Israel Medical Association Journal

Background: Tumor necrosis factor-alpha (TNFα) inhibitors are indicated for patients with psoriatic arthritis (PsA) in whom conventional disease-modifying anti-rheumatic drugs (DMARDs) are insufficient to achieve disease remission. 

Objectives: To determine the value of acute-phase reactant levels at diagnosis of psoriatic arthritis in predicting the need for biologic treatment with TNFα inhibitors.

Methods: We conducted a longitudinal observational study of an inception cohort of 71 consecutive patients diagnosed with psoriatic arthritis. C-reactive protein (CRP) was assayed for all patients at their first visit.

Results: All patients were treated with one or more DMARDs, mainly methotrexate (81.6%). Thirty-seven patients (52.11%) had an inadequate response and received at least one TNF inhibitor. CRP level at diagnosis was positively correlated with need for a TNF inhibitor (P = 0.009, HR 1.8, 95%CI 1.27–1.85). Patients with CRP > 0.9 mg/dl at diagnosis started biologic treatment significantly earlier than patients with a lower level (P = 0.003, HR 2.62, 95%CI 0.393–2.5).

Conclusions: In patients with psoriatic arthritis, CRP ≥ 0.9 mg/dl at diagnosis significantly predicts an earlier need for a TNF inhibitor to achieve disease control.

 

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: Enoxaparin is frequently used as prophylaxis for deep venous thrombosis in critically ill patients. 

Objectives: To evaluate three enoxaparin prophylactic regimens in critical care patients with and without administration of a vasopressor.

Methods: Patients admitted to intensive care units (general and post-cardiothoracic surgery) without renal failure received, once daily, a subcutaneous fixed dose of 40 mg enoxaparin, a subcutaneous dose of 0.5 mg/kg enoxaparin, or an intravenous dose of 0.5 mg/kg enoxaparin. Over 5 days anti-activated factor X levels were collected before the daily administration and 4 hours after the injection.

Results: Overall, 16 patients received the subcutaneous fixed dose, 15 received the subcutaneous weight-based dosage, and 8 received the dose intravenously. Around two-fifths (38%) of the patients received vasopressors. There was no difference between anti-activated factor X levels regarding vasopressor administration. However, in all three groups the levels were outside the recommended range of 0.1 IU/ml and 0.3 IU/ml.

Conclusions: Although not influenced by vasopressor administration, the enoxaparin regimens resulted in blood activity levels outside the recommended range.

 

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.

Abstract

Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

 

Background: Since 2006 more than 60,000 migrants arrived in Israel from the Horn of Africa (HoA: Sudan, Eritrea, Ethiopia). They were detained in prison and screened for tuberculosis (TB) by means of an interview and chest X-ray (CXR).

Objectives: To evaluate the yield of this screening process.

Methods: This cross-sectional study evaluated the validity of CXR in a random sample of 1087 of the 5335 HoA migrants (20.4%) who arrived in 2009, and assessed its related costs.

Results: Sixty-two migrants (5.7%) had CXRs with TB-suspicious findings, and 11 of them were finally diagnosed with TB (17.7% of all TB-suspicious CXRs). TB point-prevalence was 1000 cases per 100,000 migrants (1.0%). As no additional TB cases were diagnosed on arrival, CXR sensitivity, specificity and positive predictive value were 100%, 96.1% and 17.7%, respectively. The interview did not contribute to the detection of migrants with TB. Direct costs related to the detection of single TB cases in prison was 17,970 shekels (US$ 4585), lower than the treating cost of 28,745 shekels ($ 7335). During 2008–2010, 88 HoA migrants who had been screened at the prison after crossing the border were later diagnosed with TB in the community. The average annual TB incidence was 132 cases/100,000 migrants. We traced 56 (63.6%) of the CXRs that were performed during detention. Of those, 41 (73.2%) were unremarkable, 8 (14.2%) were TB suspicious and 7 (12.5%) had non-TB-related abnormalities.

Conclusions: CXR-based screening is a valid and cost-saving tool for screening  HoA migrants for TB; the interview has significant limitations. 

Objectives: To assess the role of electrocardiography-gated CT-angiography (ECG-CTA) in the routine evaluation of CHD in neonates and infants particularly for the assessment of extracardiac findings.

Methods: The study cohort comprised 40 consecutive patients who underwent trans-thoracic echocardiography (TTE) and ECG-CTA. TTE and ECG-gated CTA findings regarding extracardiac vascular structures, coronary arteries and airways were compared with surgical or cardiac catheterization findings. Scans were evaluated for image quality using a subjective visual scale (from 1 to 4). Effective radiation dose was calculated for each scan.

Results: Median age was 28 ± 88 days and mean weight 3.7 ± 1.5 kg. Diagnostic quality was good or excellent (visual image score 3–4) in 39 of 40 scans (97.5%). ECG-CTA provided important additional information regarding extracardiac vascular structures and airway anatomy, complementing TTE in 75.6% of scans. Overall sensitivity of ECG-gated CTA for detecting extracardiac findings as compared with operative and cardiac catheterization findings was 97.6%. The calculated mean effective radiation dose was 1.4 ± 0.07 mSv (range 1.014–2.3 mSv).

Conclusions: ECG-CTA is an accurate modality for demonstrating extracardiac structures in complex CHD. It provides important complementary information to TTE regarding extracardiac vascular structures and coronary artery anatomy. This modality may obviate the need for invasive cardiac catheterization, thus exposing the patient to a much lower radiation dose.