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Postoperative neurological disorders, including postoperative delirium (POD), postoperative cognitive dysfunction (POCD), postoperative covert ischemic stroke, and hemorrhagic stroke, are challenging clinical problems in the emerging aged surgical population. These disorders can deteriorate functional outcomes and long-term quality of life after surgery, resulting in a substantial social and financial burden to the family and society. Understanding predisposing and precipitating factors may promote individualized preventive treatment for each disorder, as several risk factors are modifiable. Besides prevention, timely identification and treatment of etiologies and symptoms can contribute to better recovery from postoperative neurological disorders and lower risk of long-term cognitive impairment, disability, and even death. Herein, we summarize the diagnosis, risk factors, prevention, and treatment of these postoperative complications, with emphasis on recent advances and perspectives.

Background Cachexia, characterized by involuntary muscle mass loss, negatively impacts survival outcomes, treatment tolerability, and functionality in cancer patients. However, there is a limited appreciation of the true prevalence of low muscle mass due to inconsistent diagnostic methods and limited oncologist awareness. Methods Twenty-nine French healthcare establishments participated in this cross-sectional study, recruiting patients with those metastatic cancers most frequently encountered in routine practice (colon, breast, kidney, lung, prostate). The primary outcome was low skeletal muscle mass prevalence, as diagnosed by estimating the skeletal mass index (SMI) in the middle of the third-lumbar vertebrae (L3) level via computed tomography (CT). Other objectives included an evaluation of nutritional management, physical activity, and toxicities related to ongoing treatment. Results Seven hundred sixty-six patients (49.9% males) were enrolled with a mean age of 65.0 years. Low muscle mass prevalence was 69.1%. Only one-third of patients with low skeletal muscle mass were receiving nutritional counselling and only 28.4% were under nutritional management (oral supplements, enteral or parenteral nutrition). Physicians highly underdiagnosed those patients identified with low skeletal muscle mass, as defined by the primary objective, by 74.3% and 44.9% in obese and non-obese patients, respectively. Multivariate analyses revealed a lower risk of low skeletal muscle mass for females (OR: 0.22, P 0.01) and those without brain metastasis (OR: 0.34, P 0.01). Low skeletal muscle mass patients were more likely to have delayed treatment administration due to toxicity (11.9% versus 6.8%, P = 0.04). Conclusions There is a critical need to raise awareness of low skeletal muscle mass diagnosis among oncologists, and for improvements in nutritional management and physical therapies of cancer patients to curb potential cachexia. This calls for cross-disciplinary collaborations among oncologists, nutritionists, physiotherapists, and radiologists.

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18-64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p

BACKGROUND/PURPOSE To characterize the nature of posterior segment ocular injuries in combat trauma. METHODS Eyes in the Walter Reed Ocular Trauma Database were evaluated for the presence of posterior segment injury. Final visual outcomes in open-globe versus closed-globe injuries and by zone of injury and the types of posterior segment injuries in open-globe versus closed-globe injuries were assessed. RESULTS Four hundred fifty-two of 890 eyes (50.8%) had at least one posterior segment injury. The mechanism of injury was most commonly an improvised explosive device in 280 (62.0%) eyes. Sixty-one patients (13.5%) had a Zone I injury, 50 (11.1%) a Zone II injury, and 341 (75.4%) a Zone III injury. Patients with Zone I injuries were more likely to have a final visual acuity of 20/200 or better compared with patients with either a Zone II (P < 0.001) or Zone III injury (P = 0.007). Eyes with a closed-globe injury were more likely to have a final visual acuity of 20/200 or better compared with those with an open-globe injury (P < 0.001). Furthermore, closed-globe injury compared with open-globe injury had a lower risk of vitreous hemorrhage (odds ratio 0.32, P < 0.001), proliferative vitreoretinopathy (odds ratio 0.14, P < 0.001), and retinal detachment (odds ratio 0.18, P < 0.001) but a higher risk of chorioretinal rupture (odds ratio 2.82, P < 0.001) and macular hole (odds ratio 3.46, P = 0.004). CONCLUSION Patients with combat ophthalmic trauma had similar posterior segment injury patterns to civilian trauma in open-globe versus closed-globe injuries. Zone II and III injuries were associated with a worse visual prognosis.

INTRODUCTION To compare the long-term effect after modified CO2 laser-assisted sclerectomy surgery (MCLASS) and conventional trabeculectomy (TRAB) in medically uncontrolled Chinese primary open-angle glaucoma (POAG) patients. This was a retrospective comparative study. METHODS A total of 87 patients were reviewed, including 45 in the MCLASS group and 42 in the TRAB group. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and use of supplemental medical therapy were retrospectively compared at baseline, and until 36 months postoperatively. RESULTS Patients in both groups achieved a significant IOP decrease from baseline (P

The treatment of hypercalcemia of malignancy (HCM) consists of enhancing renal calcium excretion, mostly through hydration with isotonic fluids and the use of antiresorptive therapies. Intravenous zoledronic acid is currently the first-line treatment. Subcutaneous denosumab is used for bisphosphonate-refractory hypercalcemia and in patients with renal failure. There is no evidence that bisphosphonates prevent the occurrence of HCM. Conversely, denosumab, compared with zoledronic acid, is associated with a lower risk of HCM, both first episode and recurrence, in patients with breast cancer and multiple myeloma.

Background Prior reports demonstrate the expression of estrogen and progesterone receptors in high-grade gliomas (HGGs), but the relationship between hormone receptor-positive disease and risk of HHGs in patients with breast cancer (BC) remains uncharacterized. Methods Using the SEER 18 registries (2000–2017), we examined the temporal trend of the incidence of HGGs and BC. The standardized incidence ratio was calculated to assess the risk of subsequent HGG in BC patients. Results During the study period, the incidence of BC and HGGs remained comparable for men and women. Among 976,134 patients with BC, we found a decreased incidence of HGGs in females, but not in males. Female BC patients with hormone receptor-positive disease were at a lower risk of developing glioblastoma and anaplastic astrocytoma. Conclusion Our study findings allude to the protective role of hormone exposure in the development of HGGs, which may lead to the development of therapies targeting hormonal pathways.

Pregnancy risk assessment for patients with adult congenital heart disease (ACHD) must include physiologic and anatomic impacts. We aimed to determine whether maternal cardiac and pregnancy outcomes vary by disease severity defined according to the following 3 different classifications: ACHD anatomic severity, ACHD physiologic class, and modified World Health Organization (mWHO) class. Cardiac outcomes included a composite of arrhythmia, heart failure, stroke, and thromboembolism. Pregnancy outcomes included a composite of intrauterine growth restriction, preterm birth, preeclampsia, or postpartum hemorrhage. We employed generalized estimating equations to account for multiple pregnancies. Of the 245 pregnancies, 17.1% were preterm and 45.7% were cesarean deliveries. Cardiac hospitalizations occurred in 22.0% and arrhythmias in 12.7%. Cardiac outcomes tended to be more prevalent in people with more severe heart disease. Pregnancy outcomes were U-shaped or less prevalent in people with more severe disease. There was a 2.9-fold increased risk for the composite cardiac outcome for complex anatomy (adjusted incidence rate ratio 2.90, 95% confidence interval 1.08 to 7.81, p = 0.04), a 9.4-fold increased risk for physiologic class C or D (9.37, 1.28 to 68.79, p = 0.03), and a fourfold increased risk for mWHO class III or IV (3.99, 1.53 to 10.40, p = 0.005). There was a lower risk for the composite pregnancy outcome for mWHO class II or II to III (0.54, 0.36 to 0.79, p = 0.002) but no association with anatomy or physiology. In conclusion, physiologic class may be most accurately associated with adverse outcomes and therefore efforts to optimize hemodynamics before pregnancy may help to mitigate the risk.

Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and it increases stroke risk. A preventive approach to AF is needed because virtually all treatments such as cardioversion, antiarrhythmic drugs, ablation, and anticoagulation are associated with high cost and carry significant risk. A systematic review was performed to identify effective lifestyle-based strategies for reducing primary and secondary AF. A PubMed search was performed using articles up to March 1, 2021. Search terms included atrial fibrillation, atrial flutter, exercise, diet, metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, stress, tobacco smoking, alcohol, Mediterranean diet, sodium, and omega-3 fatty acids. Additional articles were identified from the bibliographies of retrieved articles. The control of hypertension, ideally with a renin-angiotensin-aldosterone system inhibitor, is effective for preventing primary AF and recurrence. Obstructive sleep apnea is a common cause of AF, and treating it effectively reduces AF episodes. Alcohol increases the risk of AF in a dose-dependent manner, and abstinence reduces risk of recurrence. Sedentary behavior and chronic high-intensity endurance exercise are both risk factors for AF; however, moderate physical activity is associated with lower risk of AF. Recently, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists have been associated with reduced risk of AF. Among overweight/obese patients, weight loss of ≥10% is associated with reduced AF risk. Lifestyle changes and risk factor modification are highly effective for preventing AF.

Summary Background & aim Dairy products may play a beneficial role against metabolic syndrome; however, epidemiological evidence is scarce in Asian populations, who consume less dairy than Western populations. We prospectively investigated the association between dairy product intake, both overall and by fat content, and metabolic syndrome in a Japanese working population. Methods Participants were 1014 workers (aged 19–68 years) without metabolic syndrome at baseline who completed a 3-year follow-up survey. Dietary intake was assessed using a validated self-administered diet history questionnaire. Metabolic syndrome was defined according to the Joint Interim Statement (JIS) criteria. Multiple logistic regression was used to estimate the odds ratio of metabolic syndrome according to tertile of total, low-fat, and full-fat dairy product intake with adjustment for covariates. Results At the 3-year follow-up, 66 (6.5%) workers were newly identified as having metabolic syndrome. A trend towards decreased odds of developing metabolic syndrome was observed among those in the highest tertile of total and full-fat dairy product intake: multivariable-adjusted odds ratio for the highest versus lowest tertile was 0.54 (95% CI 0.26–1.12; P for trend = 0.094) for total dairy products and 0.50 (95% CI 0.24–1.05; P for trend = 0.038) for full-fat dairy products. Low-fat dairy intake was not associated with metabolic syndrome. Conclusions Our results suggest that higher intake of full-fat, but not low-fat, dairy products may be associated with a lower risk of metabolic syndrome among Japanese.

BACKGROUND: Additional real-world studies are needed to more fully elucidate the effectiveness of antifibrotic treatment in slowing the progression of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To compare mortality and hospitalization between Medicare beneficiaries with IPF who initiate antifibrotic therapy and those who did not receive treatment. METHODS: A retrospective observational study of Medicare beneficiaries using the 100% Medicare Research Identifiable File was conducted. We included patients aged 67 years and over diagnosed with IPF (≥ 1 inpatient or ≥ 2 outpatient claims with IPF diagnosis, J84.112]) during the study period (January 1, 2010-December 31, 2017). Patients who initiated antifibrotic treatment (pirfenidone or nintedanib) between October 15, 2014 (FDA approval date) and December 31, 2017 (ie, treated patients) were compared with those who did not receive treatment during a historical period (January 1, 2012-October 14, 2014) before the availability of antifibrotics (ie, untreated historical controls). Patients were matched by propensity score, and the outcomes, mortality, and hospitalization (all cause and respiratory related) were compared using a Cox proportional hazards model. RESULTS: We identified 4,641 treated patients and 4,641 propensity score-matched controls who met all study criteria; 352 treated patients who lacked matches were excluded from the study. Cox regression analysis of treated patients vs matched controls showed a significantly lower risk of mortality (HR = 0.62, 95% CI = 0.57-0.68); lower risk of hospitalization (HR = 0.71, 95% CI = 0.67-0.76; HR = 0.70, 95% CI = 0.64-0.76); and lower rate in number of hospitalizations per month (incident rate ratio [IRR] = 0.65, 95% CI = 0.60-0.71; IRR = 0.65, 95% CI = 0.58-0.73). CONCLUSIONS: This study suggests that treatment with antifibrotics may confer a survival benefit and protection against all-cause and respiratory-related hospitalization for IPF patients. DISCLOSURES: This work was sponsored by F. Hoffmann-La Roche/Genentech, Inc. Corral is employed by Genentech, Inc. Reddy, Chang, Broder, and Gokhale are employed by Partnership for Health Analytic Research LLC, a health services research company, which was hired by Genentech to conduct this research. Mooney has received advisory board/consulting fees and research support from Genentech, unrelated to this work. Mooney also reports advisory board/consulting fees and research support from Boehringer Ingelheim; personal fees from Imvaria; and grants from Celgene and Pliant, unrelated to this work. Through their employment with Partnership for Health Analytic Research, Reddy, Chang, Broder, and Gokhale have been compensated to conduct research for AbbVie, Akcea, ASPC, Amgen, AstraZeneca, BMS, Boston Scientific Corporation, Celgene, Eisai, Ethicon, GRAIL, Helsinn, Illumina, Innovation and Value Initiative, Ionis, Jazz, Kite, Novartis, Otsuka, Pathnostics, PhRMA, Prothena, Sage, Verde Technologies, Genentech, Inc., Greenwich Biosciences, Inc., Mirum Pharmaceuticals, Inc., Sanofi US Services, Inc., Sunovion Pharmaceuticals, Inc., and Dompe US, Inc., unrelated to this work. This research was presented as an abstract at CHEST 2020 Annual Meeting (virtual), October 18-21, 2020, and American Thoracic Society 2020 Virtual Meeting, June 2020.

Objective To identify determinants associated with insulin resistance and to assess the association between insulin resistance and cardiovascular events, vascular interventions and mortality in people with type 1 diabetes at high risk of cardiovascular disease. Design Prospective cohort study. Methods One hundred and ninety-five people with type 1 diabetes from the Secondary Manifestations of ARTerial disease (SMART) cohort were included. Insulin resistance was quantified by the estimated glucose disposal rate (eGDR) with higher eGDR levels indicating higher insulin sensitivity (i.e. lower eGDR levels indicating higher insulin resistance). Linear regression models were used to evaluate determinants associated with eGDR. The effect of eGDR on cardiovascular events, cardiovascular events or vascular interventions (combined endpoint) and on all-cause mortality was analysed using Cox proportional hazards models adjusted for confounders. Results In 195 individuals (median follow-up 12.9 years, IQR 6.7–17.0), a total of 25 cardiovascular events, 26 vascular interventions and 27 deaths were observed. High eGDR as a marker for preserved insulin sensitivity was independently associated with a lower risk of cardiovascular events (HR: 0.75; 95% CI: 0.61–0.91), a lower risk of cardiovascular events and vascular interventions (HR: 0.74; 95% CI: 0.63–0.87) and a lower risk of all-cause mortality (HR: 0.81; 95% CI: 0.67–0.98). Conclusions Insulin resistance as measured by eGDR is an additional risk factor for cardiovascular disease in individuals with type 1 diabetes. Modification of insulin resistance by lifestyle interventions or pharmacological treatment could be a viable therapeutic target to lower the risk of cardiovascular disease.

Background/objectives Acute pancreatitis (AP) is a procoagulant state, and markers of coagulopathy are associated with AP severity. We aimed to explore the association of systemic anticoagulation therapy before AP onset with the inpatient outcomes of patients with acute pancreatitis. Methods This case-control, retrospective study used data from the Nationwide Inpatient Sample (Jan 2014–Dec 2016). We used medical coding data to identify patients with a principal diagnosis of AP who were receiving systemic anticoagulation therapy. Patients with anticoagulation were matched to those without it on the propensity for having anticoagulation. The propensity for having anticoagulation was estimated using a logistic regression model, matching for age, gender, race, median household income for patients' zip code, Charlson comorbidity score, region of hospital, location of hospital (urban/rural), teaching status of hospital, if admission day was on a weekend, pancreatic cancer class, obesity, tobacco usage. Secondary outcomes were inpatient outcomes and hospital expenditures. Results A total of 190,474 patients admitted for acute pancreatitis were identified, out of which 7827 patients were on anticoagulation. After propensity matching, 5776 matched pairs were successfully identified. Patients with AP on anticoagulation tended to have lower risk for ICU admission, acute kidney injury, organ failure or inpatient mortality. However, the group with anticoagulation had longer hospital length of stay and higher hospital costs. Conclusions Anticoagulation therapy may have a pivotal role in the pathogenesis and progression of AP. These data suggest a potential therapeutic role for anticoagulants in AP. Further studies are needed to better understand these observations.

Objective The data showing the association between gout and dementia are inconsistent. The objective of this study was to examine whether gout is associated with the risk of dementia in the elderly. Methods This retrospective cohort study used population-based representative claims data from the National Health Insurance Service in Korea. We used the Elderly Cohort database which represents 10% of the elderly Koreans over the age of 60, from 2002 to 2013. We assessed the association of gout with a new diagnosis of dementia with Cox proportional hazard models and adjusted the data for potential covariates such as demographics (age, sex) and comorbidities. Results We included 22,178 patients with gout and 113,590 without. In each group, 2,557 (11.53%) and 18,264 (16.08%) patients, respectively, had dementia. In multivariable analyses, gout was independently associated with a significantly lower hazard ratio of incident dementia, with an adjusted hazard ratio of 0.63 (95% CI, 0.60–0.66). A sub-group analysis conducted to find out the effects of gout medication showed that febuxostat use significantly decreased incident dementia. Conclusion Gout was independently associated with a 37% lower risk of dementia in the elderly.

Aims Diabetes mellitus (DM) and atrial fibrillation (AF) commonly co-exist. Oral anticoagulants (OACs) are widely used in patients with DM. This review aims to summarise the available literature on the safety (hypoglycaemia or bleeding) and efficacy (stroke or systemic embolism) of the use of OACs in patients with DM. Methods We searched the Medline, the Excerpta Medica dataBASE (Embase) and Cochrane databases up to the 10th of December 2020. The search strategy was conducted using both keywords and MeSH terms. We included randomised controlled trials (RCTs) and observational studies that reported on the safety and efficacy of the use of OACs in patients with diabetes from all age groups. Study selection, data extraction and quality assessment were conducted independently by two reviewers. Results A total of 3,976 articles were identified through the search process, of which seven studies met the inclusion criteria of the systematic review: four observational studies and three studies that were randomised controlled trials, with a total of 703,855 patients. Two observational studies reported that the use of warfarin was associated with a higher risk of hypoglycaemic events, specifically with sulfonylurea. One observational study and three randomised controlled trials reported that the use of warfarin compared to other oral anticoagulants was associated with a higher risk of bleeding. In addition, three randomised controlled trials reported that the use of warfarin compared to other oral anticoagulants was associated with a lower risk of stroke or systemic embolism. Conclusions This systematic review found that DOACs had a better efficacy outcome and safer clinical outcomes in comparison to warfarin in patients with diabetes.

Background Concomitant anticoagulant and antiplatelet therapy increases bleeding risk, but most data are derived from patients with atrial fibrillation. Patients with venous thromboembolism (VTE) may differ. Objective To study the management of patients diagnosed with acute VTE while receiving antiplatelet treatment. The primary outcome was the number of patients discharged with concomitant therapy. Secondary outcomes were clinically relevant bleeding, cardiovascular events, recurrent VTE and death during follow-up, according to discharge therapy. Methods We performed a post-hoc analysis of patients included in two prospective registries, sharing the same case report form, from 2007 to 2017. Results Among the 1694 identified patients, 254 (15.0%) were receiving antiplatelet treatment at VTE diagnosis, of whom 61 (24.0%) were discharged with concomitant anticoagulant and antiplatelet therapy. In multivariable analysis, age ≥ 80 years-old and the use of Direct Oral Anticoagulants for VTE therapy were associated with the decision to stop the antiplatelet, while having dual anti-platelet therapy at baseline, a history of coronaropathy or peripheral arterial disease were associated with concomitant anticoagulant and antiplatelet therapy. The decision to stop antiplatelet was associated with a non-significant 46% decrease in the risk of bleeding (OR 0.54 (0.16; 1.78)), and a non-significant 68% increase in the risk of cardiovascular events (OR 1.68 (0.44; 6.46)). Conclusion At acute VTE diagnosis, over 15% of patients were receiving antiplatelet agents, of whom 24% were discharged with concomitant anticoagulant and antiplatelet therapy. This therapeutic decision may be associated with a lower risk of cardiovascular events, but an increased risk of bleeding.

Background Although several systematic reviews and meta-analyses have been conducted to assess the relationship between fruit intake and health outcomes, the results of the relationship are inconclusive. Scope and approach We conducted an umbrella evaluation of existing research on the relationship between fruit intake and various health outcomes in humans. We used A Measurement Tool to Assess Systematic Reviews 2 and Grade of Recommendations, Assessment, Development and Evaluation to comprehensively evaluate the methodological quality and evidence quality of the research. We also performed a subgroup analysis based on the study design. Key findings and conclusions The umbrella review covered 59 qualified studies, which included 77 meta-analyses and 66 health outcomes. No adverse relationships between fruit intake and health outcomes were found. Moderate-quality evidence suggested that one serving increment of fruit per day could decrease the risks of cardiovascular disease (RR: 0.97, 95% CI: 0.95 to 0.99), stroke (RR: 0.92, 95% CI: 0.88 to 0.96), coronary heart disease (RR: 0.96, 95% CI: 0.93 to 0.99), and oral cancer (OR: 0.51, 95% CI: 0.40 to 0.65). And moderate-quality evidence presented that 200 g increment of fruit intake per day was associated with lower risk of breast cancer (RR: 0.94, 95% CI: 0.89 to 0.99), and the risk of type 2 diabetes mellitus could be reduced by 8%-12% when the fruit intake increasing to 100-500 g/d. For the remaining studies, the quality of evidence was either low or very low. We also found that the study design could influence the significance of the association between fruit intake and health outcomes. Large-sample, multi-center, and multi-country randomized controlled trials or prospective studies are required to verify our results.

BACKGROUND Inhibition of the renin angiotensin aldosterone system (RAAS) improves survival and reduces adverse cardiac events in heart failure with reduced ejection fraction, but the benefit is not well-defined following left ventricular assist device (LVAD). METHODS We analyzed the ISHLT IMACS registry for adults with a primary, continuous-flow LVAD from January 2013 to September 2017 who were alive at postoperative month 3 without a major adverse event, and categorized patients according to treatment an angiotensin converting enzyme inhibitor (ACEI/ARB) or mineralocorticoid receptor antagonist (MRA). Propensity score matching was performed separately for ACEI/ARB vs none (n = 4,118 each) and MRA vs none (n = 3,892 each). RESULTS Of 11,494 patients included, 50% were treated with ACEI/ARB and 38% with MRA. Kaplan-Meier survival was significantly better for patients receiving ACEI/ARB (p < 0.001) but not MRA (p = 0.31). In Cox proportional hazards analyses adjusted for known predictors of mortality following LVAD, ACEI/ARB use (hazard ratio 0.81 [95% confidence interval 0.71-0.93], p < 0.0001) but not MRA use (hazard ratio 1.03 [95% confidence interval 0.88-1.21], p = 0.69) was independently associated with lower mortality. Among patients treated with an ACEI/ARB, there was a significantly lower unadjusted risk of cardiovascular death (p < 0.001), risk of gastrointestinal bleeding (p = 0.01), and creatinine level (p < 0.001). MRA therapy was associated with lower risk of gastrointestinal bleeding (p = 0.01) but higher risk of hemolysis (p < 0.01). Potential limitations include residual confounding and therapy crossover. CONCLUSION These findings suggest a benefit for ACEI/ARB therapy in patients with heart failure after LVAD implantation.

Aims The aim of this study was to determine if uncemented acetabular polyethylene (PE) liner geometry, and lip size, influenced the risk of revision for instability or loosening. Methods A total of 202,511 primary total hip arthroplasties (THAs) with uncemented acetabular components were identified from the National Joint Registry (NJR) dataset between 2003 and 2017. The effect of liner geometry on the risk of revision for instability or loosening was investigated using competing risk regression analyses adjusting for age, sex, American Society of Anesthesiologists grade, indication, side, institution type, surgeon grade, surgical approach, head size, and polyethylene crosslinking. Stratified analyses by surgical approach were performed, including pairwise comparisons of liner geometries. Results The distribution of liner geometries were neutral (39.4%; 79,822), 10° (34.5%; 69,894), 15° (21.6%; 43,722), offset reorientating (2.8%; 5705), offset neutral (0.9%; 1,767), and 20° (0.8%; 1,601). There were 690 (0.34%) revisions for instability. Compared to neutral liners, the adjusted subhazard ratios of revision for instability were: 10°, 0.64 (p < 0.001); 15°, 0.48 (p < 0.001); and offset reorientating, 1.6 (p = 0.010). No association was found with other geometries. 10° and 15° liners had a time-dependent lower risk of revision for instability within the first 1.2 years. In posterior approaches, 10° and 15° liners had a lower risk of revision for instability, with no significant difference between them. The protective effect of lipped over neutral liners was not observed in laterally approached THAs. There were 604 (0.3%) revisions for loosening, but no association between liner geometry and revision for loosening was found. Conclusion This registry-based study confirms a lower risk of revision for instability in posterior approach THAs with 10° or 15° lipped liners compared to neutral liners, but no significant difference between these lip sizes. A higher revision risk is seen with offset reorientating liners. The benefit of lipped geometries against revision for instability was not seen in laterally approached THAs. Liner geometry does not seem to influence the risk of revision for loosening. Cite this article: Bone Joint J 2021;103-B(12):1774–1782.

Background: Physical activity (PA) and discretionary screen time (DST; television and computer use during leisure) are both associated with obesity risk, but little longitudinal evidence exists on their combined influence. This study examined the independent and joint associations of changes in PA and DST with incident obesity, body mass index (BMI) and waist circumference (WC). Methods: We analysed the data of individuals aged 40–69 years from the UK Biobank, a large-scale, population-based prospective cohort study. PA was measured using the International Physical Activity Questionnaire and DST was defined as the total of daily TV viewing and non-occupational computer use. Changes in PA and DST over time were defined using departure from sex-specific baseline tertiles and categorised as worsened (PA decreased/DST increased), maintained, and improved (PA increased/DST decreased). We then used each exposure change to define a joint PA-DST change variable with nine mutually exclusive groups. We used multivariable adjusted mixed-effects linear and Poisson models to examine the independent and joint associations between PA and DST changes with BMI and WC and incident obesity, respectively. Development of a BMI ≥ 30 kg/m2 was defined as incident obesity. Results: Among 30,735 participants, 1,628 (5.3%) developed incident obesity over a mean follow-up of 6.9 (2.2) years. In the independent association analyses, improving PA (Incident Rate Ratio (IRR) 0.46 (0.38–0.56)) was associated with a lower risk of incident obesity than maintaining PA, maintaining DST, or improving DST. Compared to the referent group (both PA and DST worsened), all other combinations of PA and DST changes were associated with lower incident obesity risk in the joint association analyses. We observed substantial beneficial associations in the improved PA groups, regardless of DST change [e.g., DST worsened (IRR 0.31 (0.21–0.44)), maintained (IRR 0.34 (0.25–0.46)), or improved (IRR 0.35 (0.22–0.56)]. The most pronounced decline in BMI and WC was observed when PA was maintained or improved and DST was maintained. Conclusion: We found that improved PA had the most pronounced beneficial associations with incident obesity, irrespective of DST changes. Improvements in PA or DST mutually attenuated the deleterious effects of the other behaviour’s deterioration.

Summary Background & aims Epidemiologic studies are inconsistent regarding the association of dietary omega-3 polyunsaturated fatty acids (PUFA) and/or fish intake with risk of age-related macular degeneration (AMD) incidence and progression. The objective was to determine these associations by conducting a meta-analysis of available studies. Methods Three electronic databases were searched for studies that quantified dietary omega-3 PUFA and/or fish intake from inception to December 2020 without language restriction. Three investigators independently assessed for inclusion and extracted data. Study-specific risk estimates were combined using random-effects model. Potential dose–response associations were explored with the use of generalized least-squares trend estimation. Results 21 studies were included in the meta-analysis. Higher dietary intakes of omega-3 PUFA was significantly associated with 14% (relative risk [RR]: 0.86, 95% confidence interval [CI]: 0.77, 0.96) and 29% (RR: 0.71, 95% CI: 0.55, 0.91) lower risk of early and late AMD, respectively. The dose–response analysis showed a 6% and 22% decrease in the risk of early and late AMD for each additional 1 g/d omega-3 PUFA intake. For individual omega-3 PUFA, the intake of eicosapentaenoic acid and docosahexaenoic acid was inversely associated with lower AMD risk, whereas no association was found for the alpha-linolenic acid. Consistent inverse associations were also found between fish intake and AMD. The pooled RRs comparing extreme categories of fish intake were 0.79 (95% CI: 0.70, 0.90) and 0.71 (95% CI: 0.60, 0.85) for early and late AMD risk, respectively. Every 15 g/d of fish consumption was associated with 13% and 14% lower early and late AMD. In addition, fish intake was associated with a significantly reduced risk of AMD progression (RR: 0.73, 95% CI: 0.53, 1.00). Conclusions A high intake of dietary omega-3 PUFA or fish was associated with a reduced risk of developing of AMD, which further supports that consumption of omega-3 PUFA-rich foods may be a new avenue nutritional approach to preventing AMD.

Summary Background Although studies suggest that concentrations of omega-3 and omega-6 fatty acids are lower in individuals with schizophrenia, evidence for beneficial effects of fatty acid supplementation is scarce. Therefore, in this study, we aimed to determine whether omega-3 and omega-6 fatty acid concentrations are causally related to schizophrenia. Methods We did a two-sample Mendelian randomisation study, using deidentified summary-level data that were publicly available. Exposure-outcome relationships were evaluated using the inverse variance weighted two-sample Mendelian randomisation method using results from genome-wide association studies (GWASs) of fatty acid concentrations and schizophrenia. GWAS results were available for European (fatty acids) and European and Asian (schizophrenia) ancestry samples. Overall age and gender information were not calculable from the summary-level GWAS results. Weighted median, weighted mode, and Mendelian randomisation Egger regression methods were used as sensitivity analyses. To address underlying mechanisms, further analyses were done using single instruments within the FADS gene cluster and ELOVL2 gene locus. FADS gene cluster and ELOVL2 gene causal effects on schizophrenia were calculated by dividing the single nucleotide polymorphism (SNP)-schizophrenia effect estimate by the SNP-fatty acid effect estimate with standard errors derived using the first term from a delta method expansion for the ratio estimate. Multivariable Mendelian randomisation was used to estimate direct effects of omega-3 fatty acids on schizophrenia, independent of omega-6 fatty acids, lipoproteins (ie, HDL and LDL), and triglycerides. Findings Mendelian randomisation analyses indicated that long-chain omega-3 and long-chain omega-6 fatty acid concentrations were associated with a lower risk of schizophrenia (eg, inverse variance weighted odds ratio [OR] 0·83 [95% CI 0·75–0·92] for docosahexaenoic acid). By contrast, there was weak evidence that short-chain omega-3 and short-chain omega-6 fatty acids were associated with an increased risk of schizophrenia (eg, inverse variance weighted OR 1·07 [95% CI 0·98–1·18] for α-linolenic acid). Effects were consistent across the sensitivity analyses and the FADS single-SNP analyses, suggesting that long-chain omega-3 and long-chain omega-6 fatty acid concentrations were associated with lower risk of schizophrenia (eg, OR 0·74 [95% CI 0·58–0·96] for docosahexaenoic acid) whereas short-chain omega-3 and short-chain omega-6 fatty acid concentrations were associated with an increased risk of schizophrenia (eg, OR 1·08 [95% CI 1·02–1·15] for α-linolenic acid). By contrast, estimates from the ELOVL2 single-SNP analyses were more imprecise and compatible with both risk-increasing and protective effects for each of the fatty acid measures. Multivariable Mendelian randomisation indicated that the protective effect of docosahexaenoic acid on schizophrenia persisted after conditioning on other lipids, although evidence was slightly weaker (multivariable inverse variance weighted OR 0·84 [95% CI 0·71–1·01]). Interpretation Our results are compatible with the protective effects of long-chain omega-3 and long-chain omega-6 fatty acids on schizophrenia, suggesting that people with schizophrenia might have difficulty converting short-chain polyunsaturated fatty acids to long-chain polyunsaturated fatty acids. Further studies are required to determine whether long-chain polyunsaturated fatty acid supplementation or diet enrichment might help prevent onset of schizophrenia. Funding National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol.

AIM Healthcare disparities can affect access and quality of care among many in the United States (US). In addition to race, we sought to assess if geography affected rates of cardiac arrest, and the subsequent outcomes. METHODS Using the National Inpatient Sample database from 2006-2018, we assessed rates of cardiac arrest (out of hospital that survived to admission and in-hospital) and cardiac catheterization, and length of stay (LOS) in four regions: Northeast (NE), South (SO) West (W) and Midwest (MW). RESULTS Cardiac arrest increased from 27,611 (2006) to 43,333 (2018). The proportion of African American (AA) patients experiencing cardiac arrest significantly increased from 11.9% to 18.8%. The mortality decreased from 65.4% to 60.8% in all patients and 70.2% to 61.4% in AA. Mortality in AA remained higher than non-AA (OR, 1.09 [1.08-1.11], p

Pericarditis is the most common inflammatory pericardial disease in both children and adults. Since the publication of the 2015 European Society of Cardiology Guidelines for the diagnosis and management of pericardial disease were published there have been significant updates to management. Pharmacotherapy has been historically reserved for idiopathic pericarditis (IP). However, there has been increasing use of pharmacotherapies such as anti-inflammatory therapies, colchicine and immunotherapies for other causes of pericarditis, such as post cardiac injury syndromes (PCIS). Nevertheless, the quality of data varies depending on PCIS or idiopathic etiologies, as well as the adult and pediatric population. High-dose anti-inflammatory therapies should be used to manage symptoms associated with either etiology of pericarditis in both adults and children, but do not ameliorate the inflammatory disease process. Choice of anti-inflammatory should be guided by drug-drug/disease interactions, cost, tolerability, patient age, and should be tapered accordingly over several weeks to months. Colchicine should be added as adjuvant therapy to anti-inflammatory therapies in adults and children with IP, as it has been shown to lower risk of recurrence, reduce pericarditis symptoms, and improve morbidity. Colchicine is also reasonable to add to adults and children with pericarditis secondary to PCIS. Systemic glucocorticoids increase risk of recurrence in adults and children with IP and are reserved for second-line treatment in acute and recurrent IP; they are generally avoided in PCIS. Immunotherapies are regarded as third-line for recurrent IP in adults and children. Limited evidence exists to support their use in patients with pericarditis from PCIS. Pharmacovigilance strategies such as C-reactive protein and adverse drug event monitoring are also important towards balancing efficacy and safety of the various strategies used to manage pericarditis in adults and children.

Objective To separately compare the long-term risk of mortality among bariatric surgical patients undergoing either RYGB or SG to large, matched, population-based cohorts of patients with severe obesity who did not undergo surgery. Background Bariatric surgery has been associated with reduced long-term mortality compared to usual care for severe obesity which is particularly relevant in the COVID-19 era. Most prior studies involved the Roux-en-Y gastric bypass (RYGB) operation and there is less long-term data on the sleeve gastrectomy (SG). Methods In this retrospective, matched cohort study, patients with a body mass index ≥35 kg/m2 who underwent bariatric surgery from January 2005 to September 2015 in three integrated health systems in the United States were matched to nonsurgical patients on site, age, sex, body mass index, diabetes status, insulin use, race/ethnicity, combined Charlson/Elixhauser comorbidity score, and prior health care utilization, with follow-up through September 2015. Each procedure (RYGB, SG) was compared to its own control group and the two surgical procedures were not directly compared to each other. Multivariable-adjusted Cox regression analysis investigated time to all-cause mortality (primary outcome) comparing each of the bariatric procedures to usual care. Secondary outcomes separately examined the incidence of cardiovascular-related death, cancer related-death, and diabetes related-death. Results Among 13,900 SG, 17,258 RYGB, and 87,965 nonsurgical patients, the 5-year follow-up rate was 70.9%, 72.0%, and 64.5%, respectively. RYGB and SG were each associated with a significantly lower risk of all-cause mortality compared to nonsurgical patients at 5-years of follow-up (RYGB: HR = 0.43; 95% CI: 0.35,0.54; SG: HR = 0.28; 95% CI: 0.13,0.57) Similarly, RYGB was associated with a significantly lower 5-year risk of cardiovascular- (HR = 0.27; 95% CI: 0.20, 0.37), cancer- (HR = 0.54; 95% CI: 0.39, 0.76), and diabetes-related mortality (HR = 0.23; 95% CI:0.15, 0.36). There was not enough follow-up time to assess 5-year cause-specific mortality in SG patients, but at 3-years follow up, there was significantly lower risk of cardiovascular- (HR = 0.33; 95% CI:0.19, 0.58), cancer- (HR = 0.26; 95% CI:0.11, 0.59), and diabetes-related (HR = 0.15; 95% CI:0.04, 0.53) mortality for SG patients. Conclusion This study confirms and extends prior findings of an association with better survival following bariatric surgery in RYGB patients compared to controls and separately demonstrates that the SG operation also appears to be associated with lower mortality compared to matched control patients with severe obesity that received usual care. These results help to inform the trade-offs between long-term benefits and risks of bariatric surgery.

ObjectivesTo obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD).MethodsWe searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as ‘all-cause mortality (ACM) or myocardial infarction (MI)’ at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint.ResultsFive studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), pConclusionsThe 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.

ObjectivesThe aim of this study was to determine the risk factors associated with SARS-CoV-2 infection in a cohort of homeless people using survival analysis. Seroprevalence in the homeless community was also compared with that of the general population.DesignCohort study.SettingData were collected across two testing sessions, 3 months apart, during which each participant was tested for anti-SARS-CoV-2 antibodies and completed a face-to-face survey.ParticipantsAll homeless adults sleeping rough, in slums or squats, in emergency shelters or transitional accommodation in Marseille were eligible.Primary outcome measuresOccurrence of a seroconversion event defined as a biologically confirmed SARS-CoV-2 infection. Local data from a national seroprevalence survey were used for comparison between homeless people and the general population.ResultsA total of 1249 people were included. SARS-CoV-2 seroprevalence increased from 6.0% (4.7–7.3) during the first session to 18.9% (16.0–21.7) during the second one, compared with 3.0% (1.9–4.2) and 6.5% (4.5–8.7) in the general population. Factors significantly associated with an increased risk of COVID-19 infection were: having stayed in emergency shelters (1.93 (1.18–3.15)), being an isolated parent (1.64 (1.07–2.52)) and having contact with more than 5–15 people per day (1.84 (1.27–2.67)). By contrast, smoking (0.46 (0.32–0.65)), having financial resources (0.70 (0.51–0.97)) and psychiatric or addictive comorbidities (0.52 (0.32–0.85)) were associated with a lower risk.ConclusionWe confirm that homeless people have higher infection rates than the general population, with increased risk in emergency shelters. There is growing evidence that, in addition to usual preventive measures, public policies should pay attention to adapt the type of accommodation and overall approach of precariousness.Trial registration numberNCT04408131

Background: At the beginning of COVID-19 pandemic, specific COVID/PSY wards were created in France to provide care for inpatients with COVID-19 and psychiatric disorders. In this multi-center prospective study, we set out to assess the clinical features and risk factors of somatic aggravation in patients hospitalized in COVID/PSY wards. Methods: Data were collected between 28 February and 30 May, 2020. We collected demographic data, psychiatric diagnoses, medical data and COVID-19-related clinical data. Somatic aggravation was estimated by the number of patients transferred to intensive care or medicine units, the number of deaths and the number of patients presenting a confusional state. A multivariate logistic model was used to assess the risk factors of confusional state and transfer to intensive care or medicine units. The risk of death was analysed by the univariate predictors of this outcome. Outcomes: 350 patients were included in the study. The number of inclusions peaked one week after that of the general population and declined more slowly. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit (OR 17.1; CI 4.9-59.3). Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age > 55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, while smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. Interpretation: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and a high risk of confusion. COVID/PSY wards may play a role in reducing the mortality of COVID-19 in patients with psychiatric disorders. Funding Statement: There was no funding source for this study. Declaration of Interests: There are no conflicts of interest to be declared. Ethics Approval Statement: This observational study was conducted according to the principles of the Declaration of Helsinki. In accordance with French bioethics laws, it was classified as a non- interventional study, since it concerned anonymized clinical data that are routinely compiled in medical records. Compliance with French regulations on personal data collection was supervised by the personal data referent of the Centre Psychotherapique de Nancy. Patients, and their legal guardian when appropriate, were informed in writing, in agreement with national regulations for observational studies.

The diagnostic approach to sleep-related breathing disorders (SRBDs), including obstructive sleep apnea–hypopnea syndrome (OSAHS), begins with a comprehensive sleep evaluation that includes a complete sleep history and a physical examination focused on the upper airway. If the evaluation suggests an SRBD as the cause of the patient's symptoms, diagnostic testing should be performed. Patients at high risk for OSAHS can be studied by either portable monitoring (if available) or in-laboratory polysomnography. Patients with a lower risk for OSAHS, or having risk factors for a different SRBD (such as central sleep apnea) or having a negative portable-monitoring study should be studied in a sleep laboratory.

Background The effect of the overall diet quality on cardiometabolic diseases has been well studied in the Western population. However, evidence is still in need regarding dietary patterns depicting unique Chinese dietary habits and their associations with cardiometabolic diseases. Methods A prospective cohort recruited around 0.5 million Chinese residents aged 30–79 years from 10 diverse survey sites during 2004–08. Dietary patterns were obtained using factor analysis based on the habitual consumption of 12 food groups collected at baseline. Among 477,465 eligible participants free of prior heart disease, stroke and cancer, linkages to multiple registries and health insurance database recorded 137,715 cardiovascular diseases (CVD) and 17,412 diabetes cases (among 451,846 non-diabetic participants) until 31 December 2017. Adjusted hazard ratios (HRs) were estimated to compare the risks of cardiometabolic diseases across quintiles of dietary pattern scores using the Cox regression. Results Two dietary patterns were derived: the traditional northern pattern, characterised by wheat, other staples, egg and dairy products; and the modern pattern, featured with fresh fruit, meat, poultry, fish, dairy products and soybean. Adherence to either dietary pattern was associated with lower risks of major cardiometabolic diseases in a dose-response relationship way. After multivariate adjustment, participants adhering to the traditional northern pattern the most had an 8% (95%CI: 5–11%) lower risk of CVD in comparison with those adhering the least. Corresponding risk reductions were 12% (11–32%) for haemorrhagic stroke (HS), 14% (8–19%) for ischaemic stroke (IS), and 15% (6–24%) for diabetes, respectively. When comparing extreme quintiles of the modern pattern, the adjusted HR of HS was 0.67 (95%CI: 0.59–0.77). Corresponding HRs were 0.89 (0.86–0.92) for CVD, 0.88 (0.77–0.99) for MCE, 0.85 (0.80–0.89) for IS, and 0.89 (0.81, 0.97) for diabetes. Conclusion Among Chinese adults, both traditional northern and modern dietary patterns were associated with lower risks of cardiovascular disease and diabetes beyond other risk factors.

BackgroundPosttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD.MethodsGenetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals.ResultsGenetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01–1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001)ConclusionsOur findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.

Backgrounds Magnetic sphincter augmentation (MSA) is a newly-developed procedure for refractory gastroesophageal reflux disease (rGERD). A systematic review with meta-analysis was conducted to determine its effectiveness in rGERD. Methods Electronic search was performed in Pubmed, Cochrane Library, Embase, Web of Science, Opengrey and ClincalTrials.gov up to April 2020. Single-arm studies evaluating the efficacy and safety of MSA in rGERD or comparative studies with proton pump inhibitor (PPI) or laparoscopic Nissen fundoplication (LNF) served as control were included. Demographic data，postoperative PPI use，GERD-HRQL (GERD-health related quality of life)，acid exposure time (AET)，adverse events (AEs) were collected. The primary outcome was the rate of postoperative PPI use, and secondary outcomes incorporated postoperative GERD-HRQL, normalization in AET and incidence of procedure-related AEs. Results In total, 14 trials involving 1138 participants with rGERD were included: 10 single-arm studies, 1 RCT and 3 cohort studies. After MSA, PPIs withdrawal, significant improvement of GERD-HRQL and normalization of AET were achieved respectively in 87.0%, 88.0% and 75.0% of the patients. The incidence of postoperative dysphagia was 29%, and endoscopic dilation was required in 7.4% of MSA patients. MSA showed a better efficacy in symptom control as compared to PPIs (PPI cessation: 91% vs 0%; GERD-HRQL improvement: 81% vs 8%) and similar effectiveness but a lower risk of gas-bloat syndrome (RR 0.69 [0.51, 0.93]，p=0.01) and better reserved ability to belch (RR 1.48 [0.76, 2.86]，p=0.25) as compared to LNF. Conclusion MSA was an effective and safe therapy for rGERD. Well-designed randomized trials that compares the efficacy of MSA with other therapies are needed.

We aimed to summarize the associations between food sources of fructose and cardiovascular diseases (CVD), cancer, and all-cause mortality risk using a systematic review and meta-analysis. We searched PubMed, Scopus, and Web of Science up to November 2020. We included cohort studies that investigated the relationship between mortality risk (all-cause, CVD, specific CVD, and total and site-specific cancers) and intake of ���1 food source of fructose (fruit, fruit juice, breakfast cereals, sugar-sweetened beverages (SSBs), sweets, and yogurt) in general adult population. Summary hazard ratios and 95% CIs were estimated using a random-effects model for linear and nonlinear relationships. Findings indicated that each 100 g/d increase in fruit intake was associated with 8-13% lower risk of CVDs, stroke, gastrointestinal, and lung cancer mortality. For all-cause mortality, there was a beneficial relationship up to 200 g/d fruit, and then plateaued. For ischemic heart disease and cancer mortality, there was a beneficial relationship up to 300 g/d followed by a slight increase. Ingestion of breakfast cereals and sweets was also associated with lower risk of all-cause mortality. For yogurt, a non-linear marginal decrease in all-cause mortality was found. Ingestion of each 200 g/d yogurt was associated with a 14% lower risk of CVD mortality. Every 60 g/d increase in sweet intake was linked to a 5% lower risk of all-cause mortality. Contrariwise, every 250 g/d increase in SSBs intake was associated with 7���10% higher risk of all-cause and CVD mortality. In conclusion, beneficial associations were found between fruit, breakfast cereals, sweets, and yogurt with all-cause and/or CVD mortality risk. Fruit intake had also an inverse link with cancer mortality. Conversely, SSBs had a harmful relationship with all-cause and CVD mortality. Registry number: CRD42019144956

AimsTo examine the temporal trends and factors associated with national cardiac rehabilitation (CR) referral and compare the risk of hospital readmission and mortality in those referred for CR versus no referral.Methods and resultsThis cohort study includes all adult patients alive 120 days from incident heart failure (HF) identified by the Danish Heart Failure Registry (n = 33 257) between 2010 and 2018. Multivariable logistic regression models were used to assess the association between CR referral and patient factors and acute all-cause hospital readmission and mortality at 1 year following HF admission. Overall, 46.7% of HF patients were referred to CR, increasing from 31.7% in 2010 to 52.2% in 2018. Several factors were associated with lower odds of CR referral: male sex [odds ratio (OR): 0.85; 95% confidence interval: 0.80–0.89], older age, unemployment, retirement, living alone, non-Danish ethnic origin, low educational level, New York Heart Association (NYHA) class IV vs. I (OR: 0.75; 0.60–0.95), left ventricular ejection fraction >40%, and comorbidity (stroke, chronic kidney disease, atrial fibrillation/flutter, and diabetes). Myocardial infarction, arthritis, coronary artery bypass grafting, percutaneous coronary intervention, valvular surgery, NYHA class II, and use of angiotensin-converting enzyme inhibitors were associated with higher odds of CR referral. CR referral was associated with lower risk of acute all-cause readmission (OR: 0.92; 0.87–0.97) and all-cause mortality (OR: 0.65; 0.58–0.72).ConclusionAlthough increased over time, only one in two HF patients in Denmark were referred to CR in 2018. Strategies are needed to reduce referral disparities, focusing on subgroups of patients at highest risk of non-referral.

We reviewed evidence on nonspecific effects of pediatric vaccines on mortality and morbidity in countries with high child mortality. Literature search of epidemiological studies was conducted for studies published between 2000 and September 2021 using MEDLINE. Consistent evidence exists regarding the potential protective effect of measles vaccine on child survival. Vaccination with Bacillus Calmette-Guérin (BCG) vaccine was related to lower risk of mortality in young children (including low birth weight babies) and inverse associations were found between developing a scar and having a positive tuberculin test after BCG vaccination with mortality. BCG vaccine might also reduce the risk of nontuberculosis infectious diseases. Studies on the association between diphtheria-pertussis-tetanus (DPT) vaccine and child survival showed inconsistent findings, which might be affected by bias and confounding. More evidence is needed to assess the role of these and other vaccines in children's health and to better understand potential biological mechanisms and other influential factors.

Patients with sickle cell disease (SCD) have a lower risk for HIV-1 infection. We reported restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory, and hemolytic factors, including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection. Ex vivo infection of SCT PBMCs exhibited an approximately twofold reduction of HIV-1 replication and lower levels of HIV-1 reverse transcription products, 2-long terminal repeat circle, HIV-1 integration, and gag RNA expression. SCT PBMCs had higher HO-1 messenger RNA (mRNA) and protein levels and reduced ribonucleotide reductase 2 (RNR2) protein levels. HO-1 inhibition by tin porphyrin eliminated ex vivo HIV-1 restriction. Among Howard University clinic recruits, higher levels of HO-1 and RNR2 mRNA and lower HIV-1 env mRNA levels were found in SCT individuals living with HIV-1. To determine the population-level effect of SCT on HIV-1 prevalence, we assessed SCT among women living with HIV (WLH) in the WIHS (Women Interagency HIV-1 Study). Among WIHS African-American participants, the prevalence of SCT was lower among women with HIV compared with uninfected women (8.7% vs 14.2%; odds ratio, 0.57; 95% confidence interval, 0.36-0.92; P = .020). WIHS WLH with SCT had higher levels of CD4+/CD8+ ratios over 20 years of follow-up (P = .003) than matched WLH without SCT. Together, our findings suggest that HIV-1 restriction factors, including HO-1 and RNR2, might restrict HIV-1 infection among individuals with SCT and limit the pathogenicity of HIV.

Background: Preliminary evidence suggests that patients with atrial fibrillation (AF) detected after stroke (AFDAS) may have a lower prevalence of cardiovascular comorbidities and lower risk of stroke recurrence than AF known before stroke (KAF). Objective: We performed a systematic search and meta-analysis to compare the characteristics of AFDAS and KAF. Methods: We searched PubMed, Scopus, and EMBASE for articles reporting differences between AFDAS and KAF until June 30, 2021. We performed random- or fixed-effects meta-analyses to evaluate differences between AFDAS and KAF in demographic factors, vascular risk factors, prevalent vascular comorbidities, structural heart disease, stroke severity, insular cortex involvement, stroke recurrence, and death. Results: In 21 studies including 22,566 patients with ischemic stroke or transient ischemic attack, the prevalence of coronary artery disease, congestive heart failure, prior myocardial infarction, and a history of cerebrovascular events was significantly lower in AFDAS than KAF. Left atrial size was smaller, and left ventricular ejection fraction was higher in AFDAS than KAF. The risk of recurrent stroke was 26% lower in AFDAS than in KAF. There were no differences in age, sex, stroke severity, or death rates between AFDAS and KAF. There were not enough studies to report differences in insular cortex involvement between AF types. Conclusions: We found significant differences in the prevalence of vascular comorbidities, structural heart disease, and stroke recurrence rates between AFDAS and KAF, suggesting that they constitute different clinical entities within the AF spectrum. PROSPERO registration number is CRD42020202622.

Objectives:To explore the combined effect of pediatric sickle cell disease (SCD) and preterm birth on cognitive functioning.Methods:Cognitive functioning was examined in children ages 6–8 with high risk SCD genotypes born preterm (n = 20) and full-term (n = 59) and lower risk SCD genotypes/no SCD born preterm (n = 11) and full-term (n = 99) using tests previously shown to be sensitive to SCD-related neurocognitive deficits. Factorial ANOVAs and log linear analyses were conducted to examine the relationship between SCD risk, preterm birth status, and cognitive outcomes. Continuous scores were examined for specific tests. Children were categorized as having an abnormal screening outcome if at least one cognitive score was ≥1.5 standard deviations below the population mean.Results:Children with elevated risk due to high risk SCD and preterm birth performed worse than other groups on a test of expressive language but not on tests that emphasize processing speed and working memory. There was a three-way interaction between preterm status, SCD risk, and abnormal screening outcome, which was largely driven by the increased likelihood of abnormal cognitive scores for children with high risk SCD born preterm.Conclusions:The combination of SCD and preterm birth may confer increased risk for language deficits and elevated rates of abnormal cognitive screenings. This suggests that neurodevelopmental risk imparted by comorbid SCD and preterm birth may manifest as heterogenous, rather than specific, patterns of cognitive deficits. Future studies are needed to clarify the domains of cognitive functioning most susceptible to disease-related effects of comorbid SCD and preterm birth.

Background. The health crisis due to the COVID-19 pandemic is a challenge in the dispensing of outpatient hospital medication (OHM). Models of Antiretroviral Therapy (ART) based on community pharmacy support (ARTCP) have proven to be successful. The aim was to evaluate the degree of satisfaction, acceptability and limitations of the implementation of ARTCP, in the context of a pandemic, in our environment. Methods. Descriptive cross-sectional study carried out in a Barcelona hospital, during the months of July-November 2020. A telephone survey was carried out via a questionnaire on the quality dimensions of the model (degree of satisfaction, acceptability) and associated inconveniences. Data collected: demographics, antiretroviral treatment (ART), concomitant medication, drug interactions (DDIs), CD4 lymphocyte count and plasma viraemia. Data analysis included descriptive statistics. Results. A total of 533 (78.0%) HIV patients receiving ART were included. 71.9% (383/533) of these patients were very satisfied and 76.2% preferred attending the community pharmacy rather than the hospital. The mean satisfaction rating was 9.3 (DS: 1.4). The benefits reported were: 1) proximity to home (406: 76.1%); 2) lower risk of contagion of COVID-19 (318: 59.7%); 3) shorter waiting time (201: 37.1%); 4) time flexibility (104: 19.5%); 5) reduction of financial expenses (35: 6.57%). A total of 11 (2%) patients reported no benefit. Only 22.9% reported disadvantages associated with ARTCP: 1) lack of privacy (65: 12.2%); 2) lack of coordinationorganization (57: 10.7%). Conclusion. The COVID-19 pandemic has had an impact on the provision of pharmaceutical care for HIV patients. The ARTPC model has proved efficient, with patients reporting a high degree of satisfaction.

BACKGROUND Prenatal diagnosis and planned peripartum care is an unexplored concept in China. This study aimed to evaluate the effects of the "prenatal diagnosis and postnatal treatment integrated model" for newborns with critical congenital heart disease. METHODS The medical records of neonates (≤ 28 days) admitted to Fuwai Hospital were reviewed retrospectively from January 2019 to December 2020. The patients were divided into "prenatal diagnosis and postnatal treatment integrated group" (n = 47) and "non-integrated group" (n = 69). RESULTS The age of admission to the hospital and the age at surgery were earlier in the integrated group than in the non-integrated group (5.2 ± 7.2 days vs. 11.8 ± 8.0 days, P

BACKGROUND It has been reported that the risk of erectile dysfunction (ED) is significantly higher in patients with obstructive sleep apnea (OSA), compared with patients without OSA. However, there is limited evidence on whether surgical treatments in patients with OSA could decrease ED risk. OBJECTIVES To assess the impact of surgical treatments for OSA on the risk of ED by analysis of claims data from the Taiwan National Health Insurance Research Database between 1997 and 2012. MATERIAL AND METHODS We identified 20,675 male adults with newly diagnosed OSA during the study period; 16,040 patients ever received surgical treatments (treated cohort) and 4635 patients never received surgical treatments (untreated cohort). According to 3:1 propensity score matching, we analyzed 8337 patients in the treated cohort and 2779 controls in the untreated cohort. We estimated the incidence rates (IRs) and hazard ratios (HRs) of incident ED in both cohorts through the end of 2012. RESULTS In a total study follow-up of 64,916 person-years, 396 (3.6%) patients developed impotence. The IRs of ED for the treated and untreated cohorts, respectively, were 55.8 (95% confidence interval [CI], 55.6-55.9) and 76.1 (95% CI, 76.0-76.3) per 1000 person-years. Multivariate Cox proportional hazard analysis showed that surgical treatments for OSA patients were associated with a lower risk for ED (adjusted HR, 0.79; 95% CI, 0.64-0.98). Multivariate stratified analysis further verified that significant risk reduction of ED was present in OSA patients without hypertension, diabetes, hyperlipidemia, hyperuricemia, obesity, chronic kidney disease, and chronic liver disease. CONCLUSIONS We found that OSA patients who received surgical treatments were associated with a lower risk for developing ED by 21%.

To examine the associations of different lipid measures and related indices with incident hypertension during a median follow-up of 12.89 years. Fasting levels of total cholesterol (TC), triglycerides (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and related indices (TC/HDL-C and TG/HDL-C) were determined in 7335 Iranian adults (men=3270) free of hypertension, aged 39.0 [standard deviation (SD):13.2] years. Multivariate Cox proportional hazard regression was applied and lipid parameters were considered either as categorical or continuous variables. During follow-up, 2413 (men=11260) participants experienced hypertension. Using the first quartile as reference, significant trends were found between quartiles of TG, HDL-C, TC/HDL-C, and TG/HDL-C in multivariate models; moreover considering these measures as continuous variables, a 1 SD increase in each of these parameters was significantly associated with risk of incident hypertension; the corresponding hazard ratios and confidence intervals were 1.06(1.02-1.10), 0.94(0.89-0.98), 1.04(1.01-1.09), and 1.04(1.01-1.07), respectively. The association between lipid measures and incident hypertension did not change after excluding lipid lowering drug users and those with type 2 diabetes mellitus and were independent of the baseline categories of blood pressure (P for interaction > 0.08). To take into account the nutrition data, a re-analysis on a subgroup (n=1705), showed that a 1-SD increase in TG and TG/HDL-C were associated with incident hypertension, after adjusting for dietary cofounders [1.15(1.08-1.24) and 1.03(1.01-1.04), respectively]. These findings indicate that TG, TG/HDL-C, and TC/HDL-C were independently associated with higher risk while HDL-C was associated with lower risk of incident hypertension.

The aim of this study was to explore the associations between the aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT) and coronary artery lesions (CALs) among patients with Kawasaki disease (KD). Medical records of KD patients presenting to a single center between January 2019 and December 2020 were retrospectively collected and analyzed. Univariate, multivariable-adjusted analyses, subgroup analyses, restricted cubic spline test, and fitted curves were used to evaluate the associations between AST/ALT and CALs. A total of 831 patients were enrolled, of which 201 (24.2%) had CALs on admission and 21 (2.5%) developed CALs de novo after intravenous immunoglobulin (IVIG). Multivariable-adjusted analyses models revealed that a lower AST/ALT was associated with an increased risk of CALs on admission when AST/ALT was a continuous variable (P = 0.007) and when it was a categorical variable (P for trend = 0.004). Each unit increase in AST/ALT was associated with a 22% lower risk of CALs on admission (odds ratio = 0.78, 95% confidence interval 0.65–0.94). A negative linear relationship was noted between AST/ALT and the risk of CALs on admission in both observed and fitted models. However, such associations were not observed in AST/ALT and CALs de novo after IVIG. None of the variables significantly modified the association between AST/ALT and CALs on admission and CALs de novo after IVIG (P > 0.05). Our findings suggested that AST/ALT was a risk factor of CALs, but was not associated with progressive CALs.

Medical treatment and endovascular therapy are widely used for intracranial atherosclerotic stenosis, but the best treatment strategy remains uncertain. The goal of this study was to compare the safety and effectiveness of medical treatment, stenting, and primary balloon angioplasty (PBA). We searched PubMed, MEDLINE, and EMBASE for trials comparing these three treatments for intracranial stenosis up to December 24, 2020. We performed a network meta-analysis with random-effects models. The primary outcome was any stroke or death during a long-term follow-up. Secondary outcomes included ischemic stroke, intracranial hemorrhage, and death. This network meta-analysis included 14 trials with 1520 participants. No significant difference was found between the three groups in the primary outcome, while PBA was probably the best treatment according to the ranking plot. Medical treatment had significantly lower rate of any stroke or death (odds ratio (OR), 0.31; 95% CI, 0.17-0.56), ischemic stroke (OR, 0.43; 95% CI, 0.23-0.81), and intracranial hemorrhage (OR, 0.12; 95% CI, 0.02-0.71) within 30 days than stenting but did not differ from PBA. The ranking plot demonstrated that PBA was also most likely to rank the highest for ischemic stroke during the long-term follow-up and beyond 30 days, although no significant difference was identified. Medical treatment had lower risk of any stroke or death within 30 days than stenting but did not differ from PBA. All the treatments had similar effects on the prevention of long-term stroke, while PBA had the highest probability of being the most effective.

Background and Objectives: Sitagliptin is a dipepidyl peptidase inhibitor (DPP-4i) with gentle antidiabetic effects with a lower risk of hypoglycemia. The association with acute pancreatitis is controversial. The current meta-analysis aimed to assess the relationship of sitagliptin and acute pancreatitis. Methods: The literature in PubMed and Google Scholar was searched for relevant articles published in the last ten years up to September 2021. The keywords sitagliptins, DPP-4i, acute pancreatitis were used with the protean AND or OR. Among the 204 articles retrieved, 24 full-texts were assessed for eligibility and only five studies (Three from the USA, one from Asia, and one from Canada) met the inclusion criteria for the systematic review. The author name, year of publication, country, type of study, number of patients, and the duration of the study were reported. Results: There were five studies. The total number of patients were 729808 with 6459 events. The studies showed no increased rate of acute pancreatitis following sitagliptin use, odd ratio, 0.79, 95% CI, 0.29-2.15, a significant heterogeneity was observer, I2 for heterogeneity=98%, P-value

We aimed to investigate the relationship between overall nutritional status and cancer mortality. A total of 12 262 US adults from six consecutive surveys of the National Health and Nutrition Examination Survey (NHANES 2003–2014) were analyzed. The overall health nutritional biomarkers index (HNBI) score, capturing characteristics of 17 biomarkers was developed to assess the overall nutritional status. The lower the HNBI score, the healthier nutritional status would be. Hazard ratio (HR) and 95% confidence intervals (95% CIs) were calculated by Cox proportional hazards regression models to evaluate the association between the HNBI score and cancer mortality. The lower overall HNBI score was associated with decreased risk of cancer mortality, compared with participants in the 4th quartile of overall HNBI score, the HR (95% CIs) for participants in the 1st quartiles was 0.54 (0.33–0.89) (P-trend = 0.019). Healthier lifestyle habits and not obesity interacted with HNBI score, compared with participants with higher HNBI score and smoking currently/not exercising regularly/obesity, participants with lower HNBI score and not smoking currently/exercising regularly/not obesity were associated with lower risk of cancer mortality, the HR (95% CIs) were 0.43 (0.26–0.73), 0.57 (0.33–0.97), and 0.62 (0.47–0.97), respectively. These significant associations remained among participants who were followed-up more than 2 years. Our findings suggested that healthier overall nutritional status was associated with lower risk of cancer mortality among US adults. Not smoking, exercise regularly and not obesity interacted with overall nutritional status. Adherence to better overall nutritional status, lifestyle habits and optimal weight would prevent premature death from cancer.

AIMS This study aimed to analyse the prevalence of nurse-to-nurse horizontal violence in Chinese hospitals and examine the effects of head nurse's caring and nurse's group behaviour on horizontal violence. BACKGROUND Horizontal violence is a serious global problem affecting the nursing profession, but little is known of the issue in Chinese hospitals. Increasing evidence has showed that leadership and group factors are important in facilitating horizontal violence. Whether the head nurse's caring and group behaviour perceived by nurses has protective effects against horizontal violence remains unclear. METHODS A cross-sectional online-based questionnaire study was performed in seven general hospitals in Hubei Province, China. Data related to the demographic information, horizontal violence, head nurse's caring and group behaviour were collected. Descriptive analyses, chi-squared tests and logistic regression were used for data analysis. RESULTS In total, 1942 valid questionnaires were collected, with a 92.70% effective response rate (1942/2095). Of those, 59.1% (1148/1942) of respondents had experienced horizontal violence at least once in the previous 6 months. Covert negative behaviours were more frequently reported. Compared with the low level, moderate and high levels of the head nurse's caring showed a lower risk of horizontal violence (odds ratio [OR] = 0.400, p

Background Breakthrough coronavirus disease 2019 (COVID-19) may occur in fully vaccinated persons. Methods We assessed the clinical outcomes of breakthrough COVID-19 in fully vaccinated individuals. Results In this cohort of 1395 persons (mean age, 54.3 years; 60% female; median body mass index, 30.7) who developed breakthrough COVID- 19, there were 107 (7.7%) who required hospitalization by day 28. Hospitalization was significantly associated with the number of medical comorbidities. Antispike monoclonal antibody treatment was significantly associated with a lower risk of hospitalization (odds ratio, 0.227; 95% confidence interval, 0.128–0.403; P < .001). The number needed to treat (NNT) to prevent 1 hospitalization was 225 among the lowest risk patient group compared with NNT of 4 among those with highest numbers of medical comorbidity. Conclusions Monoclonal antibody treatment is associated with reduced hospitalization in vaccinated high-risk persons with mild to moderate COVID-19.

Infections are a major cause of morbidity and death in systemic lupus erythematosus (SLE). Perfecting the understanding of contributors to infection burden in SLE is pivotal to improve management and outcomes. This study aims to identify clinical predictors of infection in SLE.We conducted a prospective cohort study at a referral SLE clinic. Infections were identified at each visit and categorized as (a) any type, (b) serious, (c) non-serious, and (d) bacterial. Survival analysis followed by multivariate Cox regression with an estimation of hazard ratios (HR) with 95% confidence intervals (95%CI) was performed.We included 259 patients during a mean follow-up of 23.3 ± 5.7 months. The incidence rate of infection of any type was 59.3 cases per 100 patient-years. Multivariate Cox models showed that (a) prednisolone ≥ 7.5 mg/day (HR = 1.95, 95%CI 1.26-3.03) and female gender (HR = 2.08, 95%CI 1.12-3.86) were associated with higher risk of infection of any type; (b) prednisolone ≥ 10 mg/day was associated with higher (HR = 4.32, 95%CI 1.39-13.40), and antimalarials with lower risk (HR = 0.18, 95%CI 0.06-0.51) of serious infection; (c) female gender (HR = 1.92, 95%CI 1.04-3.57) and prednisolone ≥ 7.5 mg/day (HR = 1.89, 95%CI 1.21-2.96) were associated with higher risk of non-serious infection; (d) antimalarials were associated with lower (HR = 0.49, 95%CI 0.26-0.93) and female gender (HR = 5.12; 95%CI 1.62-16.18) with higher risk of bacterial infection.The risk of infection was higher in females in this young, well-controlled, low-comorbidity SLE cohort. Antimalarials were associated with lower and prednisolone ≥ 7.5 mg with higher risk of infection. Key Points • Lupus patients treated with prednisolone ≥ 7.5 mg/day were 89% more likely to present infections. • Lupus patients receiving prednisolone ≥ 10 mg/day were four times more likely to present serious infections. • Lupus patients receiving antimalarials were 82% less likely to present serious infections.

Gay and bisexual men (GBM) who use pre-exposure prophylaxis (PrEP) are at increased risk of sexually transmitted infections (STIs) compared to those who don't use PrEP. Since the implementation of PrEP in Australia, it is possible that attitudes towards STIs have shifted in line with changes in risk and transmission dynamics in the context of increased screening. As the extent to which GBM utilise STI prevention strategies likely depends on their attitudes towards STIs and STI prevention, the aims of this study were to use latent class analysis (LCA) to classify GBM using PrEP on the basis of their attitudes towards STIs and reported risk behaviours, and examine how these categorisations relate to risk of STI acquisition. 1225 GBM who were previously enrolled in a PrEP implementation study (The PrEPX Study) completed a survey focused on sexual behaviours and attitudes towards STIs 1 year post-study follow-up. Data on chlamydia, gonorrhoea and syphilis testing and positivity were available through a sentinel network of participating study clinics. Using LCA, participants were allocated into four classes; Class 1, "Some concern and lowest risk"; Class 2, "Low concern and lower risk"; Class 3, " High concern and higher risk"; and Class 4, "Low concern and highest risk". The majority (78%) of participants were classified into Class 3 or Class 4, two groups which were distinguished by highly disparate attitudes towards STIs but with a similar proportion of participants diagnosed with a bacterial STI in the last 12 months (48% and 57%, respectively). Findings suggest that attitudes towards STIs among GBM using PrEP in Australia vary considerably, and this will likely influence their receptivity to different STI prevention strategies.