Israel Medical Association Journal

Background: In infants, small volume nebulizers with a face mask are commonly used to facilitate aerosol therapy. However, infants may be disturbed by mask application, causing poor mask-to-face seal and thus reducing the dose delivered.

Objectives: To compare lung function response to bronchodilator nebulization via two delivery devices: hood versus mask.

Methods: We studied 26 recurrently wheezy infants aged 45.8 weeks (95% confidence interval 39.6–52.0). Inhalations of 0.30 mg/kg salbutamol were administered in two alliqots 30 minutes apart using mask and hood in alternating order (M+H or H+M). Response to inhalations was measured by maximal expiratory flows at functional residual capacity at 5 minute intervals after each dose, and area under the VmaxFRC[1] curve was documented.

Results: A small but significant response to salbutamol was observed following the second inhalation with VmaxFRC, improving by 31.7% (7.2–56.2, P < 0.02) and AUC[2] by 425 %•min (-154, 1004; P < 0.02). The improvement following salbutamol was similar by both delivery modalities but with a small but significantly better response when H was used after M (P < 0.01).

Conclusions: Nebulized salbutamol induced a variable but positive response in wheezy infants. Salbutamol via hood was as effective as conventional face mask delivery. Since it is simple and patient-friendly, it could replace the face mask method particularly with uncooperative infants.

Background: Major advances in the treatment of perinatal asphyxial–hypoxic ischemic encephalopathy followed the translation of hypothermia animal studies into successful randomized controlled clinical trials that substantially influenced the current standard of care.

Objectives: To present our preliminary experience with the first cases of clinical application of therapeutic hypothermia for PA-HIE[1] in what we believe is the first report on non-experimental hypothermia for PA-HIE from Israel.

Methods: We reviewed the medical records, imaging scans, electroencephalograms and outcome data of the six identified asphyxiated newborns who were managed with hypothermia in our services in 2008–2009.

Results: All asphyxiated newborns required resuscitation and were encephalopathic. Systemic hypothermia (33.5ºC) was begun at a median age of 4.2 hours of life (range 2.5–6 hours) and continued for 3 days. All six infants showed a significantly depressed amplitude integrated electroencephalography background, and five had electrographic seizures. One infant died (16%) after 3.5 days. Major complications included fat necrosis and hypercalcemia (n=1), pneumothorax (n=1), and meconium aspiration syndrome (n=2). None of the infants developed major bleeding. Neurodevelopmental follow-up of the five surviving infants at median age 7.2 months (4.1–18.5 months) revealed developmental delays (Battelle screening), with their motor scores ranging from -1 to +1 standard deviation (Bayley scale). None developed feeding problems, oculomotor abnormalities, spasticity or seizures.

Conclusions: Our preliminary experience with this novel modality in a large Tel Aviv neonatal service is consistent with the clinical findings of published trials.

Background: Concomitant human immunodeficiency virus and human papillomavirus infection increases both HPV[1] persistence and the risk of invasive cervical cancer. An estimation of HPV prevalence among HIV[2]-positive women in Israel would contribute to improving care for this population and preventing morbidity and mortality related to cervical cancer.

Objectives: To determine the prevalence of HPV infection and cervical cytology abnormalities, and to assess the possible influence of HIV infection on HPV carriage in HIV-positive women attending the Infectious Disease Clinic at Soroka University Medical Center.

Methods: The study population included 84 HIV-seropositive women. They were examined by a gynecologist and screened for HPV genotyping, and Pap smears were obtained for cervical cytology. Demographic, behavioral, and HIV infection variables were also recorded and analyzed.

Results: Forty-nine (58.3%) of the study participants were HPV-positive; 34 of them had oncogenic genotypes. Young age (< 16 years) at first sexual intercourse was the only variable significantly associated with HPV infection (P < 0.05). Abnormal cervical cytology was present in 17 women (20.3%); 21 women were referred to colposcopy, which was abnormal in 9 (10.7%).

Conclusions: The prevalence of HPV carriage among HIV-positive woman in our study was slightly higher than published elsewhere. The prevalence of pathological cervical cytology was much higher than in the general population. An extremely high prevalence of pathological colposcopies requiring further treatment was found. Screening for HPV and premalignant changes in the uterine cervix is highly recommended in the HIV-seropositive population. We suggest that colposcopy be considered part of the routine workup in HIV-seropositive woman.

Background: Traditionally, medication dosage was based on clinical and demographic parameters, but drug metabolism was recently recognized as an important factor for proper dosing and prediction of side effects. Metabolic considerations are crucial when administering drugs with a narrow therapeutic index, such as those of the thioguanides family (azathioprine and 6-MP). These can cause life-threatening myelosuppression due to low activity of a critical metabolic enzyme, thiopurine S-methyl transferase. A number of single nucleotide substitutions encoding variant enzymes account for most enzyme deficiencies.

Objectives: To determine the frequency of individuals from different Israeli ethnic groups who may be at risk for drug toxicity from drugs of the thioguanide family due to enzymatic variants.

Methods: DNA analysis was performed using polymerase chain reaction methods. We tested TPMT[1] allelic variants TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G) in five subpopulations in Israel: mixed-origin Israeli Jews, Arabs, Druze, Jews of Kurdish extraction, and Ethiopian Jews.

Results: The Druze (P = 0.0002) and Ethiopian Jewish (P = 0.015) subpopulations had a significantly unique distribution of allelic variants compared to the rest of the Israeli population. The Druze subpopulation showed a high number of TPMT variants with decreased activity, and a homozygote for TPMT*3A/ *3A was detected.  Ethiopian Jews were found to carry mainly the TPMT*3C variant, also observed in other studies of African populations.

Conclusions: It is advisable that Druze patients be tested for the TPMT enzyme before starting treatment with 6-MP or azathioprine. Such testing may also be considered for other Israeli ethnic subgroups.

Background: Gastric cancer continues to be a leading cause of cancer death. The treatment approach varies, and preoperative staging is therefore crucial since an exploratory laparotomy for unresectable gastric cancer will be followed by an unacceptably high morbidity and mortality rate.

Objectives: To assess the added value of diagnostic laparoscopy to conventional methods of diagnosis such as computed tomography in avoiding unnecessary laparotomies.

Methods: A retrospective study on 78 patients scheduled for curative gastrectomy based on CT staging was conducted. DL[1] was performed prior to exploratory laparotomy.

Results: In 23 of 78 patients (29.5%), unexpected peritoneal spread not detected on preoperative CT was found. Fifty-five patients underwent radical gastrectomy, 15 patients were referred for downstaging and 8 patients underwent a palliative procedure.

Conclusions: Based on our results, DL should be considered in all gastric cancer patients scheduled for curative gastrectomy.

Background: During the last few decades much effort has been invested into lowering smoking rates due to its heavy burden on the population's health and on costs for the health care services.

Objectives: To compare trends in smoking rates between adult Arab men and Jewish men and women during 2000–2008.

Methods: Six random telephone surveys were conducted by the Israel Center for Disease Control in 2000–2008 to investigate smoking rates. The number of respondents was 24,976 Jews men and women and 2564 Arab men. The percent of respondents reporting being current smokers was calculated for each population group (Jews and Arabs) by age, gender and education, and were studied in relation to time.

Results: Among Jewish men aged 21–64 smoking declined during 2000–2008 by about 3.5%. In the 21–44 age group this decline occurred only among respondents with an academic education. Among Jewish women this decline also occurred at ages 21–64, and in the 45–64 age group this decline was due only to a decline in smoking among those with an academic education. Among Arab men aged 21–64 an increase in smoking rates of about 6.5% was observed among both educated and less educated respondents.

Conclusions: Smoking prevalence is declining in Israel among Jews, but not among Arab men. The larger decrease in smoking rates among academics will, in the future, add to the inequalities in health between the lower and higher socioeconomic status groups and between Arabs and Jews. This calls for tailored interventions among the less educated Jews and all Arab men.

Background: Appropriate antibiotic use is of both clinical and economic significance to any health system and should be given adequate attention. Prior to this study, no in-depth information was available on antibiotic use patterns in the emergency department of Hadassah Medical Center.

Objectives: To describe the use and misuse of antibiotics and their associated costs in the emergency department of Hadassah Medical Center.

Methods: We analyzed the charts of 657 discharged patients and 45 admitted patients who received antibiotics in Hadassah Medical Center’s emergency department during a 6 week period (29 April – 11 June 2007). A prescription was considered appropriate or inappropriate if the choice of antibiotic, dose and duration by the prescribing physician after diagnosis was considered suitable or wrong by the infectious diseases consultant evaluating the prescriptions according to Kunin’s criteria.

Results: The overall prescribing rate of antibiotics was 14.5% (702/4830) of which 42% were broad- spectrum antibiotics. The evaluated antibiotic prescriptions numbered 1105 (96 prescriptions containing 2 antibiotics, 2 prescriptions containing 3 antibiotics), and 54% of them were considered appropriate. The total inappropriate cost was 3583 NIS[1] (1109 USD PPP[2]) out of the total antibiotic costs of 27,300 NIS (8452 USD PPP). The annual total antibiotic cost was 237,510 NIS (73,532 USD PPP) and the annual total inappropriate cost was 31,172 NIS (9648 USD PPP). The mean costs of inappropriate prescriptions were highest for respiratory (112 NIS, 35 USD PPP) and urinary tract infection (93 NIS, 29 USD PPP). There were more cases when the optimal cost was lower than the actual cost (N=171) than when optimal cost was higher than the actual cost (N=9). In the first case, the total inappropriate costs were 3805 NIS (1,178 USD PPP), and in the second case, -222 NIS (68.7 USD PPP).

Conclusions: The use of antibiotics in emergency departments should be monitored, especially in severely ill patients who require broad-spectrum antibiotics and for antibiotics otherwise restricted in the hospital wards. Our findings indicate that 12% of the total antibiotic costs could have been avoided if all prescriptions were optimal.

Background: Hypovitaminosis D has been shown to be extremely common in various regions around the world, mostly at high latitudes. Israel is characterized by certain features – cultural (e.g., ethnic isolates) and geographic (e.g., sunny climate) – that have been identified for their possible association with vitamin D status.

Objectives: To conduct an ecological study on a representative sample of the population of Israel, testing vitamin D status across age groups, genders, ethnic groups, and seasons.

Methods: We obtained serum samples from 195 healthy Israeli volunteers representing a broad demographic spectrum. Serum concentrations of 25(OH)D were measured with the commercial kit Liaison 25(OH)D Assay (DiaSorin, Italy).

Results: The mean vitamin D level for the entire cohort was surprisingly low (22.9 ± 10.1 ng/ml), with 149 subjects (78%) suffering from vitamin D insufficiency (< 30 ng/ml). Vitamin D status was better in infants than in older age groups. Differences by gender were significant only in the infant age group (i.e., vitamin D status was worse among females) and were not prominent across older ages. Israelis of Ashkenazi origin had higher vitamin D mean levels than those of Sephardic origin, who, in turn, had higher vitamin D levels than Arab subjects (31.4 ± 12, 24.1 ± 10, and 17.6 ± 9 ng/ml respectively). With regard to season, there were no differences between the samples collected in winter and the samples collected in summer.

Conclusions: The results suggest that hypovitaminosis D is common across all ages, genders and seasons in Israel, a country characterized by a sunny Mediterranean climate. Specific ethnic groups may be at especially high risk.

Background: The rate and duration of breastfeeding in Ethiopia is very high. Factors that could affect breastfeeding among women emigrating to Israel include the desire to adopt "modern" behaviors, the availability of infant formulas, and the greater awareness of AIDS and fear of transmission via breast milk.

Objectives: To examine the rate and duration of breastfeeding among recent Ethiopian immigrants to Israel.

Methods Using a structured questionnaire we interviewed 93 Ethiopian born mothers of children aged 2 months to 5 years living in northern Israel.

Results: Ninety-two percent of the children born in Ethiopia were exclusively breastfed as compared to 76.3% of the Israeli born children, in whom the rate of mixed feeding was 18.3%. Although the duration of breastfeeding of the youngest child was significantly shorter than of the firstborn (20.1 vs. 24.8 months), it remains much longer than the average duration for native Israeli mothers. No association was seen between breastfeeding rate or duration and the years since immigration, work outside the home or exposure to formula. The women’s attitude towards breastfeeding was positive despite the lack of specific knowledge concerning breast milk and infant formulas.

Conclusions: Breastfeeding patterns among Ethiopian women have changed since their immigration to Israel. These changes probably reflect the cultural and societal pressures to acculturate to the mores of the adopted society. Reinforcing traditional family and peer support for these women is important to preserve breastfeeding in this population. This should be done within the context of changes in the support for breastfeeding in the general Israeli society.

Background: Coronary CT angiography is an accurate imaging modality; however, its main drawback is the radiation dose. A new technology, the "step and shoot," which reduces the radiation up to one-eighth, is now available.

Objectives: To assess our initial experience using the "step-and-shoot" technology for various vascular pathologies.

Methods: During a 10 month period 125 consecutive asymptomatic patients (111 men and 14 women aged 25–82, average age 54.9 years) with various clinical indications that were appropriate for step-and-shoot CCTA[1] (regular heart rate < 65 beats/minute and body weight < 115 kg) were scanned with a 64-slice multidetector computed tomography Brilliance scanner (Philips, USA). The preparation protocol for the scan was the same as for the regular coronary CTA. All examinations were interpreted by at least one experienced radiologist and one experienced interventional cardiologist. The quality of the examinations was graded from 1 (excellent imaging quality of all coronary segments) to 4 (poor quality, not diagnostic). There were 99 patients without a history of coronary intervention, 13 after coronary stent deployment (19 stents), and 3 after coronary artery bypass graft.

Results: Coronary interpretation was obtained in 122 examinations (97.6%). The imaging quality obtained was as follows: 103 patients scored 1 (82.4%), 15 scored 2 (12%), 4 scored 3 (3.2%) and 3 scored 4 (2.4%). The grades were unrelated to cardiac history or type of previous examinations. Poor image quality occurred because of sudden heart rate acceleration during the scan (one patient), movement and respiration (one patient), and arrhythmia and bad scan timing (in one). Two patients were referred to percutaneous coronary intervention based on the CCTA findings, which correlated perfectly.

Conclusions: Step-and-shoot CCTA is a reliable technique and CCTA algorithm comparable to the regular CCTA. This technique requires the lowest radiation dose, as compared to other coronary imaging modalities, that can be used for all CCTA indications based on the inclusion criteria of low (> 65 bpm) and stable heart rate.