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Riva Tauman,1 Murray Berall,2 Richard Berry,3 Tamar Etzioni,4 Noam Shrater,5 Dennis Hwang,6 Ibrahim Marai,7 Prasanth Manthena,8 Anil Rama,9 Rebecca Spiegel,10 Thomas Penzel,11 Nira Koren Morag,12 Giora Pillar4 1Sleep Disorders Center, Tel Aviv Souraski Medical Center, Tel Aviv, Israel; 2Center of Sleep and Chronobiology, Toronto, ON, Canada; 3UF Health Sleep Center, University of Florida, Gainesville, FL, USA; 4Technion Faculty of Medicine, Sleep Laboratory, Carmel Medical Center, Haifa, Israel; 5Cardiology Department, Soroka Medical Center, Be’er Sheva, Israel; 6Kaiser Permanente Fontana Medical Center, Fontana, CA, USA; 7Cardiology Department, Rambam Medical Center, Haifa, Israel; 8Sleep Clinic, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA; 9Kaiser Permanente San Jose Medical Center, San Jose, CA, USA; 10Stony Brook University Hospital, Stony Brook, NY, USA; 11Charite Universitätsmedizin Berlin, Sleep Medicine Center, Berlin, Germany; 12Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Riva TaumanSleep Disorders Center, Tel Aviv Souraski Medical Center, 6 Weitzman Street, Tel Aviv 6423906, IsraelTel +972 36974614Fax +1 972 36974634Email tauman@tlvmc.gov.ilBackground: Early diagnosis and treatment of sleep apnea in patients with atrial fibrillation (AF) is critical. The WatchPAT (WP) device was shown to be accurate for the diagnosis of sleep apnea; however, studies using the WatchPAT device have thus far excluded patients with arrhythmias due to the potential effect of arrhythmias on the peripheral arterial tonometry (PAT) amplitude and pulse rate changes.Purpose: To examine the accuracy of the WP in detecting sleep apnea in patients with AF.Patients and Methods: Patients with AF underwent simultaneous WP and PSG studies in 11 sleep centers. PSG scoring was blinded to the automatically analyzed WP data.Results: A total of 101 patients with AF (70 males) were recruited. Forty-six had AF episodes during the overnight sleep study. A significant correlation was found between the PSG-derived AHI and the WP- derived AHI (r=0.80, p< 0.0001). There was a good agreement between PSG-derived AHI and WP-derived AHI (mean difference of AHI: -0.02± 13.2). Using a threshold of AHI ≥ 15 per hour of sleep, the sensitivity and specificity of the WP were 0.88 and 0.63, respectively. The overall accuracy in sleep staging between WP and PSG was 62% with Kappa agreement of 0.42.Conclusion: WP can detect sleep apnea events in patients with AF. AF should not be an exclusion criterion for using the device. This finding may be of even greater importance in the era of the COVID19 epidemic, when sleep labs were closed and most studies were home based.Keywords: home sleep apnea test, WatchPAT, obstructive sleep apnea, atrial fibrillation

Introduction: Overweight and obesity (OW/OB) are underdiagnosed. The primary aim was to assess whether a diagnosis of OW/OB recorded by a primary care physician (PCP) is associated with clinically significant weight loss, compared to a missed diagnosis. The secondary aim was to investigate the association between OW/OB diagnosis and patient attendance at dietary consultations., Methods: This retrospective, observational cohort study was conducted using a nationwide healthcare database. The study included a random sample of 200,000 adults with BMI ≥25 kg/m2, recorded on a primary care visit, between 2014 and 2020. Patients with prior diagnosis of OW/OB or obesity-related complications were excluded. The independent variable was OW/OB diagnosis recorded by the PCP immediately after BMI measurement. The outcome variable was ≥5% weight loss at a second weight measurement within 9-15 months. Multivariate regression analysis was applied., Results: Of the 200,000 people with OW/OB, 36,033 (18.0%) had a diagnosis of OW/OB, and 37,368 (18.7%) had a second body weight measurement, of which 7,635 (20.4%) lost ≥5% of their baseline body weight. The prescription rate of anti-obesity medication was 1.2% and did not differ between patients who achieved weight loss and those who did not. Those with a recorded diagnosis were 2.6 times more likely to visit a dietitian (odds ratio [OR] 2.57, 95% confidence interval [CI]: 2.56-2.64) and 2.5 times more likely to achieve weight loss (OR 2.53, 95% CI: 2.46-2.60). After adjusting for multiple confounders, including attendance at dietary consultation, people who received OW/OB diagnosis were 32% more likely to achieve weight loss (OR 1.32, 95% CI: 1.28-1.36, p < 0.001) compared to people with missed diagnosis., Conclusions: Recording a diagnosis of obesity among relatively healthy people is associated with clinically significant weight loss at 1-year follow-up, independent of attendance at dietary consultation. Early obesity diagnosis is a significant opportunity to promote weight loss in the primary care setting and may affect weight trajectory., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Aims: To investigate the potential association of chronic use of omeprazole with the occurrence of osteoporotic fractures (OF) in community-dwelling elderly subjects., Methods: The cohort consisted of community-dwelling residents aged >65 years registered with a large health maintenance organization in Israel between January 2002 and December 2016. Data were retrospectively collected from the electronic medical files on demographics, parameters known to be associated with OF, diagnoses of osteoporotic hip, wrist, and vertebral fractures, and chronic use of omeprazole (>11 prescriptions/year). Time to OF/death/end of study was calculated from the beginning of the study (2002). The risk of fractures in the chronic users of omeprazole was analyzed by multivariate Cox proportional hazard regression model., Results: In total, 46 805 subjects were included (41% men), mean age 83.4±6.4 years, of whom 10 272 (21.9%) were chronic users of omeprazole. During 14 years of follow-up, OF were diagnosed in 414 (4.0%) omeprazole users and 1007 (2.8%) omeprazole nonusers (p < 0.001). In a Cox regression model adjusted for age and gender only, chronic use of omeprazole was associated with a 16% excess of OF. However, when parameters known to be associated with OF were entered into the multivariate Cox regression model, chronic use of omeprazole was not found to be an independent risk factor for OF, either overall (adjusted hazard ratio = 0.965, 95% confidence interval 0.86-1.08, P = .55) or specifically, in the ≥85 years age group (adjusted hazard ration = 0.780, 95% confidence interval 0.635-0.958, P < .05) in which an inverse correlation between omeprazole use and OF, was demonstrated., Conclusions: Chronic use of omeprazole was not associated with the occurrence of OF in elders., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Although endothelial function is a marker for cardiovascular risk, endothelial dysfunction assessment is not routinely used in daily clinical practice. A growing challenge has emerged in identifying patients prone to cardiovascular events. We aim to investigate whether abnormal endothelial function may be associated with adverse 5-year outcomes in patients presenting to a chest pain unit (CPU)., Methods: Following endothelial function testing using EndoPAT 2000 in 300 consecutive patients without a history of coronary artery disease, patients underwent coronary computerized tomographic angiography (CCTA) or single-photon emission computed tomography according to availability., Results: Mean 10-year Framingham risk score (FRS) was 6.6 ± 5.9%; mean 10-year atherosclerotic cardiovascular disease (ASCVD) risk was 7.1 ± 7.2%; median reactive hyperemia index (RHI) as a measure of an endothelial function 2.0 and mean was 2.0 ± 0.4. During a 5-year follow-up, the 30 patients who developed major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions, had higher 10-year FRS (9.6 ± 7.8 vs. 6.3 ± 5.6%; P  = 0.032), higher 10-year ASCVD risk (10.4 ± 9.2 vs. 6.7 ± 6.9%; P  = 0.042), lower baseline RHI (1.6 ± 0.5 vs. 2.1 ± 0.4; P  < 0.001) and a greater degree of coronary atherosclerotic lesions (53 vs. 3%, P  < 0.001) on CCTA compared with patients without MACE. Multivariate analysis demonstrated that RHI below the median was an independent predictor of 5-year MACE (odds ratio 5.567, 95% confidence interval 1.955-15.853; P  = 0.001)., Conclusion: Our findings suggest that noninvasive endothelial function testing may contribute to clinical efficacy in triaging patients in the CPU and in predicting 5-year MACE., Clinical Trialsgov Identifier: NCT01618123., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: The association between long-term omeprazole use and gastric cancer (GC) risk is controversial. The aim of this study was to investigate the incidence of GC in elderly community-dwelling omeprazole chronic users with/without aspirin compared to non-users., Methods: The registry of a large health management organization was searched for all community-dwelling members aged ≥65 years from January 2002 to December 2016. Data on demographics, background parameters, and chronic omeprazole and aspirin use (>11 prescriptions/year) were retrieved. Those diagnosed with new-onset GC during the study period (from January 2003) were identified., Results: Of 51 405 subjects who met the inclusion criteria, 197 were diagnosed with GC during a mean follow-up period of 8.74 ± 4.16 years. This group accounted for 0.7% of PPI chronic users (72/11 008) and 0.3% (125/40 397) of nonusers (P < 0.001). GC risk was directly associated with omeprazole chronic use [hazard ratio (HR) 2.03, 95% confidence interval (CI): 1.51-2.73, P < 0.001] and inversely associated with aspirin chronic use (HR 0.55, 95% CI: 0.40-0.75, P < 0.001). Each year of omeprazole use increased GC risk by 9%, and each year of aspirin use decreased GC risk by 10% among omeprazole chronic users. The lowest rate of GC was found in omeprazole nonusers/ aspirin chronic users, and the highest, in omeprazole chronic users/aspirin nonusers., Conclusion: Higher GC rate was associated with omeprazole chronic use and inversely associated with aspirin chronic use relative to omeprazole nonuse in community-dwelling elderly., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Most dyspneic patients in internal medicine departments have co-morbidities that interfere with the clinical diagnosis. The role of brain natriuretic peptide (BNP) levels is well-established in the acute setting but not in hospitalized patients., Objectives: To evaluate the additive value of BNP tests in patients with dyspnea admitted to medical wards who did not respond to initial treatment., Methods: We searched the records of patients who were hospitalized in the department of internal medicine D at Sheba Medical Center during 2012 and were tested for BNP in the ward. Data collected included co-morbidity, medical treatments, diagnosis at presentation and discharge, lab results including BNP, re-hospitalization, and mortality at one year following hospitalization., Results: BNP results were found for 169 patients. BNP was taken 1.7 ± 2.7 days after hospitalization. According to BNP levels, dividing the patients into tertiles revealed three equally distributed groups with a distinctive character. The higher tertile was associated with higher rates of cardiac co-morbidities, including heart failure, but not chronic obstructive pulmonary disease. Higher BNP levels were related to one-year re-hospitalization and mortality. In addition, higher BNP levels were associated with higher rates of in-admission diagnosis change., Conclusions: BNP levels during hospitalization in internal medicine wards are significantly related to cardiac illness, the existence of heart failure, and patient prognosis. Thus, BNP can be a useful tool in managing dyspneic patients in this setting.

Introduction: Conflicting data exist on the prognostic significance of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR)., Objective: The purpose of this study was to evaluate whether PPM implantation after TAVR is associated with adverse outcomes., Methods: A retrospective analysis of a cohort comprised patients enrolled in a prospective registry between 2008 and 2019. Participants were allocated into 3 groups: patients without a prior pacemaker (n = 930 [75%]), those with previous pacemaker implantation (n = 118 [10%]), and those with pacemaker implantation after TAVR (n = 191 [15%]). The primary outcome included death and heart failure hospitalizations at 1 year. Secondary outcomes included death and heart failure hospitalizations stratified by pacing burden., Results: A total of 1239 patients underwent TAVR with a median follow-up period of 2.3 years (interquartile range 1-4 years). Patients with previous and new pacemaker implantation were older (84 [80-88], 84 [80-88], and 82 [78-86] years; P = .009) and had lower baseline left ventricular ejection fraction (50% ± 15%, 55% ± 12%, and 56% ± 12%; P < .001). Patients who underwent new pacemaker implantation had higher combined outcome of death and heart failure hospitalizations (21%,12%, and 14%; P = .01). New pacemaker implantation was associated with almost twice the risk of 1-year mortality (odds ratio 1.85; 95% confidence interval 1.13-3.02; P = .014). Pacing burden, however, was not associated with the primary outcome. Furthermore, no significant difference was observed at long-term follow-up (cumulative probability to develop the primary end point at 3 years was 57% ± 2% [without PPM], 57% ± 6% [prior PPM], 54% ± 4% [new PPM]; P = .52)., Conclusion: Pacemaker implantation after TAVR is associated with higher 1-year adverse outcome, but this attenuates over time, suggesting that competing factors may play a role. Interestingly, pacing burden is not associated with adverse clinical course., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The current categorization of cardiovascular (CV) risk broadens the indications for statin therapy. Coronary artery calcium (CAC) identifies those who are most likely to benefit from primary prevention with statin therapy. The multi-ethnic study of atherosclerosis-calcium (MESA-C) includes CAC for CV risk stratification., Objective: We aimed to establish whether the MESA-C score improves allocation to statin treatment in a cohort of asymptomatic adults. We also analyzed patient survival according to their risk score calculation., Design: A retrospective analysis of asymptomatic adults., Participants: A total of 632 consecutive subjects free of coronary artery disease (CAD) and/or stroke, mean age 56 ± 7 years, 84% male, underwent clinical evaluations and CAC measurements., Main Measures: PCE and MESA-C risk scores were calculated for each subject. According to the 10-year risk for CV events, subjects were classified into moderate and high CV risk (≥7.5%) for whom a statin is clearly indicated, or borderline and low CV risk (<7.5%)., Key Results: During mean follow-up of 6.5 ± 3.3 years, 52 subjects experienced their first CV event. Those with a MESA-C risk score < 7.5% had favorable outcomes even when the PCE indicated a risk of ≥ 7.5%. The MESA-C score improved the discrimination of CV risk with the ROC curves C-statistics increasing from 0.653 for the PCE to 0.770 for the MESA-C. Of those, 84% (99/118) with borderline CV risk (5-7.5%) according to the PCE score, were reallocated by the MESA-C score into a higher (≥7.5%) or lower (<5%) CV risk category. Furthermore, subjects with low MESA-C scores had the highest survival rate regardless of the PCE risk, while those with high MESA-C risks had the lowest survival rate regardless of the PCE risk., Conclusion: In asymptomatic subjects, the MESA-C score improves allocation to statin treatment and CV risk discrimination, while both scores are essential for more precise survival estimations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shlomai, Shemesh, Segev, Koren-Morag and Grossman.)

Background: The association between proton pump inhibitor (PPI) use and increased risk of dementia is controversial., Aim: Investigating this issue in a large population of community-dwelling elders., Methods: Our database was retrospectively searched for all community-dwelling patients aged ≥65 years who newly diagnosed with dementia/cognitive decline (DCD) between January 2002 - December 2012. Receiving ≥11 prescriptions of PPIs/year was categorized as PPI users. Clinical data were collected from the medical files. Risk of DCD in PPI users was analyzed by Cox regression models., Results: Included 48,632 elders of whom 8,848 were diagnosed with DCD (18.2%). PPI use was documented in 10,507, of whom 1,959 were subsequently diagnosed with DCD (18.6%). Among 38,125 non-PPI users, 6,889 (18.1%) were diagnosed with DCD. The hazard ratio for occurrence of DCD in PPI users compared to non-users was 0.85 (95% CI: 0.81-0.89, P <0.001) in an un-adjusted Cox regression model and 0.83 in a Cox regression model adjusted for age and sex (95% CI: 0.79-0.87, P <0.001). Multivariate Cox regression accounting for background diseases, marital status, and socioeconomic state yielded a hazard ratio of 0.77 (95% CI: 0.73-0.81, P <0.001)., Conclusion: PPI use wasn't associated with DCD development in chronic PPI users., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: The association of anemia with dementia in elders is controversial. We examined the potential association of anemia with dementia in a large population of elders., Methods: Historical-prospective registry-based study. Included 36,951 community-dwelling elders (65-113 years) that were followed during 2002-2012. Anemia of all kinds was defined according to Clalit Health Services (CHS) definitions: hemoglobin (HGB) <14 g/dL men, <12 g/dL women; and World Health Organization (WHO): HGB <13 g/dL men, <12 g/dL women. Anemia was categorized as mild (HGB 11-13 g/dL men, 11-12 g/dL women) or moderate-severe (HGB <8-10.9 g/dL men and women). Background data, laboratory values, and diagnosis of dementia and cognitive decline (DCD) were reviewed., Results: During the 10-year follow-up period, DCD was newly diagnosed in 7,180 subjects (19.4%). Subjects with DCD had a higher rate of anemia than those without DCD. Time to development of DCD was 1.5 years shorter in those with than without anemia. On multivariate Cox regression analysis adjusted for age and sex, the hazard ratio (HR) for DCD was 1.45 (95% CI: 1.37-1.54) by CHS and 1.51 (95% CI: 1.41-1.61) WHO anemia criteria. The more severe the anemia, the greater the risk of DCD development (HGB 13-14 g/dL [men only], HR = 1.20 [95% CI: 1.09-1.32]; mild anemia, HR = 1.38 [95% CI: 1.28-1.49]; moderate-severe anemia, HR = 1.64 [CI: 1.41-1.90]). Every decrease in 1 standard deviation of HGB (1.4 g/dL) increased the DCD risk by 15%. A competing risk model has weakened the association of anemia with DCD risk., Conclusions and Implications: Anemia in community-dwelling elders appears to be associated with an increased DCD risk in a dose-response manner. Application of the WHO anemia criteria in men may miss patients with mild anemia that places them at DCD risk. Further research should look at anemia as a cause of reversible dementia., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Aim: Data on cardiovascular outcomes in elderly using proton pump inhibitors (PPI) are scant. We aimed to test the association between PPI use and the occurrence of first-time ischemic stroke (FTIS) among elderly., Methods: The electronic database of a centrally located district branch of a large health maintenance organization in Israel was retrospectively screened (2002-2016) for community-dwelling individuals (≥65-95 years) for demographics and co-morbidities. Follow-up was until FTIS, death or end of study. Findings were analyzed by PPI use and occurrence of FTIS., Results: 29,639 subjects (without history of stroke and use of antiplatelet aggregation drugs) mean age of 82.2 ± 5.5 years (range: 65-95 years, 38% male) were analyzed: 8,600 (29%) used PPIs. Mean follow up was 10.58 years (SD ± 5.44). Similar total and annual occurrence rates of FTIS were depicted in PPI users and non-users (20.9% vs. 21% and 2% vs. 2.1%, respectively). On a Cox regression analysis, upon adjustment for age, gender and cardiovascular disease related risk factors, PPI use was significantly associated with lower rates of FTIS (HR 0.73, 95% C.I. 0.69-0.77, p < 0.001). The risk for FTIS was significantly lower in subjects using PPI at any dose and for any time period compared to non-users (HR 0.9, 95% C.I. 0.85-0.96 for 7-48 yearly prescriptions and HR 0.51, 95% C.I. 0.46-0.55 for ≥49 yearly prescriptions)., Conclusions: PPI use was associated with lower rates of FTIS in community-dwelling elders. Prospective large-scale studies are needed to fully elucidate the effect of PPI in this aging population., (© 2020 The British Pharmacological Society.)

Objective: The need for personalization of the reference values of thyroid function tests has been previously suggested. We aimed at determining TSH reference values in a large cohort of children according to age, sex, BMI, and ethnicity., Design: A population-based cohort study., Methods: The study cohort included 75 549 healthy children aged 5-18 years. Data analyzed included age, gender, TSH, FT4 levels, BMI and ethnicity. Multivariate logistic regression analysis examined the associations between the study parameters., Results: TSH in the Jewish population is lower than in the non-Jewish population (median: 2.1 IU/L (IQR: 1.5) vs 2.2 IU/L (IQR: 1.5), P < 0.0001). TSH is significantly affected by BMI for children defined as underweight, normal weight, overweight or obese, levels increased as weight diverged from the normal range (median levels: 2.1 IU/L (IQR: 1.4), 2.0 IU/L (IQR: 1.3), 2.1 IU/L (IQR: 1.4), 2.4 (IQR: 1.5), respectively, P < 0.001). The 2.5 percentile is affected by gender and BMI (P < 0.02 and P < 0.001, respectively), while the 97.5 percentile is affected by ethnic origin and BMI (P < 0.001 for both). New TSH reference intervals (RI) adjusted according to BMI and ethnicity are suggested. Comparison of the old and new RI demonstrate the significance of RI personalization: 25.1% of the children with TSH levels above the old RI are within the new RI, while 2.3% of the children who were in the old RI are below the new RI., Conclusions: TSH reference values in children are affected by BMI and ethnicity. Reference values should be individualized accordingly to improve future clinical decision-making and treatment.

Study Objectives: To assess the accuracy of WatchPAT (WP-Itamar-Medical, Caesarea, Israel) enhanced with a novel systolic upstroke analysis coupled with respiratory movement analysis derived from a dedicated snoring and body position (SBP) sensor, to enable automated algorithmic differentiation between central sleep apnea (CSA) and obstructive sleep apnea (OSA) compared with simultaneous in-lab sleep studies with polysomnography (PSG)., Methods: Eighty-four patients with suspected sleep-disordered breathing (SDB) underwent simultaneous WP and PSG studies in 11 sleep centers. PSG scoring was blinded to the automatically analyzed WP data., Results: Overall WP apnea-hypopnea index (AHI; mean ± SD) was 25.2 ± 21.3 (range 0.2-101) versus PSG AHI 24.4 ± 21.2 (range 0-110) (p = 0.514), and correlation was 0.87 (p < 0.001). Using a threshold of AHI ≥ 15, the sensitivity and specificity of WP versus PSG for diagnosing sleep apnea were 85% and 70% respectively and agreement was 79% (kappa = 0.867). WP central AHI (AHIc) was 4.2 ± 7.7 (range 0-38) versus PSG AHIc 5.9 ± 11.8 (range 0-63) (p = 0.034), while correlation was 0.90 (p < 0.001). Using a threshold of AHI ≥ 15, the sensitivity and specificity of WP versus PSG for diagnosing CSA were 67% and 100% respectively with agreement of 95% (kappa = 0.774), and receiver operator characteristic (ROC) area under the curve of 0.866, (p < 0.01). Using a threshold of AHI ≥ 10 showed comparable overall sleep apnea and CSA diagnostic accuracies., Conclusions: These findings show that WP can accurately detect overall AHI and effectively differentiate between CSA and OSA.

Background: Statins and selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on health outcomes in the general population. Their effect on survival in debilitated nursing home residents is unknown., Objectives: To assess the relationships between statins, SSRIs, and survival of nursing home residents., Methods: Baseline patient characteristics, including chronic medications, were recorded. The association of 5-year survival with different variables was analyzed. A sub-group analysis of survival was performed according to baseline treatment with statins and/or SSRIs., Results: The study comprised 993 residents from 6 nursing homes. Of them, 285 were males (29%), 750 (75%) were fully dependent, and 243 (25%) were mobile demented. Mean age was 85 ± 7.6 years (range 65-108). After 5 years follow-up, the mortality rate was 81%. Analysis by sub-groups showed longer survival among older adults treated with only statins (hazard ratio [HR] for death 0.68, 95% confidence intervals [95%CI] 0.49-0.94) or only SSRIs (HR 0.6, 95%CI 0.45-0.81), with the longest survival among those taking both statins and SSRIs (HR 0.41, 95%CI 0.25-0.67) and shortest among residents not taking statins or SSRIs (P < 0.001). The survival benefit remained significant after adjusting for age and after conducting a multivariate analysis adjusted for sex, functional status, body mass index, mini-mental state examination, feeding status, arrhythmia, diabetes mellitus, chronic kidney disease, and hemato-oncological diagnosis., Conclusions: Treatment with statins and/or SSRIs at baseline was associated with longer survival in debilitated nursing home residents and should not be deprived from these patients, if medically indicated.

Background: Serum alanine aminotransferase (ALT) levels below and above the reference range have been found to serve as a marker of liver injury and to predict all-cause mortality. The need to adjust the reference range by age, sex, or other parameters remains unclear. The current reference range of serum ALT in Israel is 0-34 IU/l for women and 0-45 IU/l for men. We aimed to test the applicability of the current reference range values of ALT in specific people - the elderly population., Methods: A retrospective design was used. The study population consisted of community-dwelling individuals aged at least 65 years who were tested for serum ALT in 2002 at a large health management organization and followed until the end of December 2012. Data were collected on demographics, laboratory tests, comorbidities, and mortality., Results: A total of 49 634 participants (59% women, mean age 83.2±6.3 years) were included. ALT levels between 16 and 25 IU/l were associated with the lowest mortality (hazard ratio=1), and values of less than 16 IU/l and more than 25 IU/l (unadjusted) were associated with higher mortality risk, yielding a U-shaped pattern.Highest mortality rates were also revealed at serum ALT levels more than 56 IU/l and less than 10 IU/l. A significant association of higher mortality risk was noted with lower mean values of hemoglobin, albumin, and total cholesterol, both for patients with lower serum ALT levels (<10 IU/l) and patients with higher serum levels (>56 IU/l)., Conclusion: Very low and very high levels of serum ALT within the current reference range are associated with an increased risk of death in community-dwelling individuals of at least 65 years old.

To investigate whether among patients with a negative temporal artery biopsy (TAB) there are clinical features that may differentiate between patients with an eventual diagnosis of giant cell arteritis (GCA) and those without arteritis, and to assess the eventual diagnoses of patients without arteritis. Retrospective analysis of patients with a negative TAB performed between 1/1/2000 and 31/12/2015. Information collected included baseline clinical and laboratory data. Patients' final diagnoses were obtained from medical records. Patients eventually diagnosed with GCA were compared with those without arteritis, and predictive features for GCA diagnosis were assessed. A total of 154 patients with a negative TAB were included in the study. Among them, 31 (20%) were eventually diagnosed with GCA. The leading alternative diagnoses of patients without arteritis were self-limited disease (23%), isolated polymyalgia rheumatica (PMR) (18%), and neurological conditions (17%). In the multivariate analysis, predictors for diagnosis of GCA among patients with a negative TAB included PMR (OR = 2.86, 95% CI 1.06-7.69), platelet count (OR = 1.28, 95% CI 1.07-1.53), and ACR score > 2 (OR = 13.4, 95% CI 4.27-42.03). Among patients with a negative TAB, the best predictors for diagnosis of GCA are fulfillment of the ACR criteria, a clinical diagnosis of PMR, and high platelet levels. These features may aid in the diagnostic work-up of patients with a negative TAB.

Background: Coronary artery calcification (CAC) is associated with increased cardiovascular (CV) risk. Left ventricular hypertrophy (LVH) is an independent risk factor for CV events. Our aim was to estimate the relative CV risk of LVH in the presence of CAC., Methods: We included asymptomatic hypertensive patients who were enrolled in the calcification arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). Patients had baseline echocardiography and computed tomography to assess CAC. The primary end-point was the first CV event., Results: Two hundred and fifty-two subjects (mean age 64.7 ± 5.5 years, 54% men) were followed for a mean of 13.3 ± 2.6 years. 72 patients (28.5%) had LVH and 159 patients (63%) had CAC. During follow up, 89 patients had a first CV event. The rate of CV events was higher in those with than in those without CAC (43.4% vs. 21.5%, P < 0.01) and in those with than in those without LVH (44% vs. 31.6%, P < 0.01). However, LVH had no effect on CV events in the absence of CAC, whereas LVH almost doubled the rate of CV events (61.4% vs. 36.5%, P < 0.01) in the presence of CAC. In comparison to patients without CAC and without LVH the hazard ratio for CV event in those with LVH was 1.46 (95% confidence interval [CI], 0.50-4.21) in those without CAC and 4.4 (95% CI, 2.02-9.56) in those with CAC., Conclusions: LVH and CAC independently predict CV events in asymptomatic hypertensive patients. However, the risk of LVH is mainly observed in those with CAC., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Purpose: The aim of this study was to evaluate the effects of fish oils, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on ventricular tachyarrhythmic episodes (VTEs) in implantable cardioverter defibrillator (ICD) recipients with ischemic cardiomyopathy., Methods: One hundred five ICD recipients with ischemic cardiomyopathy received 3.6 g of EPA and DHA and placebo for 6 months, each at a random order, with a 4-month washout period between treatments. Eighty-seven patients completed the 16-month study protocol. The primary end point was any VTE (including sustained and non-sustained ventricular tachycardias at a rate of >150 bpm) as recorded by the ICDs. Secondary end points included device therapy (anti-tachycardia pacing (ATP) or shocks)., Results: During treatment with fish oils, there was a significant increase in EPA and DHA concentrations in red blood cells (RBCs) and subcutaneous fat tissue. Among 87 patients who completed the study protocol, the mean number of VTEs was significantly lower during treatment with fish oil (1.7) vs. placebo (5.6; p = 0.035). Appropriate device therapy for VTE occurred in 18 (21%) patients. Fish oil therapy was associated with a trend toward fewer VTEs terminated with ATP (2.8 ± 13.7 vs. 0.5 ± 2.1, respectively; p = 0.077). VTE terminated by ICD shocks, however, was rare, and rates were similar between both groups (0.11 ± 0.6 vs. 0.10 ± 0.4, p = not significant, respectively)., Conclusions: Our data suggest that fish oil therapy may be associated with a reduction in the frequency of VTE in ICD recipients with ischemic cardiomyopathy.

Background: Bone maturation is currently assessed by subjective and automated radiography., Objectives: To evaluate the concordance and reproducibility of a quantitative ultrasound (QUS) based device versus X-ray based methods., Methods: The study population comprised 150 children, 76 males, 4-17 years of age. X-ray scans were evaluated according to wrist, carpal and phalanx areas for bone age. QUS was performed by the the BAUS™ device (SonicBone, Rishon Lezion, Israel), using speed-of-sound (SOS) and distance attenuation factor (ATN) in similar areas. Data from 100 subjects were used to establish the device conversion equation, and 50 measurements were assigned to assess inter-modality agreement., Results: BAUS showed high repeatability performance, 0.73% relative standard deviation for SOS and 3.5% for ATN. R2 for the conversion equation, including gender, SOS, and ATN, was 0.80 for all methods (P < 0.001). There was no significant bias in bone age assessments., Conclusions: Bone age assessment by SonicBone is comparable to the assessment by X-ray based methods.

Background: Endothelial function is a marker for cardiovascular risk. Thus, abnormal endothelial function may be associated with adverse 1-year outcome in patients presenting to the emergency department chest pain unit (CPU)., Methods: Following endothelial function testing, using EndoPAT 2000 in 300 consecutive subjects with chest pain and no history of coronary artery disease (CAD) presenting to CPU, patients underwent coronary computerized tomographic angiography (CCTA) or single-photon emission computed tomography according to availability., Results: Mean 10-year Framingham risk score (FRS) was 6.6±5.9%, median reactive hyperemia index (RHI) as a measure of endothelial function 2.08 and mean was 2.0±0.4. During a 1-year follow-up, the 20 (6.6%) patients who developed major adverse cardiovascular end-points (MACE), including all-cause mortality, non-fatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions, had higher 10-year FRS (10.5±8.2% vs 6.3±5.7%; p<0.001), lower baseline RHI (1.43±0.41 vs 2.10±0.44; p<0.001) and a greater extent of coronary atherosclerosis lesions (70% vs 3.9%, p<0.001) in the CPU CCTA, compared to those without MACE. RHI≤the median was associated with higher 1-year MACE (13% vs 0.7%, p<0.001) compared to RHI>the median. Multivariate analysis demonstrated that RHI≤the median is an independent predictor of coronary atherosclerosis lesions in the CPU CCTA (OR 5.98, 95% CI 03.29-10.88; p<0.001) and 1-year MACE (OR 15.207, 95% CI 2.00-115.33; p<0.01)., Conclusions: Our findings suggest that non-invasive endothelial function testing may have clinical utility in triaging patients in the CPU and in predicting 1-year MACE., (Copyright © 2017 Elsevier B.V. All rights reserved.)

To evaluate the association between blood pressure variability (BPV) and mortality in the elderly, all blood pressure measurements recorded in a cohort of individuals 65 years and older were collected and the association between BPV coefficient of variation (BPV divided by mean arterial pressure) was calculated. Mortality during a 10-year period was compared between BPV coefficient of variation quartiles. Overall, 39 502 individuals 65 years and older were included in the analysis, of which 31 737 (80.3%) were hypertensive; 12 817 (32.4%) individuals died during the study period. Mortality was lower in the second and third blood pressure quartiles compared with the first quartile in both the normotensive and hypertensive groups. In both normotensive and hypertensive individuals, mortality was higher in the fourth quartile, but it was more pronounced in normotensive individuals (odds ratio, 1.18; 95% confidence interval, 1.06-1.31 in hypertensive individuals vs odds ratio, 1.27; 95% confidence interval, 1.17-1.37 in normotensive individuals). High and low BPV are associated with mortality in both hypertensive and normotensive elders., (©2017 Wiley Periodicals, Inc.)

Background: Bacteremia is associated with high morbidity and mortality rates. Initiation of inadequate empiric antibiotic therapy is associated with a worse outcome. The aim of this study was to establish the prevalence and the factors associated with inappropriate empiric antibiotic therapy in patients hospitalized with bacteremia., Methods: A cross-sectional study was conducted during January 2010-December 2011 at the medical wards of the Chaim Sheba Medical Center, Israel. The records of all patients with bacteremia were reviewed. Clinical and laboratory characteristics, bacteremic pathogens and antimicrobial agents were retrieved from the medical records. Factors associated with appropriateness of empiric antibiotic therapy were assessed., Results: A total of 681 eligible adults were included in the study. Antibiotic therapy was found to be inappropriate in 138 (20.2%) patients (95% C.I. 17.2-23.2). The rate of appropriateness was not related to the type of antibiotic regimen and the type of bacteria. Patients with healthcare-associated infections were more likely to be administrated inappropriate antibiotic therapy. Patients with primary bloodstream infections were also more likely to be administrated inappropriate antibiotic therapy. Empiric combination therapy was more likely to be appropriate than monotherapy, except for an aminoglycosides-based combination., Conclusions: Combination empiric antibiotic therapy should be considered in patients with healthcare-associated infections and in those with primary bloodstream infections.

Objectives: Cranial ischaemic events constitute a significant component in the clinical spectrum of giant cell arteritis (GCA). Our aim was to investigate whether cardiovascular risk factors, specific medications and baseline clinical features are associated with the development of severe cranial ischaemic events in GCA patients., Methods: Retrospective analysis of GCA patients. Information collected included baseline clinical and laboratory data, comorbidities, cardiovascular risk factors and medications. GCA Patients with and without severe cranial ischaemic complications were compared., Results: A total of 83 patients with GCA were included in the study. Among them, 24 (29%) patients developed severe cranial ischaemic events. Compared with patients without severe cranial ischaemic events, those with severe cranial ischaemic events had lower erythrocyte sedimentation rate (ESR) levels at diagnosis (81±17 vs. 93±21, p=0.018) and were more likely to have jaw claudication (37.5% vs. 17%, p=0.043). Rate of cardiovascular risk factors and rate of use of anti-platelets and statins were similar between the two groups. The use of β-blockers was higher among patients with severe ischaemic events (46% vs. 20%, p=0.019). Logistic regression analysis showed that lower ESR levels (OR=0.967, 95% CI, 0.94, 0.99) and β-blockers use (OR=4.35, 95% CI, 1.33, 14.2) predicted development of severe cranial ischaemic complications., Conclusions: The present study demonstrated that GCA patients with severe cranial ischaemic events had lower inflammatory responses and were more likely to have been treated with β-blockers. Cardiovascular risk factors and antiplatelet therapy had no effect on the occurrence of severe cranial ischaemic events.

Background: Glycated hemoglobin (HgbA1C) is being increasingly used for the diagnosis of diabetes mellitus due to its high availability and reproducibility. Several studies have shown that HgbA1C levels may be affected by levels of hemoglobin and nutritional factors associated with anemia, such as vitamin B12 and iron deficiency. However, none included elderly subjects. The aim of the present study was to investigate these effects in the older nondiabetic population., Methods: A retrospective cohort study design was used. The computerized database of a large health management organization was reviewed for all subjects without diabetes mellitus who underwent at least one measurement of HgbA1C and other hemoglobin parameters in 2002 at age≥65years. HgbA1C levels were correlated with hemoglobin, hematocrit, ferritin, iron, transferrin, vitamin B12, and folic acid levels., Results: A total of 11,352 subjects met the study criteria. Those with HgbA1C levels in the highest quintile (6.21-6.49%, 44.4-47.7mmol/mol) had significantly lower levels of hemoglobin, hematocrit, and iron than patients with HgbA1C levels in the lowest quintile (<5.4%, 36mmol/mol), but no linear correlation was found. There was no correlation of HgbA1C level with levels of ferritin, vitamin B12, and folic acid., Conclusions: In elderly nondiabetic subjects, HgbA1C levels are not correlated with hemoglobin level or nutritional factors associated with anemia and may be interpreted without consideration of these factors., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

The diagnosis of giant cell arteritis (GCA) is based on clinical grounds and confirmed by characteristic histological findings on temporal artery biopsy (TAB). Patients may be diagnosed with GCA based on clinical grounds only, despite negative histological findings. We aimed to investigate which baseline clinical and laboratory features best predict an ultimate diagnosis of giant cell arteritis among patients referred to TAB. We retrospectively analyzed 224 patients who underwent TAB in our hospital between 2000 and 2014. Patients were diagnosed with GCA if TAB was positive for GCA, or by clinical grounds only despite a negative biopsy, provided they fulfilled the American College of Rheumatology 1990 criteria. Baseline clinical and laboratory features were obtained from medical records. Predictors of an ultimate GCA diagnosis were investigated. Overall, 82 patients were diagnosed with GCA-57 had histological evidence of GCA and 25 were diagnosed with GCA despite a negative biopsy. One hundred and forty-two patients were not diagnosed with GCA. Predictors of an eventual diagnosis of GCA in a multivariate logistic regression analysis were headache (OR = 6; p < 0.001), jaw claudication (OR 4.5; p = 0.007), erythrocyte sedimentation rate (ESR) (OR = 1.5; p = 0.032) and platelet count (OR = 1.74; p = 0.004). Among patients referred to TAB, headache, jaw claudication, ESR, and thrombocyte levels are predictors for an ultimate diagnosis of GCA. These clinical and laboratory features should be considered when contemplating the diagnosis and treatment of GCA.

Background: The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function., Methods and Results: Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ~50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality., Conclusions: Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies.

Objective: The association between subclinical hypothyroidism and hyperthyroidism and mortality in the elderly is poorly defined. This study was designed to evaluate the association between subclinical hypothyroidism and subclinical hyperthyroidism and mortality in the elderly and to define the thyroid-stimulating hormone values associated with excess mortality in the elderly., Methods: We performed a retrospective cohort study with a review of a computerized database of a large health care organization. Patients aged more than 65 years evaluated in the years 2002 to 2012 with documented normal free T4 values were included in the analysis. All cases of known thyroid disease or cases in which thyroid medications were dispensed were excluded. Analysis was performed only on individuals who were not treated for hyperthyroidism or hypothyroidism during the follow-up period. Subjects were divided into 3 groups based on thyroid-stimulating hormone values: normal (normal thyroid-stimulating hormone), subclinical hypothyroidism (thyroid-stimulating hormone >4.2 mIU/L), and subclinical hyperthyroidism (thyroid-stimulating hormone <0.35 mIU/L). All-cause mortality hazard ratio (HR) was compared among the 3 groups, and a subanalysis according to thyroid-stimulating hormone values was performed in those with subclinical hypothyroidism and subclinical hyperthyroidism., Results: A final analysis was performed on 17,440 individuals with subclinical thyroid disease (538 with subclinical hyperthyroidism [3.1%], 1956 with subclinical hypothyroidism [11.2%], 14,946 normal cases [85.7%], average age of 83 years, 10,289 were women) who were followed up for 10 years. Both subclinical hypothyroidism (HR, 1.75; confidence interval [CI], 1.63-1.88) and subclinical hyperthyroidism (HR, 2.33; CI, 2.08-2.63) were associated with significantly increased mortality, and this association persisted on multivariate analysis (subclinical hypothyroidism HR, 1.68; CI, 1.56-1.8, subclinical hyperthyroidism HR, 1.93; CI, 1.7-2.17). Crude mortality was elevated at 1, 2, and 5 years, but this association seemed to decrease as time from initial analysis increased (most significant association at 1 year). Thyroid-stimulating hormone values greater than 6.38 mIU/L were associated with the highest mortality in those with subclinical hypothyroidism after multivariate adjustment (HR, 1.708; CI, 1.38-2.12), whereas in subclinical hyperthyroidism, no threshold for increased mortality was identified. Mortality was higher., Conclusions: Both subclinical hypothyroidism and subclinical hyperthyroidism are associated with increased mortality in the elderly. A threshold thyroid-stimulating hormone value (>6.35 mIU/L) exists for increased mortality in subclinical hypothyroidism, but not in subclinical hyperthyroidism., (Copyright © 2016 Elsevier Inc. All rights reserved.)