Israel Medical Association Journal

Background: There is currently no standard salvage chemotherapy for the 40–50% of patients with non-Hodgkin’s lymphoma who fail first-line treatment.

Objectives: To review the experience of a major tertiary medical center with DVIP (dexamethasone, etoposide, ifosfamide and cisplatin) salvage therapy for primary refractory/relapsing NHL[1].

Methods: We reviewed the records of all patients with NHL who received DVIP salvage therapy during the period 1993 to 2005.

Results: We identified 37 adult patients (mean age 56.3 years): 29 with aggressive lymphoma and 8 with indolent lymphoma. Mean event-free survival was 13.5 months (range 0–82 months), mean time between diagnosis and DVIP treatment 18.5 months (range 2–101), and mean number of DVIP cycles 1.9. Four patients (11%) achieved a complete response and 9 (24%) a partial response (overall response 35%). Consolidation with stem cell transplantation was used in 14 patients with aggressive lymphoma and 4 with indolent lymphoma; 14 patients, all with aggressive lymphoma, responded (12 complete, 2 partial). Of the 10 patients who underwent SCT[2] despite no response to salvage DVIP, 6 achieved a complete response. Five year overall survival from diagnosis for the whole sample was 39.4 ± 8.7%, and 5 year post-DVIP overall survival 37.6 ± 8.0%. On multivariate analysis, SCT was the strongest predictor of survival (relative risk 0.73, P < 0.0001) followed by a high score on the International Prognostic Index (RR[3] 3.71, P = 0.032).

Conclusions: DVIP salvage therapy for NHL was associated with a low response rate of 35% but a 5 year post-DVIP survival rate of 37.6%. Patients who are refractory to salvage treatment with DVIP might still be salvaged with SCT.

Background: Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease. The Computer-based Clinical Decision Support System provides an opportunity to close these gaps.

Objectives: To study the impact of computerized intervention on secondary prevention of CAD[1].

Methods: The CDSS[2] was programmed to automatically detect patients with CAD and to evaluate the availability of an updated lipoprotein profile and treatment with lipid-lowering drugs. The program produced automatic computer-generated monitoring and treatment recommendations. Adjusted primary clinics were randomly assigned to intervention (n=56) or standard care arms (n=56). Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment. Compliance and lipid levels were monitored. The study group comprised all patients with CAD who were alive at least 3 months after hospitalization.

Results: Follow-up was available for 7448 patients with CAD (median 19.8 months, range 6–36 months). Overall, 51.7% of patients were adequately screened, and 55.7% of patients were compliant with treatment recommended to lower lipid level. A significant decrease in low density lipoprotein levels was observed in both arms, but was more pronounced in the intervention arm: 121.9 ± 34.2 vs. 124.3 ± 34.6 mg/dl (P < 0.02). A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs, 37% vs. 40.9% (P < 0.001).

Conclusions: This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines, presenting a major obstacle to implementing effective secondary prevention. Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation.

Background: Studies from many countries have reported an increasing prevalence of autistic spectrum disorder in childhood. No comprehensive epidemiological studies of ASD[1] have been performed in Israel.

Objectives: To describe time trends in the reported number of patients with ASD in Israel and to characterize the demographic features of the reported patients.

Methods: We reviewed the charts of the National Insurance Institute of Israel from 1972 to 2004 for all children with a diagnosis of ASD receiving disability benefits.

Results: A total of 3509 children met the study criteria. Eighty percent were boys and 98% were Jewish. The incidence data showed an increase in the number of cases from zero in 1982–84 and 2 (1.2 per million capita under 18 years) in 1985 to a high of 428 cases in 2004 (190 per million).

Conclusions: This is the first comprehensive study of the incidence of ASD in Israel. According to data derived from official health records, the rate of occurrence of ASD has substantially increased in the last 20 years. Further studies are needed to determine if this is a true increase or if the findings were confounded by external factors, such as recent improvements in diagnostic measures and social stigmas.

Background: According to the U.S. Centers for Disease Control guidelines, prolonged rupture of membranes mandates intrapartum antimicrobial prophylaxis for group B Streptococcus whenever maternal GBS[1] status is unknown.

Objectives: To evaluate the local incidence, early detection and outcome of early-onset GBS sepsis in 35–42 week old neonates born after PROM[2] to women with unknown GBS status who were not given intrapartum antimicrobial prophylaxis.

Methods: During a 1 year period, we studied all neonates born beyond 35 weeks gestation with maternal PROM ≥ 18 hours, unknown maternal GBS status and without prior administration of IAP[3]. Complete blood count, C-reactive protein, blood culture and polymerase chain reaction amplification of bacterial 16S rRNA gene were performed in blood samples collected immediately after birth. Unfavorable outcome was defined by one or more of the following: GBS bacteremia, clinical signs of sepsis, or positive PCR[4].

Results:  Of the 3616 liveborns 212 (5.9%) met the inclusion criteria. Only 12 (5.7%) of these neonates presented signs suggestive of sepsis. PCR was negative in all cases. Fifty-eight neonates (27.4%) had CRP[5] > 1.0 mg/dl and/or complete blood count abnormalities, but these were not significantly associated with unfavorable outcome. Early-onset GBS sepsis occurred in one neonate in this high risk group (1/212 = 0.47%, 95% CI 0.012–2.6). 

Conclusions: In this single-institution study, the incidence of early-onset GBS sepsis in neonates born after PROM of ≥ 18 hours, unknown maternal GBS status and no intrapartum antimicrobial prophylaxis was 0.47%.

Synovial plicae are membranous inward folds of the synovial lining of the knee joint capsula. Such folds are regularly found in the human knee, but most are asymptomatic and of little clinical consequence. However, they can become symptomatic and cause knee pain. In this review, we will discuss medial plica syndrome. Medial plica irritation of the knee is a common source of anterior knee pain. The main complaint is an intermittent, dull, aching pain in the area medial to the patella above the joint line and in the supramedial patellar area. Pain increases with activity, especially when knee flexion and extension are required. Treatment includes physiotherapy, reducing activity and rest. In cases that do not respond initially to an exercise program, corticosteroid injections and non-steroidal anti-inflammatory medication are given. Results of conservative treatment seem to be more appropriate in young patients with a short duration of symptoms. If conservative treatment fails, surgical treatment using arthroscopy is appropriate. During arthroscopy, excision of the whole plica should be achieved.

Asthma is an airway disease, yet that airway extends all the way to the alveolar tissue area. Pathohistiological as well as physiological and clinical studies have recently documented this aspect of asthma. The implications of this are important for all asthmatic patients, but particularly for those whose asthma is more difficult to control. Many of the inhaled preparations used as therapy for asthma are of relatively large particle size. 

Thus, the deposition of these medications is mainly in the central and medium sized airways and very little of a given actuation gets to the distal airways. Ultrafine inhaled steroid particles have been shown to reach the more peripheral portions of the airway, and improvement in outcome variables such as air trapping as well as symptomatic outcomes have been demonstrated. This review focuses on anatomic airway changes, physiological changes of the distal airways, clinical outcome data, and particle size of inhaled preparations.

Hereditary angioedema is a rare genetic disorder, manifested by recurrent edema leading to disfigurement, organ dysfunction and life-threatening respiratory impairment that may become fatal. The hallmark of HAE is a C1 esterase inhibitor deficiency, but recent evidence points at bradykinin as the main mediator that causes hyperpermeability of small vasculature, leading to accumulation of edema fluid. Current therapeutic options for HAE[1] are limited, and consist of drugs, replacement therapy, and supportive treatment. In view of many disadvantages of the current therapeutic modalities new approaches to the treatment of HAE are now being offered. This review summarizes our experience with a new line of medications developed for the treatment of acute exacerbations and prophylaxis of HAE – icatibant: bradykinin receptor antagonist, ecallantide: kallikrein inhibitor, and two C1 INH[2] preparations: Berinert-P, human plasma-derived concentrate, and Rhucin: novel recombinant C1-INH produced in transgenic rabbits. Preliminary results of these studies are encouraging and may bring new hope to the patients with this distressing condition. The exact number of HAE patients in Israel is unknown and because patients are treated individually and comprehensive laboratory assessment is partial, many cases might be missed or not treated according to accepted guidelines. We offer a new specialty center for HAE patients, addressing the medical and psychosocial needs of patients and their families.

The pollen of Ambrosia (ragweed) is one of the major causes of pollen-induced allergy worldwide. This family of plants has apparently evolved in North America but was later spread into Europe and Asia. Flowering of the Ambrosias starts in mid-July and continues throughout the autumn and is a cause of major morbidity to allergic sensitized patients. The invasion of new species of Ambrosia into Israel is still in progress. Plants of Ambrosia artemisiifolia (American short ragweed), Ambrosia trifida (American giant ragweed), Ambrosia confertifolia, Ambrosia grayi and Ambrosia tenuifolia are increasingly found in Israel, mainly in the Hula valley in the eastern Galilee and near the Alexander River in the Sharon plain. From experience it is known that the time it takes to eradicate a new invasive species is limited. Action should be taken immediately or this new invasion will spread and cause a significantly increased burden of morbidity and increased health costs in Israel.

Background: Insulin-dependent diabetes mellitus is dominated by a Th1 response whereas atopic diseases such as asthma, eczema and allergic rhinitis are characterized by a Th2 response. Because it is known that Th1 and Th2 cells reciprocally counteract each other, it can be speculated that the prevalence of Th2-mediated diseases is lower in patients with a Th1-mediated disease.

Objectives: To compare the prevalence of atopic diseases among children with IDDM[1] and age-matched controls.

Methods: The study group comprised 65 children with IDDM attending the pediatric endocrinology clinic at the Wolfson Medical Center. The control group consisted of 74 non-diabetic children who presented at the emergency room due to an acute illness (burns, abdominal pain, fever, head trauma). Patients were asked to complete a detailed questionnaire on their history of personal and familial atopic and autoimmune diseases. In addition, a total serum immunoglobulin E concentration and the presence of IgE[2] antibodies to a panel of relevant inhalant allergens were analyzed.

Results: Children with IDDM and their first-degree relatives had a significantly higher prevalence of other autoimmune diseases such as thyroiditis and celiac as compared to controls. The two groups had a similar prevalence of atopic diseases with respect to history, total serum IgE, or the presence of IgE antibodies to a panel of relevant inhalant allergens.

Conclusions: The prevalence of atopic diseases in IDDM patients was similar to that in the normal population. Our results suggest that the traditional Th1/Th2 theory to explain the complexity of the immune response is oversimplified. 

Background: Detrimental effects of military service among the civilian Palestinian population have been reported in soldiers.

Objectives: To examine the frequency and type of stressors encountered by soldiers in close contact with the CPP and its relationship with post-traumatic symptomatology. We also investigated coping methods and the preferred types of professional help.

Methods: Using random digit dialing methodology we conducted a phone survey of veteran soldiers, men (n=167) and women (n=59) in close contact with the CPP; the comparison group comprised male veteran soldiers with no CPP exposure (n=74). We used focus groups to develop context-related measures to assess exposure to violent incidents, coping modes and preferred modes of professional assistance. We included measures of traumatic exposure, post-traumatic stress symptoms and post-traumatic stress disorder.

Results: Soldiers who served among the CPP had greater exposure to traumatic events and to civilian-related violent incidents (more than half as victims, and a third as perpetrators); and 17.4% perceived their behavior as degrading civilians. Primary traumatic exposure, perceived health problems and avoidance coping were found to be risk factors for PTS[1] and PTSD[2]. Involvement in incidents that may have degraded Palestinian civilians predicted PTS.
Conclusions: Friction with the CPP in itself does not constitute a risk factor for psychopathology among soldiers. However, contact with this population entails more exposure to traumatic events, which may cause PTS and PTSD. Furthermore, a relative minority of soldiers may be involved in situations that may degrade civilians, which is a risk factor for PTS. To avoid violent and sometimes degrading behaviors, appropriate psycho-educational and behavioral preparation should be provided.|



 

[1] PTS = post-traumatic stress symptoms

[2] PTSD = post-traumatic stress disorder
 
 

Background: Over the last two decades, the epidemiology, treatment strategy and mortality rate for congenital diaphragmatic hernia have changed.

Objectives: To retrospectively analyze our experience with CDH[1] of the last 22 years.

Methods: We reviewed the charts of all infants suffering from CDH between 1985 and 2007. Prenatal and maternal as well as perinatal and neonatal data were collected, including outcome parameters. The 71 infants that we identified were divided them into two historical groups: from 1985 to 1995 (group 1, 123 patients) and from 1996 to 2007 (group 2, 45 patients).

Results: We found an increase in the incidence of prenatal diagnosis and a subsequent significant decrease in gestational age at diagnosis in group 2 (25 weeks gestation, compared with 30 weeks gestation in group 1, P = 0.018). In addition, we noted a trend toward a reduced number of infants with right-sided hernia and associated cardiac anomalies. The timing to post-delivery surgery was significantly longer in group 2 (20 hours in group 1 vs. 53 hours in group 2, P < 0.001). A significant reduction in postoperative mortality was demonstrated in group 2 compared with group 1 (13.5% vs. 38.7% respectively, P = 0.04),

Conclusion: Our data suggest a higher survival rate for operated infants in group 1 during the last decade, probably due to changes in preoperative methods of treatment as well as later surgery timing compared to group 1. We speculate that today’s cases of congenital diaphragmatic hernia are probably milder than in the past due to earlier and more detailed prenatal diagnosis and subsequent termination of pregnancies for the more severe forms of the disorder.