BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk-outcome associations. METHODS: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. FINDINGS: In 2017, 34·1 million (95% uncertainty interval [UI] 33·3-35·0) deaths and 1·21 billion (1·14-1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6-62·4) of deaths and 48·3% (46·3-50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39-11·5) deaths and 218 million (198-237) DALYs, followed by smoking (7·10 million [6·83-7·37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6·53 million [5·23-8·23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4·72 million [2·99-6·70] deaths and 148 million [98·6-202] DALYs), and short gestation for birthweight (1·43 million [1·36-1·51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3-6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. INTERPRETATION: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. FUNDING: Bill & Melinda Gates Foundation.
Dr. DePalma was the first editor of Clinical Orthopaedics and Related Research, established by the recently formed Association of Bone and Joint Surgeons. The idea of forming the Association of Bone and Joint surgeons had been conceived by Dr. Earl McBride of Oklahoma City in 1947, and organized by a group of twelve individuals (Drs. Earl McBride, Garrett Pipkin, Duncan McKeever, Judson Wilson, Fritz Teal, Louis Breck, Henry Louis Green, Howard Shorbe, Theodore Vinke, Paul Williams, Eugene Secord, and Frank Hand) [9]. The first organizational meeting was held in conjunction with the 1949 Annual Meeting of the AAOS [9] and the first annual meeting held April 1–2, 1949 in Oklahoma City. Drs. McBride and McKeever invited Dr. DePalma to attend that meeting and join the society. According to DePalma, ‘‘Even at this small gathering, there were whisperings of the need of another journal to provide an outlet for the many worthy papers written on clinical and basic science subjects’’ [7]. The decision to form a new journal was finalized in 1951, and Drs. DePalma and McBride signed a contract with J.B. Lippincott Company. Dr. DePalma was designated Editor-in-Chief, and the journal became a reality in 1953 with the publication of the first volume. From the outset he established the ‘‘symposium’’ as a unique feature, in which part of the articles were devoted to a particular topic. Dr. DePalma served as Editor for 13 years until 1966, when he resigned the position and recommended the appointment of Dr. Marshall R. Urist. At his retirement, Clinical Orthopaedics and Related Research was well established as a major journal. Dr. Anthony F. DePalma was born in Philadelphia in 1904, the son of immigrants from Alberona in central Foggia, Italy [1]. He attended the University of Maryland for his premedical education, then Jefferson Medical College, from which he graduated in 1929. He then served a two-year internship (common at the time) at Philadelphia General Hospital. Jobs were scarce owing to the Depression, and he felt fortunate to obtain in 1931 a position as assistant surgeon at the Coaldale State Hospital, in Coaldale, Pennsylvania, a mining town. However, he became attracted to orthopaedics and looked for a preceptorship (postgraduate training in specialties was not well developed at this time before the establishments of Boards). In the fall of 1932, he was appointed as a preceptor at the New Jersey Orthopaedic Hospital, an extension of the New York Orthopaedic Hospital. In 1939 he acquired Board certification (the first board examination was offered in 1935 for a fee of $25.00 [2]) and was appointed to the NJOH staff [1]. Dr. DePalma volunteered for military service in 1942, and served first at the Parris Island Naval Hospital in South Carolina, then on the Rixey, a hospital ship. In addition to
BACKGROUND: Although helicopters are presently an integral part of trauma systems in most developed nations, previous reviews and studies to date have raised questions about which groups of traumatically injured people derive the greatest benefit. OBJECTIVES: To determine if helicopter emergency medical services (HEMS) transport, compared with ground emergency medical services (GEMS) transport, is associated with improved morbidity and mortality for adults with major trauma. SEARCH METHODS: We ran the most recent search on 29 April 2015. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library (Cochrane Central Register of Controlled Trials; CENTRAL), MEDLINE (OvidSP), EMBASE Classic + EMBASE (OvidSP), CINAHL Plus (EBSCOhost), four other sources, and clinical trials registers. We screened reference lists. SELECTION CRITERIA: Eligible trials included randomized controlled trials (RCTs) and nonrandomized intervention studies. We also evaluated nonrandomized studies (NRS), including controlled trials and cohort studies. Each study was required to have a GEMS comparison group. An Injury Severity Score (ISS) of at least 15 or an equivalent marker for injury severity was required. We included adults age 16 years or older. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed the risk of bias of included studies. We applied the Downs and Black quality assessment tool for NRS. We analyzed the results in a narrative review, and with studies grouped by methodology and injury type. We constructed 'Summary of findings' tables in accordance with the GRADE Working Group criteria. MAIN RESULTS: This review includes 38 studies, of which 34 studies examined survival following transportation by HEMS compared with GEMS for adults with major trauma. Four studies were of inter-facility transfer to a higher level trauma center by HEMS compared with GEMS. All studies were NRS; we found no RCTs. The primary outcome was survival at hospital discharge. We calculated unadjusted mortality using data from 282,258 people from 28 of the 38 studies included in the primary analysis. Overall, there was considerable heterogeneity and we could not determine an accurate estimate of overall effect.Based on the unadjusted mortality data from six trials that focused on traumatic brain injury, there was no decreased risk of death with HEMS. Twenty-one studies used multivariate regression to adjust for confounding. Results varied, some studies found a benefit of HEMS while others did not. Trauma-Related Injury Severity Score (TRISS)-based analysis methods were used in 14 studies; studies showed survival benefits in both the HEMS and GEMS groups as compared with MTOS. We found no studies evaluating the secondary outcome, morbidity, as assessed by quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs). Four studies suggested a small to moderate benefit when HEMS was used to transfer people to higher level trauma centers. Road traffic and helicopter crashes are adverse effects which can occur with either method of transport. Data regarding safety were not available in any of the included studies. Overall, the quality of the included studies was very low as assessed by the GRADE Working Group criteria. AUTHORS' CONCLUSIONS: Due to the methodological weakness of the available literature, and the considerable heterogeneity of effects and study methodologies, we could not determine an accurate composite estimate of the benefit of HEMS. Although some of the 19 multivariate regression studies indicated improved survival associated with HEMS, others did not. This was also the case for the TRISS-based studies. All were subject to a low quality of evidence as assessed by the GRADE Working Group criteria due to their nonrandomized design. The question of which elements of HEMS may be beneficial has not been fully answered. The results from this review provide motivation for future work in this area. This includes an ongoing need for diligent reporting of research methods, which is imperative for transparency and to maximize the potential utility of results. Large, multicenter studies are warranted as these will help produce more robust estimates of treatment effects. Future work in this area should also examine the costs and safety of HEMS, since multiple contextual determinants must be considered when evaluating the effects of HEMS for adults with major trauma.
BACKGROUND: Over the past several decades, the overweight and obesity epidemic in the USA has resulted in a significant health and economic burden. Understanding current trends and future trajectories at both national and state levels is crucial for assessing the success of existing interventions and informing future health policy changes. We estimated the prevalence of overweight and obesity from 1990 to 2021 with forecasts to 2050 for children and adolescents (aged 5-24 years) and adults (aged ≥25 years) at the national level. Additionally, we derived state-specific estimates and projections for older adolescents (aged 15-24 years) and adults for all 50 states and Washington, DC. METHODS: or higher, and for individuals younger than 18 years definitions were based on International Obesity Task Force criteria. Historical trends of overweight and obesity prevalence from 1990 to 2021 were estimated using spatiotemporal Gaussian process regression models. A generalised ensemble modelling approach was then used to derive projected estimates up to 2050, assuming continuation of past trends and patterns. All estimates were calculated by age and sex at the national level, with estimates for older adolescents (aged 15-24 years) and adults aged (≥25 years) also calculated for 50 states and Washington, DC. 95% uncertainty intervals (UIs) were derived from the 2·5th and 97·5th percentiles of the posterior distributions of the respective estimates. FINDINGS: In 2021, an estimated 15·1 million (95% UI 13·5-16·8) children and young adolescents (aged 5-14 years), 21·4 million (20·2-22·6) older adolescents (aged 15-24 years), and 172 million (169-174) adults (aged ≥25 years) had overweight or obesity in the USA. Texas had the highest age-standardised prevalence of overweight or obesity for male adolescents (aged 15-24 years), at 52·4% (47·4-57·6), whereas Mississippi had the highest for female adolescents (aged 15-24 years), at 63·0% (57·0-68·5). Among adults, the prevalence of overweight or obesity was highest in North Dakota for males, estimated at 80·6% (78·5-82·6), and in Mississippi for females at 79·9% (77·8-81·8). The prevalence of obesity has outpaced the increase in overweight over time, especially among adolescents. Between 1990 and 2021, the percentage change in the age-standardised prevalence of obesity increased by 158·4% (123·9-197·4) among male adolescents and 185·9% (139·4-237·1) among female adolescents (15-24 years). For adults, the percentage change in prevalence of obesity was 123·6% (112·4-136·4) in males and 99·9% (88·8-111·1) in females. Forecast results suggest that if past trends and patterns continue, an additional 3·33 million children and young adolescents (aged 5-14 years), 3·41 million older adolescents (aged 15-24 years), and 41·4 million adults (aged ≥25 years) will have overweight or obesity by 2050. By 2050, the total number of children and adolescents with overweight and obesity will reach 43·1 million (37·2-47·4) and the total number of adults with overweight and obesity will reach 213 million (202-221). In 2050, in most states, a projected one in three adolescents (aged 15-24 years) and two in three adults (≥25 years) will have obesity. Although southern states, such as Oklahoma, Mississippi, Alabama, Arkansas, West Virginia, and Kentucky, are forecast to continue to have a high prevalence of obesity, the highest percentage changes from 2021 are projected in states such as Utah for adolescents and Colorado for adults. INTERPRETATION: Existing policies have failed to address overweight and obesity. Without major reform, the forecasted trends will be devastating at the individual and population level, and the associated disease burden and economic costs will continue to escalate. Stronger governance is needed to support and implement a multifaceted whole-system approach to disrupt the structural drivers of overweight and obesity at both national and local levels. Although clinical innovations should be leveraged to treat and manage existing obesity equitably, population-level prevention remains central to any intervention strategies, particularly for children and adolescents. FUNDING: Bill & Melinda Gates Foundation.
D uring the 20th century the united states witnessed sweeping social, political, and economic transformations as well as far‐reaching advancements in medical diagnosis and care. Despite the dramatic changes in demography, the meaning of citizenship, and the ability to treat and cure acute and chronic diseases, foreigners were consistently associated with germs and contagion. In this article we explore why, at critical junctures in American history, immigrants have been stigmatized as the etiology of a wide variety of physical and societal ills. Anti‐immigrant rhetoric and policy have often been framed by an explicitly medical language, one in which the line between perceived and actual threat is slippery and prone to hysteria and hyperbole. Our examination focuses on three periods of immigration history: (1) the late 19th century to the passage of the National Origins Act in 1924 when millions of newcomers arrived in the United States and increasingly stringent quotas were enacted; (2) an era of retrenchment and exclusion from 1924 to 1965 when far fewer immigrants entered yet their identification with disease and contamination remained intact; (3) and the period from 1965 to the present, when family reunification laws became the centerpiece of immigration policy and spawned the migration of millions of Asians and Latin Americans to this country. During the 20th century the United States witnessed social, political, and economic transformations as well as advancements in medical diagnosis and care. Despite changes in demography, the meaning of citizenship, and the ability to treat and cure acute and chronic diseases, foreigners were consistently associated with germs and contagion. This article explores why, at critical junctures in American history, immigrants have been stigmatized as the etiology of a variety of physical and societal ills. The article analyzes three periods from 1880 to the present and suggests that now, as germs progressively and, often, indiscriminately cross national, social, and economic boundaries through multiple vectors, the mistakes of the past must not be repeated. Protecting the public health in the current era of globalization requires an ecumenical, pragmatic, and historically informed approach to understanding the links between immigration and disease.
BACKGROUND: The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation. METHODS: At 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery. RESULTS: We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P < 0.001 for values at or below the 50th percentile; P = 0.008 for values at or below the 75th percentile). For the lengths measured at 28 weeks, the corresponding relative risks were 2.80, 3.52, 5.39, 9.57, 13.88, and 24.94 (P < 0.001 for values at or below the 50th percentile; P = 0.003 for values at the 75th percentile). CONCLUSIONS: The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.
BACKGROUND: The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P-1) in 1992. METHODS: Women (N=13388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35-59 years of age with a 5-year predicted risk for breast cancer of at least 1.66%, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n=6707) or 20 mg/day tamoxifen (n=6681) for 5 years. Gail's algorithm, based on a multivariate logistic regression model using combinations of risk factors, was used to estimate the probability (risk) of occurrence of breast cancer over time. RESULTS: Tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<.00001), with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44%), 50-59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided P<.002). Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69%, but no difference in the occurrence of estrogen receptor-negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95% confidence interval = 1.35-4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I (localized disease); no endometrial cancer deaths have occurred in this group. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep-vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older. CONCLUSIONS: Tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease.
Policy Points This scoping review reveals a growing literature on the effects of certain state opioid misuse prevention policies, but persistent gaps in evidence on other prevalent state policies remain. Policymakers interested in reducing the volume and dosage of opioids prescribed and dispensed can consider adopting robust prescription drug monitoring programs with mandatory access provisions and drug supply management policies, such as prior authorization policies for high-risk prescription opioids. Further research should concentrate on potential unintended consequences of opioid misuse prevention policies, differential policy effects across populations, interventions that have not received sufficient evaluation (eg, Good Samaritan laws, naloxone access laws), and patient-related outcomes. CONTEXT: In the midst of an opioid crisis in the United States, an influx of state opioid misuse prevention policies has provided new opportunities to generate evidence of policy effectiveness that can inform policy decisions. We conducted a scoping review to synthesize the available evidence on the effectiveness of US state interventions to improve patient and provider outcomes related to opioid misuse and addiction. METHODS: We searched six online databases to identify evaluations of state opioid policies. Eligible studies examined legislative and administrative policy interventions that evaluated (a) prescribing and dispensing, (b) patient behavior, or (c) patient health. FINDINGS: Seventy-one articles met our inclusion criteria, including 41 studies published between 2016 and 2018. These articles evaluated nine types of state policies targeting opioid misuse. While prescription drug monitoring programs (PDMPs) have received considerable attention in the literature, far fewer studies addressed other types of state policy. Overall, evidence quality is very low for the majority of policies due to a small number of evaluations. Of interventions that have been the subject of considerable research, promising means of reducing the volume and dosages of opioids prescribed and dispensed include drug supply management policies and robust PDMPs. Due to low study number and quality, evidence is insufficient to draw conclusions regarding interventions targeting patient behavior and health outcomes, including naloxone access laws and Good Samaritan laws. CONCLUSIONS: Recent research has improved the evidence base on several state interventions targeting opioid misuse. Specifically, moderate evidence suggests that drug supply management policies and robust PDMPs reduce opioid prescribing. Despite the increase in rigorous evaluations, evidence remains limited for the majority of policies, particularly those targeting patient health-related outcomes.
Many doctors, patients, journalists, and politicians alike do not understand what health statistics mean or draw wrong conclusions without noticing. Collective statistical illiteracy refers to the widespread inability to understand the meaning of numbers. For instance, many citizens are unaware that higher survival rates with cancer screening do not imply longer life, or that the statement that mammography screening reduces the risk of dying from breast cancer by 25% in fact means that 1 less woman out of 1,000 will die of the disease. We provide evidence that statistical illiteracy (a) is common to patients, journalists, and physicians; (b) is created by nontransparent framing of information that is sometimes an unintentional result of lack of understanding but can also be a result of intentional efforts to manipulate or persuade people; and (c) can have serious consequences for health. The causes of statistical illiteracy should not be attributed to cognitive biases alone, but to the emotional nature of the doctor-patient relationship and conflicts of interest in the healthcare system. The classic doctor-patient relation is based on (the physician's) paternalism and (the patient's) trust in authority, which make statistical literacy seem unnecessary; so does the traditional combination of determinism (physicians who seek causes, not chances) and the illusion of certainty (patients who seek certainty when there is none). We show that information pamphlets, Web sites, leaflets distributed to doctors by the pharmaceutical industry, and even medical journals often report evidence in nontransparent forms that suggest big benefits of featured interventions and small harms. Without understanding the numbers involved, the public is susceptible to political and commercial manipulation of their anxieties and hopes, which undermines the goals of informed consent and shared decision making. What can be done? We discuss the importance of teaching statistical thinking and transparent representations in primary and secondary education as well as in medical school. Yet this requires familiarizing children early on with the concept of probability and teaching statistical literacy as the art of solving real-world problems rather than applying formulas to toy problems about coins and dice. A major precondition for statistical literacy is transparent risk communication. We recommend using frequency statements instead of single-event probabilities, absolute risks instead of relative risks, mortality rates instead of survival rates, and natural frequencies instead of conditional probabilities. Psychological research on transparent visual and numerical forms of risk communication, as well as training of physicians in their use, is called for. Statistical literacy is a necessary precondition for an educated citizenship in a technological democracy. Understanding risks and asking critical questions can also shape the emotional climate in a society so that hopes and anxieties are no longer as easily manipulated from outside and citizens can develop a better-informed and more relaxed attitude toward their health.
The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the CDC and NCI, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy and is the first CBTRUS Report to provide the distribution of molecular markers for selected brain and CNS tumor histologies. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.25 (Malignant AAAIR=7.06, Non-malignant AAAIR=17.18). This overall rate was higher in females compared to males (26.95 versus 21.35) and non-Hispanics compared to Hispanics (24.68 versus 22.12). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.3% of all tumors and 49.1% of malignant tumors), and the most common non-malignant tumor was meningioma (39% of all tumors and 54.5% of non-malignant tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.21. An estimated 88,190 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US population in 2021 (25,690 malignant and 62,500 non-malignant). There were 83,029 deaths attributed to malignant brain and other CNS tumors between 2014 and 2018. This represents an average annual mortality rate of 4.43 per 100,000 and an average of 16,606 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 66.9%, for a non-malignant brain and other CNS tumors the five-year relative survival rate was 92.1%.
BACKGROUND: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. METHODS: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. FINDINGS: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5-3·0) of age-standardised female deaths and 6·8% (5·8-8·0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2-4·3) of female deaths and 12·2% (10·8-13·6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2·3% (95% UI 2·0-2·6) and male attributable DALYs were 8·9% (7·8-9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0-1·7] of total deaths), road injuries (1·2% [0·7-1·9]), and self-harm (1·1% [0·6-1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2-33·3) of total alcohol-attributable female deaths and 18·9% (15·3-22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0-0·8) standard drinks per week. INTERPRETATION: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption. FUNDING: Bill & Melinda Gates Foundation.
BACKGROUND: Controlled clinical trials have shown that beta-blockers can produce hemodynamic and symptomatic improvement in chronic heart failure, but the effect of these drugs on survival has not been determined. METHODS: We enrolled 1094 patients with chronic heart failure in a double-blind, placebo-controlled, stratified program, in which patients were assigned to one of the four treatment protocols on the basis of their exercise capacity. Within each of the four protocols patients with mild, moderate, or severe heart failure with left ventricular ejection fractions < or = 0.35 were randomly assigned to receive either placebo (n = 398) or the beta-blocker carvedilol (n = 696); background therapy with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor remained constant. Patient were observed for the occurrence death or hospitalization for cardiovascular reasons during the following 6 months, after the beginning (12 months for the group with mild heart failure). RESULTS: The overall mortality rate was 7.8 percent in the placebo group and 3.2 percent in the carvedilol group; the reduction in risk attributable to carvedilol was 65 percent (95 percent confidence interval, 39 to 80 percent; P < 0.001). This finding led the Data and Safety Monitoring Board to recommend termination of the study before its scheduled completion. In addition, as compared with placebo, carvedilol therapy was accompanied by a 27 percent reduction in the risk of hospitalization for cardiovascular causes (19.6 percent vs. 14.1 percent, P = 0.036), as well as a 38 percent reduction in the combined risk of hospitalization or death (24.6 percent vs, 15.8 percent, P < 0.001). Worsening heart failure as an adverse reaction during treatment was less frequent in the carvedilol than in the placebo group. CONCLUSIONS: Carvedilol reduces the risk or death as well as the risk of hospitalization for cardiovascular causes in patients with heart failure who are receiving treatment with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor.
BACKGROUND: Disease-associated malnutrition has been identified as a prevalent condition, particularly for the elderly, which has often been overlooked in the U.S. healthcare system. The state-level burden of community-based disease-associated malnutrition is unknown and there have been limited efforts by state policy makers to identify, quantify, and address malnutrition. The objective of this study was to examine and quantify the state-level economic burden of disease-associated malnutrition. METHODS: Direct medical costs of disease-associated malnutrition were calculated for 8 diseases: Stroke, Chronic Obstructive Pulmonary Disease, Coronary Heart Failure, Breast Cancer, Dementia, Musculoskeletal Disorders, Depression, and Colorectal Cancer. National disease and malnutrition prevalence rates were estimated for subgroups defined by age, race, and sex using the National Health and Nutrition Examination Survey and the National Health Interview Survey. State prevalence of disease-associated malnutrition was estimated by combining national prevalence estimates with states' demographic data from the U.S. Census. Direct medical cost for each state was estimated as the increased expenditures incurred as a result of malnutrition. PRINCIPAL FINDINGS: Direct medical costs attributable to disease-associated malnutrition vary among states from an annual cost of $36 per capita in Utah to $65 per capita in Washington, D.C. Nationally the annual cost of disease-associated malnutrition is over $15.5 billion. The elderly bear a disproportionate share of this cost on both the state and national level. CONCLUSIONS: Additional action is needed to reduce the economic impact of disease-associated malnutrition, particularly at the state level. Nutrition may be a cost-effective way to help address high health care costs.
Through an exploration of relevant legislation and court cases, this article discusses the contemporary constitution of neoliberal subjects via the devolution of select immigration powers to state and local governments by the federal government of the United States. Since the latter decades of the nineteenth century, the federal government has had plenary power over immigration, which has enabled it to treat “people as immigrants” (or as “nonpersons” falling outside of many Constitutional protections), simultaneously requiring that states and cities treat “immigrants as people” (or as persons protected by the Constitution). Beginning in the mid-1990s, however, the devolution of welfare policy and immigration policing powers has challenged the scalar constitution of personhood, as state and local governments have newfound powers to discriminate on the basis of alienage, or noncitizen status. In devolving responsibility for certain immigration-related policies to state and local governments, the federal government is participating in the rescaling of membership policy and, by extension, the rescaling of a defining characteristic of the nation-state. This recent rescaling is evidence of the contemporary neoliberalization of membership policy in the United States, and specifically highlights the legal (re)production of scale.
The importance of social trust has become widely accepted in the social sciences. A number of explanations have been put forward for the stark variation in social trust among countries. Among these, participation in voluntary associations received most attention. Yet there is scant evidence that participation can lead to trust. In this article, the authors examine a variable that has not gotten the attention it deserves in the discussion about the sources of generalized trust, namely, equality. They conceptualize equality along two dimensions: economic equality and equality of opportunity. The omission of both these dimensions of equality in the social capital literature is peculiar for several reasons. First, it is obvious that the countries that score highest on social trust also rank highest on economic equality, namely, the Nordic countries, the Netherlands, and Canada. Second, these countries have put a lot of effort in creating equality of opportunity, not least in regard to their policies for public education, health care, labor market opportunities, and (more recently) gender equality. The argument for increasing social trust by reducing inequality has largely been ignored in the policy debates about social trust. Social capital research has to a large extent been used by several governments and policy organizations to send a message to people that the bad things in their society are caused by too little volunteering. The policy implications that follow from the authors' research is that the low levels of trust and social capital that plague many countries are caused by too little government action to reduce inequality. However, many countries with low levels of social trust and social capital may be stuck in what is known as a social trap . The logic of such a situation is the following. Social trust will not increase because massive social inequality prevails, but the public policies that could remedy this situation cannot be established precisely because there is a genuine lack of trust. This lack of trust concerns both “other people” and the government institutions that are needed to implement universal policies.
The last words of Justice Douglas's remarkable opinion for the Court in Griswold v. Connecticut 1 were these:Marriage is a coming together for better or for worse, hopefully enduring, and intimate to the degree of being sacred.It is an association that promotes a way of life, not causes; a harmony in living, not political faiths; a bilateral loyalty, not commercial or social projects.Yet it is an association for as noble a purpose as any involved in our prior decisions. 2 At first reading, these comments seemed not so much a peroration as an afterthought, an effort to draw additional support for the Court's decision from a series of precedents protecting the freedom of political association. 3 Characteristically, Justice Douglas was content to be suggestive, and to leave to others the task of doctrinal elaboration.Before Griswold was decided, the notion of constitutional protection of the freedom of association was a First Amendment doctrine and little more. 4Yet Griswold's focus was not someone's right to give or receive information about contraception, but the right of a married couple to use devices that would accomplish it.The Court's opinion located that right within a generalized "zone of privacy," created in part by the First Amendment, but by the Third, Fourth, and Fifth * Professor of Law, University of California, Los Angeles.I am
BACKGROUND: Cholinergic deficits are prominent in patients who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients. METHODS: Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimer's Disease Cooperative Study-Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini-Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test. RESULTS: A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer's disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P<0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group, and clinically meaningful worsening was observed in 13.0 percent and 23.1 percent, respectively (mean score at 24 weeks, 3.8 and 4.3, respectively; P=0.007). Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables. The most frequent adverse events were nausea (affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001), and tremor (10.2 and 3.9 percent, P=0.01). CONCLUSIONS: In this placebo-controlled study, rivastigmine was associated with moderate improvements in dementia associated with Parkinson's disease but also with higher rates of nausea, vomiting, and tremor.
Ocular infections can be medical emergencies that result in permanent visual impairment or blindness and loss of quality of life. Bacteria are a major cause of ocular infections. Effective treatment of ocular infections requires knowledge of which bacteria are the likely cause of the infection. This survey of ocular bacterial isolates and review of ocular pathogens is based on a survey of a collection of isolates banked over a ten-year span at the Dean McGee Eye Institute in Oklahoma. These findings illustrate the diversity of bacteria isolated from the eye, ranging from common species to rare and unique species. At all sampled sites, staphylococci were the predominant bacteria isolated. Pseudomonads were the most common Gram-negative bacterial isolate, except in vitreous, where Serratia was the most common Gram-negative bacterial isolate. Here, we discuss the range of ocular infections that these species have been documented to cause and treatment options for these infections. Although a highly diverse spectrum of species has been isolated from the eye, the majority of infections are caused by Gram-positive species, and in most infections, empiric treatments are effective.
Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.