New horizons in treatment of osteoporosis

BACKGROUND: Prevalence of osteoporosis is increasing both in developed and developing countries. Due to rapid growth in the burden and cost of osteoporosis, worldwide, it seems reasonable to focus on the reduction of fractures as the main goal of treatment. Although, efficient pharmacological agents are available for the treatment of osteoporosis, there still remains a need to more specific drugs with less adverse effects. MAIN BODY: This review article provides a brief update on the pathogenesis, presenting current pharmacological products approved by the US Food and Drug Administration (FDA) or Europe, and also newer therapeutic agents to treat osteoporosis according to the clinical trial data available at PubMed, UpToDate, International Osteoporosis Foundation (IOF), and clinical practice guidelines. As well, the effect of combination therapy and recommendations for future research will be further discussed. SHORT CONCLUSION: The use of current antiresorptive and anabolic agents alone or in combinations for the treatment of osteoporosis entails several limitations. Mainly, their efficacy on non-vertebral fracture reduction is lower than that observed on vertebral fracture. In addition, they have potential adverse events on long time usage. Development of newer agents such as cathepsin k inhibitor and strontium ranelate not only have increased the available options for treating osteoporosis, but also have opened doors of opportunity to improvements in the effective treatment. However, the high cost of new agents have restricted their usage in selective patients who are at high risk of fracture or whom failed response to first line treatment options. Thus, personalized medicine should be considered for future evaluation of genetic risk score and also for environmental exposure assessment. In addition to permanent attention to early diagnosis of osteoporosis and understanding of the pathophysiology of osteoporosis for novel approach in drug discovery, there seems a need to more well-designed clinical trials with larger sample sizes and longer duration on current as well as on newer agents. Also, continuous research on plant-derived components as the source of discovering new agents, and conducting more clinical trials with combination of two or more synthetic drugs, plants, or drug-plant for the treatment of osteoporosis are recommended. GRAPHICAL ABSTRACT: Summary of treatment modalities for osteoporosis. [Image: see text

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Targeting dyslipidemia by herbal medicines : a systematic review of meta-analyses

Ethnopharmacological relevance: The worldwide increasing prevalence of dyslipidemia has become a global health concern. Various herbal remedies have been claimed to be effective for the treatment of dyslipidemia in traditional and folkloric medicine of different regions clinical trials have been conducted to investigate their efficacy. The aim of the current systematic review is to critically assess the meta-analyses of controlled trials (CT) evaluated herb medicines for dyslipidemia. Materials and methods: Relevant studies from Web of Science, PubMed, Scopus, and Cochrane Library databases based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist until January 2021 have been searched. All meta-analyses which pooled studies on the effect of herbal medicines on lipid profile including total cholesterol (TC), triglyceride (TG), and low-or high-density lipoprotein cholesterol (LDLC, HDL-C) were also included. Meta-analyses of in vitro, animal or observational studies were excluded. Results: The overall of 141 meta-analyses were revealed. Vegetable oils, phytosterols, tea, soy protein, nuts, and curcumin have been studied frequently among the herbal medicines. Among 13 meta-analyses on vegetable oils, the greater reduce of TC (18.95 mg/dl), LDL-C (16.24 mg/dl) and TG (13.69 mg/dl) were exhibited from sunflower oil. Furthermore, rice bran oil (6.65 mg/dl) increased HDL-C significantly. Phytosterols in 12 meta analyses demonstrated significant improvements in reducing TC, LDL-C and TG as 16.4, 23.7, and 8.85 mg/dl, respectively, and rise in HDL-C as 10.6 mg/dl. The highest reduction in serum level of TC, LDL-C and TG was reported while intake Green tea; 27.57, 24.75, and 31.87 mg/dl, accordingly within 9 meta-analyses. Average improvement of lipid profiles by 6 meta-analyses on plant proteins were 23.2, 21.7, 15.06, and 1.55 mg/dl for TC, LDL-C, TG, and HDL-C, respectively. Among 11 meta-analyses on nuts, almond showed better and significant alleviations in TC (10.69 mg/dl), walnut in LDL-C (9.23 mg/dl), pistachio in TG (22.14 mg/dl), and peanut in HDL-C (2.72 mg/dl). Overall, Curcumin, Curcuminoid, and Turmeric have resulted in the reduction of TC (25.13 mg/dl), LDL-C (39.83 mg/dl), TG (33.65 mg/dl), and an increase in the HDL-C (4.31 mg/dl). Conclusion: The current systematic review shed light on the use of herbal medicines for the management of dyslipidemia. However, more well-conducted CTs are required to determine effective doses of herbal medicines

Risk scores for prediction of paroxysmal atrial fibrillation after acute ischemic stroke or transient ischemic attack: A systematic review and meta-analysis

Introduction: Detection of paroxysmal atrial fibrillation (PAF) is crucial for secondary prevention in patients with recent strokes of unknown etiology. This systematic review and meta-analysis assess the predictive power of available risk scores for detecting new PAF after acute ischemic stroke (AIS). Methods: PubMed, Embase, Scopus, and Web of Science databases were searched until September 2023 to identify relevant studies. A bivariate random effects meta-analysis model pooled data on sensitivity, specificity, and area under the curve (AUC) for each score. The QUADAS-2 tool was used for the quality assessment. Results: Eventually, 21 studies with 18 original risk scores were identified. Age, left atrial enlargement, and NIHSS score were the most common predictive factors, respectively. Seven risk scores were meta-analyzed, with iPAB showing the highest pooled sensitivity and AUC (sensitivity: 89.4%, specificity: 74.2%, AUC: 0.83), and HAVOC having the highest pooled specificity (sensitivity: 46.3%, specificity: 82.0%, AUC: 0.82). Altogether, seven risk scores displayed good discriminatory power (AUC ≥0.80) with four of them (HAVOC, iPAB, Fujii, and MVP scores) being externally validated. Conclusion: Available risk scores demonstrate moderate to good predictive accuracy and can help identify patients who would benefit from extended cardiac monitoring after AIS. External validation is essential before widespread clinical adoption