Impact of comorbidities on prostate cancer-specific mortality: A population-based cohort study.

AIM: To assess the impact of comorbidities on prostate cancer mortality. METHODS: We studied 15,695 South Australian men diagnosed with prostate cancer between 2003 and 2019 from state-wide administrative linked data sets. Comorbidity was measured 1-year before prostate cancer diagnosis using Rx-Risk, a medication-based comorbidity index. Flexible parametric competing risk regression was used to estimate the independent association between comorbidities and prostate cancer-specific mortality. Specific common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and pain) were also assessed to determine their association with mortality. All models were adjusted for sociodemographic variables, tumor characteristics, and treatment type. RESULTS: Prostate cancer-specific mortality was higher for patients with a Rx-Risk score ≥3 versus 0 (adjusted sub-hazard ratio (sHR) 1.34, 95% CI: 1.15-1.56). Lower comorbidity scores (Rx-Risk score 2 vs. 0 and Rx-Risk score 1 vs. 0) were not significantly associated with prostate cancer-specific mortality. Men who were using medications for cardiac disorders (sHR 1.31, 95% CI: 1.13-1.52), chronic airway disease (sHR 1.20, 95% CI: 1.01-1.44), depression and anxiety (sHR 1.17, 95% CI: 1.02-1.35), and thrombosis (sHR 1.21, 95% CI: 1.04-1.42) were at increased risk of dying from prostate cancer compared with men not on those medications. Use of medications for diabetes and chronic pain were not associated with prostate cancer-specific mortality. All Rx-Risk score categories and the specific comorbidities were also associated with increased risk of all-cause mortality. CONCLUSION: The findings showed that ≥3 comorbid conditions and specific comorbidities including cardiac disease, chronic airway disease, depression and anxiety, and thrombosis were associated with poor prostate cancer-specific survival. Appropriate management of these comorbidities may help to improve survival in prostate cancer patients.

Risk of death, major adverse cardiac events and relapse in patients with bullous pemphigoid treated with systemic or topical corticosteroids.

BACKGROUND: According to current guidelines, systemic or topical corticosteroids are both recommended as first-line treatments for bullous pemphigoid (BP). There is evidence to suggest that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections and relapse, between systemic and topical corticosteroid treatments. OBJECTIVES: To evaluate the risk of death, MACE, infections and relapse in patients with BP treated with systemic or topical corticosteroids. METHODS: A population-based retrospective cohort study was performed using the TriNetX US Collaborative Network. As a measure against bias, propensity score matching for age, sex, 10 diseases and 6 medications was done, and 3 sensitivity analyses were conducted. RESULTS: All-time risk of death was increased in US patients with BP exposed to any dose of systemic corticosteroids (n = 2917) vs. patients treated with topical clobetasol propionate [n = 2932; hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.28-1.58 (P < 0.001)]. This was consistent in time-stratified analysis (1- and 3-year mortality rates) and in analysis contrasting prednisone (equivalent) doses of 1-10 mg (low) or 30-100 mg (medium-high) systemic corticosteroid to topical treatment. The increased risk of death in US patients with BP exposed to any dose of systemic corticosteroids vs. topical treatment was accompanied by increased risks for MACE (HR 1.33, 95% CI 1.08-1.64; P = 0.008) and infections (HR 1.33, 95% CI 1.15-1.54; P < 0.001). The risk of continued disease or relapse was decreased in patients treated with systemic vs. topical corticosteroids (HR 0.85, 95% CI 0.77-0.94; P = 0.002). Results regarding mortality and continued disease or relapse persisted in three sensitivity analyses. Potential limitations included the retrospective data collection, bias for treatment selection and miscoding. CONCLUSIONS: Pending validation in prospective studies, where feasible - and despite the heightened risk of relapse - topical corticosteroid treatment may be advantageous over systemic corticosteroid treatment owing to its significantly lower risk of death.

Bullous pemphigoid (BP) is an autoimmune skin disease that commonly affects older people. The recommended treatment is medication called corticosteroids, either taken as a tablet or injection ('systemic') or applied to the skin ('topical'). Some evidence suggests that topical corticosteroids might be safer in terms of the risk of dying. We looked at whether there was a difference between the risk of dying, having heart problems, getting sick or the condition coming back in people with BP who use the different medications. To do this, we used people's past health information and compared people of similar ages and genders, 10 diseases and 6 medications. We found that people with BP who used systemic corticosteroids had a higher chance of dying. This also meant that people taking this form of the medication had a greater chance of having heart problems and getting infections. However, the risk of BP coming back was lower for people who used systemic corticosteroids. Our findings suggest that although there is a higher risk of BP coming back, there may be fewer risks from topical corticosteroids than systemic corticosteroids.

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT-304 males (68%) and 140 females (32%)-with a median age of 3.3 years (1.8-6.5 years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6 years, body mass index (BMI) < 16 kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.

Enteral Access Outcomes in Patients Hospitalized With Cardiac Disease: A Retrospective Cohort Study.

INTRODUCTION: Patients admitted with principal cardiac diagnosis (PCD) can encounter difficult inpatient stays that are often marked by malnutrition. In this setting, enteral feeding may improve nutritional status. This study examined the association of PCD with perioperative outcomes after elective enteral access procedures. METHODS: Adult patients who underwent enteral access procedures between 2018 and 2020 at a tertiary care institution were reviewed retrospectively. Differences in baseline characteristics between patients with and without PCD were adjusted using entropy balancing. Multivariable logistic and linear regressions were subsequently developed to evaluate the association between PCD and nutritional outcomes, perioperative morbidity and mortality, length of stay, and nonelective readmission after enteral access. RESULTS: 912 patients with enteral access met inclusion criteria, of whom 84 (9.2%) had a diagnosis code indicating PCD. Compared to non-PCD, patients with PCD more commonly received percutaneous endoscopic gastrostomy by general surgery and had a higher burden of comorbidities as measured by the Charlson comorbidity index. Multivariable risk adjustment generated a strongly balanced distribution of baseline covariates between patient groups (standardized differences ranged from -2.45 × 10-8 to 3.18 × 108). After adjustment, despite no significant association with in-hospital mortality, percentage change prealbumin, length of stay, or readmission, PCD was associated with an approximately 2.25-day reduction in time to meet goal feeds (95% CI -3.76 to -0.74, P = 0.004) as well as decreased odds of reoperation (adjusted odds ratio 0.28, 95% CI 0.09-0.86, P = 0.026) and acute kidney injury (adjusted odds ratio 0.24, 95% CI 0.06-0.91, P = 0.035). CONCLUSIONS: Despite having more comorbidities than non-PCD, adult enteral access patients with PCD experienced favorable nutritional and perioperative outcomes.

Autopsy of all young sudden death cases is important to increase survival in family members left behind.

Sudden cardiac death (SCD) is an important public health problem worldwide, accounting for an estimated 6-20% of total mortality. A significant proportion of SCD is caused by inherited heart disease, especially among the young. An autopsy is crucial to establish a diagnosis of inherited heart disease, allowing for subsequent identification of family members who require cardiac evaluation. Autopsy of cases of unexplained sudden death in the young is recommended by both the European Society of Cardiology and the American Heart Association. Overall autopsy rates, however, have been declining in many countries across the globe, and there is a lack of skilled trained pathologists able to carry out full autopsies. Recent studies show that not all cases of sudden death in the young are autopsied, likely due to financial, administrative, and organizational limitations as well as awareness among police, legal authorities, and physicians. Consequently, diagnoses of inherited heart disease are likely missed, along with the opportunity for treatment and prevention among surviving relatives. This article reviews the evidence for the role of autopsy in sudden death, how the cardiologist should interpret the autopsy-record, and how this can be integrated and implemented in clinical practice. Finally, we identify areas for future research along with potential for healthcare reform aimed at increasing autopsy awareness and ultimately reducing mortality from SCD.

Age-Related Quality of Life in Cardiac Surgical Patients with Extracorporeal Life Support.

BACKGROUND: The rationale of the study was to analyze the impact of age on quality of life (QoL) in patients who had undergone cardiac surgery with consecutive extracorporeal life support (ECLS) treatment. METHODS: The study population consisted of 200 patients, operated upon between August 2006 and December 2018. The patient cohort was divided into two groups following an arbitrary cutoff age of 70 years. Comparative outcome analysis was calculated utilizing the European Quality of Life-5-Dimensions-5-Level Version (EQ-5D-5L). RESULTS: A total of 113 patients were 70 years or less old (group young), whereas 87 patients were older than 70 years (group old). In 45.7% of cases, the ECLS system was established during cardiogenic shock and external cardiac massage. The overall survival-to-discharge was 31.5% (n = 63), with a significantly better survival in the younger patient group (young = 38.9%; old = 21.8%, p = 0.01). Forty-two patients (66%) responded to the QoL survey after a median follow-up of 4.3 years. Older patients reported more problems with mobility (y = 52%; o = 88%, p = 0.02) and self-care (y = 24%; o = 76%, p = 0.01). However, the patients' self-rated health status utilizing the Visual Analogue Scale revealed no differences (y = 70% [50-80%]; o = 70% [60-80%], p = 0.38). Likewise, the comparison with an age-adjusted German reference population revealed similar QoL indices. There were no statistically significant differences in the EQ-5D-5L index values related to sex, number of comorbidities, and emergency procedures. CONCLUSION: Despite the limited sample size due to the high mortality rate especially in elderly, the present study suggests that QoL of elderly patients surviving ECLS treatment is almost comparable to younger patients.

German Heart Surgery Report 2023: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

Based on a voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (DGTHG) in 1980, a well-defined but limited dataset of all cardiac and vascular surgery procedures performed in 77 German heart surgery departments is reported annually. For the year 2023, a total of 168,841 procedures were submitted to the registry. Of these operations, 100,606 are defined as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 28,996 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 2.8:1) was 97.6%; 97.7% for the 39,859 isolated heart valve procedures (23,727 transcatheter interventions included); and 99.2% for 19,699 pacemaker/implantable cardioverter defibrillator procedures. Concerning short and long-term mechanical circulatory support, a total of 2,982 extracorporeal life support/extracorporeal membrane oxygenation implantations and 772 ventricular assist device implantations (left/right ventricular assist device, BVAD, total artificial heart) were reported. In 2023, 324 isolated heart transplantations, 248 isolated lung transplantations, and 2 combined heart-lung transplantations were performed. This annually updated registry of the DGTHG represents nonrisk adjusted voluntary public reporting and encompasses acute data for nearly all heart surgical procedures in Germany. It constitutes trends in heart medicine and represents a basis for quality management (e.g., benchmark) for all participating institutions.

Fetal heart diseases and neonatal mortality: Risk factors and management.

PURPOSE: Fetal heart diseases significantly contribute to neonatal mortality. Improved prenatal diagnostics enable defect detection before delivery, emphasizing the need for a personalized approach to address anomalies and predict outcomes. Categorizing diseases into risk classes aids obstetricians in counseling and delivery decisions. This study classifies fetal heart diseases by severity, examining factors related to maternal, fetal, and delivery that affect neonatal mortality. The aim is to identify key determinants of neonatal mortality and create an individual approach to assess and manage risks in the first days of a newborn's life. METHODS: A prospective study from 2019 to 2023 at a tertiary care institute involved pregnant women diagnosed with fetal heart disease. 382 women were categorized into three groups based on potential risk for hemodynamic instability at birth: Group-1 (no or low risk, n = 114), Group-2 (moderate risk, n = 201), and Group-3 (high risk, n = 67). Antenatal follow-up used fetal echocardiography. The study explored the association between maternal-fetal-delivery-related factors and neonatal mortality, with statistical significance set at p < 0.05. RESULTS: Significant associations with neonatal mortality were found in cases with birth weight < 2500 g (p = 0.002), presence of genitourinary system anomaly (p = 0.001), group-2 and 3 heart disease (p < 0.001), and induction of labor (p = 0.01). CONCLUSION: Factors influencing neonatal mortality in fetal heart disease cases include heart disease severity (group-3 heart disease), low birth weight, and extracardiac anomalies. While labor induction with prostaglandin ± oxytocin appears to elevate neonatal mortality, this observation requires further validation with larger sample sizes. Obstetricians should consider selective use of prostaglandin for labor induction.

Trends by age and sex and projections of disease prevalence from studying hypertensive heart disease in China over the past three decades.

BACKGROUND: Hypertensive heart disease (HHD) is a common cause of cardiovascular disease and mortality worldwide, and its burden is increasing with aging populations. OBJECTIVES: This study aimed to estimate the prevalence and mortality rates of HHD in mainland China and Taiwan Province using data from the Global Burden of Disease Study 2019 (GBD 2019), and forecast the development trend of HHD from 2020 to 2024. METHODS: We obtained data on number of cases, deaths, crude prevalence rate, crude death rate, age-standardized prevalence rate (ASPR), and age-standardized death rate (ASDR) for mainland China and Taiwan Province from 1990 to 2019 from the GBD 2019. Joinpoint software was used to estimate average annual percentage change (AAPC) with 95% confidence intervals, and the number of HHD cases in China from 2022 to 2024 was predicted by the exponential smoothing method. RESULTS: Between 1990 and 2019, HHD cases and deaths increased in mainland China, but the ASPR and ASDR decreased by 5.96% and 48.72%, respectively. In Taiwan Province, ASPR and ASDR decreased by 7.66% and 52.14%, respectively. The number of HHD cases and death rates varied by region, age, and sex, with a higher number of cases in mainland China than in Taiwan Province. By 2024, the number of HHD cases in mainland China was projected to be over 9.6 million cases, and in Taiwan Province, it was projected to surpass 120,000 cases. CONCLUSION: The differences in HHD cases between mainland China and Taiwan Province in terms of age and sex indicated the need for effective prevention and control measures, especially targeting the elderly population. These findings can inform policymakers and health professionals in the development of targeted prevention and treatment strategies and resource allocation for HHD in China.

Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk.

BACKGROUND: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS: A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). CONCLUSIONS: Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).

Hypertension in Low- and Middle-Income Countries.

In recent decades low- and middle-income countries (LMICs) have been witnessing a significant shift toward raised blood pressure; yet in LMICs, only 1 in 3 are aware of their hypertension status, and ≈8% have their blood pressure controlled. This rising burden widens the inequality gap, contributes to massive economic hardships of patients and carers, and increases costs to the health system, facing challenges such as low physician-to-patient ratios and lack of access to medicines. Established risk factors include unhealthy diet (high salt and low fruit and vegetable intake), physical inactivity, tobacco and alcohol use, and obesity. Emerging risk factors include pollution (air, water, noise, and light), urbanization, and a loss of green space. Risk factors that require further in-depth research are low birth weight and social and commercial determinants of health. Global actions include the HEARTS technical package and the push for universal health care. Promising research efforts highlight that successful interventions are feasible in LMICs. These include creation of health-promoting environments by introducing salt-reduction policies and sugar and alcohol tax; implementing cost-effective screening and simplified treatment protocols to mitigate treatment inertia; pooled procurement of low-cost single-pill combination therapy to improve adherence; increasing access to telehealth and mHealth (mobile health); and training health care staff, including community health workers, to strengthen team-based care. As the blood pressure trajectory continues creeping upward in LMICs, contextual research on effective, safe, and cost-effective interventions is urgent. New emergent risk factors require novel solutions. Lowering blood pressure in LMICs requires urgent global political and scientific priority and action.

Research Note: COVID-19 Is Not an Independent Cause of Death.

The COVID-19 pandemic has had overwhelming global impacts with deleterious social, economic, and health consequences. To assess the COVID-19 death toll, researchers have estimated declines in 2020 life expectancy at birth (e0). When data are available only for COVID-19 deaths, but not for deaths from other causes, the risks of dying from COVID-19 are typically assumed to be independent of those from other causes. In this research note, we explore the soundness of this assumption using data from the United States and Brazil, the countries with the largest number of reported COVID-19 deaths. We use three methods: one estimates the difference between 2019 and 2020 life tables and therefore does not require the assumption of independence, and the other two assume independence to simulate scenarios in which COVID-19 mortality is added to 2019 death rates or is eliminated from 2020 rates. Our results reveal that COVID-19 is not independent of other causes of death. The assumption of independence can lead to either an overestimate (Brazil) or an underestimate (United States) of the decline in e0, depending on how the number of other reported causes of death changed in 2020.

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. RESULTS: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Racial and Ethnic Disparities in Heart and Cerebrovascular Disease Deaths During the COVID-19 Pandemic in the United States.

BACKGROUND: Cardiovascular deaths increased during the early phase of the COVID-19 pandemic in the United States. However, it is unclear whether diverse racial/ethnic populations have experienced a disproportionate rise in heart disease and cerebrovascular disease deaths. METHODS: We used the National Center for Health Statistics to identify heart disease and cerebrovascular disease deaths for non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic individuals from March to August 2020 (pandemic period), as well as for the corresponding months in 2019 (historical control). We determined the age- and sex-standardized deaths per million by race/ethnicity for each year. We then fit a modified Poisson model with robust SEs to compare change in deaths by race/ethnicity for each condition in 2020 versus 2019. RESULTS: There were a total of 339 076 heart disease and 76 767 cerebrovascular disease deaths from March through August 2020, compared with 321 218 and 72 190 deaths during the same months in 2019. Heart disease deaths increased during the pandemic in 2020, compared with the corresponding period in 2019, for non-Hispanic White (age-sex standardized deaths per million, 1234.2 versus 1208.7; risk ratio for death [RR], 1.02 [95% CI, 1.02-1.03]), non-Hispanic Black (1783.7 versus 1503.8; RR, 1.19 [95% CI, 1.17-1.20]), non-Hispanic Asian (685.7 versus 577.4; RR, 1.19 [95% CI, 1.15-1.22]), and Hispanic (968.5 versus 820.4; RR, 1.18 [95% CI, 1.16-1.20]) populations. Cerebrovascular disease deaths also increased for non-Hispanic White (268.7 versus 258.2; RR, 1.04 [95% CI, 1.03-1.05]), non-Hispanic Black (430.7 versus 379.7; RR, 1.13 [95% CI, 1.10-1.17]), non-Hispanic Asian (236.5 versus 207.4; RR, 1.15 [95% CI, 1.09-1.21]), and Hispanic (264.4 versus 235.9; RR, 1.12 [95% CI, 1.08-1.16]) populations. For both heart disease and cerebrovascular disease deaths, Black, Asian, and Hispanic populations experienced a larger relative increase in deaths than the non-Hispanic White population (interaction term, P<0.001). CONCLUSIONS: During the COVID-19 pandemic in the United States, Black, Hispanic, and Asian populations experienced a disproportionate rise in deaths caused by heart disease and cerebrovascular disease, suggesting that these groups have been most impacted by the indirect effects of the pandemic. Public health and policy strategies are needed to mitigate the short- and long-term adverse effects of the pandemic on the cardiovascular health of diverse populations.

Neurodegenerative Disease Mortality among Former Professional Soccer Players.

BACKGROUND: Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized. METHODS: We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation. Causes of death were determined from death certificates. Data on medications dispensed for the treatment of dementia in the two cohorts were also compared. Prescription information was obtained from the national Prescribing Information System. RESULTS: Over a median of 18 years, 1180 former soccer players (15.4%) and 3807 controls (16.5%) died. All-cause mortality was lower among former players than among controls up to the age of 70 years and was higher thereafter. Mortality from ischemic heart disease was lower among former players than among controls (hazard ratio, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P = 0.02), as was mortality from lung cancer (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.001). Mortality with neurodegenerative disease listed as the primary cause was 1.7% among former soccer players and 0.5% among controls (subhazard ratio [the hazard ratio adjusted for competing risks of death from ischemic heart disease and death from any cancer], 3.45; 95% CI, 2.11 to 5.62; P<0.001). Among former players, mortality with neurodegenerative disease listed as the primary or a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer's disease (hazard ratio [former players vs. controls], 5.07; 95% CI, 2.92 to 8.82; P<0.001) and lowest among those with Parkinson's disease (hazard ratio, 2.15; 95% CI, 1.17 to 3.96; P = 0.01). Dementia-related medications were prescribed more frequently to former players than to controls (odds ratio, 4.90; 95% CI, 3.81 to 6.31; P<0.001). Mortality with neurodegenerative disease listed as the primary or a contributory cause did not differ significantly between goalkeepers and outfield players (hazard ratio, 0.73; 95% CI, 0.43 to 1.24; P = 0.24), but dementia-related medications were prescribed less frequently to goalkeepers (odds ratio, 0.41; 95% CI, 0.19 to 0.89; P = 0.02). CONCLUSIONS: In this retrospective epidemiologic analysis, mortality from neurodegenerative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players than among matched controls. Dementia-related medications were prescribed more frequently to former players than to controls. These observations need to be confirmed in prospective matched-cohort studies. (Funded by the Football Association and Professional Footballers' Association.).

Randomized Trial of Endoscopic or Open Vein-Graft Harvesting for Coronary-Artery Bypass.

BACKGROUND: The saphenous-vein graft is the most common conduit for coronary-artery bypass grafting (CABG). The influence of the vein-graft harvesting technique on long-term clinical outcomes has not been well characterized. METHODS: We randomly assigned patients undergoing CABG at 16 Veterans Affairs cardiac surgery centers to either open or endoscopic vein-graft harvesting. The primary outcome was a composite of major adverse cardiac events, including death from any cause, nonfatal myocardial infarction, and repeat revascularization. Leg-wound complications were also evaluated. RESULTS: A total of 1150 patients underwent randomization. Over a median follow-up of 2.78 years, the primary outcome occurred in 89 patients (15.5%) in the open-harvest group and 80 patients (13.9%) in the endoscopic-harvest group (hazard ratio, 1.12; 95% confidence interval [CI], 0.83 to 1.51; P=0.47). A total of 46 patients (8.0%) in the open-harvest group and 37 patients (6.4%) in the endoscopic-harvest group died (hazard ratio, 1.25; 95% CI, 0.81 to 1.92); myocardial infarctions occurred in 34 patients (5.9%) in the open-harvest group and 27 patients (4.7%) in the endoscopic-harvest group (hazard ratio, 1.27; 95% CI, 0.77 to 2.11), and revascularization occurred in 35 patients (6.1%) in the open-harvest group and 31 patients (5.4%) in the endoscopic-harvest group (hazard ratio, 1.14; 95% CI, 0.70 to 1.85). Leg-wound infections occurred in 18 patients (3.1%) in the open-harvest group and in 8 patients (1.4%) in the endoscopic-harvest group (relative risk, 2.26; 95% CI, 0.99 to 5.15). CONCLUSIONS: Among patients undergoing CABG, we did not find a significant difference between open vein-graft harvesting and endoscopic vein-graft harvesting in the risk of major adverse cardiac events. (Funded by the Cooperative Studies Program, Office of Research and Development, Department of Veterans Affairs; REGROUP ClinicalTrials.gov number, NCT01850082 .).

Total knee replacement in osteoarthritis patients on reducing the risk of major adverse cardiac events: a 18-year retrospective cohort study.

OBJECTIVES: Osteoarthritis (OA) is a common degenerative joint disease, and total knee replacement (TKR) is a successful surgical intervention for knee OA treatment. However, the risks of mortality and major cardiovascular events (MACEs) in patients receiving TKR remain unclear. This study investigated the risks of mortality and MACEs in knee OA patients who received TKR. METHODS: For this population-based cohort study, the Longitudinal Health Insurance Database 2000 was used. Two million individuals with knee OA defined by ICD-9-CM codes who received physical therapy between 1999 and 2017 were selected. For propensity score matching (PSM), we considered the year of knee OA diagnosis, demographics, comorbidities, co-medications, and knee OA-related hyaluronic acid or physical therapy at baseline. After PSM, regression analyses were performed to assess the association of mortality or MACEs with TKR and non-TKR individuals. RESULTS: We identified patients (n = 189,708) with a new diagnosis of knee OA between 2000 and 2017. In total, 10,314 propensity-score-paired TKR and non-TKR individuals were selected. The PSM cohort algorithm revealed that the risk of mortality or MACEs was lower in the TKR group (adjusted hazard ratio: 0.791; 95% confidence interval: 0.755-0.830) than in the non-TKR group. CONCLUSIONS: Patients with knee OA who received TKR had decreased risks of mortality and MACEs than those who did not receive TKR. Moreover, the TKR group received a reduced dosage of nonsteroidal anti-inflammatory drugs at the 1-year follow-up.

Circumstances surrounding end-of-life in pediatric patients pre- and post-heart transplant: a report from the Pediatric Heart Transplant Society.

BACKGROUND: Although mortality has decreased considerably in pediatric heart transplantation, waitlist and post-transplant death rates remain notable. End-of-life focused research in this population, however, is very limited. This Pediatric Heart Transplant Society study aimed to describe the circumstances surrounding death of pediatric heart transplant patients. METHODS: A retrospective analysis of the multi-institutional, international, Pediatric Heart Transplant Society registry was conducted. Descriptive statistics and univariate analyses were performed to 1) describe end-of-life in pediatric pre- and post-heart transplant patients and 2) examine associations between location of death and technological interventions at end-of-life with demographic and disease factors. RESULTS: Of 9217 patients (0-18 years) enrolled in the registry between 1993 and 2018, 2804 (30%) deaths occurred; 1310 while awaiting heart transplant and 1494 post-heart transplant. The majority of waitlist deaths (89%) occurred in the hospital, primarily in ICU (74%) with most receiving mechanical ventilation (77%). Fewer post-transplant deaths occurred in the hospital (22%). Out-of-hospital death was associated with older patient age (p < .01). CONCLUSIONS: ICU deaths with high use of technological interventions at end-of-life were common, particularly in patients awaiting heart transplant. In this high mortality population, findings raise challenging considerations for clinicians, families, and policy makers on how to balance quality of life amidst high risk for hospital-based death.

Trajectory of Preserved Ratio Impaired Spirometry: Natural History and Long-Term Prognosis.

Rationale: Natural history of preserved ratio impaired spirometry (PRISm), often defined as FEV1/FVC ⩾lower limit of normal and FEV1 <80% of predicted value, is not well described. Objectives: To investigate the natural history and long-term prognosis of the following PRISm trajectories: persistent PRISm trajectory (individuals with PRISm both young and middle-aged), normal to PRISm trajectory (individuals developing PRISm from normal spirometry in young adulthood), and PRISm to normal trajectory (individuals recovering from PRISm in young adulthood by normalizing spirometry while middle-aged). Methods: We followed 1,160 individuals aged 20-40 years from the Copenhagen City Heart Study from 1976 to 1983 until 2001 to 2003 to determine their lung function trajectory; 72 had persistent PRISm trajectory, 76 had normal to PRISm trajectory, 155 had PRISm to normal trajectory, and 857 had normal trajectory. From 2001-2003 until 2018, we determined the risk of cardiopulmonary disease and death. Measurements and Main Results: We recorded 198 admissions for heart disease, 143 for pneumonia, and 64 for chronic obstructive pulmonary disease as well as 171 deaths. Compared with individuals with normal trajectory, hazard ratios for individuals with persistent PRISm trajectory were 1.55 (95% confidence interval, 0.91-2.65) for heart disease admission, 2.86 (1.70-4.83) for pneumonia admission, 6.57 (3.41-12.66) for chronic obstructive pulmonary disease admission, and 3.68 (2.38-5.68) for all-cause mortality. Corresponding hazard ratios for individuals with normal to PRISm trajectory were 1.91 (1.24-2.95), 2.74 (1.70-4.42), 7.61 (4.21-13.72), and 2.96 (1.94-4.51), respectively. Prognosis of individuals with PRISm to normal trajectory did not differ from those with normal trajectory. Conclusions: PRISm in middle-aged individuals is associated with increased risk of cardiopulmonary disease and all-cause mortality, but individuals who recover from PRISm during their adult life are no longer at increased risk.