PATIENTS AND METHODS: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453).
RESULTS: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs.
CONCLUSIONS: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.
METHODS: A systematic literature search was performed in Scopus, Embase, Web of Science, and PubMed databases up to February 2020 for RCTs that investigated the effect of DHEA supplementation on testosterone levels. The estimated effect of the data was calculated using the weighted mean difference (WMD). Subgroup analysis was performed to identify the source of heterogeneity among studies.
RESULTS: Overall results from 42 publications (comprising 55 arms) demonstrated that testosterone level was significantly increased after DHEA administration (WMD: 28.02 ng/dl, 95% CI: 21.44-34.60, p = 0.00). Subgroup analyses revealed that DHEA increased testosterone level in all subgroups, but the magnitude of increment was higher in females compared to men (WMD: 30.98 ng/dl vs. 21.36 ng/dl); DHEA dosage of ˃50 mg/d compared to ≤50 mg/d (WMD: 57.96 ng/dl vs. 19.43 ng/dl); intervention duration of ≤12 weeks compared to ˃12 weeks (WMD: 44.64 ng/dl vs. 19 ng/dl); healthy participants compared to postmenopausal women, pregnant women, non-healthy participants and androgen-deficient patients (WMD: 52.17 ng/dl vs. 25.04 ng/dl, 16.44 ng/dl and 16.47 ng/dl); and participants below 60 years old compared to above 60 years old (WMD: 31.42 ng/dl vs. 23.93 ng/dl).
CONCLUSION: DHEA supplementation is effective for increasing testosterone levels, although the magnitude varies among different subgroups. More study needed on pregnant women and miscarriage.
Methods: Cross-sectional data from 21 countries in the Prospective Urban and Rural Epidemiology study were collected covering 61 229 hypertensive individuals aged 35-70 years, their households and the 656 communities in which they live. Outcomes include whether hypertensive participants have their condition detected, treated and/or controlled. Multivariate statistical models adjusting for community fixed effects were used to assess the associations of three social capital measures: (1) membership of any social organisation, (2) trust in other people and (3) trust in organisations, stratified into high-income and low-income country samples.
Results: In low-income countries, membership of any social organisation was associated with a 3% greater likelihood of having one's hypertension detected and controlled, while greater trust in organisations significantly increased the likelihood of detection by 4%. These associations were not observed among participants in high-income countries.
Conclusion: Although the observed associations are modest, some aspects of social capital are associated with better management of hypertension in low-income countries where health systems are often weak. Given that hypertension affects millions in these countries, even modest gains at all points along the treatment pathway could improve management for many, and translate into the prevention of thousands of cardiovascular events each year.
METHODS: We assessed use of antiplatelet, cholesterol, and blood-pressure-lowering drugs in 8492 individuals with self-reported cardiovascular disease from 21 countries enrolled in the Prospective Urban Rural Epidemiology (PURE) study. Defining one or more drugs as a minimal level of secondary prevention, wealth-related inequality was measured using the Wagstaff concentration index, scaled from -1 (pro-poor) to 1 (pro-rich), standardised by age and sex. Correlations between inequalities and national health-related indicators were estimated.
FINDINGS: The proportion of patients with cardiovascular disease on three medications ranged from 0% in South Africa (95% CI 0-1·7), Tanzania (0-3·6), and Zimbabwe (0-5·1), to 49·3% in Canada (44·4-54·3). Proportions receiving at least one drug varied from 2·0% (95% CI 0·5-6·9) in Tanzania to 91·4% (86·6-94·6) in Sweden. There was significant (p<0·05) pro-rich inequality in Saudi Arabia, China, Colombia, India, Pakistan, and Zimbabwe. Pro-poor distributions were observed in Sweden, Brazil, Chile, Poland, and the occupied Palestinian territory. The strongest predictors of inequality were public expenditure on health and overall use of secondary prevention medicines.
INTERPRETATION: Use of medication for secondary prevention of cardiovascular disease is alarmingly low. In many countries with the lowest use, pro-rich inequality is greatest. Policies associated with an equal or pro-poor distribution include free medications and community health programmes to support adherence to medications.
FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).
Methods: We used a Markov microsimulation model to compare the cost-effectiveness of zoledronic acid with alendronate in Chinese postmenopausal osteoporotic women with no fracture history at various ages of therapy initiation from health care payer perspective.
Results: The incremental cost-effectiveness ratios (ICERs) for the zoledronic acid versus alendronate were $23,581/QALY at age 65 years, $17,367/QALY at age 70 years, $14,714/QALY at age 75 years, and $12,169/QALY at age 80 years, respectively. In deterministic sensitivity analyses, the study demonstrated that the two most impactful parameters were the annual cost of zoledronic acid and the relative risk of hip fracture with zoledronic acid. In probabilistic sensitivity analyses, the probabilities of zoledronic acid being cost-effective compared with alendronate were 70-100% at a willingness-to-pay of $29,340 per QALY.
Conclusions: Among postmenopausal osteoporotic women in China, zoledronic acid therapy is cost-effective at all ages examined from health care payer perspective, compared with weekly oral alendronate. In addition, alendronate treatment is shown to be dominant for patients at ages 65 and 70 with full persistence. This study will help clinicians and policymakers make better decisions about the relative economic value of osteoporosis treatments in China.
METHODS: This cross-sectional study was performed from September to November 2022. Self-reported questionnaires including the Big Five Personality Questionnaire, General Self-Efficacy Scale, College Student's academic burnout Scale, Generalized Anxiety Scale and demographic characteristics were distributed to 2505 college students in a university in Hebei Province, of which 2,471 were valid. Statistical analysis was carried out through SPSS26.0 and SPSS PROCESS macro.
RESULTS: Results showed four of the big five personality characters (i.e., extraversion, agreeableness, conscientiousness, and openness) were negatively correlated with anxiety. Neuroticism was positively correlated with anxiety. Moreover, general self-efficacy was found to be negatively correlated with academic burnout and anxiety; academic burnout was positively correlated with anxiety. Finally, general self-efficacy and academic burnout mediated the relationship between personality traits (i.e., extraversion, agreeableness, neuroticism, openness) and anxiety.
CONCLUSIONS: Personality traits (i.e., extraversion, agreeableness, neuroticism, and openness) could influence anxiety through the chain mediating effects of general self-efficacy and academic burnout. Interventions focusing on anxiety reduction may be successful in increasing general self-efficacy and decreasing students' academic burnout.
METHODS: We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality.
FINDINGS: Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3·91 (SD 2·77) servings per day. During a median 7·4 years (5·5-9·3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0·90, 95% CI 0·74-1·10, ptrend=0·1301), myocardial infarction (0·99, 0·74-1·31; ptrend=0·2033), stroke (0·92, 0·67-1·25; ptrend=0·7092), cardiovascular mortality (0·73, 0·53-1·02; ptrend=0·0568), non-cardiovascular mortality (0·84, 0·68-1·04; ptrend =0·0038), and total mortality (0·81, 0·68-0·96; ptrend<0·0001). The HR for total mortality was lowest for three to four servings per day (0·78, 95% CI 0·69-0·88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality.
INTERPRETATION: Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day).
FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).
DESIGN: We conducted a systematic literature review and meta-analysis searching MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to April 1, 2017, for studies.
INTERVENTIONS: Mortality rates were compared between severely ill patients receiving piperacillin-tazobactam via prolonged infusion or intermittent infusion. Included studies must have reported severity of illness scores, which were transformed into average study-level mortality probabilities.
MEASUREMENTS AND MAIN RESULTS: Two investigators independently screened titles, abstracts, and full texts of studies meeting inclusion criteria for this systematic review and meta-analysis. Variables included author name, publication year, study design, demographics, total daily dose(s), average estimated creatinine clearance, type of prolonged infusion, prevalence of combination therapy, severity of illness scores, infectious sources, all-cause mortality, clinical cure, microbiological cure, and hospital and ICU length of stay. The review identified 18 studies including 3,401 patients who received piperacillin-tazobactam, 56.7% via prolonged infusion. Across all studies, the majority of patients had an identified primary infectious source. Receipt of prolonged infusion was associated with a 1.46-fold lower odds of mortality (95% CI, 1.20-1.77) in the pooled analysis. Patients receiving prolonged infusion had a 1.77-fold higher odds of clinical cure (95% CI, 1.24-2.54) and a 1.22-fold higher odds of microbiological cure (95% CI, 0.84-1.77). Subanalyses were conducted according to high (≥ 20%) and low (< 20%) average study-level mortality probabilities. In studies reporting higher mortality probabilities, effect sizes were variable but similar to the pooled results.
CONCLUSIONS: Receipt of prolonged infusion of piperacillin-tazobactam was associated with reduced mortality and improved clinical cure rates across diverse cohorts of severely ill patients.