IMPORTANCE Randomized clinical trials (RCTs) of lipid-lowering therapies form the evidence base for national and international guidelines. However, concerns exist that women and older patients are underrepresented in RCTs. OBJECTIVE To determine the trends of representation of women and older patients (Ն65 years) in RCTs of lipid-lowering therapies from 1990 to 2018. DATA SOURCES The electronic databases of MEDLINE and ClinicalTrials.gov were searched from January 1990 through December 2018. STUDY SELECTION RCTs of lipid-lowering therapies with sample sizes of at least 1000 patients and follow-up periods of at least 1 year were included. DATA EXTRACTION AND SYNTHESIS Two independent investigators abstracted the data on a standard data collection form. MAIN OUTCOMES AND MEASURES Patterns of representation of women and older adults were examined overall in lipid-lowering RCTs and according to RCT-level specific characteristics. The participation-to-prevalence ratio (PPR) metric was used to estimate the representation of women compared with their share of disease burden. RESULTS A total of 60 RCTs with 485 409 participants were included. The median (interquartile range) number of participants per trial was 5264 (1062-27 564). Overall, representation of women was 28.5% (95% CI, 24.4%-32.4%). There was an increase in the enrollment of women from the period 1990 to 1994 (19.5%; 95% CI, 18.4%-20.5%) to the period 2015 to 2018 (33.6%; 95% CI, 33.4%-33.8%) (P for trend = .01). Among common limiting factors were inclusion of only postmenopausal women or surgically sterile women (28.3%; 95% CI, 18.5%-40.7%) or exclusion of pregnant (23.3%; 95% CI, 14.4%-35.4%) and lactating (16.6%; 95% CI, 9.3%-28.1%) women. Women were underrepresented compared with their disease burden in lipid RCTs of diabetes (PPR, 0.74), heart failure (PPR, 0.27), stable coronary heart disease (PPR, 0.48), and acute coronary syndrome (PPR, 0.51). Only 23 RCTs with 263 628 participants reported the proportion of older participants. Overall representation of older participants was 46.7% (95% CI, 46.5%-46.9%), which numerically increased from 31.6% (95% CI, 30.8%-32.3%) in the period 1995 to 1998 to 46.2% (95% CI, 46.0%-46.5%) in the period 2015 to 2018 (P for trend = .43). A total of 53.0% (95% CI, 41.8%-65.3%) and 36.6% (95% CI, 25.6% to 49.3%) trials reported outcomes according to sex and older participants, respectively, which did not improve over time. (continued) Key Points Question Are women and older participants adequately represented in randomized clinical trials of lipidlowering therapy? Findings In this systematic review of 60 trials with 485 409 participants that were conducted between 1990 and 2018, there was a modest increase in the enrollment of women (from 19.5% to 33.6%) and older participants (from 31.6% to 46.2%); however, overall representation was low (28.5% women and 46.7% older adults). Women were underrepresented in trials compared with their relative disease burden. Meaning The results of this study suggest that despite ongoing ef...
Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of stomach contents into the esophagus causes troublesome symptoms, esophageal injury, and/or complications. Use of proton pump inhibitors (PPI) remains the standard therapy for GERD and is effective in most patients. Those whose symptoms are refractory to PPIs should be evaluated further and other treatment options should be considered, according to individual patient characteristics. Response to PPIs could be total (no symptoms), partial (residual breakthrough symptoms), or absent (no change in symptoms). Patients experiencing complete response do not usually need further management. Patients with partial response can be treated surgically or by using emerging endoscopic therapies. Patients who exhibit no response to PPI need further evaluation to rule out other causes.
Abstract. A feedback vertex set (fvs) of a graph is a set of vertices whose removal results in an acyclic graph. We show that if an undirected graph on n vertices with minimum degree at least 3 has a fvs on at most 1 3 n 1− vertices, then there is a cycle of length at most 6 (for ≥ 1/2, we can even improve this to just 6).Using this, we obtain a O(( 12 log k log log k + 6) k n ω ) algorithm for testing whether an undirected graph on n vertices has a fvs of size at most k. Here n ω is the complexity of the best matrix multiplication algorithm. The previous best parameterized algorithm for this problem took O((2k + 1) k n 2 ) time.We also investigate the fixed parameter complexity of weighted feedback vertex set problem in weighted undirected graphs.
A feedback vertex set (fvs) of a graph is a set of vertices whose removal results in an acyclic graph. We show that if an undirected graph on n vertices with minimum degree at least 3 has a fvs on at most 1 3 n 1− vertices, then there is a cycle of length at most 6 (for ≥ 1/2, we can even improve this to just 6).Using this, we obtain a O(( 12 log k log log k + 6) k n ω ) algorithm for testing whether an undirected graph on n vertices has a fvs of size at most k. Here n ω is the complexity of the best matrix multiplication algorithm. The previous best parameterized algorithm for this problem took O((2k + 1) k n 2 ) time.We also investigate the fixed parameter complexity of weighted feedback vertex set problem in weighted undirected graphs.
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