Relationship between the Bolsa Família national cash transfer programme and suicide incidence in Brazil: A quasi-experimental study

BackgroundSocioeconomic factors have been consistently associated with suicide, and economic recessions are linked to rising suicide rates. However, evidence on the impact of socioeconomic interventions to reduce suicide rates is limited. This study investigates the association of the world’s largest conditional cash transfer programme with suicide rates in a cohort of half of the Brazilian population.Methods and findingsWe used data from the 100 Million Brazilian Cohort, covering a 12-year period (2004 to 2015). It comprises socioeconomic and demographic information on 114,008,317 individuals, linked to the “Bolsa Família” programme (BFP) payroll database, and nationwide death registration data. BFP was implemented by the Brazilian government in 2004. We estimated the association of BFP using inverse probability of treatment weighting, estimating the weights for BFP beneficiaries (weight = 1) and nonbeneficiaries by the inverse probability of receiving treatment (weight = E(ps)/(1-E(ps))). We used an average treatment effect on the treated (ATT) estimator and fitted Poisson models to estimate the incidence rate ratios (IRRs) for suicide associated with BFP experience. At the cohort baseline, BFP beneficiaries were younger (median age 27.4 versus 35.4), had higher unemployment rates (56% versus 32%), a lower level of education, resided in rural areas, and experienced worse household conditions. There were 36,742 suicide cases among the 76,532,158 individuals aged 10 years, or older, followed for 489,500,000 person-years at risk. Suicide rates among beneficiaries and nonbeneficiaries were 5.4 (95% CI = 5.32, 5.47, p < 0.001) and 10.7 (95% CI = 10.51, 10.87, p < 0.001) per 100,000 individuals, respectively. BFP beneficiaries had a lower suicide rate than nonbeneficiaries (IRR = 0.44, 95% CI = 0.42, 0.45, p < 0.001). This association was stronger among women (IRR = 0.36, 95% CI = 0.33, 0.38, p < 0.001), and individuals aged between 25 and 59 (IRR = 0.41, 95% CI = 0.40, 0.43, p < 0.001). Study limitations include a lack of control for previous mental disorders and access to means of suicide, and the possible under-registration of suicide cases due to stigma.ConclusionsWe observed that BFP was associated with lower suicide rates, with similar results in all sensitivity analyses. These findings should help to inform policymakers and health authorities to better design suicide prevention strategies. Targeting social determinants using cash transfer programmes could be important in limiting suicide, which is predicted to rise with the economic recession, consequent to the Coronavirus Disease 2019 (COVID-19) pandemic.

In a quasi-experimental study, Daiane Borges Machado and colleagues investigate the association between rates of suicide and the Bolsa Familia cash transfer program in the 100 Million Brazilian Cohort.     

Changes in the associations of race and rurality with SARS-CoV-2 infection,mortality, and case fatality in the United States from February 2020 to March 2021: A population-based cohort study

BackgroundWe examined whether key sociodemographic and clinical risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and mortality changed over time in a population-based cohort study.Methods and findingsIn a cohort of 9,127,673 persons enrolled in the United States Veterans Affairs (VA) healthcare system, we evaluated the independent associations of sociodemographic and clinical characteristics with SARS-CoV-2 infection (n = 216,046), SARS-CoV-2–related mortality (n = 10,230), and case fatality at monthly intervals between February 1, 2020 and March 31, 2021. VA enrollees had a mean age of 61 years (SD 17.7) and were predominantly male (90.9%) and White (64.5%), with 14.6% of Black race and 6.3% of Hispanic ethnicity. Black (versus White) race was strongly associated with SARS-CoV-2 infection (adjusted odds ratio [AOR] 5.10, [95% CI 4.65 to 5.59], p-value <0.001), mortality (AOR 3.85 [95% CI 3.30 to 4.50], p-value < 0.001), and case fatality (AOR 2.56, 95% CI 2.23 to 2.93, p-value < 0.001) in February to March 2020, but these associations were attenuated and not statistically significant by November 2020 for infection (AOR 1.03 [95% CI 1.00 to 1.07] p-value = 0.05) and mortality (AOR 1.08 [95% CI 0.96 to 1.20], p-value = 0.21) and were reversed for case fatality (AOR 0.86, 95% CI 0.78 to 0.95, p-value = 0.005). American Indian/Alaska Native (AI/AN versus White) race was associated with higher risk of SARS-CoV-2 infection in April and May 2020; this association declined over time and reversed by March 2021 (AOR 0.66 [95% CI 0.51 to 0.85] p-value = 0.004). Hispanic (versus non-Hispanic) ethnicity was associated with higher risk of SARS-CoV-2 infection and mortality during almost every time period, with no evidence of attenuation over time. Urban (versus rural) residence was associated with higher risk of infection (AOR 2.02, [95% CI 1.83 to 2.22], p-value < 0.001), mortality (AOR 2.48 [95% CI 2.08 to 2.96], p-value < 0.001), and case fatality (AOR 2.24, 95% CI 1.93 to 2.60, p-value < 0.001) in February to April 2020, but these associations attenuated over time and reversed by September 2020 (AOR 0.85, 95% CI 0.81 to 0.89, p-value < 0.001 for infection, AOR 0.72, 95% CI 0.62 to 0.83, p-value < 0.001 for mortality and AOR 0.81, 95% CI 0.71 to 0.93, p-value = 0.006 for case fatality). Throughout the observation period, high comorbidity burden, younger age, and obesity were consistently associated with infection, while high comorbidity burden, older age, and male sex were consistently associated with mortality. Limitations of the study include that changes over time in the associations of some risk factors may be affected by changes in the likelihood of testing for SARS-CoV-2 according to those risk factors; also, study results apply directly to VA enrollees who are predominantly male and have comprehensive healthcare and need to be confirmed in other populations.ConclusionsIn this study, we found that strongly positive associations of Black and AI/AN (versus White) race and urban (versus rural) residence with SARS-CoV-2 infection, mortality, and case fatality observed early in the pandemic were ameliorated or reversed by March 2021.

George Ioannou and co-workers study the distribution of SARS-CoV-2 infections and outcomes among the United States population.     

Is There an Association between Traumatic Dental Injury and Social Capital,Binge Drinking and Socioeconomic Indicators among Schoolchildren?

ObjectivesTraumatic dental injury is defined as trauma caused by forces on a tooth with variable extent and severity. The aim of the present study was to investigate the prevalence of traumatic dental injury and its association with overjet, lip protection, sex, socioeconomic status, social capital and binge drinking among 12-year-old students.ResultsThe prevalence of traumatic dental injury was 29.9% (176/588). Traumatic dental injury was more prevalent among male adolescents (p = 0.010), those with overjet greater than 5 mm (p < 0.001) and those with inadequate lip protection (p < 0.001). In the multiple logistic regression analysis, overjet [OR = 3.80 (95% CI: 2.235–6.466), p < 0.0001], inadequate lip protection [OR = 5.585 (95% CI: 3.654–8.535), p < 0.0001] and binge drinking [OR = 1.93 (95% CI: 1.21–3.06), p = 0.005] remained significantly associated with traumatic dental injury.ConclusionsThe present findings suggest that a high level of total social capital and trust are not associated with TDI in adolescents, unlike binge drinking. The effects of social and behavioral factors on TDI are not well elucidated. Therefore, further research involving other populations and a longitudinal design is recommended.     

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care,secondary care,and death registration data in the OpenSAFELY platform

BackgroundThere is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation.Methods and findingsWith the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes.We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants.ConclusionsIn this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.

Krishnan Bhaskaran and co-workers study health outcomes after admission with COVID-19 and subsequent discharge.     

Mortality and major disease risk among migrants of the 1991–2001 Balkan wars to Sweden: A register-based cohort study

BackgroundIn recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991–2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.Methods and findingsWe conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991–2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34–1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29–1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08–1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15–1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14–1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96–10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48–0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51–0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.ConclusionsOur findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

Edda Bjork Thordardottir and co-workers study health outcomes among migrants from the former Yugoslavia to Sweden.     

Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study

BackgroundBenzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg.Methods and findingsThe retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score–stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables.ConclusionsIn US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine–opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

In a retrospective cohort study, Dr. Wayne Ray and colleagues investigate concurrent opioid and hypnotic use and mortality in older adults in US.     

The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis

BackgroundAmodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial.Methods and findingsStudies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression.The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p < 0.001) and pyronaridine (−1.2 ms, −3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented.ConclusionsWhile caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate–reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.

In this meta-analysis, Xin Hui Supanee Chan and colleagues investigate the cardiovascular effects of amodiaquine and structurally-related antimalarials using individual patient data from trials.     

Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease

BackgroundInvasive pneumococcal disease (IPD) causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.MethodsIn a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.ResultsOverall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC) count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7–12.8, p < .001); age ≥80 years (OR, 6.5; 95% CI, 2.0–21.6, p = .002); serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5–8.1, p < .001); underlying liver disease (OR, 3.5; 95% CI, 1.6–7.8, p = .002); mechanical ventilation (OR, 3.0; 95% CI, 1.7–5.6, p < .001); and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4–4.0, p = .001). Pneumococcal serotype and drug resistance were not associated with poor outcomes.ConclusionsHost factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.     

Is Time to Reach EDSS 6.0 Faster in Patients with Late-Onset versus Young-Onset Multiple Sclerosis?

MethodsThis cross-sectional cohort study was conducted to identify LOMS and YOMS patients’ with relapsing remitting course at MS diagnosis. Time (years) to reach sustained EDSS 6.0 was compared between LOMS and AOMS patients. Cox proportional hazards model was used to evaluate the demographic and clinical predictors of time to EDSS 6.0 in these cohorts.ResultsLOMS and YOMS cohorts comprised 99 (10.7%) and 804 (89.3%) patients respectively. Spinal cord presentation at MS onset was more common among LOMS patients (46.5% vs. 32.3%). The proportions of LOMS and YOMS patients reaching EDSS 6.0 during the follow-up period were 19.2% and 15.7% respectively. In multivariable Cox proportional hazards model, older age at MS onset (adjusted hazard ratio (aHR) = 3.96; 95% CI: 2.14–7.32; p < 0.001), male gender (aHR = 1.85; 95% CI: 1.22–2.81; p = 0.004) and spinal cord presentation at onset (aHR = 1.47; 95% CI: 0.98–2.21; p = 0.062) were significantly associated with shorter time to EDSS 6.0.ConclusionsLOMS patients attained EDSS 6.0 in a significantly shorter period that was influenced by male gender and spinal cord presentation at MS onset.     

Resistance exercise,alone and in combination with aerobic exercise,and obesity in Dallas,Texas, US: A prospective cohort study

BackgroundObesity is a significant and growing public health problem in high-income countries. Little is known about the relationship between resistance exercise (RE), alone and in combination with aerobic exercise (AE), and the risk of developing obesity. The purpose of this prospective cohort study was to examine the associations between different amounts and frequencies of RE, independent of AE, and incident obesity.Methods and findingsParticipants were 11,938 healthy adults ages 18–89 years with a BMI < 30 kg/m² at baseline who completed at least 2 clinical examinations during 1987–2005 as part of the Aerobics Center Longitudinal Study. Self-reported RE participation in minutes/week and days/week was collected from a standardized questionnaire. Incident obesity was defined as a BMI ≥ 30 kg/m² at follow-up. Incident obesity was also defined by waist circumference (WC) > 102/88 cm for men/women and percent body fat (PBF) ≥ 25%/30% for men/women at follow-up in participants who were not obese by WC (n = 9,490) or PBF (n = 8,733) at baseline. During the average 6-year follow-up, 874 (7%), 726 (8%), and 1,683 (19%) developed obesity defined by BMI, WC, or PBF, respectively. Compared with no RE, 60–119 min/wk of RE was associated with 30%, 41%, and 31% reduced risk of obesity defined by BMI (hazard ratio [95% CI], 0.70 [0.54–0.92], p = 0.008), WC (0.59 [0.44–0.81], p < 0.001), and PBF (0.69 [0.57–0.83], p < 0.001), respectively, after adjusting for confounders including age, sex, examination year, smoking status, heavy alcohol consumption, hypertension, hypercholesterolemia, diabetes, and AE. Compared with not meeting the RE guidelines of ≥2 d/wk, meeting the RE guidelines was associated with 18%, 30%, and 30% reduced risk of obesity defined by BMI (hazard ratio [95% CI], 0.82 [0.69–0.97], p = 0.02), WC (0.70 [0.57–0.85], p < 0.001), and PBF (0.70 [0.62–0.79], p < 0.001), respectively. Compared with meeting neither guideline, meeting both the AE and RE guidelines was associated with the smallest hazard ratios for obesity. Limitations of this study include limited generalizability as participants were predominantly white men from middle to upper socioeconomic strata, use of self-reported RE, and lack of detailed diet data for the majority of participants.ConclusionsIn this study, we observed that RE was associated with a significantly reduced risk of obesity even after considering AE. However, meeting both the RE and AE guidelines was associated with the lowest risk of obesity.

In a prospective cohort study, Angelique G. Brellenthin and colleagues investigate associations between resistance and aerobic exercise, and incident obesity in the United States.     

The burden of traumatic brain injury from low-energy falls among patients from 18 countries in the CENTER-TBI Registry: A comparative cohort study

BackgroundTraumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma.Methods and findingsWe conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer—in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations.ConclusionsWe observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required.

In a cohort study, Fiona Lecky and colleagues investigate the factors associated with traumatic brain injury resulting from low energy falls compared with injuries from high energy transfer mechanisms among patients across Europe and Israel.     

Predictive and Prognostic Value of Metabolic Tumor Volume (MTV) in Patients with Laryngeal Carcinoma Treated by Radiotherapy (RT) / Concurrent Chemoradiotherapy (CCRT)

PurposeTo evaluate the predictive and prognostic value of pretreatment metabolic tumor volume (MTV) in patients with treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).MethodsWe reviewed the records of 118 patients with newly diagnosed laryngeal carcinoma, who had been treated by RT or CCRT. Pretreatment positron emission tomography (PET) was performed, and MTV values were obtained by contouring margins of standardized uptake value. Clinical factors and MTV were analyzed for their association with survival.ResultsPatients with residual disease showed a significantly higher MTV than those with a complete response (CR) after primary treatment. Univariate analysis showed that the patients with a high MTV had a significantly lower disease-free survival (DFS) (p < 0.001). Subsite (p = 0.010), T-stage (p < 0.001), nodal metastasis (p < 0.001) and clinical stage (p < 0.001) also correlated significantly with DFS. In the multivariate analysis, MTV and clinical stage were both found to be independent prognostic factors for DFS (p = 0.001, p = 0.034, respectively). The 3-year DFS for patients with a high MTV were significantly poorer than those with a low MTV (p < 0.001).ConclusionsMTV of the primary tumor is a significant prognostic factor for DFS in patients with laryngeal carcinoma treated by RT or CCRT. The results imply that MTV could be an important factor when planning treatment and follow-up for patients with laryngeal carcinoma.     

Accumulation of Nicotinamide N-Methyltransferase (NNMT) in Cancer-associated Fibroblasts: A Potential Prognostic and Predictive Biomarker for Gastric Carcinoma

Nicotinamide N-methyltransferase (NNMT), a major metabolic regulator, has been identified as a predictor of cancer prognosis in ovarian and colorectal cancers. The study aims to evaluate the significance of stromal NNMT in gastric cancer (GC). Expression of stromal NNMT in 612 GC and 92 non-malignant tissues specimens was investigated by immunohistochemistry (IHC). The association between NNMT expression and occurrence of cancer or patient outcome was further analyzed, and the factors contributing to disease prognosis were evaluated by multiple Cox models. Stromal NNMT expression was higher in the malignant tissue (p<0.001). NNMT expression was significantly associated with GC stage (p=0.006). Compared to stromal “NNMT-low” cases, “NNMT-high” cases has lower disease-specific survival (hazard ratio [HR], 2.356; 95% confidence interval [CI] = 1.591–3.488; p<0.001) and disease-free survival (HR = 2.265; 95% CI = 1.529–3.354; p<0.001), as observed by multivariate Cox analysis after adjusting for stromal NNMT expression with other factors such as tumor grade and size. Notably, patients with stage II NNMT-low GC might be negatively affected by adjuvant chemotherapy, but lower stromal NNMT expression predicted a more favorable prognosis for GC. Our study confirmed that stromal NNMT expression is significantly increased in GC, which predicts an unfavorable post-operative prognosis for GC:     

Associations between lung function and physical and cognitive health in the Canadian Longitudinal Study on Aging (CLSA): A cross-sectional study from a multicenter national cohort

BackgroundLow lung function is associated with high mortality and adverse cardiopulmonary outcomes. Less is known of its association with broader health indices such as self-reported respiratory symptoms, perceived general health, and cognitive and physical performance. The present study seeks to address the association between forced expiratory volume in 1 second (FEV₁), an indicator of lung function, with broad markers of general health, relevant to aging trajectory in the general population.Methods and findingsFrom the Canadian general population, 22,822 adults (58% females, mean age 58.8 years [standard deviation (SD) 9.6]) were enrolled from the community between June 2012 and April 2015 from 11 Canadian cities and 7 provinces. Mixed effects regression was used to assess the cross-sectional relationship between FEV₁ with self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance. All associations were adjusted for age, sex, body mass index (BMI), education, smoking status, and self-reported comorbidities and expressed as adjusted odds ratios (aORs). Based on the Global Lung Function Initiative (GLI) reference values, 38% (n = 8,626) had normal FEV₁ (z-scores >0), 37% (n = 8,514) mild (z-score 0 to > −1 SD), 19% (n = 4,353) moderate (z-score −1 to > −2 SD), and 6% (n = 1,329) severely low FEV₁ (z-score = < −2 SD). There was a graded association between lower FEV₁ with higher aOR [95% CI] of self-reported moderate to severe respiratory symptoms (mild FEV₁ 1.09 [0.99 to 1.20] p = 0.08, moderate 1.45 [1.28 to 1.63] p < 0.001, and severe 2.67 [2.21 to 3.23] p < 0.001]), perceived poor health (mild 1.07 [0.9 to 1.27] p = 0.45, moderate 1.48 [1.24 to 1.78] p = <0.001, and severe 1.82 [1.42 to 2.33] p < 0.001]), and impaired cognitive performance (mild 1.03 [0.95 to 1.12] p = 0.41, moderate 1.16 [1.04 to 1.28] p < 0.001, and severe 1.40 [1.19 to 1.64] p < 0.001]). Similar graded association was observed between lower FEV₁ with lower physical performance on gait speed, Timed Up and Go (TUG) test, standing balance, and handgrip strength. These associations were consistent across different strata by age, sex, tobacco smoking, obstructive, and nonobstructive impairment on spirometry. A limitation of the current study is the observational nature of these findings and that causality cannot be inferred.ConclusionsWe observed graded associations between lower FEV₁ with higher odds of disabling respiratory symptoms, perceived poor general health, and lower cognitive and physical performance. These findings support the broader implications of measured lung function on general health and aging trajectory.

MyLinh Duong and colleagues investigate associations between lung function and self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance.     

Social determinants of mortality from COVID-19: A simulation study using NHANES

BackgroundThe COVID-19 epidemic in the United States is widespread, with more than 200,000 deaths reported as of September 23, 2020. While ecological studies show higher burdens of COVID-19 mortality in areas with higher rates of poverty, little is known about social determinants of COVID-19 mortality at the individual level.Methods and findingsWe estimated the proportions of COVID-19 deaths by age, sex, race/ethnicity, and comorbid conditions using their reported univariate proportions among COVID-19 deaths and correlations among these variables in the general population from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). We used these proportions to randomly sample individuals from NHANES. We analyzed the distributions of COVID-19 deaths by race/ethnicity, income, education level, and veteran status. We analyzed the association of these characteristics with mortality by logistic regression. Summary demographics of deaths include mean age 71.6 years, 45.9% female, and 45.1% non-Hispanic white. We found that disproportionate deaths occurred among individuals with nonwhite race/ethnicity (54.8% of deaths, 95% CI 49.0%–59.6%, p < 0.001), individuals with income below the median (67.5%, 95% CI 63.4%–71.5%, p < 0.001), individuals with less than a high school level of education (25.6%, 95% CI 23.4% –27.9%, p < 0.001), and veterans (19.5%, 95% CI 15.8%–23.4%, p < 0.001). Except for veteran status, these characteristics are significantly associated with COVID-19 mortality in multiple logistic regression. Limitations include the lack of institutionalized people in the sample (e.g., nursing home residents and incarcerated persons), the need to use comorbidity data collected from outside the US, and the assumption of the same correlations among variables for the noninstitutionalized population and COVID-19 decedents.ConclusionsSubstantial inequalities in COVID-19 mortality are likely, with disproportionate burdens falling on those who are of racial/ethnic minorities, are poor, have less education, and are veterans. Healthcare systems must ensure adequate access to these groups. Public health measures should specifically reach these groups, and data on social determinants should be systematically collected from people with COVID-19.

In this simulation study, Benjamin Seligman and colleagues explore socio-demographic factors associated with COVID-19 deaths in the US.     

Liveable residential space,residential density,and hypertension in Hong Kong: A population-based cohort study

BackgroundHypertension is a leading preventable risk factor of chronic disease and all-cause mortality. Housing is a fundamental social determinant of health. Yet, little is known about the impacts of liveable residential space and density on hypertension.Methods and findingsThis retrospective observational study (median follow-up of 2.2 years) leveraged the FAMILY Cohort, a large territory-wide cohort in Hong Kong, Special Administrative Region, People’s Republic of China to quantify associations of objectively measured liveable space and residential density with blood pressure outcomes among adults aged ≥16 years. Blood pressure outcomes comprised diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), and hypertension. Liveable space was measured as residential floor area, and density was assessed using the number of residential units per building block and neighborhood residential unit density within predefined catchments. Multivariable regression models examined associations of liveable floor area and residential density with prevalent and incident hypertension. We investigated effect modifications by age, sex, income, employment status, and housing type. Propensity score matching was further employed to match a subset of participants who moved to smaller residences at follow-up with equivalent controls who did not move, and generalized linear models examined the impact of moving to smaller residences upon blood pressure outcomes. Our fully adjusted models of prevalent hypertension outcomes comprised 30,439 participants at baseline, while 13,895 participants were available for incident models at follow-up. We found that each interquartile range (IQR) increment in liveable floor area was associated with lower DBP (beta [β] = −0.269 mm Hg, 95% confidence interval [CI]: −0.419 to −0.118, p < 0.001), SBP (β = −0.317 mm Hg, −0.551 to −0.084, p = 0.008), MAP (β = −0.285 mm Hg, −0.451 to −0.119 with p < 0.001), and prevalent hypertension (odds ratio [OR] = 0.955, 0.918 to 0.993, p = 0.022) at baseline. Each IQR increment in residential units per building block was associated with higher DBP (β = 0.477 mm Hg, 0.212 to 0.742, p = <0.001), SBP (β = 0.750 mm Hg, 0.322 to 1.177, p = <0.001), MAP (β = 0.568 mm Hg, 0.269 to 0.866, p < 0.001), and prevalent hypertension (OR = 1.091, 1.024 to 1.162, p = 0.007). Each IQR increase in neighborhood residential density within 0.5-mi street catchment was associated with lower DBP (β = −0.289 mm Hg, −0.441 to −0.137, p = <0.001), SBP (β = −0.411 mm Hg, −0.655 to −0.168, p < 0.001), MAP (β = −0.330 mm Hg, −0.501 to −0.159, p = <0.001), and lower prevalent hypertension (OR = 0.933, 0.899 to 0.969, p < 0.001). In the longitudinal analyses, each IQR increment in liveable floor area was associated with lower DBP (β = −0.237 mm Hg, −0.431 to −0.043, p = 0.016), MAP (β = −0.244 mm Hg, −0.444 to −0.043, p = 0.017), and incident hypertension (adjusted OR = 0.909, 0.836 to 0.988, p = 0.025). The inverse associations between larger liveable area and blood pressure outcomes were more pronounced among women and those residing in public housing. In the propensity-matched analysis, participants moving to residences of lower liveable floor area were associated with higher odds of incident hypertension in reference to those who did not move (OR = 1.623, 1.173 to 2.199, p = 0.002). The major limitations of the study are unmeasured residual confounding and loss to follow-up.ConclusionsWe disentangled the association of micro-, meso-, and macrolevel residential densities with hypertension and found that higher liveable floor area and neighborhood scale residential density were associated with lower odds of hypertension. These findings suggest adequate housing in the form of provisioning of sufficient liveable space and optimizing residential density at the building block, and neighborhood levels should be investigated as a potential population-wide preventive strategy for lowering hypertension and associated chronic diseases.

In a cohort study, Dr. Chinmoy Sarkar and colleagues investigate the association between liveable residential space, residential density and hypertension in Hong Kong.     

Assessing the risk of ketoacidosis due to sodium-glucose cotransporter (SGLT)-2 inhibitors in patients with type 1 diabetes: A meta-analysis and meta-regression

BackgroundSodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) showed benefits in type 1 diabetes mellitus (T1DM), but the risk of diabetic ketoacidosis (DKA) limits their use. Ability to predict DKA risk and therapeutic responses would enable appropriate patient selection for SGLT2i. We conducted a meta-analysis and meta-regression of randomized controlled trials (RCTs) evaluating SGLT2i in T1DM to assess moderators of the relative risk (RR) of DKA, of glycemic (HbA1c, fasting plasma glucose, continuous glucose monitoring parameters, insulin dose, and insulin sensitivity indices) and non-glycemic (body mass index (BMI), systolic BP, renal function, albuminuria, and diabetic eye disorders) efficacy, and of other safety outcomes (including hypoglycemia, infections, major adverse cardiovascular events, and death).Methods and findingsWe searched MEDLINE, Cochrane Library, EMBASE, ClinicalTrials.gov, Cochrane CENTRAL Register of Controlled Trials, and other electronic sources through August 30, 2020, for RCTs comparing SGLT2i with active comparators or placebo in adult patients with T1DM. Reviewers extracted data for relevant outcomes, performed random effects meta-analyses, subgroup analyses, and multivariable meta-regression. The strength of evidence was summarized with the GRADE approach. Among 9,914 records identified, 18 placebo-controlled RCTs (7,396 participants, 50% males, mean age 42 y (range 23 to 55 y), 5 different SGLT2i evaluated), were included. Main outcome measures were effect sizes and moderators of glycemic and non-glycemic efficacy and of safety outcomes. In a multivariable meta-regression model, baseline BMI (β = 0.439 [95% CI: 0.211, 0.666], p < 0.001) and estimated glucose disposal rate (eGDR) (β = −0.766 [−1.276, −0.256], p = 0.001) were associated with the RR of DKA (RR: 2.81; 95% CI:1.97, 4.01; p < 0.001, R² = 61%). A model including also treatment-related parameters (insulin dose change-to-baseline insulin sensitivity ratio and volume depletion) explained 86% of variance across studies in the risk of DKA (R² = 86%). The association of DKA with a BMI >27 kg/m² and with an eGDR <8.3 mg/kg/min was confirmed also in subgroup analyses. Among efficacy outcomes, the novel findings were a reduction in albuminuria (WMD: −9.91, 95% CI: −16.26, −3.55 mg/g, p = 0.002), and in RR of diabetic eye disorders (RR: 0.27[0.11, 0.67], p = 0.005) associated with SGLT2i. A SGLT2i dose-response gradient was consistently observed for main efficacy outcomes, but not for adverse events (AEs). Overall, predictors of DKA and of other AEs differed substantially from those of glycemic and non-glycemic efficacy. A limitation of our analysis was the relatively short (≤52 weeks) duration of included RCTs. The potential relevance for clinical practice needs also to be confirmed by real-world prospective studies.ConclusionsIn T1DM, the risk of DKA and main therapeutic responses to SGLT2i are modified by baseline BMI and insulin resistance, by total insulin dose reduction-to-baseline insulin sensitivity ratio, and by volume depletion, which may enable the targeted use of these drugs in patients with the greatest benefit and the lowest risk of DKA.

Giovanni Musso and colleagues conduct a meta-analysis to identify risk factors of diabetic ketoacidosis in patients with Type 1 diabetes taking SGLT2 inhibitors.     

The Impact of Opportunistic Infections on Clinical Outcome and Healthcare Resource Uses for Adult T Cell Leukaemia

We examined the impact of opportunistic infections on in-hospital mortality, hospital length of stay (LOS), and the total cost (TC) among adult T-cell leukaemia (ATL) patients. In this retrospective cohort study, we identified 3712 patients with ATL using national hospital administrative data. Analysed opportunistic infections included Aspergillus spp., Candida spp., cytomegalovirus (CMV), herpes simplex virus (HSV), pneumocystis pneumonia (PCP), tuberculosis, varicella zoster virus (VZV), Cryptococcus spp., nontuberculous mycobacteria, and Strongyloides spp. Multilevel logistic regression analysis for in-hospital mortality and a multilevel linear regression analysis for LOS and TC were employed to determine the impact of opportunistic infections on clinical outcomes and healthcare resources. We found ATL patients infected with CMV had significantly higher in-hospital mortality (adjusted odds ratio (AOR) 2.29 [1.50–3.49] p < 0.001), longer LOS (coefficient (B): 0.13 [0.06–0.20] p < 0.001) and higher TC (B: 0.25 [0.17–0.32] p < 0.001) than those without CMV. Those with CAN and PCP were associated with a lower in-hospital mortality rate (AOR 0.72 [0.53–0.98] p = 0.035 and 0.54[0.41–0.73] p < 0.001, respectively) than their infections. VZV was associated with longer LOS (B: 0.13 [0.06–0.19] p < 0.001), while aspergillosis, HSV, or VZV infections were associated with higher TC (B: 0.16 [0.07–0.24] p < 0.001, 0.12 [0.02–0.23] p = 0.025, and 0.17 [0.10–0.24] p < 0.001, respectively). Our findings reveal that CMV infection is a major determinant of poor prognosis in patients affected by ATL.