Summary Background Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used ...recent national health examination surveys. We estimated worldwide trends in population mean BMI. Methods We estimated trends and their uncertainties of mean BMI for adults 20 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (960 country-years and 9·1 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean BMI by age, country, and year, accounting for whether a study was nationally representative. Findings Between 1980 and 2008, mean BMI worldwide increased by 0·4 kg/m2 per decade (95% uncertainty interval 0·2–0·6, posterior probability of being a true increase >0·999) for men and 0·5 kg/m2 per decade (0·3–0·7, posterior probability >0·999) for women. National BMI change for women ranged from non-significant decreases in 19 countries to increases of more than 2·0 kg/m2 per decade (posterior probabilities >0·99) in nine countries in Oceania. Male BMI increased in all but eight countries, by more than 2 kg/m2 per decade in Nauru and Cook Islands (posterior probabilities >0·999). Male and female BMIs in 2008 were highest in some Oceania countries, reaching 33·9 kg/m2 (32·8–35·0) for men and 35·0 kg/m2 (33·6–36·3) for women in Nauru. Female BMI was lowest in Bangladesh (20·5 kg/m2 , 19·8–21·3) and male BMI in Democratic Republic of the Congo 19·9 kg/m2 (18·2–21·5), with BMI less than 21·5 kg/m2 for both sexes in a few countries in sub-Saharan Africa, and east, south, and southeast Asia. The USA had the highest BMI of high-income countries. In 2008, an estimated 1·46 billion adults (1·41–1·51 billion) worldwide had BMI of 25 kg/m2 or greater, of these 205 million men (193–217 million) and 297 million women (280–315 million) were obese. Interpretation Globally, mean BMI has increased since 1980. The trends since 1980, and mean population BMI in 2008, varied substantially between nations. Interventions and policies that can curb or reverse the increase, and mitigate the health effects of high BMI by targeting its metabolic mediators, are needed in most countries. Funding Bill & Melinda Gates Foundation and WHO.
Summary Background Data for trends in glycaemia and diabetes prevalence are needed to understand the effects of diet and lifestyle within populations, assess the performance of interventions, and ...plan health services. No consistent and comparable global analysis of trends has been done. We estimated trends and their uncertainties in mean fasting plasma glucose (FPG) and diabetes prevalence for adults aged 25 years and older in 199 countries and territories. Methods We obtained data from health examination surveys and epidemiological studies (370 country-years and 2·7 million participants). We converted systematically between different glycaemic metrics. For each sex, we used a Bayesian hierarchical model to estimate mean FPG and its uncertainty by age, country, and year, accounting for whether a study was nationally, subnationally, or community representative. Findings In 2008, global age-standardised mean FPG was 5·50 mmol/L (95% uncertainty interval 5·37–5·63) for men and 5·42 mmol/L (5·29–5·54) for women, having risen by 0·07 mmol/L and 0·09 mmol/L per decade, respectively. Age-standardised adult diabetes prevalence was 9·8% (8·6–11·2) in men and 9·2% (8·0–10·5) in women in 2008, up from 8·3% (6·5–10·4) and 7·5% (5·8–9·6) in 1980. The number of people with diabetes increased from 153 (127–182) million in 1980, to 347 (314–382) million in 2008. We recorded almost no change in mean FPG in east and southeast Asia and central and eastern Europe. Oceania had the largest rise, and the highest mean FPG (6·09 mmol/L, 5·73–6·49 for men; 6·08 mmol/L, 5·72–6·46 for women) and diabetes prevalence (15·5%, 11·6–20·1 for men; and 15·9%, 12·1–20·5 for women) in 2008. Mean FPG and diabetes prevalence in 2008 were also high in south Asia, Latin America and the Caribbean, and central Asia, north Africa, and the Middle East. Mean FPG in 2008 was lowest in sub-Saharan Africa, east and southeast Asia, and high-income Asia-Pacific. In high-income subregions, western Europe had the smallest rise, 0·07 mmol/L per decade for men and 0·03 mmol/L per decade for women; North America had the largest rise, 0·18 mmol/L per decade for men and 0·14 mmol/L per decade for women. Interpretation Glycaemia and diabetes are rising globally, driven both by population growth and ageing and by increasing age-specific prevalences. Effective preventive interventions are needed, and health systems should prepare to detect and manage diabetes and its sequelae. Funding Bill & Melinda Gates Foundation and WHO.
Summary Background Data for trends in blood pressure are needed to understand the effects of its dietary, lifestyle, and pharmacological determinants; set intervention priorities; and evaluate ...national programmes. However, few worldwide analyses of trends in blood pressure have been done. We estimated worldwide trends in population mean systolic blood pressure (SBP). Methods We estimated trends and their uncertainties in mean SBP for adults 25 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (786 country-years and 5·4 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean SBP by age, country, and year, accounting for whether a study was nationally representative. Findings In 2008, age-standardised mean SBP worldwide was 128·1 mm Hg (95% uncertainty interval 126·7–129·4) in men and 124·4 mm Hg (123·0–125·9) in women. Globally, between 1980 and 2008, SBP decreased by 0·8 mm Hg per decade (−0·4 to 2·2, posterior probability of being a true decline=0·90) in men and 1·0 mm Hg per decade (−0·3 to 2·3, posterior probability=0·93) in women. Female SBP decreased by 3·5 mm Hg or more per decade in western Europe and Australasia (posterior probabilities ≥0·999). Male SBP fell most in high-income North America, by 2·8 mm Hg per decade (1·3–4·5, posterior probability >0·999), followed by Australasia and western Europe where it decreased by more than 2·0 mm Hg per decade (posterior probabilities >0·98). SBP rose in Oceania, east Africa, and south and southeast Asia for both sexes, and in west Africa for women, with the increases ranging 0·8–1·6 mm Hg per decade in men (posterior probabilities 0·72–0·91) and 1·0–2·7 mm Hg per decade for women (posterior probabilities 0·75–0·98). Female SBP was highest in some east and west African countries, with means of 135 mm Hg or greater. Male SBP was highest in Baltic and east and west African countries, where mean SBP reached 138 mm Hg or more. Men and women in western Europe had the highest SBP in high-income regions. Interpretation On average, global population SBP decreased slightly since 1980, but trends varied significantly across regions and countries. SBP is currently highest in low-income and middle-income countries. Effective population-based and personal interventions should be targeted towards low-income and middle-income countries. Funding Funding Bill & Melinda Gates Foundation and WHO.
Summary Background Data for trends in serum cholesterol are needed to understand the effects of its dietary, lifestyle, and pharmacological determinants; set intervention priorities; and evaluate ...national programmes. Previous analyses of trends in serum cholesterol were limited to a few countries, with no consistent and comparable global analysis. We estimated worldwide trends in population mean serum total cholesterol. Methods We estimated trends and their uncertainties in mean serum total cholesterol for adults 25 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (321 country-years and 3·0 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean total cholesterol by age, country, and year, accounting for whether a study was nationally representative. Findings In 2008, age-standardised mean total cholesterol worldwide was 4·64 mmol/L (95% uncertainty interval 4·51–4·76) for men and 4·76 mmol/L (4·62–4·91) for women. Globally, mean total cholesterol changed little between 1980 and 2008, falling by less than 0·1 mmol/L per decade in men and women. Total cholesterol fell in the high-income region consisting of Australasia, North America, and western Europe, and in central and eastern Europe; the regional declines were about 0·2 mmol/L per decade for both sexes, with posterior probabilities of these being true declines 0·99 or greater. Mean total cholesterol increased in east and southeast Asia and Pacific by 0·08 mmol/L per decade (−0·06 to 0·22, posterior probability=0·86) in men and 0·09 mmol/L per decade (−0·07 to 0·26, posterior probability=0·86) in women. Despite converging trends, serum total cholesterol in 2008 was highest in the high-income region consisting of Australasia, North America, and western Europe; the regional mean was 5·24 mmol/L (5·08–5·39) for men and 5·23 mmol/L (5·03–5·43) for women. It was lowest in sub-Saharan Africa at 4·08 mmol/L (3·82–4·34) for men and 4·27 mmol/L (3·99–4·56) for women. Interpretation Nutritional policies and pharmacological interventions should be used to accelerate improvements in total cholesterol in regions with decline and to curb or prevent the rise in Asian populations and elsewhere. Population-based surveillance of cholesterol needs to be improved in low-income and middle-income countries. Funding Bill & Melinda Gates Foundation and WHO.
Pain radiating from the spine into the leg is commonly referred to as "sciatica," "Sciatica" may include various conditions such as radicular pain or painful radiculopathy. It may be associated with ...significant consequences for the person living with the condition, imposing a reduced quality of life and substantial direct and indirect costs. The main challenges associated with a diagnosis of "sciatica" include those related to the inconsistent use of terminology for the diagnostic labels and the identification of neuropathic pain. These challenges hinder collective clinical and scientific understanding regarding these conditions. In this position paper, we describe the outcome of a working group commissioned by the Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP) which was tasked with the following objectives: (1) to revise the use of terminology for classifying spine-related leg pain and (2) to propose a way forward on the identification of neuropathic pain in the context of spine-related leg pain. The panel recommended discouraging the term "sciatica" for use in clinical practice and research without further specification of what it entails. The term "spine-related leg pain" is proposed as an umbrella term to include the case definitions of somatic referred pain and radicular pain with and without radiculopathy. The panel proposed an adaptation of the neuropathic pain grading system in the context of spine-related leg pain to facilitate the identification of neuropathic pain and initiation of specific management in this patient population.
In this study, we aimed to validate our extensive preclinical data on phosphodiesterase 4 (PDE4) as actionable target in B-cell malignancies. Our specific objectives were to determine the safety, ...pharmacokinetics, and pharmacodynamics (PI3K/AKT activity), as well as to capture any potential antitumor activity of the PDE4 inhibitor roflumilast in combination with prednisone in patients with advanced B-cell malignancies.
Single-center, exploratory phase Ib open-label, nonrandomized study. Roflumilast (500 mcg PO) was given daily for 21 days with prednisone on days 8 to 14. Additional 21-day cycles were started if patients tolerated cycle 1 and had at least stable disease.
Ten patients, median age 65 years with an average of three prior therapies, were enrolled. The median number of cycles administered was 4 (range, 1-13). Treatment was well tolerated; the most common ≥grade 2 treatment-related adverse events were fatigue, anorexia (≥25%), and transient ≥ grade 2 neutropenia (30%). Treatment with roflumilast as a single agent significantly suppressed PI3K activity in the 77% of patients evaluated; on average, patients with PI3K/AKT suppression stayed in trial for 156 days (49-315) versus 91 days (28-139 days) for those without this biomarker response. Six of the nine evaluable patients (66%) had partial response or stable disease. The median number of days in trial was 105 days (range, 28-315).
Repurposing the PDE4 inhibitor roflumilast for treatment of B-cell malignancies is safe, suppresses the oncogenic PI3K/AKT kinases, and may be clinically active.
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Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight ...risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
Ali CMB Polarization Telescope (AliCPT) is the first Cosmic Microwave Background (CMB) polarimeter with a large focal plane camera to be deployed in the Northern Hemisphere, in the Tibetan Plateau. ...Here we present the design of a dichroic (90/150 GHz) focal plane camera capable of hosting up to 32,376 Transition-Edge Sensor (TES) bolometers operating from a base temperature of 280 mK. Detectors are fabricated as monolithic arrays of 1,704 feedhorn-coupled and polarization-sensitive TES bolometers that are packaged in independent modules and read out with a microwave multiplexing architecture. A custom RFSoC-based system manages the multiplexing readout. Prototype AliCPT pixels have been fabricated and characterized, demonstrating passband performance within 2.5% of design and cross-polarization systematic sensitivity <inline-formula><tex-math notation="LaTeX">\leq</tex-math></inline-formula>2%.
Summary Hormone receptor status is an integral component of decision-making in breast cancer management. IHC4 score is an algorithm that combines hormone receptor, HER2, and Ki-67 status to provide a ...semiquantitative prognostic score for breast cancer. High accuracy and low interobserver variance are important to ensure the score is accurately calculated; however, few previous efforts have been made to measure or decrease interobserver variance. We developed a Web-based training tool, called “Score the Core” (STC) using tissue microarrays to train pathologists to visually score estrogen receptor (using the 300-point H score), progesterone receptor (percent positive), and Ki-67 (percent positive). STC used a reference score calculated from a reproducible manual counting method. Pathologists in the Athena Breast Health Network and pathology residents at associated institutions completed the exercise. By using STC, pathologists improved their estrogen receptor H score and progesterone receptor and Ki-67 proportion assessment and demonstrated a good correlation between pathologist and reference scores. In addition, we collected information about pathologist performance that allowed us to compare individual pathologists and measures of agreement. Pathologists' assessment of the proportion of positive cells was closer to the reference than their assessment of the relative intensity of positive cells. Careful training and assessment should be used to ensure the accuracy of breast biomarkers. This is particularly important as breast cancer diagnostics become increasingly quantitative and reproducible. Our training tool is a novel approach for pathologist training that can serve as an important component of ongoing quality assessment and can improve the accuracy of breast cancer prognostic biomarkers.
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