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Clozapine is the only antipsychotic compound indicated for refractory-schizophrenia. However, it is associated with emergent metabolic dysregulation and cardiovascular risk which may lead to mortality. In this study we aimed to explore predictors for mortality in a large cohort of schizophrenia patients treated with long-term clozapine, using the electronic medical records of the largest health care provider in Israel. Among 27,929 patients diagnosed with schizophrenia, 1817 were prescribed clozapine during the years 2012-2014. We compared patients who survived (n=1705) and patients who died (n=112) during the 3-year follow-up period. Socio-demographic background, cardiovascular morbidity, medication prescriptions and health-care utilization were compared between groups. Cox proportional hazard models were used to assess the association of variables with survival. Chronic hypertension was found to be the only metabolic factor associated with significant hazard ratio (HR) for mortality (HR: 1.55 95% CI: 1.03-2.34). Moreover, those who died had more prevalent ischemic heart disease (14% vs 3%, p<0.005) as well as more frequent hospitalizations (0.01±0.02 vs 0.11±0.18 average per month, p<0.005), for longer periods (2.22±9.87 vs 20.38±33.76 days per month, p<0.005). Among those who died, less patients received prescriptions of statins for hyperlipidemia (13.7% vs. 52.9% in survivors, p<0.005) and hypoglycemics for diabetes mellitus (16.3% vs. 67.1% in survivors, p<0.005). Inadequate treatment of metabolic syndrome, under chronic clozapine treatment, was found to be an independent predictor for mortality. Adequate rigorous regimen for diagnosis and treatment of metabolic risk factors, especially hyperlipidemia and diabetes mellitus, might lower complications rate and prolong life expectancy among this population., Competing Interests: Conflict of Interest All authors declare no conflict of interests., (Copyright © 2020. Published by Elsevier B.V.)

Background: Spinal hypotension causes decreased regional cerebral oxygen saturation (ScO 2 ) in women undergoing cesarean delivery. In this study we aimed to measure the change in ScO 2 using near infrared spectroscopy in women receiving a prophylactic phenylephrine infusion during cesarean delivery under spinal anesthesia., Methods: This was a prospective, observational cohort study. Fifty-three women had ScO 2 measurements at the following time points: preoperatively, in the supine position with 30° of left lateral tilt; one and five minutes after spinal anesthesia; at the time of skin incision; immediately after delivery; one minute after commencing the oxytocin infusion; at completion of surgery, and one hour after surgery. Spinal anesthesia and a prophylactic phenylephrine infusion were administered according to a standard treatment protocol. Statistical analysis used the Wilcoxon Signed Rank test with Bonferroni's correction for multiple comparisons., Results: Blood pressure was maintained within 20% of baseline throughout surgery. The baseline mean (range) ScO 2 was 61.5% (54.0-66.3%). It decreased significantly at all subsequent measurement points. The maximum decrease was five minutes after spinal anesthesia. Thirty-four (64.2%) of the parturients exhibited ScO 2 values <20% of baseline, or a decrease to below an absolute value of 50%. There was no significant correlation between systolic blood pressure and mean ScO 2 ., Conclusion: Spinal anesthesia with phenylephrine infusion during cesarean delivery is associated with a significant decrease in ScO 2 levels, maximal five minutes later. Further studies are required to establish the clinical significance of this finding., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Oral anticoagulation (OAC) is effective in stroke prevention in elderly patients with nonvalvular atrial fibrillation (AF), but older patients are also at higher risk of bleeding., Objective: We aimed to examine whether OAC has net clinical benefit (NCB) in elderly patients with AF., Methods: This is a retrospective cohort study of patients with AF, aged 75 years and older, who were diagnosed from January 1, 2013, through December 31, 2015. Incidences of stroke and intracranial hemorrhage (ICH) were estimated as the number of events per 100 person-years. The NCBs were estimated with respect to time in therapeutic range (TTR) (<60% or ≥60%) and treatment type (warfarin and low or high dose of direct oral anticoagulants [DOACs])., Results: We included 11,760 patients, of whom 4982 (42.4%) were treated with OACs: 2042 (17.4%) with warfarin and 2940 (25.0%) with DOACs. Among patients treated with warfarin, those who achieved TTR ≥ 60% had a lower incidence of stroke (2.54 per 100 person-years vs 5.21 per 100 person-years; P = .01) but without a statistically significant lower incidence of ICH (0.68 per 100 person-years vs 1.10 per 100 person-years; P = .45) and a higher NCB (9.78 vs 6.52) than did those with TTR < 60%. Among patients treated with DOACs, patients treated with the high dose had a statistically significant similar incidence of stroke (8.40 per 100 person-years vs 9.81 per 100 person-years; P = .67), a statistically significant lower incidence of ICH (0.33 per 100 person-years vs 1.20 per 100 person-years; P = .02), and a higher NCB (4.42 vs 1.78) than did patients treated with the low dose., Conclusion: A large proportion of elderly patients are not treated with OACs. We found that the NCB of OAC in the elderly is positive, with the highest benefit in elderly patients treated with warfarin who achieved TTR ≥ 60% or high dose of DOACs., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Post stroke depression is common and pervasive. In the general population, there has been some controversy that antidepressant (AD) medication is associated with premature mortality. Data is still lacking regarding the association between adherence to antidepressants (AD) and all-cause mortality. In this retrospective analysis of a population-based cohort of patients, 32,361 post-stroke patients who purchased at least one AD were followed for all-cause mortality over 4-years. Adherence to AD was measured as a ratio between dispensed and prescribed durations and was modeled as: non-adherence (<20%, n=8619), poor (20-50%, n=5108), moderate (50-80%, n=5656), and good (>80%, n=12,978) adherence. Multivariable survival analyses, adjusted for demographic and clinical variables including physical comorbidities known to influence mortality, were conducted. Unadjusted mortality rates were 16.5%, 20.2%, 22.2% and 23.7% in those classified as non-adherent, poor, moderate and good adherence respectively (χ 2 =174.6, p<0.0001). In the adjusted model, the non-adherent and poor adherence groups had significantly increased mortality Hazard Ratios (HR) of 1.25 (95% CI: 1.17-1.33) and 1.17 (95% CI: 1.09-1.26) respectively compared to the good adherence group. This nationally representative data suggests that poor adherence to AD is associated with increased all-cause mortality among people who had a stroke. Given our findings and the high prevalence of anxiety and depression along with AD effectiveness, efforts to promote AD adherence in this population may be warranted in clinical practice., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Background: As asthma-like symptoms are common in CF, we evaluated reversible airway obstruction and associated characteristics., Methods: Retrospective analysis of charts including spirometry and bronchodilator response., Results: Of 190 CF patients (103 at Schneider's, 87 at Hadassah), aged 14.4 (4-76) years, median (range), 39% had reversible obstruction (ΔFEV1% predicted ≥12%), associated with younger age (p=0.01) and severe genotype (p=0.02). There was no association with family history of asthma, serum IgE, blood eosinophils, pancreatic status, FEV1<40% predicted, Aspergillus or pseudomonas infection. Of patients with reversible obstruction, 74% were on bronchodilator and 68% on inhaled corticosteroid therapy but 54% and 57% respectively receiving these therapies did not have reversible obstruction., Conclusions: Reversible airway obstruction is common in CF, more frequent in younger patients and with severe genotype, with no correlation to markers of atopy or CF clinical severity. Bronchodilator and inhaled corticosteroid therapies are commonly prescribed even without reversible obstruction., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an increasingly common nosocomial pathogen. We sought to identify clinical and microbiological predictors of 14-day mortality among patients with CRAB bacteraemia. This case-control study included all adult patients in one Israeli hospital with CRAB on blood culture between July 2008 and June 2011. Cases were defined as patients who died within 14 days of bacteraemia onset and controls as patients who survived over 14 days. Sequence-typing of the blaOXA-51-like gene and REP-PCR identified CRAB clone groups. Logistic regression was performed to analyze predictors of 14-day all-cause mortality. To correct for differences in treatment onset, Cox regression was used to examine the effect of receiving an active antibiotic. Eighty-three cases and 89 controls were included. Six major CRAB clone groups were identified, with 14-day mortality ranging from 17 to 66%. Independent predictors of 14-day mortality were severity of illness (OR = 1.38 for each 1-point increase in Sequential Organ Failure Assessment (SOFA) score; 95% CI, 1.21, 1.56), independence in activities of daily living (ADL) on admission (OR = 3.40; 95% CI, 1.20, 9.67, for fully dependent vs. independent), surgery before bacteraemia (OR = 0.25; 95% CI, 0.11, 0.59) and clone group (OR = 7.76; 95% CI, 2.52, 23.85, for the most virulent group vs. the reference group). In the multivariate Cox model using a propensity score to adjust for SOFA, clone, ADL and surgery, active antibiotic treatment was protective (HR = 0.30; 95% CI, 0.15, 0.60). Differences in virulence between CRAB clones may partly explain heterogeneous results in previous studies of mortality following CRAB infection., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)