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Abstract Background Gaucher disease (GD) is a rare autosomal recessive condition associated with clinical features such as splenomegaly, hepatomegaly, anemia, thrombocytopenia, and bone abnormalities. Three clinical forms of GD have been defined based on the absence (type 1, GD1) or presence (types 2 and 3) of neurological signs. Early diagnosis can reduce the likelihood of severe, often irreversible complications. The aim of this study was to validate the ability of factors from the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system to discriminate between patients with GD1 and controls using real-world data from electronic patient medical records from Maccabi Healthcare Services, Israel’s second-largest state-mandated healthcare provider. Methods We applied the GED-C scoring system to 265 confirmed cases of GD and 3445 non-GD controls matched for year of birth, sex, and socioeconomic status identified from 1998 to 2022. The analyses were based on two databases: (1) all available data and (2) all data except free-text notes. Features from the GED-C scoring system applicable to GD1 were extracted for each individual. Patients and controls were compared for the proportion of the specific features and overall GED-C scores. Decision tree and random forest models were trained to identify the main features distinguishing GD from non-GD controls. Results The GED-C scoring distinguished individuals with GD from controls using both databases. Decision tree models for the databases showed good accuracy (0.96 [95% CI 0.95–0.97] for Database 1; 0.95 [95% CI 0.94–0.96] for Database 2), high specificity (0.99 [95% CI 0.99–1]) for Database 1; 1.0 [95% CI 0.99–1] for Database 2), but relatively low sensitivity (0.53 [95% CI 0.46–0.59] for Database 1; 0.32 [95% CI 0.25–0.38]) for Database 2). The clinical features of splenomegaly, thrombocytopenia (

ObjectiveMembrane stripping in group B streptococcus (GBS) carriers poses an increased risk of inadequate antibiotic prophylaxis, potentially due to accelerated labor, thereby potentially impacting the management of GBS colonization during delivery. We compared the adequacy of intrapartum antibiotic prophylaxis between pregnant women colonized with GBS, who underwent membrane stripping and those who did not. The study aimed to determine whether the performance of membrane stripping, by potentially shortening labor duration, increases the risk of inadequate antibiotic prophylaxis dispensation.Study designA retrospective cohort study was conducted on GBS screen-positive women with a full-term singleton pregnancy in cephalic presentation, who were eligible for vaginal delivery. The exposed group consisted of women who underwent membrane stripping, while the unexposed group consisted of women who did not undergo membrane stripping. The primary outcome was defined as inadequate duration of antibiotic prophylaxis during labor, wherein less than 4 h of beta-lactam antibiotics were administered prior to delivery. Neonatal outcome was compared between the groups.ResultsThis retrospective cohort study comprised 1,609 women, with 129 in the exposed group (stripping group) and 1,480 in the unexposed group (no stripping group). Adequate intrapartum antibiotic prophylaxis was received by 64.3% (83/129) of the exposed group, compared to 46.9% (694/1,480) of the unexposed group (p = 0.003). Membrane stripping was associated with increased odds of receiving adequate prophylaxis (OR 1.897, 95% CI 1.185–3.037, p = 0.008). After excluding women who presented to the labor ward in active labor and delivered in less than 4 h, both the exposed and unexposed groups had similarly high rates of adequate intrapartum antibiotic prophylaxis (87.5% vs. 85.8%, respectively). No significant difference was observed in adverse neonatal outcomes between the groups.ConclusionThe provision of membrane stripping did not impede adequate intrapartum antibiotic prophylaxis and was correlated with a higher rate of sufficient prophylaxis in comparison to non-swept patients. These observations suggest that membrane stripping can be considered a safe option for ensuring adequate antibiotic prophylaxis in women colonized with GBS.

The increase in hip fractures (HF) due to aging of the population and the rise in attractiveness of services provided at home following the COVID-19 pandemic, emphasize the need to compare outcomes of home versus hospital HF rehabilitation. To date, studies comparing the 2 services have focused primarily on clinical outcomes rather than patient-reported outcomes (PROs). This longitudinal observational study evaluated PROs of older adults with HF in the 2 settings. The SF36 questionnaire was used to measure PROs 3 times after surgery. The first PRO was retrospective and reflected pre-fracture health status. Descriptive statistics and mixed-effect logistic regression were used. Of 86 patients participating in the study, 41 had home rehabilitation and 45 had hospital rehabilitation. In both groups, the mental and physical scores plummeted 2 weeks after the HF, compared to pre-fracture status. The difference in improvement from pre-fracture status to recovery in both groups, were not significantly ( P

BackgroundIn the last three decades, much effort has been invested in measuring and improving the quality of diabetes care. We assessed the association between adherence to diabetes quality indicators and all-cause mortality in the primary care setting.MethodsA nationwide, population-based, historical cohort study of all people aged 45-80 with pharmacologically-treated diabetes in 2005 (n = 222,235). Data on annual performance of quality indicators (including indicators for metabolic risk factor management and glycemic control) and vital status were retrieved from electronic medical records of the four Israeli health maintenance organizations. Cox proportional hazards and time-dependent models were used to estimate hazard ratios (HRs) for mortality by degree of adherence to quality indicators.ResultsDuring 2,000,052 person-years of follow-up, 35.8% of participants died. An inverse dose-response association between the degree of adherence and mortality was shown for most of the quality indicators. Participants who were not tested for proteinuria or did not visit an ophthalmologist during the first-5-years of follow-up had HRs of 2.60 (95%CI:2.49-2.69) and 2.09 (95%CI:2.01-2.16), respectively, compared with those who were fully adherent. In time-dependent analyses, not measuring LDL-cholesterol, blood pressure, HbA1c, or HbA1c>9% were similarly associated with mortality (HRs ≈1.5). The association of uncontrolled blood pressure with mortality was modified by age, with increased mortality shown for those with controlled blood pressure at older ages (≥65 years).ConclusionsLongitudinal adherence to diabetes quality indicators is associated with reduced all-cause mortality. Primary care professionals need to be supported by health care systems to perform quality indicators.

Background & Aims: Reports of a rise in childhood cancer incidence in Australia and globally prompted the investigation of cancer incidence and survival in South Australia (SA) and the Northern Territory (NT) over a 28-year period, with emphasis on Indigenous peoples. Methods: This cross-sectional analysis of two prospective longitudinal databases, the SA and NT Cancer Registries (1990–2017), included all reported cases of childhood cancers. Poisson regression provided estimates of incidence rate ratios and survival was modelled using Cox proportional hazard models for children aged N = 753) and the NT (N = 142) were ascertained. Overall and in the NT, childhood cancer incidence was higher in males compared with females (IRR 1.19 [1.04–1.35] and 1.43 [1.02–2.01], respectively). Lymphocytic leukemia was the most reported cancer type across all locations. With reference to the 1990–1999 era (181.67/100,000), cancer incidence remained unchanged across subsequent eras in the combined cohort (SA and NT) (2000–2009: 190.55/100,000; 1.06 [0.91–1.25]; 2010–2017: 210.00/100,000; 1.15 [0.98–1.35]); similar outcomes were reflected in SA and NT cohorts. Cancer incidence amongst non-Indigenous children significantly decreased from the 1990–1999 era (278.32/100,000) to the 2000–2009 era (162.92/100,000; 0.58 [0.35–0.97]). Amongst 39 Indigenous children in the NT, incidence rates remained unchanged across eras (p > 0.05). With reference to the 1990–1999 era, overall survival improved in subsequent eras in SA (2000–2009: HR 0.53 [0.38–0.73]; 2010–2017: 0.44 [0.28–0.68]); however, remained unchanged in the NT (2000–2009: 0.78 [0.40–1.51]; 2010–2017: 0.50 [0.24–1.05]). In the NT, overall survival of Indigenous patients was significantly lower compared with the non-Indigenous cohort (3.42 [1.92–6.10]). While the survival of Indigenous children with cancer significantly improved in the last two eras (p < 0.05), compared to the 1990–1999 era, no change was noted amongst non-Indigenous children in the NT (p > 0.05). Conclusions: The incidence of childhood cancers has remained unchanged over 28-years in SA and the NT. Encouragingly, improved survival rates over time were observed in SA and amongst Indigenous children of the NT. Nevertheless, survival rates in Indigenous children remain lower than non-Indigenous children.

Background Hip fracture patients (HFPs) frequently have multiple underlying conditions, necessitating that agreed-upon goals take these complications into consideration. Communication regarding goals between medical-personnel and patients is not always effective. Patient-reported outcomes (PROs) can outline personal goals and help promote quality health care in HFPs. Few studies have been published on this topic. The study’s aim was to outline the process of using PROs for goal-directed therapy among HFPs.Methods This sequential controlled trial was conducted among HFPs from two medical centres. The control and the intervention group received integrative rehabilitation. PROs were measured in both groups using the SF36 questionnaire three times postsurgery: 24–48 hours, 2 weeks and 3 months. During the first round of questioning, only the intervention group was asked ‘what matters most to you?’ during the rehabilitative process. Accordingly, agreed-upon goals that were determined by the SF36’s eight topics and were incorporated into the HFP’s rehabilitative process. A Likert scale of 1–5, ‘1’ indicating no-achievement and ‘5’ full-achievement, was used to assess the goal achievement 4–6 months post-fracture.Results 84 HFPs participated in the study: 40 and 44 in the intervention and control group, respectively. In both groups, PROs declined after the HF, then improved somewhat 3 months later, but did not return to prefracture scores. Among the intervention group, 39% reached their specific goals (Likert level 5). Patients who achieved their goals had better PROs in comparison to others. The intervention group indicated PROs helped them articulate their desires and introduced them to new areas of care.Conclusions Shifting from asking ‘what’s the matter?’ to ‘what matters most to you?’ can improve the understanding of HFPs’ own priorities, promote quality outcomes and enhance patient-centred care. Using PROs as a guide for goal-directed therapy can create a more inclusive process that includes the patients’ most important health determinants and needs.

Abstract Background Early in the coronavirus disease 2019 (COVID-19) pandemic, governments implemented exceptional public health measures (PHMs) in the face of uncertainty. This study aimed to compare mitigation policies implemented by Israel and their timing in the first wave of the pandemic to those of other countries, and to assess whether country characteristics such as democracy, trust, education, economic strength and healthcare reserve were associated with decision-making. Methods PHMs and pre-pandemic characteristics, using internationally accepted indices, of 50 countries were collected from 1/1/2020-30/06/2020; and associations between them were assessed. Time to implementation of these measures was compared among the Organisation for Economic Co-operation (OECD) nations. Log-rank test was used for univariate analysis. Cox regression was performed to assess the independent contribution of pre-pandemic characteristics to time-to-implementation of measures. Correlations between timing of specific measures and COVID-19 mortality at 60 days were assessed. Results Israel ranked in the upper third of the OECD in swiftness to implementation of eight of the ten measures compared. In univariate survival analysis, countries with an education level below the OECD median were more likely to implement a lockdown (p-value = 0.043) and to close restaurants and entertainment venues (p-value = 0.007) when compared to countries above the OECD median. In Cox regression models, controlling for geographic location, democracy level above the OECD median was associated with a longer time-to-implementation of a lockdown (HR=0.35, 95% CI=0.14-0.88, p-value=0.025). Similarly, a high level of GDP per capita was inversely associated with closing schools; and a high level of education inversely associated with closure of restaurants and entertainment venues. Earlier initiation of all PHMs was associated with lower mortality at 60 days, controlling for geographic location. Conclusions Israel's initial response to the pandemic was relatively quick, and may have been facilitated by its geographic isolation. Countries with lower pre-pandemic socio-economic indices were quicker to initiate forced social distancing. Early initiation of PHMs was associated with reduced mortality in the short run. Timing of initiation of measures relative to the country-specific spread of disease is a significant factor contributing to short-term early local pandemic control, perhaps more than the exact measures implemented. It is important to note that this study is limited to the initial pandemic response. Furthermore, it does not take into account the broader long-term effects of certain PHMs, which should be a focus of further research.

Limited awareness of harmonized guidelines among physicians while capacity is below par even for the basic strata.

Background Goal-oriented patientcare is a key element in qualityhealthcare. Medical-caregiver’s (MC) are expected to generate a shared decision-making process with patients regarding goals and expected health-outcomes. Hip-fracture patients (HFP) are usually older-adults with multiple health-conditions, necessitating that agreed-upon goals regarding the rehabilitation process, take these conditions into consideration. This topic has yet to be investigated by pairing and comparing the perception of expected outcomes and therapeutic goals of multidisciplinary MCs and their HF patient’s. Our aim was to assess in a quantitative method whether HFPs and their multidisciplinary MCs agree upon target health-outcomes and their most important goals as they are reflected in the SF12 questionnaire. Methods This was a cross-sectional, multi-center, study of HFPs and their MCs. Patients and MCs were asked to rate their top three most important goals for rehabilitation from the SF12 eight subscales: physical functioning, physical role limitation, bodily pain, general health, vitality, social functioning, emotional role limitation and mental health, and indicate their expected outcome. Descriptive statistics and mixed effect logistic-regression were used to compare concordance of the ratings. Agreement between patients and MCs was assessed using interclass coefficients (ICCs). Results A total of 378 ratings were collected from 52 patients, 12 nurses, 12 physicians and 6 paramedical personnel. Each patient had between 3 and 9 raters. Patients considered physical functioning and physical role limitation more important than did MCs. Physicians and nurses emphasized the importance of bodily pain while patients referred to it as relatively less significant. The total ICC was low (2%) indicating poor agreement between MCs and patients. With the exception of physical-functioning, MCs predicted a less optimistic outcome in all of the SF12's subscales in comparison to HFPs. Conclusion Effective intervention in HFPs requires constructive communication between MCs and patients. The study suggests that caregivers have an insufficient understanding of the expectations of HFPs. More effective communication channels are required in order to better understand HFPs’ needs and expectations.

The association between GD and cancer has been uncertain due to ascertainment bias in previously published studies. We analyzed cancer incidence using the Maccabi Healthcare Service (MHS) electronic health records among 264 patients with GD compared to 3440 matched controls. We ascertained cancers diagnosed before and after the index date (i.e., the first documentation of GD in cases and the corresponding date for controls). Before the index date, cancers were diagnosed in 18 individuals, with 11 (4.2%) in the GD group and 7 (0.2%) in the control group. After the index date, cancers were diagnosed in 57 individuals, with 20 (7.9%) in the GD group and 37 (1.1%) in the control group, with a median follow-up of almost 13 years in both groups. The most common cancers diagnosed in GD were non-melanoma skin cancer (NMSC) and hematological malignancies, with a clustering of diagnoses around the time of GD diagnosis. The incidence of cancers (excluding MNSC) was 4.1 (95% CI 2.2–7.1) and 0.7 (95% CI 0.4–0.9) per 1000 patient-years in the GD and control groups, respectively, with an incidence rate ratio of 6.37 (95% CI 3–12.7). Patients with GD underwent more cancer screening tests than their counterparts in the control group. While our study revealed an increased occurrence of cancers in patients with GD, this finding might be partly attributed to the more rigorous surveillance procedures employed in this patient population.

Background Evidence of the cardiovascular benefits of adherence to quality indicators in diabetes care over a period of years is lacking. Methods and Results We conducted a population‐based, historical cohort study of 105 656 people aged 45 to 80 with pharmacologically treated diabetes and who were free of cardiac disease in 2010. Data were retrieved from electronic medical records of the 4 Israeli health maintenance organizations. The association between level of adherence to national quality indicators (2006–2010: adherence assessment) and incidence of cardiac outcome; ischemic heart disease or heart failure (2011–2016: outcome assessment) was estimated using Cox proportional hazards models. During 529 551 person‐years of follow‐up, 19 246 patients experienced cardiac disease. An inverse dose–response association between the level of adherence and risk of cardiac morbidity was shown for most of the quality indicators. The associations were modified by age, with stronger associations among younger patients (

Abstract Among the challenges presented by the SARS-CoV2 pandemic are those related to balancing societal priorities with averting threats to population health. In this exceptional context a group of Israeli physicians and public health scholars (multidisciplinary academic group on children and coronavirus [MACC]) coalesced, examining the role of children in viral transmission and assessing the necessity and consequences of restricted in-class education. Combining critical appraisal and analytical skills with public health experience, MACC advocated for safe and monitored school re-opening, stressing the importance of education as a determinant of health, continuously weighing this stance against evolving COVID-19-risk data. MACC’s activities included offering research-based advice to government agencies including Ministries of Health, Finance, and Education. In a setting where government bodies were faced with providing practical solutions to both decreasing disease transmission and maintaining society’s vital activities, and various advisors presented decision-makers with disparate views, MACC contributed epidemiological, clinical and health policy expertise to the debate regarding school closure as a pandemic control measure, and adaptations required for safe re-opening. In this paper, we describe the evolution, activities, policy inputs and media profile of MACC, and discuss the role of academics in advocacy and activism in the midst of an unprecedented public health crisis. A general lesson learned is that academics, based on the rigor of their scientific work and their perceived objectivity, can and should be mobilized to pursue and promote policies based on shared societal values as well as empiric data, even when considerable uncertainty exists about the appropriate course of action. Mechanisms should be in place to open channels to multidisciplinary academic groups and bring their input to bear on decision-making.

Background and Aims: There is conflicting evidence regarding the association between proton pump inhibitors (PPI) and the risk of acquisition and severity of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Aim: To evaluate the association between PPI exposure and infection and development of severe disease in patients infected with SARS-CoV2in a large population-based historical cohort.Methods: Data were extracted from a health maintenance organization database in Israel that insures over 1,200,000 individuals from across the country. All patients who underwent SARS-CoV-2 testing between March and November 2020 were included. Logistic regression and matched analyses were used to compare patients prescribed and exposed to PPIs to those not prescribed PPIs regarding SARS-CoV-2 positivity. In addition, among SARS-CoV-2 positive patients (n = 44,397) the likelihood of developing severe disease, defined by a composite endpoint of death, ICU admission and prolonged hospitalization, was compared in those exposed and not exposed to PPIs.Results: Among 255,355 adult patients who underwent SARS-CoV-2 testing by PCR, 44,397 (17.4%) were positive for SARS-CoV-2 and 12,066 (4.7%) patients were prescribed PPIs in the 3 months before testing. In a multivariable logistic regression model controlling for age, gender, smoking status, BMI, diabetes mellitus, hypertension, COPD, history of ischemic heart disease and fasting blood glucose (FBG) levels, no significant association was found between PPIs and SARS-CoV-2 positivity (p = 0.09 aOR 0.94, 95% CI – 0.88–1.01). Among SARS-CoV-2 positive patients, 910 (2%) had a severe infection. Multivariate logistic regression controlling for the abovementioned confounders, showed no such association between PPIs and severe COVID-19 (p = 0.28). Elevated FBG levels were significantly associated with both PPI exposure (p < 0.001) and severe COVID-19 infection (p < 0.001). These results were reinforced by a matched analysis (n = 655 pairs).Conclusion: PPIs are spuriously associated with severe COVID-19 due to the presence of elevated FBG as a confounder. Our study accounted for the FBG levels of patients and known risk factors for severe COVID-19 infection, which may be the reason for the discrepancy in prior studies. These results may aid in understanding potential confounders when evaluating potential associations of PPIs with other respiratory or viral diseases.

Chronic hepatitis C virus (HCV) infection, associated with severe liver disease and cancer, affects 70 million people worldwide. New treatments with direct-acting-antivirals offer cure for about 95% of affected individuals; however, treatment costs may be prohibitive in both the poorest and richest nations. Opting for cure may require sacrificing essential household assets. We highlight the financial dilemmas involved, drawing parallels between Ethiopia and the United States, countries where universal health coverage does not yet exist. The World Health Organization (WHO) declaration for HCV eradication by 2030 will only become reality if universal access to efficacious and affordable treatment is guaranteed for everyone.

Abstract Objective To develop, apply, and evaluate, a novel web‐based classifier for screening for Parkinson disease among a large cohort of search engine users. Methods A supervised machine learning classifier learned to distinguish web users with self‐reported Parkinson's disease from controls based on their interactions with a search engine (Bing, Microsoft). It was then applied to groups of web users with low or high risk for actual Parkinson's disease. Textual content of web queries was used to sort surfers into the different risk groups, but not for classifying users as negative or positive for Parkinson's disease. Disease detection was unsolicited. Researchers did not have access to any identifying data on users. Results Applying the classifier (with an estimated positive predictive value of 25%) resulted in 17,843/1,490,987 (1.2%) web users over the age of 40 years screened positive for Parkinson's disease. This percentile was higher in at‐risk groups (Fisher exact P

Carriers of GBA1 gene variants have a significant risk of developing Parkinson’s disease (PD). A cohort study of GBA carriers between 40–75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40–74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7–33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14–32%), Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2–26.4%), smell assessment (12.4%, 95% CI 6.6–20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7–19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as “abnormal”. Then we calculated the percentage of “abnormal” tests for each subject; the median (range) was 4.55 (0–43.5%). Twenty-two subjects had more than 15% “abnormal” tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD.

Abstract Background Cytokines are known to be key players in dry eye syndrome (DES) and Sjogren’s syndrome (SS) pathogenesis. In this study we compared single nucleotide polymorphism (SNP) variations in genes encoding cytokine levels among SS and DES patients in Israel. Methods We recruited 180 subjects, 82 with SS and 98 with DES. Using a candidate gene approach and allele-specific PCR technique for genotyping, proportions of risk alleles in Tumor Necrosis Factor α (TNFα) (rs1800629), IinterLeukin-10 (IL-10) (rs1800896) and TNFAIP3 (rs2230926) SNPs were compared between study groups. Results Allelic distribution was found very similar to Caucasian (CEU – Utah residents with Northern and Western European roots) population distributions in these SNPs. While none of the SNPs’ variants were significantly associated with SS or DES in a recessive model, in an additive model the TNFα G risk allele was found higher among SS patients compared to DES (Homozygote-G: 84.2% vs. 70.8%; Heterozygote: 26.9% vs. 11.2%, respectively, p = 0.02). After adjustment for age, gender and ethnicity, these variants weren’t associated with SS. Genetic scoring reveals that SS patients are more likely to present variants of all three SNPs than DES subjects. Conclusions This is the first study evaluating these SNP variations among both patients with DES and patients with SS. We found the allelic distribution in each SNP to be very similar to that found in healthy Caucasian populations presented in the HapMap project. We found the TNFα allele significantly associated with DES for homozygotes, and associated with SS for heterozygotes in the additive model.

ImportancePatients with diabetes are known to be at increased risk for infections including severe coronavirus disease 2019 (COVID-19) but the relationship between COVID-19 severity and specific pre-infection glucose levels is not known.ObjectiveTo assess the differential effects of pre-infection glucose levels on the risk for severe COVID-19 amongst patients with and without diabetes.DesignPopulation based historical cohort study.SettingNational state-mandated HMO.PatientsAll adult patients with a positive SARS-COV2 test between March-October 2020.ExposureRecent fasting blood glucose (FBG) and glycated hemoglobin (HBA1C), age, gender, body mass index (BMI) and diagnoses of diabetes, hypertension, ischemic heart disease.OutcomeRisk for severe COVID-19, defined as resulting in ≥10 hospitalization days, ICU admission or death.Results37,121 patients with a positive SARS-COV2 test were identified; 707 defined as severe (1.9%). Unadjusted risk factors for severe disease were age (OR = 1.1 for every year increase; 95% CI 1.09-1.11, p < 0.001), male gender (OR = 1.34, 95% CI 1.06-1.68, p = 0.012); BMI (OR = 1.02 for 1 kg/m2 increase, 95% CI 1.00-1.04, p = 0.025). Controlling for these factors, we found an association between pre-infection FBG and the risk of severe COVID-19, with a differential effect in patients with and without a diagnosis of diabetes. For patients without diabetes, elevated FBG in the pre-diabetes range (106-125 mg/dl) was associated with severe COVID-19 (OR 1.55 95% CI 1.04-2.26 p = 0.027). For patients with a diagnosis of diabetes, we found a J-shaped association between pre-infection glucose control and the risk for severe COVID-19 where the lowest risk for was for patients with FBG 106-125 mg/dl; the risk increased with higher pre-infection glucose levels but strikingly also for patients with a low pre-infection FBG (Conclusions and relevanceElevated pre-infection blood glucose is a risk factor for severe COVID-19 even in non-diabetics. For patients with a diagnosis of diabetes both high as well as low pre-infection glucose levels are risk factors for severe COVID-19. Further research is required to assess whether these associations are causal, but we believe these findings can already have clinical implications for COVID-19 risk assessment and stratification.

Treated wastewater (TWW) is increasingly used for agricultural irrigation, especially in arid and semi-arid regions. Carbamazepine is among the most frequently detected pharmaceuticals in TWW. Moreover, its uptake and accumulation have been demonstrated in crops irrigated with TWW. A previous controlled trial found that urine concentrations of carbamazepine were higher in healthy volunteers consuming TWW-irrigated produce as compared to freshwater-irrigated produce. The aim of the current study was to assess whether carbamazepine is quantifiable in urine of Israelis consuming their usual diets and whether concentrations vary according to age, personal characteristics and diet. In this cross-sectional study, we recruited 245 volunteers, including a reference group of omnivorous healthy adults aged 18–66; pregnant women; children aged 3–6 years; adults aged >75 years; and vegetarians/vegans. Participants provided spot urine samples and reported 24-hour and “usual” dietary consumption. Urinary carbamazepine levels were compared according to group, personal characteristics, health behaviors, and reported diet. Carbamazepine was detectable (≥1.66 ng/L) in urine of 84%, 76%, 75.5%, 66%, and 19.6% of the reference group, vegetarians, older adults, pregnant women, and children, respectively. Quantifiable concentrations (≥5.0 ng/L) of carbamazepine were found in 58%, 46%, 36.7%, 14%, and 0% of these groups, respectively (p = 0.001 for comparison of proportions across groups). In adults, higher carbamazepine concentrations were significantly associated (p

ObjectivesTo compare hematologic and serological parameters among patients with Sjogren's syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations.MethodsIn a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the "Immunodot" qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI).ResultsAmong DES patients, only 2% (95%CI: 0.36-6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (PConclusionsSerologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.

Abstract Background Israel is one of the few countries that have a national program for quality assessment of community healthcare. We aimed to evaluate whether improved performance in diabetes care was associated with improved health of diabetic patients on a national level. Methods We conducted a nationwide ecological study estimating improvements in diabetes-related quality indicators and health outcomes. We estimated both correlations between composite measures of diabetes-related quality indicators and selected outcomes, and assessed through a joinpoint analysis whether trends in selected outcomes changed 4 years after the inception of the national program. Results Between 2002 and 2010, the prevalence of diabetes in Israeli adults increased from 4.8% to 7.4%. During these years, an improvement was noticed in most quality indicators (from 53% to 75% for the composite score). Declines were noted in rates of blindness, diabetes-related end-stage kidney disease, lower limbs amputations and diabetes-related mortality. Significant accelerations in decline were noted for amputations in men and diabetes-related mortality in both Arab men and women 4 years after the inception of the national program. Conclusion This study suggests that Israel’s national program for quality indicators in diabetes care in the community has probably had a significant impact on the health status of the whole population and may have contributed to narrowing gaps in life expectancy between Israeli Jews and Arabs. Future studies based on individual-level data are needed to confirm these results.

Abstract Medical professionalism refers to attributes, values, behaviors, responsibilities and commitments of physicians that are congruent with the public’s expectations. An international workshop on medical professionalism took place at the Dead Sea, Israel, on December 11–12, 2016. The meeting brought together local medical professionals, physicians and others, as well as international experts, to discuss definitions of professionalism and wrestle with current challenges facing the profession including its perceived status and physician satisfaction, unprofessional behavior and its relation to health care quality and patient safety, and professionalism as a learned competence. Individual medical schools reported on educational efforts to promote professionalism in their curricula. Patient complaints as an improvement mechanism were explored on a national and health plan level. I was found that complaints regarding physician behavior are rare in the Israeli context and need to be dealt with expeditiously at a local level in order to be effective tools for change. The meeting provided a venue to understand local and international strategies and mechanism for regulation and self-regulation, highlighting the role of the Israel Medical Association. A major focus of the meeting was on intergenerational differences in attitude and practice and the necessary adaptation of medicine to the digital age. We provide an overview of the topics addressed, synopsis, evaluation and lessons learned in this first-ever national meeting on medical professionalism in Israel.

Objectives. To assess whether there are shared exposures associated with Sjogren’s syndrome (SS), dry eye syndrome (DES), and B-cell non-Hodgkin lymphoma (B-NHL), in order to determine whether they are etiologically related. Methods. In a clinic-based case-control study, 702 participants (91 SS, 120 DES, 211 (age and sex frequency-matched) controls, and 280 B-NHL cases) were recruited and interviewed regarding exposures, medical history, and family history. Results. Female predominance was noted in SS (ratio 9.2 : 1). Eye dryness was severest in SS compared to DES and controls (P

Background: The success of Helicobacter pylori (H. pylori) eradication depends on several host and treatment factors. Serum vitamin D levels may be associated with H. pylori infection and eradication rates. We investigated the association between vitamin D and H. pylori infection and eradication, using a large electronic database based on medical records from a population-based health maintenance organization. Methods: Data regarding adults who underwent H. pylori testing and had vitamin D measurements within one month of H. pylori testing were collected. H. pylori infection was ascertained using urea breath or stool antigen tests. A negative H. pylori test following a positive result implied eradication. Multivariate regression models were constructed to assess associations between H. pylori infection, eradication, and vitamin D. Results: Among 150,483 members who underwent H. pylori testing from 2009 to 2018, 27,077 (18%) had vitamin D measurements. Vitamin D levels were inversely associated with H. pylori infection, p < 0.001. The odds of a positive H. pylori test were 31% higher among patients with vitamin D levels p < 0.001). Purchase of vitamin D supplements was associated with a negative subsequent H. pylori test (p < 0.001). Mean vitamin D levels were moderately higher in those with successful vs. failed H. pylori eradication (19.34 ± 9.55 vs. 18.64 ± 9.61, p < 0.001). Conclusions: Vitamin D levels are associated with H. pylori infection. Increased vitamin D levels are associated with successful H. pylori eradication. Vitamin D may have a role in H. pylori eradication.

BACKGROUND:Risk factors for B-cell non-Hodgkin lymphoma (B-NHL) have not been assessed among Palestinian Arabs (PA) and Israeli Jews (IJ). METHODS:In a case-control study we investigated self-reported medical and lifestyle exposures, reporting odds ratios (ORs) and 95% confidence intervals [CIs], by ethnicity, for overall B-NHL and subtypes. RESULTS:We recruited 823 cases and 808 healthy controls. Among 307 PA/516 IJ B-NHL cases (mean age at diagnosis = 51 [±17] versus 60 [±15] years, respectively) subtype distributions differed, with diffuse large B-cell lymphoma (DLBCL) being prominent among PA (71%) compared to IJ (41%); follicular lymphoma (FL), was observed in 14% versus 28%, and marginal zone lymphoma, in 2% versus 14%, respectively. Overall B-NHL in both populations was associated with recreational sun exposure OR = 1.43 [CI:1.07-1.91], black hair-dye use OR = 1.70 [CI:1.00-2.87], hospitalization for infection OR = 1.68 [CI:1.34-2.11], and first-degree relative with hematopoietic cancer, OR = 1.69 [CI:1.16-2.48]. An inverse association was noted with alcohol use, OR = 0.46 [CI:0.34-0.62]. Subtype-specific exposures included smoking (FL, OR = 1.46 [CI:1.01-2.11]) and >monthly indoor pesticide use (DLBCL, OR = 2.01 [CI:1.35-3.00]). Associations observed for overall B-NHL in PA only included: gardening OR = 1.93 [CI:1.39-2.70]; history of herpes, mononucleosis, rubella, blood transfusion (OR>2.5, P

OBJECTIVE:Stripping of the membranes is an established and widely utilized obstetric procedure associated with higher spontaneous vaginal delivery rates, reduced need for formal induction of labor and a lower likelihood of post-term pregnancy. Due to the theoretical concern of bacterial seeding during the procedure many practitioners choose not to sweep the membranes in Group B Streptococcus (GBS) colonized patients. We conducted 'the STRIP-G study' in order to determine whether maternal and neonatal outcomes are affected by GBS carrier status in women undergoing membrane stripping. STUDY DESIGN:We conducted a prospective study in a tertiary referral center, comparing maternal and neonatal outcomes following membrane stripping among GBS-positive, GBS-negative, and GBS-unknown patients. We compared the incidence of composite adverse neonatal outcomes (primary outcome) among the three study groups, while secondary outcome measure was composite adverse maternal outcomes. RESULTS:A total of 542 women were included in the study, of which 135 were GBS-positive, 361 GBS-negative, and 46 GBS-unknown status. Demographic, obstetric, and intra-partum characteristics were similar for all groups. Adverse neonatal outcomes were observed in 8 (5.9%), 31 (8.6%), and 2 (4.3%) in the GBS-positive, GBS-negative, and unknown groups, respectively (P = 0.530), (Odds Ratio between GBS-Positive vs. GBS-Negative groups 0.67 (95%, CI = 0.30-1.50)); while composite adverse maternal outcomes occurred in 9 (6.66%), 31 (8.59%), and 5 (10.87%) in the GBS-positive, GBS-negative, and unknown groups, respectively (P = 0.617). CONCLUSIONS:Antepartum membrane stripping in GBS carriers appears to be a safe obstetrical procedure that does not adversely affect maternal or neonatal outcomes.

Molecular and genetic evidence suggests that DNA repair pathways may contribute to lymphoma susceptibility. Several studies have examined the association of DNA repair genes with lymphoma risk, but the findings from these reports have been inconsistent. Here we provide the results of a focused analysis of genetic variation in DNA repair genes and their association with the risk of non-Hodgkin's lymphoma (NHL). With a population of 1,297 NHL cases and 1,946 controls, we have performed a two-stage case/control association analysis of 446 single nucleotide polymorphisms (SNPs) tagging the genetic variation in 81 DNA repair genes. We found the most significant association with NHL risk in the ATM locus for rs227060 (OR = 1.27, 95% CI: 1.13-1.43, p = 6.77×10(-5)), which remained significant after adjustment for multiple testing. In a subtype-specific analysis, associations were also observed for the ATM locus among both diffuse large B-cell lymphomas (DLBCL) and small lymphocytic lymphomas (SLL), however there was no association observed among follicular lymphomas (FL). In addition, our study provides suggestive evidence of an interaction between SNPs in MRE11A and NBS1 associated with NHL risk (OR = 0.51, 95% CI: 0.34-0.77, p = 0.0002). Finally, an imputation analysis using the 1,000 Genomes Project data combined with a functional prediction analysis revealed the presence of biologically relevant variants that correlate with the observed association signals. While the findings generated here warrant independent validation, the results of our large study suggest that ATM may be a novel locus associated with the risk of multiple subtypes of NHL.

The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near LPXN, (P(LYM) = 3.89×10(-8), OR = 1.29) and rs948562 (P(LYM) = 5.85×10(-7), OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, P(NHL) = 5.72×10(-7)) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (P(FL) = 2.69×10(-12), OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy.

Although traditionally the primary information sources for cancer patients have been the treating medical team, patients and their relatives increasingly turn to the Internet, though this source may be misleading and confusing. We assess Internet searching patterns to understand the information needs of cancer patients and their acquaintances, as well as to discern their underlying psychological states. We screened 232,681 anonymous users who initiated cancer-specific queries on the Yahoo Web search engine over three months, and selected for study users with high levels of interest in this topic. Searches were partitioned by expected survival for the disease being searched. We compared the search patterns of anonymous users and their contacts. Users seeking information on aggressive malignancies exhibited shorter search periods, focusing on disease- and treatment-related information. Users seeking knowledge regarding more indolent tumors searched for longer periods, alternated between different subjects, and demonstrated a high interest in topics such as support groups. Acquaintances searched for longer periods than the proband user when seeking information on aggressive (compared to indolent) cancers. Information needs can be modeled as transitioning between five discrete states, each with a unique signature representing the type of information of interest to the user. Thus, early phases of information-seeking for cancer follow a specific dynamic pattern. Areas of interest are disease dependent and vary between probands and their contacts. These patterns can be used by physicians and medical Web site authors to tailor information to the needs of patients and family members.

BACKGROUND: Endurance exercise may induce transient cardiac dysfunction. Data regarding the effect of caloric restriction on cardiac function is limited. We studied the effect of physical activity performed during extreme caloric deprivation on cardiac function. METHODS: Thirty-nine healthy male soldiers (mean age 20 ± 0.3 years) were studied during a field training exercise lasted 85-103 hours, with negligible food intake and unlimited water supply. Anthropometric measurements, echocardiographic examinations and blood and urine tests were performed before and after the training exercise. RESULTS: Baseline VO(2) max was 59 ± 5.5 ml/kg/min. Participants' mean weight reduction was 5.7 ± 0.9 kg. There was an increase in plasma urea (11.6 ± 2.6 to 15.8 ± 3.8 mmol/L, p