Israel Medical Association Journal

Background: Williams syndrome (WS) is a neurogenetic syndrome characterized by a variety of medical conditions and cognitive deficits along with distinct psychiatric and behavioral characteristics. To the best of our knowledge, no studies to date have comprehensively reported the prevalence of medical, cognitive deficits, and psychiatric disorders in one cohort of people with WS in one study.

Objectives: To detail the prevalence of the various clinical features of WS in a large nationwide Israeli cohort. To examine potential risk factors for attention deficit hyperactivity disorder (ADHD) in WS.

Methods: We investigated the effects of cardiovascular anomalies, intellectual quotient (IQ), and phonophobia (fear of sounds) on the likelihood of ADHD. The study included 80 participants with WS (mean age 7.76 years). Relevant medical information from medical records was obtained retrospectively. In addition, IQ testing and psychiatric assessments using structured tools were conducted. The association between ADHD and cardiovascular anomalies, IQ, and phonophobia was analyzed using a logistic regression.

Results: Supravalvular aortic stenosis and supravalvular pulmonary stenosis are the prevalent cardiovascular anomaly in WS. Phonophobia and ADHD are the most prevalent psychiatric diagnoses in people with WS. Phonophobia was significantly associated with the risk for ADHD in WS participants.

Conclusions: Our findings regarding the type and prevalence of medical, cognitive, and psychiatric characteristics in WS correspond to results in previous publications. We also showed a potential link between phonophobia and ADHD that merits further research.

Background: Increasing antibiotic resistance in the community results in greater use of empiric broad spectrum antibiotics for patients at hospital admission. As a measure of antibiotic stewardship it is important to identify a patient population that can receive narrow spectrum antibiotics.

Objectives: To evaluate resistance patterns of Escherichia coli bloodstream infection (BSI) from strictly community-acquired infection and the impact of recent antibiotic use on this resistance.

Methods: This single center, historical cohort study of adult patients with E. coli BSI was conducted from January 2007 to December 2011. Patients had no exposure to any healthcare facility and no chronic catheters or chronic ulcers. Data on antibiotic use during the previous 90 days was collected and relation to resistance patterns was assessed.

Results: Of the total number of patients, 267 BSI cases met the entry criteria; 153 patients (57%) had bacteria sensitive to all antibiotics. Among 189 patients with no antibiotic exposure, 61% of isolates (116) were pan-sensitive. Resistance to any antibiotic appeared in 114 patients and 12 were extended-spectrum beta-lactamase (ESBL) producers. Quinolone use was the main driver of resistance to any antibiotic and to ESBL resistance patterns. In a multivariate analysis, older age (odds ratio 1.1) and quinolone use (odds ratio 7) were independently correlated to ESBL.

Conclusions: At admission, stratification by patient characteristics and recent antibiotic use can help personalize primary empirical therapy.

Background: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE).

Objectives: To conduct the first nationwide survey focused on BrS patients with documented AE.

Methods: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2).

Results: The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13–84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30–53 years; 4/6 patients had familial history of sudden death age < 50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine.

Conclusions: CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.

Background: Recent studies have analyzed risk factors associated with complications after gastric cancer surgery using the Clavien-Dindo classification (CD). However, they have been based on Asian population cohorts (Chinese, Japanese, Korean).

Objectives: To prospectively analyze all post-gastrectomy complications according to severity using CD classification and identify postoperative risk factors and complications.

Methods: We analyzed all gastrectomies for gastric cancer performed 2009–2014. Recorded parameters included demographic data, existing co-morbidities, neo-adjuvant treatment, intra-operative findings, postoperative course, and histologic findings. Postoperative complications were graded using CD classification.

Results: The study comprised 112 patients who underwent gastrectomy. Mean age was 64.8 ± 12.8 years; 53 patients (47%) underwent gastrectomy, 37 (34%) total gastrectomy, and 22 (19%) total extended gastrectomy. All patients had D2 lymphadenectomy. The average number of retrieved lymph nodes was 35 ± 17. Severe complication rate (≥ IIIa) was 14% and mortality rate was 1.8%. In a univariate analysis, age > 65 years; ASA 3 or higher; chronic renal failure; multi-organ resection; and tumor, node, and metastases (TNM) stage ≥ IIIc were found to be significantly associated with CD complication grade > III (P = 0.01, P = 0.05, P = 0.04, P = 0.04, and P = 0.01, respectively). Multivariate regression analysis revealed advanced stage (≥ IIIc) and age > 65 years to be significant independent risk factors (P < 0.05).

Conclusions: Age > 65 and advanced stage (≥ IIIc) were the primary risk factors for complications of grade > III according to the CD classification following gastrectomy for gastric cancer.

Background: Acute musculoskeletal pain is one of the most commonly reported symptoms among patients visiting the emergency department (ED). Treatment with over-the-counter pain medications, given by nurses, results in improved pain management and reduces the waiting time to drug administration without significant side effects. Opioid analgesics are extensively used for acute pain in the ED. Compared to morphine, oxycodone has a much more specific pharmacological activity, higher analgesic potential, and more tolerable side effects.

Objectives: To assess the degree of pain reduction using different protocols, including dypirone and oxycodone given by nurses, in treating acute musculoskeletal pain in the emergency department (primary outcome) and to evaluate the need for rescue medications (secondary outcome).

Methods: This observational prospective clinical trial compared two groups of 50 patients, each one visiting the ED due to musculoskeletal pain. One group was treated with dipyrone syrup and the other was treated with oxycodone syrup. The primary outcome was pain reduction measured by the Numeric Rating Scale (NRS). The secondary outcome was the difference in need for rescue medications.

Results: The reduction in the NRS was greater in the patients treated with oxycodone. This finding was statistically and clinically significant (P < 0.001). The need for rescue medications was also significantly reduced in this group of patients (P = 0.007).

Conclusions: This study showed that the administration of over-the-counter oxycodone syrup by nurses decreases the post-treatment pain reported by patients, reduces the need for rescue medications, and increases the satisfaction of the medical staff.

Background: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules.

Objectives: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology.

Methods: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2–5, 6–10, and 11–15 telomeres, relative to the size of a single telomere.

Results: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group.

Conclusions: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.

Background: Gender-related differences (GRD) exist in the outcome of patients with cardiac resynchronization therapy (CRT).

Objectives: To assess GRD in patients who underwent CRT.

Methods: A retrospective cohort of 178 patients who were implanted with a CRT in a tertiary center 2005–2009 was analyzed. Primary outcome was 1 year mortality. Secondary endpoints were readmission and complication rates.

Results: No statistically significant difference was found in 1 year mortality rates (14.6% males vs. 11.8% females, P = 0.7) or in readmission rate (50.7% vs. 41.2%, P = 0.3). The complication rate was only numerically higher in women (14.7% vs. 5.6%, P = 0.09). Men more often had CRT-defibrillator (CRT-D) implants (63.2% vs. 35.3%, P = 0.003) and had a higher rate of ischemic cardiomyopathy (79.2% vs. 38.2%, P < 0.001). There was a trend to higher incidence of ventricular fibrillation/ventricular tachycardia in men before CRT implantation (29.9% vs. 14.7%, P = 0.07%). A higher proportion of men upgraded from implantable cardioverter defibrillator (ICD) to CRT-D, 20.8% vs. 8.8%, P = 0.047. On multivariate model, chronic renal failure was an independent predictor of 1 year mortality (hazard ratio [HR] 3.6; 95% confidence interval [95%CI] 1.4–9.5), CRT-D had a protective effect compared to CRT-pacemaker (HR 0.3, 95%CI 0.12–0.81).

Conclusions: No GRD was found in 1 year mortality or readmission rates in patients treated with CRT. There was a trend toward a higher complication rate in females. Men were implanted more often with CRT-D and more frequently underwent upgrading of ICD to CRT-D.

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.