Polycystic ovary syndrome: clinical and laboratory variables related to new phenotypes using machine-learning models.

PURPOSE: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. Machine learning (ML) is the area of artificial intelligence with a focus on predictive computing algorithms. We aimed to define the most relevant clinical and laboratory variables related to PCOS diagnosis, and to stratify patients into different phenotypic groups (clusters) using ML algorithms. METHODS: Variables from a database comparing 72 patients with PCOS and 73 healthy women were included. The BorutaShap method, followed by the Random Forest algorithm, was applied to prediction and clustering of PCOS. RESULTS: Among the 58 variables investigated, the algorithm selected in decreasing order of importance: lipid accumulation product (LAP); abdominal circumference; thrombin activatable fibrinolysis inhibitor (TAFI) levels; body mass index (BMI); C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c), follicle-stimulating hormone (FSH) and insulin levels; HOMA-IR value; age; prolactin, 17-OH progesterone and triglycerides levels; and family history of diabetes mellitus in first-degree relative as the variables associated to PCOS diagnosis. The combined use of these variables by the algorithm showed an accuracy of 86% and area under the ROC curve of 97%. Next, PCOS patients were gathered into two clusters in the first, the patients had higher BMI, abdominal circumference, LAP and HOMA-IR index, as well as CRP and insulin levels compared to the other cluster. CONCLUSION: The developed algorithm could be applied to select more important clinical and biochemical variables related to PCOS and to classify into phenotypically different clusters. These results could guide more personalized and effective approaches to the treatment of PCOS.

JCL Roundtable. Making prevention a priority.

Clinical lipidology belongs par excellence to the preventive mode of medical practice. This Roundtable brings two long-time advocates of cardiometabolic prevention and a newly minted preventive cardiologist into a discussion that expands their recent JCL editorial on this topic. Atherosclerosis is a single disease process that leads to approximately 25% of deaths in economically advanced nations and a growing fraction of mortality and morbidity in nations with developing and emerging economies. Our discussants suggest that at least 75% of atherosclerotic cardiovascular disease can be prevented. Diet and lifestyle including physical activity are the cornerstones for this effort. Public and private choices about diet-lifestyle are influenced by economics, education (especially in childhood), inequities, technology, misinformation, and trust. Lipid clinics perform well with pharmacologic treatment of lipid disorders and increasingly give attention to hypertension, obesity, and diabetes as needed. Cardiometabolic prevention in the clinic works best through provider teams. Business considerations and exemplary programs are highlighted.

Management of the major complications of cirrhosis: Beyond guidelines.

Along with a growing understanding of the pathophysiology of cirrhosis and its complications, new therapies and management strategies have emerged in recent years. Many of these advances have helped inform the current EASL clinical practice guidelines1 on the management of some of the key complications of cirrhosis, such as ascites, variceal bleeding and infection. However, there are still some aspects of management where the evidence base is less clear, and/or where opinions amongst practitioners remain divided. Some of these more controversial areas are explored in this section, wherein we present evidence culminating in a suggested management approach based on expert opinion and extending beyond the current guidelines.

Long-term effectiveness of population-wide multifaceted interventions for hepatocellular carcinoma in Taiwan.

BACKGROUND & AIMS: Taiwan has launched a series of population-wide interventions to prevent hepatocellular carcinoma (HCC) related to hepatitis B and C virus infection since 1984. We took this opportunity to investigate the impact of each intervention on the incidence and case-fatality rate of HCC, and assessed their relative contributions to the overall reduction in mortality during this period. METHODS: Population-based registry data on HCC mortality and incidence from individuals aged 0 to 84 years between 1979 and 2016 were collected before (Period 1) and after universal hepatitis B vaccination from 1984 (Period 2), universal health care from 1995 (Period 3), and viral hepatitis therapy from 2003 (Period 4). A Bayesian Poisson regression model was used for mortality decomposition analysis to estimate the respective contributions of these interventions to the reduction in age-specific incidence and case-fatality rates. RESULTS: Mortality declined substantially in children, young- and middle-aged groups, but only slightly decreased in the elderly group. The declining trends in mortality were in part explained by incidence reduction and in part by a remarkable decline in case-fatality rate attributed to universal health care. Hepatitis B vaccination led to a 35.9% (26.8% to 44.4%) reduction in incidence for individuals aged 30 years or below, whereas antiviral therapy reduced the incidence of HCC by 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for individuals aged 30-49 years and 50-69 years, respectively. CONCLUSIONS: Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups. LAY SUMMARY: Since 1984, a series of population-wide interventions have been launched in Taiwan to prevent viral hepatitis-related hepatocellular carcinoma, including a universal hepatitis B vaccination program (from 1984), universal health care (from 1995), and a national viral hepatitis therapy program (from 2004). Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.

Postmenopausal hormone therapy for cardiovascular health: the evolving data.

Postmenopausal (PM) hormone therapy (HT) was extremely popular for years as a treatment for many conditions, including cardiovascular (CV) disease (CVD) prevention. The adverse results from the Women's Health Initiative (WHI) ended the widespread prescriptive use of HT for nearly 20 years. The WHI findings have been broadly and unfairly applied to all hormone formulations, including modern treatments using human-identical hormones. Although CV health is indisputably linked to oestrogen status, HT involving any combination of hormones currently is not recommended for primary or secondary prevention of CVD. In the wake of more positive results from recent studies and re-evaluation of the WHI, HT has re-emerged as an issue for specialists in CVD to discuss with their patients. Rigorous scientific analysis is needed to explain the paradox of cardioprotection conferred by endogenous ovarian hormones with apparent cardiotoxicity inflicted by HT. This review will cover the origins of HT, hormone terminology and function, and key studies that contribute to our current understanding. Based on evolving evidence, if HT is to be used, we propose it be initiated immediately after cessation of ovarian hormone production and dosed as transdermal oestradiol combined with cyclic dosing of human-identical progesterone (P4).

Most important advances in preventive cardiology during this past decade: Viewpoint from the American Society for Preventive Cardiology.

The rapidly expanding field of preventive cardiology has brought with it several major advances in the past decade. Changes in guidelines for cholesterol mangement focusing on the identification of "statin eligible groups" and removal of actual low-density lipoprotein cholesterol (LDL-C) targets, in particular, as well as lower targets for blood pressure in updated hypertension guidelines, have made a major impact on healthcare. The availability of the sodium glucose transport protein-2 (SGLT2) inhibitors and glucagon-like peptide -1 receptor antagonists (GLP1-RA) for managing diabetes have shifted our focus in diabetes care beyond glucose lowering to addressing cardiovascular risk reduction. While many prior trials of fish oil therapy have failed to show benefit, the recent Reduction of Cardiovascular Events With EPA - Intervention Trial (REDUCE-IT) testing the efficacy of icosapent ethyl has shown dramatic benefit in further addressing residual atherosclerotic cardiovascular disease (ASCVD) risk beyond statin therapy not only in those with known ASCVD, but also in diabetic patients with multiple risk factors. The past decade also ushered in confirmation of the inflammation hypothesis of atherosclerosis with the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) using canakinumab, despite the fact the therapy was not approved by the Food and Drug Administration (FDA) for cardiovascular risk reduction. Also, to improve our understanding of heart disease in women, the emergence of novel concepts of ischemia or myocardial infarction in those with normal or nonobstructive atherosclerotic disease has been a major advance. Moreover, the past decade brought the emergence of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody therapy and the cardiovascular risk reduction benefits seen in the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) trials, providing further evidence-based therapy for additional reduction of ASCVD risk beyond statin therapy. The PCSK9 monoclonal antibodies have facilitated the attainment of LDL-C levels never previously thought possible. Finally with the mRNA interference therapy inclisiran in development, we may soon have a "vaccine-like" approach for addressing dyslipidemia and atherosclerosis.

A review of current strategies to improve HIV prevention and treatment in sexual and gender minority Latinx (SGML) communities.

INTRODUCTION: The HIV epidemic continues to disproportionately impact sexual and gender minority Latinxs (SGML). Several syndemic conditions have been linked with HIV acquisition and transmission among SGML including immigration, discrimination, environmental racism, substance use, and mental health. AREAS COVERED: We provide a summary of biomedical, behavioral, and social/structural interventions to reduce risks for acquiring HIV and improve outcomes along the HIV care continuum among SGML. We also discuss intervention approaches and opportunities that respond at the intersection of HIV and COVID-19 prevention and treatment. EXPERT OPINION: There is a dire need for the combination of biomedical, behavioral, and social/structural interventions to reduce risks for acquiring HIV and improve outcomes along the HIV care continuum. Interventions and combination approaches should be driven by community-based participatory action research. The inclusion of community members in all stages of the research process can assure successful implementation of program activities and deliverables, including the provision of culturally and linguistically appropriate services. Given the current COVID-19 pandemic, which is disproportionately impacting individuals living with HIV and other comorbidities, the elderly, and under-resourced communities with a ferocity not seen in other communities, intervention approaches that respond at the intersection of HIV and COVID-19 prevention and treatment are also urgently needed.

Things must not fall apart: the ripple effects of the COVID-19 pandemic on children in sub-Saharan Africa.

Zero to 19 year-old children in sub-Saharan Africa bear a disproportionate proportion of the global burden of communicable and non-communicable diseases. Significant public health gains have been made in the fight against these diseases, however, factors such as underequipped health systems, disease outbreaks, conflict, and political instability continue to challenge prevention and control. The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduces new challenges to public health programs in sub-Saharan Africa. Of particular concern are programs targeting major conditions among children, such as undernutrition, vaccine-preventable pneumonia and diarrhea, malaria, tuberculosis, HIV, and sickle cell disease. This article focuses on the impact of the COVID-19 pandemic on child health in sub-Saharan Africa. We review the epidemiology of major pediatric diseases and, referencing modeling projections, discuss the short- and long-term impact of the pandemic on major disease control. We deliberate on potential complications of SARS-CoV-2 co-infections/co-morbidities and identify critical social and ethical issues. Furthermore, we highlight the paucity of COVID-19 data and clinical trials in this region and the lack of child participants in ongoing studies. Lastly, approaches and interventions to mitigate the pandemic's impact on child health outcomes are discussed. IMPACT: Children in sub-Saharan Africa bear a disproportionate burden of communicable and non-communicable diseases globally; this remains true even as the COVID-19 pandemic persists. Amidst the fast-expanding COVID-19 literature, there is little comprehensive coverage of the pandemic's indirect impact on child health in sub-Saharan Africa. This article comprehensively outlines the threat that the pandemic poses to major disease prevention and control for children in sub-Saharan Africa. It discusses the potential impact of SARS-CoV-2 co-infections/co-morbidities, highlights research gaps, and advocates for data and action to mitigate the ripple effects of the pandemic on this population.

Change in newly diagnosed Graves' disease phenotype between the twentieth and the twenty-first centuries: meta-analysis and meta-regression.

PURPOSE: According to a few recent studies, the clinical phenotype of Graves' disease (GD) at onset is becoming milder in recent years, in terms of prevalence and severity of hyperthyroidism, goiter and overt eye disease. The aim of this study was to assess the change in GD phenotype across the late twentieth and the early twenty-first centuries. MATERIALS AND METHODS: We carried out a systematic search of studies published between 1/1/1980 and 12/31/2017 describing naïve GD patients at diagnosis. We collected epidemiological, clinical, biochemical and serological data reported in the selected studies, and (1) conducted a single-arm meta-analysis to compare clinical and biochemical characteristics of naïve GD patients before and after year 2000 and (2) performed a meta-regression to identify the trend of the observed clinical presentations. RESULTS: Eighty selected articles were related to the period before the year 2000, 30 to the years 2000-2017. According to demographics, the two defined populations were homogeneous at meta-analysis: overall estimated female prevalence was 81% [95% CI 79-82], mean estimated age of the entire population was 39.8 years [95% CI 38.4-41.1], with no significant differences between pre- and post-2000 groups (p > 0.05). The overall estimated prevalence of smokers was 40% [95% CI 33-46], with no significant difference between the two groups (p > 0.05). Mean estimated free thyroxine (FT4) and free triiodothyronine (FT3) levels at diagnosis were higher in the pre-2000 group: 4.7 ng/dl [95% CI 4.5-4.9] for FT4 and 14.2 pg/ml [95% CI 13.3-15.1] for FT3, as compared to the post-2000 group: 3.9 ng/dl [95% CI 3.6-4.2] for FT4 and 12.1 pg/ml [95% CI 11.0-13.3] for FT3 (all p < 0.01). Goiter estimated prevalence was higher in the pre-2000 group, 87% [95% CI 84-90], than in the post-2000 group, 56% [95% CI 45-67]. Estimated prevalence for Graves' Orbitopathy (GO) was 34% [95% CI 27-41] in the pre-2000 group and 25% [95% CI 19-30] in the post-2000 group (p = 0.03). Accordingly, meta-regression adjusted for covariates showed an average annual reduction of FT4 (- 0.040 ± 0.008 ng/dl, p < 0.0001), FT3 (- 0.316 ± 0.019 pg/ml, p < 0.0001), goiter prevalence (- 0.023 ± 0.008%, p = 0.006), and goiter size (- 0.560 ± 0.031 ml, p < 0.0001). CONCLUSIONS: Our meta-analysis and meta-regression confirmed that GD phenotype at diagnosis is nowadays milder than in the past; we hypothesize that conceivable factors involved in this change are iodoprophylaxis, worldwide decrease in smoking habits, larger use of contraceptive pill and micronutrient supplementation, as well as earlier diagnosis and management.

Human Immunodeficiency Virus Testing, Diagnosis, Linkage to Care, and Prevention Services Among Persons Who Inject Drugs, United States, 2012-2017.

BACKGROUND: Human immunodeficiency virus (HIV) testing and early diagnosis is associated with effective disease management and reduction in HIV transmission among persons who inject drugs (PWID). We examined trends in HIV testing outcomes among PWID during 2012-2017. METHODS: Centers for Disease Control and Prevention (CDC)-funded HIV testing data submitted by 61 health departments and 150 directly-funded community-based organizations during 2012-2017 were analyzed. We calculated estimated annual percentage changes (EAPC) to assess trends for HIV testing and testing outcomes. RESULTS: A total of 19 739 857 CDC-funded HIV tests were conducted during 2012-2017. Of these, 529 349 (2.7%) were among PWID. The percentage of newly diagnosed HIV increased from .7% in 2012 to .8% in 2017 (EAPC, 4.15%). The percentage interviewed for partner services increased from 46.7% in 2012 to 66.3% in 2017 (EAPC, 1.81%). No significant change was identified in trends for linkage to HIV medical care ≤90 days after diagnosis (EAPC, 0.52%) or referral to HIV prevention services (EAPC, 0.98%). CONCLUSIONS: Human immunodeficiency virus testing data revealed an increasing trend in newly diagnosed HIV among PWID but not linkage to HIV medical care or referral to prevention services. Expanding efforts to increase HIV testing and enhance linkage to services can lead to reductions in HIV transmission and improved health outcomes.

Global burden of oesophageal and gastric cancer by histology and subsite in 2018.

OBJECTIVES: To provide updated estimates of the global burden of oesophageal and gastric cancer by subsite and type. METHODS: Using data from population-based cancer registries, proportions of oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) out of all oesophageal as well as cardia gastric cancer (CGC) and non-CGC (NCGC) out of all gastric cancer cases were computed by country, sex and age group. Proportions were subsequently applied to the estimated numbers of oesophageal and gastric cancer cases from GLOBOCAN 2018. Age-standardised incidence rates (ASR) were calculated. RESULTS: In 2018, there were an estimated 572 000 new cases of oesophageal cancer worldwide, 85 000 OACs (ASR 0.9 per 100 000, both sexes combined) and 482 000 OSCCs (ASR 5.3). Out of 1.03 million gastric cancers, there were an estimated 181 000 cases of CGC (ASR 2.0) and 853 000 cases of NCGC (ASR 9.2). While the highest incidence rates of OSCC, CGC and NCGC were observed in Eastern Asia (ASRs 11.1, 4.4 and 17.9, respectively), rates of OAC were highest in Northern Europe (ASR 3.5). While globally OSCC and NCGC remain the most common types of oesophageal and gastric cancer, respectively, rates of OAC exceed those of OSCC in an increasing number of high-income countries. CONCLUSIONS: These updated estimates of the global burden of oesophageal and gastric cancer by subtype and site suggest an ongoing transition in epidemiological patterns. This work will serve as a cornerstone for policy-making and will aid in developing appropriate cancer control strategies.