Assessing the diagnostic utility of the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system using real-world data.

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 (< 50 × 109/L), and hyperferritinemia (300-1000 ng/mL) were found to be the three most accurate classifiers of GD in both databases. CONCLUSION: In this analysis of real-world patient data, certain individual features of the GED-C score discriminate more successfully between patients with GD and controls than the overall score. An enhanced diagnostic model may lead to earlier, reliable diagnoses of Gaucher disease, aiming to minimize the severe complications associated with this disease.

Calcium score of the entire thoracic aorta is an independent predictor of all-cause mortality in patients referred to chest computed tomography.

BACKGROUND: Thoracic arterial calcifications (TAC) are not routinely reported or quantified in chest CT scans. We aimed to evaluate the association between TAC of the entire thoracic aorta and all-cause mortality (ACM) in patients referred to standard chest CT. METHODS: A retrospective analysis of consecutive standard chest CT scans (non-gated, non-contrast) for the quantification of TAC, CAC and aortic valve calcification. TAC was divided into 4 sample-derived categories (TAC 1 = 0, TAC 2 = 1-65, TAC 3 = 66-439 and TAC 4 ≥ 440). Data regarding ACM was retrieved from the health care provider database. Multivariate Cox proportional regression models were used to assess associations between the TAC categories and ACM. RESULTS: The study cohort included 415 patients (mean age 67 years, 52% male); 107 ACM events were recorded during a median follow-up of 9 years (inter-quartile range: 7.4-10.4). The rate of ACM was 13%, 25%, 32%, 41% according to TAC category (p < 0.001). The highest TAC category (≥ 440) was a strong and independent predictor of ACM [HR = 1.69 (1.13-2.52; 0.01)] in multivariate analysis. Other independent predictors of ACM included age [HR = 1.07 (1.04-1.10; p < 0.001)], male sex [HR = 2.27 (1.49-3.46; 0.001)] and malignancy [HR = 2.21 (1.49-3.23; < 0.001)]. CONCLUSIONS: Severe TAC (≥ 440) was found to be an independent predictor of ACM. Thus, we suggest that documenting and quantifying TAC should be routinely incorporated into standard chest CT reports.

Cancer Risk in Patients with Gaucher Disease Using Real-World Data.

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.

Identifying Profiles of Patients With Uncontrolled Type 2 Diabetes Who Would Benefit From Referral to an Endocrinologist.

OBJECTIVE: To compare the outcomes of glycemic uncontrolled diabetes mellitus type 2 patients receiving treatment from endocrinologists with those treated by primary care physicians. Additionally, this research aims to identify patient profiles that would benefit from personalized referral-a novel medical approach that aims to match the most suitable specialist for effectively managing patient while considering the patient's profile. METHODS: This retrospective cohort study uses the Maccabi Healthcare Services diabetes registry to match 508 pairs of glycemic uncontrolled diabetes mellitus type 2 patients treated by endocrinologists (EndoG) and primary care physicians (PcPG). Using a generalized additive model, we analyzed the hemoglobin A1c (HbA1c) trend over 1 year for each group. We employed the odds ratio (OR) from conditional logistic regression to determine the likelihood of favorable outcomes in the EndoG compared to the PcPG, using the entire cohort and subcohort profiles. RESULTS: The generalized additive model comparison indicated an improvement in HbA1c levels in both groups, with the EndoG outperforming the PcPG. Furthermore, the EndoG group had an OR = 2.27 (95% confidence interval, 1.6 to 3.2) for reducing HbA1c by at least 1% within a year and an OR = 1.68 (95% confidence interval, 1.02 to 2.76) for achieving low-density lipoprotein levels< 100 mg/dl. We identified 96 profiles with positive outcomes, all favoring treatment by endocrinologists. CONCLUSIONS: EndoG demonstrated superior HbA1c control over time and achieved better outcomes compared to PcPG. The identification of 96 profiles benefiting from endocrinologist referral emphasizes the potential of personalized referral.

The Association Between Depression and Invasive and In-situ Cervical Tumors: A Large Population Based Cohort Study.

BACKGROUND: Depression has been shown to be associated with cervical tumors (CTs), an association mostly demonstrated in studies in which temporality could not have been ascertained. OBJECTIVES: To study the association between depression and CTs and the influence of co-morbidities of this association in a large cohort study. METHODS: A retrospective computer-based cohort study was conducted. The cohort included 357,450 female members of Maccabi Healthcare Services. The cohort was classified as depressed or non-depressed using the International Classification of Diseases 9/10 codes. For each subgroup, demographic characteristics, behavioral characteristics, co-morbidities, and CTs diagnosis were obtained. The burden of co-morbidities was defined as the sum of major co-morbidities. We used zero-inflated negative binomial regression analysis due to over-dispersion to estimate the relative risk (RR) for CTs with 95% confidence interval (95%CI). RESULTS: Depression was diagnosed in 15,789 women. Among this group, CTs were diagnosed in 1585 (10.0%). Among the 341,661 non-depressed, CTs were diagnosed in 4185 (1.2%). After adjustment to age and socioeconomic status, the association between depression and CTs was RR=9.2 (95%CI 8.7-9.9, P-value < 0.0001). The association between depression and CTs increased as the burden of clinical conditions increased (P-value < 0.0001). CONCLUSIONS: Women with depression are at a higher risk for CTs, especially among those who have several co-morbidities. Tighter gynecology surveillance is crucial among these women.

Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.

AIMS: Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). METHODS AND RESULTS: The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9-3.3], 2.0 (1.9-2.1), 4.5 (4.2-4.9), 2.8 (2.7-3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43-50) within 3 months] after adjustment for other CVD subtype incidence. CONCLUSION: Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.

Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP.

AIMS: The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an 'Add-on' to incorporate CKD measures into these algorithms, using a validated approach. METHODS: In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. RESULTS: In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004-0.008) and 0.016 (0.010-0.023), respectively, for SCORE2 and 0.012 (0.009-0.015) and 0.024 (0.014-0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062-0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. CONCLUSION: Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

Pharmacologic Treatment of Type 2 Diabetes in the U.S., Sweden, and Israel.

OBJECTIVE: To characterize and compare glucose-lowering medication use in type 2 diabetes in the U.S., Sweden, and Israel, including adoption of newer medications and prescribing patterns. RESEARCH DESIGN AND METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) from the U.S., the Stockholm CREAtinine Measurements (SCREAM) project from Sweden, and Maccabi Healthcare Services (Maccabi) from Israel. Specific pharmacotherapy for type 2 diabetes between 2007 and 2018 was examined. RESULTS: Use of glucose-lowering medications among patients with type 2 diabetes was substantially lower in NHANES and SCREAM than in Maccabi (66.0% in NHANES, 68.4% in SCREAM, and 88.1% in Maccabi in 2017-2018). Among patients who took at least one glucose-lowering medication in 2017-2018, metformin use was also lower in NHANES and SCREAM (74.1% in NHANES, 75.9% in SCREAM, and 92.6% in Maccabi) whereas sulfonylureas use was greater in NHANES (31.5% in NHANES, 16.0% in SCREAM, and 14.9% in Maccabi). Adoption of dipeptidyl peptidase 4 inhibitors and sodium-glucose cotransporter 2 inhibitors (SGLT2i) was slower in NHANES and SCREAM than in Maccabi. History of atherosclerotic cardiovascular disease, heart failure, reduced kidney function, or albuminuria was not consistently associated with greater use of SGLT2i or glucagon-like peptide 1 receptor agonists (GLP1RA) across the three countries. CONCLUSIONS: There were substantial differences in real-world use of glucose-lowering medications across the U.S., Sweden, and Israel, with more optimal pharmacologic management in Israel. Variation in access to care and medication cost across countries may have contributed to these differences. SGLT2i and GLP1RA use in patients at high risk was limited in all three countries during this time period.

Epidemiology of treatment resistant depression among major depressive disorder patients in Israel.

INTRODUCTION: Major depressive disorder (MDD) is one of the most common mental disorders worldwide, estimated to affect 10-15% of the population per year. Treatment resistant depression (TRD) is estimated to affect a third of these patients who show difficulties in social and occupational function, decline of physical health, suicidal thoughts and increased health care utilization. We describe the prevalence of MDD, TRD and associated healthcare resource utilization in Maccabi Healthcare Services (MHS), a 2.5 million-member state-mandated health service in Israel. METHODS: All MHS members with an MDD diagnosis were identified within the years 2017-2018 and prevalence assessed by age, sex and TRD. To assess the incidence of MDD, members aged 18-65 years at the start of any MDD episode were identified between 1st January 2016 and 31st May 2018 with at least one systemic first-line antidepressant treatment within three months before or after the initial episode. Treatment patterns, time on first-line treatment, and healthcare resource utilization were compared by TRD. RESULTS: A total of 4960 eligible MDD patients were identified (median age = 51 years, 65% female), representing a period prevalence of 0.218%, and of those, a high proportion of patients received drug treatment (92%). Among incident MDD cases (n = 2553), 24.4% had TRD. Factors associated with TRD included increasing age and personality disorder. Median time on treatment was 3.7 months (longer for those without TRD than those with) and 81.9% of patients purchased more than one month's supply of therapy. In the year after index, patients with TRD had a significant increased number of visits to primary care physicians, psychiatrists, emergency room visits, general hospitalizations, and psychiatric hospitalizations. CONCLUSION: Our study shows that prevalence of MDD in Israel is low compared to other countries, however once diagnosed, patients' are likely to receive drug treatment. Among patients diagnosed with MDD, the proportion of TRD is similar to other countries, increases with age and is associated with increased healthcare utilization, therefore should be a focus of continued research for finding effective long term treatment options.

All-cause mortality prediction in T2D patients with iTirps.

Mortality in the type II diabetic elderly population can sometimes be prevented through intervention, for which risk assessment through predictive modeling is required. Since Electronic Health Records data are typically heterogeneous and sparse, the use of Temporal Abstraction and time intervals mining to discover frequent Time Intervals Related Patterns (TIRPs) is employed. While TIRPs are used as features for a predictive model, the temporal relations between them in general, and among each TIRP's instances are not represented. We introduce a novel TIRP based representation called integer-TIRP (iTirp) in which the TIRPs become channels containing values that represent the TIRP instances that were detected at each time point. Then the iTirp representation is fed into a Deep Learning architecture, that learns this kind of temporal relations, using a Recurrent Neural Network or a Convolutional Neural Network. Additionally, a predictive committee is introduced in which raw data and iTirp data are concatenated as inputs. Our results show that iTirps based models outperform the use of deep learning with raw data, resulting in 82% AUC.

Advanced-Stage Parkinson's Disease: From Identification to Characterization Using a Nationwide Database.

Background: As Parkinson's disease (PD) progresses, response to oral medications decreases and motor complications appear. Timely intervention has been demonstrated as effective in reducing symptoms. However, current instruments for the identification of these patients are often complicated and inadequate. It has been suggested that anti-PD intensified therapy (IT) can serve as a proxy for increased burden of disease. Objective: To explore whether IT aligns with events reflecting advanced PD (APD) burden. Methods: This was a retrospective analysis of PD beneficiaries in the second-largest healthcare provider in Israel. Patients with PD diagnosed between January 2000 and June 2018 and treated with levodopa (l-dopa) ≥5 times/day and/or ≥1000 mg l-dopa equivalent daily dose were defined as the IT cohort (n = 2037). Treated patients with PD not fulfilling this criterion were defined as the nonintensified therapy (NIT) cohort (n = 3402). Point prevalence and 5- and 10-year cumulative incidence of IT were assessed. Baseline demographic and comorbidities, 1-year healthcare resource use, health costs, and time to clinical events were assessed and compared between cohorts. Results: IT was associated with significantly (P < 0.05) higher healthcare resource use compared with NIT. In turn, IT patients incurred higher healthcare costs (P < 0.001) and were at greater risk for mortality, hospitalization, disability, and device-aided therapy use (P < 0.001, for all comparisons). Conclusions: Treatment intensity can serve as an objective and robust indicator of more APD. This readily extractable marker can be easily integrated into electronic medical record alerts to actively target more advanced patients and to guide risk-appropriate care.

Epidemiology and Economic Burden of Atopic Dermatitis: Real-World Retrospective Data from a Large Nationwide Israeli Healthcare Provider Database.

INTRODUCTION: Real-world data on the epidemiology and economic burden of atopic dermatitis (AD) are limited. Here we describe the epidemiology and economic burden of AD using electronic healthcare data from Israel. METHODS: A retrospective study was performed using the Maccabi Healthcare Services database. AD incidence in 2008-2017 and point prevalence (ADprev) on 31 December 2017 were described using diagnosis codes for overall patients, and sex and age subgroups. For ADprev, severity was defined using recently dispensed treatments for AD. Annual healthcare resource utilization in AD prevalent patients was compared with non-AD matched controls using generalized linear modelling. Direct annual costs were estimated also. RESULTS: AD incidence was 7.0/1000 person-years; overall prevalence was 4.4% (female patients 4.5%, male patients 4.3%; age 0 to less than 6 months, 0.9%; 6 months to less than 12 years, 11.0%; 12 to less than 18 years, 5.8%; 18 years or older, 2.2%). Among ADprev (n = 94,483), mild, moderate, and severe AD comprised 57.7%, 36.2%, and 6.1% (adults 43.8%, 46.3%, 9.9%), respectively. Dermatologist and allergist visits and hospitalization rates (at least one) were 40.7%, 6.6%, and 3.8% in 2017. Compared with controls, overall and moderate-to-severe AD were associated with 36% and 52% increases in annual per-person costs (incremental costs $126 and $190). CONCLUSIONS: AD epidemiology in Israel is comparable with other real-world database studies. AD imposes an economic burden that increases with disease severity.

Occurrence and costs of atopic dermatitis in IsraelAtopic dermatitis is a disease that causes the skin to be inflamed and itchy. Atopic dermatitis is most common in children but can also occur in adolescents and adults. Using data from a large healthcare provider in Israel, this study aimed to describe how common atopic dermatitis is within the population. Costs related to the use of healthcare services (such as visits to dermatologists and creams to treat atopic dermatitis) in the year 2017 were compared between persons with versus without atopic dermatitis. For the years 2008 to 2017, approximately 7 out of 1000 people were newly diagnosed with atopic dermatitis each year (incidence). Among people alive on 31 December 2017, 4.4% had atopic dermatitis (prevalence), with 42.3% suggestive of moderate to severe disease. Patients with atopic dermatitis, particularly those with more severe disease, used healthcare services more frequently. Compared with people without atopic dermatitis, medical costs among patients with atopic dermatitis were 36% higher (corresponding to added costs of $126 per person per year). This study helps to better understand how many people have atopic dermatitis, and what healthcare resources are needed to manage this disease.

Long-Term Persistence and Monotherapy with Device-Aided Therapies: A Retrospective Analysis of an Israeli Cohort of Patients with Advanced Parkinson's Disease.

INTRODUCTION: Patients with advanced Parkinson's disease (PD) may require device-aided therapies (DAT) for adequate symptom control. However, long-term, real-world efficacy and safety data are limited. This study aims to describe real-world, long-term treatment persistence for patients with PD treated with levodopa-carbidopa intestinal gel (LCIG). The study also aims to describe patient profiles, treatment discontinuation rates, co-medication patterns, monotherapy rates, and rates of healthcare visits and their associated costs for patients receiving all forms of DAT (deep brain stimulation [DBS], continuous subcutaneous apomorphine infusion [CSAI], or LCIG). METHODS: In this retrospective analysis of the Israeli Maccabi Healthcare Services database, adult patients with PD were analyzed in three cohorts, based on DAT (DBS, CSAI, or LCIG). The primary endpoint was LCIG treatment persistence 12 months after initiation. RESULTS: This analysis included 161 DAT-treated patients (LCIG, n = 62; DBS, n = 76; CSAI, n = 23). Among those who discontinued, the mean time to discontinuation was 86.4 months for LCIG and 42.4 months for CSAI (p = 0.046). Twelve months after initiation, 14.3% LCIG, 10.7% DBS, and 5.9% CSAI patients were not receiving any additional anti-parkinsonian therapy. At the last recorded visit, 28.6% LCIG, 13.3% DBS, and 5.9% CSAI patients received DAT as monotherapy. During the first 12 months after initiation, 45.2% LCIG, 65.2% CSAI, and 1.3% DBS patients had no reported hospitalization days. Annual healthcare visit costs decreased following LCIG initiation (US$9491 vs. $8146) and increased following DBS ($4113 vs. $7677) and CSAI ($6378 vs. $8277). CONCLUSION: DAT are well maintained in patients with advanced PD. These retrospective data suggest that patients receiving LCIG may have higher long-term persistence rates compared with patients receiving CSAI. A subgroup of patients was treated with DAT as monotherapy without additional oral anti-parkinsonian therapy, with LCIG showing the highest rates.

Burden of Endometriosis: Infertility, Comorbidities, and Healthcare Resource Utilization.

The goal of our study was to evaluate the burden of endometriosis in the community by comparing healthcare resource utilization, total direct medical costs, infertility, and comorbidity rates of women with and without a diagnosis of endometriosis. A retrospective case-control study was performed using the databases of a 2.1 million-member nationwide healthcare plan. The study population included women aged 15-55 years enrolled in the healthcare plan. Women with a diagnosis (ICD-9) of endometriosis were compared to controls without diagnosed endometriosis. Women were individually matched (1:4) on age and residence area. Patient characteristics were described, including infertility, comorbidities, and annual healthcare resource utilization. Total direct medical costs were analyzed in a generalized linear model adjusting for age. Women with endometriosis (n = 6146, mean age ± SD: 40.4 ± 8.0 y) were significantly more likely than controls (n = 24,572) to have a lower BMI and a higher socioeconomic status. After adjusting for BMI and socioeconomic status, endometriosis was significantly associated with infertility (OR = 3.3; 95% CI 3.1-3.5), chronic comorbidities, higher utilization of healthcare services (hospitalization: OR = 2.3; 95% CI 2.1-2.5), pain medications, and antidepressants. Women aged 15-19 y with endometriosis had substantially higher utilization of primary care visits (57.7% vs. 14.4%) and oral contraceptive use (76.9% vs. 9.6%). Direct medical costs associated with endometriosis were higher than those for controls (OR = 1.75; 95% CI 1.69-1.85). Endometriosis is associated with a high burden of comorbidities, increased healthcare resource utilization, and excess costs, particularly for younger patients whose healthcare needs may differ widely from the older population.

Minimizing treatment-induced emergence of antibiotic resistance in bacterial infections.

Treatment of bacterial infections currently focuses on choosing an antibiotic that matches a pathogen's susceptibility, with less attention paid to the risk that even susceptibility-matched treatments can fail as a result of resistance emerging in response to treatment. Combining whole-genome sequencing of 1113 pre- and posttreatment bacterial isolates with machine-learning analysis of 140,349 urinary tract infections and 7365 wound infections, we found that treatment-induced emergence of resistance could be predicted and minimized at the individual-patient level. Emergence of resistance was common and driven not by de novo resistance evolution but by rapid reinfection with a different strain resistant to the prescribed antibiotic. As most infections are seeded from a patient's own microbiota, these resistance-gaining recurrences can be predicted using the patient's past infection history and minimized by machine learning-personalized antibiotic recommendations, offering a means to reduce the emergence and spread of resistant pathogens.

Cutaneous Comorbidities Associated With Atopic Dermatitis in Israel: A Retrospective Real-World Data Analysis.

BACKGROUND: Patients with atopic dermatitis (AD) are susceptible to infectious and inflammatory cutaneous comorbidities. OBJECTIVE: The aim of the study was to describe the prevalence of cutaneous comorbidities associated with AD, including their relationship with AD severity. METHODS: A retrospective cross-sectional analysis was performed using the Israeli Maccabi Healthcare Services database. Prevalent AD cases on December 31, 2017, were diagnosed with AD at any time since 1998 and had 1 or more recent (2013-2017) AD diagnoses. Dispensed AD treatments within 5 or fewer years served as a surrogate for AD severity. Cutaneous comorbidities in AD cases were compared with non-AD controls matched 1:1 on age, sex, and residential area. Among adults, comorbidities were compared across AD severity using multinomial logistic regression. RESULTS: The eligible population included 94,483 patients with mild (57.7%), moderate (36.2%), or severe (6.1%) AD, and 94,483 matched non-AD controls. Skin infections, inflammatory skin conditions, cutaneous manifestations of AD, and sweat gland disorders were more prevalent ( P < 0.001) in patients with AD than in controls. Most cutaneous comorbidities that were more prevalent in adult patients with AD were also significantly ( P < 0.001) associated with AD severity. CONCLUSIONS: This study suggests that AD is associated with many infectious and inflammatory cutaneous comorbidities and highlights the relationship between AD severity and comorbidity prevalence.

Leveraging Comprehensive Health Records for Breast Cancer Risk Prediction: A Binational Assessment.

Breast cancer (BC) risk models based on electronic health records (EHR) can assist physicians in estimating the probability of an individual with certain risk factors to develop BC in the future. In this retrospective study, we used clinical data combined with machine learning tools to assess the utility of a personalized BC risk model on 13,786 Israeli and 1,695 American women who underwent screening mammography in the years 2012-2018 and 2008-2018, respectively. Clinical features were extracted from EHR, personal questionnaires, and past radiologists' reports. Using a set of 1,547 features, the predictive ability for BC within 12 months was measured in both datasets and in sub-cohorts of interest. Our results highlight the improved performance of our model over previous established BC risk models, their ultimate potential for risk-based screening policies on first time patients and novel clinically relevant risk factors that can compensate for the absence of imaging history information.

Adolescent body mass index and changes in pre-pregnancy body mass index in relation to risk of gestational diabetes.

BACKGROUND: Pregestational excessive body mass index (BMI) is linked to an increased risk for gestational diabetes mellitus (GDM), but less is known on the effect of adolescent BMI on GDM occurrence. The study aimed to investigate possible associations of adolescent BMI and changes in BMI experienced before first pregnancy, with gestational diabetes risk. METHODS: This retrospective study was based on linkage of a military screening database of adolescent health status (Israel Defence Forces) including measured height and weight, with medical records (Maccabi Healthcare Services, MHS) of a state-mandated health provider. The latter covers about 25% of the Israeli population; about 90% of pregnant women undergo screening by the two-step Carpenter-Coustan method. Adolescent BMI was categorized according to Center of Disease Control and Prevention percentiles. Only first documented pregnanies were analyzed and GDM was the outcome. FINDINGS: Of 190,905 nulliparous women, 10,265 (5.4%) developed GDM. Incidence proportions of GDM were 5.1%, 6.1%, 7.3%, and 8.9% among women with adolescent normal BMI, underweight, overweight, and obesity (p<0.001), respectively. In models that accounted for age at pregnancy, birth year, and sociodemographic variables, the adjusted odd ratios (aORs) for developing GDM were: 1.2 (95%CI, 1.1-1.3), 1.5 (1.4-1.6), and 1.9 (1.7-2.1) for adolescent underweight, overweight, and obesity (reference group, normal BMI). Adolescent BMI tracked with BMI notes in the pre-pregnancy period (r=63%). Resuming normal pre-pregnancy BMI from overweight or obesity in adolescence diminished GDM risk, but this diminished risk was not observed among those who returned to a normal per-pre-pregnancy BMI from being underweight in adolescence. Sustained overweight or obesity conferred an aOR for developing GDM of 2.5 (2.2-2.7); weight gain from adolescent underweight and normal BMI to pre-pregnancy excessive BMI conferred aORs of 3.1 (1.6-6.2) and 2.6 (2.2-2.7), respectively. INTERPRETATION: Change in BMI status from adolescence to pre-pregnancy may contribute to GDM risk. Identifying at-risk populations is important for early preventive interventions. FUNDING: None.

Shifting from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: predictors, patterns and temporal trends.

BACKGROUND: Non-Vitamin K antagonist oral anticoagulants (NOACs) emerged as an alternative with comparable or superior efficacy and safety to vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). OBJECTIVES: The aim of the current study was to investigate the patterns, predictors, timelines and temporal trends of shifting from VKAs to NOACs. METHODS: In this retrospective observational study, the computerized database of a large healthcare provider in Israel, Maccabi Healthcare Services, was searched to identify patients with AF for whom either a VKA or NOAC was prescribed between 2012 and 2015. Time from diagnosis to therapy initiation and to shifting between therapies was evaluated. RESULTS: Out of 6987 eligible AF incident patients, 2338 (33.4%) initiated treatment with a VKA and 2221 (31.7%) with a NOAC. In addition, 5259 prevalent patients were analyzed. During the study period, NOAC prescriptions proportion among the newly diagnosed cases increased from 32 to 68.4% (p for trend <  0.001). The median time from diagnosis to first dispensing was greater in NOAC than VKA and decreased among patients treated with NOAC during the study period (2012: 1.9 and 0.3 months, 2015: 0.7 and 0.2 months, respectively). During follow-up, 3737 (49%) patients (54.3% and 47.1% of the incident and prevalent cases, respectively), shifted from a VKA to a NOAC, after a median of 22 months and 39 months in the incident and prevalent cases, respectively, decreasing throughout the study period. Female gender, younger age, southern district, higher CHADS2 and CHA2DS2-VASC score, non-smoking, and treatment with antiplatelets were associated with a greater likelihood for therapy shift. Shifting from a NOAC to a VKA decreased over time from 8 to 4.5% in 2012 to 0.5% and 0.7% in 2015 in the incident and prevalent groups, p <  0.001 respectively. CONCLUSIONS: Shifting from VKA to NOAC occurred in 50% of the cases, more frequently among incident cases, and younger patients with greater stroke risk. Shifting from a NOAC to a VKA was much less frequent, yet it occurred more often in incident cases and decreased over time. A socially and economically sensitive program to optimize the initiation of OAC therapy upon diagnosis is warranted.