that the scoring system can be simplified to one point for each variable.

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.

Identifying subfertile ovulatory women for timely tubal patency testing: A clinical decision rule based on medical history (Article)

2007-10-01T00:00:00Z

Background: The aim of tubal testing is to identify women with bilateral tubal pathology in a timely manner, so they can be treated with IVF or tubal surgery. At present, it is unclear for which women early tubal testing is indicated, and in whom it can be deferred. Methods: Data on 3716 women who underwent tubal patency testing as a part of their routine fertility workup were used to relate elements in their medical history to the presence of tubal pathology. With multivariable logistic regression, we constructed two diagnostic models. One in which tubal disease was defined as occlusion and/or severe adhesions of at least one tube, whereas in a second model, tubal disease was defined as the presence of bilateral abnormalities. Results: Both models discriminated moderately well between women with and women without tubal disease with an area under the receiver-operating characteristic curve (AUC) of 0.65 (95% CI: 0.63-0.68) for any tubal pathology and 0.68 (95% CI: 0.65-0.71) for bilateral tubal pathology, respectively. However, the models could make an almost perfect distinction between women with a high and a low probability of tubal pathology. A decision rule in the form of a simple diagnostic score chart was developed for application of the models in clinical practice. Conclusions: In conclusion, the present study provides two easy to use decision rules that can accurately express a woman's probability of (severe) tubal pathology at the couple's first consultation. They could be used to select women for tubal testing more efficiently.

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

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: A multicenter randomized trial (Stent-in 2 study) (Article)

2007-07-27T00:00:00Z

Background. Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. Methods/design. Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. Discussion. The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. Trial registration. Current Controlled Trials ISRCTN46462267.

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

Author response to: Improving the existing diagnostic strategy by accounting for characteristics of the women in the diagnostic work up for postmenopausal bleeding [2] (Article)

2007-05-01T00:00:00Z

Electrical stimulation and pelvic floor muscle training with biofeedback in patients with fecal incontinence: A cohort study of 281 patients (Article)

2007-04-01T00:00:00Z

Purpose: Pelvic floor rehabilitation is an appealing treatment for patients with fecal incontinence but reported results vary. This study was designed to assess the outcome of pelvic floor rehabilitation in a large series of consecutive patients with fecal incontinence caused by different etiologies. Methods: A total of 281 patients (252 females) were included. Data about medical history, anal manometry, rectal capacity measurement, and endoanal sonography were collected. Subgroups of patients were defined by anal sphincter complex integrity, and nature and possible underlying causes of fecal incontinence. Subsequently patients were referred for pelvic floor rehabilitation, comprising nine sessions of electric stimulation and pelvic floor muscle training with biofeedback. Pelvic floor rehabilitation outcome was documented with Vaizey score, anal manometry, and rectal capacity measurement findings. Results: Vaizey score improved from baseline in 143 of 239 patients (60 percent), remained unchanged in 56 patients (23 percent), and deteriorated in 40 patients (17 percent). Mean Vaizey score reduced with 3.2 points (p < 0.001). A Vaizey score reduction of ≥ 50 percent was observed in 32 patients (13 percent). Mean squeeze pressure (+5.1 mmHg; p = 0.04) and maximal tolerated volume (+11 ml; p = 0.01) improved from baseline. Resting pressure (p = 0.22), sensory threshold (p = 0.52), and urge sensation (p = 0.06) remained unchanged. Subgroup analyses did not show substantial differences in effects of pelvic floor rehabilitation between subgroups. Conclusions: Pelvic floor rehabilitation leads overall to a modest improvement in severity of fecal incontinence, squeeze pressure, and maximal tolerated volume. Only in a few patients, a substantial improvement of the baseline Vaizey score was observed. Further studies are needed to identify patients who most likely will benefit from pelvic floor rehabilitation.

Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial) (Article)

2007-03-22T00:00:00Z

Background. Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. Methods/design. Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). Discussion. The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor.

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.

Improving the existing diagnostic strategy by accounting for characteristics of the women in the diagnostic work up for postmenopausal bleeding (Article)

2007-01-01T00:00:00Z

Objectives: The aim of this study was to evaluate whether the efficiency of the current diagnostic work up following postmenopausal bleeding could be improved by diagnostic strategies that take into account characteristics of the women in addition to the currently recommended transvaginal measurement of endometrial thickness to determine for subsequent histological assessment. Design: Multicenter, prospective cohort study. Setting: A university hospital and seven teaching hospitals in the Netherlands. Sample: Consecutive women not using hormone replacement therapy, presenting with postmenopausal bleeding. Methods: Five hundred and forty women underwent transvaginal sonography, and in case of endometrial thickness (double layer) above 4 mm, subsequent endometrial sampling was performed. Presence of carcinoma was ruled out by the absence of abnormalities in histological specimen or by an uneventful follow up of at least 6 months. Main outcome measures: Probability of endometrial carcinoma was estimated by multivariable logistic regression models. For each diagnostic strategy, we calculated diagnostic accuracy (area under receiver operating characteristic curve [AUC]), negative predictive value (NPV) and the number of diagnostic procedures. Results: A strategy with transvaginal sonography alone with a fixed threshold incorrectly classified 0.7% of the women as nonmalignant (NPV: 99.3% [98.5-100%]), with 97% sensitivity and 56% specificity. A strategy integrating characteristics of the women with transvaginal sonography could result in less false reassurances (NPV: 99.6% [99.2-100%]), with only marginal decrease in diagnostic procedures, or a minor increase in false reassurances (NPV: 99.0% [98.3-100%]), with a substantial reduction (15-20%) in the procedures. AUCs associated with these strategies could improve from 0.76 (0.73-0.79) for transvaginal sonography alone to 0.90 (0.87-0.93) for the integrated strategy. Conclusion: Taking into account the characteristics of the women could increase the efficiency of the diagnostic work up for postmenopausal bleeding.

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.

Cardiologists' Use of clinical information for management decisions for patients with unstable angina: a policy analysis (Article)

1997-07-17T00:00:00Z

Previous studies of management of unstable angina have revealed substantial differences in management between different hospitals, especially with respect to the use of coronary angiography. Physicians in a hospital with angiography facilities were more inclined to perform angiography than were physicians in hospitals without these facilities, even when differences in patient populations were taken into account. The authors compared the management strategies of 18 cardiologists, working in hospitals with and without angiography facilities, using a series of paper-case summaries, in order to assess the contribution of individual variability between physicians to practice differences. Physicians who worked in a hospital with in-house angiography facilities were more inclined to request angiography in similar case summaries, but the inter-individual variation exceeded the between-hospital variation. The variation in individual policies with respect to the decision to initiate coronary angiography could be associated with differences in weighting clinical information. These results confirm that practice variations may have many causes: variability in patients' characteristics, variations in how physicians react to these, differences in the availability of services, and variability in thresholds for action.

Variation in the use of coronary angiography in patients with unstable angina is related to differences in patient population and availability of angiography facilities, without affecting prognosis (Article)

1996-01-01T00:00:00Z

OBJECTIVES: Examination of the difference in management strategies with respect to coronary angiography in patients with unstable angina pectoris, and the consequences of this difference on prognosis. DESIGN: Prospective registration of consecutive patients admitted to two different hospitals. SETTING: University and a large community hospital in Rotterdam, the Netherlands. SUBJECTS: Patients under 80 years, without recent (< 4 weeks) infarction or recent (< 6 months) coronary revascularization procedure, admitted for chest pain suspected to indicate unstable angina pectoris. MAIN OUTCOME MEASURES: Decision to initiate coronary angiography or to continue on medical treatment. At 6 months the occurrence of death and myocardial infarction was measured. RESULTS: Clinical variables associated with the decision to initiate angiography were young age, male gender, progression of angina, multiple pain episodes and use of beta-blocker or calcium antagonists before admission, abnormal ST-T segment on baseline ECG, recurrent pain in hospital, and ECG changes during pain. These associations did not differ between hospitals. Nevertheless, angiography was performed more often in the presence of angiography facilities (university hospital), independent of the variable case-mix. Survival and infarct-free survival were similar in both hospitals, 96% and 90% respectively. CONCLUSION: The difference in angiography rate for unstable angina can be explained in part by differences in patient population and hospital facilities, but no difference was observed in physicians' assessment of patient characteristics. The observed practice variation did not affect prognosis.

Angiographic risk factors of luminal narrowing after coronary balloon angioplasty using balloon measurements to reflect stretch and elastic recoil at the dilation site. The CARPORT Study Group (Article)

1992-01-01T00:00:00Z

Because many ongoing clinical restenosis prevention trials are using quantitative angiography to assess whether a drug is capable of reducing the amount of intimal hyperplasia, quantitative angiographic risk factors for angiographic luminal narrowing after balloon angioplasty were determined, including stretch and elastic recoil at the dilatation site. Quantitative analysis was performed on 666 lesions in 575 patients during angioplasty and at 6-month follow-up. Stretch was defined as balloon diameter minus minimal luminal diameter (MLD) before angioplasty/reference diameter, and recoil as balloon diameter minus MLD after angioplasty/reference diameter. Multivariate analysis was used to yield independent risk factors for luminal narrowing at follow-up. Predictors of absolute change in MLD were (1) relative gain at angioplasty (gain in millimeters normalized for reference diameter) and (2) lesion length. To allow risk stratification, logistic regression analysis was applied using the decrease in MLD as a binary outcome variable. A decrease in MLD at follow-up of greater than or equal to 0.72 mm was considered significant. Variables retained in the model were: relative gain greater than 0.3 mm (rate ratio 2.9), relative gain 0.2 to 0.3 (rate ratio 2.1), stenosis length greater than or equal to 6.8 (rate ratio 1.7), and thrombus after angioplasty (rate ratio 2.6). Although stretch was significantly related to luminal narrowing at univariate analysis, it was not retained in the multivariate models. A large gain in lumen diameter at angioplasty, dilation of long lesions, and angiographically determined thrombus after angioplasty were found to be accompanied by more severe luminal narrowing at follow-up.