Disparities in Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Prescription and Dispensing in the Israeli Population-A Retrospective Cohort Study.

OBJECTIVE: To describe disparities in prescribing and dispensing sodium-glucose cotransporter 2 inhibitors (SGLT2i) in Israel. RESEARCH DESIGN AND METHODS: This was a population-based retrospective cohort study of adults with type 2 diabetes eligible for SGLT2i treatment from 2017 to 2023. The primary outcome was the time between initial eligibility and the first prescription of SGLT2i. RESULTS: Among 32,742 eligible patients, only 53% were prescribed SGLT2i. Multivariable analyses, adjusting for death as a competing risk, revealed delays in prescription were associated with older age, Arab or Bedouin ethnicity, neoplasms, acute kidney failure, falls, previous hospitalization, urinary tract infections, and dementia. Factors associated with shorter time intervals to prescription were sex (men), medium/high socioeconomic status, and residing in an intermediate or central area of Israel. CONCLUSIONS: Disparities in drug prescription exist, even in a country with universal health coverage. Addressing these disparities requires improvements in health care systems, education, and alert systems to overcome barriers to evidence-based interventions.

Mortality and Hospitalization Risks in Patients With Cancer and the SARS-CoV-2 Omicron Variant.

This cohort study compares the mortality and hospitalization risks among patients with vs without solid cancer and diagnosed with COVID-19 during the period when the Omicron variant was dominant.

Cabergoline treatment for surgery-naïve non-functioning pituitary macroadenomas.

PURPOSE: The treatment strategy of non-functioning pituitary adenomas (NFPAs) includes surgery, radiotherapy, medical therapy, or observation without intervention. Cabergoline, a dopaminergic agonist, was suggested for the treatment of NFPA remnants after trans-sphenoidal surgery. This study investigates the efficacy of cabergoline in surgery-naive patients with NFPA. METHODS: Retrospective cohort study including surgery-naive patients with NFPA ≥ 10 mm, treated with cabergoline at a dose of ≥ 1 mg/week for at least 24 months. Patients with chiasmal damage were excluded. Data collected included symptoms, in particular visual disturbances, hormonal levels, tumor characteristics and size evaluated by MRI. Tumor growth was defined as an increase in maximal diameter of ≥ 2 mm, and shrinkage as reduction of ≥ 2 mm. RESULTS: Our cohort included 25 patients treated with cabergoline as primary therapy. Mean age was 63.3 ± 17.3 years, 56% (14/25) were males. Mean tumor size at diagnosis was 18.6 ± 6.3 mm (median 17 mm, range 10-36), and the average follow-up period with cabergoline was 4.6 ± 3.4 years. Out of the 25 tumors, five tumors (20%) decreased in size (mean decrease of 5.0 ± 3.0 mm), 12 tumors (48%) remained stable, and eight (32%) increased in size (mean growth of 5.0 ± 3.3 mm) with cabergoline treatment. During the first two years of cabergoline treatment, the median tumor size exhibited a reduction of 0.5 mm. Patients with an increase in tumor size had larger adenomas at diagnosis and a longer follow-up. Two patients (8%) underwent surgery due to tumor enlargement. CONCLUSION: Primary treatment with cabergoline is a reasonable approach for selected patients with NFPAs without visual threat.

Assessing the impact of coronavirus disease 2019 on mortality: a population-based, matched case-control study.

OBJECTIVES: Estimating the isolated effect of coronavirus disease 2019 (COVID-19) on the risk of mortality is challenging. We aimed to determine whether COVID-19 was associated with high rates of mortality independently of age, sex and underlying disorders. METHODS: A population-based, matched, case-control study of adults insured by Clalit Health Services was performed. Cases were defined as patients who died of all causes between July and December 2020. Each case was matched in a ratio of 1:1 with a living control based on age, sex and co-morbidities. An unconditional logistic regression analysis was performed to identify independent risk factors for mortality. RESULTS: A total of 2874 patients who died were successfully matched with 2874 living controls. The prevalence of COVID-19 was higher among the patients who died than among the controls (13.5% [387/2874] vs. 4% [115/2874], respectively; OR, 3.73; 95% CI, 3.01-4.63; p < 0.001). A significantly increased odds of mortality was also observed in patients with COVID-19 without underlying diseases (OR, 3.67; 95% CI, 2.58-5.23) and in patients with COVID-19 and underlying diseases (OR, 3.77; 95% CI, 2.87-4.94). A multi-variate logistic analysis showed that COVID-19 (OR, 2.01; 95% CI, 1.07-3.77), low socio-economic status (OR, 1.36; 95% CI, 1.02-1.82), dementia (OR, 2.50; 95% CI, 2.10-3.01), smoking (OR, 1.35; 95% CI, 1.13-1.63) and an interaction variable of age >80 years and COVID-19 (OR, 2.27; 95% CI, 1.14-4.54) were independent risk factors for mortality, whereas influenza vaccination and high body mass index were associated with lower rates of mortality. CONCLUSION: Testing positive for COVID-19 increased the risk of death three folds, regardless of underlying disorders. These results emphasize the effect of COVID-19 on mortality during the early period of the COVID-19 outbreak, when no vaccines or effective therapeutics were available.

Underrepresentation of women in randomized controlled trials: a systematic review and meta-analysis.

BACKGROUND: Although regulatory changes towards correcting the underrepresentation of women in randomized controlled trials (RCTs) occurred (National Institutes of Health 1994), concerns exist about whether an improvement is taking place. In this systematic review and meta-analysis, we aimed to assess the inclusion rates of women in recent RCTs and to explore the potential barriers for the enrollment of women. METHODS: RCTs published in 2017 examining any type of intervention in adults were searched in PubMed and Cochrane Library. The following predefined medical fields were included: cardiovascular diseases, neoplasms, endocrine system diseases, respiratory tract diseases, bacterial and fungal infections, viral diseases, digestive system diseases, and immune system diseases. Studies were screened independently by two reviewers, and an equal number of studies was randomly selected per calendric month. The primary outcome was the enrollment rate of women, calculated as the number of randomized women patients divided by the total number of randomized patients. Rates were weighted by their inverse variance; statistical significance was tested using general linear models (GLM). RESULTS: Out of 398 RCTs assessed for eligibility, 300 RCTs were included. The enrollment rate of women in all the examined fields was lower than 50%, except for immune system diseases [median enrollment rate of 68% (IQR 46 to 81)]. The overall median enrollment rate of women was 41% (IQR 27 to 54). The median enrollment rate of women decreased with older age of the trials' participants [mean age of trials' participants ≤ 45 years: 47% (IQR 30-64), 46-55 years: 46% (IQR 33-58), 56-62 years: 38% (IQR 27-50), ≥ 63 years: 33% (IQR 20-46), p < 0.001]. Methodological quality characteristics showed no significant association with the enrollment rates of women. Out of the 300 included RCTs, eleven did not report on the number of included women. There was no significant difference between these studies and the studies included in the analysis. CONCLUSIONS: Women are being inadequately represented, in the selected medical fields analyzed in our study, in recent RCTs. Older age is a potential barrier for the enrollment of women in clinical trials. Low inclusion rates of elderly women might create a lack of crucial knowledge in the adverse effects and the benefit/risk profile of any given treatment. Factors that might hinder the participation of women should be sought and addressed in the design of the study.

Risk factors for functional decline among survivors of Gram-negative bloodstream infection: A prospective cohort study.

OBJECTIVE: To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia. PATIENTS AND METHODS: A prospective cohort study based on a randomized controlled trial conducted between January 1, 2013 and August 31, 2017 in Israel and Italy. Hospitalized patients with Gram-negative bacteremia who survived until day 90 and were not bedridden at baseline were included. The primary end point was functional decline at 90 days. RESULTS: Five hundred and nine patients were included. The median age of the cohort was 71 years (interquartile range [IQR], 60-80 years), 46.4% (236/509) were male and 352 of 509 (69%) patients were independent at baseline. Functional decline at 90 days occurred in 24.4% of patients (124/509). In multivariable analysis; older age (odds ratio [OR], 1.03; for an one-year increment, 95% confidence interval [CI] 1.01-1.05), functional dependence in instrumental activities of daily living at baseline (OR, 4.64; 95% CI 2.5-8.6), low Norton score (OR, 0.87; 95% CI 0.79-0.96) and underlying comorbidities: cancer (OR, 2.01; 95% CI 1.14-3.55) and chronic pulmonary disease (OR, 2.23 95% CI 1.12-4.42) and longer length of hospital stay (OR 1.09; for one-day increment, 95% CI 1.04-1.15) were associated with functional decline. Appropriate empirical antibiotic treatment was associated with lower rates of functional decline within 90 days (OR, 0.4; 95% CI 0.21-0.78). CONCLUSIONS: Patients surviving bloodstream infections have poor long term trajectories after clinical recovery and hospital discharge. This has vast implications for patients, their family members and health policy makers.

Risk factors for hospital readmission following complicated urinary tract infection.

Hospital readmissions following severe infections are a major economic burden on the health care system and have a negative influence on patients' quality of life. Understanding the risk factors for readmission, particularly the extent to which they could be prevented, is of a great importance. In this study we evaluated potentially preventable risk factors for 60-day readmission in patients surviving hospitalization for complicated urinary tract infection (cUTI). This was a multinational, multicentre retrospective cohort study conducted in Europe and the Middle East. Our cohort included survivors of hospitalization due to cUTI during the years 2013-2014. The primary outcome was 60-day readmission following index hospitalization. Patient characteristics that could have influenced readmission: demographics, infection presentation and management, microbiological and clinical data; were collected via computerized medical records from infection onset up to 60 days after hospital discharge. Overall, 742 patients were included. The cohort median age was 68 years (interquartile range, (IQR) 55-80) and 43.3% (321/742) of patients were males. The all-cause 60-day readmission rate was 20.1% (149/742) and more than half were readmitted for infection [57.1%, (80/140)]. Recurrent cUTI was the most frequent cause for readmission [46.4% (65/140)]. Statistically significant risk factors associated with 60-day readmission in multivariable analysis were: older age (odds ratio (OR) 1.02 for an one-year increment, confidence interval (CI) 1.005-1.03), diabetes mellitus (OR 1.63, 95% CI 1.04-2.55), cancer (OR 1.7, 95% CI 1.05-2.77), previous urinary tract infection (UTI) in the last year (OR 1.8, 95% CI: 1.14-2.83), insertion of an indwelling bladder catheter (OR 1.62, 95% CI 1.07-2.45) and insertion of percutaneous nephrostomy (OR 3.68, 95% CI 1.67-8.13). In conclusion, patients surviving hospitalization for cUTI are frequently re-hospitalized, mostly for recurrent urinary infections associated with a medical condition that necessitated urinary interventions. Interventions to avoid re-admissions should target these patients.

Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial.

Importance: The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI). Objective: To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis. Design, Setting, and Participants: Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel. Interventions: Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection. Main Outcomes and Measures: The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events. Results: Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively). Conclusions and Relevance: Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion. Trial Registration: ClinicalTrials.gov Identifier: NCT01966653.