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Non-Hispanic Black women remain at increased risk for adverse birth outcomes, yet Black immigrant women are at lower risk than their US-born counterparts. This study examines whether neighborhood context contributes to the nativity advantage in preterm birth (PTB

OBJECTIVE Studies on the association of oral hygiene indicators with cardiovascular disease in hypertensive patients have been lacking. Oral hygiene is directly or indirectly associated with systemic inflammation, one of the essential mechanisms of cardiovascular disease. Therefore, we hypothesized that oral hygiene would be related to the risk of cardiovascular diseases in hypertensive patients. METHODS We included 52 677 hypertensive participants who completed oral health checkups from the Korean National Health Insurance Service-National Health Screening Cohort between 2003 and 2004. We collected data on periodontitis diagnosis and treatment history, number of teeth loss, number of dental caries, and frequency of tooth brushing from medical records of health claims and oral health examination. The primary outcome was defined as composite outcomes of stroke and myocardial infarction. Follow-up was done until the date of primary outcome, or 31 December 2015. RESULTS During the 11.26 ± 2.39 years (mean ± standard deviation) of the study follow-up, 3292 participants developed primary outcomes [stroke (n = 2430), myocardial infarction (n = 862)]. In multivariable Cox regression analyses, participants with dental caries (≥ 5) were independently associated with occurrence of a primary outcome [adjusted hazard ratio: 1.37; 95% confidence interval (CI):1.10-1.72; P = 0.006]. Frequent tooth brushing (≥ 2 times/day) was significantly related to lower risk of primary outcomes (adjusted hazard ratio: 0.88; 95% CI: 0.81-0.96; P = 0.002). CONCLUSION Our study demonstrated that multiple dental caries were related to the risk of cardiovascular diseases in hypertensive patients. Better oral hygiene may attenuate the risk of cardiovascular events in hypertensive patients.

Low-dose rivaroxaban is often given to patients with atrial fibrillation (AF) around the world, but the rationale for its use remains unclear. We aimed to compare the efficacy and safety of standard- or low-dose rivaroxaban in patients with AF through systematic review of literature with meta-analysis.We searched PubMed, Web of Science, EMBASE, Clinical Trials.gov, the Cochrane Library, and Bayer trial website from inception of each database until June 2020. Randomized controlled trials (RCTs) and cohort studies were included in the meta-analysis. A random-effects model was employed to calculate the pooled effect estimates.Two RCTs and 17 cohort studies were included in the qualitative analysis. Indirect comparison of RCTs showed no significant difference between the two rivaroxaban dosages in risk of efficacy or safety outcomes (p 0.05). Indirect comparison of cohort studies showed a lower risk of MACE among Caucasians in standard-dose group (HR 0.779; 95% CI 0.687-0.884; p 0.001). Bleeding outcomes did not differ significantly between the two dosage regimens in Asian or Caucasian populations, except that the standard dose was associated with higher risk of major bleeding among elderly Caucasian patients (HR 1.329; 95% CI 1.141-1.547; p 0.001). The quality of evidence was rated ranging from very low to low for all the efficacy and safety outcomes.In Caucasians with AF, standard-dose rivaroxaban may prevent MACE significantly better than low-dose treatment. Further studies in Asians are needed to verify the advantages of the standard dose.

Background The COVID‐19 pandemic has overrun hospital systems while exacerbating economic hardship and food insecurity on a global scale. In an effort to understand how early action to find and control the virus is associated with cumulative outcomes, we explored how country‐level testing capacity affects later COVID‐19 mortality. Methods We used the Our World in Data database to explore testing and mortality records in 27 countries from December 31, 2019, to September 30, 2020; we applied Cox proportional hazards regression to determine the relationship between early COVID‐19 testing capacity (cumulative tests per case) and later COVID‐19 mortality (time to specified mortality thresholds), adjusting for country‐level confounders, including median age, GDP, hospital bed capacity, population density, and nonpharmaceutical interventions. Results Higher early testing implementation, as indicated by more cumulative tests per case when mortality was still low, was associated with a lower risk for higher per capita deaths. A sample finding indicated that a higher cumulative number of tests administered per case at the time of six deaths per million persons was associated with a lower risk of reaching 15 deaths per million persons, after adjustment for all confounders (HR = 0.909; P = 0.0001). Conclusions Countries that developed stronger COVID‐19 testing capacity at early timepoints, as measured by tests administered per case identified, experienced a slower increase of deaths per capita. Thus, this study operationalizes the value of testing and provides empirical evidence that stronger testing capacity at early timepoints is associated with reduced mortality and improved pandemic control.

Post-transplant diabetes mellitus is associated with long-term immunosuppression and weight gain, and is related to an increased risk of cardiovascular disease, accelerated loss of graft and increased mortality. There is an absence of strong evidence-based dietary guidelines for the prevention and management of post-transplant diabetes mellitus in kidney transplant recipients. The aim of this study was to systematically review all dietary evidence for kidney transplant recipients on clinical outcomes relating to diabetes, patient-reported outcomes and economic outcomes. A comprehensive literature search was conducted in August 2020 using the databases Medline, Embase, CENTRAL and CINAHL. Studies were critically appraised using Cochrane risk of bias tools and GRADE. A total of 12 studies and 1928 participants were included. Four papers focused on diet and exercise, one paper on diet only, two papers on magnesium supplementation, one paper on magnesium and fibre intake, two papers on Mediterranean diet, one paper on marine n-3 fatty acid supplementation and one paper on fruit and vegetable intake. There were no significant effects on outcomes relating to dietary counselling, magnesium supplementation, magnesium and fibre intake or marine n-3 fatty acid supplementation. Low-quality evidence supports the Mediterranean diet in reducing the risk of post-transplant diabetes mellitus and fasting plasma glucose levels. Low-quality evidence suggests vegetable intake being associated with a lower risk of post-transplant diabetes mellitus. This review demonstrates limited evidence for dietary interventions in the prevention and management of diabetes in post-kidney transplantation. The findings suggest that further high-quality research with robust study designs is required.

Since patients with acute myeloid leukemia (AML) in the real world have a much different clinical picture than patients recruited in the clinical trials, obtaining real-world evidence of medication adoption is important for therapeutic efficiency and safety. This study used three population-based data in Taiwan, the National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry, between 2001 and 2015, to investigate the effect of conventional chemotherapy (CCT) versus non-conventional chemotherapy (NCCT) on the overall survival (OS) of patients with AML (n = 7,763). Cox proportional hazard regression was used to estimate the hazard ratios (HR) of different treatments on the risk of mortality. To reduce the potential selection bias, we used the inverse probability of treatment weighting based on the propensity score to balance the baseline characteristics between patients receiving CCT and NCCT. The median survival time for CCT and NCCT arms was 10.2 months (95% confidence interval (95% CI): 9.7-10.9) and 4.1 months (95% CI: 3.8-4.5), respectively. Compared to the patients received NCCT, those receiving CCT had a lower risk of mortality (HR 0.63 (95% CI: 0.59-0.67, P

Background and objective Real-life data about the use of dabigatran in patients with non-valvular atrial fibrillation are warranted. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of dabigatran, globally and stratified by dose (110/150 mg twice daily), vs vitamin K antagonists in non-Asian patients with non-valvular atrial fibrillation from "real-world" studies. Methods A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement) statement. The ROBINS-I tool was used to assess bias risk. MEDLINE and EMBASE, from inception up to May 2021, using appropriate controlled vocabulary and free search terms, were searched. RESULTS: A total of 34 studies, corresponding to 37 articles involving 1,600,722 participants (1,154,283 exposed to vitamin K antagonists and 446,439 to dabigatran) were eligible for this review. Dabigatran 150 mg reduced the risk of ischemic stroke compared with vitamin K antagonists, with a 14% risk reduction (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.74-0.98). Globally, dabigatran reduced the risk of all-cause mortality compared with vitamin K antagonists (HR 0.76, 95% CI 0.69-0.84), with a greater effect observed with dabigatran 150 mg (HR 0.65, 95% CI 0.58-0.73). There was a trend towards a lower risk of myocardial infarction with dabigatran 150 mg (HR 0.86, 95% CI 0.71-1.04). Regarding the primary safety outcomes, dabigatran (either at a dose of 150 mg or 110 mg) reduced the risk of major bleeding compared with vitamin K antagonists (HR 0.77, 95% CI 0.70-0.83), as well as the risk of intracranial bleeding (HR 0.44, 95% CI 0.39-0.50) and fatal bleeding (HR 0.76, 95% CI 0.60-0.95), but with a slight increase in gastrointestinal bleeding risk (HR 1.16, 95% CI 1.08-1.26). Conclusions Dabigatran has a favorable impact on effectiveness and safety outcomes compared with vitamin K antagonists in real-world populations.

Famotidine has been considered to be a potential treatment for COVID-19 but the current data is conflicting. This retrospective study was conducted by utilizing data of 9,565 COVID-19 hospitalized patients. Patients treated with and without famotidine were matched by propensity score using 1:1 matching scheme. 1,593 patients (16.7%) received famotidine. In-hospital mortality was similar in patients treated with and without famotidine in the propensity matched cohorts (28.3% versus 28.2%, P=0.97), which remains similar irrespective of severity or concomitant treatment by steroids. Famotidine treatment was not associated with a lower risk of in-hospital mortality of COVID-19 patients. This article is protected by copyright. All rights reserved.

OBJECTIVE This study was undertaken to investigate whether high-sensitivity cardiac troponin T (hs-cTnT) is associated with major adverse cardiovascular events (MACE) in patients with minor stroke or transient ischemic attack (TIA), and whether this association differs after risk stratification based on the Age, Blood Pressure, Clinical Features, Duration of Symptoms, Diabetes (ABCD2 ) score. METHODS INSPiRE-TMS was a randomized controlled trial allocating patients with minor stroke or TIA to an intensified support program or conventional care. In this post hoc analysis, participants were categorized using hs-cTnT levels (5th generation; Roche Diagnostics, Manheim, Germany; 99th percentile upper reference limit [URL] = 14ng/l). Vascular risk was stratified using the ABCD2 score (lower risk = 0-5 vs higher risk = 6-7). Cox proportional hazard regression was performed using covariate adjustment and propensity score matching (PSM) for the association between hs-cTnT and MACE (stroke/nonfatal coronary event/vascular death). RESULTS Among 889 patients (mean age = 70 years, 37% female), MACE occurred in 153 patients (17.2%) during a mean follow-up of 3.2 years. hs-cTnT was associated with MACE (9.3%/yr, >URL vs 4.4%/yr, ≤URL, adjusted hazard ratio [HR] = 1.63 [95% confidence interval (CI) = 1.13-2.35], adjusted HR [Q4 vs Q1 ] = 2.57 [95% CI = 1.35-4.97], adjusted HR [log-transformed] = 2.31 [95% CI = 1.37-3.89]). This association remained after PSM (adjusted HR = 1.76 [95% CI = 1.14-2.72]). There was a significant interaction between hs-cTnT and ABCD2 category for MACE occurrence (pinteraction = 0.04). In the lower risk category, MACE rate was 9.5%/yr in patients with hs-cTnT > URL, which was higher than in those ≤URL (3.8%/yr) and similar to the overall rate in the higher risk category. INTERPRETATION hs-cTnT levels are associated with incident MACE within 3 years after minor stroke or TIA and may help to identify high-risk individuals otherwise deemed at lower risk based on the ABCD2 score. If confirmed in independent validation studies, this might warrant intensified secondary prevention measures and cardiac diagnostics in stroke patients with elevated hs-cTnT. ANN NEUROL 2021;90:901-912.

Fluid therapy plays a critical role in the management of acute pancreatitis. Normal saline (NS) is commonly used in these patients. However, Lactate Ringer’s (LR) has also been shown to be useful for this condition. To assess the effect of LR compared to NS in patients with acute pancreatitis. We searched in three electronic databases from inception to December 2020 for randomized controlled trials (RCTs). Outcomes were mortality, intensive care unit (ICU) admission, hospital stay, and Systemic Inflammatory Response Syndrome (SIRS) at 24, 48, and 72 h. The risk of bias was assessed using the Risk of Bias 2.0 tool. All meta-analyses were performed using a random-effects model. Four RCTs comprising 248 patients were included. The mean age ranged from 42.3 to 63.8 years and 49% of patients were men. Patients treated with LR had similar risk of mortality (risk ratio [RR], 0.53; 95% confidence interval [CI], 0.09–3.00) and SIRS at 24 h (RR, 0.69; 95% CI, 0.32–1.51), 48 h (RR, 0.80; 95% CI, 0.46–1.41), and 72 h (RR, 0.68; 95% CI, 0.37–1.25) compared to NS. LR had significantly lower hospital stay (mean difference, − 1.10; 95% CI, − 1.92 to − 0.28) and lower risk of ICU admission (RR, 0.42; 95% CI, 0.20–0.89) compared to NS. The risk of bias was low in nearly all RCTs. No differences were found in the mortality and SIRS at 24, 48, and 72 h in patients treated with LR and NS. In contrast, patients who received LR had a lower risk of ICU admission and lower hospital stay than NS.

Background: Risk of relapse within the first months after alcohol use disorder (AUD) interventions is substantial among older adults. For this vulnerable group, little information exists on how this risk is associated with residual DSM-5 AUD symptoms after treatment. Aims: To investigate among older adults who received short-term treatment for DSM-5 AUD (1) the prediction of drinking behaviors and quality of life 12 months after treatment initiation by 6-month DSM-5 AUD symptoms, AUD severity, and AUD remission, and (2) whether these DSM-5 AUD indicators provide prognostic information beyond that gained from 6-month alcohol use (AU) status. Methods: The international multicenter RCT “ELDERLY-Study” enrolled adults aged 60+ with DSM-5 AUD. We used data from the subsample of 323 German and Danish participants with complete DSM-5 AUD criterion information 6 months after treatment initiation (61% male; mean age = 65.5 years). AU was assessed with Form 90, DSM-5 AUD with the M.I.N.I., and quality of life with the WHOQOL-BREF. Generalized linear models were applied to investigate the associations between 6-month AUD indicators and 12-month AU and quality of life. Results: Independent of AU at 6 months, having 1 (vs. no) residual AUD symptom at 6 months predicted a 12-month “slip,” defined as exceeding a blood alcohol concentration of 0.05% at least once during that time (OR: 3.7, 95% CI: 1.5 to 9.0), heavy episodic drinking, and hazardous use (p

Purpose We lack knowledge on whether the advice of “being physically active” should be the same for prevention and rehabilitation of low back pain (LBP). Sickness absence is a key outcome for LBP prevention and rehabilitation. We investigated the associations between physical activity and long-term sickness absence (LTSA) among employees with and without LBP. Methods Between 2011 and 2013, 925 Danish employees wore a Actigraph GTX3 accelerometer for 1–5 workdays to measure physical activity and reported LBP in past 7 days. Employees were followed for 4 years to determine their first register-based LTSA event (≥ 6 consecutive weeks). Results Among employees with LBP, increasing moderate-to-vigorous-intensity physical activity at work by 20 min and decreasing the remaining behaviors at work (ie., sitting, standing and light-intensity activity) by 20 min was associated with 38% (95% CI 17%; 63%) higher LTSA risk. Increasing light-intensity activity at work by 20 min and decreasing 20 min from the remaining behaviors was associated with 18% (95% CI 4%; 30%) lower risk. During leisure, increasing moderate-to-vigorous-intensity activity by 20 min or standing by 40 min was associated with 26% (95% CI 3%; 43%) lower and 37% (95% CI 0%; 87%) higher risk, respectively. Among employees without LBP, we found no such associations. Conclusions The physical activity advice ought to be different for LBP prevention and rehabilitation to reduce LTSA risk, and specified by domain and activity intensity. At work, employees with LBP should be advised to spend time on light-intensity physical activity and limit their time on moderate-to-vigorous-intensity physical activity. During leisure, employees should spend time on moderate-to-vigorous-intensity physical activity.

In the MYF2001 trial, treatment of Janus kinase (JAK) inhibitor-relapsed/refractory intermediate-2 or high-risk myelofibrosis (MF) with imetelstat 9.4 mg/kg every 3 weeks demonstrated encouraging median overall survival of 29.9 months. To provide historical context, external real-world data (RWD) were collected from a study of 96 patients who had discontinued ruxolitinib and were subsequently treated with best available therapy (BAT) at Moffitt Cancer Center. A closely matched cohort was identified using the MYF2001 eligibility criteria, including patients with MF who had discontinued ruxolitinib due to lack or loss of response. Overall survival was measured from time of JAK inhibitor discontinuation to death or censored at last follow-up. To improve comparability, propensity score weighting approaches using average treatment effect for overlap population (ATO) and stabilized inverse probability treatment weighting (sIPTW) were used for 10 critical baseline covariates. Fifty-seven patients treated with imetelstat 9.4 mg/kg from MYF2001 and 38 patients treated with BAT from RWD were analyzed with improved balanced baseline covariates after propensity score adjustment, showing significantly lower risk of death with imetelstat compared with BAT (hazard ratio: 0.35; p = 0.0019). With sIPTW, results were similar. Results of sensitivity analyses were consistent with the primary analysis. In conclusion, treatment with imetelstat was associated with longer overall survival compared to BAT (30 vs 12 months, respectively) in closely matched patients with MF after JAK inhibitor failure, warranting further evaluation of imetelstat in this poor-prognosis patient population.

Objectives: To estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA. Methods: We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models. Results: A total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status. Conclusions: Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure. Methods We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models. Results A total of 3169 TNFi treatment courses (RA/ PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status. Conclusions Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.

This study aims to evaluate risk factors associated with treatment failure and the antibiotics prescribed by primary care physicians in a large patient cohort treated for pneumonia in the community. A retrospective cohort study based on the databases of Maccabi Healthcare Services that provide healthcare to a quarter of the Israeli population. Included patients were > 12 years and diagnosed with pneumonia in the outpatient setting. Cohort 1 included patients with community-acquired pneumonia (CAP), whereas cohort 2 included patients with a documented pneumonia diagnosis following hospital discharge. Treatment failure (TF) was defined as either the use of a second line antibiotic OR hospital admission within 3–14 days OR death within 30 days of diagnosis. Risk factors for TF in the study cohorts were analyzed using multivariable logistic regression. During the study period, 148,376 patients were included in cohort 1 and 3,869 patients in cohort 2, with mean ages of 46.5 ± 20.3 and 63.8 ± 19.5 years, respectively. The most commonly used antibiotics were cephalosporins (36%) and macrolides (35.5%). TF occurred in 12% of cohort 1 and was associated with older age, comorbid conditions, use of non-respiratory fluoroquinolones, and penicillin. Atypical coverage (either macrolides or tetracyclines) was associated with a lower risk of failure. Among cohort 2, TF was higher (16.4%, p

Background Frailty is a geriatric syndrome that entails high risk of hospitalization, disability, and death. While adherence to Mediterranean diet has been associated with lower risk of frailty, the joint effect of diet and lifestyle is uncertain. This study examined the association between a Mediterranean lifestyle (diet, customs, and traditions) and frailty incidence in older adults. Methods We analyzed data from 1 880 individuals aged ≥ 60 from the prospective Seniors-ENRICA-1 cohort. Adherence to the Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (higher scores representing better adherence), divided into 3 blocks: (1) “Mediterranean food consumption,” (2) “Mediterranean dietary habits” (practices around meals),” and (3) “Physical activity, rest, social habits and conviviality.” Frailty was ascertained as the presence of ≥ 3 of the 5 Fried criteria: (a) Exhaustion; (b) Muscle weakness; (c) Low physical activity; (d) Slow walking speed; and (e) Unintentional weight loss. Main statistical analyses were performed using logistic regression models, adjusting for the main confounders. Results After a 3.3-year follow-up, 136 incident frailty cases were ascertained. Compared with participants in the lowest tertile of the MEDLIFE score, the OR (95% CI) for frailty was 0.88 (0.58–1.34) for the second tertile, and 0.38 (0.21–0.69) for the third tertile (p-trend = .003). Blocks 1 and 3 of the MEDLIFE score were independently associated with lower frailty risk. Most items within these blocks showed a tendency to reduced frailty. Conclusions Higher adherence to a Mediterranean lifestyle was associated with lower risk of frailty.

We assessed the clinical effectiveness of coronary artery bypass grafting (CABG) in comparison with that of percutaneous coronary intervention (PCI) in octogenarians with triple-vessel disease (TVD) or left main coronary artery (LMCA) disease. From the CREDO-Kyoto registry cohort-2, 527 patients, who were ≥ 80 years of age and underwent the first coronary revascularization for TVD or LMCA disease, were divided into the CABG group (N = 151) and the PCI group (N = 376). The median and interquartile range of patient’s age was 82 (81–84) in the CABG group and 83 (81–85) in the PCI group (P = 0.10). Patients > = 85 years of age accounted for 19% and 31% in the CABG and PCI groups, respectively (P = 0.01). The cumulative 5-year incidence of all-cause death was similar between CABG and PCI groups (35.8% vs. 42.9%, log-rank P = 0.18), while CABG showed a lower rate of the composite of cardiac death/MI than PCI (21.7% vs. 33.9%, log-rank P = 0.005). After adjusting for confounders, the lower risk of CABG relative to PCI was significant for all-cause death (HR 0.61, 95% CI 0.43–0.86, P = 0.005), any coronary revascularization (HR 0.25, 95% CI 0.14–0.43, P

Introduction. In clinical practice, it is difficult to define the prognosis of patients with acute encephalopathy; a syndrome characterized by cognitive dysfunction and altered sensorium. Discharges with triphasic morphology (DTM) are an electroencephalographic pattern that might be useful to establish the risk of death. The aim of this study was to define the prognostic value of DTM regarding mortality in patients with acute encephalopathy. Methods. We conducted an observational retrospective cohort study including patients with acute encephalopathy with and without DTM paired by age and gender in a 1:2 ratio. We calculated the odds ratio (OR) to determine the association between DTM and mortality. In addition, we calculated sensibility, specificity, and predictive values. Results. We included 72 patients, 24 with DTM and 48 without DTM. Mortality was higher in patients with DTM (41.6% vs 14.5%, P = .01). Factors associated with a higher risk of death were DTM (OR = 4.1, 95% confidence interval [CI] 1.3-13, P = .01) and sequential organ failure assessment score (OR = 1.3, 95% CI 1.04-1.67, P = .02). A higher Glasgow coma scale score was associated with a lower risk of death (OR = 0.65, 95% CI 0.51-0.83, P = .001). The sensibility and specificity of DTM were 59% and 75%, respectively. Positive and negative likelihood ratios were 2.36 and 0.55. Discussion. Our results revealed high mortality in patients with acute encephalopathy and DTM. This electroencephalographic pattern was associated with 4 times higher risk of death. However, its usefulness for predicting death was limited.

Background Deteriorated skeletal muscle condition, including sarcopenia, is a risk factor for disability in older adults. Promoting physical activity is a useful treatment for sarcopenia. However, optimal intensity of physical activity according to sarcopenia characteristics is unclear. Methods This longitudinal cohort study enrolled 2149 community‐dwelling older adults (women 55.7%, mean age: 75.5 ± 4.0 years). Five‐year disability incidence defined by Japanese long‐term care insurance certification and accelerometer‐measured physical activities (light‐intensity physical activity [LPA] and moderate‐to‐vigorous intensity physical activity [MVPA]), which were adjusted for potential confounders, was analysed using cox‐proportional hazard model stratified by sarcopenia characteristics based on the diagnostic algorithm by the Asian working group for sarcopenia (robust, low physical function, low muscle mass, and sarcopenia). The sarcopenia group was defined as low muscle mass and low physical function (weakness and/or slowness). The low muscle mass and low physical function groups were each defined by these characteristics alone. Muscle mass was analysed via bioelectrical impedance analysis. Each intensity of physical activity times was divided by median values. Results The disability incidence rate was 15.4%, excluding those who could not be followed up. Mean LPA times were 43.8 ± 18.0, 45.6 ± 17.5, 45.4 ± 16.6, 40.8 ± 18.6, and 41.4 ± 18.5 min/day and MVPA times were 24.6 ± 17.6, 26.3 ± 18.3, 27.2 ± 17.3, 21.6 ± 16.3, and 21.5 ± 16.4 min/day in all participants, the robust, low muscle mass, low physical function, and sarcopenia groups, respectively. For all participants, higher MVPA was associated with disability incidence [hazard ratios (HR), 0.63; 95% confidence interval (95% CI), 0.49–0.81; P

Diabetes is increasing at an alarming rate worldwide, but little is known about its risk factors in Morocco. This study aimed to investigate the prevalence and risk factors of diabetes. Data from the national survey on risk factors for non-communicable diseases conducted in 2017–2018 was used. Data collection was based on the WHO STEPwise approach to surveillance (STEPS). A total of 1522 adults aged 18 years and older were included in our analysis. The overall prevalence of prediabetes and diabetes was 12.8% and 17.9%, respectively. Women had a significantly higher likelihood of diabetes than men (p = 0.049). Adults aged 45 years or older were more likely than the 18–29-year-old group to have prediabetes (p

It has not been well studied whether transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) have lower risk of ischemic stroke (IS) in those with prior history of IS. From the Nationwide Readmission Database from October 2015 to November 2017, TAVI and SAVR above age 50 were identified with the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System codes. Transapical TAVI and SAVR with concomitant bypass, mitral, or tricuspid surgery were excluded. The primary outcome was in-hospital IS. A total of 92,435 TAVI (13,292 with prior stroke) and 68,651 SAVR (5,365 with prior stroke) were identified. In-hospital IS was significantly lower in TAVI compared with SAVR (3.7% vs 8.0%, adjusted odds ratio 0.65, 95% confidence interval 0.47 to 0.89, p0.01) with prior stroke whereas it was similar between TAVI and SAVR (1.7% vs 2.1%, adjusted odds ratio 0.97, 95% confidence interval 0.78 to 1.19, p = 0.75) in those without prior stroke (P

Background Nasopharyngeal (NP) colonization with Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) is common in children, and may evolve as the source of invasive infections. In Korea, the pneumococcal conjugate vaccines (PCVs) were introduced >10 years ago, enabling the authors to study the effect of the vaccine in preventing carriage. Methods NP swabs were taken and a household survey was conducted at daycare centres located in different regions of Korea in 2014 and 2019. Pneumococcal serotypes were identified using the Quellung method and sequencing. NTHi were identified based on pilA and bexA genes. Results In total, 1460 NP swabs were obtained with pneumococcal carriage rates of 36.4–42.1% and NTHi carriage rates of 36.5–26.7%. Among children carrying pneumococci, a significant increase was seen in serotype 23A between 2014 and 2019 (from 12.6% to 22.0%; P=0.005). Children who had received PCV were at lower risk of vaccine-type carriage (2.9% vs 0.8%; P=0.005). Conclusions Between 2014 and 2019, the proportion of children carrying serotype 23A increased significantly, while the carriage rate of NTHi decreased. Continuous surveillance is needed to assess the long-term effects of the PCVs on carriage dynamics of pneumococcus and NTHi.

Jipang Zhan, Xuhua Tang, Fang Wang, Jiande Han Department of Dermatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Jiande HanDepartment of Dermatology, the First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, Guangdong, 510080, People’s Republic of ChinaTel +86-138-0274-3924Fax +86-020-8293-8840Email hanjd@mail.sysu.edu.cnPurpose: Unlike eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the relationship between eicosatetraenoic acid (ETA) and psoriasis remains unclear. Therefore, We performed a cross-sectional study in the general American population to investigate the association between daily dietary ETA, EPA, and DHA intake and the risk of psoriasis.Participants and Methods: This study applied data from the National Health and Nutrition Examination Survey (NHANES) 2003– 2006 and 2009– 2014. Dietary n3 polyunsaturated fatty acids (PUFA) were calculated based on two 24-hour dietary recall interviews. We defined psoriasis by responding to the question “Have you ever been told by a doctor or other health care professional that you had psoriasis?”. Multivariable logistic regression analysis, trend tests, subgroup analysis, and interaction tests were used to evaluate the associations of ETA, EPA, and DHA intake with the risk of psoriasis, respectively.Results: A total of 15,733 participants were included in this study. In our optimal multivariate-adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of psoriasis were 0.30 (0.12, 0.88), 1.92 (0.78, 4.74), 1.28 (0.72, 2.27) for daily dietary ETA, EPA, and DHA intake, respectively. Trend tests showed a dose–effect relationship between daily dietary ETA intake and the lower risk of psoriasis. Subgroup analysis and tests for interaction showed that the association was stable in different subgroups.Conclusion: Our study revealed that there might be a dose–effect association of daily dietary ETA intake with the lower risk of psoriasis in American adults.Keywords: psoriasis, diet, eicosatetraenoic acid, long-chain n3 polyunsaturated fatty acid, NHANES

Background Traumatic brain injury (TBI) results in an elaborate systemic cascade of secondary injury elicited in part by an intrinsic catecholamine response, which ultimately leads to changes in inflammation and coagulopathy. Attenuation of this catecholamine response with agents such as propranolol confers a survival advantage. The related impact of propranolol on venous thromboembolism (VTE) after TBI is largely unknown. Study Design A single institution retrospective review was conducted of all TBI patients requiring intensive care unit (ICU) admission with an injury severity scale (ISS) ≥ 25 from January 2013 to May 2015. Patients who received at least one dose of propranolol within 24 hours of admission (PROP) were compared to patients who did not receive any doses of propranolol (NPROP) during their hospitalization. Results Of the 131 patients analyzed, 31 (23.7%) patients received propranolol. The PROP cohort was more severely injured overall (ISS 29 vs 26.5, P = .02). While unadjusted VTE rates were similar (16.1% vs 19.0%, P = .72), the adjusted VTE rate was lower in the PROP cohort (AOR 0.20 (95% CI 0.04-0.97), adjusted P-value < .05). Conclusion Propranolol use in TBI patients who have sustained critical injuries may mitigate the risk of VTE. The mechanism by which this outcome is achieved requires further investigation.

There is evidence that regular physical activity (PA) is associated with lower risk of non-communicable diseases, increased health status and the overall quality of life. Therefore, it is important to understand key factors that can influence PA levels and behaviours. There are several studies that investigated the determinants of PA in adults, however, they did not include environmental, behavioural, and sociodemographic factors to determine objectively measured PA behaviour. The aim of this study was to assess the association between objectively measured PA intensity of walking and sociodemographic, environmental and behavioural factors and investigate the most significant factors associated with the intensity of walking. The study included 125 randomly selected participants in Kaunas, Lithuania. Participants filled out a formalized questionnaire about sociodemographic, health-related, behavioural, and environmental factors. The intensity of PA of walking was measured using accelerometer and GPS (Global Positioning System) sensors. The results showed that the highest intensity of PA was found among the youngest age group, women, adults with normal weight and those with the lowest prevalence of chronic diseases including hypertension. In the multivariate regression models, age, noise level, and walking time remained significant covariates of the intensity of PA. Our study adds evidence on the separate and combined effects of sociodemographic, environmental, and behavioural factors on the intensity of PA during walking among adults in an urban environment using GPS and accelerometer sensors. Future studies should focus on additional factors influencing PA intensity that were not investigated in this study and explore other PAs.

BackgroundEvidence of possible beneficial effects of dietary diabetes risk reduction score (DDRRS) on reducing the risk of various chronic diseases such as metabolic syndrome (MetS) are limited. This is a prospective, population-based cohort study, which aimed to investigate the relationship of the DDRRS and its components with MetS incident in Iranian adults.MethodsIndividuals without MetS (n=3561) were recruited from participants of the Tehran Lipid and Glucose Study (2009-2011) and followed for a mean of 6.01 years. A validated food frequency questionnaire was used to determine the DDRRS using based on eight components, including higher intakes of cereal fiber, nuts, coffee, and polyunsaturated: saturated fat ratio and lower intakes of red or processed meats, sugar-sweetened beverages, trans fatty acids, and low glycemic index. We used the multivariable logistic regression analysis to determine the odds ratio (ORs) and 95 % confidence interval (CI) of MetS across the tertiles of DDRRS.ResultsThe mean (SD) age of individuals was 38.1(12.6) years at baseline. Median (25-75 interquartile range) DDRRS for all participants was 20(18-22). During the study follow-up, 682(19.1 %) new cases of MetS were reported. Based on the age and sex-adjusted model, participants in highest tertile of DDRRS had lower risk of MetS in compared with the lowest one (OR=0.64;95 %CI:0.52-0.79, P for trend=0.001). In the multivariable adjusted model, after adjustment for all possible confounding variables, the risk of MetS is decreased across tertiles of DDRRS (OR=0.60;95 %CI:0.48-0.75, P for trend=0.001). Also, higher scores of some DDRRS components including red and processed meat, sugar sweetened beverages, and coffee were related to decreased incidence of MetS.ConclusionsThe results of this study revealed that greater adherence to DDRRS can be associated with decreased risk of MetS in Iranian adult.

Previous studies have shown that ticagrelor reduced risk of pneumonia in patients with acute coronary syndrome (ACS) compared to clopidogrel, however, its effect in patients with non-ACS cardiovascular diseases remains uncertain. The aim was to investigate the effect of ticagrelor on pneumonia and pneumonia-specific death compared to clopidogrel in non-ACS patients in Hong Kong. This was a population-based cohort study. We included consecutive patients using ticagrelor or clopidogrel admitted for non-ACS conditions in Hong Kong public hospitals from March 2012 to September 2019. Patients using both drugs were excluded. The outcomes of interest were incident pneumonia, all-cause death, and pneumonia-specific death. Multivariable survival analysis models were used to estimate the effects [hazard ratio (HR) and 95% confidence interval (CI)]. Propensity score matching, adjustment and weighting were performed as sensitivity analyses. In total, 90,154 patients were included (mean age 70.66 years, males 61.7%). The majority of them (97.2%) used clopidogrel. Ticagrelor was associated with a lower risk of incident pneumonia [0.59 (0.46–0.75)], all-cause death [0.83 (0.73–0.93)] and pneumonia-specific death [0.49 (0.36–0.67)]. Sensitivity analyses yielded similar results. Ticagrelor was associated with lower risk of all-cause death, pneumonia-specific death, and incident pneumonia in patients with non-ACS cardiovascular conditions, consistent with previous evidence in patients with ACS. This additional effect of anti-pneumonia should be considered when choosing a proper P2Y12 inhibitor for patients with high risk of pneumonia.

Titanium associated risks have led to interest in resorbable hardware for open reduction and internal fixation (ORIF) of pediatric facial fractures. This study aims to systematically review and compare the outcomes of titanium/resorbable hardware used for ORIF of upper/midfacial fractures to determine which hardware carries a higher complication rate in the pediatric patient.Studies published between 1990 and 2020 on the ORIF of pediatric upper/midfacial fractures were systematically reviewed. A retrospective institutional review was also conducted, and both arms were compiled for final analysis. The primary predictor value was the type of hardware used and the primary outcome was the presence of a complication. Fisher's exact test and 2-proportion 2-tailed z-test calculations were used to determine statistical significance, which was defined as a P value.05. The low quality of published evidence precluded meta-analysis.Systematic review of 23 studies identified 659 patients, and 77 patients were identified in the institutional review. A total of 736 patients (299 resorbable, 437 titanium) were included in the final analysis. Total complication rate was 22.8%. The titanium group had a higher complication rate (27 vs 16.7%; P.01), and more often underwent elective hardware removal (87.3 vs 0%, P.01). In each hardware subgroup, the incidence of complications was analyzed by fracture site. In the titanium group, complication incidence was higher when treating maxillary fractures (32.8 vs 22.9%, P = .03). When comparing the 2 hardware groups by fracture site, maxillary fractures had a higher rate of complications when treated by titanium hardware compared with resorbable hardware (32.8 vs 18%, P.01).Upper/midfacial pediatric fractures requiring ORIF, especially maxillary fractures, may be best treated with resorbable hardware. Additional hardware-specific outcomes data is encouraged.

Purpose The aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza. Methods PubMed, Embase, Web of Science, Google Scholar, Scopus, CINAHL, Cochrane databases and clinical registration were searched from inception until February 15 2021 for relevant randomized controlled trials (RCTs). Only phase 3 RCTs evaluating the usefulness of baloxavir in the treatment of influenza were included. Results Three RCTs enrolling 3771 patients (baloxavir group, n = 1451; oseltamivir group, n = 1288; placebo group, n = 1032) were included. Compared with oseltamivir, baloxavir had an insignificantly shorter time to the alleviation of symptoms (mean difference [MD], −1.29 h; 95% CI, −6.80 to 4.21; I2 = 0%). In contrast, baloxavir had a significantly shorter time to the alleviation of symptoms than placebo (MD, −26.32 h; 95% CI, −33.78 to −18.86; I2 = 0%). Baloxavir was associated with a significant decline in influenza virus titers and viral RNA load compared to oseltamivir and placebo. Baloxavir was associated with a lower risk of any adverse events than oseltamivir (OR, 0.82; 95% CI, 0.69–0.98; I2 = 0%) and placebo (OR, 0.79; 95% CI, 0.66–0.96; I2 = 0%). Conclusions The findings of this meta-analysis suggested that baloxavir is superior to placebo in the treatment of influenza in both clinical outcome and virological response. Moreover, baloxavir was found to have a better virological response than oseltamivir and to be as effective as oseltamivir clinically. Compared with oseltamivir and placebo, baloxavir appears to be a relatively safe anti-influenza agent.

The frequency of adverse drug reactions (ADRs) in older patients is approximately 11.0%, according to scientific literature. Antibiotics are the third largest group (19.5%) of medicinal products in terms of ADR frequency in geriatric patients. Beta-lactam antibiotics are the empiric treatment of choice for older outpatients and inpatients with community-acquired pneumonia. The mortality in this group of patients accounts for 85% of the overall mortality from community-acquired pneumonia. The aim of the study was to analyse scientific data on risk factors and characteristics of adverse drug reactions associated with the use of beta-lactam antibiotics in older patients. Specificity of ADRs to beta-lactam antibiotics in this group of patients is due to age-related changes in pharmacokinetics and pharmacodynamics as well as polymorbidity and polypharmacy. The analysis of scientific literature demonstrated that there have not been so many pharmacoepidemiological studies in this group of patients, and their results have been inconsistent. The frequency, causes, and clinical manifestations of ADRs in geriatric patients are diverse and differ considerably from those in younger patients. Of the most widely used antibiotics, ceftriaxone and cefaclor exhibited a statistically lower risk of ADRs in older patients than in younger patients. At the same time, ceftriaxone was associated with a relatively higher frequency of serious ADRs in older patients as compared to younger patients, whereas the frequency of serious ADRs was lower with cefaclor. The likelihood of nephrotoxic, neurotoxic, and hepatotoxic ADRs associated with the use of beta-lactam antibiotics is becoming more and more obvious but it is still underestimated in clinical and geriatric practice. Safety monitoring, therapeutic drug monitoring with due consideration of ADR risk factors in older patients, and inclusion of older patients in clinical trials of antimicrobial drugs, would improve efficacy and safety of antibiotic treatment.

Optimal timing of open-heart surgery for the treatment of patients with cerebral hemorrhage remains controversial because systemic heparinization may lead to catastrophic bleeding. Several recent reports have shown that patients who undergo open-heart surgery .within a few weeks of cerebral hemorrhage have a much lower risk of exacerbated bleeding than previously considered. Herein, we report a case of left atrial myxoma and large hemorrhagic embolic stroke, which was successfully operated on with no exacerbation of cerebral hemorrhage. Careful assessment of time-course changes in cerebral hemorrhage by neurological imaging and adjustment of anticoagulation can help prevent the exacerbation of postoperative cerebral hemorrhage and neurological deterioration. Learning Objective Evaluation of hemorrhagic activity is equally or more important than hemorrhagic size to prevent postoperative hemorrhagic deterioration in patients with preoperative cerebral hemorrhage. Careful assessment of time-course changes in cerebral hemorrhage by neurological imaging and adjustment of anticoagulation can help prevent the exacerbation of postoperative cerebral hemorrhage and neurological deterioration. Early open-heart surgery can be performed if the hemorrhage is judged as inactive, even if it is large.

Objective To assess the utility of the preoperative Sarcopenia index (SI) as a predictive marker of the risk of postoperative complications following hip fracture surgery in older adults. Study design This observational study enrolled older adults with hip fracture who were hospitalized in the Department of Orthopedics of West China Hospital, Sichuan University, from December 7, 2010 - June 14, 2017, and who underwent hip fracture surgery. Primary outcome and measures Clinical data were collected from medical records and serum creatinine and cystatin C were measured before surgery. Outcomes included postoperative complications such as pneumonia, urinary tract infection, respiratory failure, heart failure, and non-grade A healing. Binary logistic regression analyses were used to analyze association between SI and postoperative complications. Results A total of 897 patients aged 60 years and over were enrolled in this study (age range: 60 – 100 years), of whom 306(34.1%)were male, and 591(65.9%)were female. Postoperative complications included pneumonia (12%), urinary tract infections (1.8%), respiratory failure (1.5%), heart failure (1.6%), and non-A- grade healing (3.6%). In the patient group that received joint replacements, the incidence of pneumonia was negatively associated with SI values. After adjusting for potential confounding factors, binary logistic regression analyses showed that a higher SI was independently associated with a lower risk of pneumonia after joint replacement surgery (OR:0.39, 95% CI:0.18-0.89, P Conclusion The SI based on serum creatinine and cystatin C can predict pneumonia rather than other postoperative complications among older patients with hip fracture after joint replacement surgery.

Background Subtotal cholecystectomy is recognized as a rescue procedure performed in grossly suboptimal circumstances that would deem a total cholecystectomy too risky to execute. An earlier systematic review based on 30 studies published between 1985 and 2013 concluded that subtotal cholecystectomy had a morbidity rate comparable to that of total cholecystectomy. This systematic review appraises 17 clinical outcomes in patients undergoing subtotal cholecystectomy. Methods The study protocol was registered with the International Prospective Register for Systematic Reviews (CRD42020172808). MEDLINE, Embase, Cochrane bibliographic databases, and Google Scholar were used to identify papers published between 1985 and June 2020. Data related to the surgical setting, approach, intervention on the hepatic wall of the gallbladder, type of completion of subtotal cholecystectomy, year of study, and study design were collected. Seventeen clinical outcomes were considered. Meta-analyses were performed using a random-effects model, and the effect size was presented as risk ratios with 95% confidence intervals. Results From 1,017 records, 85 eligible studies were identified and included. These included 3,645 patients who underwent subtotal cholecystectomy. Laparoscopic (80.1%, n = 2,918) and reconstituting (74.6%, n = 2,719) approaches represented the majority of all subtotal cholecystectomy cases. Seven (0.2%) cases of injury to the bile duct were reported. Bile leak was reported in 506 (13.9%) patients. Reconstituting subtotal cholecystectomy was associated with a lower risk for 11 clinical outcomes. Open subtotal cholecystectomy was associated with an increased rate of 30-day mortality and wound infections. Conclusion Subtotal cholecystectomy is associated with significant morbidity. Laparoscopic and reconstituting surgery may reduce the risks of some perioperative complications and long-term sequelae after subtotal cholecystectomy.

Background Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season. Methods This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days. Results A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2–48.0%). Conclusions This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715

Background The characteristics, outcomes, and risk factors for in-hospital death of critically ill intensive care unit (ICU) patients with coronavirus disease-2019 (COVID-19) have been described in patients from Europe, North America and China, but there are few data from COVID-19 patients in Middle Eastern countries. The aim of this study was to investigate the characteristics, outcomes, and risk factors for in-hospital death of critically ill patients with COVID-19 pneumonia admitted to the ICUs of a University Hospital in Egypt. Methods Retrospective analysis of patients with COVID-19 pneumonia admitted between April 28 and July 29, 2020 to two ICUs dedicated to the isolation and treatment of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Cairo University Hospitals. Diagnosis was confirmed in all patients using real-time reverse transcription polymerase chain reaction on respiratory samples and radiologic evidence of pneumonia. Results Of the 177 patients admitted to the ICUs during the study period, 160 patients had COVID-19 pneumonia and were included in the analysis (mean age: 60 ± 14 years, 67.5% males); 23% of patients had no known comorbidities. The overall ICU and hospital mortality rates were both 24.4%. The ICU and hospital lengths of stay were 7 (25–75% interquartile range: 4–10) and 10 (25–75% interquartile range: 7–14) days, respectively. In a multivariable analysis with in-hospital death as the dependent variable, ischemic heart disease, history of smoking, and secondary bacterial pneumonia were independently associated with a higher risk of in-hospital death, whereas greater PaO2/FiO2 ratio on admission to the ICU was associated with a lower risk. Conclusion In this cohort of critically ill patients with COVID-19 pneumonia, ischemic heart disease, history of smoking, and secondary bacterial pneumonia were independently associated with a higher risk of in-hospital death.

Gastrointestinal (GI) bleeding is the most frequent single site of oral anticoagulant (OAC)-associated major bleeding. Patients with major GI bleeding experience morbidity and a substantial risk of short-term all-cause mortality up to 10%. While OACs are frequently discontinued during acute bleeding, there is substantial uncertainty about whether, when, and how OACs should be resumed after bleeding has resolved. Limited evidence suggests a lower risk of thromboembolism and death, and a higher risk of recurrent bleeding with OAC resumption. However, the absolute risks and optimal timing of anticoagulation remain uncertain based on these observational studies at risk of bias, particularly due to baseline confounding. In addition to an individualized approach to determining the benefits and harms of treatment decisions informed by the best available evidence about thrombosis and recurrent bleeding, discussions should meaningfully incorporate patient values and preferences. The objective of this review is to provide a framework for decision-making by summarizing the epidemiology and clinical outcomes of OAC-associated GI bleeding, providing an approach for assessment and risk stratification for OAC resumption and its timing, and outlining strategies for the prevention of recurrent GI bleeding.

Background Many breast cancer clinical trials with PARPi have been completed or are currently carried out, either by monotherapy or combined with chemotherapy. We aim to assess the efficacy and safety of PARPi in breast cancer patients as compared to chemotherapy. Methods A comprehensive literature search of PubMed, EMBASE, CENTRAL, conference meetings and clinical trial registry was performed. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR). The secondary outcome was safety profile. The comparative effects were measured using hazard ratio (HR) or relative risk (RR) with 95% confidence interval. Subgroup analyses were conducted based on types of intervention and baseline characteristics of patients. Results Six RCTs (n = 1953) were included. Two RCTs were recognized as high risk. PARPi was associated with an improved PFS (HR, 0.65; 95% CI, 0.56–0.74), OS (HR, 0.86; 95% CI, 0.73–1.01), and a higher ORR (RR, 1.38; 95% CI, 1.05–1.82). PARPi, however, significantly increased risk of grade 3–4 thrombocytopenia (RR, 1.63; 95% CI, 1.06–2.52). Monotherapy was observed with lower risk of disease progression and higher ORR rate than combination therapy, 0.56 to 0.65 and 2.21 to 1.05, respectively. For patients without prior platinum treatment, PARPi significantly improved PFS (HR, 0.64; 95% CI, 0.52–0.79). Conclusions PARPi was observed with a significantly improved efficacy in aspects of PFS and ORR, but also higher risk of grade 3–4 thrombocytopenia as compared to chemotherapy. PARPi was a better choice for patients who had not received previous platinum treatment., Highlights • PARPi showed improved efficacy in PFS and ORR. • PARPi presented higher risk of grade 3–4 thrombocytopenia. • PARPi is better for patients who had not received prior platinum treatment.

Objective: to evaluate clinical efficacy, safety and tolerability of long-term inhaled iloprost treatment in the daily practice for the management of pulmonary arterial hypertension (PAH). Methods: a total of 115 patients with PAH on inhaled iloprost treatment were included. New York Heart Association (NYHA) functional class, brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and 6-minute walk distance (6MWD) were recorded at baseline and at 3rd to 24th month visits. Safety and tolerability of iloprost treatment were also evaluated during follow-up, as were the survival, clinical worsening, and the related risk factors. Results: the treatment was associated with an increase in the percentage NYHA functional class II (from 0.0% at enrolment to 36.2% at 24th month visit) patients but no significant difference was noted in 6MWD values. Clinical worsening was observed in 63.5% patients, while survival rate was 69.6%. NT-proBNP levels were significantly higher in non-survivors than in survivors (p=0.042). Cox regression analysis revealed the association of female sex [odds ratio (OR)=0.318; 95% confidence interval (CI), 0.128-0.792; p=0.014] and scleroderma-related PAH (OR=0.347; 95% CI, 0.140-0.860; p=0.022) with significantly lower risk (3.14 fold and 2.88 fold, respectively) of mortality. Conclusion: our findings indicate favorable efficacy, safety, and tolerability of long-term iloprost treatment in the management of PAH, whereas improved NYHA functional class was not accompanied with a significant change in 6MWD values. Patient age was a risk factor for clinical worsening, while female sex, scleroderma subtype, and lower NT-proBNP levels were associated with significantly lower mortality risk., Bayer Türk

Objectives The goal of this study was to evaluate the prevalence, characteristics, and outcomes of patients with advanced heart failure (HF) in a geographically defined population. Background Some patients with HF progress to advanced HF, characterized by debilitating HF symptoms refractory to therapy. Limited data are available on the epidemiology and outcomes of patients with advanced HF. Methods This was a population-based cohort study of all Olmsted County, Minnesota, adults with and without HF from 2007 to 2017. The 2018 European Society of Cardiology advanced HF diagnostic criteria were operationalized and applied to all patients with HF. Hospitalization and mortality in advanced HF, overall and according to ejection fraction (EF) type (reduced EF Results Of 6,836 adults with HF, 936 (13.7%) met criteria for advanced HF. The prevalence of advanced HF increased with age and was higher in men. At advanced HF diagnosis, 396 (42.3%) patients had HFrEF, 134 (14.3%) had HFmrEF, and 406 (43.4%) had HFpEF. The median (interquartile range) time from advanced HF diagnosis to death was 12.2 months (3.7-29.9 months). The mean rate of hospitalization was 2.91 (95% CI: 2.78-3.06) per person-year in the first year after advanced HF diagnosis. There were no differences in risks of all-cause mortality or hospitalization by EF. Patients with advanced HFpEF were at lower risk for cardiovascular mortality compared with advanced HFrEF (HR: 0.79; 95% CI: 0.65-0.97). Conclusions In this population-based study, more than one-half of patients with advanced HF had mid-range or preserved EF, and survival was poor regardless of EF.

Introduction Oral anticoagulant (OAC)-related adverse events are high post-hospitalization. We planned to develop and validate a prediction model for OAC-related harm within 30 days of hospitalization. Methods We undertook a population-based study of adults aged ≥66 years who were discharged from hospital on an OAC from September 2010 to March 2015 in Ontario, Canada. The primary outcome was a composite of time to first hospitalization or emergency department visit for a hemorrhagic or thromboembolic event, or mortality within 30 days of hospital discharge. Cox proportional hazards regression was used to build the model. Results We included 120,721 patients of which 5423 experienced the outcome. Most patients were aged ≥75 years (59.5%) and were female (55.6%). Sixty percent of the cohort had a follow-up visit with a healthcare provider within 7 days of discharge. Patients discharged on a direct acting OAC versus warfarin (apixaban: Hazard Ratio [HR] 0.82, 95% confidence interval [CI] 0.71-0.94; dabigatran: HR 0.73, 95% CI 0.63-0.84; rivaroxaban: HR 0.79, 95% CI 0.71-0.88), were prevalent users of the dispensed OAC versus incident users (HR 0.82, 95% CI 0.69-0.96), had a joint replacement in the past 35 days (HR 0.40, 95% CI 0.33-0.50) or major surgery during index hospital stay (HR 0.69, 95% CI 0.60-0.80) had a lower risk for the outcome. The Cox model was stable with acceptable discrimination but poor goodness-of-fit. Conclusions A model for OAC-related harm in the early post-discharge period was developed. External validation studies are required to understand the model's poor calibration.

Background We applied an artificial intelligence-based model to predict fragility fractures in postmenopausal women, using different dual-energy x-ray absorptiometry (DXA) parameters. Methods One hundred seventy-four postmenopausal women without vertebral fractures (VFs) at baseline (mean age 66.3 ± 9.8) were retrospectively evaluated. Data has been collected from September 2010 to August 2018. All subjects performed a spine x-ray to assess VFs, together with lumbar and femoral DXA for bone mineral density (BMD) and the bone strain index (BSI) evaluation. Follow-up exams were performed after 3.34 ± 1.91 years. Considering the occurrence of new VFs at follow-up, two groups were created: fractured versus not-fractured. We applied an artificial neural network (ANN) analysis with a predictive tool (TWIST system) to select relevant input data from a list of 13 variables including BMD and BSI. A semantic connectivity map was built to analyse the connections among variables within the groups. For group comparisons, an independent-samples t-test was used; variables were expressed as mean ± standard deviation. Results For each patient, we evaluated a total of n = 6 exams. At follow-up, n = 69 (39.6%) women developed a VF. ANNs reached a predictive accuracy of 79.56% within the training testing procedure, with a sensitivity of 80.93% and a specificity of 78.18%. The semantic connectivity map showed that a low BSI at the total femur is connected to the absence of VFs. Conclusion We found a high performance of ANN analysis in predicting the occurrence of VFs. Femoral BSI appears as a useful DXA index to identify patients at lower risk for lumbar VFs.

Summary Objectives Limited data exist on the optimal treatment duration for chronic pulmonary aspergillosis (CPA). We investigated the treatment outcome and recurrence rate according to treatment duration in CPA patients. Methods A total of 196 patients who completed at least 6 months of antifungal therapy (99% oral itraconazole) and achieved favorable treatment responses were analyzed. A Cox's proportional hazards regression model was used to adjust for potential confounding factors in the association between the duration of antifungal therapy (6–12 months vs. ≥ 12 months) and recurrence. Results All patients were treated with antifungal agents for at least 6 months (median: 12.5, interquartile range: 8.5–18.4 months) and categorized into 6–12 months group (79/196, 40%) and ≥ 12 months group (117/196, 60%). The 6–12 months group had significantly higher recurrence rates owing to CPA aggravation after the completion of treatment compared with the ≥ 12 months group (51% vs. 25%, P = 0.003). In a Cox's proportional hazards regression model, treatment duration ≥ 12 months was independently associated with a lower risk of recurrence (adjusted hazard ratio: 0.48, 95% confidence interval: 0.28–0.80). Conclusions Our data suggest that prolonging antifungal therapy beyond 12 months could reduce the recurrence rate in CPA patients.

Supplemental Digital Content is available in the text., Longer time in target range (TTR) for systolic blood pressure (SBP) is associated with a lower risk of cardiovascular events. Team-based care improves SBP control but its effect on the consistency of SBP control over time is unknown. This post hoc analysis used data from a cluster-randomized trial of a physician/pharmacist collaborative model that randomized medical offices to either a 9- or 24-month pharmacist intervention or control group. TTR for SBP was calculated using linear interpolation and an SBP range of 110 to 130 mm Hg. TTR is reported as median values and group comparisons assessed using the Kruskal-Wallis test. Of the 625 participants enrolled, 524 had 9-month and 366 had 24-month SBP data. Participants were a median 59 years old, 59% female, and 52% minority. After 24 months, the median TTR for SBP was 31.9% and 29.8% for the 9- and 24-month intervention groups, respectively, compared with 19% in the control group (P=0.0068). This observation persisted in the subgroup of participants with diabetes or chronic kidney disease and minorities. A longer TTR was not associated with an increased risk of adverse drug events. Time to first observed SBP in the target range was shorter in the intervention group compared with control (270 versus 365 days; P=0.0047). A physician/pharmacist collaborative care model achieved longer TTR for SBP compared with control (usual care).

AIMS: This study aimed to examine whether socioeconomic differences exist in long-term outcomes after out-of-hospital cardiac arrest (OHCA).METHODS: We included 2309 30-day OHCA survivors ≥ 30 years of age from the Danish Cardiac Arrest Registry, 2001-2014, divided in tertiles of household income (low, medium, high). Absolute probabilities were estimated using logistic regression for 1-year outcomes and cause-specific Cox regression for 5-year outcomes. Differences between income-groups were standardized with respect to age, sex, education and comorbidities.RESULTS: High-income compared to low-income patients had highest 1-year (96.4% vs. 84.2%) and 5-year (87.6% vs. 64.1%) survival, and lowest 1-year (11.3% vs. 7.4%) and 5-year (13.7% vs. 8.6%) risk of anoxic brain damage/nursing home admission. The corresponding standardized probability differences were 8.2% (95%CI 4.7-11.6%) and 13.9% (95%CI 8.2-19.7%) for 1- and 5-year survival, respectively; and -4.5% (95%CI -8.2 to -1.2%) and -5.1% (95%CI -9.3 to -0.9%) for 1- and 5-year risk of anoxic brain damage/nursing home admission, respectively. Among 831 patients < 66 years working prior to OHCA, 72.1% returned to work within 1 year and 80.8% within 5 years. High-income compared to low-income patients had the highest chance of 1-year (76.4% vs. 58.8%) and 5-year (85.3% vs. 70.6%) return to work with the corresponding absolute probability difference of 18.0% (95%CI 3.8-32.7%) for 1-year and 9.4% (95%CI -3.4 to 22.3%) for 5-year.CONCLUSION: Patients of high socioeconomic status had higher probability of long-term survival and return to work, and lower risk of anoxic brain damage/nursing home admission after OHCA compared to patients of low socioeconomic status.

The REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) trial demonstrated that high-dose icosapent-ethyl reduced the risk of ischemic events in statin-treated patients with elevated triglycerides (TG) and either atherosclerotic cardiovascular disease (ASCVD) or diabetes plus at least one risk factor.Using data from REACH (Reduction of Atherothrombosis for Continued Health), a large international registry of outpatients with or at risk of ASCVD, we evaluated the proportion of patients potentially eligible for enrolment in REDUCE-IT and compared their outcomes to those excluded because of low TG. Among 62,464 patients with either ASCVD or diabetes enrolled in the REACH Registry, 1036/8418 (12.3%) patients in primary prevention and 6049/54046 (11.2%) patients in secondary prevention (11.3% overall) would have been eligible for inclusion in REDUCE-IT. Compared with patients excluded for low TG level, adjusted risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, or coronary revascularization was higher in the REDUCE-IT eligible group (HR:1.06, 95%CI:1.00-1.13, p = 0.04). In addition, unstable angina, non-fatal MI, percutaneous coronary intervention and coronary artery bypass grafting were also more frequent in the REDUCE-IT eligible group (HR:1.17, 95%CI:1.07-1.27, p 0.001; HR:1.25, 95%CI:1.07-1.45, p 0.001; HR:1.42, 95%CI:1.27-1.57, p 0.001; HR:1.43, 95%CI:1.19-1.71, p 0.001, respectively), whereas the adjusted risk of non-fatal stroke was lower (HR:0.64, 95%CI:0.54-0.75, p 0.001).In this large international registry of patients with or at high-risk of ASCVD, 11.3% met the REDUCE-IT trial selection criteria. REDUCE-IT eligible patients were found to be at higher risk of cardiac atherothrombotic events, but at lower risk of stroke than trial-ineligible patients with lower TG.

BACKGROUND AND AIMS: Dynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up. DESIGN: A secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014–17. SETTING: Eight community addiction treatment programs in the United States. PARTICIPANTS: English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%). INTERVENTION(S): Participants were treated with daily sublingual buprenorphine–naloxone (BUP–NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use. MEASUREMENTS: Outcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP–NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant. FINDINGS: We estimated that increasing BUP–NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = −32.17, −6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6. CONCLUSIONS: In people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine–naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2.

Background Secondhand smoke (SHS) exposure can affect physical development in children. An understanding of parental risk perception of SHS could guide efforts to develop measures for prevention of SHS exposure among children. This study aimed to assess parental risk perceptions of SHS and action taken by parents to minimise SHS exposure in their children. Methods This cross-sectional nationwide study conducted in 2018 recruited convenience sample of 289 parents with children up to age 12 at public areas. Parents were asked to rate the risk level from 1 (no risk) to 5 (extremely high risk) by looking at photographs of an adult smoking in the presence of a child in 8 different situations. The implementation of smoking restriction rules was assessed. Mean scores were calculated with higher scores representing higher risk perception of SHS to child’s health. Linear regression analysis was used to determine factors associated with the level of parental risk perception of SHS exposure to their children’s health. Results A total of 246 parents responded. Their mean age was 35 years (SD 6.4). The majority were mothers (75.6%), Malays (72.0%) and had tertiary education level (82.5%), and non-smoker (87.1%). The mean age of respondents’ youngest child was 3 years (SD 3.1). The risk perception level was high [mean scores: 4.11 (SD: 0.82)]. Most parents implemented household (65.0%) and car (68.3%) smoking restriction rules. Lower levels of risk perception were observed among participants who were current smokers (p p p = 0.027). Conclusion Most parents perceived that risks of SHS exposure to their children were high but only two-thirds of them had set rules prohibiting smoking. Health policymakers should pay attention to factors associated with lower risk perception among parents. Trial registration This study was approved by the Medical Research Ethics Committee, Ministry of Health Malaysia (Registration Number: NMRR-18-3299-44967).

BACKGROUND: Mechanical ventilation immediately after lung transplantation may impact the development of primary graft dysfunction (PGD), particularly in cases of donor-recipient size mismatch as ventilation is typically based on recipient rather than donor size. METHODS: We conducted a retrospective cohort study of adult bilateral lung transplant recipients at our center between January 2010 and January 2017. We defined donor-based lung protective ventilation (dLPV) as 6 to 8 ml/kg of donor ideal body weight and plateau pressure

Purpose To identify prognostic factors of invasive–disease free survival (iDFS) in women with non-metastatic hormone receptor positive (HR+) breast cancer (BC) in daily routine practice. Methods We performed a retrospective study using data from the Côte d’Or breast and gynecological cancer registry in France. All women diagnosed with primary invasive non-metastatic HR + BC from 1998 to 2015 and treated by endocrine therapy (ET) were included. Women with bilateral tumors or who received ET for either metastasis or relapse were excluded. We performed adjusted survival analysis and Cox regression to identify prognostic factors of iDFS. Results A total of 3976 women were included. Age at diagnosis, ET class, SBR grade, treatment, stage and comorbidity were independently associated with iDFS. Women who had neither surgery nor radiotherapy had the highest risk of recurrence (HR = 3.75, 95%CI [2.65–5.32], p, Highlights • Treatment with AI was associated with a lower risk of recurrence. • Comorbidities are strong predictor of iDFS in breast cancer. • Radiotherapy after BCS was associated with a lower recurrence risk. • Age, comorbidity and histological type predict the choice of endocrine therapy.

Objectives To examine the risk of serious infections (SIs) among patients with rheumatoid arthritis (RA) treated with tocilizumab compared with tumor necrosis factor inhibitor (TNFi) in Korea. Methods We conducted a retrospective cohort study using the Korean National Health Insurance data. The study cohort included patients ≥18 years with RA who were initiated with tocilizumab or TNFi between January 2013 and June 2018. The primary outcome was a composite endpoint of SIs, defined as an infection resulting in intravenous antimicrobial therapy or hospitalization. Secondary outcomes were organ-specific SIs. To control for confounders, we used inverse probability of treatment weighting (IPTW) using propensity score. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a multivariable Cox regression model. Results A total of 8794 patients were identified: 1395 and 7399 patients initiated with tocilizumab and TNFi, respectively. The mean follow-up durations were 1.2 years for tocilizumab initiators and 1.0 year for TNFi initiators. After IPTW and adjustment, no increased risk of SIs was observed in tocilizumab versus TNFi (HR, 1.00; 95%CI, 0.90–1.11). In the secondary analysis, tocilizumab was associated with a higher risk of skin and subcutaneous tissue infections (HR, 1.26; 95%CI, 1.02–1.54) and a lower risk of urological and gynecological infections (HR, 0.65; 95%CI, 0.49–0.87) compared to TNFi. Conclusion In this population-based cohort of RA patients in Korea, tocilizumab was not associated with a higher risk of SI compared to TNFi. However, tocilizumab should be carefully used for patients at high risk for skin-related infections.