Determining the optimal daily gonadotropin dose to maximize the oocyte yield in elective egg freezing cycles.

OBJECTIVE: Ovarian stimulation (OS) with high daily gonadotropin doses are commonly offered to patients attempting social/elective egg freezing. However, the optimal daily gonadotropin dose that would allow a higher oocyte yield in the successive IVF cycle attempt was not settled and should be determined. PATIENTS AND METHODS: Data from all women admitted to our IVF unit for social/EEF, who underwent two consecutive IVF cycle attempts, with only those who used in the first attempt a starting daily gonadotropin dose of 300IU were analyzed. Patients characteristics and OS variables were used in an attempt to build a logistic model, helping in determining the daily gonadotropin dose that should be offered to patient during their second EEF attempt, aiming to further increase their oocyte yield. RESULTS: Three hundred and thirteen consecutive women undergoing two successive IVF cycle attempts were evaluated. Using logistic regression model, two equations were developed using individual patient-level data that determine the daily gonadotropin dose needed aiming to increase the oocyte yield in the successive cycle. (a): X=-0.514 + 2.87*A1 + 1.733*A2-0.194* (E2/1000) and (b): P = EXP(X) / [1 + EXP(X)]. CONCLUSIONS: Using the aforementioned equations succeeded in determining the daily gonadotropin dose that might result in increasing oocyte yield, with an AUC of 0.85. Any additional oocyte retrieved to these EEF patients might get them closer to fulfil their desire to parenthood.

Serum Magnesium Is Associated with Long-Term Survival of Non-ST-Elevation Myocardial Infarction Patients.

BACKGROUND: Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease. OBJECTIVE: To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients. METHODS: A retrospective analysis of all patients admitted to a single tertiary center with a primary diagnosis of NSTEMI. Patients with advanced chronic kidney disease were excluded. Clinical data were collected and compared between lower sMg quartile patients (Q1; sMg < 1.9 mg/dL) and all other patients (Q2-Q4; sMg ≥ 1.9 mg/dL). RESULTS: The study cohort included 4552 patients (70% male, median age 69 [IQR 59-79]) who were followed for a median of 4.4 (IQR 2.4-6.6) years. The median sMg level in the low sMg group was 1.7 (1.6-1.8) and 2.0 (2.0-2.2) mg/dL in the normal/high sMg group. The low sMg group was older (mean of 72 vs. 67 years), less likely to be male (64% vs. 72%), and had higher rates of comorbidities, including diabetes, hypertension, and atrial fibrillation (59% vs. 29%, 92% vs. 85%, and 6% vs. 5%; p < 0.05 for all). Kaplan-Meier survival analysis demonstrated significantly higher cumulative death probability at 4 years in the low sMg group (34% vs. 22%; p log rank <0.001). In a multivariable analysis model adjusted for sex, significant comorbidities, coronary interventions during the hospitalization, and renal function, the low sMg group exhibited an independent 24% increased risk of death during follow up (95% CI 1.11-1.39; p < 0.001). CONCLUSIONS: Low sMg is independently associated with higher risk of long-term mortality among patients recovering from an NSTEMI event.

Different effects of chronic omeprazole use on osteoporotic fractures rate in the elderly.

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.

Gastric cancer risk in the elderly is associated with omeprazole use and inversely associated with aspirin use.

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 ±â€…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.

Endothelial function predicts 5-year adverse outcome in patients hospitalized in an emergency department chest pain unit.

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 ±â€Š5.9%; mean 10-year atherosclerotic cardiovascular disease (ASCVD) risk was 7.1 ±â€Š7.2%; median reactive hyperemia index (RHI) as a measure of an endothelial function 2.0 and mean was 2.0 ±â€Š0.4. 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 ±â€Š7.8 vs. 6.3 ±â€Š5.6%; P  = 0.032), higher 10-year ASCVD risk (10.4 ±â€Š9.2 vs. 6.7 ±â€Š6.9%; P  = 0.042), lower baseline RHI (1.6 ±â€Š0.5 vs. 2.1 ±â€Š0.4; 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.

The Use of Brain Natriuretic Peptide as a Decision-supporting Tool in Hospitalized Patients.

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.

The Multi-Ethnic Study of Atherosclerosis-Calcium Score Improves Statin Treatment Allocation in Asymptomatic Adults.

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.

Pacing burden and clinical outcomes after transcatheter aortic valve replacement-A real-world registry report.

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.

Association of Anemia with Dementia and Cognitive Decline among Community-Dwelling Elderly.

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.

Chronic omeprazole use in the elderly is associated with decreased risk of dementia and cognitive decline.

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.

Use of proton pump inhibitors is associated with lower rates of first-time ischemic stroke in community-dwelling elderly.

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.

Watch-PAT is Useful in the Diagnosis of Sleep Apnea in Patients with Atrial Fibrillation.

BACKGROUND: 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.

Pediatric reference values of TSH should be personalized according to BMI and ethnicity.

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.

Detecting central sleep apnea in adult patients using WatchPAT-a multicenter validation study.

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.

Statins and Selective Serotonin Reuptake Inhibitors are Associated with Longer Survival in Nursing Home Residents.

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.

Long-term adherence to growth hormone therapy in a large health maintenance organization cohort.

OBJECTIVE: Adherence to treatment regimen is a key factor in the success of Growth Hormone (GH) therapy. Our objective was to assess the long time adherence to treatment in a large cohort of patients. DESIGN: It is a retrospective study. The data was collected from a single central computerized data center well maintained and checked for quality. All patient aged 1-16 years, treated with GH during 2006-2015 for >2 years, who were insured by "Clalit" Health Maintenance Organization. Adherence was measured by the number of months of pharmacy purchased GH annually: good (11-12), moderate (7-10), and poor (<7) months per year. RESULTS: 2263 patients (59% males) were treated for >2 years. Mean age at treatment initiation was 8.3 ±â€¯3.6 years, 74% were secular Jews, 6.8% ultra-religious Jews and 18.9% of Arab origin. Only 30% of patients had good adherence to GH therapy. Patients who started treatment before age 8 years had poorest adherence rate. No association was found between adherence to GH therapy and gender or socioeconomic status. In a multivariate analysis (gender, age groups, ethnicity and clinic SES) we found the ultra-religious population had higher risk for non adherence (OR 2.16, CI 95% 1.46-3.19). The poorest adherence by age was in the youngest patients. In patients treated for >5 years (n = 668), adherence rate declined slightly over the years. CONCLUSIONS: Long term adherence to GH therapy is suboptimal. Measures for improving adherence especially among younger and ultra- religious patients are needed.

Risk of mortality and level of serum alanine aminotransferase among community-dwelling elderly in Israel.

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.

Negative temporal artery biopsy: predictive factors for giant cell arteritis diagnosis and alternate diagnoses of patients without arteritis.

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.

Left Ventricular Hypertrophy Predicts Cardiovascular Events in Hypertensive Patients With Coronary Artery Calcifications.

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.

Bone Age Assessments by Quantitative Ultrasound (SonicBone) and Hand X-ray Based Methods are Comparable.

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.