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February 2023
Doron Carmi MD MHA, Ziona Haklai MA, Ethel-Sherry Gordon PHD, Ada Shteiman MSC, Uri Gabbay MD MPH

Background: Acute appendicitis (AA) is a medical emergency. The standard of care for AA had been surgical appendectomy. Recently, non-operative management (NOM) has been considered, mainly for uncomplicated AA.

Objectives: To evaluate AA NOM trends over two decades.

Methods: We conducted a retrospective cohort study based on Israel’s National Hospital Discharges Database (NHDD). Inclusion criteria were AA admissions from 1 January 2000 to 31 December 2019, with either primary discharged diagnosis of AA, or principal procedure of appendectomy. Predefined groups were children (5 ≤ 18 years) and adults (≥ 18 years). We compared the last decade (2010–2019) with the previous one (2000–2009).

Results: The overall AA incidence rate over two decades was 126/100,000/year; higher in children 164/100,000/year than 113/100,000/year in adults. Surgery was the predominant AA treatment in 91.9%; 93.7% in children and 91.1% in adults. There was an increase in AA NOM rates when comparing the previous decade (5.6%) to the past decade (10.2%); 3.2% vs. 9.1% in children and 6.8% vs. 10.7% in adults, respectively. Annual trends revealed a mild increase in AA NOM rates. Delayed appendectomy (within 90 days of AA NOM) was 19.7% overall; 17.3% in adults and 26.3% in children.

Conclusions: There was an increase in AA NOM rates during the last decade in the overall population. Since 2015, there has been a noticeable increase in AA NOM rates, probably associated with World Society of Emergency Surgery Jerusalem guidelines. Surgery is still the predominant treatment for AA despite the increasing trend in NOM.

January 2023
Doron Carmi MD MHA, Ziona Haklai MA, Ethel-Sherry Gordon PhD, Ada Shteiman MSC, Uri Gabbay MD MPH

Background: Bacterial meningitis (BM) remains a considerable cause of morbidity.

Objectives: To evaluate BM incidence rate trends in diverse age groups.

Methods: We conducted a retrospective cohort study based on the Israeli national registry. Inclusion criteria were acute admissions 2000 to 2019 with primary diagnosis of BM. Predefined age groups were neonates (≤ 30 days), infants (31 days to 1 year), younger children (1 ≤ 5 years), older children (5 ≤ 18 years), and adults (≥ 18 years). Average annual incidence rates per 100,000/year were calculated for the entire period and by decade. Incidence rates for neonates and infants were calculated per 100,000 live births (LB).

Results: There were 3039 BM cases over 2 decades, 60% were adults. The overall BM incidence rate was 2.0/100,000/year, neonates, 5.4/100,000/year LB, infants 17.6/100,000/year LB. First year of life incidence rate (neonates and infants combined) was 23.0/100,000/year, younger children 1.5/100,000/year, older children 0.9/100,000/year, and adults 1.8/100,000/year. All age groups presented a decrease in incidence rate (last decade vs. previous) except neonates, which increased by 34%. Younger and older children presented the most considerable decrease: 48% and 37% (last decade vs. previous).

Conclusions: Adults showed the highest number of BM cases. The incidence rate was highest during the first year of life (neonates and infants combined). All age groups, except neonates, showed a decreasing trend. Younger and older children presented the most considerable decrease, most likely attributable to vaccination. The observed increase in BM incidence rate in neonates may influence whether preventive strategy is considered.

December 2014
Yehoshua Shapira DMD, Itay Blum DMD, Ziona Haklai MSc, Nir Shpack DMD and Yona Amitai MD MPH

Background: Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnical, racial and gender differences.

Objectives: To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.

Methods: We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993–2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.

Results: Of 976,578 liveborn infants, 684 presented unilateral or bilateral clefts, with a prevalence of 7.00/10,000 live births; 479 were Jews and 205 were Arabs. The prevalence was higher among Arabs compared to Jews (11.12 and 6.22 per 10,000 live births in Arabs and Jews, respectively, P < 0.00001). Males had higher cleft rates than females (7.69/10,000 and 6.17/10,000 live births, respectively, P = 0.05). Males had more cleft lips with or without cleft palate, while females had more isolated cleft palates


(P < 0.001). There was left-side predominance. Newborns of younger mothers (age < 20 years) and of older mothers (age ≥ 45 years) had higher cleft rates than those with mothers in the 20–44 year bracket (P < 0.009). Children born at or above the 5th birth order had a higher cleft rate (P < 0.001).


Conclusions: The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring. 

July 2014
Adi Klein-Kremer MD, Irena Liphshitz MA, Ziona Haklai MA, Shai Linn PhD and Micha Barchana MD MPH
Background: Physicians’ occupational environment includes exposures to potential carcinogenic. Factors on a regular basis. The prevalence of specific tumor types and subsequent mortality are reported to be elevated in physicians.

Objectives: To assess the incidence of various cancer types among Israeli physicians of various specialties, as compared with the general population, and to determine the role, if any, of gender and ethnicity.

Methods: This historical retrospective cohort analysis incorporated data on Israeli officially licensed physicians and information retrieved from the Israel National Cancer Registry database (INCR). Physicians were divided into five groups: 1) non-specialists, 2) internists, 3) pediatricians, 4) surgeons, and 5) potentially at-risk specialties. Data were collected retrospectively for the years 1980–2007.

Results: The study cohort comprised 37,789 physicians, of whom 33,393 (88.37%) were Jews and 4396 (11.63%) were Arabs. Comparing Jewish physicians to the general population revealed higher rates of: a) breast cancer among female specialized physicians, and b) melanoma among specialized male and female physicians. All cancer types were more prevalent in the Arab physicians than in the general Arab population.

Conclusions: This study revealed incidences of specific cancer types among different medical specialties as compared to the general population. Hopefully, these findings will prompt changes in the occupational environment of physicians of particular specialties in order to reduce their high risk for cancer occurrence.
September 2010
J. Zlotogora, Z. Haklai, N. Rotem, M. Georgi and L. Rubin

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.

January 2009
A. Dortort Lazar, O. Shpilberg, M. Shaklai and O. Bairey

Background: There is currently no standard salvage chemotherapy for the 40–50% of patients with non-Hodgkin’s lymphoma who fail first-line treatment.

Objectives: To review the experience of a major tertiary medical center with DVIP (dexamethasone, etoposide, ifosfamide and cisplatin) salvage therapy for primary refractory/relapsing NHL[1].

Methods: We reviewed the records of all patients with NHL who received DVIP salvage therapy during the period 1993 to 2005.

Results: We identified 37 adult patients (mean age 56.3 years): 29 with aggressive lymphoma and 8 with indolent lymphoma. Mean event-free survival was 13.5 months (range 0–82 months), mean time between diagnosis and DVIP treatment 18.5 months (range 2–101), and mean number of DVIP cycles 1.9. Four patients (11%) achieved a complete response and 9 (24%) a partial response (overall response 35%). Consolidation with stem cell transplantation was used in 14 patients with aggressive lymphoma and 4 with indolent lymphoma; 14 patients, all with aggressive lymphoma, responded (12 complete, 2 partial). Of the 10 patients who underwent SCT[2] despite no response to salvage DVIP, 6 achieved a complete response. Five year overall survival from diagnosis for the whole sample was 39.4 ± 8.7%, and 5 year post-DVIP overall survival 37.6 ± 8.0%. On multivariate analysis, SCT was the strongest predictor of survival (relative risk 0.73, P < 0.0001) followed by a high score on the International Prognostic Index (RR[3] 3.71, P = 0.032).

Conclusions: DVIP salvage therapy for NHL was associated with a low response rate of 35% but a 5 year post-DVIP survival rate of 37.6%. Patients who are refractory to salvage treatment with DVIP might still be salvaged with SCT.






[1] NHL = non-Hodgkin’s lymphoma



[2] SCT = stem cell transplantation



[3] RR = relative risk



 
August 2007
J. Zlotogora, Z. Haklai and A. Leventhal

Background: The national program for the prevention of Down syndrome includes screening (using the triple test) and invasive diagnostic tests in women at risk for a Down syndrome pregnancy. However, despite the program, the majority of Down syndrome infants are born alive (approximately 1/1000 live births)

Objectives: To determine whether the relatively high incidence of Down syndrome at birth in Israel is the result of failure of the preventive program or due to informed choices of the mothers.

Methods: We conducted a retrospective study using the national registry of Down syndrome for the years 1997 and 2004, according to the mothers' religion and place of residence and the reasons for prenatal diagnosis.

Results: Most of the babies affected with Down syndrome are born in religious or traditional conservative communities where termination of pregnancy is usually not an option.

Conclusions: In a pluralistic society like Israel with its diverse communities and dissimilar religious backgrounds and traditions, the different attitudes concerning utilization of the national program should be respected. It is necessary to tailor different approaches and solutions for the various ethnic and religious communities according to their need.
 

May 2005
S. Dollberg, Z. Haklai, F.B. Mimouni, I. Gorfein and E.S. Gordon
 Background: Lacking curves of “intrauterine” growth, most birthing centers in Israel use United States-based curves as standards.

Objective: To establish population-based standards of birth weight of singletons in Israel.

Methods: Data on birth weight and gestational age were obtained from the registries of the Israel Ministry of Health and Ministry of the Interior. During the 8 year study period there were 1,074,122 infants delivered in Israel; 787,710 (73%) were included in this analysis.

Results: In this study we provide data of birth weight by gestational age of live infants born in Israel between 1993 and 2001. Ranges of birth weight by gestational age are also depicted for singleton and multiple pregnancies. Fetuses in multiple pregnancies grow in a similar manner to singletons until 30 weeks of gestation, after which their growth slows down.

Conclusions: Use of these data as a standard for “intrauterine” growth better represents the Israeli neonatal population than the American standards. In addition, curves of multiple pregnancies are significantly different from those of singleton pregnancies and might be more appropriate in these pregnancies.

March 2004
O. Bairey, Y. Zimra, E. Rabizadeh and M. Shaklai

Background: The highly tissue-specific trafficking of normal and malignant lymphocytes to particular organs is mediated by adhesion molecules, or “homing receptors.” Among our patients with B cell chronic lymphocytic leukemia 15% demonstrate predominantly splenic manifestations and are classified as stage II(S).

Objective: To investigate whether expression of cell surface adhesion molecules can distinguish stage II(S) patients from stage 0 or stage 0 and I CLL[1] patients.

Methods: Expression of adhesion molecules belonging to different families was studied in CD19-positive cells isolated from the blood of 42 patients by dual color flow cytometry. The families included: immunoglobulin superfamily (CD54, CD58), integrin family (β1, β2 and β3 chains, CD11a, CD11c CD49d), selectin family (L-selectin), and lymphocyte homing receptor family (CD44).

Results: The average percentage of leukemic cells expressing CD11c in the 23 patients with stage II(S) was 25.7 compared with 13.2% in the 14 patients with stage 0 disease (P = 0.047). The average percentage of leukemic cells expressing CD44 in patients with stage II(S) was 90.5 compared with 77.2% in patients with stage 0 (P = 0.007) and 80% in patients with stages 0 and I together (n=19, P = 0.008). Other adhesion molecules tested did not show a statistically significance difference in expression between the different disease stages.

Conclusions: The higher expression of CD44 and CD11c in cells of CLL patients with predominantly splenic manifestations may account for the tendency of their lymphocytes to home to the spleen.






[1] CLL = chronic lymphocytic leukemia


November 2000
Jochanan Benbassat, MD, Ziona Haklai, MSc, Shimon Glick, MD and Nurit Friedman, MSc
 Background: In 1995 hospital costs constituted about 42% of the health expenditures in Israel. Although this proportion remained stable over the last decade, hospital discharge rates per 1,000 population increased, while hospitalization days per 1,000 population and average length of stay declined.

Objective: To gain an insight into the forces behind these changes, we compared the trends in hospital utilization in Israel with those in 21 developed countries with available data.

Materials and Methods: Our data were derived from The "Hospitals and Day Care Units, 1995" report by the Health Information and Computer Services of the Israel Ministry of Health, and the Organization for Economic Cooperation and Development Health Data, 98. We examined the numbers of acute care hospital beds, of patients on dialysis and of doctors' consultations, health expenditures and age structure of the population in 1995 or closest year with available data, as well as changes in DRs, HDs and ALOS between 1976 and 1995.

Results: In Israel the DRs increased from 130 in 1976 to 177 in 1995 (36%), HDs declined from 992 to 818 (18%), and ALOS declined from 7.60 to 4.51 days (41%). Relative to other countries, in 1995 Israel had the lowest ALOS; low HDs similar to those in the UK, Portugal, Spain, the USA and Sweden; and intermediate DRs similar to those in Belgium, Germany, Sweden and Australia. The number of acute care beds per 1,000 population was directly related to HDs (r=0.954, P=0.000) and to DRs (r=0.419, P=0.052). Health expenditures (% of the gross national product) correlated with the number of patients on dialysis per 1,000,000 population (r=0.743, P=0.000). Between 1976 and 1995, HDs and ALOS declined in most countries, however the trends in DRs varied from an increase by 119% in the UK to a decline by 29% in Canada.

Conclusions and hypotheses: The increase in DRs in Israel from 1976 to 1995 was shared by many but not all countries. This variability may be related to differences in trends in local practice norms and in available hospital beds. If the number of patients on dialysis is a valid index for use of expensive treatment modalities, the correlation of health expenditures with the number of patients on dialysis suggests that the use of expensive technology is a more important determinant of health care costs than the age of the population or hospital utilization. Since the use of expensive technology is highest during the first few days in hospital, decisions about health care policy should consider the possibility that the savings incurred by a further decline in HDs and ALOS may be offset by a possible increase in per diem hospital costs and in health care expenditures after discharge from hospital.

May 2000
Ziona Haklai MSc, Shimon Glick MD and Jochanan Benbassat MD

Background: The increasing utilization of general internal medicine hospital wards in Israel during the last decade is a source of concern for health policy makers.

Objectives: To report on the distribution of selected main and secondary diagnoses among GIM inpatients, and to estimate the proportion of disorders for which appropriate care in the community will reduce the need for hospital admissions and re-admissions.

Methods: Data from the Health Information and Computer Services of the Israel Ministry of Health (national hospitalization database) for a one year period were analyzed by distribution of diagnostic entities (ICD-9-CM) in GIM and in medical subspecialty wards.

Results: Of the 313,824 discharges from hospital divisions of medicine in 1995, 256,956 (81.9%) were from GIM and 56,868 (18.1%) from specialty wards. Main and secondary discharge diagnoses were available for 188,807 GIM and 35,992 specialty patients. Of all main diagnoses in GIM wards, 27% were coded as "general or systemic symptoms and signs" or as "abnormal laboratory or ill defined manifestations" (ICD-9-CM codes 780-799, 276,277), and heart diseases comprised another 27%. The remaining main diagnoses covered almost all medical conditions. The combined proportion of "ambulatory care sensitive hospital admissions" (bronchial asthma, hypertension, congestive heart failure, chronic obstructive pulmonary disease, diabetes) constituted 12% of all main diagnoses in GIM, and respiratory symptoms or signs comprised another 11%. A by-product of this analysis was an insight into the experience of undergraduate medical students in GIM.

Conclusions: Assuming that 12-75% of admissions for "ambulatory care sensitive disorders" are preventable, an improved review before hospital discharge and a closer outpatient follow-up may reduce the load on GIM wards by 1-17%. This wide range justifies controlled trials to determine the effect of improved community care on hospital utilization. GIM wards offer valuable learning opportunities, but they cannot be a substitute for primary care clinics. The unexplained high proportion of GIM inpatients who were discharged with an unspecified main diagnosis could be detrimental for the accuracy of hospitalization statistics, and justifies investigation by chart audits into physicians' habits of documentation.

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GIM= general internal medicine

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