Israel Medical Association Journal

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. 

 

Background: The practice of administering intravenous contrast to children varies by institution depending on their routine. 

Objectives: To assess the necessity of routine contrast administration in brain magnetic resonance imaging (MRI) of pediatric outpatients referred for chronic headache workups. 

Methods: We conducted a retrospective review of consecutive pediatric brain MRI examinations performed during January and February 2014 in 30 pediatric outpatients referred for evaluation of chronic headache. Independent review was performed by two board-certified neuroradiologists. The raters reviewed each MRI first as a non-contrast examination (without seeing the post-contrast images) and then with post-contrast images. 

Results: No abnormalities were found in six patients. One patient had an indeterminate finding of a tubular cerebellar lesion requiring follow-up. In the remaining patients (n=23), the findings were subclinical and included: mucosal thickening in the paranasal sinuses in 9 patients, cystic changes of the pineal gland in 8 (size 2–9 mm), small developmental venous anomalies in 6, non-specific FLAIR hyperintensities in 4, opacification of the mastoids in 2, and telangiectasia in 1 patient. The subclinical cases that were missed on pre-contrast images were: one small developmental venous anomaly, one telangiectasia and one small pineal cyst, none of which hold clinical significance. All kappa inter-rater and intra-rater agreement scores resulted in values above 0.75, excellent agreement according to Fleiss guidelines.

Conclusions: There seems to be little reason to medically justify large-scale use of routine IV contrast administration to evaluate a brain MRI of pediatric patients referred for chronic headache. 

 

Objectives: To characterize the clinical features and outcomes of body packers hospitalized at the Sheba Medical Center.

Methods: We conducted a retrospective case series of body packers hospitalized between January 2010 and October 2012 in our medical center. Electronic medical records and imaging files were reviewed to extract clinical, laboratory and radiological data as well as details on medical treatments.

Results: We identified 23 body packers (mean age 38 ± 10 years), 20 of whom smuggled cocaine from South America. The number of packets transported ranged from 1 to 242 (median 42) and duration of hospitalization from 1 to 14 days (median 2). Two subjects required surgical intervention. All others were treated conservatively by polyethylene glycol-electrolyte lavage solution, laxatives, or watchful waiting. Ten patients underwent a urinary screen for illicit drugs, 7 of whom tested positive for cocaine and 2 for cannabinoids. Abdominal X-rays were performed in all patients at admission, and 14 had follow-up imaging, including abdominal CT scans without contrast media in 8.

Conclusions: The main treatment goals for body packers are the rapid excretion of drug packets and early detection of complications, i.e., drug intoxication and bowel obstruction. We suggest the use of a structured treatment approach for the in-hospital management of body packers.

[1] MHC = mother and child health

Background: Infections with blood-borne viruses are a major health problem among illicit drug users. There is little information about infection rates and risk factors for hepatitis virus B, C or the human immunodeficiency virus in drug users in Israel.

Objectives: To determine the prevalence of HCV[1], HBV[2] and HIV[3] infections in a large cohort of drug users in Israel; to compare rates of HCV, HBV and HIV between injecting versus non-injecting drug users and between different origin countries; and to identify risk factors for HCV among illicit drug users.

Methods: We conducted a cross-sectional interviewer-administered questionnaire and serological screening for HCV, HBV and HIV in 1443 consecutive drug users diagnosed at the Israeli National Center for Diagnosis of Drug Addicts between January 2003 and December 2005.

Results: Fourteen (0.9%), 51 (3.5%) and 515 (35.7%) subjects tested positive for HIV, HBV and HCV, respectively. All three infections (HIV, HBV and HCV) were significantly more common among injecting drug users and immigrants from the former Soviet Union and other East European countries compared to native Israelis. Multivariate analysis showed that HCV infection was associated with age (> 40 years) (OR=2.06, 95% CI 1.40–3.03), immigration from East European countries and the former Soviet Union (OR=4.54, 95% CI 3.28–6.28), and injecting drug use (OR=16.44, 95% CI 10.79–25.05).

Conclusions: HIV, HBV and HCV prevalence among drug users in Israel is significantly lower than in North America and West Europe. Risk factors for HCV infection in this population include injecting drug use, older age, and immigration from the former Soviet Union.

Background: Interleukin-8 is a prototypical inflammatory chemokine that induces leukocyte migration to inflammatory sites. Leukocyte recruitment in response to gradients of this chemokine is attenuated at advanced stages of inflammation to prevent damage to surrounding healthy tissues. Our published studies suggest that over-phosphorylation of focal adhesion kinase in migration-desensitizing conditions is involved in cessation of cell motility. This over-phosphorylation of FAK[1] was induced by IL-8[2] only when the receptor transmitting the chemokine signals was CXCR2, and not CXCR1, indicating that the two IL-8 receptors diverge in their signaling properties.

Objectives: To analyze the regulation of FAK in CXCR2-expressing hematopoietic cells under conditions of migratory desensitization, focusing on the roles played by adhesion-related components in this process.

Methods: Under conditions of migratory desensitization, we determined IL-8-induced cell spreading and FAK localization following disruption of actin filaments, and evaluated the role of integrins in FAK phosphorylation.

Results: The disturbance of intact activity of actin filaments resulted in inhibition of cell spreading and modification of FAK intracellular localization upon IL-8 stimulation. Also, adhesion-dependent pre-stimulation of integrins was required for IL-8-induced FAK phosphorylation.
Conclusions: Intact actin filaments and integrins are required for optimal IL-8-induced FAK phosphorylation in conditions of migratory desensitization. These observations suggest that lack of adequate activity/regulation of adhesion-related components may give rise to FAK activities that are not appropriately controlled, possibly leading to pathological conditions that are associated with perturbed leukocyte migration phenotypes

Background: Oral anticoagulation with warfarin can lead to life-threatening events as a result of either over-anticoagulation or undertreatment. One of the main contributors to an undesirable warfarin effect is the need to adjust its daily dose for a specific patient. The dose is adjusted empirically based on the experience of the clinician, a method that is often imprecise. There is currently no other well-accepted method for predicting the maintenance dose of warfarin.

Objective: To describe the application of an artificial neural network to the problem of warfarin maintenance dose prediction.

Methods: We designed a neural network that predicts the maintenance dose of warfarin. Data on 148 patients attending a large anticoagulant clinic were collected by file review. Using correlational analysis of the patients' data we selected the best input variables. The network was trained by using the back-propagation algorithm on a subset of our data and the results were validated against the rest of the data. We used a multivariate linear regression to create a comparable model.

Results: The neural network generated reasonable predictions of the maintenance dose (r = 0.823). The results of the linear regression model were similar (r = 0.800).

Conclusion: Neural networks can be applied successfully for warfarin maintenance dose prediction. The results are promising, but further investigation is needed.