Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis.

OBJECTIVE: To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. DESIGN: Model based on a population-based cohort study. SETTING: The Swedish health service. POPULATION: Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099). METHODS: Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. MAIN OUTCOME MEASURE: Additional cost per RhD immunisation averted. RESULTS: Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. CONCLUSION: Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. TWEETABLE ABSTRACT: Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP.

The combined effects of overweight and smoking in late adolescence on subsequent disability pension: a nationwide cohort study.

BACKGROUND: Smoking and obesity are two of the most important risk factors for chronic disease today. Their combined effect on the risk of disability pension is not known. METHODS: A nationwide cohort of 45 920 Swedish men (18.7 + or - 0.5 years) were followed for 38 years. The body mass index (BMI), based on measured height and weight, was used to define underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9) and obesity (> or = 30.0). The hazard ratios (HRs) associated with BMI and smoking status at baseline for receiving disability pension were adjusted for socio-economic index (SEI), muscular strength, geographic region and place of residence. RESULTS: During 1.6 million person-years, 4631 disability pensions and 2897 deaths occurred. After adjustment, overweight (HR 1.34, 95% CI 1.19-1.51) and obesity (HR 1.55, 1.18-2.05) were associated with an increased risk of disability pension, independent of smoking, whereas underweight (18.5; HR 1.07, 0.97-1.17) was not compared with normal weight. Similarly, smoking 1-10 (HR 1.37, 1.27-1.49) or >10 cigarettes per day (HR 2.01, 1.86-2.17) showed independent risk increases versus non-smoking. Although obese individuals smoking >10 daily cigarettes were at greatly increased risk (HR 2.98, 1.98-4.47), no evidence of interaction between the two risk factors could be detected. CONCLUSIONS: Both increased adiposity and smoking are strong and independent predictors of disability pension, but they do not act synergistically.

Long-term changes in blood pressure following orlistat and sibutramine treatment: a meta-analysis.

Previous meta-analyses investigating blood pressure effects of anti-obesity drugs have included studies using non-licensed doses, but not data from head-to-head studies. Furthermore, although diabetes is an important comorbidity in obesity, variation in blood pressure effects across diabetes status has not been investigated. The objective of this study was to estimate the effects on systolic (SBP) and diastolic blood pressure (DBP) of orlistat and sibutramine. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles from 1990 to February 2009 were searched. All placebo-controlled randomized controlled trials of 12-month duration or randomized head-to-head studies of any duration on adults using standard doses were included. Studies/study arms were excluded if they only evaluated weight maintenance after weight loss. Randomized controlled trials were identified, subjected to inclusion and exclusion criteria, and reviewed. Random effects models were used for assessment of weighted mean differences. Eighteen placebo-controlled (12 orlistat, 5540 patients; 6 sibutramine, 1495 patients) and four head-to-head trials (348 patients) met the inclusion criteria. Three orlistat and three sibutramine studies examined overweight subjects with type 2 diabetes (T2DM), as did two head-to-head trials. Mean baseline SBP ranged from 119 to 153 mmHg, and mean DBP from 69 to 98 mmHg. Overall, the placebo-controlled SBP change was -1.9 (95% CI; -2.7, -1.1) mmHg for orlistat, and 0.5 (-1.1, 2.1) mmHg for sibutramine. The corresponding values for DBP were -1.5 (-2.2, -0.8) and 1.7 (0.7, 2.6). Compared with patients without diabetes, diabetic patients treated with orlistat experienced smaller and non-significant reductions of SBP (-0.9; -2.6, 0.7 vs. -2.2; -3.0, -1.3) and DBP (-1.0; -2.4, 0.3 vs. -1.6; -2.4, -0.8). For sibutramine, higher on-treatment elevations in SBP (1.6; -1.3, 4.5 vs. 0.1; -1.8, 2.0) and DBP (2.4; 0.6, 4.1 vs. 1.4; 0.3, 2.5) were seen in patients with vs. without diabetes. In head-to-head trials, the overall differences between sibutramine and orlistat were small and non-significant for both SBP (1.0; -2.3, 4.3) and DBP (-0.2; -2.9, 2.5). In conclusion, in the studies using approved sibutramine doses, the drug caused significant elevations in DBP, while the overall SBP effect was near null. Moreover, absence of a blood pressure-lowering effect of orlistat ad a higher DBP elevation by sibutramine were observed for persons with diabetes. Head-to-head studies indicated that an indirect comparison of placebo-adjusted blood pressure effects may overestimate the adverse effects associated with sibutramine, but these studies were small, of shorter duration and of lower quality.

Discontinuation due to adverse events in randomized trials of orlistat, sibutramine and rimonabant: a meta-analysis.

The objective of this article was to estimate the risk of discontinuation due to adverse events in trials of orlistat, sibutramine and rimonabant. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles were searched from 1990 to May 2008. All randomized placebo-controlled trials of 12-24 months of duration on adults using licensed doses were included. Studies/study arms were excluded if they evaluated weight maintenance after weight loss. Trials were identified, subjected to inclusion and exclusion criteria and reviewed. Data on participants, interventions and discontinuation were extracted and trials rated for quality based on established criteria. A random effects model was used to estimate pooled risk ratios, risk differences and number needed to harm (NNH). A total of 28 trials met the inclusion criteria (16 orlistat, 7 sibutramine and 5 rimonabant). The risk ratios for discontinuation due to adverse events were significantly elevated for rimonabant (2.00; 1.66-2.41) and orlistat (1.59; 1.21-2.08), but not sibutramine (0.98, 0.68-1.41). Compared with placebo, the risk difference was the largest for rimonabant (7%, 5-9%; NNH 14, 11-19), followed by orlistat (3%, 1-4%; NNH 39, 25-83), while no significant difference was seen for sibutramine (0.2%, -3 to 4%; NNH 500). The most common adverse events leading to withdrawal were gastrointestinal for orlistat (40%) and psychiatric for rimonabant (47%). Corresponding information was unavailable for sibutramine. In conclusion, available weight loss drugs differ markedly regarding risk of discontinuation due to adverse events, as well as in underlying causes of these events. Given the large number of patients eligible for treatment, the low NNH for rimonabant is a concern.

Obesity status and sick leave: a systematic review.

This review identified 36 studies on the relation between obesity status and sick leave. Pooling of effect estimates was not possible due to great heterogeneity between studies regarding definition of sick leave (short-term/long-term), measure of obesity (body mass index/waist circumference/percentage body fat), definition of obesity status (World Health Organization standards/other), study population (sex/age/occupation/country) and exposure and outcome ascertainment (self-reported/objectively assessed). Nevertheless, a clear trend towards greater sick leave among obese compared with normal weight workers could be discerned, especially for spells of longer duration. In studies from the USA, which consistently reported about five times lower number of sick leave days per person-year than European, obese workers had about 1-3 extra days of absence per person-year compared with their normal weight counterparts. In European studies, the corresponding difference was about 10 d. For overweight workers the data were conflicting, indicating either increased or neutral level of sick leave compared with normal weight. Regarding underweight, the studies were very few and concerns regarding direction of causality were greater. Finally, in all four interventional studies identified substantial weight loss in obese subjects resulted in reduced sick leave, at least temporarily. In conclusion, increasing obesity in children and adults is likely to negatively affect future productivity as obesity increases the risk of sick leave, disability pension and death.

Disability pension, employment and obesity status: a systematic review.

Disability pensions incur huge societal costs in many countries. In Sweden, the three greatest drivers of such productivity losses are musculo-skeletal, circulatory and psychiatric disorders, all closely associated with weight status. We identified 16 studies investigating the body mass index (BMI)-disability pension relation. In cross-sectional studies, a significantly greater proportion of obese compared with normal weight subjects were disability pensioners. In longitudinal studies, a J-shaped relation with BMI was generally found in both men and women of various ages. Different definitions of obesity status complicated interpretation, as several studies mixed the underweight and normal weight, which appear to have different disability pension risks. In middle-aged men, relative risks were elevated for circulatory causes only for the overweight and obese, while associations for mental disorders were similar in the underweight and overweight but much higher in the obese. In both sexes, monotonic increases and decreases were seen for circulatory and respiratory causes respectively. In intervention studies, reduced disability pension incidence and increased gainful employment were reported after surgery. In summary, BMI was significantly associated with disability pension, but the direction of causality may vary with underlying cause. Interventions had positive productivity effects in the morbidly obese, but whether this holds for the overweight remains to be proven.