Israel Medical Association Journal

The coronavirus disease-2019 (COVID-19) and its management in patients with epilepsy can be complex. Prescribers should consider potential effects of investigational anti-COVID-19 drugs on seizures, immunomodulation by anti-seizure medications (ASMs), changes in ASM pharmacokinetics, and the potential for drug-drug interactions (DDIs). The goal of the Board of the Israeli League Against Epilepsy (the Israeli Chapter of the International League Against Epilepsy, ILAE) was to summarize the main principles of the pharmacological treatment of COVID-19 in patients with epilepsy. This guide was based on current literature, drug labels, and drug interaction resources. We summarized the available data related to the potential implications of anti-COVID-19 co-medication in patients treated with ASMs. Our recommendations refer to drug selection, dosing, and patient monitoring. Given the limited availability of data, some recommendations are based on general pharmacokinetic or pharmacodynamic principles and might apply to additional future drug combinations as novel treatments emerge. They do not replace evidence-based guidelines, should those become available. Awareness to drug characteristics that increase the risk of interactions can help adjust anti-COVID-19 and ASM treatment for patients with epilepsy

Background: Vitamin D is essential for skeletal health. Because peak bone mass accrual occurs during childhood and adolescence, vitamin D insufficiency during this period of life could cause adverse health outcomes.

Objectives: To explore the potential sex differences in anthropometric indicators and vitamin D status among primary school-age children.

Methods: A modified food-frequency intake questionnaire was completed by 116 pre-pubertal children (52 girls, 64 boys). Body measurements were recorded and blood was drawn to assess vitamin D status. All children were of Arab-Israeli origin and lived in villages or rural areas in the north-east area of Israel.

Results: Prevalence of obesity was higher among girls (34%) compared to boys (21.9%, P = 0.018). All the children were vitamin D insufficient, and 80% were deficient. Plasma vitamin D was significantly higher among boys (12.4 ng/ml) compared to girls (9.1 ng/ml, P < 0.01). A significant negative correlation was found between vitamin D status and weight percentile for girls (r = -0.43, P < 0.05) but not for boys. There was a trend toward a statistically significant inverse correlation between vitamin D status and body fat percent in the girls (r = -0.37, P = 0.07). Sex frameworks are important for the understanding of the determinants of health and the development of effective health promotion programs.

Conclusions: Pre-pubertal girls in Arab villages should be provided with tailor-made nutrition and physical activity programs for promoting health.

Background: Burn injuries are an extreme form of traumatic injury and are a global health issue. The Israeli National Burn Unit at the Sheba Medical Center, a tertiary level 1 trauma center and hence the national referral center, treats burn patients admitted both directly and referred from other medical centers. The transfer and handover of patients is a critical step in patient care. In Israel, to date, there is no standardized and accepted transfer request form for burn patients from one medical facility to another.

Objectives: To construct a transfer request form to be used in all future burn patient referrals.

Methods: After reviewing publicly available international transfer forms and comparing them to the admission checklist used at our unit, a structured transfer request form was constructed.

Results: After a pilot study period, testing the form in various scenarios and adapting it, the first standardized transfer form for burn patients in Israel in both English and Hebrew was implemented beginning May 2020.

Conclusions: Implementation of a standardized transfer process will improve communication between healthcare professionals to help maintain a continuum of care. We believe that implementation of a burn transfer form in all future referrals can standardize and assure better care for burn patients, thus improving overall patient care.

Background: There is limited clinical information on coronavirus disease-19 (COVID-19) patients in Israel.

Objectives: To describe the characteristics, outcomes, and potential associations of hospitalized COVID-19 patients in Israel.

Methods: We conducted a single-center, retrospective study of 58 consecutive laboratory-confirmed COVID-19 patients admitted to Laniado Hospital, Israel, between 14 March 2020 and 14 May 2020. Demographic, clinical, and laboratory data on admission were collected and analyzed, and the association to subsequent respiratory failure was assessed.

Results: Mean age of patients was 70.7 ± 16.9 years (53% males, 47% females.); 74% had at least one co-morbidity. Most patients were of Jewish Ashkenazi descent. During hospitalization 15 patients (mean age 78.18 ± 10.35 years); 80% male, 73% Sephardi descent developed respiratory failure rates of 60% occurring on average 10.6 days following intubation. Laboratory tests at admission displayed a significant increase in C-reactive protein (CRP) and creatine kinase (CK) and a decrease in absolute lymphocyte count (ALC) in patients who eventually developed respiratory failure (163.97 mg/L, 340.87 IU/L, 0.886 K/μl vs. 50.01 mg/L and 123.56 IU/L, 1.28 K/μl, respectively). Multivariate logistic analysis revealed an integrated parameter of CRP, CK, and ALC highly correlated with respiratory failure. Receiver operating characteristic curve revealed the area under the curve of CRP, CK, and ALC and the integrated parameter to be 0.910, 0.784, and 0.754, respectively. CRP was the strongest predictor to correlate with respiratory failure.

Conclusions: CRP, CK, and ALC levels on admission could possibly be used to detect high-risk patients prone to develop respiratory failure.

Background: Patients with severe chronic obstructive pulmonary disease (COPD) experience frequent exacerbations and need to be hospitalized, resulting in an economic and social burden. Although data exist regarding reasons of frequent hospitalizations, there is no data available about the impact on the length of stay (LOS).

Objectives: To characterize the causes of prolonged hospitalizations in COPD patients.

Methods: A retrospective study was conducted of patients who were diagnosed and treated in the pulmonary department for severe COPD exacerbations. All patient demographic data and medical history were collected. Data regarding the disease severity were also collected (including Global Initiative for Obstructive Lung Disease [GOLD] criteria, pulmonologist follow-up, prior hospitalizations, and LOS).

Results: The study comprised 200 patients, average age 69.5 ± 10.8 years, 61% males. Of these patients, 89 (45%) were hospitalized for up to 4 days, 111 (55%) for 5 days or more, and 34 (17%) for more than 7 days. Single patients had longer LOS compared with married patients (48% vs. 34%, P = 0.044). Multivariate analysis showed that the number of prior hospital admissions in the last year was a predictor of LOS (P = 0.038, odds ratio [OR] = 0.807, 95% confidence interval [95%CI] = 0.659–0.988), as well as the use of non-invasive respiratory support by bilevel positive airway pressure (BiPAP) during the hospitalization (P = 0.024, OR = 4.662, 95%CI = 1.229–17.681).

Conclusions: Fewer previous hospitalizations due to COPD exacerbations and the need for non-invasive respiratory support by BiPAP were found as predictors of longer LOS.

Background: The reported mortality rates of patients with polymyositis and dermatomyositis are highly variable worldwide. The excess mortality of patients with polymyositis/dermatomyositis has not been evaluated in an Israeli population.

Objectives: To investigate the overall mortality in a large and well-established cohort of patients with polymyositis/dermatomyositis as compared to the mortality expected in the matched general population in a tertiary medical center.

Methods: In this retrospective cohort study, the mortality of 166 patients with polymyositis/dermatomyositis was compared to age- and sex-matched control subjects in the general population. All-cause standardized mortality ratios (SMRs) were estimated.

Results: Overall, 47 (28.3%) deaths were observed among patients with polymyositis/dermatomyositis during a mean follow-up period of 5.8 ± 4.8 years, which was 7 times higher than in the control group (SMR 7.4, 95% confidence interval [95%CI] 5.5–9.8). The SMRs were comparable in patents with polymyositis (7.7, 95%CI 4.8–12.3) and dermatomyositis (7.2, 95%CI 5.0–10.3). The 1-, 5-, 10-, and 15-year overall survival rates were 90.0%, 82.8%, 51.5%, and 26.1%, respectively, in patients with polymyositis, and 80.3%, 59.6%, 40.0%, and 17.1%, respectively, in patients with dermatomyositis.

Conclusions: The overall mortality among Israeli patients with polymyositis/dermatomyositis is 7.4 times greater than for the general population. Although long-term mortality was comparable between patients with dermatomyositis and polymyositis, patients in the former group died at a notably earlier stage.

Background: Neonatal hypothermia (< 36°C) has been associated with both neonatal morbidity and mortality.

Objectives: To develop a multifactorial approach to reduce the incidence of neonatal hypothermia at admission to the neonatal intensive care unit.

Methods: The approach involved a detailed quality improvement (QI) plan, which included the use of occlusive wrapping and exothermic mattresses as well as higher delivery and operating room environmental temperatures. The improvement plan was implemented over a 10-month period. Retrospective comparison to the same 10-month period during the previous year assessed the effectiveness of the approach in reducing the incidence of admission hypothermia.

Results: The QI project included 189 patients. These patients were compared to 180 patients during the control period. The characteristics of the patient groups were similar and included preterm infants, who were subsequently analyzed as a subgroup. We found a significant reduction in the incidence of hypothermia, which was most profound for the subgroup of premature infants born at < 32 weeks gestation. Neonatal hyperthermia was identified as an unintended consequence of the project, and subsequently improved after initiating simple preventive measures.

Conclusions: Occlusive wrapping, exothermic mattresses, and higher delivery and operating room environmental temperature may be successful in reducing admission neonatal hypothermia

Background: Emergency department (ED) overcrowding is associated with worse patient outcomes.

Objectives: To determine whether physician assistants (PAs), fairly recently integrated into the Israeli healthcare system, improve patient outcomes and ED timings.

Methods: We compared patients seen by physicians with patients seen by PAs and then by physicians between January and December 2018 using propensity matching. Patients were matched for age, gender, triage level, and decision to hospitalize. Primary endpoints included patient mortality, re-admittance. and leaving on own accord rates. Secondary endpoints were ED timing landmarks.

Results: Patients first seen by PAs were less likely to leave on their own accord (MD1 1.5%, PA 1.0%, P = 0.015), had lower rates of readmission within 48 hours (MD1 2.1%, PA 1.5%, P= 0.028), and were quicker to be seen, to have medications prescribed, and to undergo imaging without differences in timings until decisions were made or total length of stay. Patients seen by a physician with the assistance of a PA were attended to quicker (MD2 47.79 minutes, range 27.70–78.82 vs. MD + PA 30.59 minutes, range 15.77–54.85; P < 0.001) without statistically significant differences in primary outcomes. Mortality rates were similar for all comparisons.

Conclusions: Patients first seen by PAs had lower rates of re-admittance or leaving on their own accord and enjoyed shorter waiting times. Pending proper integration into healthcare teams, PAs can further improve outcomes in EDs and patient satisfaction.

Background: While the ratio of male to female births (sex-ratio at birth [SRB]) in humans is remarkably stable on the population level, there are many families with multiple same-sex offspring.

Objectives: To identify a putative sub-population with skewed SRB and explore potential factors affecting the SRB.

Methods: A retrospective cohort study including 66,054 families with up to nine same-sex offspring evaluated between 2003 and 2015 at Hadassah-Hebrew University Medical Center. Outcome measures were observed prevalence and SRB of families with up to nine same-sex offspring in a single family. Analyses included the effect of parity, month and year of delivery, inter-delivery interval, and presence of a sequence of previous same-sex offspring on the SRB.

Results: The study comprised 193,411 live-born babies with SRB of 1.057 in favor of males. The proportion of SRB in families with up to nine same-sex offspring did not differ from the calculated presumed proportion. Furthermore, none of the tested factors (parity, month and year of delivery, inter-delivery interval, and the sequence of previous same-sex offspring) were significantly associated with SRB.

Conclusions: SRB was not associated with any of the tested demographic characteristics. We could not identify a skew in SRB even in families with up to nine consecutive same sex offspring. This finding suggests that in the majority of the population the chance of a male or female fetus in each pregnancy remains similar in every pregnancy, regardless of any of the tested variables.

Background: Left ventricular assist devices (LVADs) are used more commonly in patients with advanced-stage heart failure. Some of these patients may require elective or urgent abdominal surgical procedures.

Objectives: To determine the outcomes of the management of LVAD-supported patients who underwent elective and urgent abdominal surgical procedures in our institution.

Methods: A retrospective review was conducted on 93 patients who underwent LVAD implantation between August 2008 and January 2017. All abdominal surgeries in these patients were studied, and their impact on postoperative morbidity and mortality was evaluated.

Results: Ten patients underwent abdominal surgical procedures. Of these procedures, five were emergent and five were elective. The elective cases included one bariatric surgery for morbid obesity, one hiatal hernia repair, two cholecystectomies, and one small bowel resection for a carcinoid tumor. The emergency cases included suspected ischemic colitis, right colectomy for bleeding adenocarcinoma, laparotomy due to intraabdominal bleeding, open cholecystectomy for gangrenous cholecystitis, and laparotomy for sternal and abdominal wall infection. All patients undergoing elective procedures survived. Of the five patients who underwent emergency surgery, three died (60%, P = 0.16) and one presented with major morbidity. One of the two survivors required reintervention. In total, 12 interventions were performed on this group of patients.

Conclusions: It is safe to perform elective abdominal procedures for LVAD-supported patients. The prognosis of these patients undergoing emergency surgery is poor and has high mortality and morbidity rates.

Background: Rapid response teams (RRT) reduce in-hospital mortality and cardiac arrests. There are only a few articles describing RRT activations outside of North America and Australia.

Objectives: To describe demographic and clinical variables of RRT activations using 13 years of data.

Methods: Schneider Children's Medical Center of Israel is a pediatric hospital with the busiest pediatric emergency department in the country. We analyzed demographic and clinical data of RRT activation from 1 January 2008 to 31 December 2018.

Results: During the study period there were 614 RRT activations with an average of 55.8 activations per year (range 43–76). RRT activations occurred most commonly for children aged 0–12 months (43%) as compared to children 1–5 years of age (25%), 6–10 years of age (12%), 11–18 years of age (18%), and adults (2%). The most common reason for activation was respiratory deterioration (45.8%) followed by neurologic alteration (21%), and cardiac arrest (18%). Following resuscitation, 47% of the patients were admitted to the pediatric intensive care unit and 12% were pronounced dead. Intubation was performed in 48.9% of activations, chest compressions in 20.5%, intraosseous line insertion in 9.4%, and defibrillation in 3.4%. Procedures were usually performed in the emergency department (ED).

Conclusions: We describe RRT including RRT activations in the ED. The high frequency of interventions should be utilized to direct staff training for the RRT and the ED. The lack of standardization of reporting data for RRT activations makes comparisons among hospitals difficult.

Background: In February 2020, the World Health Organisation designated the name COVID-19 for a clinical condition caused by a virus identified as a cause for a cluster of pneumonia cases in Wuhan, China. The virus subsequently spread worldwide, causing havoc to medical systems and paralyzing global economies. The first COVID-19 patient in Israel was diagnosed on 27 February 2020.

Objectives: To present our findings and experiences as the first and largest center for COVID-19 patients in Israel.

Methods: The current analysis included all COVID-19 patients treated in Sheba Medical Center from February 2020 to April 2020. Clinical, laboratory, and epidemiological data gathered during their hospitalization are presented.

Results: Our 162 patient cohort included mostly adult (mean age of 52 ± 20 years) males (65%). Patients classified as severe COVID-19 were significantly older and had higher prevalence of arterial hypertension and diabetes. They also had significantly higher white blood cell counts, absolute neutrophil counts, and lactate dehydrogenase. Low folic acid blood levels were more common amongst severe patients (18.2 vs. 12.9 vs. 9.8, P = 0.014). The rate of immune compromised patients (12%) in our cohort was also higher than in the general population. The rate of deterioration from moderate to severe disease was high: 9% necessitated non-invasive oxygenation and 15% were intubated and mechanically ventilated. The mortality rate was 3.1%.

Conclusions: COVID-19 patients present a challenge for healthcare professionals and the whole medical system. We hope our findings will assist other providers and institutions in their care for these patients.