Harms of third- and fourth-generation combined oral contraceptives in premenopausal women: A systematic review and meta-analysis.

We assessed the available evidence regarding adverse effects on surrogate and patient-important health outcomes of third- and fourth-generation combined oral contraceptives among premenopausal women. We performed a systematic review and meta-analysis including randomized controlled trials and observational studies comparing third- and fourth-generation combined oral contraceptives with other generation contraceptives or placebo. Studies that enrolled women aged 15 to 50 years, with at least three cycles of intervention and 6 months of follow-up were included. A total of 33 studies comprising 629,783 women were included. Low-density lipoprotein cholesterol levels were significantly lower in fourth-generation oral contraceptives (mean differences (MD): -0.24 mmol/L; [95% CI -0.39 to -0.08]), while total cholesterol was significantly increased in levonorgestrel users when compared to third-generation oral contraceptives (MD: 0.27 mmol/L; [95% CI 0.04 to 0.50]). A decreased arterial thrombosis incidence was shown in fourth-generation oral contraceptive users, as compared to levonorgestrel (incidence rate ratio (IRR): 0.41; [95% CI 0.19 to 0.86]). No difference was found in the occurrence of deep venous thrombosis between fourth-generation oral contraceptives and levonorgestrel users (IRR: 0.91; [95% CI 0.66 to 1.27]; p = 0.60; I2 = 0%). Regarding the remaining outcomes, data were heterogeneous and showed no clear difference. In premenopausal women, the use of third- and fourth-generation oral contraceptives is associated with an improved lipid profile and lower risk of arterial thrombosis. Data were inconclusive regarding the rest of outcomes assessed. This review was registered in PROSPERO with CRD42020211133.

Low-Dose ACTH Stimulation Test in Obesity: A Randomized Dose Assessment.

Background: The short cosyntropin test is widely used for adrenal insufficiency screening and diagnosis. Lower cosyntropin doses may have greater sensitivity vs. the standard dose in detecting adrenal dysfunction. Obesity and overweight are increasing, impacting the clinical presentation of some diseases. Currently more than 50% of the subjects diagnosed with autoimmune adrenal insufficiency have a BMI greater than 25, and hence individuals living with overweight and obesity are more frequently requiring evaluation of the adrenal cortical function. Fixed-dose cosyntropin stimulation may not be appropriate for individuals with obesity. Objective: The primary objective was to compare cortisol response to a weight-adapted cosyntropin dose vs. a fixed low dose (1 µg) and a more physiologically fixed dose (10 µg). Methods: Twenty individuals with obesity and 20 age-matched healthy controls underwent in a randomized sequence at least one-week apart, to the The short cosyntropin test with three different doses, 0.2 µg/kg of body weight, 1 or 10 µg fixed dose stimuli. The assessment and data analysis were blinded to the individual and the investigator. Results: Cortisol response was reduced in the group with obesity with the 1 µg fixed dose stimuli at 30 minutes (median, IQR) 649.6 µg, 567.3-738.4 µg for the control group vs. 568.6 µg, 528.4-623.13 µg, p=0.04; there was a lower cortisol peak at 60' in all the three evaluated doses, with a dose-dependent trend. A weight-adapted cosyntropin dose of 0.2 µg in obesity produces a similar response to the one observed in individuals without obesity. The 1 µg ACTH test falls short on stimulating the cortisol adrenal response in individuals with obesity.

Interventions supporting cost conversations between patients and clinicians: A systematic review.

BACKGROUND AND AIM: Discussing cost during medical encounters may decrease the financial impact of medical care on patients and align their treatment plans with their financial capacities. We aimed to examine which interventions exist and quantify their effectiveness to support cost conversations. METHODS: Several databases were queried (Embase; Ovid MEDLINE(R); Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; the Cochrane databases; and Scopus) from their inception until January 31, 2020 using terms such as "clinician*", "patient*", "cost*", and "conversation*". Eligibility assessment, data extraction and risk of bias assessment were performed independently and in duplicate. We extracted study setting, design, intervention characteristics and outcomes related to patients, clinicians and quality metrics. RESULTS: We identified four studies (1327 patients) meeting our inclusion criteria. All studies were non-randomised and conducted in the United States. Three were performed in a primary care setting and the fourth in an oncology. Two studies used decision aids that included cost information; one used a training session for health care staff about cost conversations, and the other directly delivered information regarding cost conversations to patients. All interventions increased cost-conversation frequency. There was no effect on out-of-pocket costs, satisfaction, medication adherence or understanding of costs of care. CONCLUSION: The body of evidence is small and comprised of studies at high risk of bias. However, an increase in the frequency of cost conversations is consistent. Studies with higher quality are needed to ascertain the effects of these interventions on the acceptability, frequency and quality of cost conversations.

The validity of cost-effectiveness analyses of tight glycemic control. A systematic survey of economic evaluations of pharmacological interventions in patients with type 2 diabetes.

PURPOSE: Currently available randomized trial evidence has shown no reductions in type 2 diabetes (T2D) complications important to patients with tight glycemic control. Yet, economic analyses consistently find tight glycemic control to be cost-effective. To understand this apparent paradox, we systematically identified and appraised economic analyses of tight glycemic control for T2D. METHODS: We searched multiple databases from January 2016 to January 2018 for cost-effectiveness or cost-utility analyses of any glucose-lowering treatments for adults with T2D using simulations with long-40 years to lifetime-time horizons. Reviewers selected and appraised each study independently and in duplicate with good reproducibility. RESULTS: We found 30 analyses, most comparing the glycemic impact of glucose-lowering drugs and applying their impact on HbA1c to model (most commonly IMS CORE or Cardiff T2DM) their impact on the incidence of diabetes-related complication. Models drew from observational evidence of the correlation of HbA1c levels and diabetes-related complication rates; none used estimates of the effect of lowering HbA1c on these outcomes from systematic reviews of randomized trials. Sensitivity analyses, when conducted, demonstrate substantial loss of cost-effectiveness as simulations approach the results seen in these trials. CONCLUSIONS: Reliance on the association between glycemic control and diabetes-related complications evident in observational studies but not apparent in randomized trial bias the estimates of the cost-effectiveness of interventions to improve glycemic control.

Benefits and harms of intensive glycemic control in patients with type 2 diabetes.

Diabetes is a major and costly health concern worldwide, with high morbidity, disability, mortality, and impaired quality of life. The vast majority of people living with diabetes have type 2 diabetes. Historically, the main strategy to reduce complications of type 2 diabetes has been intensive glycemic control. However, the body of evidence shows no meaningful benefit of intensive (compared with moderate) glycemic control for microvascular and macrovascular outcomes important to patients, with the exception of reduced rates of non-fatal myocardial infarction. Intensive glycemic control does, however, increase the risk of severe hypoglycemia and incurs additional burden by way of polypharmacy, side effects, and cost. Additionally, data from cardiovascular outcomes trials showed that cardiovascular, kidney, and mortality outcomes may be improved with use of specific classes of glucose lowering drugs largely independently of their glycemic effects. Therefore, delivering evidence based, patient centered care to people with type 2 diabetes requires a paradigm shift and departure from the predominantly glucocentric view of diabetes management. Instead of prioritizing intensive glycemic control, the focus needs to be on ensuring access to adequate diabetes care, aligning glycemic targets to patients' goals and situations, minimizing short term and long term complications, reducing the burden of treatment, and improving quality of life.