Israel Medical Association Journal

Background: Halofuginone is a novel antifibrotic agent that can reserve the fibrotic process by specific inhibition of collagen type I synthesis.

Objectives: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/ 6 nephrectomy rat model.

Methods: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, Sirius red staining and in situ hybridization.

Results: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen α1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo.

Conclusions: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.  
 

Background: Hip fracture rates are increasing worldwide, and the risk for a second hip fracture is high. The decision to administer antiresorptive treatment is based mainly on bone mineral density and/or a history of previous osteoporotic fractures.

Objectives: To evaluate the contribution of BMD[1], previous fractures, clinical and laboratory parameters to hip fracture risk assessment.

Methods: The study population included 113 consecutive hip fracture patients, aged 72.5 ± 9.4 years, discharged from the Department of Orthopedic Surgery113 consecutive patients, 87 women and 26 men, aged 50-90 years, mean ag. BMD was assessed at the lumbar spine, femoral neck and total hip. The results were expressed in standard deviation scores as T-scores – compared to young adults and Z-scores – compared to age-matched controls. Plasma or serum levels of parathyroid hormone, 25-hydroxyvitamin 3 and urinary deoxypyridinoline cross-links were evaluated.

Results: We observed T-scores ≤-2.5 in 43 patients (45.3%) at the lumbar spine, in 47 (52.2%) at the femoral neck and in 33 (38%) at the total hip. Twenty-eight patients (29.5%) had neither low BMD nor previous osteoporotic fractures. Using a T-score cutoff point of (-1.5) at any measurement site would put 25 (89%) of these patients into the high fracture risk group. Mean DPD level was 15.9 ± 5.8 ng/mg (normal 4–7.3 ng/mg creatinine). Vitamin D inadequacy was observed in 99% of patients.

Conclusions: Using current criteria, about one-third of elderly hip fracture patients might not have been diagnosed as being at risk. Lowering the BMD cutoff point for patients with additional risk factors may improve risk prediction yield.

Background: Syndromic surveillance systems have been developed for early detection of bioterrorist attacks, but few validation studies exist for these systems and their efficacy has been questioned.

Objectives: To assess the capabilities of a syndromic surveillance system based on community clinics in conjunction with the WSARE[1] algorithm in identifying early signals of a localized unusual influenza outbreak.

Methods: This retrospective study used data on a documented influenza B outbreak in an elementary school in central Israel. The WSARE algorithm for anomalous pattern detection was applied to individual records of daily patient visits to clinics of one of the four health management organizations in the country.

Results: Two successive significant anomalies were detected in the HMO’s[2] data set that could signal the influenza outbreak. If data were available for analysis in real time, the first anomaly could be detected on day 3 of the outbreak, 1 day after the school principal reported the outbreak to the public health authorities.

Conclusions: Early detection is difficult in this type of fast-developing institutionalized outbreak. However, the information derived from WSARE could help define the outbreak in terms of time, place and the population at risk.

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: Ethnicity has been associated with variance in warfarin treatment regimens in various settings.

Objectives: To determine whether ethnicity is associated with variance in patient management in Israel.

Methods: Data were extracted from the electronic patient records of Clalit Health Services clinics in the Sharon Shomron region. The study group comprised all patients treated with warfarin who performed international normalized ratio tests for at least 6 months in 2003. The proportion of tests of each patient within the target range was calculated, as was the crude average rates and 95% confidence intervals for Jewish and Arab patients. The data were then stratified by patient's gender, specialty of attending physician, patient's age, and the country where the physician studied medicine.

Results: We identified 2749 Jews and 293 Arabs who met the inclusion criteria of the study. The crude average rate of patients’ INR[1] tests within the target range was 62.3% among Jews (95% CI[2] 61.5–63.1) and 52.7% (95% CI 49.9–55.5) among Arabs. When stratified by gender, age, and the treating physician's specialty and country of education, the stratum-specific rates among Jewish patients were consistently higher than among Arabs.

Conclusions: These results suggest that cultural differences regarding adherence to recommendations for drug therapy in addition to genetic factors may be associated with this variance.

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.
 

Background: The significance of arrhythmia occurring after successful recanalization of an occluded artery during treatment following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction is controversial.

Objectives: To study the association of reperfusion arrhythmia with short and long-term survival.

Methods: We used a prospective registry of consecutive STEMI[1] patients undergoing PPCI[2]. Patients with an impaired epicardial flow (TIMI flow grade < 3) at the end of the procedure were excluded.

Results: Of the 688 patients in the study group, 22% were women. Mean (± SD) age of the cohort was 61 (± 14) years and frequent co-morbidities included diabetes mellitus (25%), dyslipidemia (55%), hypertension (43%) and smoking (41%). RA[3] was recorded in 200 patients (29%). Patients with RA had lower rates of diabetes (16% vs. 30%, P < 0.01) and hypertension (48% vs. 62%, P < 0.01), and a shorter median pain-to-balloon time (201 vs. 234 minutes, P < 0.01) than patients without RA. Thirty day mortality was 3.7% and 8.3% for patients with and without RA, respectively (P = 0.04). After controlling for age, gender and pain-to-balloon time the hazard ratio for mortality for patients with RA during a median follow-up period of 466 days was 0.46 (95% confidence interval 0.23–0.92).

Conclusions: The occurrence of RA immediately following PPCI for acute STEMI is associated with better clinical characteristics and identifies a subgroup with a particularly favorable prognosis.

Background: Necrotizing enterocolitis is a common progressive gastrointestinal disease affecting more than 5% of very low birth weight infants and associated with a high mortality rate.

Objectives: To determine whether excessive weight gain in preterm infants is an early sign of NEC[1].

Methods: Seventeen preterm infants with perforated NEC were identified and matched with 17 control subjects for birth weight and gestational age. The postnatal age (days) at diagnosis of NEC was identified, and weight changes as well as clinical and laboratory data were recorded and compared for 7 days prior through 7 days post-diagnosis.

Results: A significant difference in weight gain was noticed between D-1 and D 0. The NEC and control groups gained 5.1% and 1.2%, respectively (P = 0.002). None of the sick infants lost weight on days -1 to D 0.

Conclusions: Excessive weight gain was observed in premature infants who subsequently developed NEC. Daily evaluation of weight changes should be considered part of a strategy for early identification of infants at risk for developing NEC. Future studies are needed to confirm this finding in a prospective manner and to investigate its pathogenesis.

Objectives: To study the necessity of bone marrow examination for the diagnosis and clinical course of MGUS[1].

Methods: We retrospectively screened the medical records of all patients in whom monoclonal protein was found in the serum during 2001–2002 in the medical laboratories of Sapir Medical Center. Asymptomatic patients who had serum monoclonal immunoglobulin G < 3.0 g/dl or IgA[2] < 2.0 g/dl or IgM < 1.0 g/dl without anemia, renal failure, hypercalcemia or any bone lesions on skeletal survey were eligible. Full records of patients who were evaluated in the hematology clinic were available (group 1). The remaining patients were followed by their family physicians; thus we had access only to their electronic files including laboratory results and new diagnoses (group 2). Demographic and clinical parameters as well as clinical course were evaluated.

Results: Both groups (57 and 255 patients, respectively) had similar demographic, laboratory and clinical characteristics. Bone marrow examination was performed in 30 of 57 patients (group 1): 16 were normal, 8 had an excess of normal plasma cells, and 6 had excess of pathologic plasma cells. However, only in two of the latter six could a diagnosis of multiple myeloma be established. All group 1 patients were followed for 22 ± 11 months and only two developed overt multiple myeloma. During the same period, 6 of 255 patients (group 2) were diagnosed as multiple myeloma and 3 as MGUS in other hospitals. The rest had a stable course with no change in their laboratory values.

Conclusions: Our findings suggest that bone marrow examination should not be performed routinely in patients who fulfill strict clinical and laboratory criteria of MGUS.

Objectives: To investigate and compare the epidemiologic, clinical and laboratory characteristics of cancer and non-cancer patients hospitalized with venous thromboembolism in a large referral medical center in Israel.

Methods: Between February 2002 and February 2003, patients diagnosed at the Rambam Medical Center as suffering from VTE[1] (deep vein thrombosis and/or pulmonary embolism), based on diagnostic findings on Doppler ultrasonography, spiral computed tomography scan or lung scan showing high probability for pulmonary embolism, were prospectively identified and evaluated. In addition, at the conclusion of the study period, the reports of spiral chest CT scans, performed during the aforementioned period in this hospital, were retrospectively reviewed to minimize the number of unidentified cases. Blood samples were drawn for evaluation of the coagulation profile.

Results: Altogether, 147 patients were identified and 153 VTE events diagnosed, accounting for 0.25% of all hospitalizations during the study period. The cancer group included 63 patients (43%), most of whom had advanced disease (63%). The most common malignancies were cancer of the lung (16%), breast (14%), colon (11%) and pancreas (10%). Of 121 venous thromboembolic events (with or without pulmonary embolism) there were 14 upper extremity thromboses (12%). The most common risk factors for VTE, except malignancy, were immobilization (33%), surgery/trauma (20%) and congestive heart failure (17%). There was no difference in prevalence of various risk factors between cancer and non-cancer patients. During an acute VTE event, D-dimer levels were higher in cancer patients than non-cancer patients (4.04 ± 4.27 vs. 2.58 ± 1.83 mg/L respectively, P = 0.0550). Relatively low values of activated protein C sensitivity ratio and normalized protein C activation time were observed in both cancer and non-cancer groups (2.05 ± 0.23 vs. 2.01 ± 0.33 and 0.75 ± 0.17vs. 0.71 ± 0.22, respectively). These values did not differ significantly between the groups.

Conclusion: The proportion of cancer patients among patients suffering from VTE was high. Their demographic, clinical and laboratory characteristics (during an acute event) were not different from those of non-cancer patients, except for higher D-dimer levels.