Israel Medical Association Journal

Background: Ultrasound examination of the fetus enables diagnosis of many major malformations during pregnancy, providing the possibility to consider interruption of the pregnancy. As a result, in many cases the incidence of malformations at birth does not represent their true incidence.

Objectives: To determine the impact of prenatal diagnosis and termination of pregnancy on the relative incidence of malformations at birth among Jews and Muslim Arabs in Israel.

Methods: Data on selected major malformations in 2000–2003 were collected from the two large central databases of the Ministry of Health and the Central Bureau of Statistics which contain information regarding births, stillbirths and terminations of pregnancies.

Results: For many malformations the total incidence was much higher than the incidence at birth. For almost all of the malformations studied, the total incidence was higher in Muslims than in Jews and the differences were further accentuated among the liveborn because of the differences in the rate of pregnancy terminations.

Conclusions: In order to detect possible influences of environmental or genetic factors on major malformations in Israel, it is critical to look at data including pregnancy terminations, stillbirths and live births.

Background: Continuous use of combined oral contraceptives is currently attracting growing interest as a means of improving menstrual related symptoms and reducing the number of bleeding days.

Objectives: To evaluate bleeding patterns, menstrual symptoms and quality of life with an extended 84/7 oral contraceptive regimen versus 21/7 cycles.

Methods: In two consecutive run-in cycles, 30 µg ethinyl estradiol and 3 mg drospirenone tablets taken on days 1–21 were followed by a tablet-free period from days 22 to 28 of each cycle and then by two 84 day cycles of pill use with a 7 day tablet-free interval. The primary outcome was the total number of bleeding/spotting days. Secondary outcomes were severity of daily symptoms, general well-being determined by the PGWBI questionnaire, and overall treatment satisfaction.

Results: Of the 137 women invited to participate in the study 109 (aged 18–40 years) were enrolled. The number of bleeding days decreased by about one-third from a calculated 31.8 days of bleeding under a cyclic 21/7 regimen to an expected total of 21.8 days for the extended 84/7 regimen. The incidence of menorrhagia, intermenstrual bleeding, dysmenorrhea, abdominal bloating, breast tenderness, depressive moods and irritability – when compared at enrollment and at the end of the second extended study period – was significantly lower (P < 0.005) among women on the continuous pill regimen. The median (range) global PGWBI scores were not substantially different before and after the extended use cycles: 78.2 (39.1–96.4) and 77.3 (30.9–96.4), respectively. Body weight and skin condition also remained constant. At the completion of the study: 65.5% of the women were either highly satisfied (41.4%) or satisfied (24.1%) with the extended regimen.

Conclusions: The extended 84/7 regimen was found to be satisfactory for the majority of participants and was associated with a decrease in the number of bleeding days and an improvement in menstrual symptoms compared to 21/7 cycles. 

Background: There is controversy as to which is the preferred treatment for distal radius intra-articular fractures – anatomic reduction or external fixation.

Objectives: To evaluate the radiologic and functional outcome following external fixation of these fractures.

Methods: Between January 2003 and March 2005, 43 patients with distal radius intra-articular fractures were treated using a mini-external AO device. Follow-up of 38 of the patients included X-rays at 1 week, 6 weeks and 6 months postoperatively. The Visual Analogue Scale was used to assess pain levels, and the Lidstrom criteria scale to evaluate functional outcome and wrist motion. Clinical and radiographic results were correlated.

Results: According to the Lidstrom criteria, the results were excellent in 31%, good in 61% and fair in 5.5%; 2.5% had a poor outcome. The results of the VAS[1] were good. Thirty-five patients gained a good range of wrist movement, but 3 had a markedly reduced range. We found statistical correlation between the radiographic and clinical results, emphasizing the value of good reduction. There was no correlation between fracture type (Frykman score) and radiologic results or clinical results.

Conclusions: External fixation seems to be the preferred method of treatment for distal radius intra-articular fractures, assuming that good reduction can be achieved. The procedure is also quick, the risk of infection is small, and there is little damage to the surrounding tissues.

Background: An outbreak of pertussis occurred in a daycare center with 87.5% vaccination coverage.

Objectives: To assess the effectiveness of the acellular pertussis vaccine and prevention of pertussis after chemoprophylaxis with azithromycin.

Methods: We studied 31 daycare children aged 3–5.5 years exposed to a child with pertussis. Nasopharyngeal swabs were obtained for Bordetella pertussis culture and polymerase chain reaction initially, and at days 21 and 60 of follow-up, in cases exhibiting symptoms.

Results: Of the 31 daycare children 6 (19%) tested positive for B. pertussis by PCR[1], 4 of whom had not been vaccinated against the disease. Of the two vaccinated children who contracted pertussis, one had milder symptoms and the other was asymptomatic. The incidence of pertussis was significantly lower in the vaccinated group (2/27) than in the unvaccinated group (4/4) (P = 0.000), with efficacy of the vaccine calculated to be 92.5%. Azithromycin chemoprophylaxis was taken only by 14 of the 25 exposed children (56%). On day 21 follow-up, there was no further laboratory-diagnosed B. pertussis cases in any of the exposed children, regardless of whether or not chemoprophylaxis was taken.

Conclusions: Based on the children’s clinical manifestations and PCR findings a pertussis outbreak had occurred in the daycare center studied. Our findings support the importance of pertussis vaccination since all the unvaccinated children in the daycare center contracted the infection.

Background: Hyperbilirubinemia of the newborn is common. Rarely is an underlying disease other than physiologic hyperbilirubinemia considered the cause of high bilirubin levels. Some of the laboratory tests recommended by the American Academy of Pediatrics are expensive and do not always lead to diagnosis.

Objective: To evaluate the efficacy of standard laboratory tests performed on newborn infants requiring phototherapy for hyperbilirubinaemia.

Methods: We conducted a retrospective chart review that included neonates born during a 6 month period with birth weight > 2500 g treated with phototherapy for hyperbilirubinemia (n=282) according to published guidelines. The main outcome measures were primary and maximal bilirubin values (mg/dl), time to jaundice (in days), the number of bilirubin tests undertaken and whether the patient showed abnormal functioning, and the number of days in follow-up.

Results: Thirty-three neonates (11.7%) were positive in at least one laboratory test (defined as "Abnormal" in our study), 45.5% of whom met the criteria for phototherapy during the first 48 hours of life. Among the newborns who were negative for all laboratory tests (defined as "Normal"), only 6.8% met phototherapy criteria within their first 48 hours of life (P < 0.001). In the Normal group there was a consistent decrease in total serum bilirubin values shortly after phototherapy was begun, while the Abnormal group presented an increase in serum bilirubin values during the first 12 hours of phototherapy. None of the infants had conjugated (direct) hyperbilirubinemia during the study period.

Conclusions: Most neonates presenting with a laboratory identifiable etiology for hyperbilirubinemia (i.e., hemolysis) can be distinguished from those who test negative, mainly based on the timing of presentation and response to phototherapy. A more meticulous selection of patients and reduction in the magnitude of routine laboratory testing can safely reduce discomfort to infants with hyperbilirubinemia as well as costs.

Background: While the burden of rotavirus infection with regard to hospitalizations has been extensively investigated, there are sparse data regarding the impact and the cost of this infection on the ambulatory part of the health system in Israel.

Objectives: To investigate the burden of rotavirus infection on the ambulatory system in Israel.

Methods: Infants younger than 3 years old examined for acute gastrointestinal symptoms in four pediatric clinics had their stool tested for rotavirus. The parents were contacted 7–10 days later and questioned about the symptoms of illness, medications given, use of diapers, consumption of formula, and any loss of parents' workdays.

Results: Rotavirus was detected in 71 of the 145 stool samples tested (49%). A total of 51 parents responded to the telephonic survey. Patients' mean age was 15.4 months. Three patients were hospitalized due to the illness. The mean duration of fever was 1.7 days. Infants with rotavirus gastroenteritis had on average 2.25 days of vomiting and 7.5 days of diarrhea. The average number of workdays lost was 2.65 days per RVGE[1] case. The cost of the average case of RVGE in Israel is 257 euros; 69.64% of this cost (179 euros) is due to parental work loss.

Conclusions: Our results indicate that the economic impact of the ambulatory cases in Israel is quite significant.

Background: Research on synergistic effects of patient-targeted interventions combined with physician-targeted interventions has been limited.

Objectives: To compare a combined physician-patient intervention to physician feedback alone on a composite outcome of glycemic, lipid and blood pressure control.

Methods: In this cluster study 417 patients with adult-type 2 diabetes from four primary care clinics were randomized to receive either a physician-only intervention or a combined physician-plus-patient intervention. Physicians in all clinics received diabetes-related quality performance feedback during staff meetings. Patients at combined-intervention clinics also received a letter encouraging them to remind their doctors to address essential aspects of diabetes care at the next visit. At 1 year follow-up, outcome measurements included hemoglobin A1c, low density lipoprotein-cholesterol and systolic blood pressure; the proportion of patients with HbA1c[1] < 9%, LDL[2] < 130 mg/dl and SBP[3] < 140 mmHg both as separate outcomes and combined.

Results: After adjusting for patient characteristics and baseline measures, follow-up levels of HbA1c (7.5% vs. 7.8%, P = 0.09), LDL (104.7 vs. 110.7 mg/dl, P < 0.05) and SBP (135.6 vs. 139.9, P = 0.10) were marginally better for combined-intervention patients compared to physician-only intervention patients. Significantly more patients in the combined-intervention (38.8%) than physician-only intervention (24.2%) met all three targets (HbA1c < 9%, LDL < 130 mg/dl and SBP < 140 mmHg) as a single combined outcome (adjusted odds ratio 2.4, P < .01).

Conclusions: Compared to physician-feedback alone, a dual intervention combining a patient letter with physician feedback produced modest improvements in glycemic, lipid and blood pressure control individually, but substantial improvement in a combined measure of these three outcomes together. Using composite outcomes may detect meaningful improvements in the management of complex chronic disease. 

Background: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the human gastrointestinal tract.

Objectives: To review our accumulated experience using surgery to treat gastrointestinal stromal tumors.

Methods: We reviewed all patient charts and histological diagnoses of leiomyomas, leiomyosarcomas, leiomyoblastomas and schwannomas. Only tumors that displayed c-kit (CD117) immunopositivity were defined as GISTs[1].

Results: The study group comprised 40 female and 53 male patients (age 26–89 years); 40.9% of the tumors were classified as malignant, 39.8% as benign, and 19.4% as of uncertain malignancy. Fifty-six GISTs were located in the stomach (60.2%), 29 in the small bowel (31.2%), 4 in the duodenum (4.3%), 2 in the colon (2.1%) and 2 in the rectum (2.1%). Incidental GISTs were found in 23.7% of our patients. Mean overall survival time for malignant gastric GISTs was 102.6 months (95% confidence interval 74.2–131.1) as compared to 61.4 months mean overall survival for malignant small bowel GISTs (95% CI[2] 35.7–87) (P = 0.262). The mean disease-free survival period for patients with malignant gastric GISTs was 97.5 months (95% CI 69.7–125.2) as compared to only 49.6 months (95% CI 27.4–71.7) for patients with small bowel malignant GISTs (P = 0.041).

Conclusions: We found a high percentage of incidental GISTs. Gastric GISTs are more common than small bowel GISTs. Patients with malignant gastric GISTs have a significantly better prognosis than patients with malignant small bowel GISTs. A statistically significant correlation was found between age and malignant potential of the GIST.

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: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress.

Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure.

Methods: Baseline serum MPO[1] levels were measured in 285 consecutive CHF[2] patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality.

Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 ± 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP[3] was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values.

[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

[3] NT-proBNP = N-terminal pro-brain natriuretic peptide

Background: Locally delivered steroids by inhalers or nebulizers have been shown in small trials to be effective in acute asthma attack, but evidence-based data are insufficient to establish their place as routine management of adult asthma attacks.

Objectives: To determine the efficacy of nebulized compared to systemic steroids in adult asthmatics admitted to the emergency department following an acute attack.

Methods: Adult asthmatics admitted to the ED[1] were assigned in random consecutive case fashion to one of three protocol groups: group 1 – nebulized steroid fluticasone (Flixotide Nebules®), group 2 – intravenous methylprednisolone, group 3 – combined treatment by both routes. Objective and subjective parameters, such as peak expiratory flow, oxygen saturation, heart rate, and dyspnea score, were registered before and 2 hours after ED treatment was initiated. Steroids were continued for 1 week following the ED visit according to the protocol arm. Data on hospital admission/discharge rate, ED readmissions in the week after enrollment and other major events related to asthma were registered.

Results: Altogether, 73 adult asthmatics were assigned to receive treatment: 24 patients in group 1, 23 in group 2 and 26 in group 3. Mean age was 44.4 ± 16.8 years (range 17–75 years). Peak expiratory flow and dyspnea score significantly improved in group 1 patients compared with patients in the other groups after 2 hours of ED treatment (P = 0.021 and 0.009, respectively). The discharge rate after ED treatment was significantly higher in groups 1 and 3 than in group 2 (P = 0.05). All 73 patients were alive a week after enrollment. Five patients (20.8%) in the Flixotide treatment arm were hospitalized and required additional systemic steroids. Multivariate analysis of factors affecting hospitalization rate demonstrated that severity of asthma (odds ratio 8.11) and group 2 (OD[2] 4.17) had a negative effect, whereas adherence to chronic anti-asthma therapy (OD 0.49) reduced the hospitalization rate.

Conclusions: Our study cohort showed the advantage of nebulized steroid fluticasone versus systemic corticosteroids in adult asthmatics managed in the ED following an acute attack. Both these and previous results suggest that nebulized steroids should be used, either alone or in combination with systemic steroids, to treat adults with an acute asthma attack.