Israel Medical Association Journal

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Background: Clinical toxicology is not a certified specialty in Israel, consequently there are a limited number of toxicologists and toxicology services available for consultation.

Objectives: To establish a medical toxicology consultation service focusing on bedside consultations, which had not previously been available in Israel.

Methods: This single-center, retrospective chart review of toxicology consults was conducted during the first years after the initiation of a new toxicology service.

Results: From September 2017 to December 2021, 1703 toxicology consultations were conducted. The most common exposures and reasons for consultation included psychotropic medications (427, 23%), analgesics and anti-inflammatory medications (353, 19%), household products (312, 17%), substances of abuse (240, 13%), and natural toxins (142, 8%). Bedside medical toxicology consultations were performed in 1036 cases (62%) during daytime and night shifts. The number of consultation requests increased steadily over the study period.

Conclusions: The new toxicology service led to a significant change in the institution’s approach to toxicological patients. A bedside toxicology service could help reduce the healthcare burden on national poison centers and can offer readily available, personalized, medical toxicology care.

Background: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications.

Objectives: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM.

Methods: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared.

Results: The cohort included 89 women: 49 with HbA1c 6–8%, 29 with HbA1c 8–10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes.

Conclusions: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Background: Treatment of gestational diabetes mellitus (GDM) has been shown to improve both maternal and neonatal outcomes. For women with GDM who require glucose-lowering medication, insulin is regarded as the drug of choice by most medical societies. Oral therapy, with metformin or glibenclamide, is a reasonable alternative in certain medical circumstances.

Objectives: To compare the efficacy and safety of insulin detemir (IDet) vs. glibenclamide for GDM when glycemic control cannot be achieved through lifestyle modification and diet.

Methods: We conducted a retrospective cohort analysis of 115 women with singleton pregnancy and GDM treated with IDet or glibenclamide. GDM was diagnosed via the two-step oral glucose tolerance test (OGTT) of 50 grams glucose, followed by 100 grams. Maternal characteristics and outcomes (preeclampsia and weight gain) and neonatal outcomes (birth weight and percentile, hypoglycemia, jaundice, and respiratory morbidity) were compared between groups.

Results: In total, 67 women received IDet and 48 glibenclamide. Maternal characteristics, weight gain, and the incidence of preeclampsia were similar in both groups. Neonatal outcomes were also similar. The proportion of large for gestational age (LGA) infants was 20.8% in the glibenclamide group compared to 14.9% in the IDet group (P = 0.04).

Conclusions: In pregnant women with GDM, glucose control on IDet yielded comparable results as on glibenclamide, except for a significantly lower rate of LGA neonates.

Background: Data regarding risk factors for superficial thrombophlebitis (STP) cases presenting to a hospital is limited.

Objectives: To investigate and stratify clinical and laboratory risk factors for STP

Methods: We conducted a retrospective case control study comparing patients presenting to the emergency department with STP and age- and gender-matched controls. We collected data on multiple risk factors and five blood indices.

Results: The study comprised 151 patients and matched controls. Patients with STP were more likely to have varicose veins (43.7% vs. 5.3%, P < 0.001), recent immobilization (14.6% vs. 1.3%, P < 0.001), obesity (36.4% vs. 18.5%, P = 0.001), a history of venous thromboembolism (VTE) or STP (27.2% vs. 0.7%, P < 0.001), and inherited thrombophilia (9.3% vs. 1.3%, P = 0.002). Following multivariate analysis, all five risk factors remained significant, with a history of VTE or STP associated with the largest risk (odds ratio [OR] 35.7), followed by immobilization (OR 22.3), varicose veins (OR 12.1), inherited thrombophilia (OR 6.1), and obesity (OR 2.7). Mean platelet volume was higher (8.5 vs 7.9 fl, P = 0.003) in STP cases.

Conclusions: A history of VTE or STP, immobilization, varicose veins, inherited thrombophilia, and obesity serve as independent clinical risk factors for STP presenting to hospital.

Background: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and tenderness with associated neuropsychological symptoms such as fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. Osteoporosis is defined as a reduction of bone density. Previous studies to determine an association of FMS with osteoporosis showed mixed results, partially due to small sample sizes and lack of statistical power.

Objectives: To evaluate the association of FMS with osteoporosis.

Methods: We conducted a case-control study utilizing the database from Israel’s largest health maintenance organization. FMS patients were compared to age- and sex-matched controls. Data were analyzed using chi-square and t-tests. Multivariable logistic regression models assessed the association between osteoporosis and FMS. Spearman’s rho test was used for correlation.

Results: We utilized data from 14,296 FMS patients and 71,324 age- and sex-matched controls. Spearman's rho test showed a significant correlation between FMS and osteoporosis (correlation coefficient 0.55, P < 0.001). A logistic regression for osteoporosis showed an odds ratio [OR] of 1.94 (95% confidence interval [95%CI] 1.83–2.06, P < 0.001) for FMS compared to controls and found higher body mass index to be slight protective (OR 0.926, 95%CI 0.92–0.93, P < 0.001).

Conclusions: There is a significant correlation between FMS and osteoporosis. Early detection of predisposing factors for osteoporosis in FMS patients and implementation of suitable treatments and prevention measures (such as dietary supplements, resistance or weight bearing exercise, and bone-mineral enhancing pharmacological therapy) may reduce both occurrence rate and severity of osteoporosis and its complications, such as fractures.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Previous studies showed that rhythm and rate control strategies are associated with similar rates of mortality and serious morbidity. Beta blockers (BB) and calcium channel blockers (CCB) are commonly used and the selection between these two medications depends on personal preference.

Objectives: To compare real-time capability of BB and CCB for the treatment of rapid AF and to estimate their efficacy in reducing hospitalization duration.

Methods: We conducted a retrospective cohort study of 306 patients hospitalized at Soroka Hospital during a 5-year period with new onset AF who were treated by a rate control strategy.

Results: A significant difference between the two groups regarding the time (in hours) until reaching a target heart rate below 100 beats/min was observed. BB were found to decrease the heart rate after 5 hours (range 4–14) vs. 8 hours (range 4–18) for CCB (P = 0.009). Patients diagnosed with new-onset AF exhibited shorter duration of hospitalization after therapy with BB compared to CCB (median 72 vs. 96 hours, P = 0.012) in the subgroup of patients discharged with persistent AF. There was no significant difference between CCB and BB regarding the duration of hospitalization (P = 0.4) in the total patient population.

Conclusions: BB therapy is more potent for rapid reduction of the heart rate compared to CCB and demonstrated better efficiency in shortening the duration of hospitalization in a subgroup of patients. This finding should be reevaluated in subsequent research.

Background: Salmonella, Shigella, and Campylobacter are highly prevalent among children. Reports on risk factors of patients infected with all three pathogens, not simultaneously, are scarce.

Objectives: To identify risk factors for multiple infection with Salmonella, Shigella, and Campylobacter in the same child.

Methods: Using the Israel Sentinel Laboratory-Based Surveillance Network, we conducted a retrospective observational case-case–control study among children aged 0–9 years. A case was defined as a child infected with Salmonella, Shigella, and Campylobacter at different occasions between January 1999 and December 2020. A control was defined as a child infected with a single pathogen once, during the same period. Logistic regression models were applied to determine the association between multiple infections and demographic characteristics.

Results: We identified 109 cases (0.1%) infected with Salmonella, Shigella, and Campylobacter, and 86,511 controls (99.9%) infected with only one bacteria type. In a multivariable analysis, we showed that being Jewish (odds ratio [OR] 2.4, 95% confidence interval [95%CI] 1.3–4.4), having residency in Jerusalem (OR 3.2, 95%CI 1.3–7.7), or in the southern district (OR 3.7, 95%CI 1.5–8.8) were independent risk factors for multiple infection.

Conclusions: Although very rare, non-simultaneous infection with multiple bacteria does occur in Israel. National and local authorities should promote programs to encourage proper hygiene practices, which are culture-adjusted.

Background: Only a small proportion of schizophrenia patients present with catatonic symptoms. Imaging studies suggest that brain motor circuits are involved in the underlying pathology of catatonia. However, data about diffusivity dysregulation of these circuits in catatonic schizophrenia are scarce.

Objectives: To assess the involvement of brain motor circuits in schizophrenia patients with catatonia.

Methods: Diffusion tensor imaging (DTI) was used to measure white matter signals in selected brain regions linked to motor circuits. Relevant DTI data of seven catatonic schizophrenia patients were compared to those of seven non-catatonic schizophrenia patients, matched for sex, age, and education level.

Results: Significantly elevated fractional anisotropy values were found in the splenium of the corpus callosum, the right peduncle of the cerebellum, and the right internal capsule of the schizophrenia patients with catatonia compared to those without catatonia. This finding showed altered diffusivity in selected motor-related brain areas.

Conclusions: Catatonic schizophrenia is associated with dysregulation of the connectivity in specific motoric brain regions and corresponding circuits. Future DTI studies are needed to address the neural correlates of motor abnormalities in schizophrenia-related catatonia during the acute and remitted state of the illness to identify the specific pathophysiology of this disorder.

Background: Evaluation of children's anthropometrics poses challenges due to age-related changes. The main focus is on height and weight. However, since weight is height-dependent, body mass index (BMI) is the best surrogate measurement of adiposity. Israel has not developed national growth tables; therefore, researchers and clinicians utilize either World Health Organization (WHO) or U.S. Centers for Disease Control and Prevention (CDC) tables as benchmarks.

Objectives: To evaluate the anthropometrics of Israeli children benchmarked by CDC and WHO tables.

Methods: A retrospective review was conducted of the 1987–2003 birth cohort (age 4–18 years) from Clalit Health Services databases. Anthropometrics were retrieved twice: at study entry and one year later. We evaluated them as separate cohorts. Gender-specific age-matched median height and BMI were compared with CDC and WHO height and BMI tables.

Results: The study consisted of 15,650, mean age at study entry 9.5 years (range 4–18). Gender-specific median heights of the Israeli children were similar to CDC and WHO values at younger ages, but were slightly shorter than the age-matched CDC and WHO toward the age of final height in both cohorts. However, gender-specific median BMI was considerably and statistically significant higher compared to CDC and WHO values consistently along the entire age range in both cohorts.

Conclusions: Israeli children were slightly shorter toward the age of final height, compared to WHO and CDC. However, BMI in Israeli children was significantly higher compared to the CDC and WHO consistently along the age range, which raises an alarm regarding obesity patterns

Background: Non-alcoholic fatty liver disease (NAFLD) is emerging as an important public health condition. The effect of Ramadan fasting on several metabolic conditions has been previously assessed.

Objectives: To assess the impact of Ramadan fasting on non-alcoholic steatohepatitis (NASH) severity scores.

Methods: A retrospective, case control study was conducted in Nazareth Hospital between 2017 and 2019. We included NAFLD patients who had been diagnosed by abdominal ultrasonography. The study population was divided in two matched groups: NASH subjects who fasted all of Ramadan and NAFLD/NASH subjects who did not fast (control). Metabolic/NASH severity scores, homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR), NAFLD Fibrosis Score (NFS), BARD scores, and fibrosis-4 (FIB4) scores were assessed in both groups before and after the Ramadan month.

Results: The study included 155 NASH subjects, 74 who fasted and 81 who did not. Among the fasting group, body mass index decreased from 36.7 ± 7.1 to 34.5 ± 6.8 after fasting (P < 0.003), NFS declined from 0.45 ± 0.25 to 0.23 ± 0.21 (P < 0.005), BARD scores declined from 2.3 ± 0.98 to 1.6 ± 1.01 (P < 0.005), and FIB4 scores declined from 1.93 ± 0.76 to 1.34 ± 0.871 (P < 0.005). C-reactive protein decreased from 14.2 ± 7.1 to 7.18 ± 6.45 (P < 0.005). Moreover, HOMA-IR improved from 2.92 ± 1.22 to 2.15 ± 1.13 (P < 0.005).

Conclusions: Ramadan fasting improved on inflammatory markers, insulin sensitivity, and noninvasive measures for NASH severity assessment.

Background: Autoimmune hepatitis (AIH) may be associated with other autoimmune diseases. Autoantibodies are common in AIH suggesting their potential role in the pathogenesis of the disease. Among these autoantibodies, thyroid autoantibodies have been reported in patients with chronic hepatitis, with greater prevalence in patients with chronic hepatitis C infection.

Objectives: To assess the prevalence of thyroid dysfunction among patients with AIH.

Methods: In this case-control, retrospective study, we examined patients diagnosed with AIH according to both the original and revised international AIH group scoring systems. Patients with other hepatic pathologies were excluded AIH was evaluated as an independent risk factor for thyroid disease by a logistic regression model. Univariate and multivariate regression analyses were conducted using hypothyroidism and hyperthyroidism as the dependent variables.

Results: Our cohort comprised 163 patients diagnosed with AIH and 1104 healthy age- and gender-matched controls. Hypothyroidism was more prevalent among those with AIH compared to controls (17.7% vs. 5%, respectively, 95% confidence interval [95%CI] 1.68–2.48, P <  0.001). Hyperthyroidism was more prevalent in AIH patients compared to controls (odds ratio 3.2% and 1.2%, respectively, 95%CI 1.68–2.47, P <  0.001). Using a multivariate logistic analysis, we found an independent association between AIH and hypothyroidism but not with hyperthyroidism.

Conclusions: Thyroid dysfunction is more prevalent in patients with AIH. Whether thyroid dysfunction is the cause or a risk factor for AIH, or vice versa, is still unclear. Screening for thyroid dysfunction is warranted after AIH is diagnosed.

Background: A history of childhood sexual abuse (CSA) has been linked to a variety of physical and psychiatric illnesses, including ischemic heart disease and post-traumatic stress disorder (PTSD).

Objectives: To determine the prevalence of past CSA and re-traumatization among hospital psychiatric consultations and to determine whether a CSA group in a hospital setting shared characteristics with community samples described in the literature.

Methods: We divided 228 consecutive psychiatric consultations into two groups. One group comprised patients with a past history of CSA while the other group had no such history. Both groups were further divided into a subgroup that presented with features of re-traumatization.

Results: In the cohort, 38% described a history of CSA. Twenty patients were identified as presenting with features of re-traumatization. There were significant differences between the two groups. The patients with a history of CSA were more likely to have arrived at the emergency department (ED) during the preceding 12 months with a diagnosis of PTSD, personality disorder, and substance use disorder. There was a greater proportion of patients in the CSA group who had grown up in an ultra-Orthodox Jewish household and who currently identified as being secular.

Conclusions: The characteristics of the patients with past CSA in this study are similar to community-based samples, except for a significant gender difference. To the best of our knowledge, this study is the first to investigate CSA history during hospital ED psychiatric consultations. A history of CSA should be considered during psychiatric consultations in a general hospital ED admission.

Background: Burn injury pathophysiology is characterized by severe catabolic state and poor glycemic control. A tight glycemic control protocol using insulin for burn victims has yielded inconsistent mortality and morbidity outcomes.

Objectives: To compare the effect of standard and tight glycemic control protocols on mortality and hypoglycemia events in critical care burn patients.

Methods: We conducted a case-control study of burn victims admitted to the burn intensive care unit between 2005 and 2011. Patients were assigned to either a standard or a tight glycemic control protocol.

Results: Of the 38 burn patients in the study, 28 were under a tight glycemic control protocol. No differences in glucose area-under-the-curve per day levels were observed between the groups (148.3 ± 16 vs. 157.8 ± 16 mg/dl in the standard and tight glycemic control protocol groups respectively, P < 0.12). The hypoglycemic event rate was higher in the tight glycemic control protocol group (46.4% vs. 0%, P < 0.008). No difference in mortality rate was noted (67.9% vs. 50%, P < 0.31). Mortality-independent risk factors found on multivariate analysis included total body surface area (adjusted hazard ratio [AHR] 1.039, 95% confidence interval  [95%CI] 1.02–1.06, P < 0.001), white blood cell count on admission (AHR 1.048, 95%CI 1.01–1.09, P < 0.02) and surgery during hospitalization (AHR 0.348, 95%CI 0.13–0.09, P < 0.03).

Conclusions: The tight glycemic control protocol in burn patients was associated with higher rates of hypoglycemic events, and no association was found with improved survival in the acute setting of burn trauma care.