Kruijshaar, M.E.

Enzyme replacement therapy and fatigue in adults with Pompe disease (Article)

2013-04-19T00:00:00Z

Background: Pompe disease is a hereditary metabolic myopathy, for which enzyme replacement therapy (ERT) has been available since 2006. We investigated whether ERT reduces fatigue in adult patients with Pompe disease. Methods: In this prospective international observational survey, we used the Fatigue Severity Scale (FSS) to measure fatigue. Repeated measures ANOVA was used to analyze the data over time. In a subgroup of patients, we also evaluated muscle strength using the Medical Research Council Scale, measured pulmonary function as Forced Vital Capacity, and assessed depression using the Hospital Anxiety and Depression Scale. Results: We followed 163 patients for a median period of 4 years before ERT and for 3 years during ERT. Before ERT, the mean FSS score remained stable at around 5.3 score points; during ERT, scores improved significantly by 0.13 score points per year (p < 0.001). Fatigue decreased mainly in women, in older patients and in those with shorter disease duration. Patients' improvements in fatigue were moderately correlated with the effect of ERT on depression (r 0.55; CI 95% 0.07 to 0.70) but not with the effect of ERT on muscle strength or pulmonary function. Conclusions: Fatigue is a common and disabling problem in patients with early and advanced stages of Pompe disease. Our finding that ERT helps to reduce fatigue is therefore important for this patient population, irrespective of the mechanisms underlying this effect.

Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: An open-label single-center study (Article)

2012-09-28T00:00:00Z

Abstract. Background: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods. Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3-6 months and analyzed using repeated-measures ANOVA. Results: Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (-1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness.Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC. Conclusions: We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.

Physiotherapy management in late-onset Pompe disease: Clinical practice in 88 patients (Article)

2012-09-01T00:00:00Z

Pompe disease is an inherited metabolic, neuromuscular disorder. With the introduction of enzyme replacement therapy skeletal muscle and respiratory function can be stabilized or improved. Additional physiotherapy to advance physical functioning of patients might be beneficial, but evidence and guidelines are lacking. In order to get an insight into current practices of referral and treatment, and perceived benefit, we performed a survey among 88 Dutch adult Pompe patients and 31 physiotherapists. Sixty percent of patients were ever referred for physiotherapy, whereas currently less than 40% receive physiotherapy. Approximately 50% of patients were referred for loss of muscle strength; while 74% received muscle strengthening exercises, often combined with aerobic endurance training. In 47% of patients the intervention did not match the referral reason. More than two-thirds of patients and physiotherapists perceived physiotherapy as beneficial, and the majority highlighted the need for guidance. Physiotherapeutic care can be improved by tailoring interventions to referral reasons and treatment objectives. More high quality studies are urgently needed to assess which interventions are most useful in this patient group.

A labelled discrete choice experiment adds realism to the choices presented: preferences for surveillance tests for Barrett esophagus. (Article)

2009-07-02T00:00:00Z

BACKGROUND: Discrete choice experiments (DCEs) allow systematic assessment of preferences by asking respondents to choose between scenarios. We conducted a labelled discrete choice experiment with realistic choices to investigate patients' trade-offs between the expected health gains and the burden of testing in surveillance of Barrett esophagus (BE). METHODS: Fifteen choice scenarios were selected based on 2 attributes: 1) type of test (endoscopy and two less burdensome fictitious tests), 2) frequency of surveillance. Each test-frequency combination was associated with its own realistic decrease in risk of dying from esophageal adenocarcinoma. A conditional logit model was fitted. RESULTS: Of 297 eligible patients (155 BE and 142 with non-specific upper GI symptoms), 247 completed the questionnaire (84%). Patients preferred surveillance to no surveillance. Current surveillance schemes of once every 1-2 years were amongst the most preferred alternatives. Higher health gains were preferred over those with lower health gains, except when test frequencies exceeded once a year. For similar health gains, patients preferred video-capsule over saliva swab and least preferred endoscopy. CONCLUSION: This first example of a labelled DCE using realistic scenarios in a healthcare context shows that such experiments are feasible. A comparison of labelled and unlabelled designs taking into account setting and research question is recommended.

Different perceptions of the burden of upper GI endoscopy: An empirical study in three patient groups (Article)

2007-10-01T00:00:00Z

Background: Few studies have evaluated patients' perceived burden of cancer surveillance tests. Cancer screening and surveillance, however, require a large number of patients to undergo potentially burdensome tests with only some experiencing health gains from it. We investigated the determinants of patients' reported burden of upper gastrointestinal (GI) endoscopy by comparing data from three patient groups. Patients and methods: A total of 476 patients were included: 180 patients under regular surveillance for Barrett esophagus (BE), a premalignant disorder; 214 patients with non-specific upper GI symptoms (NS), and 82 patients recently diagnosed with upper GI cancer (CA). We assessed pain, discomfort and overall burden experienced during endoscopy, symptoms in the week afterwards and psychological distress over time (Hospital Anxiety and Depression scale and Impact of Event Scale). Results: Two-thirds (66%) of patients reported discomfort and overall burden of upper GI endoscopy. Only 23% reported any pain. BE patients reported significantly less discomfort, pain and overall burden than the other patients: those with NS reported more discomfort, CA patients more pain, and both more overall burden. These differences could be statistically explained by the number of previous endoscopies and whether sedation was provided or not, but not by patient characteristics. Conclusion: The perception of upper GI endoscopy varies by patient group, due to potential adaptation after multiple endoscopies and aspects of the procedure.

Evidence-based guidelines, time-based health outcomes, and the Matthew effect (Article)

2007-09-01T00:00:00Z

Background: Cardiovascular risk management guidelines are 'risk based'; health economists' practice is 'time based'. The 'medical' risk-based allocation model maximises numbers of deaths prevented by targeting subjects at high risk, for example, elderly and smokers. The time-based model maximises numbers of life years gained by treating the young and non-smokers, or 'the one who has will be given more' (Matthew 25:29). We explored practical consequences of risk- or time-based allocation. Methods: We used epidemiological modelling to generate semi-quantitative scenarios comparing the distributional effects of allocating a fixed number of prescriptions of a (hypothetical) preventive cardiovascular drug ('CVStop') either to avert the maximum number of deaths (risk-based) or to save the maximum number of life years (time based) in the male Dutch population. We subsequently asked 123 Dutch guideline developers which distribution they preferred. Results: Time- and risk-based allocations resulted in different distributions of the drug across the population. There were also differences in absolute numbers of life years gained and deaths averted, and in the distribution of these across the population. For example, risk-based allocation of 'CVStop' resulted in preferential treatment of elderly, leading to more deaths averted (mostly among 70 and above) but fewer life years gained, if compared with time-based allocation. The guideline developers experienced the choice dilemmas as difficult. No priority choice was dominant among the respondents. Conclusion: In evidence-based resource allocation the choice to save time or to avert deaths may introduce moral choices because of the various origins of increased disease risk. Evidence-based guideline development inevitably has moral implications.

Modelling a population with Barrett's oesophagus from oesophageal adenocarcinoma incidence data (Article)

2007-02-28T00:00:00Z

Objective. A recent study of adenocarcinoma of the oesophagus (ACO) incidence rates in Denmark showed a steep fall in the over-80 population, interpreted as the result of a decline in the prevalence of Barrett's oesophagus (BO) in this age group, for which three hypotheses were advanced: the specific mortality from ACO and, superimposed, either excess mortality from causes of death unrelated to ACO or a birth cohort effect. The aim of this study was to create models estimating the BO population fitting each of these three hypotheses, in order to select the most plausible hypothesis and to gain insight into the Danish BO population. Material and methods. Models were designed for these three hypotheses, conforming to the generally accepted 0.4-0.5% annual ACO incidence in BO patients. These models employed expectation-maximization (EM) algorithms, Danish life tables and the observed ACO incidence rates. The models enabled the estimation of a BO population for each hypothesis. Results. After testing against set criteria, the most plausible model was found to be that describing a birth cohort effect which predicted a ±5% annual rise in the prevalence of BO and, consequently, in the incidence rate of ACO in Denmark. This prediction was borne out over the subsequent decade. Conclusions. This rising ACO incidence rate is likely to continue into the foreseeable future. The use of EM algorithms enabled a first estimate of the BO population at risk of ACO, although, owing to the limitations imposed by the models, the age- and gender-specific ACO risk for the entire Danish BO population could not as yet be ascertained.

Patients with Barrett's esophagus perceive their risk of developing esophageal adenocarcinoma as low (Article)

2007-01-01T00:00:00Z

Background: The risk of developing esophageal adenocarcinoma (EAC) for patients with Barrett's esophagus (BE) is approximately 0.5% per year. Objective: To investigate how patients with BE estimate and perceive their risk of developing EAC. Design: Questionnaire study. Setting: Patients with BE who were undergoing surveillance endoscopy based on histologic and flow cytometric results. Patients: A total of 192 patients with BE were included. Main Outcome Measurements: Individual patients were asked to estimate the numerical risk to develop EAC for patients with BE in general and for themselves. How patients perceived their own risk was measured on a scale from "very small" to "very large.". Results: At least 1 question was filled out by 169 patients (88% response). Sixty percent of respondents underestimated the numerical risk for patients with BE, in general, to develop EAC, while even more patients (69%) underestimated their own risk. Most respondents perceived their own risk as very small or small (63%). Limitations: Risk estimations may depend on the response scale used. Conclusions: Most patients with BE underestimated the numerical risk and perceived their risk of developing EAC as (very) low. Despite a low perceived risk, all patients in this group adhered to endoscopic surveillance.

Estimating the prevalence of breast cancer using a disease model: data problems and trends (Article)

2003-01-01T00:00:00Z

BACKGROUND: Health policy and planning depend on quantitative data of disease epidemiology. However, empirical data are often incomplete or are of questionable validity. Disease models describing the relationship between incidence, prevalence and mortality are used to detect data problems or supplement missing data. Because time trends in the data affect their outcome, we compared the extent to which trends and known data problems affected model outcome for breast cancer. METHODS: We calculated breast cancer prevalence from Dutch incidence and mortality data (the Netherlands Cancer Registry and Statistics Netherlands) and compared this to regionally available prevalence data (Eindhoven Cancer Registry, IKZ). Subsequently, we recalculated the model adjusting for 1) limitations of the prevalence data, 2) a trend in incidence, 3) secondary primaries, and 4) excess mortality due to non-breast cancer deaths. RESULTS: There was a large discrepancy between calculated and IKZ prevalence, which could be explained for 60% by the limitations of the prevalence data plus the trend in incidence. Secondary primaries and excess mortality had relatively small effects only (explaining 17% and 6%, respectively), leaving a smaller part of the difference unexplained. CONCLUSION: IPM models can be useful both for checking data inconsistencies and for supplementing incomplete data, but their results should be interpreted with caution. Unknown data problems and trends may affect the outcome and in the absence of additional data, expert opinion is the only available judge.