Israel Medical Association Journal

Background: Bloodstream infections (BSI) are associated with high morbidity and mortality. Inappropriate empirical antimicrobial therapy leads to poor outcomes.

Objectives: To evaluate the impact of clinical pharmacist intervention on the appropriateness of antibiotic treatment in patients hospitalized with bacteremia.

Methods: A retrospective study was conducted at the Soroka Medical Center in Israel. The intervention was implemented starting in July 2018. We compared 170 patients who received pharmacist intervention (August 2018 to June 2019) to 173 control patients (January 2017 to July 2018). The primary outcome was a composite of appropriate antibiotic choice and dosage.

Results: Pharmacist intervention significantly improved appropriate antibiotic dosing (97.6% vs. 91.3%, P = 0.011) and selection based on pathogen sensitivity (100% vs. 95.4%, P = 0.007). The most significant effect was observed in patients with intermediate renal function (CrCl 30–60 ml/min). Multivariate analysis confirmed pharmacist intervention as a strong predictor of appropriate treatment (odds ratio 5.00, 95% confidence interval 1.64–15.25, P = 0.005). The intervention group had longer hospital stays (median 15 vs. 9 days, P < 0.001) and lower 7-day relapse rates (2.4% vs. 8.7%, P = 0.010).

Conclusions: Clinical pharmacist interventions significantly improved the appropriateness of antibiotic treatment in patients with bacteremia, particularly in those with intermediate renal function. Despite longer hospital stays, the intervention group had lower early relapse rates than the control group. These findings support the integration of clinical pharmacists into antimicrobial stewardship programs.

Background: Healthcare utilization in patients with psoriasis has been described from the perspective of psoriasis healthcare centers. Psoriasis healthcare utilization at the population level, including appointments with family physicians, impacts the overall financial expenditure.

Objectives: To describe the utilization of healthcare services in patients with psoriasis compared to the general non-psoriasis population.

Methods: We conducted a cross-sectional, population-based analysis of data from Clalit Health Services, the largest public health service provider in Israel, comparing the annual healthcare utilization and medication consumption of all Clalit members with psoriasis in 2023 with an age- and sex-matched group at a primary care clinic. We compared up to five non-psoriasis items.

Results: The study included 835,422 people (140,927 individuals with psoriasis and 694,671 without). Patients with psoriasis had more annual physician appointments than controls, and the meetings were longer. Patients with psoriasis took more sick leave and required more hospital admission compared to the control group. Tumor necrosis factor (TNF) inhibitors were prescribed much more often to patients with psoriasis than to the control group (3147 patients vs. 1857 in the matched control). More IL-17 blockers and IL-23 blockers were also prescribed more in the psoriasis group, although at a much lower level than the TNF inhibitors.

Conclusions: Patients with psoriasis used more healthcare services than the control group. Healthcare providers should allocate more resources to psoriasis care, both for primary care and at specialized psoriasis centers.

Background: Vitamin B6 is an essential cofactor in amino acid metabolism. Its deficiency is linked to neuropathy, anemia, and cardiovascular risk. Deficiency is common among hemodialysis patients due to dialytic losses and restrictive diets; however, data related to high-flux (HF) dialysis membranes and Mediterranean dietary patterns are scarce.

Objectives: To assess the prevalence and determinants of deficiency in unsupplemented Israeli hemodialysis patients.

Methods: This retrospective chart review, utilizing a cross-sectional design, was conducted in August 2024. We included 27 chronic hemodialysis patients not receiving vitamin B6 supplementation, representing the available unsupplemented cohort from a unit of approximately 150 patients. Vitamin B6 status was assessed by measuring plasma pyridoxal-5'-phosphate (PLP); deficiency < 20 ng/ml. Clinical and nutritional parameters were evaluated to identify deficiency.

Results: Vitamin B6 deficiency was noted in 63% of patients (median PLP 18 ng/ml, interquartile range 13–23). The cohort was 67% male, median age 74 years. All patients were treated with HF dialyzers. No significant correlations were found between PLP levels and nutritional indices or laboratory markers. A non-significant trend was observed between older age and lower PLP levels (r = -0.35, P = 0.098).

Conclusions: Vitamin B6 deficiency was common among Israeli hemodialysis patients treated with HF dialyzers, despite a presumed Mediterranean diet. It was not associated with nutritional status, suggesting dialysis-related losses, potentially augmented by high-flux membranes, may outweigh intake. Given the high prevalence of deficiency and low cost, routine low-dose vitamin B6 supplementation may be warranted, particularly in older patients.

Background: Elbow range of motion (ROM) is commonly assessed during initial evaluation and follow-up. While goniometry is considered the current gold standard, previous studies have raised concerns regarding its user dependence and measurement consistency.

Objective: To evaluate whether smartphone application-based elbow ROM measurements are comparable to visual estimation and goniometry in patients following elbow trauma.

Methods: We conducted a prospective cohort study of 18 patients with elbow injuries. Demographic and medical data were collected. Maximal flexion-extension active ROM was measured by goniometry, smartphone application, and visual estimation by orthopedic surgeons. Measurements were compared to determine agreement and accuracy among different modalities.

Results: Eighteen patients with elbow injuries were included. Inter-rater reliability was good to excellent across all rater groups (intraclass correlation coefficient 0.78–0.93). Using paired t-tests with Bonferroni correction, only one attending surgeon showed a significant underestimation of extension compared to goniometry (16.9° vs. 22.5°, P < 0.05). No significant differences were found for residents, other attendings, or smartphone measurements in either extension or flexion (P > 0.05). Bland-Altman analysis revealed modest mean bias within ± 6° for all methods, although limits of agreement were wide (up to ± 20–30°). Smartphone-based measurements demonstrated significantly higher and less variable Pearson correlation coefficients with goniometry compared to surgeon visual estimations (0.91–0.95 vs. 0.81–0.93, P < 0.05).

Conclusions: Smartphone-based elbow ROM measurements were statistically comparable to goniometry and demonstrated superior correlation and accuracy relative to clinical visual assessments. These findings support the integration of smartphone tools in the clinical setting.

Background: Prophylactic intravenous antibiotics are not routinely administered prior to direct peroral cholangiopancreatoscopy. The frequency of post-procedure bacteremia has not been well studied.

Objectives: To evaluate the risk of bacteremia following endoscopic retrograde cholangiopancreatography (ERCP) with cholangiopancreatoscopy. To assess the prevalence of other infectious complications and the effect of real-life practices regarding prophylactic antibiotic administration.

Methods: We conducted a retrospective analysis on consecutive patients (2016–2022) who underwent cholangiopancreatoscopy using the single-operator SpyGlass System (Boston Scientific Corporation, USA). Prophylactic antibiotic treatment was administered based on clinical discretion. Demographic and clinical data, including procedure indication, procedure reports, blood culture results, pre- and post-procedure antibiotic treatment, hospital length, mortality, and infectious and non-infectious complications, were collected.

Results: Our single-center cohort included 75 patients who underwent ERCP with direct cholangiopancreatoscopy. We involved 63 patients in the analysis. In 17/63 patients (27%), post-procedural blood cultures were drawn based on clinical suspicion of infection. Positive cultures were found in 4/17 (23.5%) of all cultures and 4/63 (6.3%) of the entire cohort; 2/63 (3.2%) had clinically significant bacteremia. Antibiotic prophylaxis was administered to 35 patients (55.6%), with no evidence of significant reduction in bacteremia, cholangitis, hospitalization length, or mortality rates when compared to patients who did not receive prophylactic antibiotics (P > 0.05). Post-procedural cholangitis was observed in 5/63 patients (7.9%). There were no cases of acute cholecystitis or liver abscess.

Conclusions: The prevalence of bacteremia and cholangitis following ERCP with direct cholangiopancreatoscopy was 6.3% and 7.9%, respectively. Prophylactic antibiotics did not reduce post-procedural infectious adverse events.

Background: Gangrenous appendicitis falls to the midpoint of the continuum between uncomplicated and complicated appendicitis. We present an eight-year single-center retrospective review of uncomplicated, complicated and gangrenous appendicitis.

Objectives: To analyze the presentation of gangrenous appendicitis in our population.

Methods: We reviewed the presentation, as well as the laboratory, surgical, and pathological findings for complicated, uncomplicated, and gangrenous appendicitis. Logistic regression analysis was conducted to identify predictors of gangrenous and of complicated appendicitis.

Results: During the study period, 865 children had uncomplicated appendicitis and 134 had complicated appendicitis. Younger age, duration of illness as well as vomiting, diarrhea, and fever were more common in complicated than uncomplicated appendicitis. White blood cell count, neutrophil count and C-reactive protein were higher in complicated appendicitis. Logistic regression showed that vomiting and presence of fever occurred more frequently in children with non-perforated gangrenous appendicitis than with other uncomplicated appendicitis. Laboratory results for non-perforated gangrenous appendicitis were comparable to those of complicated appendicitis, as was usage of radiography and computed tomography.

Conclusion: Gangrenous appendicitis shares similar historical elements with complicated appendicitis and has a similar laboratory. These children, like those with complicated appendicitis, may not be optimal candidates for non-operative management.

Background: The coronavirus disease 2019 (COVID-19) pandemic has disrupted healthcare systems globally, affecting chronic disease management like osteoporosis and the prevention of fragility hip fractures. We hypothesized that it led to suboptimal prevention of secondary femoral neck fractures, reduced treatment frequency, and delayed treatment initiation.

Objectives: To evaluate the treatment initiation rate for secondary prevention of femoral neck fractures, comparing pre-COVID-19, COVID-19, and post-COVID periods, considering patient demographics.

Methods: This retrospective diagnostic cohort study used automated electronic medical records database from Clalit Health Services. Data regarding patients with hip fractures from January 2017 through September 2021 were extracted from the database. Treatment for osteoporosis included one of the following treatments: alendronate, risedronate, zoledronate, abaloparatide, denosumab, romosozumab, and teriparatide. The primary outcome variable in the study is the time taken to initiate appropriate therapy for the secondary prevention of femoral neck fractures.

Results: Treatment frequency decreased over time, with rates declining from 40.4% in 2019 to 33.5% in 2021 (P-value < 0.05). However, the percentage of prompt care management (within 3 months) increased between 2020 and 2021 (47.3%–62.5%) and between 2019 and 2021 (48.7%–62.5%), P < 0.05.

Conclusions: The COVID-19 pandemic reduced the rate of appropriate treatment initiation following hip fractures. However, adherence to timely treatment within 3 months of the fracture has improved. The findings highlight the effectiveness of the health system response in managing crises and ensuring the timely delivery of critical treatment.

Background: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular events, especially following acute exacerbation (AECOPD). However, there is insufficient data to identify high-risk subjects.

Objectives: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, and the risk of cardiovascular events following exacerbation.

Methods: This retrospective cohort included patients with COPD who were hospitalized with AECOPD between January 2016 and December 2022. We took the reference NLR before index admission and evaluated the incidence of major adverse cardiovascular events (MACE) or cardiovascular death over the following year. Multivariate analysis and competing risk regression were used to assess hazard ratio (HR) and NLR threshold for increased cardiovascular risk.

Results: In total, 15,224 patients with AECOPD completed one 1-year follow-up session. The majority were male (54%) with a mean age of 69 ± 3 years. The risk for MACE of patients in the highest NLR quartile was higher over the first year following AECOPD; however, the magnitude of effect decreased over time. After adjustment to other confounders that may increase NLR, a value > 3.5 was found with the strongest predictive power

Conclusion: Community NLR can be used to identify patients at increased risk of cardiovascular events following AECOPD, together with other risk factors. Every effort should be made to reduce exacerbation risk, and target intervention to those patients at highest risk.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to a wide spectrum of clinical severity. The gold standard diagnosis of infection is reverse transcription polymerase chain reaction of nasopharyngeal swabs, which also provides a semiquantitative assessment of viral loads by measuring cycle threshold (CT) values.

Objective: To assess whether CT values at admission can predict mortality and oxygen needs among individuals hospitalized for coronavirus disease 2019 (COVID-19).

Methods: The retrospective study included adults hospitalized for COVID-19 between 1 August 2020 and 30 April 2021 at Barzilai University Medical Center. Patients were categorized according to initial CT values as high (≥ 25) or low (< 25) values. The primary outcome was the association between CT values during admission and overall mortality.

Results: The study group included 636 patients, with a mean age of 67.2 years, 54.4% males. Overall mortality of patients with CT values < 25 was significantly higher (odds ratio for mortality 1.78 vs. patients with CT ≥ 25, P = 0.002). Significantly more patients in the low CT group required oxygen support than in the high CT group, 50% vs. 31.9% (P < 0.001). An inverse association between CT values and mortality rates remained significant in multivariate regression analysis, such that a 1-unit decrease in CT was associated with a 6% increased mortality.

Conclusions: Lower CT values at admission were associated with increased mortality among patients hospitalized for COVID-19. CT values can be used to predict outcomes among such patients.

Background: The association between new-onset atopic dermatitis (AD) and the coronavirus disease 2019 (COVID-19) pandemic was scarcely documented in the literature.

Objectives: To evaluate the incidence of AD in a large nation-wide cohort over 6 years, focusing on changes in incidence following the onset of the COVID-19 pandemic.

Methods: This retrospective cohort study included all members of the largest HMO in Israel (n=4.8 million) from 2017 to 2022. Patients with newly diagnosed AD were identified using the ICD-10 code for AD (L20). Incidence rates were calculated as the number of new diagnoses per 1000 person-years. The pre-COVID period was 1/2017 to 1/2020, and post-COVID 2/2020 to 12/2022. Age-adjusted incidence rates were calculated based on the World Health Organization's standard population.

Results: The overall crude incidence of AD across the study period was 3.38/1000 person-years (PYs). From 2017 to 2022, there was a 36.97% increase in the crude incidence and a 40.44% increase in the age-adjusted incidence, with a mean annual incidence change of +6.5% and +7.1%, respectively. Both crude and adjusted annual incidence increases were significant (P < 0.001, R² = 0.98; P < 0.001, R² = 0.99, respectively). The incidence of AD at the follow-up before the COVID-19 pandemic was 3.07/1000 PYs, and after was 3.71/1000 PYs.

Conclusions: We observed a significant and nearly consistent annual increase in AD incidence from 2017 to 2022, across various sex and age groups. Further research is needed to explore the impact of the COVID-19 pandemic on rising trends in AD incidence.

Background: The management of chronic hepatitis C virus (HCV) infection in patients with concurrent severe mental illness and substance use disorder poses significant challenges to treatment initiation, adherence, and completion. Multiple barriers impede successful treatment outcomes in this population, including cognitive impairments associated with mental illness, ongoing psychoactive substance use, and inadequate social and environmental support systems.

Objectives: To implement a treatment program for HCV-infected patients during their psychiatric hospitalization. To establish a multidisciplinary task force comprising a hepatologist, psychiatric ward team (psychiatrists, nurses, social workers), and a project administrator.

Methods: We conducted a retrospective cohort study of patients hospitalized with dual diagnosis (DD) of severe mental illness and substance use disorder who tested positive for HCV antibodies. Patients underwent clinical evaluations and received treatment with direct antiviral agents during hospitalization under the supervision of the joint team. Demographic and clinical characteristics were analyzed.

Results: Between January 2018 and June 2023, 694 DD patients were hospitalized, of whom 119 tested positive for HCV antibodies (prevalence 17.1%). Twenty-seven patients (23%) completed treatment; 17 (63%) achieved confirmed sustained virologic response. Treatment discontinuation occurred primarily post-discharge from the mental health facility. Significant efforts were made to engage community caregivers to maintain continuity of care.

Conclusions: Our findings demonstrate that treating HCV in patients with concurrent severe mental illness and substance use disorder requires collaborative efforts across medical disciplines. This integrated approach during psychiatric hospitalization provides a unique opportunity for initiating and monitoring HCV treatment in this complex patient population.

Background: The Iron Swords war created stressful circumstances that could negatively impact glycemic control in individuals with type 1 diabetes (T1D).

Objectives: To evaluate changes in continuous glucose monitoring (CGM) metrics in pediatric T1D patients during the war.

Methods: This retrospective study included T1D patients monitored by CGM. Metrics from three selected 2-week periods were compared (before the war, after the war outbreak, and 4 months later). Study variables included time-in-range (70–180 mg/dl; 3.9–10 mmol/L), time-in-tight-range (70–140 mg/dl; 3.9–7.8 mmol/L), time-in-marked-hypoglycemia (< 54 mg/dl; < 3 mmol/liter), and time-in-severe-hyperglycemia (> 250 mg/dl; >13.3 mmol/liter). Patients were treated with either a multiple daily insulin (MDI) regimen or insulin pump, with or without an open-source automated insulin delivery (OS-AID) system.

Results: Data of 99 patients were analyzed (mean age 12.2 ± 4.0 years, mean diabetes duration 4.6 ± 3.9 years, 52.5% males). No significant changes in CGM metrics were observed across the entire cohort at any time point. Patients with higher socioeconomic position (SEP; cluster > 7) had better CGM metrics, with an increase in time-in-tight-range in the lower SEP group and in time-in-severe-hyperglycemia in the higher SEP group (P = 0.003). OS-AID users (n=20) had superior pre-war CGM metrics and maintained stable glycemia during the war, MDI users showed increased time-in-severe-hyperglycemia post-outbreak (P = 0.05).

Conclusions: Throughout the war, children and adolescents with T1D treated with insulin pumps maintained relatively stable glycemic control. Susceptibility to change following the onset of war was influenced by SEP and mode of insulin therapy.

Scleromyxedema is a rare, chronic cutaneous mucinosis characterized clinically by diffuse indurated plaques, numerous waxy papules, and potential for systemic involvement, including neurological, pulmonary, and gastrointestinal complications. It can significantly impact the clinical course and patient prognosis [1].

Histologically, scleromyxedema typically manifests in two main forms. The classic form, the most common variant, is characterized by dense mucin deposition within the dermis, an increase in fibroblasts, and thickened collagen. The granuloma annulare-like variant, accounting for approximately 23% of cases, mimics granuloma annulare and is characterized by interstitial granulomatous infiltration and, in some cases, palisaded granulomas within the dermis. This unusual variant presents a significant diagnostic challenge due to its overlap with other granulomatous conditions, potentially causing diagnostic delays [2].

The lack of standardized treatment regimens makes managing scleromyxedema complex. Intravenous immunoglobulin (IVIG) has emerged as a leading therapeutic option, demonstrating efficacy in controlling both cutaneous and systemic manifestations. Other options include systemic steroids, thalidomide, retinoids, and melphalan [3].

These cases underscore the challenges of recognizing the clinical and histologic variability of scleromyxedema, which may lead to a delay in the diagnosis. Early diagnosis is critical given the potential for systemic involvement (neurological, gastrointestinal, and muscular) and the association of scleromyxedema with monoclonal gammopathy of undetermined significance (MGUS), which might progress to multiple myeloma. Consequently, timely hematologic evaluation and ongoing surveillance are warranted.

Background: Inflammatory and thrombotic markers play crucial roles in risk stratification for various diseases.

Objectives: To investigate the relative importance of inflammation, measured by C-reactive protein (CRP), and platelet turnover, indicated by immature platelet fraction (IPF), in predicting outcomes for patients with cardiovascular disease, coronavirus disease 2019 (COVID-19), and bacterial infections.

Methods: In this retrospective observational study, we analyzed data from 1473 individuals admitted to the Samson Assuta Ashdod University Hospital between 2018 and 2022. Patients were categorized based on CRP and IPF levels, with a focus on 280 patients in the high CRP/low IPF or high IPF/low CRP tertiles.

Results: The high CRP low IPF group demonstrated significantly higher mortality rates compared to the low CRP high IPF group (13.5% vs. 0.8%, P < 0.001). Logistic regression analysis revealed that the high CRP and low IPF combination was the strongest predictor of mortality (odds ratio 12.951, 95% confidence interval 1.409–119.020, P = 0.024).

Conclusions: The combination of inflammatory (CRP) and thrombotic (IPF) markers provides superior prognostic information compared to individual disease diagnoses in patients with cardiovascular disease, COVID-19, and bacterial infections.

Background: Radiofrequency-skin interaction is considered self-limited for treating acquired pigmentation such as melasma. Alternatively, skin perforation with microneedling radiofrequency (MNRF) may increase skin bioavailability for depigmenting-mediated ingredients or drugs for the treatment of melasma.

Objectives: To examine the clinical feasibility of topical tranexamic acid (TA) mediated with MNRF-assisted transepidermal delivery in patients with mixed melasma.

Methods: The study protocol included 14 women with centrofacial or malar pattern of distribution of melasma (skin types II-VI; age 35–48 years). Patients underwent four treatments at 3-week intervals between treatments. Treatment protocol included non-insulated MNFR (Intensif, EndyMed Ltd, Caesarea, Israel) followed by TA (hexakapron 4%) solution application. The improvement was evaluated based on clinical photographs (Quantificare, Biot, France) and modified Melasma Area and Severity Index (mMASI) scores. Baseline Photographs were analyzed 3 months after the last treatment.

Results: In 13 patients (93%), mMASI scores were significantly lower after 3 months (mean 3.6) than at baseline (5.22). In one patient, mMASI was higher at 3 months compared to baseline. Overall, mMASI improved by 31% (P < 0.01). Physician and patient satisfaction was high. Minimal adverse reactions were recorded.

Conclusions: MNRF-assisted transepidermal delivery with topical TA is a safe and effective modality for the treatment of melasma.