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: 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: In Israel, critically ill patients are ventilated and managed in intensive care units or general wards.

Objectives: To compare the mortality rates and long-term cognitive and functional outcomes of ventilated patients who underwent tracheostomy insertion in the Medical ICU (MICU) versus those cared for in the in-patient wards.

Methods: The study comprised 170 patients who underwent percutaneous dilatational tracheostomy (PDT) over an 18-month period in the MICU (n=102) and in in-patient wards (internal medicine and neurology) (n=68). Telephone interviews were conducted with living patients and/or their relatives at least 6 months after discharge from the hospital.

Results: Ward patients were 10 years older than ICU patients undergoing PDT (P = 0.003). The length of stay (LOS) in the wards was longer than in the ICU (P < 0.001), whereas the total LOS in the hospital was similar (P = 0.43). ICU mortality was lower than in the wards (P = 0.001) but hospital mortality was comparable between the two groups (P = 0.17). At 6 months follow-up more ICU patients were fully conscious, weaned from ventilation, and decannulated. More patients in the ICU group were at home and were independent or had mildly impaired activities of daily living. More patients in the ward group were residing in long-term care facilities with functional limitations.

Conclusions: MICU patients who undergo tracheostomy may have a good long-term functional and cognitive outcome. More studies are needed to further assess long-term outcomes in these patients.

Histiocytic sarcoma (HS) is a rare hematopoietic malignancy originating from the monocyte/macrophage bone marrow lineage. HS can occur in isolation or in association with other hematological neoplasms such as non-Hodgkin lymphoma (NHL), myelodysplasia, or acute leukemia. Clinically, HS can affect lymph nodes, gastrointestinal tract, skin, bone marrow, and spleen as well as the central nervous system. Most cases of HS follow an aggressive clinical course, with most patients dying of progressive disease within one year of diagnosis

Background: The World Health Organization classified coronavirus disease-19 (COVID-19) as a pandemic and recommends strict restrictions regarding most aspects of daily activities.

Objectives: To evaluate whether the pandemic has changed the prenatal care and pregnancy outcome in pregnant women without COVID-19.

Methods: The authors conducted a cross-sectional study to describe changes in outpatient clinic visits and to compare the rates of cesarean and instrumental deliveries between two periods of time: March–April 2020 (during the COVID-19 outbreak) with March–April of the preceding year, 2019.

Results: During the COVID-19 outbreak, visits to obstetric triage, gynecologic triage, high-risk clinic, and ultrasound units decreased by 36.4%, 34.7%, 32.8%, and 18.1%, respectively. The medical center experienced a 17.8% drop in the total number of births (610 births) compared with March and April 2019 (742 births). During the outbreak women were more likely to be nulliparous (33.3% vs. 27.6%, P = 0.02) and present with hypertensive disorders during pregnancy (7.5% vs. 4%, P = 0.005) or gestational diabetes (13% vs. 10%, P = 0.03). More epidural analgesia was used (83.1% vs. 77.1%, P = 0.006). There were more operative vaginal deliveries during the outbreak (16.7% vs. 6.8%, P = 0.01). All other maternal and neonatal outcomes were comparable between the two periods.

Conclusions: The medical facility experienced a major decline in all aspects of the routine obstetrics activities during the time of the pandemic. The higher rate of operative vaginal deliveries among nulliparous may be associated with the pandemic effect on the rate of high-risk patients

Background: Acetaminophen is the most common drug involved in pediatric poisonings, both intentionally and accidentally, and is the leading cause of acute liver failure among all age groups.

Objectives: To define the characteristics of patients admitted to a pediatric emergency department (ED) where serum acetaminophen concentrations were measured, and to determine which variables are associated with significant risk of acetaminophen toxicity.

Methods: Acetaminophen serum concentrations were measured, in a retrospective case series, of patients younger than 18 years who had been admitted to the ED at Shamir Medical Center between 1 January 2008 and 31 December 2015.

Results: During the study period 180,174 children were admitted to the ED. Acetaminophen serum concentrations were measured in 209 (0.12%) patients. Mean age was 12.4 ± 5.9 years. Elevated liver enzymes were found in 12 patients, 5 of whom had documented acute liver injury. All five were older than 11years.Two cases of acute liver injury were attributable to acetaminophen ingestion. In both cases the cause was intentional overdose. Univariate analysis showed a significant (P < 0.05) correlation between detectable acetaminophen blood level and a positive history of drug or acetaminophen ingestion, and suicide attempt. Not all children with non-severe acetaminophen poisoning had been diagnosed during the study period. A positive history of acetaminophen ingestion was associated with a 28-fold higher risk for detectable acetaminophen blood level.

Conclusions: In the absence of a positive history of acetaminophen ingestion and in young children with accidental intoxication, the risk of hepatotoxicity is relatively low.

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Methods: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.

Results: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.

Conclusions: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

Background: Channeling medical resources for coronavirus disease-2019 (COVID-19) management can potentially endanger routine healthcare practices. As a preventive measure, a department of obstetrics and gynecology in Israel constructed a separate, designated complex for its COVID-19-exposed patients.

Objectives: To evaluate the effect of the COVID-19 pandemic infection control measures on obstetric care in the obstetrical emergency department and delivery unit.

Methods: The authors collected data retrospectively from February 2020 to March 2020 and compared it to data of a parallel period in 2019.

Results: From 1 February 2020 to 28 March 2020, 3897 women were referred to the emergency department (ED), compared to 4067 the previous year. Mean duration of treatment until decision and referral indications did not differ between 2020 and 2019 (207 vs. 220 minutes, P = 0.26; urgent referrals 58.8% vs. 59.2%, P = 0.83). A per-week comparison showed a significant reduction in ED referrals only in the last week of the period (337 [2020] vs. 515 [2019], P < 0.001). The proportion of women admitted to the delivery unit in active labor was significantly higher in the last three weeks (39.1% vs. 28.2%, P = 0.005). During February and March 2020, 1666 women delivered, compared to 1654 during February and March 2019. The proportion of types and modes of delivery did not differ. In a per-week comparison, the number of deliveries did not differ (mean 208 vs. 206, P = 0.88).

Conclusions: With timely preparation and proper management, negative impact of COVID-19 can be reduced in obstetrical emergency departments.

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: Transanal minimally invasive surgery (TAMIS) is a single port access platform used for full thickness local excision of rectal lesions. It is an appealing alternative to a radical resection of rectum that often can cause a significant bowel dysfunction described as low anterior resection syndrome (LARS). LARS is evaluated using a validated score. Functional outcomes of patients undergoing TAMIS has not yet been evaluated using the LARS score.

Objectives: To evaluate long-term bowel function in patients who underwent TAMIS.

Methods: In this case series, all patients who underwent TAMIS in a single tertiary institute between 2011 and 2017 were retrospectively reviewed. We evaluated bowel function using the LARS score questionnaire through telephone interviews.

Results: The study consisted of 23 patients, average age of 67 ± 6.98 year; 72% were male. The median follow-up from the time of surgery was 5 years. Six patients (26.08%) had malignant type lesions. The average height of the lesion from the anal verge was 7.4 cm. The average size of the specimen was 4 cm. The total LARS score revealed that 17 patients (73.91%) had no definitive LAR syndrome following the surgery. Four patients (17.39%) fit the description of minor LARS and only two (8.69%) presented with major LARS.

Conclusions: TAMIS provides relatively good long-term functional outcomes in terms of bowel function. Further randomized studies with larger cohorts are still needed to better evaluate the outcomes.

Background: Following an intestinal anastomotic leak, stoma creation may be the safest approach. However, this method may be challenging and cause significant morbidity. In selected cases, a T drain approach can be beneficial and a stoma can be avoided.

Objectives: To present one group's experience with a T drain approach for anastomotic leaks.

Methods: Data on patients who underwent emergent re-laparotomy following gastrointestinal anastomotic leaks were retrieved retrospectively and assessed with a new intra-operative leak severity score.

Results: Of 1684 gastrointestinal surgeries performed from 2014 to 2018, 41 (2.4%) cases of anastomotic leaks were taken for re-laparotomy. Cases included different sites and etiologies. Twelve patients were treated with a T-tube drain inserted through the leak site, 18 had a stoma taken out, 6 re-anastomosis, 4 were treated with an Endosponge, and one primary repair with a proximal ileostomy was conducted. T drain approach was successful in 11 of 12 patients (92%) with full recovery. One patient did not improve and underwent reoperation with resection and re-anastomosis. A severity score of anastomotic integrity is provided to help surgeons in decision making.

Conclusions: A T drain approach can be an optimal solution in selected cases following an intestinal anastomotic leak. When the leak is limited, the remaining anastomosis is intact and the abdominal environment allows it, a T drain can be used and a stoma can be avoided.