Statistical Analysis in the German National Cohort (NAKO) - Specific Aspects and General Recommendations.

The German National Cohort (NAKO) is an ongoing, prospective multicenter cohort study, which started recruitment in 2014 and includes more than 205,000 women and men aged 19-74 years. The study data will be available to the global research community for analyses. Although the ultimate decision about the analytic methods will be made by the respective investigator, in this paper we provide the basis for a harmonized approach to the statistical analyses in the NAKO. We discuss specific aspects of the study (e.g., data collection, weighting to account for the sampling design), but also give general recommendations which may apply to other large cohort studies as well.

Future health spending forecast in leading emerging BRICS markets in 2030: health policy implications.

BACKGROUND: The leading emerging markets of Brazil, Russia, India, China and South Africa (BRICS) are increasingly shaping the landscape of the global health sector demand and supply for medical goods and services. BRICS' share of global health spending and future projections will play a prominent role during the 2020s. The purpose of the current research was to examine the decades-long underlying historical trends in BRICS countries' health spending and explore these data as the grounds for reliable forecasting of their health expenditures up to 2030. METHODS: BRICS' health spending data spanning 1995-2017 were extracted from the Institute for Health Metrics and Evaluation (IHME) Financing Global Health 2019 database. Total health expenditure, government, prepaid private and out-of-pocket spending per capita and gross domestic product (GDP) share of total health spending were forecasted for 2018-2030. Autoregressive integrated moving average (ARIMA) models were used to obtain future projections based on time series analysis. RESULTS: Per capita health spending in 2030 is projected to be as follows: Brazil, $1767 (95% prediction interval [PI] 1615, 1977); Russia, $1933 (95% PI 1549, 2317); India, $468 (95% PI 400.4, 535); China, $1707 (95% PI 1079, 2334); South Africa, $1379 (95% PI 755, 2004). Health spending as a percentage of GDP in 2030 is projected as follows: Brazil, 8.4% (95% PI 7.5, 9.4); Russia, 5.2% (95% PI 4.5, 5.9); India, 3.5% (95% PI 2.9%, 4.1%); China, 5.9% (95% PI 4.9, 7.0); South Africa, 10.4% (95% PI 5.5, 15.3). CONCLUSIONS: All BRICS countries show a long-term trend towards increasing their per capita spending in terms of purchasing power parity (PPP). India and Russia are highly likely to maintain stable total health spending as a percentage of GDP until 2030. China, as a major driver of global economic growth, will be able to significantly expand its investment in the health sector across an array of indicators. Brazil is the only large nation whose health expenditure as a percentage of GDP is about to contract substantially during the third decade of the twenty-first century. The steepest curve of increased per capita spending until 2030 seems to be attributable to India, while Russia should achieve the highest values in absolute terms. Health policy implications of long-term trends in health spending indicate the need for health technology assessment dissemination among the BRICS ministries of health and national health insurance funds. Matters of cost-effective allocation of limited resources will remain a core challenge in 2030 as well.

Metabolic risk factors and fertility disorders: A narrative review of the female perspective.

Metabolic risk factors such as obesity are considered major obstacles to female fertility. Chronic infertility imposes psychological and social burdens on women because infertility violates societal gender roles. Although the prevalence of obesity among women is expected to increase in the future, the relevance of metabolic status for fertility is still underestimated. However, the assessment of metabolic risk factors is highly relevant for understanding fertility disorders and improving infertility treatment. This narrative review discusses the associations of metabolic risk factors (e.g. obesity, female athlete triad, oxidative stress) with significant infertility. An electronic search was conducted for studies published between 2006 and 2020 in Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, PubMed, Scopus, Google Scholar and related databases. In total, this search identified 19,309 results for polycystic ovary syndrome, 28,969 results for endometriosis, and only 1611 results for idiopathic and/or unknown infertility. For the present narrative review, 50 relevant studies were included: 19 studies were on obesity, 24 studies investigated the female athlete triad, and seven studies addressed other risk factors, including reactive oxygen species. This narrative review confirms the direct impact of obesity on female infertility, while the effect of other risk factors needs to be confirmed by large-scale population studies.

Corona-Triggered Global Macroeconomic Crisis of the Early 2020s.

Long-lasting economic recessions spreading from initial cradle markets worldwide should be a periodic event inherent to capitalism as a prevailing socio-economic model [...].

Biomarkers for demographic research: sperm counts and other male infertility biomarkers.

Some male infertility biomarkers are etiologically linked to idiopathic infertility in men, the direct cause of which often cannot be determined with conventional sperm count parameters. Open questions remain regarding the universal and generic infertility definitions that cover and combine the clinical, epidemiological, and demographic perspectives. The main effort in the application of these infertility biomarkers are accounted by more or less strict discrimination criteria. For male infertility, beyond classical sperm count assessments, the DNA fragmentation index (DFI) is an adequate biomarker. DFI strongly correlates with pregnancy rates and even strict discrimination criteria for infertility outcomes. Other common biomarkers are reactive oxygen species (ROS) and antisperm antibodies (ASAs), which can explain some biomedical infertility disorders within major constraints. More frequently applied in demographic research, telomere length component analysis is based on identifying the genetic impact of cellular longevity. Sperm telomere length is becoming established as a potential biomarker in infertility research. The aim of this review is to provide an overview of the current status and limitations to the application of novel biomarkers, including TEX101, for infertility research. The review also discusses potential options for the use of biomarkers in population-based studies.Abbreviations: ASAs: antisperm antibodies; DFI: DNA fragmentation index; DNA: deoxyribonucleic acid; ECM1: extracellular matrix protein 1; FSH: follicle stimulating hormone; HS: hypospermatogenesis: IVF: in vitro fertilization; LDHC: L-lactata dehydrogenase C chain; MA: maturation arrest; microTESE: microdissection testicular sperm extraction; NOA: nonobstructive azoospermia; NP: nonprogressive; OA: obstructive azoospermia; pH: potential Hyrogenii (pH-value); PR: progressive; PTGDS: prostaglandin D synthese; ROS: reactive oxygen species; SA: semen analysis; SCO: sertoli cell only; SCSA: sperm chromatin structure assay (SCSA); TL: telomere length; TESE: testicular sperm extraction; TEX101: a glycoprotein that belongs to Ly6/urokinase type plasminogen activator receptor-like protein (uPAR)(LU) superfamily, to be a germ-cell-specific molecular sperm extraction; TUNEL: terminal deoxnucleotidyl dispersion tranferase dUTP nick-end labeling; WHO: World Health Organization.

Avoidable Cancer Mortality in Germany Since Reunification: Regional Variation and Sex Differences.

Background: Regional comparisons of cancer-related mortality in Germany are traditionally focused on disparities between East and West Germany. Recent improvements in all-cause and cancer-related mortality show a diverse regional pattern beyond the known East-West mortality divide. A generalized approach of the avoidable/amenable cancer mortality definition is applied for suitable regional comparisons of long-term trends. Methods: Standardized death rates of preventable and amenable cancer mortality for men and women were computed for the period 1990-2014 to observe sex-specific excess mortality due to specific cancers after the German reunification. For regional comparison, three German super regions were defined in Eastern, Northwestern, and Southwestern Germany to account for similarities in long-term regional premature and cancer-related mortality patterns, socioeconomic characteristics, and age structure. Results: Since preventable and amenable cancer mortality rates typically have driven the recent trends in premature mortality, our findings underline the current regional pattern of preventable cancer mortality for males with disadvantages for Eastern Germany, and advantages for Southwestern Germany. Among women, the preventable cancer mortality has increased in Northwestern and Southwestern Germany after the German reunification but has decreased in Eastern Germany and converged to the pattern of Southwestern Germany. Similar patterns can be observed for females in amenable cancer mortality. Conclusions: Although the "traditional" East-West gap in preventable cancer mortality was still evident in males, our study provides some hints for more regional diversity in avoidable cancer mortality in women. An establishing north-south divide in avoidable cancer mortality could alter the future trends in regional cancer-related mortality in Germany.

Is the Rise in the Prevalence of Renal Replacement Therapy at Older Ages the Price for Living Longer?

BACKGROUND: Renal replacement therapy (RRT) is one of the most expensive in renal medicine. Cross-sectional studies suggest that life expectancy increases in the general population are associated with a higher burden of RRT. This study tests this hypothesis in a prospective setting among people aged 75+ living in Western Europe. METHODS: We gathered sex-specific data for 11 Western European countries in 2005-2014. RRT prevalence on country level was extracted from the ERA-EDTA registry, while data on population size and life expectancy for the 75+ age group came from the Eurostat database. GDP per capita was extracted from the OECD database. To measure the association between RRT prevalence and life expectancy, we performed Poisson regression models separately for each country and for all countries combined. To adjust for confounding, GDP per capita as well as time and country-fixed effects were included. RESULTS: Our analysis revealed that living longer coincides with rising RRT prevalence at ages 75+ in Western Europe between 2005 and 2014. On average, a 1-year increase in life expectancy was associated with a roughly 20% increase in RRT prevalence [(95% CI) 21-23% in men and 19-22% in women]. However, after adjustments for confounding were made, the association became insignificant among women and became weaker among men, falling to a level of 11% [(95% CI) 6-17%]. CONCLUSION: Living longer was not necessarily associated with a higher burden of RRT in Western European countries.

Strategies to Improve Stroke Care Services in Low- and Middle-Income Countries: A Systematic Review.

BACKGROUND: The burden of stroke in low- and middle-income countries (LMICs) is large and increasing, challenging the already stretched health-care services. AIMS AND OBJECTIVES: To determine the quality of existing stroke-care services in LMICs and to highlight indigenous, inexpensive, evidence-based implementable strategies being used in stroke-care. METHODS: A detailed literature search was undertaken using PubMed and Google scholar from January 1966 to October 2015 using a range of search terms. Of 921 publications, 373 papers were shortlisted and 31 articles on existing stroke-services were included. RESULTS: We identified efficient models of ambulance transport and pre-notification. Stroke Units (SU) are available in some countries, but are relatively sparse and mostly provided by the private sector. Very few patients were thrombolysed; this could be increased with telemedicine and governmental subsidies. Adherence to secondary preventive drugs is affected by limited availability and affordability, emphasizing the importance of primary prevention. Training of paramedics, care-givers and nurses in post-stroke care is feasible. CONCLUSION: In this systematic review, we found several reports on evidence-based implementable stroke services in LMICs. Some strategies are economic, feasible and reproducible but remain untested. Data on their outcomes and sustainability is limited. Further research on implementation of locally and regionally adapted stroke-services and cost-effective secondary prevention programs should be a priority.

The Burden of Mental Disorders in the Eastern Mediterranean Region, 1990-2013.

The Eastern Mediterranean Region (EMR) is witnessing an increase in chronic disorders, including mental illness. With ongoing unrest, this is expected to rise. This is the first study to quantify the burden of mental disorders in the EMR. We used data from the Global Burden of Disease study (GBD) 2013. DALYs (disability-adjusted life years) allow assessment of both premature mortality (years of life lost-YLLs) and nonfatal outcomes (years lived with disability-YLDs). DALYs are computed by adding YLLs and YLDs for each age-sex-country group. In 2013, mental disorders contributed to 5.6% of the total disease burden in the EMR (1894 DALYS/100,000 population): 2519 DALYS/100,000 (2590/100,000 males, 2426/100,000 females) in high-income countries, 1884 DALYS/100,000 (1618/100,000 males, 2157/100,000 females) in middle-income countries, 1607 DALYS/100,000 (1500/100,000 males, 1717/100,000 females) in low-income countries. Females had a greater proportion of burden due to mental disorders than did males of equivalent ages, except for those under 15 years of age. The highest proportion of DALYs occurred in the 25-49 age group, with a peak in the 35-39 years age group (5344 DALYs/100,000). The burden of mental disorders in EMR increased from 1726 DALYs/100,000 in 1990 to 1912 DALYs/100,000 in 2013 (10.8% increase). Within the mental disorders group in EMR, depressive disorders accounted for most DALYs, followed by anxiety disorders. Among EMR countries, Palestine had the largest burden of mental disorders. Nearly all EMR countries had a higher mental disorder burden compared to the global level. Our findings call for EMR ministries of health to increase provision of mental health services and to address the stigma of mental illness. Moreover, our results showing the accelerating burden of mental health are alarming as the region is seeing an increased level of instability. Indeed, mental health problems, if not properly addressed, will lead to an increased burden of diseases in the region.

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study.

IMPORTANCE: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. EVIDENCE REVIEW: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. FINDINGS: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. CONCLUSION AND RELEVANCE: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

Microcalcification-Associated Breast Cancer: Presentation, Successful First Excision, Long-Term Recurrence and Survival Rate.

INTRODUCTION: In this study we evaluated mammographic, histological and immunohistochemical findings for microcalcification-associated breast cancer with regards to breast-conserving therapy, recurrence and survival rate. PATIENTS AND METHODS: We retrospectively analyzed 99 consecutive, non-palpable and microcalcification-associated breast cancers (94 women) that were treated surgically between January 2002 and December 2003 at a national academic breast cancer center. Calcifications were classified according to the Breast Imaging Reporting and Data System (BI-RADS). Descriptors, surgical outcome and histological findings were assessed. Recurrences and survival rates were evaluated based on medical records, standardized patient questionnaires and/or contacting the physician. RESULTS: 42 of the 99 lesions (42.4%) were invasive carcinomas, 57 (57.6%) were pure ductal carcinoma in situ (DCIS). 6 out of 99 (6.1%) lesions were triple negative, and 29 (29.3%) were HER2/neu positive. Successful first excision rate was 76/99 lesions (76.8%). Breast conservation was achieved in 73.7% (73/99). 10 women showed local recurrences without negatively impacting survival. The recurrences included round/punctate, amorphous, fine pleomorphic, and fine linear or fine-linear branching descriptors. The breast cancer-specific long-term survival rate was 91/94 (96.8%) for a mean follow-up of 81.4 months. The 3 patients who died due to breast carcinoma showed fine pleomorphic calcifications, and had nodal-positive invasive carcinoma at diagnosis. CONCLUSION: Microcalcification-associated breast cancers are frequently treated with breast-conserving therapy. Continuous clinical and mammographic follow-up is recommended for all descriptors.

Testosterone and type 2 diabetes in men.

OBJECTIVE: To assess from observational data if low testosterone in men is an independent risk factor for high fasting glucose (FG) and for a diagnosis of type 2 diabetes (T2D). METHODS: Multivariate analysis of data from 991 male US Air Force veterans who completed six medical examinations over 20 years. RESULTS: Low testosterone was moderately related to high FG, independent of age and obesity. Low testosterone is a very weak predictor of a diagnosis of T2D. CONCLUSIONS: In men, low testosterone is an independent risk factor for high FG, comparable to aging and obesity. Low testosterone is a weak predictor of a diagnosis of T2D.

Is rising obesity causing a secular (age-independent) decline in testosterone among American men?

The testosterone of men in industrial societies peaks in their twenties and tends to decline with increasing age. Apart from this individual-level decline, there have been reports of a secular (age-independent population-level) decline in testosterone among American and Scandinavian men during the past few decades, possibly an indication of declining male reproductive health. It has been suggested that both declines in testosterone (individual-level and population-level) are due to increasing male obesity because men in industrial society tend to add body fat as they age, and overall rates of obesity are increasing. Using an unusually large and lengthy longitudinal dataset (991 US Air Force veterans examined in six cycles over 20 years), we investigate the relationship of obesity to individual and population-level declines in testosterone. Over twenty years of study, longitudinal decline in mean testosterone was at least twice what would be expected from cross-sectional estimates of the aging decline. Men who put on weight intensified their testosterone decline, some greatly so, but even among those who held their weight constant or lost weight during the study, mean testosterone declined 117 ng/dl (19%) over 20 years. We have not identified the reason for secular decline in testosterone, but we exclude increasing obesity as a sufficient or primary explanation, and we deny the supposition that men who avoid excessive weight will maintain their youthful levels of testosterone.