Israel Medical Association Journal

Background: There has been a rapid increase in vulnerable subpopulations of very old with co-morbidity, dementia, frailty, and limited life expectancy. Being treated by many specialists has led to an epidemic of inappropriate medication use and polypharmacy (IMUP) with negative medical and economic consequences. For most medications there are no evidence-based studies in older people and treatments are based on guidelines proven in much younger/healthier populations.

Objectives: To evaluate whether the benefits of reducing IMUP by poly-de-prescribing (PDP) outweighs the negative outcomes in older people with polypharmacy.

Methods: The Garfinkel method and algorithm were used in older people with polypharmacy (≥ 6 prescription drugs).

Results: We found that in nursing departments, of 331 drugs de-prescribed only 32 (10%) had to be re-administered. Annual mortality and severe complications requiring referral to acute care facility were significantly reduced in PDP (P < 0.002). In community dwelling older people, successful de-prescribing was achieved in 81% with no increase in adverse events or deaths. Those who de-prescribed ≥ 3 prescription drugs showed significantly more improvement in functional and cognitive status, sleep quality, appetite, serious complications, quality of life, and general satisfaction compared to controls who stopped ≤ 2 medications (P < 0.002). Rates of hospitalization and mortality were comparable. Clinical improvement by polydeprescribing was usually evident within 3 months and persisted for several years. The main barrier to polydeprescribing was physician’s unwillingness to deprescribe (P < 0.0001)

Conclusions: Applying the Garfinkel method of PDP may improve the lives of older people and save money.

Cannabis and cannabinoids have been known for thousands of years for their promising potential as analgesics. Chronic pain is a common complaint among many patients with rheumatic conditions. These disorders have revisited the medical approach toward cannabis and its potential role in pain relief. In addition, in recent years, information has mounted about the immunomodulatory effects of cannabis. In this review we discuss findings on the benefits cannabis may have in rheumatic and autoimmune disorders.

Background: Data on how the coronavirus disease 2019 (COVID-19) affected consultations in ophthalmic departments are sparse.

Objectives: To examine the epidemiology of ophthalmic consultations in a large pediatric emergency medicine department (PED) during the first nationwide COVID-19 lockdown in Israel.

Methods: The database of a tertiary pediatric medical center was retrospectively reviewed for patients aged < 18 years who attended the PED from 17 March to 30 April 2020 (first COVID-19 lockdown) and the corresponding period in 2019. Background, clinical, and disease-related data were collected from the medical charts and compared between groups.

Results: The study included 757 PED visits. There were no significant differences in demographics between the groups. The 2020 period was characterized by a decrease in PED visits (by 52%), increase in arrivals during late afternoon and evening (P = 0.013), decrease in visits of older children (age 5–10 year), and proportional increase in younger children (age 1–5 years) (P = 0.011). The most common diagnoses overall and during each period was trauma followed by conjunctivitis and eyelid inflammation. The mechanisms of trauma differed (P = 0.002), with an increase in sharp trauma and decrease in blunt trauma in 2020 (P < 0.001 for both). In 2020, 95% of traumatic events occurred in the home compared to 54% in 2019 (P < 0.001).

Conclusions: Parents need to learn appropriate preventive and treatment measures to prevent serious and long-term ophthalmic injury while minimizing their exposure to the COVID-19. PEDs and ophthalmic pediatric clinics should consider increasing use of telemedicine and the availability of more senior physicians as consultants during such times.

Background: The reduced immune response of maintenance hemodialysis patients to coronavirus disease 2019 (COVID-19) vaccines is a major concern.

Objectives: To analyze the late (6 months after full vaccination) antibody response and compare it to early post-vaccination titer.

Methods: We conducted a multicenter prospective study of 13 hemodialysis units in Israel.

Results: We demonstrated that the low titers observed among ESRD patients 2–3 months after vaccination with the Comirnaty vaccine (median 63.8 AU/ml) declined to critically lower values 6 months after full vaccination. (Mediananti S antibodies, 31 AU/ml). Seropositivity significantly declined among hemodialysis patients from 89% to 74% (P < 0.0001), although it did not significantly change among controls.

Conclusions: We recommend all patients on hemodialysis receive a booster COVID-19 vaccine 6 months after the second dose.

Background: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently used method for obtaining tissue samples for the diagnosis of various respiratory conditions, including lung cancer staging. In most cases, EBUS-TBNA is performed under moderate sedation (MS). However, in cases of respiratory compromised patients, if this procedure is performed, it is conducted under general anesthesia (GA).

Objective: To assess the diagnostic yield of EBUS-TBNA among respiratory compromised patients.

Methods: Data of consecutive patients (n=191) who underwent EBUS-TBNA at our medical center between January 2019 and December 2019 were retrospectively analyzed. Respiratory compromised patients underwent GA and patients without respiratory compromise were mostly moderately sedated (MS). Characteristics, diagnostic yield, and complication rates were compared.

Results: Diagnostic yield was similar between the two sedation modes (89% in GA group and 78% in the MS group, P = 0.11). The number of total samples obtained per procedure was significantly higher in the GA vs. the MS group (4.1 ± 2.1 vs. 2.1 ± 1.33, P < 0.01). The overall complication rate was 13% and 20.9% in the GA vs. the MS groups, respectively (P = 0.14), with the most frequent complication being minor bleeding. Interestingly, while the number of brushings, bronchoalveolar lavage, and endobronchial biopsy were similar, the percent of subjects who underwent transbronchial biopsy was significantly higher in the GA group (49% vs. 24.2%, P < 0.01).

Conclusion: EBUS-TBNA performed under GA among respiratory compromised patients is safe and has similar diagnostic yield to that of patients without a respiratory compromise

Background: Patients with juvenile myoclonic epilepsy (JME) are especially prone to having antiseizure medications (ASMs) withdrawal seizures (WS).

Objectives: To clarify whether WS in JME patients are caused by a high tendency of non-adherence from seizure-free patients or by a constitutive increased sensitivity to drug withdrawal.

Methods: Epilepsy patients followed in a tertiary epilepsy clinic between 2010 and 2013 were included in the study. WS prevalence was compared between drug-responsive and drug-resistant JME patients and patients with other types of epilepsy.

Results: The study included 23 JME patients (16 drug-responsive and 7 drug-resistant) and 138 patients with other epilepsies (74 drug-responsive and 64 drug-resistant). JME patients were younger and included more women than non-JME patients. Significantly more WS were seen in JME than in non-JME patients (P = 0.01) and in the drug-resistant fraction of JME patients in comparison to drug-resistant non-JME patients (P = 0.02). On logistic regression, the type of epilepsy, but not the patient’s sex, was found to significantly predict WS. No significant difference was found in the prevalence of WS between drug-responsive and drug-resistant JME patients. The main ASM discontinued in JME was valproic acid (VPA), especially in women.

Conclusion: Our findings suggest a higher sensitivity of JME patients to withdrawal of medications. It is important to educate JME patients about treatment adherence and to explain to their physicians how to carefully reduce or replace ASMs to mitigate the morbidity and mortality related to ASM withdrawal

Background: The CHA₂DS₂-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF).

Objectives: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA₂DS₂-VASc score in SR.

Methods: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA.

Results: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA₂DS₂-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA₂DS₂-VASc group (45, interquartile ratio [IQR] 36–49) vs. 37 (IQR 28–46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7–9.3) vs. 1.6 (IQR 0.78–5.4), P < 0.001; NLR 2.7 (IQR 2.1–3.8) vs. 2.1 (IQR 1.6–2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups.

Conclusions: Patients in SR with high CHA₂DS₂-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA₂DS₂-VASc score.

Background: In response to the coronavirus disease-2019 (COVID-19) pandemic, routine clinical visits to the ophthalmic emergency department (OED) were deferred, while emergency cases continued to be seen.

Objectives: To assess the consequences of the COVID-19 pandemic for ophthalmic emergencies.

Methods: A retrospective chart analysis of patients who presented to the OED during the peak of the COVID-19 pandemic was conducted. The proportions of traumatic, non-traumatic-urgent, and non-traumatic-non-urgent presentations in 2020 were compared to those of the same time period in 2019. Duration of chief complains and best-corrected visual acuity were also assessed.

Results: There were 144 OED visits in 2020 compared to 327 OED visits during the same 3-week-period in 2019. Lower mean age of OED patients was present in 2020. Logarithmic expression (LogMAR) best corrected visual acuity (BVCA) was similar in both years. In 2020 there was a reduction in traumatic, non-traumatic-urgent, and non-traumatic-non-urgent cases compared to 2019 (15.4% reduction, P = 0.038; 57.6% reduction, P = 0.002; 74.6% reduction, P = 0.005, respectively). There was a higher proportion of same-day presentations at commencement of symptoms in 2020 compared with 2019 (52.8% vs. 38.8%, respectively P = 0.006).

Conclusions: During the COVID-19 pandemic, the number of OED visits at a tertiary hospital dropped by more than half. Although the drop in visits was mostly due to decrease in non-traumatic-non-urgent cases, there was also decrease in non-traumatic-urgent presentations with possible important visual consequences. Additional studies should elucidate what happened to these patients

Background: Endocardial leads of permanent pacemakers (PPM) and implantable defibrillators (ICD) across the tricuspid valve (TV) can lead to tricuspid regurgitation (TR) or can worsen existing TR with subsequent severe morbidity and mortality.

Objectives: To evaluate prospectively the efficacy of intraprocedural 2-dimentional-transthoracic echocardiography (2DTTE) in reducing/preventing lead-associated TR.

Methods: We conducted a prospective randomized controlled study comparing echocardiographic results in patients undergoing de-novo PPM/ICD implantation with intraprocedural echo-guided right ventricular (RV) lead placement (Group 1, n=56) versus non-echo guided implantation (Group 2, n=55). Lead position was changed if TR grade was more than baseline in Group 1. Cohort patients underwent 2DTTE at baseline and 3 and/or 6 months after implantation. Excluded were patients with baseline TR > moderate or baseline ≥ moderate RV dysfunction.

Results: The study comprised 111 patients (74.14 ± 11 years of age, 58.6% male, 19% ICD, 42% active leads). In 98 patients there was at least one follow-up echo. Two patients from Group 1 (3.6%) needed intraprocedural RV electrode repositioning. Four patients (3.5%, 2 from each group, all dual chamber PPM, 3 atrial fibrillation, 2 RV pacing > 40%, none with intraprocedural reposition) had TR deterioration during 6 months follow-up. One patient from Group 2 with baseline mild-moderate aortic regurgitation (AR) had worsening TR and AR within 3 months and underwent aortic valve replacement and TV repair.

Conclusions: The rate of mechanically induced lead-associated TR is low; thus, a routine intraprocedural 2DTTE does not have a significant role in reducing/preventing it

Background: The extent and impact of obesity as an isolated risk factor for coronary artery disease is not clear since co-morbidities serve as confounders and may mask this association.

Objectives: To examine whether obesity is associated with extensive coronary artery disease among metabolically healthy patients presenting with ST-elevation myocardial infarction (STEMI) and to explore the outcomes according to body mass index (BMI).

Methods: We stratified STEMI patients who had a metabolically healthy phenotype and available weight and height data according to BMI: 18.5–25 kg/m² (lean), 25.01–30 kg/m² (overweight), and > 30 kg/m² (obese).

Results: Overall 381 patients were included, 42% lean, 41% overweight, and 17% obese. Patients with increased BMIs had higher levels of low-density proteins and triglycerides (P < 0.05). Obese patients presented with the lowest rates of multi-vessel disease (12.9% vs. 22.9% for overweight and 28% for lean). In a univariable analysis, obese patients were 60% less likely to be diagnosed with multi-vessel disease (odds ratio 0.4, 95% confidence interval 0.2–0.9, P = 0.021) compared to lean patients. The association remained significant in a multivariable model adjusted for baseline characteristics (P = 0.029). There were no differences in 30-day or long-term mortality (median follow-up 3.2 years) among the groups (P > 0.1 for all comparisons).

Conclusions: Metabolically healthy phenotype obesity was associated with lower rates of multi-vessel disease despite higher levels of triglycerides. However, this association did not translate into increased mortality.

Background: Lumbar spinal stenosis (LSS) is a narrowing of the lumbar canal causing lower back pain, gluteal pain, and neurogenic claudication. LSS has been associated with cardiovascular co-morbidities. Metabolic syndrome (MetS), a pro-inflammatory condition involving a cluster of risk factors for cardiovascular disease and diabetes, is increasingly prevalent worldwide.

Objectives: To evaluate the prevalence of MetS in patients with LSS, compared to age- and sex-matched healthy controls, and to explore potential associations between MetS and LSS-related clinical parameters and cardiovascular risk factors.

Methods: We conducted a cross-sectional study including 64 patients diagnosed as symptomatic LSS (NASS criteria) and 32 controls. MetS was diagnosed using the 2009 Harmonizing criteria adjusted for South Americans. Multivariate logistic regression was used to identify independent risk factors for MetS. The level of statistical significance was set at 5%.

Results: The prevalence of MetS was significantly higher in the LSS group than in the control group (76.6% vs. 31.3%; P < 0.001). LSS patients displayed greater waist circumference (P = 0.003), blood glucose levels (P = 0.009) and arterial pressure (P < 0.001) than controls. The variables with independent influence on MetS in the logistic regression model were: diabetes (P = 0.008), blood glucose (P = 0.004), and body mass index (P = 0.005).

Conclusions: MetS was significantly more prevalent among LSS patients, and diabetes and elevated body mass index were found to be risk factors for MetS in these LSS patients

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06–5.62; P = 0.036) for patients with moderate-severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: Mean platelet volume (MPV), an essential component of the complete blood count (CBC) indices, is underutilized in common practice. In recent years, MPV has drawn strong interest, especially in clinical research. During inflammation, the MPV has a higher value because of platelet activation.

Objectives: To verify whether high MPV values discovered incidentally in healthy naïve patients indicates the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes.

Methods: A cohort study was used to assess the diagnostic value of high MPV discovered incidentally, in naïve patients (without any known cause of an abnormal high MPV, greater than  upper limit of the normal range, such as active cardiovascular diseases and metabolic syndrome).

Results: The mean MPV value in the patient group was 12.3 femtoliter. There was a higher incidence of metabolic syndrome in our research group than in the general population and a non-significant tendency of pre-diabetes. Family doctors more frequently meet naïve patients with high MPV than a hospital doctor. The results of our study are more relevant for him, who should know the relevance of such a finding and search for a hidden pre-diabetes or metabolic syndrome.

Conclusions: High MPV values discovered incidentally in healthy naïve subjects suggest the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes. No statistically significant association was found between MPV and the presence of cardiovascular disease

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