Israel Medical Association Journal

Background: The association between use of renin-angiotensin-aldosterone (RAAS) inhibitors and both SARS-CoV-2 infection and the development of severe COVID-19 has been presented in the recent medical literature with inconsistent results.

Objectives: To assess the association between RAAS inhibitor use and two outcomes: infection with SARS-CoV-2 (Model 1) and severe COVID-19 among those infected (Model 2).

Methods: We accessed used electronic health records of individuals from Israel who were receiving anti-hypertensive medications for this retrospective study. For Model 1 we used a case-control design. For Model 2 we used a cohort design. In both models, inverse probability weighting adjusted for identified confounders as part of doubly robust outcome regression.

Results: We tested 38,554 individuals for SARS-CoV-2 who had hypertension and were being treated with medication; 691 had a positive test result. Among those with a positive test, 119 developed severe illness. There was no association between RAAS inhibitor use and a positive test. Use of RAAS inhibitors was associated with a decreased risk for severe COVID-19 (adjusted odds ratio [OR] 0.47, 95% confidence interval [95%CI] 0.29–0.77) compared with users of non-RAAS anti-hypertensive medication. The association remained significant when use of angiotensin-converting-enzyme inhibitors (adjusted OR 0.46, 95%CI 0.27–0.77) and angiotensin II receptor blockers (adjusted OR 0.39, 95%CI 0.16–0.95) were analyzed separately.

Conclusions: Among individuals with hypertension using RAAS inhibitors, we found a lower risk of severe disease compared to those using non-RAAS anti-hypertensive medications. This finding suggests that RAAS inhibitors may have a protective effect on COVID-19 severity among individuals with medically treated hypertension.

Extermination via starvation was described in detail as an alternative or precursor to the final solution during the Holocaust in World War II. The main causes of death in the ghettos were exhaustion, environmental conditions (inadequate protection in extreme climates), infectious diseases, or starvation. In previous studies on the Lodz Ghetto, the causes of death via typhus exantematicus, tuberculosis, and heart failure were investigated [1,2]. In this article, we introduce the topic of diabetes in the presence of starvation and assess the incidence of malignancies in the years 1941–1944. The findings from the Lodz Ghetto would retroactively support the Warburg theory

Medical records discovered after the liberation of ghettos in Nazi-occupied Europe are unique documents that report on the suffering of inmates, on ravaging infectious diseases, and on starvation-related organ degeneration and the resulting mortality. We offer a pathogenetic explanation for the scarcity of acute myocardial infarction in the Lodz Ghetto, Poland, 1941–1944

Background: Risk factors for severe coronavirus disease-2019 (COVID-19) infection include old age, chronic illness, and neurological conditions. In contrast, high vitamin D levels are known to augment immune activity and to reduce the severity of viral infections. Recently, a possible association between the likelihood of COVID-19 infection, COVID-19 severity, and vitamin D blood levels was reported.

Objective: To assess the possible association between vitamin D long-term supplementation and COVID-19 symptomatic severity and complications of COVID-19 infection in elderly psychiatric inpatients, a high at-risk group.

Methods: We conducted a retrospective case series study. Data of 14 elderly COVID-19 positive inpatients, presenting with dementia or schizophrenia and other medical conditions were extracted from medical records. All patients maintained a 800 IU daily dose of vitamin D prior to the infection.

Results: Most of the inpatients were asymptomatic or presented very few symptoms. No need for intensive care unit intervention or deaths were reported. Cognitive functioning of the patients remained unchanged.

Conclusions: Pre-existing vitamin D supplementation may reinforce immunity and reduce COVID-19 severity in elderly psychiatric inpatients.

Background: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited.

Objectives: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest©.

Methods: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two‐dimensional SWE or FibroTest©; APRI and FIB-4 scores.

Results: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6–33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5–100), 13.4 kPa (range 5.5–51) at 6 months, and 11.4 kPa (range 6.1–35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment.

Conclusions: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis

Background: Enhanced recovery after surgery (ERAS) protocols are evidence-based protocols designed to standardize medical care, improve outcomes, and lower healthcare costs.

Objectives: To evaluate the implementation of the ERAS protocol and the effect on recovery during the hospitalization period after gynecological laparotomy surgeries.

Methods: We compared demographic and clinical data of consecutive patients at a single institute who underwent open gynecological surgeries before (August 2017 to December 2018) and after (January 2019 to March 2020) the implementation of the ERAS protocol. Eighty women were included in each group.

Results: The clinical and demographic characteristics were similar among the women operated before and after implementation of the ERAS protocol. Following implementation of the protocol, decreases were observed in post-surgical hospitalization (from 4.89 ± 2.56 to 4.09 ± 1.65 days, P = 0.01), in patients reporting nausea symptoms (from 18 (22.5%) to 7 (8.8%), P = 0.017), and in the use of postoperative opioids (from 77 (96.3%) to 47 (58.8%), P < 0.001). No significant changes were identified between the two periods regarding vomiting, 30-day re-hospitalization, and postoperative minor and major complications.

Conclusions: Implementation of the ERAS protocol is feasible and was found to result in less postoperative opioid use, a faster return to normal feeding, and a shorter postoperative hospital stay. Implementation of the protocol implementation was not associated with an increased rate of complications or with re-admissions

Background: Israel has experienced three waves of coronavirus disease-2019 (COVID-19) infection since late February 2020, with lockdown and other measures employed to contain infection rates. In cooperation with the Israel Ministry of Health, serological testing was conducted by all four health maintenance organizations (HMO) in order to estimate national infection rates and the proportion of previously undetected disease.

Objectives: To estimate the proportion of the population that was seropositive, identify factors associated with seropositive outcome, and approximate the proportion of residents that were asymptomatic.

Methods: Seroconversion rates (IgG) were measured in a representative sample of over 17,000 members of Maccabi Healthcare Services. Direct standardization was used to estimate the seropositive rates for COVID-19 infection for members of the HMO. Rates were adjusted for sensitivity and specificity of the testing products used. In addition to blood sampling, respondents were asked to complete a digital survey regarding potential exposures and symptoms experienced.

Results: It was estimated that 1.9% of the adult HMO population was seropositive 4 months after the first infected person was identified in the country. Seroconversion was associated with travel abroad and exposure to infected individuals. Loss of smell and taste, fever, cough, and fatigue are associated with infection. Of those found to be seropositive for COVID-19, 160 (59%) had a prior negative polymerase chain reaction (PCR) or no PCR test at all.

Conclusions: Adult seropositive rates of infection were low relative to other countries. The findings suggest that early initiatives to limit infection entry and spread were effective

Background: Extra peritoneal packing (EPP) is a quick and highly effective method to control pelvic hemorrhage.

Objectives: To determine whether EPP can be as safely and efficiently performed in the emergency department (ED) as in the operating room (OR).

Methods: Retrospective study of 29 patients who underwent EPP in the ED or OR in two trauma centers in Israel 2008–2018.

Results: Our study included 29 patients, 13 in the ED-EPP group and 16 in the OR-EPP group. The mean injury severity score (ISS) was 34.9 ± 11.8. Following EPP, hemodynamic stability was successfully achieved in 25 of 29 patients (86.2%). A raise in the mean arterial pressure (MAP) with a median of 25 mmHg (mean 30.0 ± 27.5, P < 0.001) was documented. All patients who did not achieve hemodynamic stability after EPP had multiple sources of bleeding or fatal head injury and eventually succumbed. Patients who underwent EPP in the ED showed higher change in MAP (P = 0.0458). The overall mortality rate was 27.5% (8/29) with no difference between the OR and ED-EPP. No differences were found between ED and OR-EPP in the amount of transfused blood products, surgical site infections, and length of stay in the hospital. However, patients who underwent ED-EPP were more prone to develop deep vein thrombosis (DVT): 50% (5/10) vs. 9% (1/11) in ED and OR-EPP groups respectively (P = 0.038).

Conclusions: EPP is equally effective when performed in the ED or OR with similar surgical site infection rates but higher incidence of DVT

Background: Adherence to treatment by adolescents and adults with cystic fibrosis (CF) is often poor.

Objectives: To assess the impact of a focused clinical intervention on adherence in individual patients, including help in problem-solving key barriers to adherence. To implement a patient-centered problem-solving intervention using CF My Way tools. To identify and overcome a selected barrier to adherence.

Methods: Medication possession ratios (MPRs), number of airway clearance sessions, forced expiratory volume (FEV₁), body mass index (BMI), and health-related quality of life (HRQoL) were measured before and after the intervention.

Results: Sixteen patients with CF, aged 23.4 ± 6.7 years, participated. MPR increased for colistimethate sodium and tobramycin inhalations from a median of 21 (range 0–100) to 56 (range 0–100), P = 0.04 and 20 (range 0–100) to 33.3 (range 25–100), P = 0.03, respectively. BMI standard deviation score rose from -0.37 to -0.21, P = 0.05. No significant improvements were found in FEV₁, airway clearance, or HRQoL scores.

Conclusions: The CF My Way problem-solving intervention increased adherence to medical treatments by removing barriers directly related to the needs and goals of young adults with CF

Background: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust.

Objectives: To describe changes in teaching during the first phase of the COVID-19 pandemic.

Methods: We described the steps implemented at the Technion–Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. 

Results: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. 

Conclusions: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching

Background: Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL).

Objectives: To characterize medication burden during the last hospitalization in children dying from cancer

Methods: We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters.

Results: Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with “Do not resuscitate” (DNR) orders (P = 0.055).

Conclusions: Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.

Germany was a scientifically advanced country in the 19th and early 20th centuries, particularly in medicine, with a major interest in research and the treatment of tuberculosis. From 1933 until 1945, Nazi Germany perverted scientific research through criminal experimentations on captured prisoners of war and on "subhumans" by scientifically untrained, but politically driven, staff. This article exposes a series of failed experiments on tuberculosis in adults, experiments without scientific validity. Nonetheless, Dr. Kurt Heißmeyer repeated the experiment on Jewish children, who were murdered for the sake of personal academic ambition. It is now 75 years since liberation and the murdered children must be remembered. This observational review raises questions of medical and ethical values