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: A good physical exam is necessary to help pediatricians make the correct diagnosis and can save unnecessary imaging or invasive procedures. Distraction by medical clowns may create the optimal conditions for a proper physical examination.

Methods: Children aged 2–6 years who required physical examination in the pediatric emergency department were recruited and randomly assigned to one of two groups: physical exam by a pediatrician in the presence of caregivers vs. physical exam with the assistance of a medical clown. Outcome measures consisted of the level of child's discomfort, anxiety, and the quality of the physical examination.

Results: Ninety three children participated. Mean age was 3.3 ± 3.6 years (range 2–6). The duration of the physical exam was similar between the clown and control groups (4.6 ± 1.4 minutes vs. 4.5 ± 1.1 minutes (P = 0.64). The duration of discomfort was shorter in the clown group (0.2 ± 0.6 minutes) than the control group(1.6 ± 2.0 minutes, P = 0.001). In the medical clown group, 94% of pediatricians reported that the medical clown improved their ability to perform a complete physical examination. A trend of less hospitalization in the medical clown group was also noticed (11.3% in the medical clown group vs. 18.3% in the control group, P = 0.1); however, further study is required to verify this observation.

Conclusions: Integration of a medical clown in physical examination improves the overall experience of the child and the caregivers and helps the pediatrician to perform a complete physical examination.

Background: Magnetic resonance imaging (MRI), which has recently become the leading imaging modality in the study of ankylosing spondylitis (AS), has not been evaluated in the assessment of disease-specific changes at the craniocervical junction (CCJ) in patients with AS.

Objectives: To describe the spectrum of active inflammatory lesions at the CCJ using MRI in a cohort of patients with AS and neck pain.

Methods: The study included 18 patients with AS presenting with neck pain and a control group of 9 fibromyalgia patients matched for age and levels of neck pain. All patients underwent a focused rheumatologic examination, X-ray of the cervical spine, and a 3T MRI study, which included STIR, CUBE T2, FSE and FSE FAT SAT sequences before and after administration of gadolinium.

Results: The median age of AS patients was 43 years with a median disease duration of 7 years. Fifteen of 18 patients were under biologic treatment. Seven of 18 AS patients had evidence of cervical syndesmophytes on X-ray films. Active inflammatory lesions of atlanto-occipital joints and apical and alar ligaments were detected in MRIs in 2 out of the 18 patients with AS and in none of the patients with fibromyalgia. Both AS patients with active inflammation of CCJ detected on MRI received treatment with biological agents prior to and during the study.

Conclusions: Active inflammation of both entheses and joints of the CCJ can be demonstrated by MRI in patients with AS.

Background: Percutaneous dilatational tracheostomy (PDT) has become a standard technique for critically ill patients who require long-term ventilation. The most common early post-operative complication is bleeding related to anatomical variation in vasculature. The procedure is performed at the patient's bedside unless this is deemed unsafe and then the accepted alternative is open tracheostomy in the operating room. 

Objectives: To evaluate the use of pre-procedural ultrasound to aid in the decision of whether PDT in critical care patients should be performed at the patient's bedside or by open surgical tracheostomy.

Methods: Patients were jointly evaluated by a critical care physician and a head and neck surgeon. Based on this evaluation, the method of tracheostomy was determined. Subsequently, pre-procedural ultrasound examination of the anterior neck was performed. The final decision whether to perform PDT or open surgical tracheostomy was based on the ultrasound findings. Changes in management decisions following ultrasound were recorded. 

Results: We included 36 patients in this prospective study. Following ultrasound examination, the management decision was changed in nine patients (25%).

Conclusions: Pre-procedural ultrasound for critically ill patients undergoing tracheostomy can influence management decisions regarding the performance of tracheostomy. 

 

Background: During the past 6 years the Israel Defense Forces Medical Corps (IDF-MC) deployed three humanitarian delegation field hospitals (HDFHs) in disaster zones around the globe: Haiti (2010), the Philippines (2013), and Nepal (2015). 

Objectives: To compare the activity of these HDFHs and the characteristics of the patients they served.

Methods: This retrospective study was based on the HDFHs’ operation logs and patients medical records. The study population included both the staff who participated and the patients who were treated in any of the three HDFHs.

Results: The Philippine HDFH was a "hybrid" type, i.e., it was integrated with a local hospital. Both the Haitian and the Nepali HDFHs were the "stand-alone" type, i.e., were completely autonomic in resources and in function. The Nepali HDFH had a larger staff, departed from Israel 4 hours earlier and was active 7 hours earlier as compared to the Haitian one. In total, 5465 patients, 55% of them female, were treated in the three HDFHs. In Haiti, Nepal and the Philippines, disaster-related injuries accounted for 66%, 26% and 2% of the cases, respectively. Disaster-related injuries presented mainly in the first days of the HDFHs' activity.

Conclusions: The next HDFH should be planned to care for a significant proportion of routine medical illnesses. The IDF-MC continuous learning process will enable future HDFHs to save more lives as we "extend a helping hand" to foreign populations in crisis. 

 

Background: Resective epilepsy surgery is an accepted treatment option for patients with drug-resistant epilepsy (DRE). Presurgical evaluation consists of a phase 1 non-invasive evaluation and a phase 2 invasive evaluation, when necessary.

Objectives: To assess the results of phase 1 evaluation in patients with focal DRE.

Methods: This observational retrospective study was performed in all consecutive DRE patients admitted to our clinic from January 2001 to July 2010, and who underwent a presurgical evaluation which included at least magnetic resonance imaging (MRI) scan and long-term video EEG monitoring (LTVEM).

Results: A total of 253 consecutive patients with a diagnosis of DRE (according to the ILAE recommendations) who underwent presurgical evaluation were extracted from our clinic and department registry. In 45 of these patients either imaging or ictal video EEG data were missing; the final analysis therefore involved 208 patients. The combined result of the LTVEM and the MRI scan were as follows: 102 patients (49% of the cohort) had a lesion on the MRI scan, in 77 patients (37% of the cohort) the LTVEM results were localizing and congruent with the MRI findings, and in 25 patients (12% of the cohort) the LTVEM results were either non-localizing or incongruent with the MRI findings. In 106 patients (51% of the cohort) the MRI scan was normal or had a non-specific lesion. The LTVEM was localizing in 66 of these patients (31.7% of the cohort) and non-localizing in 40 (19.2% of the cohort).

Conclusions: Although some of the patients with focal DRE can be safely treated with resective surgery based solely on the findings of phase 1 evaluation, a substantial percent of patients do need to undergo a phase 2 evaluation before a final surgical decision is made.

 

Background: Atherosclerosis is a systemic disease. Nevertheless, the role of specific biomarkers as indicators for both coronary and carotid diseases is debatable.

Objectives: To evaluate the association of biomarkers with coronary and carotid disease.

Methods: We studied 522 consecutive patients with stable angina. All underwent coronary angiography and carotid duplex study on the same day. Patients with no apparent carotid plaques were evaluated for carotid intima-media thickness (CIMT) using an automated system that sampled over 100 samples in each carotid artery. Biochemical markers of cardiovascular disease risk were obtained at the time of coronary angiography, including serum lipid levels, hemoglobin A1C (HbA1c), white blood cell count, fibrinogen and high sensitivity C-reactive protein (hs-CRP).

Results: The mean age of the patients was 66 ± 11; 73% were males. Significant carotid stenosis was associated with higher hs-CRP (9.4 ± 17 vs. 6.3 ± 13 mg/L, P = 0.001), while high HbA1c (6.7 ± 1.6 vs. 5.8 ± 0.8%, P < 0.001) and low high density lipoprotein levels (40 ± 9 vs. 47 ± 14 mg/dl, P < 0.001) were linked with advanced coronary artery disease severity. In contrast, CIMT was not related to any of the biomarkers evaluated.

Conclusions: Although atherosclerosis is considered a systemic disease, different biomarkers are associated with coronary and carotid artery disease. Identifying the specific biomarkers for each disease is important for both prevention and for exposing the underlying pathophysiologic mechanism.

 

Background: Anemia confers an adverse prognosis in patients with ST-elevation myocardial infarction (STEMI). Several mechanisms have been implicated in the etiology of anemia in this setting, including inflammation, blood loss, and the presence of comorbidities such as renal failure.

Objectives: To evaluate the adequacy of bone marrow response as potentially reflected by elevation in blood and reticulocyte counts.

Methods: Consecutive men with STEMI who underwent primary percutaneous intervention within 6 hours of symptom onset and who presented to our catheterization laboratory during a 36 month period were included in the study. The cohort was divided into quartiles according to hemoglobin concentration, and differences in clinical and laboratory characteristics between the groups were evaluated.

Results: A total of 258 men with STEMI were recruited, 22% of whom suffered from anemia according to the World Health Organization classification (hemoglobin < 13 g/dl). Men in the lowest quartile of hemoglobin concentration presented with significantly lower white blood cell and platelet counts (9.6 ± 2.9 vs. 12.6 ± 3.6 x103/µl, P < 0.001) and (231 ± 79 vs. 263 ± 8 x103/µl, P < 0.01), respectively, despite higher inflammatory biomarkers (C-reactive protein and fibrinogen) compared with patients in the upper hemoglobin concentration quartile. Reticulocyte production index was not significantly higher in anemic patients with a value of 1.8, 1.4, 1.5 and 1.6 in the ascending hemoglobin quartiles, respectively (P = 0.292). 

Conclusions: Anemic men with STEMI have relatively lower leukocyte and platelet counts as well as a reduced reticulocyte count despite higher inflammatory biomarkers. These findings might suggest inadequate bone marrow response. 

 

Abstract

During recent months, the Centers for Disease Control and Prevention (CDC) announced the occurrence of three major biosafety incidents, raising serious concern about biosafety and biosecurity guideline implementation in the most prestigious agencies in the United States: the CDC, the National Institutes of Health (NIH) and the Federal Drug Administration (FDA). These lapses included: a) the mishandling of Bacillus anthracis spores potentially exposing dozens of employees to anthrax; b) the shipment of low pathogenic influenza virus unknowingly cross-contaminated with a highly pathogenic strain; and c) an inventory lapse of hundreds of samples of biological agents, including six vials of variola virus kept in a cold storage room for decades, unnoticed. In this review we present the published data on these events, report the CDC inquiry’s main findings, and discuss the key lessons to be learnt to ensure safer scientific practice in biomedical and microbiological service and research laboratories.