Israel Medical Association Journal

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

Parenteral nutrition (PN) must be initiated as soon as possible after delivery in very low birth weight (VLBW) preterm infants in order to prevent postnatal growth failure and improve neurodevelopmental outcome. When administered early, high levels of parenteral amino acids (AA) are well tolerated and prevent negative nitrogen balance. Although proteins are the driving force for growth, protein synthesis is energy demanding. Intravenous lipid emulsions (ILE) constitute a good energy source because of their high energy density and provide essential fatty acids (FA) along with their long-chain polyunsaturated fatty acid (LC-PUFA) derivatives necessary for central nervous system and retinal development. Early supply of ILE is not associated with increased morbidity. No significant differences were found between ILE based on soybean oil only and mixed ILE containing soybean oil in combination with other fat sources, except for a reduction in the incidence of sepsis with non-pure soybean ILE, and possibly less PN-associated liver disease with mixed ILE containing some fish oil. In preterm infants glucose homeostasis is still immature in the first days of life and abnormalities of glucose homeostasis are common. VLBW infants may not tolerate high levels of glucose infusion without hyperglycemia. Administering lower levels of glucose infusion as part of full early PN seems more successful than insulin at this stage. Postpartum there is a transition period when the water and electrolyte balance may be severely disturbed and should be closely monitored. Avoiding fluid overload is critical for preventing respiratory and other morbidities

This paper summarizes the difficulties that may emerge when the same care-provider attends to private and public patients within the same or different clinical settings. First, I argue that blurring the boundaries between public and private care may start a slippery slope leading to “black” under-the-table payments for preferential patient care. Second, I question whether public hospitals that allow their doctors to attend to private patients provide an appropriate learning environment for medical students and residents. Finally, I propose a way to both maintain the advantages of private care and avoid its negative consequences: complete separation between the public and the private health care systems.

 

Background: Several trials support the trans-radial route of percutaneous coronary intervention (PCI) since it reduces access site vascular complications and bleeding. 

Objectives: To examine the effects of trans-radial interventions (TRI) on clinical outcomes in a 'real world' cohort of patients undergoing PCI.

Methods: We analyzed 4873 consecutive patients who underwent PCI at a tertiary center and identified 373 patients who underwent TRI. Patients (radial vs. femoral) were compared using a propensity score analysis to best match between groups. Outcome parameters included total mortality, myocardial infarction (MI), repeat target vessel revascularization (TVR) rates, length of hospitalization and ∆Ht/Hb/creatinine values during hospitalization. These were evaluated at 6 months and 1 to 3 years after PCI.

Results: The rates of major adverse cardiovascular event (MACE) and its constituents were similar in the trans-radial vs. trans-femoral groups at all time intervals: 6.7% vs. 5.5% at 6 months, 10.3% vs. 10% at 1 year, 15.7% vs. 15% at 2 years, 15.7% vs. 16% at 3 years, respectively (P = 0.6). The length of hospitalization was shorter in the TRI group (2.87 days ± 2.04 vs. 3.3 days ± 3.12, P = 0.023). We did not find significant differences between the groups in the mean ∆Ht/Hb/creatinine values during the hospitalization course.

Conclusions: In a 'real-world' setting of PCI, the TRI route of PCI is as safe and efficient as the femoral approach. TRI is associated with shorter duration of hospitalization.

 

Abstract

Background: Findings of studies addressing outcomes of war-related famine in non-Jewish populations in Europe during the Second World War (WWII) confirmed an association between prenatal/early life exposure to hunger and adult obesity, diabetes, hypertension, cardiovascular heart disease and the metabolic syndrome. Fetal programming was suggested as the explanatory mechanism.

Objectives: To study the association between being born during WWII in Europe and physical long-term outcomes in child Holocaust survivors.   

Methods: We conducted a cross-sectional study on all Jewish Clalit Health Services (CHS) North District members born in 1940–1945 in Europe ('exposed', n=653) or in Israel to Europe-born parents ('non-exposed', n=433). Data on socio-demographic variables, medical diagnoses, medication procurement, laboratory tests and health services utilization were derived from the CHS computerized database and compared between the groups.

Results: The exposed were significantly more likely than the non-exposed to present with dyslipidemia (81% vs. 72%, respectively), hypertension (67% vs. 53%), diabetes mellitus (41% vs. 28%), vascular disease (18% vs. 9%) and the metabolic syndrome (17% vs. 9%). The exposed also made lower use of health services but used anti-depressive agents more often compared to the non-exposed. In multivariate analyses, being born during WWII remained an independent risk marker for hypertension (OR = 1.52), diabetes mellitus (OR = 1.60), vascular disease (OR = 1.99) and the metabolic syndrome (OR = 2.14).

Conclusions: The results of this cross-sectional study based on highly validated data identify a high risk group for chronic morbidity. A question regarding potential trans-generational effects that may impact the ‘second generation’ is also raised.

Abstract

Background: The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF.

Objectives: To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine.

Methods: We reanalyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants without worsening of the sixth criterion).

Results: In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered responders to rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept.

Conclusions: The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study. 

Abstract

Background: Diabetes mellitus-related lower extremity amputation is a major complication severely affecting patient survival and quality of life.

Objectives: To analyze epidemiological and clinical trends in the incidence and survival of lower extremity amputations among diabetes patients.

Methods: We conducted a retrospective observational cohort study of 565 consecutive diabetes patients who underwent their first non-traumatic lower extremity amputation between January 2002 and December 2009.

Results: Major amputations were performed in 316 (55.9%) patients: 142 above the knee (25.1%) and 174 below (30.8%); 249 (44.1%) had a minor amputation. The incidence rates of amputations decreased from 2.9 to 2.1 per 1000 diabetes patients. Kaplan-Meier survival analysis showed that first year mortality rates were lower among patients with minor amputations (31.7% vs. 39.6%, P = 0.569). First year mortality rates following below-knee amputation were somewhat lower than above-knee amputation (33.1 vs.45.1%, respectively). Cox regression model of survival at 1 year after the procedure found that age (HR 1.06 per year, 95% CI 1.04–1.07, P < 0.001), above-knee amputation (HR 1.36, 95% CI 1.01–1.83, P = 0.045) and ischemic heart disease (HR 1.68, 95% CI 1.26–2.24, P < 0.001) significantly increased one year mortality risk.

Conclusions: In this population-based study the incidence rate of non-traumatic amputations in diabetes patients between January 2002 and December 2009 decreased slightly. However, one year mortality rates after the surgery did not decline and remained high, stressing the need for a multidisciplinary effort to prevent amputations in diabetes patients.

Abstract

Background: Gaucher disease is the most common lysosomal storage disorder and is caused by a deficiency of the enzyme glucocerebrosidase. Enzyme deficiency leads to the accumulation of undegraded substrates, mainly in cells of the monocyte/macrophage lineage, which is responsible for the clinical manifestations of the disease. To date, no study has attempted to identify the mutation spectrum of the glucocerebrosidase gene (GBA) in Slovak patients

Objectives: To identify mutations in 14 Slovak patients with confirmed glucocerebrosidase deficiency.

Methods: Using molecular genetics methods PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and direct sequencing of coding region GBA we identified the spectrum of mutations in our patients.

Results: Five mutations (N370S, L444P, G377S, D409H and RecNciI) accounted for 75% of the mutant alleles. The remaining 25% were rare and probably individual mutations.

Conclusions: The mutational spectrum in our patients is similar to that observed in other European countries and corresponds to a Caucasian population, with N370S, L444P, RecNciI being the most common mutation. Interestingly, mutation G377S was more frequent in our patients as compared to other published data. The C4W, L96P, H311N, 745delG and 1127_1128delTT mutations are described here for the first time in Gaucher disease, contributing to the panel of published GBA mutations.