Israel Medical Association Journal

Background: The Israel Poison Information Center (IPIC), Rambam Health Care Campus, provides 24-hour telephone consultations on clinical toxicology and drug and reproductive toxicology. It participates in research, teaching and regulatory activities, and provides laboratory services. In 2014, nurse specialists in poison information joined the IPIC.

Objectives: To report the epidemiology of poison exposures in Israel.

Methods: We present computerized queries and a descriptive analysis of the medical records database of the IPIC for 2017.

Results: A total of 39,928 poison exposure cases were recorded, reflecting increases of 226.3% and 26.7% compared with 1995 and 2012, respectively. Children < 6 years of age were involved in 47.0% of cases; 80.4% of calls were made by the public and 17.8% by physicians; 74.2% of exposures were unintentional and 7.3% intentional. Pharmaceuticals were involved in 51.4% of cases, chemicals in 36.9%, bites and stings in 2.2%, and plants and mushrooms in 1.5%. Substances most frequently involved were analgesics, cleaning products, and antimicrobials. Clinical severity was moderate/major in 3.3%, mainly due to insecticides, drugs of abuse, and corrosives. Three fatalities were recorded (due to colchicine, organophosphates, and volatile substance inhalant abuse).

Conclusions: Poison exposures and poisonings have markedly increased in Israel, contributing substantially to morbidity. The IPIC prevented unnecessary referrals to emergency departments. Its database is a valuable national resource for collecting and monitoring poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory, and its activities adequately supported by national resources.

Background: Catheter ablation (CA) is a well-established therapeutic option for patients with recurrent symptomatic atrial fibrillation (AF). Data on gender-related differences are limited with regard to baseline characteristics and long-term success rates of catheter ablation for AF.

Methods: We analyzed a cohort of 251 consecutive patients who underwent a first catheter ablation for AF in our institute during the period 2008 through 2015. All patients were followed by regular annual clinic visits, electrocardiograms, periodic 24–48 hour Holter monitoring, and loop recorders. The primary endpoint was first recurrence of AF during 1 year of follow-up.

Results: The cohort comprised 26% women (n=65), who were older (62.1 ± 9.6 vs. 54.4 ± 11.3 years, P < 0.01) and had a higher proportion of diabetes mellitus (23.1 vs. 5.4%, P < 0.001) than male patients. No other significant differences were evident. At 1 year follow-up, the cumulative survival free of AF was significantly higher in women compared with men (83% vs. 66%, respectively, log rank P value = 0.021). Subgroup analysis showed an interaction between female and small indexed left atrial diameter (LADi < 23 mm/m²).

Conclusions: Our findings suggest that women experience a significantly lower rate of AF recurrence post-CA compared with men. This gender-related advantage appears to be restricted to women without significant left atrial enlargement. It further implies that left atrial enlargement has a stronger negative impact on post-CA AF recurrence in females than in males. Due to the relatively small sample number of females further research is warranted to validate our conclusions.

Background: The aggregation of autoimmune diseases in relatives (AID-R) of patients with systemic sclerosis (SSc) has been reported.

Objectives: To analyze the prevalence of autoimmune diseases in SSc relatives and to compare their features to those of SSc patients without AID-R (controls).

Methods: A case-control analysis compared SSc patients with AID-R to those without AID-R (25 patients) with similar disease duration.

Results: Among 322 patients, 25 (7.7%; 21 females, 41.4 ± 15.6 years of age, disease duration 11 ± 8.6 years) had AID-R (21 had a first-degree relative, 4 had a second-degree relative, and 2 had both). Fourteen patients (56%) and five controls (20%) had an additional autoimmune disease (P < 0.009). Diffuse SSc (48% vs. 24%) and arthritis (72% vs. 28%) were more frequent among the patients with AID-R than the controls (P < 0.05). No significant differences were found regarding lung, heart, vascular, and digestive system involvement. The mean number of additional autoimmune diseases was 0.84 ± 0.94 in AID-R vs. 0.24 ± 0.52 in controls (P < 0.038). The mean number of autoantibodies was 2.8 ± 1.5 and 2.2 ± 0.9 (P < 0.047). Five patients died during follow-up, four of whom had AID-R. Relatives of SSc patients had diverse autoimmune diseases; the prevalence of SSc in scleroderma relatives was 1.86% (2 in first-degree and 6 in second-degree relatives). SSc patients with AID-R had an obvious tendency to polyautoimmunity.

Conclusion: A precise family history is an important clue in prognosis and prediction of autoimmune diseases in SSc patients and their relatives.

Background: The lack of organs for liver transplantation has prompted transplant professionals to study potential solutions, such as the use of livers from donors older than 70 years. This strategy is not widely accepted because potential risks of vascular and biliary complications and recurrence of hepatitis C.

Objectives: To examine the efficacy and safety of liver grafts from older donors for transplantation.

Methods: A retrospective analysis of data on 310 adults who underwent deceased donor liver transplantation between 2005 and 2015 was conducted. We compared graft and recipient survival, as well as major complications, of transplants performed with grafts from donors younger than 70 years (n=265, control group) and those older than 70 years (n=45, older-donor group), followed by multivariate analysis, to identify risk factors.

Results: There was no significant difference between the control and older-donor group at 1, 5, and 10 years of recipient survival (79.5% vs. 73.3%, 68.3% vs. 73.3%, 59.2% vs. 66.7%, respectively) or graft survival (74.0% vs. 71.0%, 62.7% vs. 71.0%, 54.8% vs. 64.5%, respectively). The rate of biliary and vascular complications was similar in both groups. Significant risk factors for graft failure were hepatitis C (hazard ratio [HR] = 1.92, 95% confidence interval [95%CI] 1.16–2.63), older donor age (HR = 1.02, 95%CI 1.007–1.031), and male gender of the recipient (HR = 1.65, 95%CI 1.06–2.55).

Conclusion: Donor age affects liver graft survival. However, grafts from donors older than 70 years may be equally safe if cold ischemia is maintained for less than 8 hours.

Background: Recurrence of tracheoesophageal fistula (TEF) is reported in 8–20% patients. Factors that may influence recurrence of fistula beyond the postoperative period are not clear.

Objectives: To evaluate possible factors associated with recurrence of TEF beyond the immediate postoperative period.

Methods: A single center, retrospective comparison of patients with and without recurrence of TEF was conducted. Medical records of patients previously operated for TEF who were followed in our pediatric pulmonary institute between January 2007 and December 2016 were reviewed.

Results: The medical records of 74/77 patients previously operated for TEF were evaluated. Nine patients (12%) had a recurrence of TEF and 65 did not. These groups had similar age and gender distribution and similar prevalence of VACTERL association. In addition, they had similar length of atretic gap, rates of thoracoscopic surgery, rates of prolonged need for respiratory assistance post-surgery, and frequency of gastrointestinal symptoms. Notably, the patients who had recurrent TEF had significantly more hospitalizations for respiratory symptoms (P = 0.011) and significantly more episodes of clinical bronchiolitis per patient (P < 0.0001). In addition, the patients with recurrent TEF had significantly more episodes of positive polymerase chain reaction for viruses (P = 0.009).

Conclusions: Hospitalizations for respiratory symptoms as well as clinical and/or viral bronchiolitis are associated with recurrence of TEF. Even though cause and effect cannot be established, these patients should undergo meticulous evaluation for the possibility of recurrence of TEF.

Background: Anemia management strategies among chronic hemodialysis patients with high ferritin levels remains challenging for nephrologists.

Objectives: To compare anemia management in stable hemodialysis patients with high (≥ 500 ng/ml) vs. low (< 500 ng/ml) ferritin levels

Methods: In a single center, record review, cohort study of stable hemodialysis patients who were followed for 24 months, an anemia management policy was amended to discontinue intravenous (IV) iron therapy for stable hemodialysis patients with hemoglobin > 10 g/dl and ferritin ≥ 500 ng/ml. Erythropoiesis-stimulating-agents (ESA), IV iron doses, and laboratory parameters were compared among patients with high vs. low baseline ferritin levels before and after IV iron cessation.

Results: Among 87 patients, 73.6% had baseline ferritin ≥ 500 ng/ml. Weekly ESA dose was greater among patients with high vs. low ferritin (6788.8 ± 4727.8 IU/week vs. 3305.0 ± 2953.9 IU/week, P = 0.001); whereas, cumulative and monthly IV iron doses were significantly lower (1628.2 ± 1491.1 mg vs. 2557.4 ± 1398.9 mg, P = 0.011, and 82.9 ± 85 vs. 140.7 ± 63.9 mg, P = 0.004). Among patients with high ferritin, IV iron was discontinued for more than 3 months in 41 patients (64%) and completely avoided in 6 (9.5%).ESA dose and hemoglobin levels did not change significantly during this period.

Conclusions: Iron cessation in chronic hemodialysis patients with high ferritin levels did not affect hemoglobin level or ESA dose and can be considered as a safe policy for attenuating the risk of chronic iron overload.

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: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation.

Objectives: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies.

Methods: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies.

Results: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006).

Conclusions: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.

Background: The closure of an atrial septal defect is procedure that is frequently performed in both adults and children. Currently, the most commonly used devices are the Amplatzer® and Occlutech® Figulla® atrial septal occluders. Studies conducted in adults have shown that these devices all have similar performance efficiency for the closure of secundum atrial septal defects. No study to date has examined their performance in the pediatric population.

Objectives: To evaluate and compare the performance of Amplatzer® and Occlutech® Figulla® atrial septal occluders in the pediatric population.

Methods: A consecutive retrospective study of exclusively pediatric patients who underwent percutaneous closure of atrial septal defect with these devices was conducted at our institute. 

Results: The study comprised 110 children, 50 in the Amplatzer® device group and 60 in the Occlutech® Figulla® device group. The groups had similar demographic and defect characteristics, except for defect size per transesophageal echocardiography (TEE), which was 2.1 mm larger in the Amplatzer® device group (P = 0.02). No adverse events were recorded in either of the study groups. Complete defect closure at 12 months follow-up (procedural success) was achieved in all but one of the patients in the Amplatzer® group and all but two in the Figulla® group (P = 1). The residual shunt rates of fenestrated defects were similar in the two groups. 

Conclusions: For children with an isolated secundum atrial septal defect, percutaneous closure is equally safe and effective with either Amplatzer® or Occlutech® Figulla® devices.

Background: The prevalence of major malformations in the general population is estimated at 5% of all live births. Prenatal diagnosis is an important scientific tool that allows reliable consultation and improves pregnancy outcome. In 2008, congenital malformations were the leading cause of death in Muslim infants and the second cause of death in Jewish infants in Israel. It is known that folic acid consumption prior to pregnancy decreases the rate of several fetal malformations.

Objectives: To assess the folic acid consumption rate and to characterize variables associated with its use among pregnant women attending a rural medical center. 

Methods: A cross-sectional observational study was conducted at our institution. Pregnant women in the second or third trimester of pregnancy or within 3 days postpartum were interviewed. The main variable measured was the use of folic acid. Demographic variables and the rate of prenatal testing were assessed. A secondary analysis of the population that reported no consumption of folic acid was carried out. 

Results: Out of 382 women who participated in the study, 270 (71%) reported consumption of folic acid. Using a multivariate analysis model, we found that maternal education, planning of pregnancy, and low parity were independent predictors of folic acid consumption. Women who were not consuming folic acid tended to perform fewer prenatal tests during pregnancy.

Conclusions: High maternal educational level, planning of pregnancy, and low parity are related to high consumption rates of folic acid. Women who were not taking folic acid performed fewer prenatal tests during pregnancy. 

Pseudoexfoliation syndrome (PES) is a common age-related disorder affecting 60–70 million people worldwide. Patients with PES have abnormal production and deposition of fibrillar material in the anterior chamber of the eye. These exfoliated fibrils, easily detected by ocular slit-lamp examination, have also been found to exist systematically in the skin, heart, lungs, liver and kidneys. Recently, myriad studies have associated PES with systemic conditions such as increased vascular risk, risk of dementia and inflammatory state. We review here the most current literature on the systemic implications of PES. Our aim is to encourage further studies on this important clinical entity.