Age, Motion, Medical, and Psychiatric Associations With Incidental Findings in Brain MRI.

Importance: Few investigations have evaluated rates of brain-based magnetic resonance imaging (MRI) incidental findings (IFs) in large lifespan samples, their stability over time, or their associations with health outcomes. Objectives: To examine rates of brain-based IFs across the lifespan, their persistence, and their associations with phenotypic indicators of behavior, cognition, and health; to compare quantified motion with radiologist-reported motion and evaluate its associations with IF rates; and to explore IF consistency across multiple visits. Design, Setting, and Participants: This cross-sectional study included participants from the Nathan Kline Institute-Rockland Sample (NKI-RS), a lifespan community-ascertained sample, and the Healthy Brain Network (HBN), a cross-sectional community self-referred pediatric sample focused on mental health and learning disorders. The NKI-RS enrolled participants (ages 6-85 years) between March 2012 and March 2020 and had longitudinal participants followed up for as long as 4 years. The HBN enrolled participants (ages 5-21 years) between August 2015 and October 2021. Clinical neuroradiology MRI reports were coded for radiologist-reported motion as well as presence, type, and clinical urgency (category 1, no abnormal findings; 2, no referral recommended; 3, consider referral; and 4, immediate referral) of IFs. MRI reports were coded from June to October 2021. Data were analyzed from November 2021 to February 2023. Main Outcomes and Measures: Rates and type of IFs by demographic characteristics, health phenotyping, and motion artifacts; longitudinal stability of IFs; and Euler number in projecting radiologist-reported motion. Results: A total of 1300 NKI-RS participants (781 [60.1%] female; mean [SD] age, 38.9 [21.8] years) and 2772 HBN participants (976 [35.2%] female; mean [SD] age, 10.0 [3.5] years) had health phenotyping and neuroradiology-reviewed MRI scans. IFs were common, with 284 of 2956 children (9.6%) and 608 of 1107 adults (54.9%) having IFs, but rarely of clinical concern (category 1: NKI-RS, 619 [47.6%]; HBN, 2561 [92.4%]; category 2: NKI-RS, 647 [49.8%]; HBN, 178 [6.4%]; category 3: NKI-RS, 79 [6.1%]; HBN, 30 [1.1%]; category 4: NKI-RS: 12 [0.9%]; HBN, 6 [0.2%]). Overall, 46 children (1.6%) and 79 adults (7.1%) required referral for their IFs. IF frequency increased with age. Elevated blood pressure and BMI were associated with increased T2 hyperintensities and age-related cortical atrophy. Radiologist-reported motion aligned with Euler-quantified motion, but neither were associated with IF rates. Conclusions and Relevance: In this cross-sectional study, IFs were common, particularly with increasing age, although rarely clinically significant. While T2 hyperintensity and age-related cortical atrophy were associated with BMI and blood pressure, IFs were not associated with other behavioral, cognitive, and health phenotyping. Motion may not limit clinical IF detection.

Estimated glomerular filtration rate and the risk of stroke in individuals with diabetes mellitus and atrial fibrillation insight from a large contemporary population study.

BACKGROUND: Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Impaired renal function (IRF) increases the risk of stroke as well, but this finding is not consistent among all studies. Our aim was to assess the incidence rates and risk of ischemic stroke and mortality by baseline Estimated Glomerular Filtration Rate (eGFR) levels Among individuals with AF and DM. METHODS: A prospective, historical cohort study using the Clalit Health Services electronic medical records database. Among patients with AF and DM, we compared three groups according to eGFR levels: eGFR ≥ 60, between 30 and 60, and ≤ 30 (mL/min/1.73m2). RESULTS: A total of 17,567 cases were included in the final analysis; of them, 11,013 (62.7%) had eGFR ≥ 60, 4930 (28%) had eGFR between 30 and 60, and 1624 (9.24%) with eGFR ≤ 30. The incidence of stroke per 100 person-years in the three study groups was: 1.88, 2.69, and 3.34, respectively (p < 0.001). IRF was associated with increased risk of stroke in univariate analysis, but not after multivariate adjustment (Adjusted Hazard Ratio (AHR) 0.96 {95%CI; 0.74-1.25} for eGFR 30-60 and 0.96 {95%CI; 0.60-1.55} for eGFR ≤ 30). Mortality per 100 person-years was 10.78, 21.49, and 41.55, respectively (p < 0.001). IRF was associated with increased mortality risk in univariate analysis, as well as in multivariate analysis (AHR 1.08 {95%CI; 0.98-1.18} for eGFR 30-60, and 1.59 {95%CI; 1.37-1.85} for eGFR ≤ 30. CONCLUSION: In patients with NVAF and DM, IRF was not associated with an increased risk of stroke, but severe IRF (eGFR ≤ 30) was associated with increased mortality risk.

The value of parental medical records for the prediction of diabetes and cardiovascular disease: a novel method for generating and incorporating family histories.

OBJECTIVE: To determine whether data-driven family histories (DDFH) derived from linked EHRs of patients and their parents can improve prediction of patients' 10-year risk of diabetes and atherosclerotic cardiovascular disease (ASCVD). MATERIALS AND METHODS: A retrospective cohort study using data from Israel's largest healthcare organization. A random sample of 200 000 subjects aged 40-60 years on the index date (January 1, 2010) was included. Subjects with insufficient history (<1 year) or insufficient follow-up (<10 years) were excluded. Two separate XGBoost models were developed-1 for diabetes and 1 for ASCVD-to predict the 10-year risk for each outcome based on data available prior to the index date of January 1, 2010. RESULTS: Overall, the study included 110 734 subject-father-mother triplets. There were 22 153 cases of diabetes (20%) and 11 715 cases of ASCVD (10.6%). The addition of parental information significantly improved prediction of diabetes risk (P < .001), but not ASCVD risk. For both outcomes, maternal medical history was more predictive than paternal medical history. A binary variable summarizing parental disease state delivered similar predictive results to the full parental EHR. DISCUSSION: The increasing availability of EHRs for multiple family generations makes DDFH possible and can assist in delivering more personalized and precise medicine to patients. Consent frameworks must be established to enable sharing of information across generations, and the results suggest that sharing the full records may not be necessary. CONCLUSION: DDFH can address limitations of patient self-reported family history, and it improves clinical predictions for some conditions, but not for all, and particularly among younger adults.

Lifetime risk, life expectancy, and years of life lost to type 2 diabetes in 23 high-income jurisdictions: a multinational, population-based study.

BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting. METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping. FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1 577 234 194), there were 5 119 585 incident cases of type 2 diabetes, 4 007 064 deaths in those with type 2 diabetes, and 11 854 043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years). INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes. FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia.

Relation of Hemoglobin A1C Levels to Risk of Ischemic Stroke and Mortality in Patients With Diabetes Mellitus and Atrial Fibrillation.

Diabetes mellitus (DM) is associated with an increased risk of complications in atrial fibrillation (AF). This study aimed to assess the incidence and risks of ischemic stroke and mortality according to baseline HbA1c levels in patients with DM and AF. We conducted a cohort study using Clalit Health Services electronic medical records. The study population included all Clalit Health Services members aged ≥25 years, with the first diagnosis of AF between January 1, 2010, and December 31, 2016, who had a diagnosis of DM. The risk of stroke and all-cause death were compared according to HbA1c levels at the time of AF diagnosis: <7.0%, between 7% and 9%, and ≥9%. A total of 44,451 patients with DM and AF were identified. The median age was 75 years (interquartile 65 to 83), and 52.5% were women. During a mean follow-up of 38 months, higher levels of HbA1c were associated with an increased risk of stroke with a dose-dependent response when compared with patients with HbA1c <7% (Adjusted hazard ratio [aHR] =1.30 [95% confidence interval 1.10 to 2.05] for levels between 7% and 9% and 1.60 (95% confidence interval 1.25 to 2.03) for HbA1c >9%, even after adjusting for CHA2DS2-Vasc risk factors and use of oral anticoagulants. The risk for overall mortality was significantly higher in the HBA1C >9% group (aHR = 1.17 [1.07 to 1.28]). In conclusion, in this cohort of patients with AF and DM, HbA1c levels were associated with the risk of stroke in a dose-dependent manner even after accounting for other recognized risk factors for stroke.

Statin Medications and Amyotrophic Lateral Sclerosis Incidence and Mortality.

Studies of statins and amyotrophic lateral sclerosis (ALS) incidence and survival have had conflicting findings possibly related to difficulties with confounding by indication. We considered potency of statins used and duration of use to explore confounding by indication. Within the Clalit Health Services in Israel, we identified 948 ALS case patients from 2004 through 2017 and matched them with 1,000 control subjects each. Any statin use up to 3 years before ALS onset was not associated with ALS incidence but was associated with a reduced hazard ratio (HR) for death. Odds of ALS did not vary by statin potency, but use of only lower-potency statins was associated with longer survival (HR = 0.82, 95% CI: 0.68, 0.98), whereas the association with higher-potency statins was null compared with those case patients who did not use statins. However, duration of statin use appeared to account for these findings. Those who used statins only up to 3 years had longer survival (HR = 0.77, 95% CI: 0.61, 0.96) than did case patients who did not use statins, but those who used statins for >3 years did not. Although other explanations are possible, these findings could suggest a protective effect of statins on ALS survival that is partially masked by a worse prognosis from underlying reasons for taking statins that deserves further exploration.

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Using population-level incidence of hepatitis C virus and immigration status for data-driven screening policies: a case study in Israel.

BACKGROUND: Most studies estimate hepatitis C virus (HCV) disease prevalence from convenience samples. Consequently, screening policies may not include those at the highest risk for a new diagnosis. METHODS: Clalit Health Services members aged 25-74 as of 31 December 2009 were included in the study. Rates of testing and new diagnoses of HCV were calculated, and potential risk groups were examined. RESULTS: Of the 2 029 501 included members, those aged 45-54 and immigrants had lower rates of testing (12.5% and 15.6%, respectively), higher rates of testing positive (0.8% and 1.1%, respectively), as well as the highest rates of testing positive among tested (6.1% and 6.9%, respectively). DISCUSSION: In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases.

Diagnoses and Health Care Utilization for After-Hours Telemedicine Versus Primary Care Visits.

OBJECTIVE: The use of a nation-wide, pediatricians online (PO) after-hours telemedicine service has been offered in Israel for more than a decade. We sought to compare PO visits with those to the primary care pediatrician (PCP). METHODS: This is a retrospective cross-sectional study using Israel's largest health care provider database. We included children aged 0 to 18 years using either PO or PCP between 2015 and 2018. We compared the baseline characteristics, matching by socioeconomic status, chronic illness, and diagnosis, and compared their admission rates, laboratory testing, and medication prescription. RESULTS: During this study period there were 262,541 PO visits and a random 10% sample of PCP visits which yielded 1,813,103 visits. Users of PO were more likely to have a higher socioeconomic status (43% vs 28.9%), fever (13.3% vs 4.4%) and less likely to have acute respiratory conditions (8.8% vs 16.7%). Users of PO had higher rates of emergency department admissions (2.9% vs 0.4%), hospital admissions (0.9% vs 0.2%), and lower rates of laboratory testing (3.7% vs 7.4%) and medication prescription (42.0% vs 52.0%) within 24 hours. All differences were statistically significant (P < .005). CONCLUSIONS: Our pediatric telemedicine service operating after-hours has been found to be feasible, and widely used, for a myriad of clinical conditions. Significant differences exist between PO and PCP visit characteristics and outcomes. However, it remained unclear whether these differences reflect the difference in the patient population or whether they are the result of the different clinical services. Further research is warranted to clarify this matter.

Trends in the incidence of diagnosed diabetes: a multicountry analysis of aggregate data from 22 million diagnoses in high-income and middle-income settings.

BACKGROUND: Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. METHODS: In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995-2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. FINDINGS: Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from -1·1% to -10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. INTERPRETATION: The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Pre-Diabetes Increases Stroke Risk in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Diabetes mellitus (DM) increases the risk of embolism in nonvalvular atrial fibrillation (NVAF). The association between pre-diabetes and risk of ischemic stroke has not been studied separately in this population. OBJECTIVES: The purpose of this study was to evaluate whether pre-diabetes is associated with increased risk of stroke and death in patients with NVAF. METHODS: We conducted a historical cohort study using the Clalit Health Services electronic medical records. The study population included all members aged ≥25 years, with a first diagnosis of NVAF between January 1, 2010, and December 31, 2016. We compared 3 groups of individuals: those with pre-diabetes, those with diabetes, and normoglycemic patients. RESULTS: A total of 44,451 cases were identified. The median age was 75 years, and 52.5% were women. During a mean follow-up of 38 months, the incidence rates of stroke (per 100 person-years) were: 1.14 in normoglycemic individuals, 1.40 in those with pre-diabetes, and 2.15 in those with diabetes. In both univariate and multivariate analyses, pre-diabetes was associated with an increased risk of stroke compared with normoglycemic persons (adjusted hazard ratio [adjHR]: 1.19; 95% confidence interval [CI]: 1.01 to 1.4) even after adjustment for CHA2DS2-Vasc risk factors and use of anticoagulants, while diabetes conferred an even higher risk (vs. normoglycemia (adjHR: 1.56; 95% CI: 1.37 to 1.79). The risk for mortality was higher for individuals with diabetes (adjHR: 1.47; 95% CI: 1.41 to 1.54) but not for those with pre-diabetes (adjHR: 0.98; 95% CI: 0.92 to 1.03). CONCLUSIONS: In this cohort of patients with incident NVAF, pre-diabetes was associated with an increased risk of stroke even after accounting for other recognized risk factors.

Environmental Tobacco Smoke Exposure Among Children by Urinary Biomarkers and Parent Report.

OBJECTIVE: The goal of this study was to describe environmental tobacco smoke (ETS) exposure using urinary biomarkers and its correlation with parent report, among children presenting to emergency room. METHODS: This is a case control study among children aged 3 to 12 years at a tertiary pediatric emergency department in Israel. Children with respiratory (case) or gastrointestinal (control) symptoms were recruited and their accompanying parent completed a short survey. Urine samples were obtained and analyzed for nicotine, cotinine trans-3'-hydroxycotine. Clinical data were extracted from medical records. We compared tobacco exposure using urinary biomarkers, parent report, and Pearson's product-moment correlation, including 95% confidence intervals, between cases and controls. RESULTS: Forty-nine cases with respiratory symptoms and 96 controls with gastrointestinal symptoms were enrolled in the study. Parent-reported ETS exposure in the previous month was higher in the cases compared to control (71.4% vs 57.3%), although the difference was not statistically significant. The mean values of detectable biomarkers did not differ by between cases and controls. However, there was a correlation between urinary biomarkers and reported ETS exposure (0.278-0.460 for various biomarkers) only among cases. CONCLUSIONS: The majority of children in this study had detectable nicotine urinary biomarkers, regardless of their symptoms. However, correlation between parental report and urinary biomarkers was only found among children with symptoms potentially related to ETS. These findings imply that parents of children without respiratory symptoms may underestimate exposure. Efforts to educate parents and caregivers on the risks associated with exposure to ETS should be intensified, regardless of illness.

Validating reported cause of death using integrated electronic health records from a nation-wide database.

BACKGROUND: To compare the underlying cause of death reported by the Israeli Central Bureau of Statistics (CBS) with diagnoses in the electronic health records (EHR) of a fully integrated payer/provider healthcare system. METHODS: Underlying cause of death was obtained from the CBS for deaths occurring during 2009-2012 of all Clalit Health Service members in Israel. The final cohort consisted of members who had complete medical records. The frequency of a supportive diagnosis in the EHR was reported for 10 leading causes of death (malignancies, heart disease, cerebrovascular disease, diabetes, kidney disease, septicemia, accidents, chronic lower respiratory disease, dementia and pneumonia and influenza). RESULTS: Of the 45 680 members included in the study, the majority of deaths had at least one diagnosis in the EHR that could support the cause of death. The lowest frequency of supportive diagnosis was for septicemia (52.2%) and the highest was for malignancies (94.3%). Sensitivity analysis did not suggest an alternative explanation for the missing documentation. CONCLUSIONS: The underlying cause of death coded by the CBS is often supported by diagnoses in Clalit's EHR. Exceptions are septicemia or accidents that cannot be anticipated from a patient's EHR, and dementia which may be under-reported.

Elective caesarean section and bronchiolitis hospitalization: A retrospective cohort study.

BACKGROUND: We sought to evaluate whether elective caesarean section is associated with subsequent hospitalization for bronchiolitis. METHODS: This is a retrospective cohort study that used the electronic medical record database of Clalit Health Services, the largest healthcare fund in Israel, serving over 4.5 million members and over half of the total population. The primary outcome was bronchiolitis admission in the first 2 years of life. We performed logistic regression analyses to identify independent associations. We repeated the analysis using boosted decision tree machine learning techniques to confirm our findings. RESULTS: There were 124 553 infants enrolled between 2008 and 2010, and 5168 (4.1%) were hospitalized for bronchiolitis in the first 2 years of life. In logistic regression models stratified by seasons, elective caesarean section birth was associated with 15% increased odds (95% CI: 1.02-1.30) for infants born in the fall season, 28% increased odds (95% CI: 1.11, 1.47) for those born in the winter, 35% increased odds (95% CI: 1.12-1.62) for those born in the spring and 37% increased odds (95% CI: 1.18-1.60) for those born in the summer. In the boosted gradient decision tree analysis, the area under the curve for risk of bronchiolitis admission was 0.663 (95% CI: 0.652, 0.674) with timing of birth as the most important feature. CONCLUSION: Elective caesarean section, a potentially modifiable risk factor, is associated with increased odds of hospitalization for bronchiolitis in the first 2 years of life. These data should be considered when scheduling elective caesarean sections especially for infants born in spring and summer months.

Choosing Wisely: Determining performance of unjustified imaging in a large healthcare system.

AIMS: The Choosing Wisely Campaign identifies procedures and treatments that lack clinical justification for routine use according to expert opinion and evidence-based medicine. This study describes the rates and features of two such examples over a 10-year period. METHODS: This is a cross-sectional rolling cohort study between 2008 and 2017 in Clalit Health Services, the largest healthcare delivery system in Israel, with seven main hospitals and over 4.5 million members nationwide. All adult members who visited a Clalit Emergency Department (ED), and all children members who visited a Clalit ED for abdominal pain or appendicitis were eligible to be included in this study. Our measures were routine chest radiograph (CXR) in the context of pre-admission assessment for adults and abdominal computed tomography (CT) to rule out appendicitis for children. RESULTS: Of the 3 689 869 adult visits without a clinical indication for a CXR, 9.1% or 337 058 of them received a chest radiograph. Of the 35 973 children visits for presumed appendicitis, 7.2% of them had no imaging performed, 82.3% had an ultrasound (US), 6.9% had an US followed by a CT, and 3.6% or 1293 of them received a CT. There were several independent risk factors such as BMI, hospital, sex, year and diagnosis that are associated with having imaging that is not clinically indicated. CONCLUSIONS: Overall, this study found that diagnostic imaging practices are applied inconsistently by hospital and by population. Intervention efforts should be focused on subpopulations at greatest risk to further reduce exposure to such imaging.

The relationship between inpatient hyperglycaemia and mortality is modified by baseline glycaemic status.

AIMS: There is a well-established association between inpatient hyperglycaemia and mortality. However, evidence is inconsistent regarding whether this association is differential among those with and without type 2 diabetes mellitus (T2DM). Most studies are based on convenience samples or are unable to adjust for comorbidities. We examined whether the association between hyperglycaemia and 30-day mortality was modified by baseline glycaemic status. MATERIALS AND METHODS: This was a retrospective cohort study of 174,671 eligible hospitalized individuals between 2012 and 2015. Thirty-day mortality was assessed during the first inpatient stay up to 30 days post discharge. The adjusted association between hyperglycaemia and mortality was assessed with logistic regression models. Then, four interaction terms were entered into the model to assess if the association between hyperglycaemia and mortality differed by baseline glycaemic status. RESULTS: The multivariate model demonstrated a 2.18-fold risk of mortality associated with hyperglycaemia (odds ratio [OR] [95%CI]: 2.19 [2.08-2.31]). Adding the interaction terms between hyperglycaemia and baseline glycaemic status the ORs of 30-day mortality were 1.41 (1.25-1.60) in non-T2DM status, 1.32 (1.16-1.51) in pre-diabetes status and 1.30 (1.04-1.62) in unscreened status, as compared to T2DM status with hyperglycaemia. CONCLUSIONS: Hyperglycaemia is positively associated with mortality and both those without and with controlled T2DM are at highest risk. These findings may help medical staff identify potential increased risk of mortality upon hospital entry and discharge, and direct further research to assess how hyperglycaemia control and proactive deterioration prevention throughout the entire inpatient stay may prevent adverse outcomes.

Characteristics and Symptoms of App Users Seeking COVID-19-Related Digital Health Information and Remote Services: Retrospective Cohort Study.

BACKGROUND: Patient-facing digital health tools have been promoted to help patients manage concerns related to COVID-19 and to enable remote care and self-care during the COVID-19 pandemic. It has also been suggested that these tools can help further our understanding of the clinical characteristics of this new disease. However, there is limited information on the characteristics and use patterns of these tools in practice. OBJECTIVE: The aims of this study are to describe the characteristics of people who use digital health tools to address COVID-19-related concerns; explore their self-reported symptoms and characterize the association of these symptoms with COVID-19; and characterize the recommendations provided by digital health tools. METHODS: This study used data from three digital health tools on the K Health app: a protocol-based COVID-19 self-assessment, an artificial intelligence (AI)-driven symptom checker, and communication with remote physicians. Deidentified data were extracted on the demographic and clinical characteristics of adults seeking COVID-19-related health information between April 8 and June 20, 2020. Analyses included exploring features associated with COVID-19 positivity and features associated with the choice to communicate with a remote physician. RESULTS: During the period assessed, 71,619 individuals completed the COVID-19 self-assessment, 41,425 also used the AI-driven symptom checker, and 2523 consulted with remote physicians. Individuals who used the COVID-19 self-assessment were predominantly female (51,845/71,619, 72.4%), with a mean age of 34.5 years (SD 13.9). Testing for COVID-19 was reported by 2901 users, of whom 433 (14.9%) reported testing positive. Users who tested positive for COVID-19 were more likely to have reported loss of smell or taste (relative rate [RR] 6.66, 95% CI 5.53-7.94) and other established COVID-19 symptoms as well as ocular symptoms. Users communicating with a remote physician were more likely to have been recommended by the self-assessment to undergo immediate medical evaluation due to the presence of severe symptoms (RR 1.19, 95% CI 1.02-1.32). Most consultations with remote physicians (1940/2523, 76.9%) were resolved without need for referral to an in-person visit or to the emergency department. CONCLUSIONS: Our results suggest that digital health tools can help support remote care and self-management of COVID-19 and that self-reported symptoms from digital interactions can extend our understanding of the symptoms associated with COVID-19.

Pediatric measles cases by residence status in Tel Aviv, Israel.

BACKGROUND: Measles is a vaccine-preventable infectious disease whose outbreaks generally originate from exposure to populations with low vaccination coverage. METHODS: This study compared the rates and morbidity of measles cases in the district of Tel-Aviv during two outbreaks (2012 and 2018-2019) by citizenship and geographic location. RESULTS: There were 67 pediatric cases reported in 2012 and 222 in 2018-2019. Cases were more likely to have pneumonia in 2012 as compared to in 2018-2019 (58.2% versus 6.3%) and less likely to report a single vaccination dose (9.5% versus 22.8%, respectively). In 2012, the majority of cases were among children without legal residence (CWLR), while in 2018-2019, they were the minority of cases (N = 54, 80.6% versus N = 51, 23.0%, respectively). In both outbreaks, CWLR were more likely to be less than one year old (the recommended age for the first dose of measles vaccination), unvaccinated or with unknown vaccine status, to be treated in a tertiary care center, and to have pneumonia than children with Israeli citizenship (CC). In both outbreaks, CWLR lived in a concentrated neighborhood in Southern Tel Aviv. CONCLUSION: While the two measles outbreaks differed in overall morbidity, in both outbreaks CWLR presented with a more severe clinical presentation and were less likely to be vaccinated (in part due to their younger age) than CC. The geographically concentration of CWLR was distinct from that of the CC in both outbreaks. Healthcare professionals should promote vaccination uptake and increase parents' awareness to early signs of the disease.

A comprehensive descriptive assessment of obesity related chronic morbidity and estimated annual cost burden from a population-based electronic health record database.

BACKGROUND: The growing prevalence of obesity and its complications pose a huge burden on the individual and health care systems worldwide. This study presents the frequency of multiple prevalent co-morbidities and estimated annual cost burden by body mass index (BMI) groups, age, and sex among the Israeli adult population to provide policy makers with further evidence to appropriately target interventions. METHODS: This cross-sectional study utilized population-based electronic medical records from the largest payer-provider health fund in Israel. The population included individuals ≥25 years as of 01/01/2014. A new approach assessing body system-related morbidity (BSRM) prevalence was assessed along with estimated annual cost burden for the year 2015 and presented across BMI group, age, and sex via heat maps. RESULTS: Among 1,756,791 adults, 65% had an elevated BMI (BMI > 25 kg/m2). Heat map analysis demonstrated a higher multi-BSRM prevalence and relative estimated annual cost burden among participants with obesity in all age groups. There was a notably higher multi-BSRM prevalence among men and women aged 25-29 with class III obesity (26 and 30%, respectively) compared to the corresponding BMI groups between 18·5- < 25 kg/m2 (5 and 9%, respectively). Healthcare costs were 1·72 times higher among men aged 25-29 with class III obesity and 2·75 times among women aged 25-29 with class III obesity compared to those of healthy weight. CONCLUSIONS: The detailed analysis describes the uneven distribution of burdens across BMI groups, age, and sex allowing policy makers to identify sub-populations for targeted interventions.

Long-term effectiveness of the Diabetes Conversation Map™ Program on health outcomes: A case-control retrospective cohort study.

AIM: To evaluate the clinical and health behavioural outcomes of a large sample of participants from the Diabetes Conversation Map™ Program. DESIGN: A matched-case-control study that was performed on a retrospective cohort study. METHODS: Participants were 11,053 Clalit Health Services members with type 2 diabetes who enrolled in the Diabetes Conversation Map™ Program between January 2010 - April 2016. The matched-control group was formulated using sequential matching, by matching cases to controls at a ratio of 1:3, based on age, sex, and HbA1c level. The associations between the programme group and annual clinical and health behaviours were assessed between cases and controls at five time points using linear and Poisson regression analyses. RESULTS: The intervention group had significantly lower HbA1c, glucose, and low-density lipoprotein levels and more frequent glucose blood testing each year up to 36 month post-enrolment compared with the matched controls. Other outcomes were significantly different for shorter time periods, including higher high-density lipoprotein and lower triglyceride levels at 6- and 12-month follow-up and lower diastolic blood pressure and greater medication adherence at 6-month follow-up. CONCLUSIONS: Enrolment in the programme was associated with improved clinical and health behaviour outcomes for at least 6 months and most outcomes persisted for up to 36 months. IMPACT: This is the first study to evaluate the Diabetes Conversation Map™ Program with a large sample over long period of time. This nurse-led group intervention evaluation adds to the literature on health outcomes on the lives of patients with type 2 diabetes. STUDY REGISTRATION: This study was registered retrospectively to the Open Science Framework, the registration form can be found at: https://osf.io/63cse.