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Rationale & Objective: Although multiple lines of evidence suggest a negative impact of secondary hyperparathyroidism on patients with kidney failure treated by hemodialysis, it is uncertain whether patients can detect associated symptoms. The objective was to determine whether changes in parathyroid hormone (PTH) levels are associated with changes in symptoms within this patient population., Study Design: Prospective cohort., Setting & Participants: 165 adults with hyperparathyroidism secondary to kidney failure diagnosed, a range of dialysis vintages, and receiving regular hemodialysis from a US single-provider organization., Exposure: Change in PTH levels over 24 weeks., Outcomes: 19 putative symptoms of secondary hyperparathyroidism measured up to 4 times using a self-administered questionnaire that assessed severity on a 5-level ordinal scale., Analytical Approach: Longitudinal associations between changes in PTH levels and symptom severity were assessed using generalized additive models., Results: The 165 participants studied represented 81% of enrollees (N=204) who had sufficiently complete data for analysis. Mean age was 56 years and 54% were women. Increases in PTH levels over time were associated (P<0.1) with worsening of bone aches and stiffness, joint aches, muscle soreness, overall pain, itchy skin, and tiredness, and the effects were more pronounced with larger changes in PTH levels., Limitations: Findings may have been influenced by confounding by unmeasured comorbid conditions, concomitant medications, and multiple testing coupled with a P value threshold of 0.10., Conclusions: In this exploratory study, we observed that among patients with secondary hyperparathyroidism, increases in PTH levels over time were associated with worsening of 1 or more cluster of symptoms. Replication of these findings in other populations is needed before concluding about the magnitude and shape of these associations. If replicated, these findings could inform clinically useful approaches for measuring patient-reported outcomes related to secondary hyperparathyroidism., (Published by Elsevier Inc.)

Objectives: Non-randomised clinical trial designs involving comparisons against external controls or specific standards can be used to support regulatory submissions for indications in diseases that are rare, with high unmet need, without approved therapies and/or where placebo is considered unethical. The objective of this review was to summarise the characteristics of non-randomised trials submitted to the European Medicines Agency (EMA) or Food and Drug Administration (FDA) for indications in haematological cancers, haematological non-malignant conditions, stem cell transplants or rare metabolic diseases., Methods: We conducted systematic searches of EMA databases of conditional approvals, exceptional circumstances, or orphan drug designations and FDA inventories of orphan drug designations, accelerated approvals, breakthrough therapy, fast-track and priority approvals. Products were included if reviewed by at least one agency between 2005 and 2017, the primary evidence base was non-randomised trial(s) and the indication was for haematological cancers, stem cell transplantation, haematological conditions or rare metabolic conditions., Results: We identified 43 eligible indication-specific products using non-randomised study designs involving comparisons with external controls, submitted to the EMA (n=34) and/or FDA (n=41). Of the 43 indication-specific products, 4 involved matching external controls to the population of a non-randomised interventional study using individual patient-level data (IPD), 12 referred to external controls without IPD and 27 did not explicitly reference external controls. The FDA approved 98% of submissions, with 56% accelerated approvals; most required postapproval confirmatory randomised controlled trials (RCT). The EMA approved 79% of submissions, with a quarter of approvals conditional on completion of a postapproval RCT or additional non-randomised trials., Conclusions: There has been a large increase in submissions to the EMA and FDA using non-randomised study designs involving comparisons with external controls in recent years. This study demonstrated that regulators may be willing to approve such submissions, although approvals are often conditional on further confirmatory evidence from postapproval studies., Competing Interests: Competing interests: AT is an employee of Takeda. EEK, TJJL and KM are employees of ICON, a CRO that was paid by Takeda to perform this study and to draft this manuscript. SG was an employee and is a consultant for ICON. ARL is a consultant for ICON. NF has received funding for research, travel or consultation from Sanofi Aventis, Takeda, Allegan, Biopharma, Ipsen, Servier, Pfizer and Novo Nordisk., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The Patient Protection and Affordable Care Act of 2010 (ACA) will increase insurance coverage for US citizens and for breast and cervical cancer screening through insurance expansions and regulatory changes. The primary objective of this study was to estimate the number of low-income women who would gain health insurance after implementation of the ACA and thus be able to obtain cancer screening. A secondary objective was to estimate the size and characteristics of the uninsured low-income population and the number of women who would still need National Breast and Cervical Cancer Early Detection Program (NBCCEDP) services., Methods: We used the nationally representative 2009 American Community Survey to estimate the determinants of insurance status for women in Massachusetts, assuming full implementation of the ACA. We extrapolated findings to simulate the effects of the ACA on each state. We used individual-level predicted probabilities of being uninsured to generate estimates of the number of women who would gain health insurance after implementation of the ACA and to predict demand for NBCCEDP services., Results: Approximately 6.8 million low-income women would gain health insurance, potentially increasing the annual demand for NBCCEDP cancer screenings initially by about 500,000 mammograms and 1.3 million Papanicolaou tests. Despite a 60% decrease in the number of low-income uninsured women, the NBCCEDP would still serve fewer than one-third of the estimated number of women eligible for services. The NBCCEDP-eligible population would comprise a larger number of women with language and literacy-related barriers to care., Conclusion: Implementation of the ACA would increase insurance coverage and access to cancer screening for millions of women, but the NBCCEDP will remain essential for the millions who will remain uninsured.

Objectives: Administering proton pump inhibitors (PPI) intravenously (iv) after endoscopic treatment of bleeding peptic ulcers reduces the incidence of rebleeding, the need for operative procedures, and hospitalizations. We assessed the cost implications of iv PPI initiated in all patients presenting to the emergency department (ED) with signs of upper gastrointestinal (UGI) bleeding., Methods: From a third-party payer perspective with a time horizon of 60 days, we built a decision analytic model comparing standard endoscopic therapy to a strategy in which all patients presenting to the ED with UGI bleeding would start iv PPI before endoscopy. After endoscopy, only those with peptic ulcers would be kept on iv PPI added to standard therapy. Probabilities of health events were extracted from published literature. Resource utilization profiles and costs (iv PPI, hospital stay for medical and operative procedures, and professional fees) were based on Medicare reimbursement data from a large hospital in Alabama. All costs were expressed in 2000 US dollars. Uncertainty was investigated through one-way sensitivity analyses and probabilistic analyses using Monte Carlo simulations., Results: In a hypothetical group of 1000 individuals, routine use of iv PPI prevented 40 rebleeds, 9 surgical procedures, and 223 hospital days, and led to incremental savings of dollars 920 per subject. Probabilistic sensitivity analyses indicated that the strategy of using iv PPI was likely to be dominant even when accounting for uncertainty., Conclusions: Based on available evidence, routine administration of iv PPI to all persons presenting with UGI bleeding represents good value for money and merits consideration as standard hospital policy.