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Introduction: Climate change has a disproportionate impact on women in comparison to men, and women have a key role to play in climate adaptation. However, evidence is lacking on how gender inequalities may be associated with climate vulnerability and ability to respond at country level. Methods: This ecological study investigated the association between climate adaptation, measured by the Notre Dame Global Adaptation Initiative Country Index (ND-GAIN), and gender equality, measured by the Global Gender Gap Index (GGGI) developed by the World Economic Forum and the Gender Inequality Index (GII) developed by the United Nations. Simple linear regression was used to estimate the associations between the indices and their subdomains for 146 countries. Results: There was an approximately linear association between the GGGI and climate adaptation. Each 1% increase in gender equality was associated with a 0.6% increase in the ND-GAIN score (the slope was 0.59, with a 95% confidence interval [0.33 to 0.84]). This was driven by a negative association between gender equality and vulnerability (-0.41 [-0.62 to -0.20]), and a positive association between gender equality and readiness (0.77 [0.44 to 1.10]). The strongest associations between gender equality and climate adaptation were observed for the education domain of the GGGI. There was a strong negative linear association between the GII and climate adaptation, which explained most (86%) of the between-country variation in climate adaptation. Each 1% increase in gender inequality was associated with a 0.5% decrease in the ND-GAIN score (-0.54 [-0.57 to -0.50]). The association between gender inequality and readiness was stronger than the association with vulnerability (0.41 [0.37 to 0.44] for vulnerability versus − 0.67 [-0.72 to -0.61] for readiness). Conclusions: Gender inequality, measured broadly across different domains of life, is associated with climate adaptation at country level, both in terms of vulnerability to impact and readiness to respond. [ABSTRACT FROM AUTHOR]

Introduction: Reporting of sex and gender analysis in medical research has been shown to improve quality of the science and ensure findings are applicable to women and men. There is conflicting evidence on whether efforts by funding agencies and medical journals to encourage reporting of sex and gender analysis have resulted in tangible improvements. This study mapped the inclusion of sex and gender analysis in stroke and dementia research conducted in the Asia-Pacific region. Methods: A systematic search for Asia-Pacific stroke and dementia research was conducted in PubMed and papers included from the period 2012 to 2022. Eligible studies were reviewed for inclusion of a primary sex or gender focus and categorized by type of sex and gender analysis. Author gender was determined using an algorithm and its associations with inclusion of sex and gender analysis were examined. Results: Total Asia-Pacific publications increased from 109 in 2012 to 313 in 2022, but the rate of studies with a primary sex or gender focus did not increase significantly (R2 = 0.06, F(1, 9) = 0.59, p = 0.46). Australia, China, India, Japan, and South Korea produced the most publications over the study period and were the only countries with at least 50 publications. The impact of author gender was mixed, with female first authorship associated with inclusion of sex or gender analysis and last female authorship associated with studies having a primary sex or gender focus. Conclusions: In the Asia-Pacific, brain health research is currently centred around high-income countries, and efforts are needed to ensure research findings are applicable throughout the region. While there was a general increase in brain health publications over the last decade, the rate of sex and gender analysis was unchanged. This demonstrates that even with efforts in some countries in place, there is currently a lack of progress in the Asia-Pacific region to produce more research focussing on sex and gender analysis. [ABSTRACT FROM AUTHOR]

Sex and gender are fundamental aspects of health and wellbeing. Yet many research studies fail to consider sex or gender differences, and even when they do this is often limited to merely cataloguing such differences in the makeup of study populations. The evidence on sex and gender differences is thus incomplete in most areas of medicine. This article presents a roadmap for the systematic conduct of sex- and gender-disaggregated health research. We distinguish three phases: the exploration of sex and gender differences in disease risk, presentation, diagnosis, treatment, and outcomes; explaining any found differences by revealing the underlying mechanisms; and translation of the implications of such differences to policy and practice. For each phase, we provide critical methodological considerations and practical examples are provided, taken primarily from the field of cardiovascular disease. We also discuss key overarching themes and terminology that are at the essence of any study evaluating the relevance of sex and gender in health. Here, we limit ourselves to binary sex and gender in order to produce a coherent, succinct narrative. Further disaggregation by sex and gender separately and which recognises intersex, non-binary, and gender-diverse identities, as well as other aspects of intersectionality, can build on this basic minimum level of disaggregation. We envision that uptake of this roadmap, together with wider policy and educational activities, will aid researchers to systematically explore and explain relevant sex and gender differences in health and will aid educators, clinicians, and policymakers to translate the outcomes of research in the most effective and meaningful way, for the benefit of all. [ABSTRACT FROM AUTHOR]

Key Features The Zahedan Adult Cohort Study (ZACS) was established to investigate the incidence of non-communicable diseases and their risk factors in Zahedan, and is the first cohort study in the Baluch and Sistani ethnic groups. Importantly, cardiovascular disease, cancers and chronic respiratory disease have been the main drivers of reducing premature avertable mortality from NCDs.[3] Moreover, evidence shows that premature mortality among drug users, chronic kidney disease, acute glomerulonephritis and diabetes increases. Therefore, identifying risk factors for NCDs at the local and national levels is essential for policy makers to decide on effective policies for reducing the burden of NCDs in Iran.[9] Cohort studies are the best type of research to identify and quantify the relationship between exposure and outcome. The ZACS outcomes of interest are death, non-communicable diseases and changes in risk factors or protective factors. [Extracted from the article]

Background: Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes in Australia with rates trebling over the past decades partially explained by rising obesity rates and maternal age among childbearing women. Percentage of GDM attributable to obesity has been documented, mostly focusing on metropolitan populations. In parts of regional (areas outside capital cities) and rural Australia where overweight, obesity and morbid obesity are more prevalent, intertwined with socioeconomic disadvantage and higher migrant communities, trends over time in adjusted percentages of GDM attributed to obesity are unknown. Methods: In this population-based retrospective panel study, women, without pre-existing diabetes, delivering singletons between 2010 and 2017 in a tertiary regional hospital that serves 26% of Victoria's 6.5 million Australian population were eligible for inclusion. Secular trends in GDM by body mass index (BMI) and age were evaluated. The percentage of GDM that would have been prevented each year with the elimination of overweight or obesity was estimated using risk-adjusted regression-based population attributable fractions (AFp). Trends in the AFp over time were tested using the augmented Dickey-Fuller test. Results: Overall 7348 women, contributing to 10,028 births were included. The age of expecting mothers, their BMI, proportion of women born overseas, and GDM incidence significantly rose over time with GDM rising from 3.5% in 2010 to 13.7% in 2017, p < 0.001, increasing in all BMI categories. The incidence was consistently highest among women with obesity (13.8%) and morbid obesity (21.6%). However, the highest relative increase was among women with BMI < 25 kg/m2, rising from 1.4% in 2010 to 7.0% in 2017. Adjusting for age, country of birth, socioeconomic status, comorbidities, antenatal and intrapartum factors, an estimated 8.6% (confidence interval (CI) 6.1–11.0%), 15.6% (95% CI 12.2–19.0%), and 19.5% (95% CI 15.3–23.6%) of GDM would have been prevented by eliminating maternal overweight, obesity, and morbid obesity, respectively. However, despite the rise in obesity over time, percentages of GDM attributable to overweight, obesity, and morbid obesity significantly dropped over time. Scenario analyses supported these findings. Conclusions: Besides increasing prevalence of obesity over time, this study suggests that GDM risk factors, other than obesity, are also increasing over time. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide but has been primarily recognised as a man's disease. The major components of CVD are ischaemic heart disease (IHD), stroke and peripheral arterial disease (PAD). Compared with IHD or stroke, individuals with PAD are at significantly greater risk of major cardiovascular events. Despite this, they are less likely to receive preventative treatment than those with IHD. Women are at least as affected by PAD as men, but major sex-specific knowledge gaps exist in the understanding of relevant CVD risk factors and efficacy of treatment. This prompted the American Heart Association to issue a "call to action" for PAD in women, in 2012. Despite this, PAD and CVD risk in women continues to be under-recognised, leading to a loss of opportunity to moderate and prevent CVD morbidity. This review outlines current evidence regarding cardiovascular risk in women and men with PAD, the relative significance of traditional and non-traditional risk factors and sex differences in cardiovascular risk management. [ABSTRACT FROM AUTHOR]

Introduction and Aim: Internationally, women are underrepresented as leaders in major scientific organizations and conferences. We aimed to determine gender differences in leadership roles and annual scientific conferences of the Stroke Society of Australasia (SSA). Methods: In a retrospective review of SSA data (2014–2019), committee members were obtained through the SSA Web site, and moderators, speakers, and award recipients were identified from SSA annual scientific conference programs. Gender was determined by name inspection and Web search. Absolute numbers and proportions of women and men were recorded for all roles examined, overall and per year. Associations between representation of women in conferences and percentage of women in speaking roles were tested using multinomial regression. Results: Presidential leadership of the SSA was held by men in 2014–2016 and 2019 and women in 2017–2018. SSA committee membership was predominantly women (55%), being lowest (47%) in 2014 and 2019 and highest (65%) in 2017. There was a wide gender variation at scientific conferences, with 41% of keynote speakers being women overall, from 20% in 2016 to 75% in 2015. From 2014 to 2019, 55% of all speakers were women, ranging from 32% (in 2016) to 71% (in 2015). A higher percentage of women as speakers or moderators was associated with a program committee with over a third of its members composed of women (p ≤ 0.044). Conclusions: Representation of women varied from 2014 to 2019 in the SSA organization and its conferences, although men are more often elected president in the organization and women are less often keynote speakers. When more women were included in the program committee, the representation of women as speakers increased. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes in Australia with rates trebling over the past decades partially explained by rising obesity rates and maternal age among childbearing women. Percentage of GDM attributable to obesity has been documented, mostly focusing on metropolitan populations. In parts of regional (areas outside capital cities) and rural Australia where overweight, obesity and morbid obesity are more prevalent, intertwined with socioeconomic disadvantage and higher migrant communities, trends over time in adjusted percentages of GDM attributed to obesity are unknown.Methods: In this population-based retrospective panel study, women, without pre-existing diabetes, delivering singletons between 2010 and 2017 in a tertiary regional hospital that serves 26% of Victoria's 6.5 million Australian population were eligible for inclusion. Secular trends in GDM by body mass index (BMI) and age were evaluated. The percentage of GDM that would have been prevented each year with the elimination of overweight or obesity was estimated using risk-adjusted regression-based population attributable fractions (AFp). Trends in the AFp over time were tested using the augmented Dickey-Fuller test.Results: Overall 7348 women, contributing to 10,028 births were included. The age of expecting mothers, their BMI, proportion of women born overseas, and GDM incidence significantly rose over time with GDM rising from 3.5% in 2010 to 13.7% in 2017, p <  0.001, increasing in all BMI categories. The incidence was consistently highest among women with obesity (13.8%) and morbid obesity (21.6%). However, the highest relative increase was among women with BMI < 25 kg/m2, rising from 1.4% in 2010 to 7.0% in 2017. Adjusting for age, country of birth, socioeconomic status, comorbidities, antenatal and intrapartum factors, an estimated 8.6% (confidence interval (CI) 6.1-11.0%), 15.6% (95% CI 12.2-19.0%), and 19.5% (95% CI 15.3-23.6%) of GDM would have been prevented by eliminating maternal overweight, obesity, and morbid obesity, respectively. However, despite the rise in obesity over time, percentages of GDM attributable to overweight, obesity, and morbid obesity significantly dropped over time. Scenario analyses supported these findings.Conclusions: Besides increasing prevalence of obesity over time, this study suggests that GDM risk factors, other than obesity, are also increasing over time. [ABSTRACT FROM AUTHOR]

Background: It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction (MI) in women.Methods: We used data from 263 295 female UK Biobank participants [mean age 56.2; standard deviation (SD) 8.0 years] without previous cardiovascular disease (CVD). Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, ag- and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels.Results: After a mean follow-up of 9 years, 2206 incident cases of MI had been recorded, including 230 events among the 57 204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with an HR [95% confidence interval (CI) for MI of 0.73 (0.58; 0.92)]. After adjusting for age, this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, it was 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, contraceptive pill use and the use of hormone replacement therapy. The multivariable-adjusted HR for the 171 431 women (mean age 59) with undetectable levels of oestradiol, compared with those with detectable levels, was 0.97 (0.92; 1.02).Conclusions: Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age and further confounded by other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Objective: Diabetes has shown to be a stronger risk factor for myocardial infarction (MI) in women than men. Whether sex differences exist across the glycemic spectrum is unknown. We investigated sex differences in the associations of diabetes status and glycated hemoglobin (HbA1c) with the risk of MI.Research Design and Methods: Data were used from 471,399 (56% women) individuals without cardiovascular disease (CVD) included in the UK Biobank. Sex-specific incidence rates were calculated by diabetes status and across levels of HbA1c using Poisson regression. Cox proportional hazards analyses estimated sex-specific hazard ratios (HRs) and women-to-men ratios by diabetes status and HbA1c for MI during a mean follow-up of 9 years.Results: Women had lower incidence rates of MI than men, regardless of diabetes status or HbA1c level. Compared with individuals without diabetes, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes were associated with an increased risk of MI in both sexes. Previously diagnosed diabetes was more strongly associated with MI in women (HR 2.33 [95% CI 1.96; 2.78]) than men (1.81 [1.63; 2.02]), with a women-to-men ratio of HRs of 1.29 (1.05; 1.58). Each 1% higher HbA1c, independent of diabetes status, was associated with an 18% greater risk of MI in both women and men.Conclusions: Although the incidence of MI was higher in men than women, the presence of diabetes is associated with a greater excess relative risk of MI in women. However, each 1% higher HbA1c was associated with an 18% greater risk of MI in both women and men. [ABSTRACT FROM AUTHOR]

Background: Sex differences have been described in diabetes cardiovascular outcome trials (CVOTs).Purpose: We systematically reviewed for baseline sex differences in cardiovascular (CV) risk factors and CV protection therapy in diabetes CVOTs.Data Sources: Randomized placebo-controlled trials examining the effect of diabetes medications on major adverse cardiovascular events in people ≥18 years of age with type 2 diabetes.Study Selection: Included trials reported baseline sex-specific CV risks and use of CV protection therapy.Data Extraction: Two reviewers independently abstracted study data.Data Synthesis: We included five CVOTs with 46,606 participants. We summarized sex-specific data using mean differences (MDs) and relative risks (RRs) and pooled estimates using random effects meta-analysis. There were fewer women than men in included trials (28.5-35.8% women). Women more often had stroke (RR 1.28; 95% CI 1.09, 1.50), heart failure (RR 1.30; 95% CI 1.21,1.40), and chronic kidney disease (RR 1.33; 95% CI 1.17; 1.51). They less often used statins (RR 0.90; 95% CI 0.86, 0.93), aspirin (RR 0.82; 95% CI 0.71, 0.95), and β-blockers (RR 0.93; 95% CI 0.88, 0.97) and had a higher systolic blood pressure (MD 1.66 mmHg; 95% CI 0.90, 2.41), LDL cholesterol (MD 0.34 mmol/L; 95% CI 0.29, 0.39), and hemoglobin A1c (MD 0.11%; 95% CI 0.09, 0.14 [1.2 mmol/mol; 1.0, 1.5]) than men.Limitations: We could not carry out subgroup analyses due to the small number of studies. Our study is not generalizable to low CV risk groups nor to patients in routine care.Conclusions: There were baseline sex disparities in diabetes CVOTs. We suggest efforts to recruit women into trials and promote CV management across the sexes. [ABSTRACT FROM AUTHOR]

Aims: To explain, and document, the epidemiological work associated with the action in diabetes and vascular disease: preterax and diamicron‐modified release controlled evaluation (ADVANCE) clinical trial. Materials and methods: ADVANCE was designed as a randomized controlled multicentre factorial trial in high‐risk patients with diabetes. The two interventions were blood pressure lowering medications versus placebo, and intensive glucose control versus standard glucose control. Following termination of the trial, an observational study of surviving participants, able to join, was mounted: the ADVANCE ‐ observational study (ADVANCE‐ON). Other epidemiological analyses that were undertaken treated the trial as a cohort study, including using biomarkers from the blood samples taken from ADVANCE subjects as risk exposures. Results: More than 50 publications have reported epidemiological results from ADVANCE. The main results from ADVANCE‐ON suggested attenuated benefits of ADVANCE's blood pressure lowering treatment on all‐cause and cardiovascular death, but no such long‐term benefits for intensive glucose control, although this did give persistent benefit for end‐stage renal disease. The other epidemiological studies found, amongst other things, strong effects of NT‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity cardiac troponin T on macrovascular events, microvascular events and all‐cause death. Conclusions: Embedding post‐randomization and epidemiological analyses into clinical trials is worthwhile and can be highly productive in advancing scientific knowledge. [ABSTRACT FROM AUTHOR]

Summary: Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta‐analysis. Compared with body mass index–defined lower‐normal weight (18.5‐22.4 kg/m2), the risk of all‐cause dementia was higher among underweight individuals but lower among those with upper‐normal (22.5‐24.9 kg/m2) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all‐cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non‐linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative. [ABSTRACT FROM AUTHOR]

Adopting Arabic clothing styles and in other ways mimicking Saudi Arabian cultural practice is one of the defining characteristics of the Indonesian tarbiyah (Islamic education) movement and the more general influence of Saudi Arabian Wahhabism and other forms of Middle Eastern style Salafism that has emerged in Indonesia since the early 1980s. This paper includes a translation of and extended commentary on a short story by Professor Komaruddin Hidayat of Syarif Hidayatullah State Islamic University in Jakarta that is highly critical of this trend. This is a counter narrative that references two Indonesian national heroes: Kyai Hasyim Asy'ari (1875-1947) one of the founders of Nahdatul Ulama, the country's largest Muslim organization and Mohammad Hatta (1902-1980), the first Vice President. Professor Hidayat uses a short story to make the point that Islamic authenticity need not be based on the emulation of Saudi Arabian cultural practices and that Islam, Indonesian cultures, and nationalism are entirely compatible. [ABSTRACT FROM AUTHOR]

Background: Understanding of sex differences, especially in terms of the influence of sex on therapeutic interventions, can lead to improved treatment and management for all. Aim: We examined temporal and regional trends in female participation and the reporting of sex differences in stroke randomized controlled trials. Methods: Randomized controlled trials from 1990 to 2018 were identified from ClinicalTrials.gov, using keywords "stroke" and "cerebrovascular accidents." Studies were selected if they enrolled ≥100 participants, included both sexes and were published trials (identified using PubMed, Google Scholar, and Scopus). Results: Of 1700 stroke randomized controlled trials identified, 277 were published and eligible for analysis. Overall, these randomized controlled trials enrolled only 40% females, and in the past 10 years, this percentage barely changed, peaking at 41% in 2008–2009 and 2012–2013. North American randomized controlled trials recruited the most women, at 43%, and Asia the lowest, at 40%. Among the 277 randomized controlled trials, 101 (36%) reported results according to sex, of which 91 (33%) were pre-specified analyses. The increasing trend in the number of studies reporting sex-differentiated results from 2008 to 2018 merely paralleled the increase in the number of papers published during the same time period. North American randomized controlled trials most often reported sex-specific results (42%), and Australia and Europe least often (31%). Conclusion: Little progress has been made in the inclusion of females and the reporting of sex in stroke randomized controlled trials. This highlights the need for key stakeholders, such as funders and journal editors, to provide clear guidance and effective implementation strategies to researchers in the scientific reporting of sex. [ABSTRACT FROM AUTHOR]

The article discusses a study on the association of diabetes with a greater risk of fatal COVID-19, influenza/pneumonia, and coronary heart disease in both sexes. Highlights include sex-specific associations of death by influenza/pneumonia, the use of Cox regression to obtain sex-specific hazard ratios, and the association of undiagnosed diabetes with a 3.5-fold excess risk of COVID-19 mortality in men.

Background: The ENhanced Control of Hypertension And Thrombolysis strokE study (ENCHANTED) trial was initiated as a 2 × 2 partial-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial to evaluate in thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A – low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B – early intensive blood pressure (BP) lowering (systolic target 130–140 mmHg) has superior efficacy and lower risk of ICH compared with guideline-recommended BP control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now concluding. Objective: To outline in detail and make public the predetermined statistical analysis plan (SAP) for the 'BP control' arm of this study. Methods: All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. Results: A SAP was developed for the results of the BP control arm of this study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. Conclusions: We have developed a predetermined SAP for the ENCHANTED BP control arm to be followed to avoid analysis bias arising from prior knowledge of the study findings. Clinical trial registration: ClinicalTrials.gov (NCT01422616); ISRCTN Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical Trials Registry – India (REF/2017/05/014334). [ABSTRACT FROM AUTHOR]

Background: The capacity of spot urine samples for detecting changes in population sodium and potassium excretion is unclear.Methods: Changes in urinary sodium and potassium excretion, over a 6-month to 2-year interval, were measured from 24-h urine samples and estimated from spot urine samples using several published methods in 3270 Chinese. Additional estimates were made by multiplying individual spot sodium and potassium concentrations by a single estimated 24-h urine volume derived from external data.Results: The measured difference in 24-h urinary excretion between intervention and control groups was -0.35 g (95% CI: -0.68 to -0.02; P = 0.039) for sodium and 0.66 g (95% CI: 0.52 to 0.80; P < 0.001) for potassium, based upon 24-h urine samples. The corresponding estimates of sodium differences for the Tanaka (-0.06 g), Kawasaki (-0.09 g), Intersalt without potassium (-0.09 g) and Intersalt with potassium (-0.14 g) equations were all smaller and identified no reduction in sodium excretion (all P > 0.10). The estimates were -0.65 g for sodium and 1.11 g for potassium using individual spot urine concentrations and an externally derived standard urine volume (both P < 0.01).Conclusions: The published equations were unable to detect the differences in sodium excretion measured by 24-h urine samples. A method based upon spot urine electrolyte concentrations and a standard urine volume may offer an alternative approach to measuring differences in sodium and potassium excretion between population groups without requiring 24-h urine, but will need further investigation. [ABSTRACT FROM AUTHOR]

Over recent years routine ultrasound scanning has identified increasing numbers of neonates as having hydronephrosis and pelvi-ureteric junction obstruction (PUJO). This patient group presents a diagnostic and management challenge for paediatric nephrologists and urologists. In this review we consider the known molecular mechanisms underpinning PUJO and review the potential of utilising this information to develop novel therapeutics and diagnostic biomarkers to improve the care of children with this disorder. [ABSTRACT FROM AUTHOR]

Aims: First, to conduct a detailed exploration of the prospective relations between four commonly used anthropometric measures with incident diabetes and to examine their consistency across different population subgroups. Second, to compare the ability of each of the measures to predict five-year risk of diabetes.Methods: We conducted a meta-analysis of individual participant data on body mass index (BMI), waist circumference (WC), waist-hip and waist-height ratio (WHtR) from the Obesity, Diabetes and Cardiovascular Disease Collaboration. Cox proportional hazard models were used to estimate the association between a one standard deviation increment in each anthropometric measure and incident diabetes. Harrell's concordance statistic was used to test the predictive accuracy of each measure for diabetes risk at five years.Results: Twenty-one studies with 154,998 participants and 9342 cases of incident diabetes were available. Each of the measures had a positive association with incident diabetes. A one standard deviation increment in each of the measures was associated with 64-80% higher diabetes risk. WC and WHtR more strongly associated with risk than BMI (ratio of hazard ratios: 0.95 [0.92,0.99] - 0.97 [0.95,0.98]) but there was no appreciable difference between the four measures in the predictive accuracy for diabetes at five years.Conclusions: Despite suggestions that abdominal measures of obesity have stronger associations with incident diabetes and better predictive accuracy than BMI, we found no overall advantage in any one measure at discriminating the risk of developing diabetes. Any of these measures would suffice to assist in primary diabetes prevention efforts. [ABSTRACT FROM AUTHOR]

Background: There is evidence to indicate that the lying flat head position increases cerebral blood flow and oxygenation in patients with acute ischemic stroke, but how these physiological effects translate into clinical outcomes is uncertain. The Head Position in Stroke Trial aims to determine the comparative effectiveness of lying flat (0°) compared to sitting up (>30°) head positioning, initiated within 24 h of hospital admission for patients with acute stroke. Design: An international, pragmatic, cluster-randomized, crossover, open, blinded outcome assessed clinical trial. Each hospital with an established acute stroke unit (cluster) site was required to recruit up to 140 consecutive cases of acute stroke (one phase of head positioning before immediately crossing over to the other phase of head positioning), including both acute ischemic stroke and intracerebral hemorrhage, in each randomized head position as a 'business as usual' policy. Objective: To outline in detail the predetermined statistical analysis plan for the study. Methods: All accumulated data will be reviewed and formally assessed. Information regarding baseline characteristics of patients, their process of care and management will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons are described. Results: A statistical analysis plan was developed that is transparent, verifiable, and predetermined before completion of data collection. Conclusions: We developed a predetermined statistical analysis plan for Head Position in Stroke Trial to avoid analysis bias arising from prior knowledge of the findings, in order to reliably quantify the benefits and harms of lying flat versus sitting up early after the onset of acute stroke. [ABSTRACT FROM AUTHOR]

Objectives: There is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank. Methods: The UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40–69 years) women and men between 2006 and 2010. Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone–binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men. Results: Data were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women. Conclusions: A higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI. Plain Language Summary: There are conflicting findings surrounding the association of sex hormones and myocardial infarction (MI) (heart disease). In particular, high oestradiol levels in women are often thought to be protective and explain why the rates of heart disease are lower in women than men. For men, those with low levels of testosterone are often thought to be more prone to develop heart disease in their lifetimes. Our study presents a comprehensive analysis of the association of sex hormones (in isolation and also together via their ratios), in women and men using the large-scale UK Biobank. We found that neither oestrogen nor testosterone alone were associated with heart disease in women and men after accounting for cardiovascular risk factors, but the ratio of testosterone and oestrogen was associated with a lower risk of heart disease in men, though not in women. We also saw the association of sex hormone–binding globulin (SHBG), and free androgen index (FAI) (calculated by the ratio of total testosterone level to SHBG) with heart disease was different between women and men, and between pre- and post-menopausal women. This paper highlights the complex interplay between sex hormones with heart disease in the presence of age and cardiovascular risk factors. In particular the balance (ratio) of sex hormones maybe more important, rather than each in isolation, when exploring their association with heart disease. Highlights: Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, higher oestrogen/testosterone ratio was associated with a lower risk of MI after adjustment for traditional CVD risk factors. Higher SHBG was associated with a lower risk of MI in men, but not women overall. Higher FAI was associated with a higher risk of MI in men but not women overall. There were differential effects in SHBG and FAI between pre- and post-menopausal women. [ABSTRACT FROM AUTHOR]

Background Sex and gender differences in chronic kidney disease (CKD), including epidemiology and response to treatment, remain poorly understood. This study aimed to investigate how women are represented in CKD clinical trials and whether sex- and gender-disaggregated outcomes were reported. Methods Clinical trials on CKD were identified from ClinicalTrials.gov. Randomised, phase 3/4 trials with ≥100 participants were selected to quantify women's representation among participants by computing the participation:prevalence ratio (PPR) and investigating whether sex-disaggregated analyses had been performed. Results In total, 192 CKD trials registered on ClinicalTrials.gov and published between 1995 and 2022 were included. Overall, women accounted for 66 875 (45%) of the 147 136 participants. Women's participation in clinical trials was lower than their representation in the underlying CKD population globally (55%). The PPR was 0.75 (95% confidence interval 0.72–0.78), with no significant variation irrespective of mean age, CKD stage, dialysis, location, type of intervention or funding agency. A total of 39 (20%) trials reported sex-disaggregated efficacy outcomes and none reported sex-disaggregated safety outcomes. Conclusion Women's participation in CKD clinical trials was lower than their representation in the underlying CKD population. Sex-disaggregated efficacy and safety outcomes were rarely reported. Improving women's enrolment into clinical trials is crucial to enable sex- and gender-disaggregated analysis and thus identify potential differences in treatment response between women and men. [ABSTRACT FROM AUTHOR]

Background: Microvascular disease is associated with a high risk of macrovascular events in patients with type 2 diabetes, but the impact of macrovascular disease on the risk of microvascular events remains unknown. We sought to evaluate the respective effects of prior microvascular and macrovascular disease on the risk of major outcomes, including microvascular events, in these patients. Methods: Participants in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) trial (n = 11,140) and the ADVANCE-ON post-trial study (n = 8494) were categorized into 4 groups at baseline: dual absence of microvascular or macrovascular disease (n = 6789), presence of microvascular disease alone (n = 761), macrovascular disease alone (n = 3196), and both (n = 394). Outcomes were all-cause mortality, major macrovascular events (MACE), and major clinical microvascular events. Results: All-cause mortality, MACE, and major clinical microvascular events occurred in 2265 (20%), 2166 (19%), and 807 (7%) participants respectively, during a median follow-up of 9.9 (inter-quartile interval 5.6-10.9) years. The adjusted hazard ratios [95% CI] of death, MACE, and major clinical microvascular events were each greater in patients with baseline microvascular disease (1.43 [1.20-1.71], 1.64 [1.37-1.97], and 4.74 [3.86-5.82], respectively), macrovascular disease (1.43 [1.30-1.57], 2.04 [1.86-2.25], and 1.26 [1.06-1.51]) or both (2.01 [1.65-2.45], 2.92 [2.40-3.55], and 6.30 [4.93-8.06]) compared with those without these conditions. No interaction was observed between baseline microvascular and macrovascular disease for these events. The addition of microvascular disease (change in c-statistic [95% CI] 0.005 [0.002-0.008], p = 0.02) or macrovascular disease (0.005 [0.002-0.007], p < 0.0001) considered separately or together (0.011 [0.007-0.014], p < 0.0001) improved the discrimination and the classification (integrated discrimination improvement (IDI): 0.013 [0.010-0.016], p < 0.001; net reclassification improvement (NRI): 0.021 [0.011-0.032], p < 0.001) of the risk of all-cause mortality. Microvascular disease improved discrimination (0.009 [0.003-0.014]) and classification (IDI: 0.008 [0.006-0.010]; NRI: 0.011 [0.001-0.020]) of MACE. Baseline macrovascular disease modestly enhanced IDI (0.002 [0.001-0.002]) and NRI (0.041 [0.002-0.087]), but not discrimination, of major clinical microvascular events. Conclusions: Microvascular and macrovascular disease are independently associated with the 10-year risk of death, MACE, and major clinical microvascular events in patients with type 2 diabetes. The coexistence of these conditions was associated with the highest risks. [ABSTRACT FROM AUTHOR]

This article argues that in practice, concepts of magico-spiritual power (Javanese: kesekten; Indonesian: kesaktian) are linked with sexuality, particularly female sexuality, in some segments of contemporary Central and East Javanese Muslim society. Few scholars have turned attention to the interconnectedness of these seemingly contradictory topics. Feminist studies tend to focus on the ways in which women locate themselves within and critique Sharia-based discursive and social orders, without considering the roles that magico-spiritual power and associated practices play in these Islamic systems or in Islam in a more general sense. Similarly, male scholarship that considers the cultural relevance of Islam and magic rarely refers to gendered and sexual dimensions as praxis from a feminist perspective. By drawing on examples of 'magical women' including the Javanese spirit queen of the southern ocean Gusti Kanjeng Ratu Kidul, the historical Hindu figure Ken Dedes, and contemporary ritual sex practices at a Muslim saint's grave, we show how women, female spiritual beings and female sexuality, and sexuality in general, can be considered sources of magico-spiritual power in Muslim Java. Our arguments conclude that in Javanese Islam, transgression of Sharia sexual norms can be both a sign and a source of magico-spiritual power. [ABSTRACT FROM AUTHOR]

Objective: The burden of vascular diseases remains substantial in patients with type 2 diabetes, requiring identification of further risk markers. We tested the absence of dorsalis pedis and posterior tibial pulses as predictors of major macrovascular and microvascular events, death, and cognitive decline in this population.Research Design and Methods: Data were derived from 11,120 patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study. Absent peripheral pulses at baseline were defined as absence of at least one dorsalis pedis or posterior tibial pulse.Results: Absent compared with present peripheral pulses (n = 2,218) were associated with increased 5-year risks for major macrovascular events (hazard ratio 1.47 [95% CI 1.28-1.69], P < 0.0001), myocardial infarction (1.45 [1.13-1.87], P = 0.003), stroke (1.57 [1.23-2.00], P = 0.0003), cardiovascular death (1.61 [1.33-1.95], P < 0.0001), heart failure (1.49 [1.21-1.84], P = 0.0002), all-cause mortality (1.48 [1.29-1.71], P < 0.0001), major microvascular events (1.17 [1.00-1.36], P = 0.04), nephropathy (1.24 [1.00-1.54], P = 0.04), end-stage renal disease or renal death (2.04 [1.12-3.70], P = 0.02), and peripheral neuropathy (1.13 [1.05-1.21], P = 0.0008) after multiple adjustment. Participants with absent dorsalis pedis or posterior tibial pulses had comparable hazard ratios. Risks increased proportionally with the number of absent peripheral pulses, with the highest risks observed in patients with three or four absent pulses. Every additional absent pulse increases the risk of all outcomes.Conclusions: Absent dorsalis pedis and/or posterior tibial pulses are independent predictors of major vascular outcomes in patients with type 2 diabetes. These simple clinical indicators should be used to improve risk stratification and treatment of these patients. [ABSTRACT FROM AUTHOR]

Objective: Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis in type 2 diabetes, but the relationship between other vascular diseases and PAD has been poorly investigated. We examined the impact of previous microvascular and macrovascular disease on the risk of major PAD in patients with type 2 diabetes.Research Design and Methods: We analyzed 10,624 patients with type 2 diabetes free from baseline major PAD in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) clinical trial. The primary composite outcome was major PAD defined as PAD-induced death, peripheral revascularization, lower-limb amputation, or chronic ulceration. The secondary end points were the PAD components considered separately.Results: Major PAD occurred in 620 (5.8%) participants during 5 years of follow-up. Baseline microvascular and macrovascular disease were both associated with subsequent risk of major PAD after adjustment for age, sex, region of origin, and randomized treatments. However, only microvascular disease remained significantly associated with PAD after further adjustment for established risk factors. The highest risk was observed in participants with a history of macroalbuminuria (hazard ratio 1.91 [95% CI 1.38-2.64], P < 0.0001) and retinal photocoagulation therapy (1.60 [1.11-2.32], P = 0.01). Baseline microvascular disease was also associated with a higher risk of chronic lower-limb ulceration (2.07 [1.56-2.75], P < 0.0001) and amputation (1.59 [1.15-2.22], P = 0.006), whereas baseline macrovascular disease was associated with a higher rate of angioplasty procedures (1.75 [1.13-2.73], P = 0.01).Conclusions: Microvascular disease, particularly macroalbuminuria and retinal photocoagulation therapy, strongly predicts major PAD in patients with type 2 diabetes, but macrovascular disease does not. [ABSTRACT FROM AUTHOR]

Aim: To estimate and compare the results from all randomised trials of triple combinations of anti-diabetes therapies that reported the reduction of glycated haemoglobin (HbA1c) and associated effects on body weight and hypoglycaemia.Methods: PubMed and the Cochrane Library were searched for trials with at least one study arm on triple therapy and which reported the differences in mean change in HbA1c between two study arms. These were included in a network meta-analysis.Results: Altogether, 15,182 participants from 40 trials with treatment duration of 6-12months were included. Compared with none/placebo added to dual therapy, the addition of a drug therapy from six of eight drug classes to existing dual therapy resulted in significant additional mean reductions in HbA1c from -0.56% (-6.2mmol/mol; dipeptidyl peptidase 4 inhibitors) to -0.94% (-10.3mmol/mol; thiazolidinediones). Of the six drug classes, three were associated with less favourable weight change and two were associated with more favourable weight change when compared with none/placebo added to dual therapy. Furthermore, five drug classes were associated with greater odds of hypoglycaemia. Similar results were observed in analyses of studies with a 6month treatment duration and after excluding study arms that contained insulin.Conclusions: Overall triple therapy combinations were similar in improving diabetes control although there were some differences in adverse effects. By balancing the risks and benefits of each therapy, the estimates of pairwise comparisons of triple therapies for HbA1c, body weight and hypoglycaemia provided in this study may further inform evidence based practice. [ABSTRACT FROM AUTHOR]

Objective: We aimed to estimate the impact of past and future changes in obesity and diabetes prevalence in mid-life on disability prevalence for adult Australians.Methods: We analysed data from the Australian Diabetes, Obesity and Lifestyle study (AusDiab) including participants aged 45-64years, disability-free at baseline (1999/2000) with disability information at follow-up (2011/12) (n=2107). We used coefficients from multinomial logistic regression to predict 10-year probabilities of disability and death from baseline predictors (age, sex, obesity, smoking, diabetes and hypertension). We estimated the prevalence of disability attributable to past (1980) and expected future (2025) changes in obesity and diabetes prevalence using the life table approach.Results: We estimated that the prevalence of disability for those aged between 55 and 74years would have been 1697 cases per 100,000 persons less in 2010 (10.3% less) if the rates of obesity and diabetes observed in 2000 had been as low as the levels observed in 1980. However, if instead the prevalence of obesity and diabetes had been as high as the levels expected in 2025, then the prevalence of disability would have been an additional 2173 per 100,000 persons (an additional 13.2%).Conclusions: We demonstrate, for the first time, a substantial potential impact of obesity and diabetes trends on disability amongst those aged 55-74years. In Australian adults by 2025 we estimate that around 26% of disability cases would have been avoidable if there had been no change in obesity and diabetes prevalence since 1980. A similar impact is likely around the world in developed countries. [ABSTRACT FROM AUTHOR]

Background: Theoretical links between seasonal lack of sunlight, hypovitaminosis D and excess cardiovascular disease and death prompted our adding novel to conventional cohort analyses.Methods: We tested three postulates on 13,224 Scottish Heart Health Extended Cohort participants, assayed for 25-hydroxyvitamin D (25OHD) and followed for 22 years. (i) Endpoints enumerated by month of occurrence mirror annual seasonal oscillation in 25OHD. (ii) Endpoint seasonality is increased in people with below median 25OHD. (iii) Low 25OHD predicts endpoints independently of major risk factors.Results: Baseline median 25OHD level was 36.4 (other quartiles 26.7, 51.7) nmol/l. The March trough was half the August peak, both well after seasonal solstices. (i) There was no demonstrable monthly variation in First Cardiovascular Event (n = 3307). Peaks and troughs for All Death and Cardiovascular Death (n = 2987, 1350) were near the solstices, earlier than extremes of 25OHD. (ii) Endpoint variability showed no difference between those above and below median 25OHD. (iii) Cox model hazard ratios (HR), by decreasing 25OHD, increased modestly and nonspecifically for all endpoints examined, with no threshold, the gradients diminishing by ∼ : 60% following multiple adjustment. For Cardiovascular Disease, HR, by 20 (∼ SD) nmol/l decrease, =1.224 (1.175, 1.275) adjusted for age and sex; additionally adjusted for family history, deprivation index, smoking, systolic blood pressure, total and HDL cholesterol, =1.093 (1.048, 1.139); All Deaths = 1.238 (1.048, 1.139) and 1.098 (1.050, 1.149). 25OHD made no independent contribution to cardiovascular discrimination and reclassification.Conclusions: Our analyses challenge vitamin D's alleged role as major prime mover in cardiovascular disease and mortality. [ABSTRACT FROM AUTHOR]

Objective: This study explored whether activation of the receptor for advanced glycation end products (RAGE) is implicated in the development of diabetes complications.Research Design and Methods: A case-cohort study was performed in 3,763 participants with prevalent diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. The hazard ratios (HRs) for death, major cardiovascular events, and new or worsening nephropathy were derived using Cox regression models, and the ability of sRAGE and AGE levels to reclassify the risk of nephropathy was assessed.Results: After adjustment for a range of possible confounders and other risk factors, sRAGE levels were associated with all-cause mortality (HR 1.11 for a 1-SD increase of log sRAGE [95% CI 1.00-1.22]; P = 0.045) and new or worsening nephropathy (HR 1.20 for a 1-SD increase of log sRAGE [95% CI 1.02-1.41]; P = 0.032). Circulating AGE levels were also independently associated with new or worsening nephropathy (HR 1.21 for a 1-SD increase [95% CI 1.08-1.36]; P = 0.001). Both markers also significantly improved the accuracy with which the 5-year risk of new or worsening nephropathy could be predicted (net reclassification index in continuous model, 0.25 for sRAGE and 0.24 for AGE levels).Conclusions: In adults with type 2 diabetes, increased levels of sRAGE are independently associated with new or worsening kidney disease and mortality over the next 5 years. Higher levels of AGE are also associated with an increased risk of adverse renal outcomes. The AGE/RAGE axis may be of importance in the prevention and management of diabetes complications. [ABSTRACT FROM AUTHOR]

Women are under-represented among authors of scientific papers. Although the number of retractions has been rising over the past few decades, gender differences among authors of retracted papers remain poorly understood. Therefore, this study investigated gender differences in authorship of retracted papers in biomedical sciences available on RetractionWatch. Among 35,635 biomedical articles retracted between 1970 and 2022, including 20,849 first authors and 20,413 last authors, women accounted for 27.4% [26.8 to 28.0] of first authors and 23.5% [22.9 to 24.1] of last authors. The lowest representation of women was found for fraud (18.9% [17.1 to 20.9] for first authors and 13.5% [11.9 to 15.1] for last authors) and misconduct (19.5% [17.3 to 21.9] for first authors and 17.8% [15.7 to 20.3] for last authors). Women's representation was the highest for issues related to editors and publishers (35.1% [32.2 to 38.0] for first authors and 24.8% [22.9 to 26.8] for last authors) and errors (29.5% [28.0 to 31.0] for first authors and 22.1% [20.7 to 23.4] for last authors). Most retractions (60.9%) had men as first and last authors. Gender equality could improve research integrity in biomedical sciences. [ABSTRACT FROM AUTHOR]

Aims: Diabetes has been associated with a greater excess risk of cardiovascular disease (CVD) in women than men. We investigated whether there are also sex differences in the association of diabetes duration and the risk of CVD.Methods: Data were used from 18,961 (40% women) individuals with type 2 diabetes, without a history of CVD, in the UK Biobank. Sex-specific incidence rates were calculated by diabetes duration. Cox proportional hazards analyses estimated multiple-adjusted sex-specific hazard ratios (HR) and women-to-men ratio of HRs (RHR).Results: Over a median follow-up of 11 years, 1,506 (29% women) CVD events were documented. Compared with men, women had lower multiple-adjusted incidence rates of CVD per 10,000 person-years for all categories of diabetes duration. Duration of diabetes was associated with an increased risk of CVD in both sexes. A 5-year increase in diabetes duration was associated with an approximately similar excess risk of about 20% for each of the three endpoints, in both sexes.Conclusions/interpretation: The increased risk of CVD associated with longer duration of diabetes is similar in women and men, and thus cannot explain the higher excess risk from diabetes in women in this study population. [ABSTRACT FROM AUTHOR]

OBJECTIVE We investigated microvascular event risk in people with type 2 diabetes and assessed whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) improved prediction. RESEARCH DESIGN AND METHODS We performed a case-cohort study, including 439 incident cases of microvascular events (new or worsening nephropathy or retinopathy) and 2,946 noncase subjects identified from participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. NT-proBNP and hsTnT were measured in stored plasma samples using automated commercial assays. RESULTS After adjustment for age, sex, and randomized treatment, the hazard ratios for microvascular events per 1-SD increase in the log-transformed hsTnT and NT-proBNP were 1.67 (95% CI 1.51-1.85) and 1.63 (1.44-1.84), respectively. After further adjustment for classical and diabetes-related cardiovascular disease risk factors, the hazard ratios attenuated to 1.40 (1.24-1.58) and 1.41 (1.24-1.60), respectively. While the C statistic did not improve on addition of hsTnT or NT-proBNP for the total microvascular end point, a combination of both markers improved the prediction of nephropathy (P = 0.033) but not retinopathy (P = 0.72). The corresponding net reclassification indices in a three-risk category model (<10%, 10-15%, and >15% 5-year risk) for all microvascular events were 7.31% (95% CI 2.24-12.79) for hsTNT addition, 6.23% (1.74-11.5) for NT-proBNP addition, and 7.1% (1.5-12.9) for both markers together. CONCLUSIONS These data suggest that cardiac biomarkers moderately improve microvascular event risk prediction, in particular the risk of nephropathy. Further studies examining the value of this approach for trial design and clinical use are warranted. [ABSTRACT FROM AUTHOR]

: In a systematic review and meta-analysis, Kazem Rahimi and colleagues examine the burden of heart failure in low- and middle-income countries. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6) are associated with cardiovascular disease (CVD) and death in general populations. However, studies of these factors in type 2 diabetes are limited. We studied their associations with the risk of major macrovascular events, microvascular complications, and mortality in patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Study. Plasma CRP, fibrinogen, and IL-6 levels were determined in a case-cohort study (n = 3,865) nested within the 11,140 men and women with type 2 diabetes and baseline CVD or risk factors in the ADVANCE Study. All three biomarkers of inflammation were associated with an increased risk of macrovascular events and death in analyses adjusted for age, sex, and treatment groups. After further adjustment, only IL-6 was an independent predictor of macrovascular events (hazard ratio per SD increase 1.37 [95% CI 1.24-1.51]) and death (1.35 [1.23-1.49]). IL-6 significantly improved the prediction of macrovascular events and death. After adjustment, none of the markers predicted microvascular complications. We conclude that IL-6 levels, but not CRP or fibrinogen levels, add significantly to the prediction of macrovascular events and mortality in individuals with type 2 diabetes who have baseline CVD or risk factors. [ABSTRACT FROM AUTHOR]

The proportional hazards model assumes that the log hazard ratio is a linear function of parameters. In the current paper, we model the log relative risk as an inverse polynomial, which is particularly suitable for modeling bounded and asymmetric functions. The parameters estimated by maximizing the partial likelihood are consistent and asymptotically normal. The advantages of the inverse polynomial model over the ordinary polynomial model and the fractional polynomial model for fitting various asymmetric log relative risk functions are shown by simulation. The utility of the method is further supported by analyzing two real data sets, addressing the specific question of the location of the minimum risk threshold. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

There is strong evidence from meta-analyses of prospective epidemiological studies that increasing plasma fibrinogen levels are associated with an increasing risk of cardiovascular disease ( CVD) and all-cause mortality. However, there are few published direct comparisons of the several different available fibrinogen assays in association with CVD or mortality. We therefore prospectively compared the standardized von Clauss assay of clottable fibrinogen with three other assays: prothrombin time ( PT)-derived clottable fibrinogen, immunonephelometric fibrinogen, and heat precipitable fibrinogen in the Scottish Heart Health Extended Cohort. Hazard ratios ( HRs) for a standard deviation increase in fibrinogen for risk of CVD, adjusted for age and sex, were 1·17 (95% confidence interval [ CI] 1·14; 1·21) for the von Clauss assay; 1·19 (1·06; 1·33) for the heat precipitation assay; 1·16 (1·01; 1·35) for the PT-derived assay; and 1·28 (1·10; 1·51) for the immunonephelometric assay. HRs for all-cause mortality were 1·21 (1·18; 1·24); 1·13 (1·01; 1·26), 1·17 (1·00; 1·37) and 1·17 (0·99; 1·39), respectively. No significant differences were observed between the assays in such comparisons. We therefore conclude that the choice between plasma fibrinogen assays in routine clinical haematology and biochemistry laboratories should depend on practical factors, and not on expected differences in the strength of associations. [ABSTRACT FROM AUTHOR]

While Islamist forms of terrorism have received a great deal of attention from scholars, insider accounts by indigenous scholars are still under-represented. This Special Issue of the Asian Journal of Social Psychology brings together three articles on religious terrorism and sacred violence in Indonesia, the world's most populous Islamic state. They bring together qualitative methods, including interviews with terrorist members of KOMPAK and Jemaah Islamiyah (including the Bali Bombers), with quantitative methods using structural equation modelling to explain a national representative sample's attitudes towards sacred violence. The articles converge towards an indigenous theory of Islamist terrorism for Indonesia involving three steps: (i) existential threat (triggered by violence inflicted on Muslims, nationally or internationally, and perceptions of the impurity of the secular Indonesian government), (ii) self-categorization of the world into infidels and believers (thus arguing that the current situation is a state of war where violence against non-combatants is justified), and (iii) jihadi ideology as the trigger for turning existential threat into religious violence. It is the interpretation of scripture offered by trusted leaders, often reinforced by oaths of obedience, rather than scripture itself that fuels the indigenous psychology of violent (lesser) jihad presented here. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Participants in ADVANCE were drawn from many countries. We examined whether the effects of intensive glycemic control on major outcomes in ADVANCE differ between participants from Asia, established market economies (EMEs), and eastern Europe. RESEARCH DESIGN AND METHODS--ADVANCE was a clinical trial of 11,140 patients with type 2 diabetes, lasting a median of 5 years. Demographic and clinical characteristics were compared across regions using generalized linear and mixed models. Effects on outcomes of the gliclazide modified release-based intensive glucose control regimen, targeting an HbA1c of ≤6.5%, were compared across regions using Cox proportional hazards models. RESULTS--When differences in baseline variables were allowed for, the risks of primary outcomes (major macrovascular or microvascular disease) were highest in Asia (joint hazard ratio 1.33 [95% CI 1.17-1.50]), whereas macrovascular disease was more common (1.19 [1.00-1.42]) and microvascular disease less common (0.77 [0.62-0.94]) in eastern Europe than in EMEs. Risks of death and cardiovascular death were highest in eastern Europe, and the mean difference in glycosylated hemoglobin between the intensive and standard groups was lowest in EMEs. Despite these and other differences, the effects of intensive glycemic control were not significantly different (P≥0.23) between regions for any outcome, including mortality, vascular end points, and severe hypoglycemic episodes. CONCLUSIONS--Irrespective of absolute risk, the effects of intensive glycemic control with the gliclazide MR-based regimen used in ADVANCE were similar across Asia, EMEs, and eastern Europe. This regimen can safely be recommended for patients with type 2 diabetes in all of these regions. [ABSTRACT FROM AUTHOR]

Background--A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. Methods and Results--We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86-1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81-1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41-0.88). Substantial statistical heterogeneity was evident for the case-control studies (I² = 66%, P = 0.01), but not for the cohort studies (I²; = 0%, P = 0.48) or randomized trials (I² = 30%, P = 0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. Conclusions--We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs. [ABSTRACT FROM AUTHOR]

The article presents a study on the risk of cigarette smoking among women with coronary heart disease other than men. It estimates the effects of smoking through a systematic review and meta-analysis of prospective cohort studies from 1996 up to 2010. Data were collected by measure of relative risk (RR) and associated variability from both sexes. Using a random effects model with inverse variance weighting and estimated RR ratios, data have been gathered in uncovering risks in different sexes.

In 1965 the Indonesian Communist Party (PKI) was the second largest communist party in Asia. Indonesian politics was predicated on a precarious balance of nationalist (PNI), Muslim (Masyumi) and communist (PKI) political parties, the military, and the country's charismatic president, Sukamo (Feith 2006; Lev 1967). In the wake of an abortive coup on 30 September, the military, Muslim, and nationalist death squads killed at least 200,000 people thought to be party members or supporters. This orgy of violence brought the authoritarian military-dominated New Order government of Indonesia's second president, Soeharto, to power. He was to rule Indonesia with an iron hand until 1998. [ABSTRACT FROM AUTHOR]

The article presents results of a national survey on physicians' opinions about reimbursement reform proposals. Findings reveal physicians' dissatisfaction with Medicare, and little consensus for major proposals that carried risks of reduced reimbursement to health care providers. Opposition to bundled care payment system and high level of support for incentive-based reform are highlighted. Successful adoption of reforms are said to require a better understanding of physicians' concerns.

Abstract: Background: The pro-inflammatory cytokines, interleukin (IL)-18 and tumour necrosis factor-α (TNFα) may play a role in coronary heart disease (CHD). We aimed to extend data on their relationships to the risk of CHD in generally healthy populations. Methods: During 5.5years follow-up in the Fletcher Challenge general population cohort there were 256 CHD cases, and 615 controls were matched for age and sex. Baseline plasma levels of IL-18 and TNFα were related to CHD risk in available samples (77%). Results: Plasma levels of IL-18 (11% increase in mean, p =0.01) and TNFα (10% increase in mean p =0.024) were significantly elevated in CHD cases versus controls. In univariable models IL-18 was associated with CHD risk (odds ratio [OR] upper third to lower third, 1.63; 95% CI 1.08, 2.46), but TNFα was not (OR 1.33; 95% CI 0.87, 2.02).After adjusting for major CHD risk factors and CRP, the association of IL-18 with CHD risk was attenuated (OR 1.69; 95% CI 0.94, 3.03). Conclusions: IL-18, but not TNFα, had a non-negligible association with CHD risk, although the association of IL-18 with risk was weak after full adjustment. These cytokines may play a role in CHD pathology, but may not be robust risk biomarkers. [Copyright &y& Elsevier]

Plasma fibrinogen is an established risk factor for cardiovascular disease (CVD), but it has not been established whether it adds predictive value to risk scores. In the Scottish Heart Health Extended Cohort Study, we measured plasma fibrinogen in 13 060 men and women, aged 30–74 years, initially free of CVD. After follow-up for a median of 19·2 years, 2626 subjects had at least one CVD event. After adjusting for classical CVD risk factors and socio-economic status, the hazard ratios (95% confidence interval) for a one unit (g/l) increase in plasma fibrinogen were 1·09 (1·02, 1·16) for men and 1·10 (1·02, 1·19) for women. Although fibrinogen added significantly to the discrimination of the Framingham risk score for women, it failed to do so for men. Fibrinogen did not add significantly to the ASSIGN risk score. Fibrinogen added between 1·3% and 3·2% to the classification of CVD status by the existing risk scores. We conclude that the added value of fibrinogen to two currently used risk scores is low; hence population screening with fibrinogen for this purpose is unlikely to be clinically useful or cost-effective. [ABSTRACT FROM AUTHOR]