A case-control study for comorbidity and laboratory factors associated with food-induced anaphylaxis.

Background: Food-induced anaphylaxis (FIA) is a serious and potentially life-threatening allergic reaction triggered by food allergens. Objective: This case-control study aimed to investigate comorbidities and laboratory factors associated with FIA in the pediatric population of Israel. Methods: Retrospective data from the electronic health records of Leumit Health Care Services were used to identify 711 pediatric patients with FIA and 2560 subjects with food allergy and without anaphylaxis matched for age, gender, and ethnicity. Comorbidities were identified based on medical billing diagnosis codes, and laboratory characteristics were compared between the two groups. Results: The mean ± standard deviation age of patients with FIA was 4.1 ± 4.1 years, and 37.3% were girls. Laboratory analysis revealed increased eosinophil counts (p < 0.001), elevated immunoglobulin E (IgE) (p < 0.001), and IgA levels (p = 0.001) in the FIA group compared with the controls. With regard to comorbidities, the FIA group had higher prevalence rates of allergic diseases, including allergic rhinitis (odds ratio [OR] 1.72; p < 0.001), allergic conjunctivitis (OR 1.84; p = 0.001), asthma (OR 1.36; p < 0.001), angioedema (OR 6.37; p < 0.001), atopic dermatitis (OR 1.77; p < 0.001), and contact dermatitis (OR 1.42; p = 0.001). There was a trend toward significance for chronic spontaneous urticaria (p = 0.051). There was a significant negative association between helminthiases, particularly enterobiasis, and FIA (OR 0.76 [95% confidence interval, 0.59-0.98]; p = 0.029). Conclusion: This study provides valuable epidemiologic evidence on the associations among FIA, comorbidities, and laboratory factors in the pediatric population.

Glucose-6-Phosphate Dehydrogenase Deficiency and Coronavirus Disease 2019.

In this cohort study conducted in a national healthcare organization in Israel, we found that individuals with glucose-6-phosphate dehydrogenase deficiency had an increased risk of coronavirus disease 2019 (COVID-19) infection and severity, with higher rates of hospitalization and diagnosed long COVID.

Greater temporal regularity of primary care visits was associated with reduced hospitalizations and mortality, even after controlling for continuity of care.

BACKGROUND: Previous studies have shown that more temporally regular primary care visits are associated with improved patient outcomes. OBJECTIVE: To examine the association of temporal regularity (TR) of primary care with hospitalizations and mortality in patients with chronic illnesses. Also, to identify threshold values for TR for predicting outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: We used data from the electronic health record of a health maintenance organization in Israel to study primary care visits of 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease). MAIN MEASURES: We calculated TR for each patient during a two-year period (2016-2017), and divided patients into quintiles based on TR. Outcomes (hospitalization, death) were observed in 2018-2019. Covariates included the Bice-Boxerman continuity of care score, demographics, and comorbidities. We used multivariable logistic regression to examine TR's association with hospitalization and death, controlling for covariates. KEY RESULTS: Compared to patients receiving the most regular care, patients receiving less regular care had increased odds of hospitalization and mortality, with a dose-response curve observed across quintiles (p for linear trend < 0.001). For example, patients with the least regular care had an adjusted odds ratio of 1.40 for all-cause mortality, compared to patients with the most regular care. Analyses stratified by age, sex, ethnic group, area-level SES, and certain comorbid conditions did not show strong differential associations of TR across groups. CONCLUSIONS: We found an association between more temporally regular care in antecedent years and reduced hospitalization and mortality of patients with chronic illness in subsequent years, after controlling for covariates. There was no clear threshold value for temporal regularity; rather, more regular primary care appeared to be better across the entire range of the variable.

Patient-level predictors of temporal regularity of primary care visits.

BACKGROUND: Patients with chronic diseases should meet with their primary care doctor regularly to facilitate proactive care. Little is known about what factors are associated with more regular follow-up. METHODS: We studied 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease), cared for by Leumit Health Services, an Israeli health maintenance organization. Patients were divided into the quintile with the least temporally regular care (i.e., the most irregular intervals between visits) vs. the other four quintiles. We examined patient-level predictors of being in the least-temporally-regular quintile. We calculated the risk-adjusted regularity of care at 239 LHS clinics with at least 30 patients. For each clinic, compared the number of patients with the least temporally regular care with the number predicted to be in this group based on patient characteristics. RESULTS: Compared to older patients, younger patients (age 40-49), were more likely to be in the least-temporally-regular group. For example, age 70-79 had an adjusted odds ratio (AOR) of 0.82 compared to age 40-49 (p < 0.001 for all findings discussed here). Males were more likely to be in the least-regular group (AOR 1.18). Patients with previous myocardial infarction (AOR 1.07), atrial fibrillation (AOR 1.08), and current smokers (AOR 1.12) were more likely to have an irregular pattern of care. In contrast, patients with diabetes (AOR 0.79) or osteoporosis (AOR 0.86) were less likely to have an irregular pattern of care. Clinic-level number of patients with irregular care, compared with the predicted number, ranged from 0.36 (fewer patients with temporally irregular care) to 1.71 (more patients). CONCLUSIONS: Some patient characteristics are associated with more or less temporally regular patterns of primary care visits. Clinics vary widely on the number of patients with a temporally irregular pattern of care, after adjusting for patient characteristics. Health systems can use the patient-level model to identify patients at high risk for temporally irregular patterns of primary care. The next step is to examine which strategies are employed by clinics that achieve the most temporally regular care, since these strategies may be possible to emulate elsewhere.

Prevalence of neurological diseases among patients with selective IgA deficiency.

Background: There are no published epidemiologic studies with regard to the prevalence of neurologic diseases among subjects with selective immunoglobulin A (IgA) deficiency (sIgAD). Objective: To investigate the prevalence of neurologic diseases among the Israeli population with sIgAD. Methods: A population-based case-control study among members of a large nationwide health maintenance organization in Israel providing services to > 700,000 members. The sIgAD group included individuals ≥4 years of age with a serum IgA level of <0.07 g/L and with a diagnosis of sIgAD. The control group was randomly sampled from the entire study population with a case-control ratio of five controls for each case (1:5), with exact matching for age, gender, ethnic group, and socioeconomic status category. Results: A total of 796 subjects ages 20.58 ± 15.46 years; 391 female subjects (49.1%) were identified as having sIgAD. The control group was constituted of 3980 matched subjects. The sIgAD group was characterized by a higher prevalence of autism spectrum disorder and tic disorders. Migraine was less prevalent in the sIgAD group (19 [2.39%]) than in the control group (168 [4.22%]), odds ratio (OR) 0.55 (95% confidence interval {CI}, 0.34-0.90); p = 0.016]. More cases of subjects with epilepsy were observed in the sIgAD group (14 [1.76%]) than in the control group (31 [0.80%]), OR 2.28 (95% CI, 1.12 - 4.44; p = 0.015). Conclusion: Our observation raises the question of the role of IgA in noninfectious diseases of the central nervous system. Further basic studies are needed to explain our observation.

Clinical and prognostic significance of elevated ferritin levels in hospitalised adults.

PURPOSE OF THE STUDY: Elevated ferritin levels are associated with a variety of infectious, malignant and inflammatory diseases. We aimed to investigate the prognostic value of markedly elevated ferritin levels in hospitalised patients with various medical conditions. STUDY DESIGN: Retrospective analysis of patients with a ferritin level higher than 2000 ng/mL hospitalised in Sheba Medical Center between 1 January 2007 and 31 December 2015. Medical conditions of these patients were recorded. In-hospital, 30-day and 1-year mortality rates were evaluated according to ferritin ranges and clinical categories. RESULTS: The study included 722 patients (63.4% men) with a mean age of 63.9±16.7 years. The most common clinical conditions associated with markedly elevated ferritin were infectious diseases and malignancies. The highest mean ferritin levels were associated with rheumatological/inflammatory conditions (16 241.3 ng/dL), particularly in patients with macrophage activation syndrome (MAS) (96 615.5 ng/dL). In-hospital, 30-day and 1-year mortality rates were 32.3%, 46.7% and 70.8%, respectively. The highest in-hospital, 30-day and 1-year mortality rates were observed among patients with solid malignancies (40.1%, 64.7% and 90.3%, respectively), whereas the lowest rates were found among patients with rheumatological/inflammatory conditions, including MAS (21.4%, 38.1% and 45.2%, respectively). Ferritin levels were not associated with mortality. CONCLUSIONS: In hospitalised patients, ferritin levels higher than 2000 ng/mL are mainly associated with infectious and malignant diseases but do not predict mortality.

Chronic spontaneous urticaria after BNT162b2 mRNA (Pfizer-BioNTech) vaccination against SARS-CoV-2.

Background: The factors that trigger and exacerbate chronic spontaneous urticaria (CSU) are well known, but it is not unclear whether messenger RNA (mRNA) vaccination against severe acute respiratory syndrome coronavirus 2 can trigger new cases of CSU or a relapse of CSU after long-term remission. Objective: To study the clinical cases of patients with new-onset CSU and CSU in remission who relapsed within 3 months after BNT162b2 mRNA vaccination. Methods: All patients with a CSU diagnosis within 12 weeks of BNT162b2 mRNA vaccination were retrospectively identified and included in the new-onset CSU and the relapsed CSU groups. The first control group (CSU control group) retrospectively consisted of patients diagnosed with CSU in complete clinical remission for ≥ 6 months, with no CSU relapse after vaccination. The second control group (healthy control group) consisted of subjects who were fully vaccinated and without CSU, matched 1:2 for age and sex with patients with CSU. Results: Twenty-seven patients were included in the relapsed CSU group, 32 patients in the new-onset CSU group, 179 patients in the CSU control group, and 476 subjects in the healthy control group. The relapsed CSU and new-onset CSU groups had more allergic comorbidities overall (19 [70.4%] and 13 [40.6%], respectively) than the CSU control group and the healthy control group (50 [27.9%] and 110 [23.1%], respectively; p < 0.001). Multiple logistic regression analysis showed that a positive autologous serum skin test result, overall allergic comorbidities, and basopenia were positively associated with the probability of CSU relapse within 3 months after BNT162b2 mRNA vaccination (odds ratio [OR] 5.54 [95% confidence interval {CI}, 2.36-13.02], p < 0.001); OR 6.13 [95% CI, 2.52-14.89], p = 0.001; and OR 2.81 [95% CI, 1.17-6.72, p = 0.020, respectively). Conclusion: It is possible that BNT162b2 mRNA vaccination serves as a provoking and/or relapsing factor of CSU in individuals with allergic diseases and/or predisposed autoimmunity.

Patent Foramen Ovale Closure among Patients with Hypercoagulable States Maintained on Antithrombotic Therapy.

BACKGROUND: Percutaneous device closure was shown to effectively prevent recurrent strokes in patients with patent foramen ovale (PFO). Whether this protective effect is relevant for patients with hypercoagulable states (HCSs) is unknown as they were not represented in prior studies. METHODS: Data on 136 consecutive patients with a PFO and clinically significant HCS were retrospectively collected. PFO closure and antithrombotic regimen were decided on an individual basis by the treating physicians, and adherence to therapy was routinely evaluated. The outcome was the occurrence of cerebrovascular accident (CVA) or transient ischemic attack (TIA). RESULTS: HCS types consisted of antiphospholipid syndrome (31%), factor-5 Leiden mutation (22%), prothrombin mutation (18%), protein S deficiency (15%), protein C deficiency (7%), methyl-tetra-hydro folate reductase mutation (5%), and essential thrombocytosis (2%). 102 patients (75%) were maintained on anticoagulants and the remaining on antiplatelet therapy. PFO closure was undertaken in 85 (63%); antithrombotic therapy was not interrupted prior to or after the procedures. At a mean follow-up of 46 ± 8 months, 23 patients (17%; 95% confidence interval, 9.3-22%) experienced an outcome event, mainly in the form of CVAs (n = 15, 65%). In multivariable analysis, PFO closure was associated with a 5-fold decrease in the risk of CVA/TIA (p = 0.02). This effect was independent of the type of HCS or antithrombotic therapy. CONCLUSIONS: Among patients with HCSs maintained on anticoagulant or antiplatelet therapies, PFO closure was associated with a significantly lower risk of CVA or TIA.

Physical fitness mediates the association between age and cognition in healthy adults.

BACKGROUND: Physical fitness is an important contributor to healthy aging that improves cognition. Older adults who engage in cardiorespiratory fitness activities show less cognitive decline. AIMS: To examine whether physical fitness acts as a potential protective mechanism shielding against the negative associations between age and cognition. Specifically, we examined whether physical fitness mediates the relationship between age and processing speed. METHODS: 114 (M = 63.80, SD = 10.63) senior executives completed a computerized cognitive battery composed of four processing speed tasks. Level of physical fitness was assessed on a treadmill stress test and reported in metabolic equivalents (METs). RESULTS: Older age was associated with slower processing speed (r = 0.25, p = 0.007), whereas greater physical fitness was associated with faster processing speed (r = -0.30, p = 0.001). Path analysis indicated that the association between age and processing speed was fully mediated by the level of physical fitness (Indirect effect: ß = 0.10, p = 0.008; Direct effect: ß = 0.16, p = 0.20). CONCLUSIONS AND DISCUSSION: The findings indicate that physical fitness is a strong mediator of the relationship between age and processing speed and imply that physical fitness makes a major contribution to cognitive reserve during the aging process. The results may suggest that the decrease in physical fitness during aging may partially account for slower cognitive processing.

Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients.

BACKGROUND: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from long-standing adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Because obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature. OBJECTIVE: To define the blood profile and associated biomarkers of early moderate-to-severe pediatric AD. METHODS: We compared microarrays and reverse transcription polymerase chain reaction (RT-PCR) of blood cells from 28 AD children (<5 years and within 6 months of disease onset) to healthy control blood cells. Differentially expressed genes (DEGs) in blood (fold change [FCH] > 1.2 and false discovery rate [FDR] < 0.05) were then compared with skin DEGs. RESULTS: Eosinophil and Th2 markers (IL5RA, IL1RL1/ST2, HRH4, CCR3, SIGLEC8, PRSS33, CLC from gene arrays; IL13/IL4/CCL22 from RT-PCR) were up-regulated in early pediatric AD blood, whereas IFNG/Th1 was decreased. Th1 markers were negatively correlated with clinical severity (EASI, pruritus, transepidermal water loss [TEWL]), whereas Th2/Th17-induced interleukin (IL)-19 was positively correlated with SCORAD. Although a few RT-PCR-defined immune markers (IL-13/CCL22) were increased in blood, as previously also reported for skin, minimal overlap based on gene array DEGs was seen. CONCLUSION: The whole blood signature of early moderate-to-severe pediatric AD blood cells show predominantly a Th2/eosinophil profile; however, markers largely differ from the skin profile. Given their complementarity, pooling of biomarkers from blood and skin may improve profiling and predictions, providing insight regarding disease course, allergic comorbidity development, and response to systemic medications.

Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations.

BACKGROUND: Although atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need for better treatments. OBJECTIVE: We sought to globally profile the skin of infants with AD compared with that of adults with AD and healthy control subjects. METHODS: We performed microarray, RT-PCR, and fluorescence microscopy studies in infants and young children (<5 years old) with early-onset AD (<6 months disease duration) compared with age-matched control subjects and adults with longstanding AD. RESULTS: Transcriptomic analyses revealed profound differences between pediatric patients with early-onset versus adult patients with longstanding AD in not only lesional but also nonlesional tissues. Although both patient populations harbored TH2-centered inflammation, pediatric AD also showed significant TH17/TH22 skewing but lacked the TH1 upregulation that characterizes adult AD. Pediatric AD exhibited relatively normal expression of epidermal differentiation and cornification products, which is downregulated in adults with AD. Defects in the lipid barrier (eg, ELOVL fatty acid elongase 3 [ELOVL3] and diacylglycerol o-acyltransferase 2 [DGAT2]) and tight junction regulation (eg, claudins 8 and 23) were evident in both groups. However, some lipid-associated mediators (eg, fatty acyl-CoA reductase 2 and fatty acid 2-hydroxylase) showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H and DGAT2) showed inverse correlations with transepidermal water loss, a functional measure of the epidermal barrier. CONCLUSIONS: Skin samples from children and adult patients with AD share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease.

Sonographic large fetal head circumference and risk of cesarean delivery.

BACKGROUND: Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. OBJECTIVE: In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. STUDY DESIGN: This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. RESULTS: In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4-2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5-minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. CONCLUSION: Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management.

The association of total cholesterol with processing speed is moderated by age in mid- to late-age healthy adults.

OBJECTIVES: To investigate the nature of the association of normal levels of total cholesterol with cognitive function and the contribution of age to this association. METHODS: A sample of 61 senior executives, who were summoned for an annual medical examination with approximately four measurements of total cholesterol during 4 years, were examined with a computerized cognitive battery assessing mental processing speed as a sensitive measure of cognitive decline. We examined the association of total cholesterol with processing speed and the moderating effect of age on this association. RESULTS: A multiple regression analysis yielded a significant interaction between cholesterol and age for processing speed (p = .045). In order to examine the source of the interaction, simple slope analysis was performed. A significant negative high correlation was found for young subjects (p = .021), while no significant correlation was observed at middle (p = .286) or older (p = .584) age. The difference in slopes was robust to adjustment for potential confounding factors, including body mass index, and fasting glucose. CONCLUSIONS: Within the normal range, higher total cholesterol levels were associated with better processing speed in younger ages and this association diminished with increasing age. Our findings highlight the important role of brain cholesterol in good cognitive functioning.

Bisphenol-A exposure and gene expression in human luteinized membrana granulosa cells in vitro.

STUDY QUESTION: Does bisphenol-A (BPA) affect gene expression in human membrana granulosa cells (MGC)? SUMMARY ANSWER: In vitro, short exposure to supra-physiological concentrations of BPA alters human MGC gene expression. WHAT IS KNOWN ALREADY: Exposure to BPA may interfere with reproductive endocrine signaling. In vitro studies, mostly in animal models, have shown an inverse correlation between exposure to BPA and follicular growth, meiosis, and steroid hormone production in granulosa cells. STUDY DESIGN, SIZE, DURATION: Primary cultures of MGC obtained from 24 patients undergoing IVF (for PGD, male factor infertility or unexplained infertility) were exposed to various concentrations of BPA (0, 0.02, 0.2, 2 or 20 µg/ml) for 48 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted in a university-affiliated hospital. Microarray analysis was used to identify genes exhibiting expression changes following BPA exposure. Genes significantly altered were identified based on changes greater than 2-fold relative to the control group (not treated by BPA) and a Student's t-test P-value <0.05. Statistical significance was adjusted for multiple comparisons using the Benjamini-Hochberg method. Alterations in the expression of genes that are involved in the enriched functional annotations altered by BPA at the concentration of 20 µg/ml were confirmed by real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE: A distinct pattern of gene expression was observed in primary cultures of MGC exposed to the highest BPA concentration compared with untreated cells. We identified 652 genes that exhibited at least 2-fold differences in expression after BPA exposure (all P < 0.05 versus untreated). These genes were significantly enriched for annotations related to cell cycle progression, segregation of chromosomes, steroid metabolism, apoptosis, lipid synthesis, oocyte maturation and chromosomal alignment. No significant changes in gene expression were found at the lower doses of BPA most relevant to human exposure. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Human exposure to BPA in vivo occurs over long periods of time. In this in vitro model, cells were exposed to the chemical for 48 h only. Thus, the effects of BPA on the human follicle might be underestimated. WIDER IMPLICATIONS OF THE FINDINGS: As BPA exposure is ubiquitous, understanding the effects of the chemical on the ovary, specifically in women of reproductive age, has public health significance. The clinical evidence to date points to an association between BPA exposure and impaired IVF outcome, although not all studies have shown negative effects. Our study adds valuable mechanistic information showing that exposure to BPA alters granulosa cell gene expression at high and supra-physiological doses. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grant number 1936/12 from the ISF. The authors have nothing to disclose.

Predicting age by mining electronic medical records with deep learning characterizes differences between chronological and physiological age.

Determining the discrepancy between chronological and physiological age of patients is central to preventative and personalized care. Electronic medical records (EMR) provide rich information about the patient physiological state, but it is unclear whether such information can be predictive of chronological age. Here we present a deep learning model that uses vital signs and lab tests contained within the EMR of Mount Sinai Health System (MSHS) to predict chronological age. The model is trained on 377,686 EMR from patients of ages 18-85 years old. The discrepancy between the predicted and real chronological age is then used as a proxy to estimate physiological age. Overall, the model can predict the chronological age of patients with a standard deviation error of ∼7 years. The ages of the youngest and oldest patients were more accurately predicted, while patients of ages ranging between 40 and 60 years were the least accurately predicted. Patients with the largest discrepancy between their physiological and chronological age were further inspected. The patients predicted to be significantly older than their chronological age have higher systolic blood pressure, higher cholesterol, damaged liver, and anemia. In contrast, patients predicted to be younger than their chronological age have lower blood pressure and shorter stature among other indicators; both groups display lower weight than the population average. Using information from ∼10,000 patients from the entire cohort who have been also profiled with SNP arrays, genome-wide association study (GWAS) uncovers several novel genetic variants associated with aging. In particular, significant variants were mapped to genes known to be associated with inflammation, hypertension, lipid metabolism, height, and increased lifespan in mice. Several genes with missense mutations were identified as novel candidate aging genes. In conclusion, we demonstrate how EMR data can be used to assess overall health via a scale that is based on deviation from the patient's predicted chronological age.

Use of exercise capacity to improve SCORE risk prediction model in asymptomatic adults.

AIMS: The SCORE risk estimation system is used for cardiovascular risk stratification in apparently healthy adults and is based on known cardiovascular risk factors. The purpose of the current study was to evaluate whether exercise capacity can improve the accuracy of the SCORE overall survival risk estimation. METHODS AND RESULTS: We investigated 22 878 asymptomatic men and women who were annually screened in a tertiary medical centre. All subjects were free of known ischaemic heart disease, and had completed maximal exercise stress test according to the Bruce protocol. The SCORE risk estimation system was used to evaluate individual cardiovascular risk for all subjects. The primary endpoint was mortality, after exclusion of patients with metastatic cancer during follow-up. The incremental contribution of exercise capacity in predicting the risk of death was evaluated by net reclassification improvement (NRI) and area under the receiver operating curve (AUROC). Mean age of the study population was 47.4 ± 10.3, and 71.6% were men. There were 505 (2.21%) deaths during a mean follow-up of 9.2 ± 4.1 years. Kaplan-Meier survival analysis showed that both SCORE and low exercise capacity were associated with reduced survival. When added to the SCORE risk prediction, exercise capacity allowed more accurate risk stratification: NRI analysis showed an overall improvement of 56.8% in the accuracy of classification and the AUROC increased (0.782 vs. 0.766). CONCLUSION: Both SCORE and exercise capacity are strong independent predictors of all-cause mortality. The addition of exercise capacity to the SCORE risk model can improve the accuracy of the model.

[Low ALT activity amongst patients hospitalized in internal medicine wards is a widespread phenomenon associated with low vitamin B6 levels in their blood].

BACKGROUND: Monitoring the activity of ALT (SGPT) in the blood is part of the routine, clinical-laboratory follow-up in hospitalized patients. In most cases, activity levels which are above the normal range are considered pathology, mostly related to lysis of hepatocytes, as in cases of hepatitis. Little has been investigated and published in regard to cases in which the ALT activity level is lower than normal. PATIENTS AND METHODS: Since normal ALT activity is regarded essential for normal metabolism and homeostasis, we decided to evaluate the extent to which low ALT levels are found in healthy and hospitalized patient populations and to characterize its circumstances and etiology. Furthermore, we measured the blood concentration of vitamin B6 (being the source for the ALT co-factor, Pyridoxal-5-Phosphate) in a random sample of patients with lower than normal ALT activity level. RESULTS AND CONCLUSIONS: The results of the current study showed a high prevalence, exceeding a third of hospitalized patients in internal medicine departments have low levels of ALT in the serum, and that a linear correlation (p = 0.0004, r = 0.47) exists between lower than normal ALT activity and low concentrations of vitamin B6 in the serum. The authors attribute these findings to a high prevalence of frailty amongst hospitalized patients. We aim to conduct further investigations intended to better characterize quantifiable parameters of frailty amongst our patient population.

Clinical characteristics and healthcare utilisation associated with undiagnosed cognitive impairment in elderly patients with diabetes in a primary care setting: a population-based cohort study.

OBJECTIVES: The objective of this study is to report the prevalence, clinical characteristics and healthcare utilisation of patients with type 2 diabetes (T2DM) and previously undiagnosed cognitive impairment who were identified as having a low Montreal Cognitive Assessment (MoCA) score. DESIGN: A population-based cohort study comparing clinical characteristics, medications, outpatient and inpatient care of patients with a MoCA score <19 to MoCA >26 using descriptive statistics, linear regression and multivariate logistic regression. SETTING: Electronic medical records of a large health maintenance organisation in Israel. PARTICIPANTS: 350 patients, age >65 with T2DM who participated in a cognitive function screening initiative using MoCA, and had a follow-up visit during the 12 months after screening. RESULTS: 130 (37.1%) had a MoCA score >26 and 68 (19.4%) <19. Patients with MoCA<19 had more diabetes-related complications, poorer glycaemic and lipid control, fewer visits to their main primary care physician (PCP; 3.9±3.2 vs 7.3±4.2 visits/year p=0.008), shorter duration of PCP visits (8.3±4.5 vs 4.0±3.5 min, p=0.007), fewer nutritionist and endocrinologist visits, and lower participation in diabetes or smoking cessation workshops. They were less likely to be treated with glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 inhibitor (DPP-4), or sodium-glucose transport protein 2 (SGLT-2) inhibitors and more likely to receive insulin or sulfonylurea. Moreover, they had more emergency room visits (ER; 15 (11.5%) vs 16 (23.5%), p=0.019), hospitalisations (8 (6.2%) vs 22 (32.4%), p=0.001), and longer hospital stays (4.3±3.2 vs 14.5±9.8, p=0.001). Using statistical models, MoCA<19 was identified as a risk factor for fewer and shorter PCP visits and more ER visits and hospitalisations. CONCLUSIONS: This study highlights the high prevalence of undiagnosed severe cognitive impairment in elderly patients with T2DM and its association with poor outpatient care. Appropriate interventions are needed to improve outcomes and prevent hospitalisation in this high-risk population.

Hepatitis B virus infection and risk of colorectal cancer: a large, population-based cohort study from Israel.

BACKGROUND: Recent population-based studies have suggested a possible link between hepatitis B (HBV) infection and extra-hepatic malignancies. We aimed to evaluate the association between HBV and colorectal cancer (CRC) using a large, population-based cohort study utilizing data from a large health maintenance organization (HMO). METHODS: The study included patients with non-cirrhotic HBV based on relevant ICD-9-CM codes and supportive serology identified from the HMO's database. Age-, sex-, ethnicity-, and BMI-matched non-HBV patients in a 1:10 ratio were included in the control group. We assessed the overall diagnosis rate of CRC and hepatocellular carcinoma (HCC) during the study period and calculated the diagnosis rate of CRC in each age category (≤50, 51-70, and ≥70) in both groups. RESULTS: A total of 3430 HBV patients and 34,300 controls were included in the study. The mean age, sex, BMI, and ethnic composition were similar, and the rates of family history of CRC did not differ between both groups. The overall follow-up period was 134±16 months. The diagnosis rate of HCC (1.6% vs. 0.1%; P<0.0001) was significantly higher in the HBV patients. However, the proportion of CRC was comparable for both groups (0.6% vs. 0.8%, P=0.404), which was evident in all age subgroups. CONCLUSIONS: Our findings suggest that HBV infection is associated with an increased risk of HCC diagnosis but is not linked to an elevated risk of CRC. These findings may inform future clinical practice and research regarding the relationship between HBV and extrahepatic malignancies.