Incidence of stroke, subsequent clinical outcomes and health care resource utilization in people with type 2 diabetes: a real-world database study in France: "INSIST" study.

BACKGROUND: People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France. METHODS: We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs. RESULTS: Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47-7.15] versus 1.38 [1.24-1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7-159.0] versus 126.4 [117.2-136.4]; stroke recurrence: 86.7 [66.4-113.4] versus 66.5 [59.2-74.6]; mortality 291.5 [259.1-327.9] versus 144.1 [134.3-154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66-2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378). CONCLUSIONS: The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.

Survival of patients with chronic acid sphingomyelinase deficiency (ASMD) in the United States: A retrospective chart review study.

Background: Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease type A, A/B, and B, is a rare lysosomal storage pathology with multisystemic clinical manifestations. The aims of this study were to estimate the survival probability in patients in the United States with chronic ASMD (ASMD types B and A/B), and to describe the disease characteristics of these patients. Methods: This observational retrospective study included medical chart records of patients with chronic ASMD with retrievable data abstracted by 69 participating physicians from 25 medical centers in the United States. Included patients had a date of ASMD diagnosis or first presentation to a physician for ASMD symptoms (whichever occurred first) between January 01, 1990, and February 28, 2021. Medical chart records were excluded if patients were diagnosed with ASMD type A. Eligible medical chart records were abstracted to collect demographic, medical and developmental history, and mortality data. Survival outcomes were analyzed using Kaplan-Meier survival analyses from birth until death. Results: The overall study population (N = 110) included 69 patients with ASMD type B, nine with type A/B, and 32 with ASMD "non-type A" (ASMD subtype was unknown, but patients were confirmed as not having ASMD type A). The majority of patients were male with a median age at diagnosis of 3.8 years. Thirty-eight patients died during the study observation period, at a median age of 6.8 years. The median (95% confidence interval) survival age from birth was 21.3 (10.2; 60.4) years. At diagnosis or first presentation, 42.7% patients had ≥1 ASMD-related complication; splenic (30.0%) and hepatobiliary (20.9%) being the most common, and 40.9% required ≥1 medical visit due to complications. Conclusion: Patients with chronic ASMD in the United States have poor survival and significant burden of illness.

BNT162b2 mRNA COVID-19 Vaccine Effectiveness in Patients with Coeliac Disease Autoimmunity: Real-World Data from Mass Vaccination Campaign.

BACKGROUND: Data on COVID-19 vaccine effectiveness among patients with coeliac disease are currently lacking because patients with immune conditions were excluded from clinical trials. We used our coeliac disease autoimmunity (CDA) cohort to explore the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in preventing SARS-CoV-2 infection among patients with CDA. METHODS: This retrospective cohort study included patients with positive autoantibodies against tissue transglutaminase (tTG-IgA). In the primary analysis, the cohort included CDA patients who received two vaccine doses against COVID-19 and matched patients in a 1:3 ratio. Patients were divided into subgroups based on their positive tTG-IgA level at diagnosis and their current serology status. RESULTS: The cohort included 5381 vaccinated patients with CDA and 14,939 matched vaccinated patients. The risk for breakthrough SARS-CoV-2 infection evaluated with Kaplan-Meier survival analysis via log-rank tests was similar between groups (p = 0.71). In a Cox regression survival analysis, the hazard ratio for breakthrough infection among patients with CDA compared to matched patients was 0.91 (95% confidence interval = 0.77-1.09). CONCLUSIONS: COVID-19 vaccination is effective in patients with coeliac disease autoimmunity. Vaccine effectiveness was comparable to the reference population.

Pre-morbid Laboratory Tests, Diseases, and Medications in Amyotrophic Lateral Sclerosis in Israel.

BACKGROUND: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations. OBJECTIVES: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations. To understand pathogenic mechanisms preceding the clinical presentation of ALS. METHODS: At the ALS clinic at Tel Aviv Sourasky Medical Center, 259 ALS patients insured by Maccabi Healthcare Services and seen between January 1998 and December 2017 were included. Comparisons of demographics, co-morbidities, medications taken, history of trauma, and laboratory tests prior to disease onset were performed between patients and 1295 matched controls. RESULTS: Prior to disease presentation, ALS patients had a higher frequency of hypertension and cardiovascular disease; presented more frequently with trauma and viral infections; more frequently used analgesics, non-steroidal anti-inflammatory drugs, narcotics, antibiotics, and antiviral medications; and had higher creatine kinase levels. CONCLUSIONS: ALS patients showed higher frequency of cardiovascular disease prior to diagnosis, as well as higher frequency of trauma, infections, and pain medication usage.

Glucose levels are not the same for everyone: a real-world big data study evaluating fasting serum glucose levels by sex and age among children.

OBJECTIVES: Understanding the normal range of laboratory values as pertained to different age groups and males or females is paramount in health care delivery. We aimed to assess the distribution of morning fasting serum glucose levels by age and sex in the general population of children using a large-scale population-based cohort. METHODS: A retrospective study with real-world de-identified data from a large, state mandated health fund in Israel among children aged 2-18 years old between 2006 and 2019. Age, sex, and BMI differences in mean glucose levels were evaluated. RESULTS: Study included 130,170 venous blood samples from 117,411 children, 53.3 % were female. After adjusting for age boys had higher fasting serum glucose levels than girls, with a mean of 89.21 ± 8.66 mg/dL vs. 87.59 ± 8.35 (p<0.001) [4.95 ± 0.48 mmol/L vs. 4.86 ± 0.46]. Compared to the 15 to 18 year-olds (88.49 ± 7.63 mg/dL) [4.92 ± 0.42 mmol/L], 2 to 5 year-olds had lower glucose levels (84.19 ± 10.65, [4.68 ± 0.59] (p<0.001)), 11 to 14 year-olds had higher glucose (90.40 ± 7.42 [5.02 ± 0.41], (p<0.001)) and 6 to 10 year-olds showed no difference (88.45 ± 8.25) [4.91 ± 0.46]. 33.0 % (n=42,991) had a BMI percentile record the same year as their glucose test result. There was a weak yet significant positive association between blood glucose levels and BMI. CONCLUSIONS: Our large cohort indicates that boys have slightly higher fasting serum glucose levels than girls, as do adolescents compared to younger children. This finding is important for the delivery of adequate health care, screening for illness and avoiding unnecessary investigations and tests.

Mild Hyponatremia as an Early Marker for Intrathoracic Cancer: A Cohort Study.

BACKGROUND: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer. OBJECTIVES: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia. METHODS: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130-134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications. RESULTS: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22-6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08-6.28. CONCLUSIONS: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.

Risk of major osteoporotic fractures among ultra-orthodox Jews.

The Ultra-Orthodox Jewish population has behaviors that can influence the risk for osteoporotic fractures. We investigated whether this population is more prone to osteoporotic fractures than non-Orthodox Jewish. We did not find a significant difference in osteoporotic fracture rates between the two populations despite major differences in exposure to potential risk factors. INTRODUCTION: The Ultra-Orthodox Jewish population is a conservative population with unique cultural behaviors such as modest clothing and specific dietary restrictions, which can influence bone density and risk for osteoporotic fractures. The aim of this study is to investigate whether the Ultra-Orthodox Jewish population is more prone to osteoporotic fractures than the non-Orthodox Jewish population. METHODS: This retrospective cohort study utilized computerized records from Maccabi Health Service. Study population included patients 65 years and older without a history of osteoporotic fracture, who reside in regions of Ultra-Orthodox and non-Orthodox Jews. The primary outcome was the adjusted risk to osteoporotic fracture during 9 years of follow-up. Cox regression included patient characteristics and risk factors for osteoporosis. RESULTS: A total of 115,134 patients were included in this study: 5397 patients residing in Ultra-Orthodox regions (51.0% female) and 109,737 patients residing in non-Orthodox regions (52.6% female). A total of 16,352 (14.2%) patients had an osteoporotic fracture during the study period. There was no significant difference in fracture rate between Ultra-Orthodox and non-Orthodox (14.3% vs. 14.2%, p = 0.827). Among Ultra-Orthodox and non-Orthodox females and males, there were no significant differences in fracture rates (19.1% vs. 19.1% p = 0.982 and 9.3% vs. 8.8% p = 0.311, respectively). The adjusted hazard risk for the Ultra-Orthodox Jews was 1.026, 95% CI: 0.95-1.11, p = 0.512. CONCLUSION: We did not find a significant difference in the rate of osteoporotic fractures between Ultra-Orthodox and non-Orthodox populations despite major differences in exposure to potential risk factors. Results suggest that the perception of risk factors relevant for the religious communities should be re-evaluated.

Treatment patterns, persistence with therapy, and outcomes of ustekinumab in Crohn's disease: Real-world data analysis.

BACKGROUND AND AIM: In 2017, ustekinumab (UST) was included in Israel's National Basket of Health Services for treatment of biologic-experienced Crohn's disease (CD) patients with moderately to severely active disease. This study aims to provide real-world evidence on persistence and clinical outcomes among early users of UST. METHODS: This retrospective cohort study was conducted using data from Maccabi Healthcare Services (MHS; 2.5-million-member state-mandated health provider, Israel). Adult patients with a CD diagnosis code who had ≥1 dispensed UST prescription in 2017-2018 and at least 12 months of prior continuous health plan enrollment were included. Outcomes, including treatment discontinuation, dose-escalation (based on shortened intervals between purchases), CD-related surgery, CD-related hospitalization, corticosteroid (CS) discontinuation, and use of opioids were evaluated from the date of first dispensed UST through the end of 2019 using Kaplan-Meier analysis. RESULTS: A total of 162 eligible patients (81 [49.4%] female; median age 34.4 years [IQR 23.2-46.3]; median years since CD diagnosis 8.6 [IQR 4·8-16.0]) were enrolled in the study. Discontinuation rate after 365 and 540 days of follow-up was 27.8% and 35.6%. Dose escalation was estimated at 15.4% and 28.6%, respectively. The first-year cumulative rate of CD-related surgery and CD-related hospitalization were estimated at 4.7% and 9.8%, respectively. CONCLUSION: In this real-world CD cohort of UST users, results suggest persistence is relatively high as compared to other biologics for CD. Comparative effectiveness of different biologic treatments for CD in this population should be further explored.

Evaluating red blood cell distribution width from community blood tests as a predictor of hospitalization and mortality in adults with SARS-CoV-2: a cohort study.

BACKGROUND: Red blood cell distribution width (RDW) has been assessed during COVID-19 patient hospitalization, however, further research should be done to evaluate RDW from routine community blood tests, before infection, as a risk factor for COVID-19 related hospitalization and mortality. PATIENTS AND METHODS: RDW was measured as a predictor along with age, sex, chronic illnesses, and BMI in logistic regressions to predict hospitalization and mortality. Hospitalization and mortality odds ratios (ORs) were estimated with 95% confidence intervals (CI). RDW was evaluated separately as continuous and discrete (High RDW ≥ 14.5) variables. RESULTS: Four thousand one hundred and sixty-eight patients were included in this study, where 824 patients (19.8%) had a high RDW value ≥14.5% (High RDW: 64.7% were female, mean age 58 years [±22] vs. Normal RDW: 60.2% female, mean age 46 years [±19]). Eight hundred and twenty-nine patients had a hospitalization, where the median time between positive PCR and hospital entry was 5 [IQR 1-18] days. Models were analyzed with RDW (continuous) and adjusted for age, sex, comorbidities, and BMI suggested an OR of 1.242 [95% CI = 1.187-2.688] for hospitalization and an OR of 2.911 [95% CI = 1.928-4.395] for mortality (p < .001). RDW (discrete) with the same adjustments presented an OR of 2.232 [95% CI = 1.853-1.300] for hospitalization and an OR of 1.263 [95% CI = 1.166-1.368] for mortality (p < .001). CONCLUSIONS: High RDW values obtained from community blood tests are associated with greater odds of hospitalization and mortality for patients with COVID-19.KEY MESSAGESRDW measures before SARS-CoV-2 infection is a predictive factor for hospitalization and mortality.RDW threshold of 14.5% provides high sensitivity and specificity for COVID-19 related mortality, comparatively to other blood tests.Patient records should be accessed by clinicians for prior RDW results, if available, followed by further monitoring.

Detection of occult atrial fibrillation with 24-hour ECG after cryptogenic acute stroke or transient ischaemic attack: A retrospective cross-sectional study in a primary care database in Israel.

BACKGROUND: Ischaemic stroke or cerebrovascular accident (CVA) due to occult atrial fibrillation (AF) may cause severe morbidity and mortality. Diagnosing occult AF can be challenging and there is no consensus regarding the optimal duration of screening. A 24-hour Holter electrocardiogram (ECG) is frequently employed to detect occult AF following ischaemic CVA. OBJECTIVES: Demonstration of occult AF detection rate using a 24-hour Holter ECG in a primary care setting with descriptive analyses of independent variables to compare AF detected and non-detected patients. METHODS: This retrospective cross-sectional study utilised primary care data and included patients 50 years and older with a new CVA or transient ischaemic attack (TIA) diagnosis followed by a 24-hour Holter examination within 6 months, between 01 January 2013 and 01 June 2019. The analyses included descriptive statistics comparing demographics and clinical characteristics in patients who had AF or Atrial Flutter (AFL) detection to those who did not. RESULTS: Out of 5015 eligible patients, 66 (1.3%) were diagnosed with AF/AFL, with a number needed to screen of 88.5. Compared with those without AF/AFL detection, those diagnosed were older (75.42 ± 7.89 vs. 69.89 ± 9.88, p = 0.050), had a higher prevalence of hypertension (80.3% vs. 66.8%, p = 0.021) and chronic kidney disease (CKD) (71.2% vs. 44.2%, p < 0.001). CONCLUSION: 24-hour Holter has a low AF/AFL detection rate. Older persons and those with hypertension or CKD are more likely to be detected with AF/AFL using this method.

The effectiveness of insulin glargine 300 U/mL among type 2 diabetes patients: Analysis of a real-world data in Israel.

AIMS: Randomized controlled trials have shown that insulin glargine 300 U/mL (Gla-300) has a more stable and prolonged glucose lowering effect among patients with type 2 diabetes (T2DM) compared to insulin glargine 100 U/mL (Gla-100), resulting in a reduced risk of hypoglycaemia while maintaining a similar efficacy of lowering HbA1c. We aimed to investigate if the effectiveness of Gla-300 is reproducible in real-world settings. MATERIAL AND METHODS: In this retrospective cohort study, data from a large state-mandated health organization were used to identify adult T2DM patients who were previously on insulin and initiated Gla-300 therapy between 6/ 2016 and 12/2017. Changes in HbA1c levels, body weight and insulin dose were calculated from baseline period and over a follow-up period of 180 days. Documented hypoglycaemia events were also explored. RESULTS: A total of 1797 patients were included in this study with a mean age of 64.2 (SD = ±11.0y), baseline HbA1c was 8.7 ± 1.6% and 42.5% were females. Among all patients with HbA1c measurement during follow-up (n = 1508), HbA1c was significantly reduced by -0.6% (95% CI -0.6,-0.5; P < .001) from baseline, with a significant reduction in body weight (-0.4 kg; P = <.001).Additionally, a significant (P = .04) reduction of 40.5% in patients with hypoglycaemia events was recorded during follow-up period, from 2.1% (n = 37) at the baseline period to 1.2% (n = 22). CONCLUSIONS: This real-world study supports evidence from RCTs regarding the effectiveness of Gla-300 among T2DM patients by improving glycaemic control.