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Sequential multiple assignment randomized trial designs tailor individual treatment by rerandomizing participants to subsequent therapies based on their response to initial treatment. Misclassification of participant responses to initial treatment can lead to inappropriate treatment assignment and thus impact the final outcome. The aim of this study is to derive a series of formulas for quantifying potential misclassification effects on the mean, variance, and statistical inference of a single sequential treatment (SST) effect with continuous outcome. Relative bias is expressed as a function of sensitivity, specificity, and the probability of being true responders. Results show that misclassification can introduce bias to the estimated treatment effect. Though the magnitude of bias varies, there are a few general conclusions: (1) for any fixed sensitivity (or specificity) the relative bias of the mean of responders (or nonresponders) always approaches 0 in a monotonic nonlinear pattern as specificity (or sensitivity) increases; (2) the relative bias of SST variance always has nonmonotone nonlinear relationship with sensitivity or specificity; (3) the SST variance under misclassification is always over-estimated. Furthermore, the results show that misclassification can affect statistical inference, with power exhibiting either monotonic or nonmonotonic patterns and resulting in either under- or over-estimation. [ABSTRACT FROM AUTHOR]

Summary: Hydroxyurea (hydroxycarbamide) (HU) for sickle cell anaemia (SCA) is underutilised. Case management is an evidence‐based health management strategy and in this regard patient navigators (PNs) may provide case management for SCA. We hypothesised that HU‐eligible patients exposed to PNs would have improved indicators of starting HU and HU adherence. We randomised 224 HU‐eligible SCA adults into the Start Healing in Patients with Hydroxyurea (SHIP‐HU) Trial. All patients received care from trained physicians using standardised HU prescribing protocols. Patients in the Experimental arm received case management and education from PNs through multiple contacts. All other patients were regarded as the Control arm and received specialty care alone. Study physicians were blinded to the study arms and did not interact with PNs. At baseline, 6 and 12 months we assessed and compared laboratory parameters and HU adherence indicators. Experimental patients had higher 6‐month mean fetal haemoglobin (HbF) levels than controls. But at 12 months, mean HbF was similar, as were white blood cell count, absolute neutrophil count, total haemoglobin, platelet count and mean corpuscular volume. At 12 months there were fewer experimental patients missing HU doses than controls (mean 1·8 vs. 4·5, P = 0·0098), and more recent HU prescriptions filled than for controls (mean 53·8 vs. 92 days, median 27·5 vs. 62 days, P = 0·0082). Mean HU doses were largely similar. We detected behavioural improvements in HU adherence but no haematological improvements by adding PNs to specialty care. [ABSTRACT FROM AUTHOR]

Almost two out of five women over the age of 60 suffer from urinary incontinence (UI), and many of these women also have the need to urinate frequently at night. The medical, social, and psychological consequences of bladder incontinence are difficult to cope with, and the economic consequences have been estimated to reach seven billion dollars a year. A 'bladder discipline' or 'bladder drill' program was developed twenty-five years ago, and has been used primarily for women with uninhibited bladder contractions (detrusor instability, or DI), which affects 10 to 20 percent of women who are incontinent. Cure rates for women with DI range from 44 percent to 100 percent, but controlled trials are few. This study of 123 women over 55 included those with urethral sphincter incompetence (SI) as well. Women with SI were generally excluded from other studies because this was considered an anatomical condition. Bladder training reduced the number of UI episodes, the amount of fluid lost, and frequency of urination both during the day and at night. For 12 percent of the women there were no UI episodes, and there was a 50 percent improvement in 75 percent of the women. Other studies report a cure rate of 44 percent to 78 percent, but their methods of patient selection are not known. Other therapies report significant cure rates as well. Bladder training significantly reduced all the adverse outcomes, and was dependent on the severity of the symptoms at the beginning of the study. Surprisingly, outcomes were the same for women with SI and with DI, indicating that these conditions may not be independent. Bladder training has no adverse consequences, and should be considered before surgery and drug therapy, both of which have significant risks and side effects. (Consumer Summary produced by Reliance Medical Information, Inc.)

Abstract Background Sickle cell disease (SCD) is a chronic disease associated with high degrees of morbidity and increased mortality. Health-related quality of life (HRQOL) among adults with sickle cell disease has not been widely reported. Methods We administered the Medical Outcomes Study 36-item Short-Form to 308 patients in the Pain in Sickle Cell Epidemiology Study (PiSCES) to assess HRQOL. Scales included physical function, physical and emotional role function, bodily pain, vitality, social function, mental health, and general health. We compared scores with national norms using t-tests, and with three chronic disease cohorts: asthma, cystic fibrosis and hemodialysis patients using analysis of variance and Dunnett's test for comparison with a control. We also assessed whether SCD specific variables (genotype, pain, crisis and utilization) were independently predictive of SF-36 subscales, controlling for socio-demographic variables using regression. Results Patients with SCD scored significantly worse than national norms on all subscales except mental health. Patients with SCD had lower HRQOL than cystic fibrosis patients except for mental health. Scores were similar for physical function, role function and mental health as compared to asthma patients, but worse for bodily pain, vitality, social function and general health subscales. Compared to dialysis patients, sickle cell disease patients scored similarly on physical role and emotional role function, social functioning and mental health, worse on bodily pain, general health and vitality and better on physical functioning. Surprisingly, genotype did not influence HRQOL except for vitality. However, scores significantly decreased as pain levels increased. Conclusion SCD patients experience health related quality of life worse than the general population, and in general, their scores were most similar to patients undergoing hemodialysis. Practitioners should regard their HRQOL as severely compromised. Interventions in SCD should consider improvements in health related quality of life as important outcomes.