Israel Medical Association Journal

Background: Antibiotic treatment of Clostridium difficile infection (CDI) has a high failure rate. Fecal microbiota transplantation (FMT) has proven very effective in treating these recurrences. 

Objectives: To determine which method of fecal microbiota transplantation (upper or lower gastrointestinal) and which type of donor (a relative or unrelated) is superior.

Methods: This is a retrospective analysis of treatment protocols and outcomes in 22 patients with refractory or recurrent CDI who underwent FMT at two Israeli facilities. Each center used a different donor type, stool preparation and method of delivery. The Tel Aviv Sourasky Medical Center used unrelated fecal donors and frozen stool samples and delivered them primarily (92%) via the lower gastrointestinal (GI) tract. Shaare Zedek Medical Center used fresh donor stool of relatives and delivered them primarily (90%) via the upper GI tract.

Results: FMT had an overall 2 month cure rate of 89%. Patients treated with FMT that was executed through the lower GI tract recovered faster from the infection (1.6 ± 1.08 vs. 2.4 ± 1 days for the upper tract, P = 0.03). The results also showed that patients who received lower GI tract FMTs were more likely to be cured of CDI (100% vs. 75% for upper tract FMTs, P = 0.16). Five patients (22%) died of CDI/FMT-unrelated causes and two (10%) died of CDI/FMT-related causes during the study period.

Conclusions: Lower GI tract FMT is a safe and effective treatment for refractory and recurrent CDI, and yields quicker results than upper GI tract FMT. 

 

Background: Despite the increased worldwide recognition of attention deficit/hyperactivity disorder (ADHD), there is a variability in the diagnostic rate of both ADHD and its co-morbidities. These diversities are probably related to the methodology and instruments used for the diagnosis of ADHD and to awareness and cultural interpretation of its existence. 

Objectives: To identify consistent differences in the clinical profile of Arab and Jewish children with ADHD in Israel who differ in their cultural, ethnic and socioeconomic background. 

Methods: We analyzed the data of 823 children and adolescents with ADHD (516 Jews and 307 Arabs) and compared the clinical characteristics between these two ethnic groups. All patients were evaluated in two neuropediatric and child development centers in northern Israel: one in Haifa and one in Hadera. Children with autism and intellectual disabilities were excluded. 

Results: The distribution of ADHD subtypes was similar in both populations. However, learning disorders and psychiatric co-morbidities (behavioral difficulties and anxiety) were reported more frequently in the Jewish population. The most commonly reported adverse effects to psychostimulants were mood changes, anorexia, headache, insomnia and rebound effect, and were more frequently reported in the Jewish population (42.0% vs.18.0%, P < 0.05).

Conclusions: We assume that these differences are related to cultural and socioeconomic factors. We suggest that the physician take cultural background into consideration when treating patients with ADHD.

 

Background: The long-term significance of apparent life-threatening events (ALTE) has not been thoroughly studied. 

Objectives: To evaluate, at age 5 years, the health status of consecutive children diagnosed with ALTE in infancy. 

Methods: Based on the diagnostic workup, patients were classified into two groups: a ‘broad’ evaluation group (at least one test/procedure related to each of the five main causes: infectious, metabolic, cardiopulmonary, gastroenterological, neurological), and a ‘narrow’ workup group whose evaluation did not cover all five domains. Health status around age 5 was obtained from hospital records, community clinics and parents/caregivers.

Results: We identified 132 children with ALTE. Choking (49.2%) was the most common description, followed by apnea (13.6%), suspected seizure (12.9%), cyanosis (12.1%), breath-holding spell (8.3%), and pallor (3.8%). A broad diagnostic workup was performed in 62.1% of the infants, and a narrow workup in 37.9%. At age 5 years, 56.8% of the children were healthy; 27.3% reported chronic conditions unrelated to ALTE. Twenty-one children (15.9%) had unrelated neurodevelopmental conditions, mostly attention deficit disorder. One of the 132 ALTE patients relapsed and was eventually diagnosed with epilepsy.

Conclusions: A single episode of ALTE in infancy was neither predictive of nor associated with chronic systemic or neurological disease at age 5 years. 

 

Background: Predictive biomarkers for personalized treatment of neoplasms are suggested to be a major advancement in oncology and are increasingly used in clinical practice, albeit based on level II evidence. Target Now® (TN) employs immunostaining and RNA expression on tumor samples to identify potentially beneficial or ineffective drugs. 

Objectives: To explore retrospectively the predictive value of TN for patients with colorectal and gastric carcinomas. 

Methods: The study group comprised colorectal and gastric carcinoma patients with TN test reports. We identified chemotherapy regimens given for stage IV disease for which TN reports indicated prediction. Protocols were classified as having clinical benefit (CB; i.e., stable disease or any objective response) or progressive disease, and this was compared with the TN prediction. 

Results: Nineteen patients – 12 colorectal and 7 gastric carcinomas – met the inclusion criteria. There were 26 evaluable treatment protocols; of 18 with a CB 15 were predicted to have a CB while 3 were predicted to have a lack of CB. Of eight protocols that had no CB, seven were predicted to have a CB and one was predicted to have a lack of CB. A chi-square test was non-significant (P = 0.78). An exploratory analysis yielded a positive predictive value of 68% and a sensitivity of 83% for the TN test. 

Conclusions: This study emphasizes the need for larger multicenter studies to validate the TN test before it is adopted into clinical practice. 

 

Clostridium difficile-associated diarrhea is a problem most hospital-based physicians will face in their career. This review aims to refresh current knowledge with regard to Clostridium difficile infection and bring physicians up to date with the latest developments in the growing field of fecal microbiota transplantation, the benefits it offers, and the promise this and other developments hold for the future. 

Background: Benign prostate hyperplasia (BPH) is a common age-dependent urological condition that can disrupt quality of life if the patient's treatment choice is inappropriate. 

Objectives: To examine whether patients’ demography and personality affect their decision regarding the type of treatment: namely, conservative or surgical. 

Methods: A total of 105 BPH patients treated during the period 2005–2008 were retrospectively categorized into three groups according to treatment received: (i) medication only (n=056), (ii) combined treatment (the initial medication treatment was switched to surgical treatment) (n=32), and (iii) surgery only (n=17). A prerequisite for inclusion in the study was use of BPH medication for at least half a year before the study (groups 1 and 2). These groups completed the International Prostate Symptom Score (IPSS) questionnaire at the start of BPH medical treatment (IPSS 1) and at the start of the trial (IPSS 2), and the staff calculated the difference (IPSS 1-IPSS 2 = Delta IPSS = DIPSS).  All three groups provided demographic data (age, country of origin, education) and completed tri-dimensional personality questionnaires (TPQ) to measure three independent "temperament" personality dimensions to evaluate how different individuals feel or behave: novel seeking (NS), harm avoidance (HA), and reward dependence (RD). Data were analyzed using chi-square, t-test, one-way ANOVA and logistic regression.

Results: Demographic variables and the RD dimension differed according to choice of BPH treatment. 

Conclusions: Our study suggests that symptomatic BPH treatment is influenced less by the patient's personality and more by his life circumstances. Israeli-born patients were more conservative, Russian-born patients were ambivalent, and other foreign-born patients predominantly preferred surgical treatment. We assume that personality has a more decisive effect on patients with malignant disease and they accept the medical advice more easily. 

 

Background: The number of patients awaiting organ transplantation continues to exceed the number of available organs. 

Objectives: To document changes in the demographic characteristics of brain-dead, heart-beating organ donors over the past 10 years which may impact on organ utilization. 

Methods: Data were extracted from the Israel Transplant Registry and the Donor Action database for the 10 year period 2004–2013, inclusive. 

Results: The median age of the donors increased from 44 (range 3–73 years) to 53.5 years (range 1–79 years) (P < 0.001). There was a significant increase in the median age of donors of kidney (33 to 51 years, P < 0.001), liver (41 to 53 years, P < 0.001) and lung (40 to 49.5 years, P < 0.001). The number of donors dying from trauma decreased (34.5% to 20%, P < 0.001), while those with anoxic brain damage increased (14.5% to 25%, P < 0.001). The percent of male donors decreased over the study period, from 63% to 53%. An increase was noted in the mean number of organs transplanted per donor, from 3.29 to 3.82 per donor, due mainly to a significant increase in the utilization of lungs (31.5% to 51.3%, P < 0.001) and livers (76.3% to 82.4%, P < 0.001) while heart utilization decreased significantly since 2006 (40.9% to 17.5%, P < 0.001). 

Conclusion: Trends in the heart-beating, brain-dead organ donor pool in Israel over the past 10 years reveal significant changes in demographic characteristics which in the future will impact on the number of organs available for transplantation. 

 

Background: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.

Objectives: To analyze the impact of genetic diagnosis on the clinical management of HCM.

Methods: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.

Results: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.

Conclusions: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determine the indication for genetic testing and interpretation of the results.

Methods: In this retrospective multicenter open-label study we examined the efficacy and tolerability of VNS in patients in five adult and pediatric epilepsy centers in Israel. All patients had drug-resistant epilepsy and after VNS implantation in 2006–2007 were followed for a minimum of 18 months. Patients were divided into two age groups: < 21 and > 21 years old.

Results: Fifty-six adults and children had a stimulator implanted in 2006–2007. At 18 months post-VNS implantation, none of the patients was seizure-free, 24.3% reported a reduction in seizures of ≥ 75%, 19% reported a 50–75% reduction, and 10.8% a 25–50% reduction. The best response rate occurred in patients with complex partial seizures. Among these patients, 7 reported a ≥ 75% reduction, 5 patients a 50–75% reduction, 3 patients a 25–50% reduction, and 8 patients a < 25% reduction. A comparison of the two age groups showed a higher reduction in seizure rate in the older group (< 21 years old) than the younger group.

Conclusions: VNS is a relatively effective and safe palliative method for treating refractory epilepsy in both adults and children. It is an alternative treatment for patients with drug-resistant epilepsy, even after a relatively longed disease duration, who are not candidates for localized epilepsy surgery.

 Background: Patients with transient ischemic attack (TIA) at a high risk of stroke can be identified and should be managed urgently.

Objectives: To investigate whether recognized recommendations are being implemented in Israel.

Methods: An Israeli nationwide registry on patients admitted with stroke and TIA was conducted in all acute care hospitals (NASIS registry) within 2 successive months during 2004, 2007 and 2010. A revised ABCD² score was applied retrospectively. Patients with TIA were divided into a low risk group (LRG, 0–3 points) and a high risk group (HRG, 4–6 points) and were compared to patients with minor ischemic strokes (MIS, NIHSS score ≤ 5 points).

Results: A total of 3336 patients were included (1023 with TIA: LRG 484, HRG 539, and MIS 2313). LRG patients were younger and had lower rates of most traditional risk factors as compared with HRG and MIS patients. Brain imaging was performed in almost all the patients. Ancillary tests (vascular and cardiac) were overall underused, yet were performed more in LRG (53.2% and 26.9% respectively) than in HRG patients (41.6%, 18.9%). Between periods there was no change in usage of ancillary tests for the LRG and a modest increase in both HRG and MIS patients. For performance of vascular investigations overall, the odds ratio was 1.69 (95% confidence interval 1.42–2.00) comparing 2010 with 2004, but 0.7 (95% CI 0.5–0.9) comparing HRG with LRG. Between periods an increase in statin usage was observed in all groups (OR 2.69, 95% CI 2.25–3.21) but was more marked in MIS patients (OR 3.06, 95% CI 2.47–3.8). 

Conclusions: The approach to TIA risk stratification and management in Israeli hospitals does not follow standards set by current guidelines. Standardized protocols for TIA should be used to assure effective management.

Objectives: To report our first year experience with a CPU located in an internal medicine department as compared to the year before establishment of the CPU.

Methods: We retrospectively evaluated the medical records of consecutive patients who were admitted to our internal medicine department for the investigation of chest pain for 2 different years: a year before and a year after the establishment of the CPU in the department. We focused on the patients' characteristics and the impact of the CPU regarding the investigational modalities used and the length of in-hospital stay.

Results: In the year before establishment of the CPU, 258 patients were admitted to our department with chest pain, compared to 417 patients admitted to the CPU in the first year of its operation. All patients were followed for serial electrocardiographic and cardiac enzyme testing. All CPU patients (100%) underwent investigation compared to only 171 patients (66%) in the pre-CPU year. During the year pre-CPU, 164 non-invasive tests were performed (0.64 tests per patient) compared to 506 tests (1.2 tests/patient) in the CPU population. Coronary arteriography was performed in 35 patients (14%) during the pre-CPU year, mostly as the first test performed, compared to 61 patients (15%) during the CPU year, mostly as a second test, with only 5 procedures (1.1%) being the first test performed. The length of hospitalization was significantly shorter during the CPU year, 37.8 ± 29.4 hours compared to 66.8 ± 46 hours in the pre-CPU year.

Conclusions: Establishment of a CPU in an internal medicine department significantly decreased the need for invasive coronary arteriography as the first modality for investigating patients admitted with chest pain, significantly decreased the need for invasive procedures (especially where no intervention was performed), and significantly shortened the hospitalization period. CPU is an effective facility for rapid and effective investigation of patients admitted with chest pain. 

Background: Since clinical signs of meningeal irritation in infants may be absent or misleading, the American Academy of Pediatrics in 1996 recommended that a lumbar puncture be performed in young children following a febrile seizure. Recent evidence supports a conservative approach in children who do not look ill at the time of the physician's assessment. Moreover, seizures as the presenting or sole symptom of bacterial meningitis are very rare.

Objectives: To assess physicians’ compliance with the Academy’s recommendations and to determine the incidence of meningitis among febrile seizure patients, including those who did not undergo the puncture.

Methods: We conducted a retrospective analysis of the number of punctures obtained in febrile seizure patients aged 6–24 months, focusing on the clinician's indications for performing the procedure and on the clinical course of children who did not undergo the puncture.

Results: Among 278 patients (84% simple febrile seizure), 52 (18.7%) underwent the procedure. It was performed in 38% of 45 complex febrile seizure cases and in 48% of 91 infants younger than 12 months of age. Aseptic meningitis occurred in two infants, both with post-ictal apathy. Bacterial meningitis was not found and in none of the patients who did not undergo the puncture was meningitis later diagnosed.

Conclusions: Compliance with the Academy’s recommendations was low, as emergency room physicians based their decision whether to obtain a lumbar puncture solely on clinical grounds. No case of bacterial meningitis was detected among 278 young children with a febrile seizure, including those who did not undergo the puncture.
 

Background: Skin-prick tests (SPT), food-specific immunoglobulin E level (sIgE) and clinical history have limited value individually in predicting the severity of outcome of the oral food challenge (OFC). 

Objectives: To develop a score that accounts for SPT, sIgE and clinical history to predict the risk of severe reaction to the OFC. 

Methods: A 5 year retrospective chart review was performed on 983 children who underwent OFC to egg, milk and peanut. 

Results: Using multilogistic regression, four major indicators were found to be independently associated with failed OFC: sIgE (odds ratio = 1.04, P < 0.0001) , wheal size of the SPT (OR = 1.23, P < 0.0001), a history of any prior reaction to the food (OR = 1.13, P < 0.01), and a history of a prior non-cutaneous reaction (OR = 1.99, P < 0.01)  and three were independently associated with anaphylaxis: wheal size (OR = 1.16, P < 0.001), a history of a prior non-cutaneous reaction (OR = 4.24, P < 0.01), and age (OR = 1.07, P < 0.03). A Food Challenge Score (0–4) was developed which accounted for SPT wheal, sIgE, a history of a prior non-cutaneous reaction, and age. A score of 0–1 had a negative predictive value for multisystem reaction to the OFC: 95% for milk, 91% for egg and 93% for peanut. A score of 3–4 had a positive predictive value for anaphylaxis:  62% for milk, 92% for egg and 86% for peanut.

Conclusions: Severe reaction to milk, egg and peanut OFC can be predicted using a simple score that takes into account clinical data that are commonly available prior to the challenges.