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Concept: Medical statistics

363

Knee osteoarthritis (OA) is believed to be highly prevalent today because of recent increases in life expectancy and body mass index (BMI), but this assumption has not been tested using long-term historical or evolutionary data. We analyzed long-term trends in knee OA prevalence in the United States using cadaver-derived skeletons of people aged ≥50 y whose BMI at death was documented and who lived during the early industrial era (1800s to early 1900s; n = 1,581) and the modern postindustrial era (late 1900s to early 2000s; n = 819). Knee OA among individuals estimated to be ≥50 y old was also assessed in archeologically derived skeletons of prehistoric hunter-gatherers and early farmers (6000-300 B.P.; n = 176). OA was diagnosed based on the presence of eburnation (polish from bone-on-bone contact). Overall, knee OA prevalence was found to be 16% among the postindustrial sample but only 6% and 8% among the early industrial and prehistoric samples, respectively. After controlling for age, BMI, and other variables, knee OA prevalence was 2.1-fold higher (95% confidence interval, 1.5-3.1) in the postindustrial sample than in the early industrial sample. Our results indicate that increases in longevity and BMI are insufficient to explain the approximate doubling of knee OA prevalence that has occurred in the United States since the mid-20th century. Knee OA is thus more preventable than is commonly assumed, but prevention will require research on additional independent risk factors that either arose or have become amplified in the postindustrial era.

Concepts: Medical statistics, United States, Industrial Revolution, Osteoarthritis, Body mass index, United Kingdom, Gerontology, Life expectancy

332

Background Whether hydrocortisone reduces mortality among patients with septic shock is unclear. Methods We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days. Results From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P=0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia. Conclusions Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109 .).

Concepts: Epidemiology, Medical statistics, Intensive care medicine, Shock, Interquartile range, Septic shock, Sepsis, Blood transfusion

309

Choir singing is known to promote wellbeing. One reason for this may be that singing demands a slower than normal respiration, which may in turn affect heart activity. Coupling of heart rate variability (HRV) to respiration is called Respiratory sinus arrhythmia (RSA). This coupling has a subjective as well as a biologically soothing effect, and it is beneficial for cardiovascular function. RSA is seen to be more marked during slow-paced breathing and at lower respiration rates (0.1 Hz and below). In this study, we investigate how singing, which is a form of guided breathing, affects HRV and RSA. The study comprises a group of healthy 18 year olds of mixed gender. The subjects are asked to; (1) hum a single tone and breathe whenever they need to; (2) sing a hymn with free, unguided breathing; and (3) sing a slow mantra and breathe solely between phrases. Heart rate (HR) is measured continuously during the study. The study design makes it possible to compare above three levels of song structure. In a separate case study, we examine five individuals performing singing tasks (1-3). We collect data with more advanced equipment, simultaneously recording HR, respiration, skin conductance and finger temperature. We show how song structure, respiration and HR are connected. Unison singing of regular song structures makes the hearts of the singers accelerate and decelerate simultaneously. Implications concerning the effect on wellbeing and health are discussed as well as the question how this inner entrainment may affect perception and behavior.

Concepts: Scientific method, Medical statistics, Effect, Heart, Affect, Singing, Vocal range, Vocal music

277

Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice.

Concepts: Childbirth, Infant, Epidemiology, Medical statistics, Infant mortality, Preterm birth, Perinatal mortality, Human Development Index

262

Diabetes and high body-mass index (BMI) are associated with increased risk of several cancers, and are increasing in prevalence in most countries. We estimated the cancer incidence attributable to diabetes and high BMI as individual risk factors and in combination, by country and sex.

Concepts: Epidemiology, Disease, Medical statistics, Risk, The Canon of Medicine, Obesity, Body mass index, Squamous cell carcinoma

261

OBJECTIVE: Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence. DATA SOURCES: MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year’s follow-up period were included. REVIEW METHODS: Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting. RESULTS: We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07-1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98-1.24) and 0.98 (0.78-1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results. CONCLUSION: Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.

Concepts: Scientific method, Epidemiology, Clinical trial, Medical statistics, Risk, Evidence-based medicine, Actuarial science, Relative risk

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252

To determine the proportion of avoidable deaths (due to acts of omission and commission) in acute hospital trusts in England and to determine the association with the trust’s hospital-wide standardised mortality ratio assessed using the two commonly used methods - the hospital standardised mortality ratio (HSMR) and the summary hospital level mortality indicator (SHMI).

Concepts: Epidemiology, Medical statistics, Actuarial science, Ratio, Statistical terminology, Trust, Inheritance, Standardized mortality ratio

246

In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 252,710 new cases of invasive breast cancer and 40,610 breast cancer deaths are expected to occur among US women in 2017. From 2005 to 2014, overall breast cancer incidence rates increased among Asian/Pacific Islander (1.7% per year), non-Hispanic black (NHB) (0.4% per year), and Hispanic (0.3% per year) women but were stable in non-Hispanic white (NHW) and American Indian/Alaska Native (AI/AN) women. The increasing trends were driven by increases in hormone receptor-positive breast cancer, which increased among all racial/ethnic groups, whereas rates of hormone receptor-negative breast cancers decreased. From 1989 to 2015, breast cancer death rates decreased by 39%, which translates to 322,600 averted breast cancer deaths in the United States. During 2006 to 2015, death rates decreased in all racial/ethnic groups, including AI/ANs. However, NHB women continued to have higher breast cancer death rates than NHW women, with rates 39% higher (mortality rate ratio [MRR], 1.39; 95% confidence interval [CI], 1.35-1.43) in NHB women in 2015, although the disparity has ceased to widen since 2011. By state, excess death rates in black women ranged from 20% in Nevada (MRR, 1.20; 95% CI, 1.01-1.42) to 66% in Louisiana (MRR, 1.66; 95% CI, 1.54, 1.79). Notably, breast cancer death rates were not significantly different in NHB and NHW women in 7 states, perhaps reflecting an elimination of disparities and/or a lack of statistical power. Improving access to care for all populations could eliminate the racial disparity in breast cancer mortality and accelerate the reduction in deaths from this malignancy nationwide. CA Cancer J Clin 2017. © 2017 American Cancer Society.

Concepts: Epidemiology, Cancer, Breast cancer, Death, Medical statistics, Demography, United States, American Cancer Society

240

Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.

Concepts: Antiretroviral drug, HIV, AIDS, Protease inhibitor, Epidemiology, Medical statistics, Evaluation, Prevalence