Israel Medical Association Journal

Background: Influenza and coronavirus disease 2019 (COVID-19) are respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged after it had been undetected since March 2020 and the Omicron variant replaced the Delta variant. Data directly comparing the two diseases are scarce.

Objectives: To compare the outcomes of patients with both the Omicron variant and influenza during 2021–2022.

Methods: We performed a retrospective study conducted in Beilinson hospital, Israel, from December 2021 to January 2022. We included all hospitalized patients with either laboratory-confirmed COVID-19 or influenza. The primary outcome was 30-day mortality.

Results: We identified 167 patients diagnosed with Omicron and 221 diagnosed with Influenza A. The median age was 71 years for Omicron and 65 years for influenza. Patients with Omicron had a significantly higher Charlson Comorbidity Index score (4 vs. 3, P < 0.001). Patients with Omicron developed more respiratory failure that needed mechanical ventilation (7% vs. 2%, P = 0.05) and vasopressors (14% vs. 2%, P < 0.001) than patients with influenza. In a multivariate model, 30-day mortality was lower in patients diagnosed with influenza than in patients diagnosed with Omicron (19/221 [9%] vs. 44/167 [26%], hazard ratio 0.45, 95% confidence interval 0.25–0.81).

Conclusions: Patients diagnosed with Omicron had higher mortality than patients diagnosed with seasonal influenza. This finding could be due to differences in co-morbidities, the virus pathogenicity, and host responses to infection.

Background: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many patients presented with acute hypoxemic respiratory failure, requiring ventilatory support. One treatment method was the addition of a reservoir mask to a high flow nasal cannula (HFNC) (dual oxygenation).

Objectives: To evaluate the clinical outcomes of combining reservoir mask on top of a high-flow nasal cannula.

Methods: A retrospective cohort of adult patients who were admitted due to COVID-19 during the first year of the pandemic to Rambam Health Care Campus. The primary endpoint was 30-day mortality. Secondary endpoints were incidence of invasive positive pressure ventilation initiation and admission to the intensive care unit (ICU). Patients who received positive pressure ventilation for reasons other than hypoxemic respiratory failure or who were transferred to another facility while still on HFNC were excluded.

Results: The final analysis included 333 patients; 166 were treated with dual oxygenation and 167 with HFNC only (controls). No significant differences in baseline characteristics were noted between the groups. The dual oxygenation group was slightly older (69.2 ± 14.8 years vs. 65.6 ± 15.5 years, P = 0.034). The 30-day mortality (24.1% vs. 36.5%, P = 0.013), rates of invasive positive pressure ventilation (47% vs. 59.3%, P = 0.024), and ICU admissions (41.6% vs. 52.7%, P = 0.042) were all significantly lower in the dual oxygenation group.

Conclusions: The addition of reservoir masks to HFNC may improve the oxygenation and overall prognosis in patients with severe hypoxemia due to COVID-19.

Background: Polymyositis (PM) and dermatomyositis (DM) are inflammatory mediated myopathies characterized by progressive symmetric proximal muscle weakness and associated with extra-muscular involvement. Central nervous system complications are rarely reported with these diseases.

Objectives: To investigate the association between dementia and PM/DM.

Methods: A retrospective cohort study was conducted using a database from Clalit Health Care, the largest health maintenance organization in Israel. Patients with a first recorded diagnosis of PM/DM were included and were compared with age- and sex-matched controls by a ratio of 1:5. The prevalence of dementia among PM/DM patients compared to controls was assessed using a univariate and a multivariable model. Binary logistic regression analysis was conducted to assess the association of different factors with dementia within the PM/DM cohort.

Results: The study included 2085 PM/DM cases (17.0%) and 10,193 age- and sex-matched controls (83.0%). During the follow-up time, 36 PM/DM patients were diagnosed with dementia compared to 160 controls, with a univariate hazard ratio (HR) of 1.10 (95% confidence interval [95%CI] 0.77–1.58). Within the PM/DM cohort, significant predictors for the development of dementia included increased age at diagnosis (5 years increment; OR 1.86, 95%CI 1.57–2.21, P < 0.001) and treatment with glucocorticoids (OR 5.40, 95%CI 1.67–17.67, P = 0.005).

Conclusions: In our cohort, inflammatory myopathies were not associated with dementia. Age and treatment with glucocorticoids were associated with dementia. If dementia is diagnosed in patients with inflammatory myopathies, other systemic causes should be investigated.

Background: In Israel, breast cancer prevalence is lower among Arab than Jewish women, but incidence is increasing among Arab women at a younger age.

Objectives: To explore differences between Arab and Jewish women with breast cancer with respect to age at diagnosis, associated risk factors, and use of hormonal medications.

Methods: We conducted a retrospective database study comparing Arab and Jewish women with breast cancer focusing on age at diagnosis, smoking history, obesity, and previous hormonal medication usage, including oral combined contraceptive pills (OCCP), progestogens, hormonal medications for treatment of infertility, and hormone replacement therapy (HRT).

Results: The study included 2494 women who were diagnosed with breast cancer during 2004–2015. Age at diagnosis was lower among Arab women (50.7 ± 13.1 years vs. 55.4 ± 12.6 years, P < 0.0001). The rate of smoking was higher among Jewish women (16.0% vs. 4.3%, P < 0.0001). The rate of obesity was higher in Arab women older than 50 years at diagnosis (59.0% vs. 42.4%, P < 0.0001). Arab women demonstrated a lower overall chance of previous use of all types of hormonal medications (odds ratio [OR] 0.6, 95% confidence interval [95%CI] 0.6–0.8) compared to Jewish women. Arab women were more likely to have used progestogens (OR 1.7, 95%CI 1.4–2.2) and medications for treatment of infertility (OR 2.3, 95%CI 1.5–3.4) and less likely OCCP (OR 0.4, 95%CI 0.3–0.6) and HRT (OR 0.4, 95%CI 0.3–0.5).

Conclusions: Previous use of hormonal medications may contribute to incidence of breast cancer in Arab women.

Background: Infants younger than 6 months of age are not eligible for coronavirus disease 2019 (COVID-19) vaccinations. Maternal variables during pregnancy and the postnatal period may affect the clinical and laboratory course of COVID-19 positive infants.

Objective: To assess the clinical manifestation and laboratory differences in infants with three maternal variables: breastfeeding, vaccinated, and co-illness.

Methods: We conducted a single-center retrospective cohort study of positive COVID-19 infants with three subgroups of maternal variables. The population included infants under 6 months of age hospitalized due to COVID-19. Data about clinical features, laboratory tests, and maternal information including vaccination status, breastfeeding status and maternal positive COVID-19 infection was gathered. All variables were compared among the three subgroups.

Results: Breastfed infants had shorter hospitalization period (mean 2.61 ± 1.378 days) compared to non-breastfed infants (mean 3.8 ± 1.549) (P = 0.051). COVID-19 infants of positive COVID-19 mothers had a higher absolute neutrophil count (mean 4.4 ± 3.8) compared to infants of COVID-19 negative mothers (mean 2.7 ± 2.4) (P = 0.042).

Conclusion: Breastfeeding was associated with shorter periods of hospitalization in COVID-19 positive infants. In addition, positive COVID-19 infants of mothers who were positive for COVID-19 are likely to have a higher absolute neutrophils count.

Background: Treatment of gestational diabetes mellitus (GDM) has been shown to improve both maternal and neonatal outcomes. For women with GDM who require glucose-lowering medication, insulin is regarded as the drug of choice by most medical societies. Oral therapy, with metformin or glibenclamide, is a reasonable alternative in certain medical circumstances.

Objectives: To compare the efficacy and safety of insulin detemir (IDet) vs. glibenclamide for GDM when glycemic control cannot be achieved through lifestyle modification and diet.

Methods: We conducted a retrospective cohort analysis of 115 women with singleton pregnancy and GDM treated with IDet or glibenclamide. GDM was diagnosed via the two-step oral glucose tolerance test (OGTT) of 50 grams glucose, followed by 100 grams. Maternal characteristics and outcomes (preeclampsia and weight gain) and neonatal outcomes (birth weight and percentile, hypoglycemia, jaundice, and respiratory morbidity) were compared between groups.

Results: In total, 67 women received IDet and 48 glibenclamide. Maternal characteristics, weight gain, and the incidence of preeclampsia were similar in both groups. Neonatal outcomes were also similar. The proportion of large for gestational age (LGA) infants was 20.8% in the glibenclamide group compared to 14.9% in the IDet group (P = 0.04).

Conclusions: In pregnant women with GDM, glucose control on IDet yielded comparable results as on glibenclamide, except for a significantly lower rate of LGA neonates.

Background: Uterine tachysystole during labor can lead to a decrease in fetal oxygen saturation and intracerebral oxygen saturation. Acute tocolysis using atosiban can inhibit uterine smooth muscle activity, potentially improving fetal status and facilitating vaginal delivery or allowing time to prepare for operative delivery.

Objectives: To compare maternal and neonatal outcomes in cesarean and vaginal deliveries following atosiban administration during fetal prolonged deceleration and tachysystole at gestational age 37 0/7 to 43 0/7 weeks.

Methods: We conducted a single-center, descriptive retrospective cohort study at a large tertiary referral center.

Results: Of the 275 patients treated with atosiban, 186 (68%) delivered vaginally (either spontaneous delivery or instrumental delivery) and 89 (32%) underwent a cesarean delivery. In a univariate analysis, cesarean delivery was associated with higher body mass index (27.9 ± 4.3 vs. 30.2 ± 4.8, P = 0.003). Second stage atosiban administration was associated with vaginal delivery (89.3% vs. 10.7%, P = 0.01). Cesarean delivery was associated with lower Apgar at 1 and 5 minutes and a higher rate of neonatal intensive care unit admissions. The incidence of PPH among women treated with atosiban in our study (2.3–4.3%) was higher than the incidence reported in the literature (1–3%)  

Conclusions: Atosiban may be an effective acute intervention for non-reassuring fetal heart rate during tachysystole, increasing the rate of vaginal delivery and potentially reducing the need for cesarean delivery. However, the potential risk of postpartum hemorrhage should be taken into consideration.

Background: Thiamine is an essential co-factor for aerobic intracellular respiration, nerve conduction, and muscle contraction. Thiamine deficiency is common in the intensive care unit (ICU). Delirium is a frequent unwanted symptom among critical ill patients. Although the exact cause of ICU-associated delirium is unknown, abnormal nutrition and thiamine deficiency may contribute to the etiology.

Objectives: To compare the prevalence of delirium among ICU patients who received thiamine with those who did not and to compare morbidity and mortality.

Methods: A retrospective study was conducted among ICU patients admitted 2014–2018. Routine thiamine administration began in 2016. Collected data included patient demographics, medical history, indication for ICU admission, hospital admission times, ventilation days, inotropic therapy, hemodialysis, tracheostomy, 28-day mortality, and need for anti-psychotic therapy. Group A received thiamine, group B did not. All data were statistically analyzed according to type.

Results: The study included 930 patients: 465 patients in group A and 465 in group B. At admission and throughout the hospitalization severity of disease parameters was worse in group A compared to group B, including acute physiology and chronic health evaluation (APACHE) score, admission lactate level, ventilation days, inotropic support, renal replacement therapy, tracheostomy, and ICU hospitalization. Group A had fewer delirium events without difference of maximal delirium score. No difference in mortality rate was observed.

Conclusions: Thiamine administration was associated with lower delirium prevalence despite longer ICU admission times and higher disease severity parameters at admission and during ICU stay.

Background: Polyp detection rate (PDR) is a convenient quality measure indicator. Many factors influence PDR, including the patient's background, age, referral (ambulatory or hospitalized), and bowel cleansing.

Objectives: To evaluate whether years of professional experience have any effect on PDR.

Methods: A multivariate analysis of a retrospective cohort was performed, where both patient- and examiner-related variables, including the experience of doctors and nurses, were evaluated. PDR, as the dependent variable was calculated separately for all (APDR), proximal (PPDR), and small (SPDR) polyps.

Results: Between 1998 and 2019, 20,996 patients underwent colonoscopy at a single center. After controlling for covariates, the experience of both doctors and nurses was not found to be associated with APDR (odds ratio [OR] 0.99, 95% confidence interval [95%CI] 0.98–1.00, P = 0.15 and OR 1.03, 95%CI 1.02–1.04, P < 0.0001, respectively). However, after 2.4 years of colonoscopy experience for doctors, and 9.5 years of experience for nurses, a significant increase in APDR was observed. Furthermore, results revealed no association for PPDR and SPDR, as well.

Conclusions: Years of colonoscopy experience for both doctors and assisting nurses were not associated with APDR, PPDR, and SPDR. In doctors with 2.4 years of experience and nurses with 9.5 years of experience, a significant increase in APDR was observed.

Background: School closures due to the coronavirus disease 2019 (COVID-19) outbreak affected students physically, socially, and psychologically with an increase in the number of children and adolescent presenting with anxiety, depression, and drug abuse.

Objectives: To examine the impact of COVID-19 and lockdown on the mental health of minors during the pandemic period and to characterize the type and number of referrals to a regional psychiatric outpatient clinic.

Methods: This study included 380 children evaluated in an outpatient child psychiatric clinic. They were divided into two groups: before the lockdowns (BLD) (n=248), from January 2019 to February 2020, and during the lockdowns (LD) (n=132), from March 2020 to April 2021.

Results: When comparing the LD to BLD, there was increase in suicide attempts (9.8% vs. 2.8%) and in the use of psychotherapy (81% vs. 56%). There was a decrease in the diagnoses of behavior disorders (29.5% vs. 44.8%) and ADHD (29.5% vs. 50%); as well as a decrease in stimulant usage (22.7% vs. 38%). There was a statistically non-significant increase in the number of children with depression, anxiety, and drug-use disorder.

Conclusions: Many children developed educational, social, emotional, and behavioral gaps during LD, and they lost skills to deal with everyday problems due to social isolation. It is important to follow the long-term impact of the lockdowns and social isolation.

Background: Acute mesenteric ischemia (AMI) is a medical condition with high levels of morbidity and mortality. However, most patients suspected of AMI will eventually have a different diagnosis. Nevertheless, these patients have a high risk for co-morbidities.

Objectives: To analyze patients with suspected AMI with an alternative final diagnosis, and to evaluate a machine learning algorithm for prognosis prediction in this population.

Methods: In a retrospective search, we retrieved patient charts of those who underwent computed tomography angiography (CTA) for suspected AMI between January 2012 and December 2015. Non-AMI patients were defined as patients with negative CTA and a final clinical diagnosis other than AMI. Correlation of past medical history, laboratory values, and mortality rates were evaluated. We evaluated gradient boosting (XGBoost) model for mortality prediction.

Results: The non-AMI group comprised 325 patients. The two most common groups of diseases included gastrointestinal (33%) and biliary-pancreatic diseases (27%). Mortality rate was 24.6% for the entire cohort. Medical history of chronic kidney disease (CKD) had higher risk for mortality (odds ratio 2.2). Laboratory studies revealed that lactate dehydrogenase (LDH) had the highest diagnostic ability for predicting mortality in the entire cohort (AUC 0.70). The gradient boosting model showed an area under the curve of 0.82 for predicting mortality.

Conclusions: Patients with suspected AMI with an alternative final diagnosis showed a 25% mortality rate. A past medical history of CKD and elevated LDH were associated with increased mortality. Non-linear machine learning algorithms can augment single variable inputs for predicting mortality.

Background: Antibiotic resistance is a worldwide problem associated with increased morbidity and mortality.

Objectives: To evaluate multidrug resistant (MDR) bacteria carriage in selected populations.

Methods: Data were collected from all patients under 18 years who met our internal guidelines from 2015–2016. They were screened for carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-actamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Indications for screening were non-resident non-Israeli patients (from the Palestinian Authority, Syria, and foreign patients), internal transfers from intensive care units, admission to high-risk departments, recent carriage of MDR bacteria, transfer from other hospitals, and recent hospitalization. Data were analyzed for MDR bacteria from at least one screening site (rectal, nasal, axillary, groin, throat). All data were analyzed per patient and per sample.

Results: During the study period 185/2632 positive screening sets (7%) were obtained from 725 patients. Of these, 165 patients (22.7%) were positive for at least one pathogen. Significantly fewer Israeli residents (120/615, 19.5%) tested positive compared to non-Israeli residents (45/110, 40.9%; P < 0.001). Past MDR bacteria carriage was the only significant screening indication (25/61, 41%; P < 0.001). CRE, VRE, MRSA, and ESBL prevalence rates were 0.6% (5/771), 0.5% (3/560) 0.5%, 4.2% (37/888), and 33.7% (139/413), respectively. Among non-ESBL carriers, MRSA was predominant with 38 positive cultures (n=34).

Conclusions: Non-Israeli non-residents and patients with previous positive MDR screening are at higher risk for MDR bacteria. Indications used to identify high-risk patients for drug resistant pathogens were efficacious. More effort is needed to reduce excessive sampling.

Background: Data regarding risk factors for superficial thrombophlebitis (STP) cases presenting to a hospital is limited.

Objectives: To investigate and stratify clinical and laboratory risk factors for STP

Methods: We conducted a retrospective case control study comparing patients presenting to the emergency department with STP and age- and gender-matched controls. We collected data on multiple risk factors and five blood indices.

Results: The study comprised 151 patients and matched controls. Patients with STP were more likely to have varicose veins (43.7% vs. 5.3%, P < 0.001), recent immobilization (14.6% vs. 1.3%, P < 0.001), obesity (36.4% vs. 18.5%, P = 0.001), a history of venous thromboembolism (VTE) or STP (27.2% vs. 0.7%, P < 0.001), and inherited thrombophilia (9.3% vs. 1.3%, P = 0.002). Following multivariate analysis, all five risk factors remained significant, with a history of VTE or STP associated with the largest risk (odds ratio [OR] 35.7), followed by immobilization (OR 22.3), varicose veins (OR 12.1), inherited thrombophilia (OR 6.1), and obesity (OR 2.7). Mean platelet volume was higher (8.5 vs 7.9 fl, P = 0.003) in STP cases.

Conclusions: A history of VTE or STP, immobilization, varicose veins, inherited thrombophilia, and obesity serve as independent clinical risk factors for STP presenting to hospital.

Background: Patients with systemic sclerosis (SSc) are at increased risk for autoimmune thyroid diseases, but information regarding thyroid nodules and cancer in SSc is scarce.

Objectives: To evaluate the thyroid gland in patients with SSc at a single Israeli center.

Methods: Thyroid workup was conducted in consecutive SSc patients: thyroid-stimulating hormone (TSH), free thyroxine (fT4), anti-thyroid peroxidase, and anti-thyroglobulin antibodies, as well as thyroid ultrasound and fine needle aspiration (FNA) when appropriate.

Results: Fifty patients, mean age 51.3 ± 13.5 years (44 women) were evaluated. Ten were previously diagnosed with thyroid disease. Median TSH level was 2.0 (normal range 0.23–4 mIU/l) and median fT4 level was 1.0 (normal range 0.8–2.0 ng/dL). Among the 40 thyroid disorder-naive patients, 3 had subclinical hypothyroidism and 5 had positive anti-thyroid antibodies; 22 (44%) had 1–6 thyroid nodules, which were ≥ 1 cm in 12 (24%). Accordingly, six patients underwent FNA, and five were diagnosed as colloid nodules and one as papillary carcinoma.

Conclusions: New cases of clinically significant autoimmune thyroid disease were not detected in our cohort of patients with SSc. Nevertheless, almost half had thyroid nodules. The clinical significance of these findings and their relation to thyroid cancer remains to be determined.

Intravesicular administration of Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has long been used as adjuvant therapy for treatment of non-muscle invasive bladder carcinoma. BCG is usually well tolerated; however, infectious complications can range from 1–5% of cases. Infectious complications of BCG [1] can be divided into localized disease, which is considered a late onset disease occurring 3 months following treatment such as cystitis, Epididymo-orchitis, and pyelonephritis. Another form is a systemic disease, which is an early onset manifestation including sepsis syndrome that usually occurs directly after treatment and is the most common form of disseminated BCG infection.