METHODS: In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death.
FINDINGS: From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease.
INTERPRETATION: Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men.
FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).
METHODOLOGY: This is a retrospective cohort study recruiting all kidney transplant recipients in South Australia from January 2010 till December 2018. Following that, the incidence of blood transfusion within one week post-operatively were traced (transfusion group). The outcomes were compared with all other transplant recipients (non-transfusion group). Recipient's demographic, donor characteristics and immunological risk profiles were obtained from the transplant unit database, while the biopsy report, history of blood transfusion, latest serum creatinine and follow-up status was gathered from the electronic medical system (OASIS). The HLA-DSA and HLA-Ab results were collected from the NOMS database. Finally, the survival data were merged with the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for South Australia recipients graft survival.
RESULTS: A total of 699 patients were eligible for analysis. The mean age was 50.64 ± 13.23 years old. There were more elderly (>65 years old) and females who needed transfusion. The majority had glomerulonephritis as the primary disease. There was no statistical difference in donor characteristics, cold ischemic time and immunological risk between the transfusion and non-transfusion group. There was no difference in the development of de novo HLA-DSA, HLA-Ab and rejection episodes between the group and the results were consistent in a model adjusted for all potential confounders. Median graft survival in days between the transfusion vs non-transfusion group was 1845 IQR (961,2430) and 1250 IQR (672,2013).
CONCLUSION: Blood transfusion under strong immunosuppressive cover within a one-week post-operative period is safe with no significant association with the development of de novo HLA-DSA, HLA-Ab or clinical rejection.
METHODS: We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489.
RESULTS: A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance.
CONCLUSIONS: This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.
METHODS: We adapted a dynamic model of HIV transmission among MSM/TW in Lima to incorporate stimulant use and increased HIV risk, suicide and CVD mortality. Among 6% to 24% of MSM/TW using stimulants (mostly cocaine), we modelled an increased risk of unprotected anal sex (RR = 1.35 [95%CI: 1.17 to 1.57]) obtained from local data, and increased risk of suicide (SMR = 6.26 [95%CI: 2.84 to 13.80]) and CVD (SMR = 1.83 [95%CI: 0.39 to 8.57]) mortality associated with cocaine use based on a global systematic review. We estimated the proportion of health harms occurring among MSM/TW who use stimulants in the next year (01-2020/01-2021). We also investigated the 10-year impact (01-2020/01-2030) of: (1) PrEP prioritization for stimulant-using MSM/TW compared to random allocation, and (2) integrating PrEP with a theoretical intervention halving stimulant-associated risk.
RESULTS: MSM/TW in Lima will experience high HIV incidence, suicide mortality and CVD mortality (1.6/100 py, and 0.018/100 py, 0.13/100 py respectively) in 2020. Despite stimulant using MSM/TW comprising an estimated 9.5% (95%CI: 7.8 to 11.5) of all MSM/TW, in the next year, 11% 95%CI (i.e. 2.5% to 97.5% percentile) 10% to 13%) of new HIV infections, 39% (95%CI: 18% to 60%) of suicides and 15% (95%CI: 3% to 44%) of CVD deaths could occur among this group. Scaling up PrEP among all stimulant using MSM/TW could prevent 19% (95%CI: 11% to 31%) more HIV infections over 10 years compared to random allocation. Integrating PrEP and an intervention to halve stimulant-associated risks could reduce new HIV infections by 20% (95%CI: 10% to 37%), suicide deaths by 14% (95%CI: 5% to 27%) and CVD deaths by 3% (95%CI: 0% to 16%) over a decade.
CONCLUSIONS: MSM/TW who use stimulants experience a disproportionate burden of health harms. Prioritizing PrEP based on stimulant use, in addition to sexual behaviour/gender identity criteria, could increase its impact. Integrated substance use, harm reduction, mental health and HIV care among MSM/TW is needed.
METHODS: We conducted a community-based cross-sectional study in 15 sub-districts of Kuantan Singingi regency from May-June 2017. We selected 320 mothers from 15 sub-districts who delivered in the last 3 months (February-April 2017). Trained data enumerators collected the relevant data by using a pre-tested semi-structured questionnaire. We used Cox regression analysis to determine the factors associated with delivery at healthcare facilities. Prevalence Ratio (PR) with a 95% confidence interval (CI) for childbirth at healthcare facilities was the key outcome measure.
RESULTS: Only 54.4% (174) of the 320 mothers delivered at healthcare facilities. Knowledge about pregnancy danger signs (PR = 1.59, 95%CI:1.15-2.2), attitude towards healthcare services (PR = 0.79, 95%CI:0.33-1.89), and access to health care services (PR = 0.39, 95%CI:0.18-0.84) were the dominant factors of childbirth at healthcare facilities. There was an interaction between attitude and access to healthcare influencing delivery at healthcare facilities.
CONCLUSIONS: Utilization of healthcare facilities for childbirth was low in Kuantan Singingi regency. Knowledge of pregnancy danger signs was an independent correlate of childbirth at healthcare facilities. Also, the interaction between attitude and access to healthcare showed a significant influence on childbirth at healthcare facilities. We recommend strengthening of existing maternal and child health program with a particular emphasis on complete and quality antenatal care, health education on danger signs of pregnancy and childbirth, and promoting positive attitudes towards healthcare facilities.
METHODS: We report a case series of 16 patients who successfully underwent fixation of the clavicle under the wide-awake technique. The clavicle fractures were grouped under the AO Fracture Classification. The WALANT solution comprised 1% lidocaine, 1:100,000 epinephrine, and 10:1 sodium bicarbonate. A total of 40 mL was injected in each patient with 10 mL subcutaneously along the clavicle followed by 30 mL subperiosteally at multiple intervals and directions.
RESULTS: The Numerical Pain Rating Score was 0 during WALANT injection and during surgery except for 2 patients with Numerical Pain Rating Scores of 1 and 2, respectively, during reduction.
CONCLUSION: We conclude that clavicle plating under WALANT is a good alternative option of anesthesia.
METHODS: A total of 32 female Sprague Dawley rats were taken and randomly divided into four groups (n = 8). Throughout the experimental period of 6 weeks, negative control-NC (vehicle deionized water), positive control-CD (Cd at 5 mg/kg), Tualang honey followed by Cd exposure-TH (Tualang honey at 200 mg/kg and Cd at 5 mg/kg) and Tualang honey control-THC (Tualang honey at 200 mg/kg) groups, were administered orally on a daily basis.
RESULTS: Rats exposed to Cd were significantly higher in ovarian weight, number of antral and atretic follicles as compared to the NC group. The disruptive effects of Cd on ovarian follicles were associated with a disruption in gonadotropin hormones and decreases in follicular stimulating hormone (FSH) and luteinizing hormone (LH). Moreover, a significant formation of oxidative stress in ovarian Cd-exposed rats has been proven by increasing the level of lipid peroxidation products (malondialdehyde) and decreasing the levels of enzymatic antioxidant (catalase). Interestingly, a daily supplementation of high antioxidant agents such as Tualang honey in these animals, caused significant improvements in the histological changes. Additionally, less atretic follicles were observed, restoring the normal level of LH and FSH (P
METHODS: A historical review of official reports, news articles, and gray literature was undertaken to identify tobacco industry tactics and strategies to hamper government efforts in implementing stronger pictorial health warning regulations in four Asian jurisdictions (Cambodia, Hong Kong, Malaysia, and the Philippines).
RESULTS: Nineteen countries/jurisdictions in the WHO Western Pacific region currently require pictorial health warnings on cigarette packs, including some of the world's largest, in line with the WHO Framework Convention on Tobacco Control Article 11 Guidelines. In the four jurisdictions examined, tobacco industry interference consisted of lobbying and misinformation of high-level government officers and policy-makers, distributing industry-friendly legislative drafts, taking government to court, challenging government timelines for law implementation, and mobilizing third parties. Strong political leadership and strategic advocacy enabled governments to successfully overcome this industry interference.
CONCLUSION: The tobacco industry uses similar tactics in different jurisdictions to derail, delay, and weaken the implementation of effective health warning policies. Identifying and learning from international experiences can help anticipate and defeat such challenges.
OBJECTIVES: Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers.
METHODS: In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this review.
RESULTS: The published results of SARS-CoV-2 structures and interactomics have been used to identify potential therapeutic candidates. We illustrate recent publications on SARS-CoV-2, concerning its molecular, epidemiological, and clinical characteristics, and focus on innovative diagnostics technologies in the production pipeline. This objective of this review is to enhance the comprehension of the unique characteristics of SARS-CoV-2 and strengthen future control measures.
Lay Summary: An innovative analysis is evaluating the nature of the COVID-19 pandemic. The aim is to increase knowledge of possible viral detection methods, which highlights several new technology limitations and advantages. We have assessed some drugs currently for patients (Lopinavir, Ritonavir, Anakinra and Interferon beta 1a), as the feasibility of COVID-19 specific antivirals is not presently known. The study explores the race toward vaccine development and highlights some significant trials and candidates in various clinical phases. This research addresses critical knowledge gaps by identifying repurposed drugs currently under clinical trials. Findings will be fed back rapidly to the researchers interested in COVID 19 and support the evidence and potential of possible therapeutics and small molecules with their mode of action.
OBJECTIVE: To examine the risk and protective factors contributing to suicidality among undergraduate college students in seven provinces in China.
METHODS: We conducted a cross-sectional study involving 13,387 college students from seven universities in Ningxia, Shandong, Shanghai, Jilin, Qinghai, Shaanxi, and Xinjiang. Data were collected using self-report questionnaires.
RESULTS: Higher scores in the psychological strain, depression, anxiety, stress, and psychache (psychological risk factors for suicidality) and lower scores in self-esteem and purpose in life (psychological protective factors against suicidality) were associated with increased suicidality among undergraduate students in China. Demographic factors which were associated with higher risks of suicidality were female gender, younger age, bad academic results, were an only child, non-participation in school associations, and had an urban household registration. Perceived good health was protective against suicidality.
CONCLUSIONS: Knowing the common risk and protective factors for suicidality among Chinese undergraduate students is useful in developing interventions targeted at this population and to guide public health policies on suicide in China.
METHODS: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis.
RESULTS: There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58-0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69-1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83-1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70-0.87) and death within 28 days (RR 0.88, 95% CI 0.82-0.94).
CONCLUSIONS: Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury.
TRIAL REGISTRATION: ISRCTN15088122 , registered on 19 July 2011; NCT01402882 , registered on 26 July 2011.
METHODS: In this non-interventional study involving 49 sites across five countries in Southeast Asia and South Korea, 379 stable NVAF patients who switched from VKA therapy to dabigatran during routine clinical practice were recruited and followed up for 6 months. Treatment convenience and satisfaction were evaluated using Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2). Through post hoc analysis, factors associated with improved treatment convenience scores at visit 2 were described.
RESULTS: Treatment convenience and satisfaction significantly improved after switching from VKAs to dabigatran at visit 2 and visit 3 (convenience: p<0.001 each vs baseline; satisfaction: p=0.0174 (visit 2), p=0.0004 (visit 3) compared with baseline). Factors predictive of higher (>80th percentile) response on treatment convenience were female sex, younger age (<75 years), higher baseline stroke risk, higher creatinine clearance and absence of concomitant hypertension, stroke or gastrointestinal diseases.
CONCLUSION: Dabigatran was associated with a significant improvement in treatment convenience and satisfaction after switching from VKAs when used for stroke prevention in NVAF patients from Southeast Asia and South Korea.
OBJECTIVES: To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants.
SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers.
DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS: We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D supplementation compared to lactating mother supplementation may increase infant 25-OH vitamin D levels (MD 14.35 nmol/L, 95% CI 9.64 to 19.06; participants = 269; studies = 4; low-certainty). Infant vitamin D supplementation may reduce the incidence of vitamin D insufficiency (RR 0.61, 95% CI 0.40 to 0.94; participants = 334; studies = 4) and may reduce vitamin D deficiency (RR 0.35, 95% CI 0.17 to 0.72; participants = 334; studies = 4) but the evidence is very uncertain. Infant BMC and radiological rickets were not reported and there was insufficient evidence to determine if maternal supplementation has an effect on infant biochemical rickets. All studies enrolled patient populations at high risk of vitamin D deficiency. Studies compared an infant dose of vitamin D 400 IU/day with varying maternal vitamin D doses from 400 IU/day to > 4000 IU/day. We are uncertain about adverse effects including hypercalcaemia.
AUTHORS' CONCLUSIONS: For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.