Israel Medical Association Journal

Background: Cystinuria is an autosomal recessive disease that is manifested by kidney stones   and is caused by mutations in two genes: SLC3A1 on chromosome 2p and SLC7A9 on chromosome 19q. Urinary cystine levels in obligate carriers are often, but not always, helpful in identifying the causative gene.

Objectives: To characterize the clinical features and analyze the genetic basis of cystinuria in an inbred Moslem Arab Israeli family.

Methods: Family members were evaluated for urinary cystine and amino acid levels. DNA was initially analyzed with polymorphic markers close to the two genes and SLC7A9 was fully sequenced.

Results: Full segregation was found with the marker close to SLC7A9. Sequencing of this gene revealed a missense mutation, P482L, in the homozygous state in all three affected sibs.

Conclusions: A combination of urinary cystine levels in obligate carriers, segregation analysis with polymorphic markers, and sequencing can save time and resources in the search for cystinuria mutations.
 

Background: Iron deficiency is the most prevalent anemia in infants and is known to be a major public health problem.

Objective: To examine mothers’ knowledge and adherence with recommendations regarding iron supplementation and assess their association with the prevalence of anemia in infants.

Methods: Data on 101 infants and mothers of infants born between November 2000 and February 2001, living in a small Jewish town in southern Israel, were collected using a structured questionnaire and the infants’ medical charts. Anemia was defined as serum hemoglobin less than 11 g/dl. Independent variables include socioeconomic data, mothers' knowledge, and adherence to treatment as reported by them. Chi-square test was used to analyze categorical variables, t-test was used for continuous variables, and hemoglobin was tested at 9–12 months of age.

Results: Of the 101 infants in the study, 47% had serum hemoglobin under 11 g/dl. Of the mothers, 62 (62%) were partially or completely non-compliant with iron supplementation; 34 (34%) had low level of knowledge regarding anemia. Multivariate logistic regression analysis revealed a significant and inverse relationship between the presence of anemia and the level of maternal knowledge (odds ratio = 5.6, 95% confidence interval 1.6–9.7; P = 0.006) and reported adherence with iron supplementation (3.2, 1.1–9.7; P = 0.04) after controlling for confounding factors: maternal education, socioeconomic status, breastfeeding, and meat consumption.

Conclusions: The presence of iron deficiency anemia in infants in southern Israel is inversely affected by the level of maternal knowledge of anemia and adherence to iron supplementation. Low level of knowledge is also directly related to low adherence.
 

Background: Patients with end-stage renal disease are at high risk of mycobacterial infection.

Objectives: To analyze the difficulties in reaching an accurate diagnosis of tuberculosis in dialysis patients.

Methods: We conducted a retrospective follow-up of patients who attended our peritoneal and hemodialysis units during the 10 year period 1995–2005.

Results: Our dialysis unit diagnosed 10 cases of tuberculosis caused by Mycobacterium tuberculosis and 9 cases of Mycobacterium other than tuberculosis. In the former group, five patients had mycobacterium in the sputum, which was diagnosed by intraabdominal mass biopsy in one, culture of the gastric juices in one, and pleural fluid culture or pleural biopsy in three. One of these patients was suffering from pleural TB[1] as well as Potts disease. Of the patients with Mycobacterium other than tuberculosis, five were diagnosed by sputum cultures, three by urine cultures and one in peritoneal fluid. Differences in treatment and outcome were also reviewed.

Conclusions: The diagnosis of TB in dialysis patients should be approached with a high index of suspicion. It is clear that extensive diagnostic procedures are required to ensure an accurate diagnosis of the disease. Tuberculosis incurs a significant added burden due to the need for isolation of infected patients within the dialysis unit. Treatment of patients with Mycobacterium other than tuberculosis should be addressed individually.

Background: The cognitive impairment (frontal, parietal) in many patients with multiple sclerosis does not correlate with the degree of neurological disability and disease duration. Frontal/prefrontal cognitive impairment requires neuropsychological diagnostic tools.

Objectives: To evaluate the clinical effect of IFNβ-1b[1] (Betaferon®) treatment on cognitive function and event-related potential as compared to the clinical course (EDSS[2]) in MS patients during 1 year of follow-up.

Methods: This prospective open-label design study included 16 consecutive patients with relapsing forms of MS attending the MS outpatient clinic. Mean EDSS score was calculated prior to starting treatment. Parietal lobe event-related potential P300 was elicited using an auditory physical stimulus to an alert subject. Mean P300 amplitude and latency were calculated for the group before treatment. The Wisconsin Card Sorting Test, which measures frontal lobe functions, was performed before the treatment. After 1 year of treatment a second P300 and Wisconsin Card Sorting Test were performed and the mean change between visit 1 and baseline was calculated for each parameter. Correlation between the change in P300 and the Wisconsin Card Sorting Test score at baseline was measured using the paired t-test.

Results: There was a significant reduction in P300 amplitude and latency after 1 year of treatment with IFNβ-1b: from 20.3 ± 8.3 μv to 13.1 ± 10.6 μv (P = 0.026) for amplitude, and from 312.9 ± 15.6 msec to 302.0 ± 17.0 msec (P = 0.002) for latency. The Perseverative Response (raw score) and the Perseverative Response U.S. Census age-matched standard score showed a significant improvement – from 20.7 ± 30.7 to 13.1 ± 10.6 (P = 0.001) and 96.7 ± 15.7 to 100.1 ± 11.1 (P = 0.0025) respectively – after 1 year of treatment. A mild but not significant improvement was observed on the EDSS after 1 year of treatment: 2.9 ± 0.5 to 2.8 ± 1.1.

Conclusions: A cognitive decline in MS patients may have a negative impact on the quality of life, affecting all active daily living domains. IFNβ-1b, a disease-modifying therapy, has demonstrated a positive therapeutic effect on cognitive dysfunction, unrelated to its effect on the EDSS score and course of the disease.

Background: The extent of medical and financial problems of polypharmacy in the elderly is disturbing, particularly in nursing homes and nursing departments.

Objectives: To improve drug therapy and minimize drug intake in nursing departments.

Methods: We introduced a geriatric-palliative approach and methodology to combat the problem of polypharmacy. The study group comprised 119 disabled patients in six geriatric nursing departments, and the control group 71 patients of comparable age, gender and co-morbidities patients in the same wards. After 12 months, we assessed whether any change in medications affected the death rate, referrals to acute care facility and costs.

Results: A total of 332 different drugs were discontinued in 119 patients (average of 2.8 drugs per patient) and was not associated with significant adverse effects. The overall rate of drug discontinuation failure was 18% of all patients and 10% of all drugs. The 1 year mortality rate was 45% in the control group but only 21% in the study group (P < 0.001, chi-square test). The patients’ annual referral rate to acute care facilities was 30% in the control group but only 11.8% in the study group (P < 0.002). The intervention was associated with a substantial decrease in the cost of drugs.

Conclusions: Application of the geriatric-palliative methodology in the disabled elderly enables simultaneous discontinuation of several medications and yields a number of benefits: reduction in mortality rates and referrals to acute care facilities, lower costs, and improved quality of living.

Background: Asthma control and treatment compliance are widely investigated issues around the world. Studies have demonstrated relatively low asthma compliance and control in 40–90% of asthma patients in different countries. There are no available data on the Israeli adult asthmatic population

Objectives: To investigate the level of asthma control and compliance in adult asthmatic patients.

Methods: This cross-sectional study of consecutive adult asthmatic patients visiting the pulmonary clinic used a combined questionnaire that included demographics, data on asthma severity and management, and asthma control and compliance scores. Each patient was interviewed and questionnaires were filled out during a routine visit.

Results: The study group comprised 142 males (35.4%) and 259 females (64.6%). Compliance was found optimal in 8 patients (2%), fair in 146 (36%), partial in 156 (39%) and poor in 92 (23%) of the participating asthmatic patients. Asthma control was found optimal in 26 (7%), fair in 124 (31%), partial in 122 (30%) and poor in 129 (32%) patients. Sephardic and Ashkenazi Jewish origin, higher level of education, and treatment protocol including either single fixed-dose inhalers or short-acting beta-agonist bronchodilators significantly improved compliance in our cohort. Socioeconomic status and compliance were found to positively affect asthma control, whereas active smoking negatively affected asthma control in the study patients.

Conclusions: The figures of optimal asthma control and compliance to treatment in Israeli adult asthmatics are low and worse than reported in other studies abroad.
 

Background: The patient package insert, an information leaflet included by law in the packaging of prescription drugs, contains information for the user on the specific medication.

Objectives: To explore how patient information leaflets influence patient anxiety and adherence.

Methods: A prospective cohort study was conducted in the practices of 15 family physicians. All patients receiving a new prescription for antibiotics, analgesics or antihypertensives were included. Physicians completed a questionnaire containing demographic data, assessment of the patient’s anxiety, a prediction about adherence to the treatment, and response to the information leaflet. Patients were contacted by telephone for a follow-up structured interview. Patients' reactions to the information leaflet, adherence to treatment, and use of other sources of information on medication were assessed.

Results: The study group comprised 200 patients. The patient information leaflet was read by 103 of them (51.5%). A higher educational level and a chronic medication were associated with reading the leaflet (P = 0.02 and 0.01 respectively). In 36 (34.9%), an increase in anxiety was reported after reading the leaflet. Among those who read the leaflet, 9.7% had decreased adherence. Patients who stated that reading the leaflet caused anxiety were more likely to reduce their use of the medication – 7/36 (19.5%) vs. 3/67 (4.5%), P = 0.01.

Conclusions: The proportion of patients reading the drug information leaflet is about 50%, lower than that found in previous studies. Reading the leaflet did not greatly affect adherence but aroused anxiety and decreased adherence in some patients.
 

Background: Femoral artery vascular complications are the most common adverse events following cardiac catheterization. Smaller diameter introducer sheaths and catheters are likely to lower the puncture site complication rate but may hinder visualization.

Objectives: To evaluate the safety and angiographic quality of 4 French catheters.

Methods: The study was designed to simulate real-life operator-based experience. Diagnostic angiography was performed with either 4F or 6F diagnostic catheters; the size of the catheter used in each patient was predetermined by the day of the month. Patients undergoing 4F and 6F diagnostic angiography were ambulated after 4 and 6 hours, respectively. The following technical parameters were recorded by the operator: ease of introducer sheath insertion, ease of coronary intubation, ease of injection, coronary opacification, collateral flow demonstration, and overall assessment. Adverse events were recorded in all patients and included minor bleeding, major bleeding (necessitating blood transfusion), minor hematoma, major hematoma, pseudo-aneurysm formation and arteriovenous fistula.

Results: The study group included 177 patients, of whom 91 were in the 4F arm and 86 in the 6F arm. Demographic and procedural data were similar in both groups. Seventy-seven percent of 6F and 50% of 4F procedures were evaluated as excellent (P < 0.05). This difference was attributed to easier intubation of the coronary ostium and contrast material injection, increased opacification of the coronary arteries, and demonstration of collateral flow with 6F catheters. Complications occurred in 22% of patients treated with 6F catheters and 10% of those treated with 4F catheters (P = 0.11). Of the 50 patients who switched from 4F to 6F 12% had complications. In patients undergoing diagnostic angiography, the complication rate was 10% vs. 27% (most of them minor) in the 4F and 6F groups, respectively (P < 0.05).
Conclusions: Patients catheterized with 4F have fewer complications compared with 6F diagnostic catheters even when ambulated earlier. Although 4F had a reduced quality compared to 6F angiographies, they were evaluated as satisfactory or excellent in quality 85% of the time. 4F catheters have a potential for reduced hospitalization stay and are a good option for primary catheterization in patients not anticipated to undergo coronary intervention

Background: When encountering complaints of pain in the area of Achilles tendon with a suspected lesion, the clinician seldom reaches a precise diagnosis based only on X-ray and clinical examination. Ultrasonography is useful for evaluating the pathology and treatment.

Objectives: To assess the relative contribution of real-time intraoperative ultrasound examination and immediate postoperative ultrasound in patients with acute rupture of the Achilles tendon treated by percutaneous suture method. The combination of both procedures provides a unique advantage that could facilitate better results.

Methods: Ultrasound examination was used in 20 patients with acute rupture of the Achilles tendon who were treated surgically. Intraoperative as well as postoperative ultrasound examinations were performed in 5 patients whereas 15 patients underwent an immediate postoperative ultrasound.

Results: Ultrasound pathologies were found in all patients. Percutaneous surgical correction of ruptured Achilles tendon with accurate positioning of the foot using real-time sonography was successful in all the patients.

Conclusion: As in many other soft tissue lesions, ultrasonography is a useful tool for evaluating the pathology and for planning the surgical correction of ruptures in the Achilles tendon.

Background: In 2003 a total of 43 soldiers in the Israel Defense Forces committed suicide; only 20% of them were known to the IDF[1] mental health services. Somatic symptoms are often the only presentation of emotional distress during the primary care visit and may be the key to early identification and treatment.

Objectives: To examine whether the information in the medical records of soldiers can be used to identify those suffering from anxiety, affective or somatoform disorder.

Methods: We conducted a case-control study using the information in the electronic medical records of soldiers who during their 3 year service developed affective disorder, anxiety, or somatoform disorder. A control group was matched for recruitment date, type of unit and occupation in the service, and the Performance Prediction Score. The number and reasons for physician visits were collated.

Results: The files of 285 soldiers were examined: 155 cases and 130 controls. The numbers of visits (mean SD) during the 3 and 6 month periods in the case and control groups were 4.7 ± 3.3 and 7.1 ± 5.0, and 4.1 ± 2.9 and 5.9 ± 4.6 respectively. The difference was statistically significant only for the 6 month period (P < 0.05). The variables that remained significant, after stepwise multivariate regression were the Performance Prediction Score and the presenting complaints of back pain and diarrhea.

Conclusions: These findings may spur the development of a computer-generated warning for the primary care physician who will then be able to interview his or her patient appropriately and identify mental distress earlier. 

Inherited forms of proteinuria constitute a rare and heterogeneous group of diseases, the most prominent of which is glomerular dysfunction, which leads to proteinuria. Investigation of the genetic background underlying these diseases has provided significant data on the normal operation of the glomerular filter. Among the different components of the glomerulus, the podocyte slit diaphragm is considered the main source for genetically derived protein alteration, which leads in turn to proteinuria. Investigation of the different proteins revealed that the lack of nephrin and podocin is the leading cause of several inherited forms of proteinuria. It was also proposed that the lack of podocin is linked to cardiac anomalies. This review suggests that the absence of slit diaphragm proteins and the open zipper phenomenon are associated with cardiac anomalies.

Background: Recently the Joint National Committee (7th report) introduced the term “pre-hypertension.” Little is known on its prevalence in the general population.

Objectives: To assess the prevalence of pre-hypertension in a large national cohort.

Methods: We analyzed the database of all ≥ 18 year old members of Leumit Health Services, one of the four health management organizations in Israel, from which we retrieved the recorded blood pressure levels. Pre-hypertension was defined according to the JNC-7[1] criteria.

Results: Of the 426,033 subjects 18.6% had a diagnosis of hypertension or used antihypertensive medications. Only 40.8% of the other 346,799 subjects had had their BP[2] measured in the preceding 2 years. BP recording rates were higher in females than in males (45.1% vs. 36.3%) and higher in elderly subjects than in young subjects (56% aged 66–75 years vs. 32% aged 18–25). Pre-hypertension was observed in 80,625 (23.2%) of the 346,799 while only 56,113 (16.2%) had normal BP records. The prevalence of pre-hypertension increased with age (13.3% aged 18–25 vs. 44.8% aged 66–75), and was more prevalent in men than in women (24.0% vs. 22.5%).

Conclusions: BP levels among young people are low, even though the prevalence of pre-hypertension in this population may be high. Thus, more emphasis should be given to routine BP measurements and confirmation of the findings in all age groups.

Background: The association between antibiotic use in the community and antimicrobial resistance is known. Attention has recently focused on the type of agents being prescribed.

Objectives: To implement, evaluate and compare the efficacy of two community interventions programs – continuous versus seasonal medical education – oriented to primary care physicians with emphasis on appropriate use of antimicrobial drugs.

Methods: From October 2000 to April 2003 we conducted two interventions: a) a monthly educational campaign in selected clinics promoting appropriate diagnosis of common infectious diseases and prudent antibiotic use (continuous intervention group); and b) a massive educational campaign, conducted before two consecutive winters, promoting the judicious use of antibiotics for treating respiratory infections (continuous intervention group and seasonal intervention group). Sixteen similar clinics were randomized (8 to each group). The total antibiotic use was measured as defined daily dose/1000 patients/day, and compared between the groups. 

Results: The total use of antibiotics decreased between 1999-2000 and 2002-2003 in both groups, but slightly more significantly in the continuous intervention group. The DDD/1000 patients/day for the seasonal group in 1999-2000 was 27.8 vs. 23.2 in 2002-2003; and for the continuous group 28.7 in 1999-2000 vs. 22.9 in 2002-2003, a reduction of 16.5% and 20.0% respectively (p<0.0001). The main change in antibiotic use was noted for broad-spectrum antibiotics.

Conclusions: We present a successful community intervention program aimed to reduce unnecessary antibiotic use. Amplification of this type of intervention is imperative to stop the increase in antimicrobial resistance.