Israel Medical Association Journal

Background: Pain management is fundamental in the treatment of a trauma casualty. Adequate pain management is associated with decreased long-term morbidity and chronic pain. Nonetheless, pain is frequently not documented nor adequately treated in the prehospital setting, a phenomenon described as oligoanalgesia. Gender bias has been suggested as a risk factor for oligoanalgesia.

Objectives: To examine the association between casualty gender and pain management in the prehospital trauma setting.

Methods: We conducted a retrospective cohort study of the Israel Defense Forces Trauma Registry between 2015 and 2020. Univariable analysis followed by multivariable logistic regression was used to assess the association between casualty gender and pain management. For adult patients for whom gender was known, pain scores were documented.

Results: A total of 1044 casualties were included in the study; 894 (85.6%) were male. Females and males differed in several demographic and injury characteristics, including age in years (mean 36 vs. 27.6, P value < 0.001) and injury mechanism (16%% vs. 34.5% penetrating injury, P value < 0.001). Female casualties were less likely to be treated for pain (odds ratio [OR] 0.708, 95% confidence interval [95%CI] 0.5–1, P = 0.05). However, after adjustment for various factors, including pain severity, this association was insignificant (OR 0.748, 95%CI 0.46–1.23, P = 0.25).

Conclusions: In this prehospital study, gender bias in pain management was not apparent. As women’s role on the battlefield continues to increase, further studies regarding the role of

Background: Diabetes mellitus (DM) is one of the risk factors for progression from latent to active tuberculosis. However, the effect of DM on subsequent tuberculosis treatment is still inconclusive.

Objectives: To compare tuberculosis treatment outcomes and the rate of drug resistance of tuberculosis patients with or without DM.

Methods: This case-control study was conducted between 2005 and 2015 at the only tuberculosis ward in Israel. All 80 tuberculosis patients who had DM and were hospitalized during the study period were included in this study, as were a randomized sample of 213 tuberculosis patients without DM. Demographic, clinical, and laboratory data were collected from patient files in the hospital and clinics after discharge.

Results: Tuberculosis patients with DM were more often older and more likely to be Israeli citizens with a lower socioeconomic status than patients without DM. No statistically significant differences were found in clinical presentation, radiological findings, and sputum smear tests between the two groups. Culture converting times were prolonged in patients with DM compared to normoglycemic patients. Multidrug drug resistance tuberculosis was more common among normoglycemic tuberculosis patients than tuberculosis patients with DM (9.2% vs. 1.6%, P = 0.12). Treatment success rates were 76.2% and 83.1% for tuberculosis patients with or without DM, respectively (P = 0.18). DM was not statistically significant in the multivariate analysis predicting treatment success, which controlled for age, citizenship, compliance, addictions, and chronic diseases.

Conclusions: The presence of DM does not necessarily affect tuberculosis treatment outcomes as long as treatment compliance is optimal.

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: Patients with autoimmune disease (AID) and coronavirus disease 2019 (COVID-19) could have higher mortality due to the co-morbidity and the use of immunosuppressive therapy.

Objectives: To analyze the risk factors and outcomes of patients with AID and COVID-19 versus a control group.

Methods: A prospective cohort study included patients with and without AID and COVID-19. Patients were paired by age and sex. Clinical, biochemical, immunological treatments, and outcomes (days of hospital stay, invasive mechanical ventilation [IMV], oxygen at discharge, and death) were collected.

Results: We included 226 COVID-19 patients: 113 with AID (51.15 ± 14.3 years) and 113 controls (53.45 ± 13.3 years). The most frequent AIDs were Rheumatoid arthritis (26.5%), systemic lupus erythematosus (21%), and systemic sclerosis (14%). AID patients had lower lactate dehydrogenas, C-reactive protein, fibrinogen, IMV (P = 0.027), and oxygen levels at discharge (P ≤ 0.0001) and lower death rates (P ≤ 0.0001). Oxygen saturation (SaO₂) ≤ 88% at hospitalization provided risk for IMV (RR [relative risk] 3.83, 95% confidence interval [95%CI] 1.1–13.6, P = 0.038). Higher creatinine and LDH levels were associated with death in the AID group. SaO₂ ≤ 88% and CO-RADS ≥ 4 were risk factors for in-hospital mortality (RR 4.90, 95%CI 1.8–13.0, P = 0.001 and RR 7.60, 95%CI 1.4–39.7, P = 0.016, respectively). Anticoagulant therapy was protective (RR 0.36, 95%CI 0.1–0.9, P = 0.041)

Conclusions: Patients with AID had better outcomes with COVID-19 than controls. Anticoagulation was associated with a lower death in patients with AID.

Background: Solid organ transplant recipients (SOTRs) are at increased risk for both skin and internal malignancies (IM). The risk of IM after the occurrence of non-melanoma skin cancer (NMSC) has been studied in the general population but very little is known about this association in SOTRs.

Objectives: To evaluate the risk of IM following a prior diagnosis of post transplantation NMSC in SOTRs.

Methods: This single center retrospective cohort study included a study population of 329 SOTRs from Rabin Medical Center who had a post-transplant diagnosis of skin malignancy, internal malignancy, or both from 2012 to 2018.

Results: In total, 135 (41.03%) SOTRs were diagnosed with IM without a preceding diagnosis of NMSC while only 42 (12.76%) patients diagnosed with IM had a preceding diagnosis of NMSC. SOTRs with a diagnosis of NMSC showed a significantly decreased risk of developing subsequent IM (hazard ratio [HR] 0.64, 95% confidence interval [95%CI] 0.44–0.94, P = 0.02) compared to those without a prior NMSC diagnosis. Liver and lung transplant patients showed a significantly decreased risk of developing subsequent IM after a diagnosis of NMSC (HR 0.09 and 0.43, respectively). When stratified by type of IM, only patients who were diagnosed with a hematological malignancy had a significantly lower risk of developing this malignancy if they had a prior NMSC (HR 0.26).

Conclusions: The findings of this study suggest a protective effect of NMSC on subsequent IM in the organ transplant population.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of nosocomial infections. Active surveillance for CRAB carriage to identify and isolate colonized patients is used to reduce transmission.

Objectives: To assess the rate and risks of clinical infection among CRAB-carrier and non-carrier patients.

Methods: Hospitalized patients from whom CRAB screening-cultures were obtained between January and June 2018 were identified retrospectively. All CRAB-carriers were compared to a convenient sample of non-carriers and were followed to detect development of CRAB clinical infection during admission.

Results: We compared 115 CRAB carriers to 166 non-carriers. The median age in the study group was 76 years (IQR 71–87) vs. 65 years (55–79) in the non-carriers group (P < 0.001). Residence in a nursing facility, debilitated state, and admission to medical wards vs. intensive care units were more frequent among CRAB-carriers (P < 0.001). Mechanically ventilated patients included 51 CRAB carriers (44%) and 102 non-carriers (61%). Clinical infection developed in 49 patients (17%), primarily CRAB pneumonia. Of the CRAB-carriers and non-carriers, 26/115 (23%) and 23/166 (14%), respectively, developed a clinical infection (P = 0.05). One-third of the ventilated patients were infected. Debilitated state and antibiotic treatment during hospitalization were linked to higher infection rates (P = 0.01). Adjusted analysis showed that mechanical ventilation and CRAB colonization were strongly associated with clinical infection (P < 0.05).

Conclusion: The rate of CRAB infection among carriers was high. Mechanical ventilation and CRAB colonization were associated with CRAB clinical infection, primarily pneumonia

Background: Patients with high-risk prostate cancer are at higher risk of treatment failure, development of metastatic disease, and mortality. There is no consensus on the treatment of choice for these patients, and either radical prostatectomy (RP) or external beam radiation therapy (EBRT) is recommended. Surgery is less common as the initial treatment for high-risk patients, possibly reflecting the concerns regarding morbidity as well as oncological and functional outcomes. Another high-risk group includes patients with failure of previous EBRT or focal treatment. For these patients, salvage radical prostatectomy (SRP) can be offered.

Objectives: To describe our experience with surgery of high-risk patients and SRP.

Methods: This cohort included all high-risk patients undergoing RP or SRP at our institution between January 2012 and December 2019. We reviewed the electronic medical charts and collected pathological, functional, and oncological outcomes.

Results: Our cohort included 39 patients; average age was 67.8 years, and average follow-up duration was 40.9 months. The most common postoperative morbidity was transfusion of packed cells. There were no life-threatening events or postoperative mortality. Continence was preserved (zero to one pad) in 76% of the patients. Twenty-three patients (59%) had undetectable prostate specific antigen levels following the surgery, 11 (30%) were treated with either adjuvant or salvage EBRT, and 12 patients (31%) were found with no evidence of disease and no additional treatment was needed.

Conclusions: Radical prostatectomy and SRP are safe options for patients presenting with high-risk prostate cancer, with good functional and oncological outcomes.

Background: The 2015 American Thyroid Association (ATA2015) and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS) are two widely used thyroid sonographic systems.

Objectives: To compare the two systems for accuracy of cancer risk prediction.

Methods: Preoperative ultrasound images from 265 patients who underwent thyroidectomy at our hospital from January 2012 to March 2019 were retrospectively categorized by the ACR TI-RADS and ATA2015 systems. Diagnostic performances were compared.

Results: Of 238 nodules assessed, 115 were malignant. Malignancy risks for the five ACR TI-RADS categories were 0%, 7.5%, 11.4%, 59.6%, and 90.0%. Malignancy risks for the five ATA2015 categories were 0%, 6.8%, 17.0%, 55.5%, and 92.1%. The proportion of total nodules biopsied was higher with the ATA2015 system than the ACR TI-RADS system: 88.7% vs. 66.3%. Proportions of malignant nodules and benign nodules biopsied were higher with ATA2015 than with ACR TI-RADS: 93.3% vs. 87.8% and 84.4% vs. 46.3%, respectively. Specificity and sensitivity rates were 53.6% and 84.3%, respectively, for ACR TI-RADS, and 15.5% and 93.3%, respectively, for ATA2015. The two systems showed similarly accurate diagnostic performance (AUC > 0.88). False negative rates for ACR TI-RADS and ATA2015 were 15.6% and 6.6%, respectively. Rates of missed aggressive cancer were similar for the two systems: 3.4% and 3.7%, respectively.

Conclusion: ACR TI-RADS was superior to ATA2015 in specificity and avoiding unnecessary biopsies. ATA2015 yielded better sensitivity and a lower false negative rate. Identification of aggressive cancers was identical in the two systems

Background: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts.

Objectives: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding.

Methods: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26–33 weeks gestation) were randomized 1:1 to receive insulin 400 μU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels.

Results: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59–8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20–9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29–2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group.

Conclusions: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26–33 weeks.

Background: Proximal femoral fractures (PFF) are among the most common injuries in the elderly population treated by orthopedic surgeons. Postoperative complications, especially infections, are of great importance due to their effect on patient mortality and morbidity and healthcare costs.

Objectives: To assess the main causes for postoperative infection among PFF patients.

Methods: We conducted a retrospective analysis of PFF patients in our medical center between 2015 and 2017. Patients were divided into two groups based on whether there was postoperative infection during immediate hospitalization and 30 days after surgery. Factors such as time from admission to surgery, duration of surgery, and length of stay were analyzed. Groups were analyzed and compared using a t-test, chi-squared and Fisher’s exact tests.

Results: Of 1276 patients, 859 (67%) underwent closed reduction internal fixation, 67 (5%) underwent total hip arthroplasty, and 350 (28%) underwent hemiarthroplasty. Of the total, 38 patients (3%) were diagnosed with postoperative infection. The demographics and co-morbidities were similar between the two study groups. The incident of infection was the highest among patients undergoing hemiarthroplasty (6%, P < 0.0001). Length of hospitalization (15 vs. 8 days, P = 0.0001) and operative time (117 vs. 77 minutes, P = 0.0001) were found to be the most significant risk factors for postoperative infection.

Conclusions: Predisposition to postoperative infections in PPF patients was associated with prolonged length of surgery and longer hospitalization. We recommend optimizing fast discharge, selecting the appropriate type of surgery, and improving surgical planning to reduce intraoperative delays and length of surgery.

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: Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for new-onset atrial fibrillation (AF) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, the optimal time frame to measure CRP for risk stratification is not known.

Objectives: To evaluate the relation between the change in CRP over time (CRP velocity [CRPv]) and new-onset AF among STEMI patients treated with primary PCI.

Methods: We included 801 STEMI patients who underwent PCI between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 hours after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements. Patient medical records were reviewed for occurrence of new-onset AF.

Results: New onset AF occurred in 45 patients (6%). Patients with new onset AF had significantly higher median CRPv (1.27 vs. 0.43 mg/l/h, P = 0.002). New-onset AF during hospitalization occurred in 3.4%, 4.5 %, and 9.1% of patients in the first, second and third CRPv tertiles, respectively (P for trend = 0.006). In a multivariable logistic regression, adjusting for clinical variables the odds ratios for new onset AF was 1.93 (95% confidence interval 1.0–3.59, P = 0.04) for patients in the third CRPv tertile.

Conclusion: CRPv might be an independent and rapidly measurable biomarker for new-onset AF following primary PCI in STEMI patients.