Anxiety is often studied at the individual level, with societal and environmental effects remaining under-researched. This study examines the impact of national security instability on short-term anti-anxiety medication purchases in Israel. A retrospective cohort study using electronic medical records from an Israeli health fund covering over 2.6 million people, spanning January 1, 2006 to July 31, 2024. We assessed the association between ‘military operations’, the ‘Second Lebanon War’ and the ‘October 7th War’ and the incidence of short-term benzodiazepine purchases (a proxy for acute anxiety or stress responses prompting pharmacological treatment), differentiating first-ever from repeated purchases. 1,142,641 members aged 21 or older contributed 12,027,931 person-years at risk. The risk of first-time benzodiazepine purchases was 28

SF sensitivity analysis for the diagnosis of cancer

Comparison of MHS members who did or did not perform SF test, based on synthetic data of members who performed lab tests in 2016

Background: Ferritin, an iron storage protein and acute phase reactant, has been implicated in various aspects of human health and disease, including cancer. Previous studies have identified elevated serum ferritin (SF) levels in several cancer types, but a comprehensive examination across different malignancies remains lacking. This study aims to fill this gap by utilizing anonymized data from Maccabi Health Services (MHS), one of Israel's largest health organizations, to explore the association between elevated SF levels and the diagnosis of different malignancies.Methods: An extensive dataset from MHS, comprising 2.7 million members, including 1.3 million individuals who underwent SF level testing, was analyzed. ORs and 95% confidence intervals were calculated to assess the association between high SF levels and cancer diagnosis. Subgroup analysis was conducted to investigate variations across different malignancies.Results: The analysis revealed a significant association between elevated SF levels and cancer diagnosis among MHS members, with an OR of 1.9 (95% confidence interval, 1.71-2.15). Subgroup analysis unveiled differences in the association across malignancy types, with hematologic, hepatobiliary, and respiratory malignancies more strongly associated with high SF levels.Conclusions: This study provides further support for the link between elevated SF levels and malignancy, leveraging a vast dataset from MHS, underscoring potential utilities of elevated SF levels as a potential indicator for cancer with a variable role among different malignancy types.Impact: The identification of elevated SF levels as a potential indicator for underlying malignancy for seemingly healthy individuals

Detail on the different malignancies defining each sub-group used in the study

ICD codes used in the study as confounding variables for the connection between SF and malignancy

FDR-Adjusted p values of subgroup analysis

Introduction: We map the patient journey from symptom onset to intervention and describe primary treatment in a retrospective population-based cohort study of patients in a large healthcare-provider. Methods: Newly diagnosed adult patients diagnosed with stages I-III non-small cell lung cancer (NSCLC) between 2016 and 2019 were identified from the Israel National Cancer Registry and chart review was performed to extract de-identified data. The following timelines were constructed: from symptom onset to imaging, imaging to biopsy, and biopsy to primary treatment initiation. Cutoff: 31st December 2021. The initial symptom was captured up to one year prior to biopsy. Results: Among 302 patients (41 % female, 70 % >=65 years, 79 % former or current smoking, 62 % adenocarcinoma), 34.1 % stage I, 10.3 % stage II, 42.1 % stage III and 13.6 % unknown (AJCC ver. 8). In the baseline year, 80.5 % of patients reported at least one symptom to their physician, and 12.3 % reported four or more symptoms. The most common symptoms reported were cough (29.8 %), pneumonia (24.2 %), chest pain (18.5 %), bronchitis (17.5 %) and wheezing (17.2 %). For patients with an initial symptom (n=243) median time from symptom onset to imaging was 5.5 months (95% CI:4.8-6.3), and time from imaging to primary treatment initiation was 2.6 (2.3-2.9) months in all patients. Total duration from symptom to intervention was 8.5 months (7.6-9.3). Over 93 % of stage I patients underwent surgery and 4.9 % received definitive radiation. Over 83 % of stage II patients underwent surgery; of these, 54.8 % received adjuvant/neoadjuvant chemotherapy. Of stage III patients, 68.5 % received definitive chemoradiation (half received durvalumab), and the remaining underwent surgery with adjuvant/neoadjuvant treatment. Conclusion: A total of 80.5 % of patients were symptomatic and the median duration from symptom onset to treatment initiation was 8.5 month long. Improving patient and physician awareness to lung cancer symptoms, and the introduction of screening programs are essential for reducing those delays.

BACKGROUND:Ocular manifestations (OMs) in patients with inflammatory bowel disease (IBD) are uncommon, particularly in children. We aimed to explore the prevalence and characteristics of IBD-associated OM in a large cohort study. METHODS:A cross-sectional study was performed using the Maccabi Healthcare Services (MHS) database. The eligible population included all patients diagnosed with IBD as children (<18 years) between January 2005 and July 2023. RESULTS:Out of 2567 children with IBD (males 55%, Crohn's disease 64%), 78 (3%) were diagnosed with OM at any time during the disease course. In 54 patients (69%), the ocular disease occurred after IBD diagnosis with a median time of 2.6 (0.47-7) years between the 2 events, whereas in 24 patients (31%), ocular involvement preceded IBD diagnosis with a median time of 2.1 (0.6-5.7) years. The presence of ocular involvement was associated with increased usage of systemic corticosteroids (P < .001) and biologic agents (P = .04). There were 55 patients with ocular involvement during childhood who were ever diagnosed with IBD. In this population, ocular involvement was also associated with increased usage of systemic corticosteroids (P < .001). The prevalence of OM among patients with IBD did not change significantly over time (P = .75), with a prevalence of 2.3% at the end of the study period. CONCLUSIONS:The prevalence of ocular involvement in children with IBD is rare and steady; it is also associated with a greater usage of systemic corticosteroids and biologic agents, potentially representing a more severe disease course.

BACKGROUND:Eosinophilic gastrointestinal disorders (EGIDs) are primary immune-mediated disorders, with significant morbidity and long-term sequelae. Temporal trends in incidence and prevalence are on the rise, but studies outside Europe and North America are sparse. METHODS:Based on retrospective Electronic Medical Records (EMR) data, we studied a large population cohort during the years 2014-2021 of all patients diagnosed with EGIDs. Incidence rate and prevalence were calculated for each year during the study cohort stratified by disease location, age, and sex. RESULTS:Between 2014 and 2021, among a population of 2.4 million persons, the incidence rate of EGIDs tripled from 2.51 (95% CI: 1.78-3.23) to 7.88 (95% CI: 6.75-9.01) per 100 000 person-years. Most (85.1%) were patients with eosinophilic esophagitis (EoE). The increased temporal trend was almost identical among all subgroups, including patients with EoE, patients with non-EoE EGIDs, and patients with EGIDs with esophageal involvement. The prevalence of EGIDs increased from 14.53 (95% CI: 12.80-16.26) to 51.43 (95% CI: 48.60-54.26) per 100 000 persons. In 2021, at the end of the study, the prevalence of EoE was 39.54 (95% CI: 37.05-42.02) per 100 000 persons, and the prevalence of non-EoE EGID was 11.89 (95% CI: 10.53-13.26) per 100 000 persons. CONCLUSIONS:The incidence and prevalence of EGIDs in Israel have risen steeply during the last decade. The main contribution came from the increased incidence rate of patients with EoE. By the end of the surveillance period, the increased temporal trends did not reach a plateau.

Objective: Hemolytic disease of the fetus and newborn (HDFN) can cause severe prenatal and postnatal outcomes. The main objective of this study is to understand the clinical impact of HDFN on pregnant women and newborns. Study Design: A retrospective cohort study was performed on de-identified data extracted from a large nationwide health organization. The cohort included women and newborns diagnosed with HDFN between 1998-2021. Cohort characteristics and outcomes are described. Result: Over the 24-year study period, incidence rate of HDFN among pregnant women was stable while incidence rate among newborns declined. Severe HDFN was diagnosed in 28.8% of 73 HDFN affected pregnancies. One third of 450 HDFN newborns were diagnosed with anemia or jaundice; 5 cases of kernicterus were observed. Conclusion: Severe prenatal and postnatal outcomes following HDFN were observed. Further studies are needed to evaluate treatment regimens and assess the association between treatment management and short- and long-term outcomes.

OBJECTIVE:The diagnosis of Gaucher disease (GD) presents a major challenge due to the high variability and low specificity of its clinical characteristics, along with limited physician awareness of the disease's early symptoms. Early and accurate diagnosis is important to enable effective treatment decisions, prevent unnecessary testing, and facilitate genetic counseling. This study aimed to develop a machine learning (ML) model for GD screening and GD early diagnosis based on real-world clinical data using the Maccabi Healthcare Services electronic database, which contains 20 years of longitudinal data on approximately 2.6 million patients. STUDY DESIGN AND SETTING:We screened the Maccabi Healthcare Services database for patients with GD between January 1998 and May 2022. Eligible controls were matched by year of birth, sex, and socioeconomic status in a 1:13 ratio. The data were partitioned into 75% training and 25% test sets and trained to predict GD using features obtained from medical and laboratory records. Model performances were evaluated using the area under the receiver operating characteristic curve and the area under the precision-recall curve. RESULTS:We detected 264 confirmed patients with GD to which we matched 3,429 controls. The best model performance (which included known GD signs and symptoms, previously unknown clinical features, and administrative codes) on the test set had an area under the receiver operating characteristic curve = 0.95 ± 0.03 and area under the precision-recall curve = 0.80 ± 0.08, which yielded a median GD identification of 2.78 years earlier than the clinical diagnosis (25th-75th percentile: 1.29-4.53). CONCLUSION:Using an ML approach on real-world data led to excellent discrimination between GD patients and controls, with the ability to detect GD significantly earlier than the time of actual diagnosis. Hence, this approach might be useful as a screening tool for GD and lead to earlier diagnosis and treatment. Furthermore, advanced ML analytics may highlight previously unrecognized features associated with GD, including clinical diagnoses and health-seeking behaviors.

Early, simple predictors for long-term survival in Parkinson’s disease (PD) may help identify patients at elevated risk and are crucial for more personalized treatment. This large, retrospective study examined whether higher levodopa equivalent daily dose (LEDD) a year after diagnosis predicts long-term survival. Mortality risk was increased among 292 patients receiving ≥ 600 mg LEDD versus 2233 patients receiving < 600 mg LEDD (hazard ratio 1.5; 95

BackgroundTreatment for first-line (1L) metastatic non-small cell cancer (mNSCLC) changed with the introduction of immunotherapy. We describe treatment utilization and clinical outcomes in a real-world mNSCLC cohort in a 2.7-million-member state-mandated health provider.MethodsNewly diagnosed mNSCLC patients initiating systemic anti-cancer treatment (January 2017–December 2020) were identified from the National Cancer Registry. Real-world time on treatment (rwToT) was defined as the length of time between the first and last administration date of treatment. Real-world overall survival (rwOS) was estimated using Kaplan–Meier analysis. Outcomes were assessed at a minimum of 6 months’ follow-up (cutoff: 30 June 2021).ResultsAmong 843 patients, 85% had adenocarcinoma (NSQ) and 15% had squamous cell carcinoma (SQ) histology: of these, 43% and 26% were women, median age was 67 and 69 years, and 55% and 48% had 0–1 ECOG performance status, respectively (missing: 27% and 30%, respectively). Median follow-up for the entire cohort was 27.1 months (95% CI: 24.7–29.6). NSQ patients with no known EGFR/ALK/ROS1 aberrations received PD-1 inhibitor monotherapy (PDM) (N = 147) or combination (PDC) (N = 194) or platinum-based chemotherapy (PBC, N = 133). Median rwToT was 4.5 (95% CI: 3.5–7.6), 5.2 (95% CI: 4.6–7.6), and 2.3 (95% CI: 2.1–3.0) months, respectively; for the subgroup of patients with ECOG PS 0–1, rwToT was 9.4 (95% CI: 5.0–20.8), 7.1 (95% CI: 5.0–10.1), and 2.9 (95% CI: 2.2–4.1) months, respectively. Median rwOS from 1L was 12.5 (95% CI: 9.9–17.9), 14.8 (95% CI: 10.5–19.4), and 9.1 (95% CI: 7.1–11.5) months; for the subgroup of patients with ECOG PS 0–1, median rwOS was 25.1 [95% CI: 14.9–not reached (NR)], 17.6 (95% CI: 14.3–NR), and 11.3 (95% CI: 9.2–21.3) months, respectively. For ECOG PS 0–1 and PD-L1 ≥50% patients, median rwOS was 25.1 months (95% CI: 13.9–NR) and NR for PDM and PDC, respectively. For ECOG PS 0–1 and PD-L1 <50% patients, median rwOS was 14.3 (95% CI: 10.1–NR) and 11.2 (95% CI: 9.1–21.3) months for PDC and PBC, respectively.ConclusionOur real-world data support the benefit of single-agent PD-1 inhibitor monotherapy for patients with PD-L1 high expression or PD-1 inhibitor combination for all patients diagnosed with mNSCLC with no known EGFR/ALK/ROS1 aberrations, initiating 1L treatment.

Low levels of vitamin D are associated with a shorter time to first treatment (TTFT) and inferior overall survival in patients with Chronic Lymphocytic leukemia.But whether vitamin D supplement affects the clinical course of CLL patients, remains an open question.In the current study, we aimed to retrospectively explore the clinical benefit of Vitamin D supplement, or one of its analogues, on TTFT and treatment-free survival (TFS) in a large cohort of patients with asymptomatic CLL, who were under watch and wait approach.Among the 3,474 patients included in the study, 931 patients (26.8%) received either vitamin D supplement or its analogue, for a minimum of 6 months.We found that vitamin D supplement was statistically significant for longer TTFT in the young cohort (age<=65) and was associated with a longer TFS for all ages (p-value=0.004). Among non-vitamin D users, the median TFS was found to be 84 months, while among vitamin D supplement users the median TFS extended to 169 months.In conclusion, our long-term retrospective study demonstrates that the administration of vitamin D to patients with CLL in a watch and wait active surveillance is significantly associated with a longer treatment free survival (in any age) and a longer time to first treatment among young patients (age<=65). A prospective clinical trial is needed to validate results.

The integration of genetic information (GI) into the electronic health record (EHR) seems inevitable as the mainstreaming of genomics continues. Such newly provided accessibility to GI could be beneficial for improving health care, as well as for supporting clinical decision-making and health management. Notwithstanding these promising benefits, the automatic integration of GI into the EHR, allowing unrestricted access to one's GI through patient portals, carries various knowledge-related risks for patients. This article is focused on the potential case of inadvertently revealing misattributed parentage through such practice. The article aims to identify key clinical and ethical implications of such revelation for adult patients. Clinical implications include, for example, altering the physician-patient interaction and the need to enhance physician's genetic literacy to improve genetic-information-specific communication skills. Ethical implications yield arguments supporting disclosure of MP, such as autonomy, individuals' right to know medical information pertaining to them, and the right to know one's genetic origins. Arguments opposing disclosure of MP centre on the right not to know GI and concerns for post-disclosure family relationships. Following the clinical and ethical analyses of these respective implications, we consider how such integration of GI into the EHR ought to be carried out, ethically. We therefore suggest a solution, featuring an autonomy-based approach, built around EHR users' right not to know. Our solution of nuanced consent options (including a 'genetic ignorance option') is designed to enable patients' informed exposure to GI through the EHR, allowing them some control over their self- and familial narrative.

Background Treatment approach for metastatic non-small cell lung cancer (mNSCLC) has revolutionized in the recent decade with the introduction of immunotherapy and targeted medications in first-line (1L) therapy. We present real-world data on clinical outcomes and direct healthcare resource utilization (HCRU) and cost in a 2.7-million-member Israeli health provider.Patients and methods Newly diagnosed mNSCLC patients between January 2017 and December 2020 were categorized by 1L treatment: platinum-based chemotherapy, targeted therapy, or immunotherapy. HCRU and costs were calculated based on the Ministry of Health Prices and were assessed at a minimum of 6 months' follow-up (cutoff: 30 June 2021).Results A total of 886 patients were included in the study: 40.6% female, median age 68 years (IQR 61-74), 24.3% never smokers, 80.6% with adenocarcinoma, and 54% with a 0-1 performance status. The median follow-up was 27.12 months (95% CI, 24.7-29.6) and the median duration of first-line (1L) treatment was 2.3 months for platinum-based chemotherapy (n = 177), 12.3 months for targeted therapy (n = 255), and 4.8 months for immunotherapy (n = 463). The median overall survival was 9.09, 27.68, and 12.46 months, respectively. Total 1L costs were driven by radiotherapy for platinum-based chemotherapy and medication for targeted therapy or immunotherapy. Total costs for deceased patients over the entire follow-up were 121 155, 129 458, and 110 716, respectively.Conclusion The treatment of mNSCLC carries a high economic burden, primarily driven by first-line therapy, especially with targeted and immune therapies. Further studies are needed to evaluate the impact of innovative treatments on the disease management costs of mNSCLC. Treatment of metastatic non-small cell lung cancer has changed in the past decade with the introduction of immunotherapy and targeted medications in first-line therapy. This article presents real-world data on clinical outcomes and direct healthcare resource utilization and cost from a 2.7-million-member Israeli health provider.