Israel Medical Association Journal

Background: Syncope is a common reason for emergency department (ED) visits; however, the decision to admit or discharge patients after a syncopal episode remains challenging for emergency physicians. Decision rules such as the Boston Syncope Criteria have been developed in an attempt to aid clinicians in identifying high-risk patients as well as those who can be safely discharged, but applying these rules to different populations remains unclear.

Objectives: To determine whether the Boston Syncope Criteria are valid for emergency department patients in Israel.

Methods: This retrospective cohort convenience sample included patients who visited a tertiary care hospital in Jerusalem from August 2018 to July 2019 with a primary diagnosis of syncope. Thirty-day follow-up was performed using a national health system database. The Boston Syncope Criteria were retrospectively applied to each patient to determine whether they were at high risk for an adverse outcome or critical intervention, versus low risk and could be discharged.

Results: A total of 198 patients fulfilled the inclusion criteria and completed follow-up. Of these, 21 patients had either an adverse outcome or critical intervention. The rule detected 20/21 with a sensitivity of 95%, a specificity of 66%, and a negative predictive value of 99%.

Conclusions: The Boston Syncope Criteria may be useful for physicians in other locations throughout the world to discharge low-risk syncope patients as well as identify those at risk of complications

Background: There is a lack of real-life clinical data for biosimilar etanercept, an anti-TNF blocking fusion protein. We describe the comparable efficacy and safety of originator and biosimilar etanercept in rheumatoid arthritis (RA) patients in a real-life clinical setting. Our data confirm that a biosimilar etanercept can be safely used as first-line treatment as well as in patients switched from a previous originator compound.

Objectives: To compare the efficacy and safety of originator and biosimilar etanercept in a cohort of RA patients attending two Italian hospitals.

Methods: The study involved 81 consecutive adult RA patients treated for at least 6 months with originator or biosimilar etanercept and considered their clinical and laboratory data, concomitant medications, and adverse events at baseline, and after 3 and 6 months of treatment.

Results: Group 1 included 51 patients taking originator etanercept; group 2 included 30 taking biosimilar etanercept, including 19 who had been switched from the reference product. Despite a significant baseline difference in clinical disease activity, one-way analysis of variance showed that the two groups were clinically comparable after 6 months of treatment, and the same was true when only those receiving etanercept as first-line biological treatment were considered. Nine patients discontinued the treatment due to inefficacy or adverse events, which were never serious and were only reported in group 1.

Conclusions: The efficacy and safety profiles of originator and biosimilar etanercept are comparable in RA patients in a real-life clinical setting. Further studies are needed to confirm these preliminary findings

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection in immunocompromised patients. Clusters of PJP, especially among organ transplant recipients in clinic settings were described. Data regarding nosocomial PJP infection among inpatients are limited.

Objectives: To assess the magnitude and characteristics of inpatient healthcare-associated PJP infection (HCA-PJP) in HIV-negative patients.

Methods: A retrospective chart review of hospitalized PJP patients was performed to identify HCA-PJP. The study was performed at six medical centers in Israel from 2006 to 2016. HCA-PJP was defined as cases of hospital-onset or those with documented contact with a PJP patient. We reviewed and cross-matched temporal and spatial co-locations of patients. Clinical laboratory characteristics and outcomes were compared.

Results: Seventy-six cases of PJP were identified. Median age was 63.7 years; 64% men; 44% hematological malignancies; 18% inflammatory diseases; and 61% steroid usage. Thirty-two patients (42%) were defined as HCA-PJP: 18/32 (23.6%) were hospitalized at onset and 14/32 (18.4%) had a previous encounter with a PJP patient. Time from onset of symptoms to diagnosis was shorter in HCA-PJP vs. community-PJP (3.25 vs. 11.23 days, P = 0.009). In multivariate analysis, dyspnea at presentation (odds ratio [OR] 16.79, 95% confidence interval [95%CI] 1.78–157.95) and a tendency toward higher rate of ventilator support (72% vs. 52%, P = 0.07, OR 5.18, 95%CI 0.7–30.3) were independently associated with HCA-PJP, implying abrupt disease progression in HCA-PJP.

Conclusion: HCA-PJP was common. A high level of suspicion for PJP among selected patients with nosocomial respiratory infection is warranted. Isolation of PJP patients should be considered

Background: The coronavirus disease-2019 (COVID-19) social-distancing strategy, including 7 weeks of strict lockdown, enabled an extraordinary test of stay-at-home regulations, which forced a sedentary lifestyle on all children and adolescents.

Objectives: To assess the lockdown effect on pediatric weight.

Methods: A retrospective-prospective cohort study at our hospital’s pediatric outpatient clinics following the COVID-19 lockdown. Patients aged 0–18 years visiting the clinic were weighed and previous weight and other clinical data were collected from the medical charts. Weight-percentile-for-age standardization was calculated according to the U.S. Centers for Disease Control and Prevention and the World Health Organization growth tables. Pre- and post-lockdown weight-percentiles-for-age were compared using paired t-test. Multivariate analysis was conducted using linear regression model.

Results: The study was comprised of 229 patients; 117/229 (51.1%) were boys, 60/229 (26.2%) aged under 6 years. Total mean weight-percentile was significantly higher following the lockdown (40.44 vs. 38.82, respectively, P = 0.029). Boys had a significant post-lockdown weight-percentile rise (37.66 vs. 34.42, P = 0.014), whereas girls had higher baseline pre-quarantine weight-percentile of 43.42, which did not change. Patients younger than 6 years had a significant increase in weight-percentiles (39.18 vs. 33.58, P = 0.021). In multivariate analysis these correlations were preserved.

Conclusions: A general weight gain among children was noted, especially in boys during the lockdown, with substantial effect under the age of 6 years. This collateral side-effect should be considered in further quarantine regulations

Background: Low folate levels are associated with megaloblastic anemia, neural tube defects, and an increased risk of cancer. Data are scarce regarding the sex aspect of this deficiency.

Objectives: To assess sex differences in folate levels in a large cohort of patients and to investigate the effect of low folate levels on homocysteine concentrations.

Methods: Data were collected from medical records of patients examined at a screening center in Israel between 2000 and 2014. Cross sectional analysis was conducted on 9214 males and 4336 females.

Results: The average age was 48.4 ± 9.5 years for males and 47.6 ± 9.4 years for females. Average folate levels were 19.2 ± 8.6 and 22.4 ±10.3 nmol/L in males and females, respectively (P < 0.001). The prevalence of folate levels below 12.2 nmol/L was 19.5% in males compared to 11.6% in females (P < 0.001). In patients with low folate levels and normal B12 levels, homocysteine levels above 15 μmol/L were found in 32.4% of males and 11.4% of females (P < 0.001). Males had a significantly higher odds ratio (OR) of having folate levels below 12.2 nmol/L: OR 1.84 (95% confidence interval [95%CI] 1.66–2.05) in a non-adjusted model, and OR 2.02 (95%CI 1.82–2.27) adjusted for age, smoking status, body mass index, kidney function, albumin, and triglycerides levels.

Conclusions: Folate levels are lower in males compared to females, which may contribute to the higher homocysteine levels found in males and thus to their increased risk of developing atherosclerosis and coronary artery disease.

Background: Sheba Medical Center, Tel Hashomer, is a tertiary hospital located in the center of Israel. It is the largest hospital in Israel and was the first to face coronavirus disease-2019 (COVID-19) patients in the country at the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic.

Objectives: To describe our experience with the COVID-19 pandemic, focusing on our triage method in the emergency department (ED). Our goal was to keep the main hospitalization buildings clean of infection by separating COVID-19 positive patients from COVID-19 negative patients.

Methods: We divided our ED into two separate sections: a regular non-COVID-19 ED and an advanced biological ED. We created clear protocols of triage for suspected and confirmed COVID-19 patients. We reviewed the data of patients admitted to our ED during the month of March and analyzed the results of our triage method in separating COVID-19 positive from negative patients.

Results: During the month of March 2020, 7957 patients were referred to our ED. Among them 2004 were referred to the biological ED and 5953 were referred to the regular ED. Of the 2004 patients referred to the biological ED, 1641 (81.8%) were sampled for SARS-CoV-2 polymerase chain reaction of whom 143 (8.7%) were positive. Only two COVID-19 positive patients unintentionally entered the main clean hospital, making our triage almost full proof.

Conclusions: Our triage method was successful in separating COVID-19 positive from negative patients and maintained the regular hospital clean of COVID-19 allowing treatment continuation of regular non-COVID-19 patients.

Background: Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs.

Objectives: To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type.

Methods: A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration.

Results: The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route.

Conclusions: RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.

Background: Internal thoracic impedance (ITI) measurement is a sensitive method for detecting preclinical pulmonary edema and pleural effusion.

Objectives: To investigate the efficacy of this non-invasive method for detecting early pleural effusion among geriatric patients and to monitor increased ITI during its resolution.

Methods: This prospective, controlled study was conducted between July 2012 and August 2015. The study comprised 70 patients aged 65 to 94 years; and 39 of the patients had pleural effusion. ITI was measured continuously with a RS-207 monitor. The predictive value of ITI monitoring was determined based on a total of eight measurements taken at 12-hour intervals over 84 hours.

Results: As a result of medical treatment, the median ITI of the study group increased from 31 (interquartile range [IQR] 28–33 ohms) to 41 ohms (IQR 38–41 ohms; P < 0.001) compared to non-significant changes in the control group. Average respiratory rate (per minute) in the study group decreased from 29 (IQR 28–34) to 19 (IQR 18–20).

Conclusions: ITI monitoring is efficient for diagnosis and for ongoing clinical evaluation of the treatment of elderly patients with pleural effusion. Timely treatment may prevent serious complications of effusions avoiding extended hospitalization.

Background: Many procedures requiring sedation in the pediatric emergency department are performed by consultants from outside the department. This team usually includes orthopedic surgeons and general surgeons. As sedation is now a standard of care in such cases, we evaluated consultants' views on sedation.

Objectives: To evaluate consultants' views on sedation.

Methods: A questionnaire with both open-ended questions and Likert-type scores was distributed to all orthopedic surgeons and general surgeons performing procedures during the study period. The questionnaire was presented at three medical centers.

Results: The questionnaire was completed by 31 orthopedic surgeons and 16 general surgeons. Although the vast majority (93–100%) considered sedation important, a high percentage (64–75%) would still perform such procedures without sedation if not readily available.

Conclusions: Sedation is very important for patients and although consultants understand its importance, the emergency department staff must be vigilant in both being available and not allowing procedures to "escape" the use of sedation.

Background: Patients with right bundle branch block (RBBB) prior to transcatheter aortic valve implantation (TAVI) are at high risk for immediate post-procedural heart block and long-term mortality when discharged without a pacemaker.

Objectives: To test whether prophylactic permanent pacemaker implantation (PPI) is beneficial.

Methods: Of 795 consecutive patients who underwent TAVI, 90 patients had baseline RBBB. We compared characteristics and outcomes of the prophylactic PPI with post-TAVI PPI. Need for pacing was defined as  greater than 1% ventricular pacing.

Results: Forty patients with RBBB received a prophylactic PPI (group 1), and in 50 the decision was based on standard post-procedural indications (group 2). There were no significant differences in clinical baseline characteristics. One patient developed a tamponade after a PPI post-TAVI. A trend toward shorter hospitalization duration in group 1 patients was observed (P = 0.06). On long-term follow-up of 848 ± 56 days, no differences were found in overall survival (P = 0.77), the composite event-free survival of both mortality and hospitalizations (P = 0.66), or mortality and syncope (P = 0.65). On multivariate analysis, independent predictors of the need for pacing included baseline PR interval increase of 10ms (odds ratio [OR] 1.21 per 10 ms increment 95% confidence interval [95%CI] 1.02–1.44, P = 0.028), and the use of new generation valves (OR 3.92, 95%CI 1.23–12.46, P = 0.023).

Conclusions: In patients with baseline pre-TAVI RBBB, no outcome differences were found with prophylactic PPI. On multivariate analysis, predictors of the need for pacing included baseline long PR interval, and the use of newer generation valves.

Background: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed.

Objectives: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential.

Methods: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases.

Results: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10).

Conclusion: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.

Background: Kidney transplantation is associated with early improvement in cardiac function and structure; however, data on cardiac adaptation and its relation to kidney allograft function remain sparse.

Objectives: To investigate the relationship between post-transplant kidney function and echocardiographic measures in patients with normal/preserved pre-transplant cardiac structure and function.

Methods: The study included 113 patients who underwent kidney transplantation at a single tertiary medical center from 2000 to 2012. The patients were evaluated by echocardiography before and after transplantation, and the relation between allograft function and echocardiographic changes was evaluated. Echocardiography was performed at a median of 510 days after transplantation.

Results: The post-transplantation estimated glomerular filtration rate (eGFR) was directly correlated with left ventricular (LV) systolic function and inversely correlated with LV dimensions, LV wall thickness, left atrial diameter, and estimated systolic pulmonary arterial pressure. In patients with significant allograft dysfunction (eGFR ≤ 45 ml/min), LV hypertrophy worsened, with no improvement in LV dimensions. In contrast, in patients with preserved kidney function, there was a significant reduction in both LV diameter and arterial pulmonary systolic pressure.

Conclusions: Our results show that in kidney transplant recipients, allograft function significantly affects cardiac structure and function. Periodic echocardiographic follow-up is advisable, especially in patients with kidney graft dysfunction.