Israel Medical Association Journal

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: In many hospitals a chest X-ray is performed routinely at each patient’s admission. There are scant data regarding its usefulness in contemporary patient populations, which are characterized by patients’ increasing age, severity of illness, and different comorbidities.

Methods: We studied consecutive patients admitted during a 2 month period to a single department of medicine, where hospital policy mandates performing a CXR[1] on admission or soon after. Two senior clinicians who were not involved in the care of these patients assessed the discharge summaries for a clinical indication to perform CXR on admission, as well as its contribution to patient management (major positive, major negative, minor positive, or no contribution). Logistic regression analysis was performed with the SPSS 12 software program.

Results: The study population comprised 675 patients whose mean age was 64.5 ± 17.2 years. Their presenting complaints included chest pain (18%), dyspnea (12%), weakness (10.5%), fever (9%), abdominal pain (8%) and neurologic complaints (7.5%). Physical examination of the chest was normal in 585 (87%) of the cases and abnormal in 87 (13%). Examination of the heart was normal in 518 (77%) and abnormal in 129 (19%). In 19.6% (130 cases) CXR was not performed. Of the 545 CXRs done, 260 (48%) were normal. In only 128 (23.5%) did the admission CXR make a major positive contribution to diagnosis or treatment. In 61 (11.2%) it provided a minor positive contribution and in 153 (28.1%) a major negative contribution. In 184 patients (33.8%) the CXR did not affect either diagnosis or management. It made a major positive contribution to management in patients for whom there was an indication for performing the X-ray (odds ratio 10.3, P < 0.0005) and in those with a relevant finding on physical examination (OR[2] 1.63, P = 0.110). For a major negative contribution of the CXR to management (i.e., ruling out clinically important possibilities), the clinical indication was also very important (OR 72.9, P < 0.005). When patients with either a clinical indication for performing a CXR or an abnormal chest examination were excluded, 329 patients remained (60% of the 545 who had a CXR) in only 12 of them (3.6%) did the routine admission CXR contribute to patient management.

Conclusions: A routine admission CXR has a significant impact on patient management only in those patients in whom there are relevant findings on physical examination or a clear clinical indication for performing the test. There is no need to routinely order CXR on admission to hospital.

[1] CXR = chest X-ray

[2] OR = odds ratio

Background: Obstruction of urine outflow can result from mechanical blockade as well as from functional defects. In adults, urinary tract obstruction is due mainly to acquired defects, such as pelvic tumors, calculi, and urethral stricture. In childhood it is mostly due to congenital malformations. In this article we present two rare cases of acute obstructive renal failure that presented with hydronephrosis. These cases underline the wide range of causes that may lead to this clinical feature. 

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: The prognostic significance of biologic markers in women with ductal carcinoma in situ is not fully understood. HER2/neu is a marker of prognostic significance that is routinely assessed in invasive cancer but its correlation with clinical outcome in DCIS[1] is still obscure.

Objectives: To evaluate the significance of HER-2/neu expression as a prognostic marker in DCIS.

Methods: Clinical and pathologic data from 84 patients treated for DCIS were analyzed. HER-2/neu expression was determined by immunohistochemical staining. Histopathologic parameters (nuclear grade, histologic subtype, necrosis, calcifications, margins) were reviewed by an experienced pathologist. Local recurrence and/or metastatic spread were used as endpoints to determine the prognostic significance of HER-2/neu expression.

Results: With a median follow-up of 94.8 months, nine recurrences were reported. Neither univariate nor multivariate analysis showed a significant correlation between HER-2/neu expression and disease recurrence or the time to disease recurrence. Although HER-2/neu expression demonstrated a significant association with high nuclear grade (P < 0.0001) and comedo subtype (P < 0.0001), there was no correlation between these histologic features and recurrence rate. The correlation between high nuclear grade and disease recurrence approached statistical significance (P = 0.07).

Conclusions: No significant association was found between HER-2/neu expression in DCIS and disease recurrence. However, HER-2/neu correlated with negative markers such as nuclear grading and comedo necrosis, and its role should therefore be investigated in larger studies.
 

[1] DCIS = ductal carcinoma in situ

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: Epidemiological data show significant associations of vitamin D deficiency and autoimmune diseases. Vitamin D may prevent autoimmunity by stimulating naturally occurring regulatory T cells.

Objectives: To elucidate whether vitamin D supplementation increases Tregs[1] frequency (%Tregs) of circulating CD4+ T cells.

Methods: We performed an uncontrolled vitamin D supplementation trial among 50 apparently healthy subjects including supplementation of 140,000 IU at baseline and after 4 weeks (visit 1). The final follow-up visit was performed 8 weeks after the baseline examination (visit 2). Blood was drawn at each study visit to determine 25-hydroxyvitamin D levels and %Tregs. Tregs were characterized as CD4+CD25++ T cells with expression of the transcription factor forkhead box P3 and low or absent expression of CD127.

Results: Forty-six study participants (65% females, mean age ± SD 31 ± 8 years) completed the trial. 25(OH)D[2] levels increased from 23.9 ± 12.9 ng/ml at baseline to 45.9 ± 14.0 ng/ml at visit 1 and 58.0 ± 15.1 ng/ml at visit 2. %Tregs at baseline were 4.8 ± 1.4. Compared to baseline levels we noticed a significant increase of %Tregs at study visit 1 (5.9 ± 1.7, P < 0.001) and 2 (5.6 ± 1.6, P < 0.001).

Conclusions: Vitamin D supplementation was associated with significantly increased %Tregs in apparently healthy individuals. This immunomodulatory effect of vitamin D might underlie the associations of vitamin D deficiency and autoimmune diseases. Hence, our finding provides a rationale for further studies to investigate vitamin D effects on autoimmunological processes.

Background: Left atrial volume and exercise capacity are strong predictors of cardiovascular risk. Decreased exercise capacity is expected when LAV[1] is increased due to its association with abnormal left ventricular filling pressure. However, LAV enlargement is expected in chronic mitral regurgitation as well.

Objectives: To examine the linkage between LAV and exercise capacity in chronic MR[2] and to determine whether larger LAV has indeed better exercise capacity in patients with chronic severe degenerative MR and good LV systolic function.

Methods: The study included asymptomatic patients with severe chronic degenerative MR and normal LV[3] systolic function that underwent stress echocardiography. LAV was measured at rest using the biplane Simpson’s method and indexed to body surface area. The cutoff of good exercise capacity was determined at 7 METS.

Results: The patient group comprised 52 consecutive patients (age 60 ± 14 years, 36 males). Two subgroups (19 vs. 33 patients), age- and gender-matched, were formed according to LAVi[4] cutoff of 42 ml/m². Those with higher LAVi had lower exercise capacity (P = 0.004) albeit similar MR grade, baseline blood pressure, LV function and size. Receiver-operator curve analysis revealed indexed LAV value of ≤ 42 as 51% sensitive and 88% specific for predicting exercise capacity > 7 METS (AUC[5] = 0.7, P = 0.03). In multivariate analysis, age, gender and LAVi were identified as independent predictors of exercise capacity.

Conclusions: In asymptomatic patients with severe chronic degenerative MR and normal LV systolic function, mild enlargement of the left atrium (≤ 42 ml/m²) is associated with good exercise capacity.

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: Tuberculosis is the most common opportunistic infection among people infected with human immunodeficiency virus and its first cause of morbidity and mortality.

Objectives: To analyze the characteristics of a population in Israel with both tuberculosis disease and HIV[1] infection in order to identify factors that contribute to outcome.

Methods: The study group comprised patients hospitalized in the Pulmonary and Tuberculosis Department of Shmuel Harofeh Hospital during the period January 2000 to December 2006. They were located by a computer search in the hospital registry and the pertinent data were collected.

Results: During the study period 1059 cases of active tuberculosis disease were hospitalized; 93 of them were co-infected with HIV. Most of them came from endemic countries (61.2% from Ethiopia and 20.4% from the former Soviet Union; none of them was born in Israel). Ten percent of the cases were multiple-drug resistant and 32% showed extrapulmonary involvement. The response rate to the treatment was good, and the median hospitalization time was 70 days. The mortality rate was 3.2%.

Conclusions: Despite the high prevalence of pulmonary disease in our group, the short-term outcome was good and the Mycobacterium was highly sensitive to first-line drugs. These encouraging results can be attributed to the fact that tuberculosis patients in Israel are identified early and treated continuously and strictly, with early initiation of antiretroviral therapy, which ensures that the development of drug resistance is low.