Israel Medical Association Journal

Background: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations.

Objectives: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations. To understand pathogenic mechanisms preceding the clinical presentation of ALS.

Methods: At the ALS clinic at Tel Aviv Sourasky Medical Center, 259 ALS patients insured by Maccabi Healthcare Services and seen between January 1998 and December 2017 were included. Comparisons of demographics, co-morbidities, medications taken, history of trauma, and laboratory tests prior to disease onset were performed between patients and 1295 matched controls.

Results: Prior to disease presentation, ALS patients had a higher frequency of hypertension and cardiovascular disease; presented more frequently with trauma and viral infections; more frequently used analgesics, non-steroidal anti-inflammatory drugs, narcotics, antibiotics, and antiviral medications; and had higher creatine kinase levels.

Conclusions: ALS patients showed higher frequency of cardiovascular disease prior to diagnosis, as well as higher frequency of trauma, infections, and pain medication usage.

Background: Hepatitis D virus may cause a disease at various severities in the presence of hepatitis B virus, using hepatitis B surface antigen (HBsAg) on the external envelope in its replication process. Thus, people identified with HBsAg in blood tests should also be tested for hepatitis D virus.

Objectives: To describe the situation of performance of blood tests for detection of hepatitis D virus in patients positive for hepatitis surface antigen during 9 years in a population with heterogeneous origins in the north region of Israel.

Methods: We conducted a retrospective study using the database of Clalit Health Services.

Results: We found 3367 people were positive for HBsAg during the study period; 613 (18%) were tested for hepatitis D. People who tested for hepatitis D were younger (47.3 ± 15 years vs. 50.5) and showed a higher rate of visiting the gastroenterology clinic (80.6% vs. 41%). The rate of positive blood tests for hepatitis D was too small for analysis, but it still demonstrated tendency for higher rates in the Ethiopian Jewish group.

Conclusion: The recommendation for performance of blood test for hepatitis D virus was followed to a small extent. Considering the ethnic diversity of the population in Israel, activities to raise rates of performance should be considered.

Abstract

Background: The mass influx of immigrants from tuberculosis-endemic countries into Israel was followed by a considerable increase in the incidence of tuberculosis (TB). All contacts of active TB patients are obliged to be screened by tuberculin skin tests (TST) and, if found positive, prophylactic treatment is considered.

Objectives: To assess the utility of interferon-gamma (IFNγ)-release assay with a prolonged follow-up in preventing unnecessary anti-TB therapy in individuals with suspected false positive results.

Methods: Between 2008 and 2012 the QuantiFERON TB gold-in-tube test (QFT-G) was performed in 278 sequential individuals who were mostly TST-positive and/or were in contact with an active TB patient. In all, whole blood was examined by the IFNγ-release assay. We correlated the TST diameter with the QFT-G assay and followed those patients with a negative assay.

Results: The QFT-G test was positive in only 72 (42%) of all 171 TST-positive individuals. There was no correlation between the diameter of TST and QFT-G positivity. Follow-up over 5 years was available in 128 (62%) of all QFT-G-negative individuals. All remained well and none developed active TB.

Conclusions: A negative QFT-G test may obviate the need for anti-TB therapy in more than half of those with a positive TST.

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: Most studies on asbestos-related diseases describe the associations between exposure and disease and the factors influencing that association. It is recognized that there is a long latency period between exposure and disease, but the health status of affected individuals after long-term non-exposure is uncertain.

Objectives: To describe the changes in pulmonary function tests (PFTs) and computed tomographic imaging of the thorax over a 15 year period after cessation of exposure to asbestos in a cohort of Israeli power plant workers.

Methods: Israeli power plant workers whose PFTs and thoracic CT imaging between 1993 and 1998 revealed asbestos-related disease underwent a second clinical, functional and imaging evaluation up to 15 years later. The two sets of results were compared.

Results: Of the original cohort of 59 males, 35 were still alive, and 18 of them agreed to take part in the current study. The mean length of their exposure was 30 ± 10.06 years (range 7–43 years). Comparison of the initial and follow-up examination findings revealed a significant increase in calcification of the pleural plaques (from 37% to 66%, P = 0.008) and a deterioration in PFTs (P = 0.04). Of the 24 men who died, malignant disease was the cause of death in 53%, mostly in sites other than the respiratory system.

Conclusions: PFTs declined and CT findings worsened in subjects who were formerly exposed to asbestos and had not been exposed to it for over a decade. Continued monitoring of individuals exposed to asbestos, even decades after the cessation of exposure, is recommended.
 

Background: Hyperbilirubinemia of the newborn is common. Rarely is an underlying disease other than physiologic hyperbilirubinemia considered the cause of high bilirubin levels. Some of the laboratory tests recommended by the American Academy of Pediatrics are expensive and do not always lead to diagnosis.

Objective: To evaluate the efficacy of standard laboratory tests performed on newborn infants requiring phototherapy for hyperbilirubinaemia.

Methods: We conducted a retrospective chart review that included neonates born during a 6 month period with birth weight > 2500 g treated with phototherapy for hyperbilirubinemia (n=282) according to published guidelines. The main outcome measures were primary and maximal bilirubin values (mg/dl), time to jaundice (in days), the number of bilirubin tests undertaken and whether the patient showed abnormal functioning, and the number of days in follow-up.

Results: Thirty-three neonates (11.7%) were positive in at least one laboratory test (defined as "Abnormal" in our study), 45.5% of whom met the criteria for phototherapy during the first 48 hours of life. Among the newborns who were negative for all laboratory tests (defined as "Normal"), only 6.8% met phototherapy criteria within their first 48 hours of life (P < 0.001). In the Normal group there was a consistent decrease in total serum bilirubin values shortly after phototherapy was begun, while the Abnormal group presented an increase in serum bilirubin values during the first 12 hours of phototherapy. None of the infants had conjugated (direct) hyperbilirubinemia during the study period.

Conclusions: Most neonates presenting with a laboratory identifiable etiology for hyperbilirubinemia (i.e., hemolysis) can be distinguished from those who test negative, mainly based on the timing of presentation and response to phototherapy. A more meticulous selection of patients and reduction in the magnitude of routine laboratory testing can safely reduce discomfort to infants with hyperbilirubinemia as well as costs.

Pathological gambling is classified in the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders) and in the ICD-10 (International Classification of Disease) as an impulse control disorder. The association between impulsivity and pathological gambling remains a matter of debate: some researchers find high levels of impulsivity within pathological gamblers, others report no difference compared to controls, and yet others even suggest that it is lower. In this review we examine the relationship between pathological gambling and impulsivity assessed by various neurocognitive tests. These tests – the Stroop task, the Stop Signal Task, the Matching Familiar Figures Task, the Iowa Gambling Task, the Wisconsin Card Sorting Test, the Tower of London test, and the Continuous Performance Test – demonstrated less impulsivity in gambling behavior. The differences in performance between pathological gamblers and healthy controls on the neurocognitive tasks could be due to addictive behavior features rather than impulsive behavior.

Background: Infants who have experienced an apparent life-threatening event typically undergo an extensive evaluation to rule out serious underlying conditions.

Objectives: To evaluate the yield of different tests performed after an apparent life-threatening event and to identify high risk groups in which more extensive diagnostic tests are required.

Methods: A retrospective study was conducted in a children's hospital over a 4 year period during which the charts of infants who were admitted with an apparent life-threatening event were reviewed. The yield for each diagnostic test was established according to the ratio of positive results contributing to the diagnosis of the apparent life-threatening event.

Results: The study included 69 infants between the ages of 1 week and 1 year. There were abnormal findings in 36% of the cases. Gastroesophageal reflux was the most common diagnosis (60%). In the remaining patients the diagnosis was either seizures (12%) or respiratory tract infections (28%). Tests used for the diagnosis of cardiac, metabolic and non-respiratory infections had no yield. A positive correlation was found between abnormal test results and abnormal physical examination (P = 0.001), an abnormal perinatal history (P = 0.017), and age older than 2 months (P = 0.002).

Conclusions: The yield of most of the tests performed after an apparent life-threatening event is low, especially in infants with a normal perinatal history and physical examination.

Background: A high incidence of abnormal pulmonary function tests has been reported in cross-sectional studies among patients with rheumatoid arthritis. Few patients have been enrolled in longitudinal studies.

Objectives: To perform PFT[1] in rheumatoid arthritic patients without pulmonary involvement and to identify variables related to changes in PFT over 5 years of follow-up.

Methods: Consecutive RA[2] patients underwent PFT according to American Thoracic Society recommendations. All surviving patients were advised to repeat the examination 5 years later.

Results: PFT was performed in 82 patients (21 men, 61 women). Their mean age was 55.7 (15.9) years and the mean RA duration was 11.1 (10) years. Five years later 15 patients (18.3%) had died. Among the 67 surviving patients, 38 (56.7%) agreed to participate in a follow-up study. The initial PFT revealed normal PFT in only 30 patients (36.6%); an obstructive ventilatory defect in 2 (2.4%), a small airway defect in 12 (17%), a restrictive ventilatory defect in 21 (25.6%), and reduced DLco in 17 (20.7%). Among the 38 patients participating in the 5 year follow-up study, 8 developed respiratory symptoms, one patient had a new obstructive ventilatory defect, one patient developed a restrictive ventilatory defect, and 5 patients had a newly developed small airway defect. The DLco had improved in 7 of the 8 patients who initially had reduced DLco, reaching normal values in 5 patients. Over the study period a new reduction in DLco was observed in 7 patients. Linear regression analyses failed to identify any patient or disease-specific characteristics that could predict a worsening in PFT. The absolute yearly decline in forced expiratory volume in 1 sec among our RA patients was 47 ml/year, a decline similar to that seen among current smokers.

Conclusions: Serial PFT among patients with RA is indicated and allows for earlier identification of various ventilatory defects. Small airways disturbance was a common finding among our RA patients.