Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Impact of different hypopnea definitions on obstructive sleep apnea severity and cardiovascular mortality risk in women and elderly individuals

To assess the impact of three hypopnea definitions on the severity classification of obstructive sleep apnea (OSA) and its association with cardiovascular mortality risk in women and elderly individuals. We analyzed two Spanish clinical cohorts (1116 women and 939 elderly individuals) who were studied for suspicion of OSA between 1998 and 2007. A calibration model was used to apply different definitions of hypopnea to our two cohorts. Hypopnea was defined as a 30–90% reduction in oronasal flow for ≥10 s followed by (1) ≥4% fall in oxyhemoglobin saturation—AHI4%; (2) ≥3% fall in oxyhemoglobin saturation—AHI3%; or (3) ≥3% fall in oxyhemoglobin saturation or an event-related arousal—AHI3%a. In both cohorts, the prevalence of an AHI ≥30 events/h increased by 14% with AHI3%a, compared to AHI4% criteria. The percentage of women with an AHI <5 events/h decreased from 13.9% with AHI4% to 1.1% with the AHI3%a definition. In fully adjusted multivariable analyses, AHI ≥30 events/h was associated with increased cardiovascular mortality risk in women, regardless of the hypopnea definition, and in elderly individuals diagnosed using the AHI4% and AHI3% but not the AHI3%a definition. Our findings suggest that hypopnea definitions substantially influence OSA prevalence and severity classification, and also affect the association with cardiovascular outcomes. With the currently recommended criterion (AHI3%a), a threshold of 30 events/h is appropriate to identify women, but not elderly individuals with increased risk of cardiovascular death. •We analyzed two cohorts of 1116 women and 939 elderly individuals studied for suspicion of obstructive sleep apnea (OSA).•Hypopnea definitions influenced OSA prevalence and severity classification.•The current hypopnea definition is associated with cardiovascular death in women.•The current hypopnea criteria are not associated with cardiovascular death in elderly individuals

Continuous positive airway pressure adherence declines with age in elderly obstructive sleep apnoea patients

Peer reviewe

Increased Incidence of Stroke, but Not Coronary Heart Disease, in Elderly Patients With Sleep Apnea. Role of Continuous Positive Airway Pressure Treatment

[Background and Purpose] The influence of age on the relationship between obstructive sleep apnea (OSA) and the incidence of hard cardiovascular events remains controversial. We sought to analyze the relationship between OSA and the incidence of stroke and coronary heart disease in a large cohort of elderly patients, as well as to investigate the role of continuous positive airway pressure (CPAP) treatment in these associations.[Methods] Post hoc analysis of a prospective observational study of consecutive patients ≥65 years studied for OSA suspicion at 2 Spanish University Hospitals. Patients with an apnea-hypopnea index (AHI) <15 were the reference group. OSA was defined by an AHI ≥15 and classified as untreated (CPAP not prescribed or compliance <4 hours/day), mild-moderate (AHI 15–29), untreated severe (AHI ≥30), and CPAP-treated (AHI ≥15 and CPAP compliance ≥4 hours/day).[Results] 859 and 794 elderly patients were included in the stroke and coronary heart disease analyses, respectively. The median (interquartile range) follow-up was 72 (50–88.5) and 71 (51.5–89) months, respectively. Compared with the reference group, the fully adjusted hazard ratios for the incidence of stroke were 3.42 (95% CI, 1.37–8.52), 1.02 (95% CI, 0.41–2.56), and 1.76 (95% CI, 0.62–4.97) for the untreated severe OSA group, CPAP-treated group, and untreated mild-moderate OSA group, respectively. No associations were shown between any of the different OSA groups and coronary heart disease incidence.[Conclusions]The incidence of stroke, but not coronary heart disease, is increased in elderly patients with untreated severe OSA. Adequate CPAP treatment may reduce this risk

Increased Incidence of Stroke, but Not Coronary Heart Disease, in Elderly Patients With Sleep Apnea.

Background and Purpose- The influence of age on the relationship between obstructive sleep apnea (OSA) and the incidence of hard cardiovascular events remains controversial. We sought to analyze the relationship between OSA and the incidence of stroke and coronary heart disease in a large cohort of elderly patients, as well as to investigate the role of continuous positive airway pressure (CPAP) treatment in these associations. Methods- Post hoc analysis of a prospective observational study of consecutive patients ≥65 years studied for OSA suspicion at 2 Spanish University Hospitals. Patients with an apnea-hypopnea index (AHI

Good long‐term adherence to continuous positive airway pressure therapy in patients with resistant hypertension and sleep apnea

Although adequate adherence is paramount in achieving the beneficial effects of continuous positive airway pressure therapy in patients with obstructive sleep apnea, long‐term adherence and the variables involved in continuous positive airway pressure compliance in patients with resistant hypertension and obstructive sleep apnea are yet unknown. We conducted a prospective, multicentre, observational study in 177 patients recruited from hypertensive units with resistant hypertension confirmed by means of 24‐hr blood pressure monitoring (blood pressure ≥ 130 and/or ≥ 80 mmHg, despite taking at least three antihypertensive drugs or  3 drugs) and obstructive sleep apnea (apnea–hypopnea index ≥ 5 in a respiratory polygraph) who were prescribed continuous positive airway pressure treatment. Good adherence was defined as an average cumulative continuous positive airway pressure use of ≥ 4 hr per night at the end of the follow‐up. A multivariate Cox regression analysis was performed to identify independent predictors of continuous positive airway pressure adherence. Patients were followed for a median of 57.6 (42–72) months after initiating continuous positive airway pressure therapy. At the end of the follow‐up, the median continuous positive airway pressure use was 5.7 (inter‐quartile range 3.9–6.6) hr per night, and 132 patients (74.5%) showed good continuous positive airway pressure adherence. The only baseline variable associated with poor adherence was the presence of previous stroke (hazard ratio 4.00, 95% confidence interval 1.92–8.31). Adequate adherence at 1 month also predicted good adherence at the end of the follow‐up (hazard ratio 14.4, 95% confidence interval 4.94–56). Both variables also predicted adherence at a threshold of 6 hr per night. Our results show that good continuous positive airway pressure adherence is an achievable and feasible goal in patients with resistant hypertension and obstructive sleep apnea. Previous stroke and short‐term adherence predicted long‐term adherence.Peer reviewe

Effect of continuous positive airway pressure on blood pressure and metabolic profile in women with sleep apnoea.

Continuous positive airway pressure (CPAP) reduces blood pressure levels in hypertensive patients with obstructive sleep apnoea (OSA). However, the role of CPAP in blood pressure and the metabolic profile in women has not yet been assessed. In this study we investigated the effect of CPAP on blood pressure levels and the glucose and lipid profile in women with moderate-to-severe OSA.A multicentre, open-label, randomised controlled trial was conducted in 307 women diagnosed with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events·h-1) in 19 Spanish Sleep Units. Women were randomised to CPAP (n=151) or conservative treatment (n=156) for 12 weeks. Changes in office blood pressure measures as well as in the glucose and lipid profile were assessed in both groups.Compared with the control group, the CPAP group achieved a significantly greater decrease in diastolic blood pressure (-2.04 mmHg, 95% CI -4.02- -0.05; p=0.045), and a nonsignificantly greater decrease in systolic blood pressure (-1.54 mmHg, 95% CI -4.58-1.51; p=0.32) and mean blood pressure (-1.90 mmHg, 95% CI -4.0-0.31; p=0.084). CPAP therapy did not change any of the metabolic variables assessed.In women with moderate-to-severe OSA, 12 weeks of CPAP therapy improved blood pressure, especially diastolic blood pressure, but did not change the metabolic profile, compared with conservative treatment

Prognostic Factors Associated with Acute Heart Failure in Patients Admitted for COVID-19: Analysis of the SEMI-COVID-19 Registry

Introduction: Since the beginning of the COVID-19 pandemic in March 2020, an intimate relationship between this disease and cardiovascular diseases has been seen. However, few studies assess the development of heart failure during this infection. This study aims to determine the predisposing factors for the development of heart failure (HF) during hospital admission of COVID-19 patients. Methodology: A retrospective and multicenter study of patients with HF admitted for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). A bivariate analysis was performed to relate the different variables evaluated in patients developing heart failure during hospital admission. A multivariate analysis including the most relevant clinical variables obtained in bivariate analyses to predict the outcome of heart failure was performed. Results: A total of 16.474 patients hospitalized for COVID-19 were included (57.5% men, mean age 67 years), 958 of them (5.8%) developed HF during hospitalization. The risk factors for HF development were: age (odds ratio [OR]): 1.042; confidence interval 95% (CI 95%): 1.035-1.050; p 30 kg/m(2) (OR: 1.460 CI 95%: 1.230-1.733; p < 0001), and peripheral vascular disease (OR: 1.564; CI 95%: 1.217-2.201; p < 0.001). Patients who developed HF had a higher rate of mortality (54.1% vs. 19.1%, p < 0.001), intubation rate (OR: 2,36; p < 0.001), and ICU admissions (OR: 2.38; p < 0001). Conclusions: Patients who presented a higher risk of developing HF were older with cardiovascular risk factors. The risk factors for HF development were age, atrial fibrillation, obesity, and peripheral vascular disease. In addition, patients who developed HF more frequently required to be intubated or admitted to the ICU