Israel Medical Association Journal

Background: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment.

Objectives: To evaluate the “real-life” safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers.

Methods: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3–4 months. Adverse events were obtained from patients’ medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response.

Results: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1–7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%).

Conclusions: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.

Background: In March 2009 the pandemic influenza A (H1N1) strain was identified. The disease initially appeared to be accompanied by complications and high mortality rates. It became an endemic virus during the influenza season in our region, along with the classical seasonal H3N2.

Objectives: To identify the burden of pandemic influenza, its effect in pediatric patients, and complicated hospitalizations, compared to seasonal influenza years after the pandemic.

Methods: A retrospective observational study was conducted at a tertiary hospital. Data were collected from the medical records of all children who were hospitalized from April 2009 to 2011 with laboratory-confirmed influenza.

Results: Of 191 patients with influenza, 100 had the 2009 pandemic influenza, 62 had seasonal influenza, and 29 had H1N1 in 2010–2011. Patients with the 2009 H1N1 were characterized by older age, more co-morbidity conditions and more symptoms including fever, cough and rhinitis on admission. No significant differences in outcomes between the groups were recorded. Of patients hospitalized with pandemic influenza in 2009, 28% had complicated hospitalizations, compared with 17.7% of patients hospitalized with seasonal influenza in 2010–11. Children with pandemic influenza received more oseltamivir (Tamiflu®) (94% vs. 19.4%, P < 0.001) and more antibiotics than the other groups.

Conclusions: The type of influenza had no effect on outcome. There were no significant differences between groups in the percentages of in-hospital mortality, admission to intensive care units, prolonged hospitalization (> 9 days), or the development of complications during hospitalization.

 

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, impulsivity and hyperactivity. Recently, increases in ADHD prevalence and methylphenidate use have been reported. There is evidence that children and adolescents use ADHD medication only during the school year. 

Objectives: To investigate trends in methylphenidate dispensing over a period of 3 years (2010–2012) at the monthly level and to investigate whether there is any monthly variation, especially during the summer season.

Methods: The database of Clalit Health Services (the largest of the four health funds in Israel) was used to identify (i) patients aged 6–17 years with a diagnosis of ADHD, and (ii) methylpenidate dispensation during the period 2010–2012. 

Results: Among children aged 6–17 years diagnosed with ADHD, 43% were treated with methylphenidate. For the period 2010 to 2012 there was an annual drop in methylphenidate dispensing, beginning in June and continuing through the 2 months of summer vacation, with a 2.5-fold reduction from July as compared to May. This decline was consistently followed by a rise in medications dispensed starting August. A similar small drop was observed during the Passover school vacation. The summer drop decreased over the years.

Conclusions: Our findings showed a decrease in the number of methylphenidate prescriptions dispensed during the summer months and Passover as compared to the rest of the year. However, this phenomenon appears to be decreasing. Given that ADHD is a chronic disease state that can effectively be managed with pharmacotherapy, discontinuation of treatment may be harmful for patients and should be considered only on a patient-by-patient basis.

 

Background: During 2013–2014 Israel experienced a continuous circulation of wild poliovirus type 1 (WPV1) but with no clinical cases. WPV1 circulation was gradually terminated following a national vaccination campaign of bivalent oral poliovirus vaccine (bOPV) for 943,587 children < 10 years. Four cases of children with neurological manifestations that appeared following bOPV vaccinations were reported during the campaign: three of Guillain-Barré syndrome (GBS) and one of acute disseminated encephalomyelitis (ADEM). 

Objectives: To present an analysis of these cases, the rapid response and the transparent publication of the results of this analysis. 

Methods: The clinical, laboratory and epidemiological data of these four patients were available during the analysis. In addition, data regarding the incidence of GBS and ADEM during previous years, and reported cases of acute flaccid paralysis (AFP) and the incidence of Campylobacter jejuni enteritis were collected from the Epidemiology Department of the Israel Ministry of Health.

Results: The incidence of GBS among bOPV-vaccinated children was not higher than among bOPV-unvaccinated children. For all the cases reviewed the "incubation period" from vaccination to the event was longer than expected and other more plausible causes for the neurologic manifestations were found. There is no evidence in the literature of a causal relationship between bOPV and ADEM. 

Conclusions: There was no association between the bOPV vaccine and the reported neurological manifestations. We believe that our experience may assist other public health professionals when confronting a similar problem of alleged side effects during a mass medical intervention.

 

Background: Due to a shortage of individualized erythromycin ointment (IEO), we switched to shared erythromycin drops (SED). Following this change, nurses claimed observing more cases of eye discharge. 

Objectives: To test whether switching from IEO to SED affected the rate of neonatal conjunctivitis (NC).

Methods: The study group included 14,916 neonates > 35 weeks of gestation, further divided into two birth periods of 12 months each: 1 January 2013 to 31 December 2013 (IEO) and 1 February 2014 to 31 January 2015 (SED). We compared the two birth periods with regard to three variables: clinical NC (number of conjunctival swabs/1000 neonates), bacterial NC (number of culture-positive swabs/1000 neonates), and bacterial growth percentage (number of culture-positive swabs/100 samples).  

Results: Compared to 2012–2013, the period 2014–2015 included fewer cesarean deliveries and shorter length of stay (LOS). Clinical NC, bacterial NC and bacterial-growth percentage were not different between the two periods. Variables that were independently significantly associated with increased clinical NC included male gender (OR 1.48, CI 1.21–1.81) and LOS (OR 1.24, CI 1.18–1.29). LOS was associated with bacterial NC (OR 1.19, CI 1.11–1.28). Coagulase-negative staphylococci, Escherichia coli and Pseudomonas aeruginosa were the prevalent pathogens, though without difference between periods. 

Conclusions: Rates of clinical NC, bacterial NC and bacterial-growth percentage were not different between the study periods. Switching from IEO to SED had no effect on the NC rate.

 

Background: Fertility treatments are responsible for the rise in high order pregnancies in recent decades and their associated complications. Reducing the number of embryos returned to the uterus will reduce the rate of high order pregnancies.     

Objectives: To explore whether obstetric history and parity have a role in the clinician’s decision making regarding the number of embryos transferred to the uterus during in vitro fertilization (IVF).

Methods: In a retrospective study for the period August 2005 to March 2012, data were collected from twin deliveries > 24 weeks, including parity, mode of conception (IVF vs. spontaneous), gestational age at delivery, preeclampsia, birth weight, admission to the neonatal intensive care unit (NICU), and Apgar scores. 

Results: A total of 1651 twin deliveries > 24 weeks were recorded, of which 959 (58%) were at term (> 37 weeks). The early preterm delivery (PTD) rate (< 32 weeks) was significantly lower with increased parity (12.6%, 8.5%, and 5.6%, in women with 0, 1, and ≥ 2 previous term deliveries, respectively). Risks for PTD (< 37 weeks), preeclampsia and NICU admission were significantly higher in primiparous women compared to those who had one or more previous term deliveries. Primiparity and preeclampsia, but not IVF, were significant risk factors for PTD. 

Conclusions: The risk for PTD in twin pregnancies is significantly lower in women who had a previous term delivery and decreases further after two or more previous term deliveries. This finding should be considered when deciding on the number of embryos to be transferred in IVF.  

 

Background: Chronic kidney disease (CKD) is often accompanied by impairment of cardiac function that may lead to major cardiac events. Erythropoietin (EPO), a kidney-produced protein, was shown to be beneficial to heart function. It was suggested that reduced EPO secretion in CKD may play a role in the initiation of heart damage. 

Objectives: To investigate molecular changes in the EPO/erythropoietin receptor (EPO-R) axis in rat cardiomyocytes using a rat model for CKD.

Methods: We established a rat model for CKD by kidney resection. Cardiac tissue sections were stained with Masson’s trichrome to assess interstitial fibrosis indicating cardiac damage. To evaluate changes in the EPO/EPO-R signaling cascade in the myocardium we measured cardiac EPO and EPO-R as well as the phosphorylation levels of STAT-5, a downstream element in this cascade.

Results: At 11 weeks after resection, animals presented severe renal failure reflected by reduced creatinine clearance, elevated blood urea nitrogen and presence of anemia. Histological analysis revealed enhanced fibrosis in cardiac sections of CKD animals compared to the sham controls. Parallel to these changes, we found that although cardiac EPO levels were similar in both groups, the expression of EPO-R and the activated form of its downstream protein STAT-5 were significantly lower in CKD animals.

Conclusions: CKD results in molecular changes in the EPO/EPO-R axis. These changes may play a role in early cardiac damage observed in the cardiorenal syndrome.

 

Chikungunya fever (CHIK-F) has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular tourist sites.  We present three Israeli travelers who developed fever, maculopapular rash and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic. We also present an epidemiological review of the chikungunya epidemic over the past decades. Rare systemic manifestations of this disorder, like catastrophic antiphospholipid syndrome (CAPS) and adult onset still’s syndrome, are discussed. The present era of international travel poses a novel diagnostic and epidemiologic challenge and we must increase our awareness to the possibility of an exotic tropical infectious disease.

Background: Cachibol (known as kadureshet in Hebrew) is a team ball game whose characteristics are similar to those of volleyball. The game is becoming increasingly popular, particularly among adult women and is the fastest growing female sport in Israel. Despite its growing popularity, data on the epidemiology of injuries incurred from this sport are sparse. 

Objectives: To investigate the incidence and severity of injuries among adult female cachibol players.

Methods: We conducted a cross-sectional survey and observational cohort study of 612 amateur female cachibol players participating in a 3 day national tournament; 355 players completed questionnaires relating to traumatic injuries incurred during previous cachibol activity (58% response rate). All injuries sustained during the tournament were reported. 

Results: Fingers were the most commonly injured part of the body, mostly due to a direct hit by the ball. Finger injuries, though considered mild, may have long-term implications: over 50% of the injured players reported long-term finger discomfort. After finger injuries, ankles and knees were the second most commonly injured parts of the body, with a higher rate of absence from sports activity and work and for a longer time compared to finger injuries. 

Conclusions: Due to the unique characteristics of cachibol, the rate of finger injuries is higher in this game than in volleyball. Injuries are a growing cause for concern in view of the rapidly increasing number of cachibol players. Our findings may be useful for developing effective injury prevention programs for cachibol players.