Factors associated with continuity of care in hypertension and type 2 diabetes among forcibly displaced persons in the Bidibidi refugee settlement in Uganda: Protocol for a cross-sectional, mixed-methods study.

BACKGROUND: Non-communicable diseases in humanitarian settings are generally under-researched, particularly in Africa and have been called a neglected crisis. Little is known about factors affecting access to and (dis)continuity of care for chronic conditions, such as hypertension (HTN) and type 2 diabetes among forcibly displaced persons (FDPs) in Uganda. AIM: To investigate factors affecting access to and (dis)continuity of HTN and/or type 2 diabetes care among FDPs in the Bidibidi refugee settlement, Uganda. METHODS: A sequential explanatory mixed-methods design incorporating methodological and investigator triangulation will be conducted. The study aims to employ a community-based participatory research approach to equitably engage community members, researchers, and other stakeholders in the research process, recognising and maximising their diverse contributions. In phase 1, the quantitative arm of the study, 960 FDPs with HTN and/or type 2 diabetes will be interviewed about their sociodemographic characteristics, health status, migration experiences, social capital, and awareness, treatment, and control of these diseases. Participants will be purposively recruited from phase 1 as well as village health teams, healthcare providers, and policymakers to participate in phase 2, the qualitative study, in order to gain more insight into how mobility and social factors affect (dis)continuity of care among FDPs with HTN and/or type 2 diabetes. DISCUSSION: The findings from phase 1 and phase 2 of the study will be integrated through a triangulation process to provide a more holistic and comprehensive insight into the factors affecting access to and (dis)continuity for HTN and/or type 2 diabetes care among FDPs. Understanding these factors is expected to pave the way for conceptualizing health-enabling environments and strengthening health systems for FDPs with chronic conditions. It is anticipated that the study will generate baseline evidence that might be beneficial in developing and implementing HTN and diabetes care models for FDPs in the region.

Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study.

OBJECTIVES: To investigate the regulatory handling of cancer drugs that were granted accelerated approval by the US Food and Drug Administration (FDA) but failed to improve the primary endpoint in post-approval trials and to evaluate the extent to which negative post-approval trials changed the recommendations in treatment guidelines. DESIGN: Retrospective observational study. SETTING: FDA and National Comprehensive Cancer Network (NCCN) reports. INCLUDED DRUGS: Cancer drugs that received accelerated approval from the FDA and had negative post-approval trials. MAIN OUTCOME MEASURES: Regulatory outcomes, including withdrawal, conversion to regular approval, and no action. RESULTS: 18 indications for 10 cancer drugs that received accelerated approval but failed to improve the primary endpoint in post-approval trials were identified. Of these, 11 (61%) were voluntarily withdrawn by the manufacturer and one (bevacizumab for breast cancer) was revoked by the FDA. Of the 11 withdrawals, six occurred in 2021 alone. The remaining six (33%) indications remain on the label. The NCCN guidelines provide a high level of endorsement (category 1 endorsement for one and category 2A endorsement for seven) for accelerated approval drugs that have failed post-approval trials, sometimes even after the approval has been withdrawn or revoked. CONCLUSION: Cancer drug indications that received accelerated approval often remained on formal FDA approved drug labelling and continued to be recommended in clinical guidelines several years after statutorily required post-approval trials showed no improvement in the primary efficacy endpoint. Clinical guidelines should better align with the results of post-approval trials of cancer drugs that received accelerated approval.

Association between age and sex and mortality after adjuvant therapy for renal cancer.

BACKGROUND: In phase 3 trials of patients with resected high-risk renal cell carcinoma, adjuvant sunitinib has demonstrated no overall survival (OS) benefit, an uncertain disease-free survival (DFS) benefit, and increased toxicity versus placebo. To identify patients who may derive benefit or harm from adjuvant therapy, the authors assessed the effects of age and sex on treatment outcomes in the phase 3 Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Cancer (ASSURE) trial. METHODS: The authors conducted a post hoc subgroup analysis of age and sex among patients in the ASSURE trial. Adjusted hazard ratios (HRs) for OS and DFS were evaluated with sunitinib or sorafenib versus placebo in 4 patient subgroups defined by sex and median age at the time of the study. RESULTS: Sunitinib treatment was associated with decreased OS (HR, 2.21; 95% confidence interval, 1.29-3.80) among women aged >56 years, but not in women aged ≤56 years or men of any age. Similar associations with age and sex were observed for DFS, but these were not statistically significant (women aged >56 years: HR, 1.41 [95% confidence interval, 0.94-2.10]). No such association was found for sorafenib. The interaction by age and sex on mortality was found to be statistically significant for sunitinib (P = .01), but not sorafenib (P = .10). CONCLUSIONS: Adjuvant sunitinib may increase mortality among older women with renal cell carcinoma. Given the recent approval of adjuvant sunitinib for patients with high-risk resected renal cell carcinoma, additional studies are needed to confirm these findings.

Affordability and Price Increases of New Cancer Drugs in Clinical Guidelines, 2007-2016.

In response to the rising cost of cancer drugs, the National Comprehensive Cancer Network (NCCN) recently developed a value framework, known as "Evidence Blocks," to grade the efficacy, safety, evidence quality, evidence consistency, and affordability of treatments included in its clinical guidelines. The value scores were available for 55 of the 69 new cancer drugs approved by the US Food and Drug Administration from 2007 to 2016. Overall, the treatment costs for 95% of new cancer medicines in NCCN clinical guidelines were scored as "very expensive" or "expensive". In multivariable ordered logistic regression models, there was no association between the affordability of new cancer drugs and efficacy and safety data available in clinical guidelines. Most guideline-recommended drugs were subject to annual list price increases exceeding inflation.

Ischemic Stroke and Impact of Thyroid Profile at Presentation: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND: Stroke is the fifth leading cause of mortality in the United States and a leading cause of disability. A complex relationship between thyroid hormone levels and severity of, and outcome after, stroke has been described. AIM: Our objective is to identify the association between baseline thyroid function profile and outcome after acute ischemic stroke. METHODS: Studies looking at the association between thyroid function and functional stroke outcomes were identified from available electronic databases from inception to December 16, 2016. Study-specific risk ratios were extracted and combined with a random effects model meta-analysis. RESULTS: In the analysis of 12 studies with 5218 patients, we found that subclinical hypothyroidism was associated with better modified Rankin scale scores at 1 and 3 months (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.13-5.91, P = .03 and OR 2.28, 95% CI 1.13-3.91, P = .003, respectively) compared with the euthyroid cases. Likewise, patients with higher initial thyrotropin-releasing hormone (TSH) and fT3 or T3 levels had favorable outcomes at discharge (mean differences of TSH .12 [95% CI .03-.22, P = .009] and of fT3 .36 (CI .20-.53, P < .0001]) and at 3 months (mean differences of TSH .25 [95% CI .03-.47, P = .03] and of T3 8.60 [CI 4.58-12.61, P < .0001]). CONCLUSIONS: Elevated initial TSH (clinical or subclinical hypothyroidism) may correspond to better functional outcomes, whereas low initial T3/fT3 might correlate with worse outcomes in acute ischemic stroke among clinically euthyroid patients. This complex relation merits further well-designed investigations. Whether correcting thyroid profile with hormone supplementation or antagonism may lead to improved outcomes will require large, prospective, interventional studies.