Israel Medical Association Journal

Mixed cryoglobulinemia is a systemic vasculitis described as a triad characterized by purpura, weakness and arthralgias. Since the first description of the disease in 1964 by Meltzer and Franklin our understanding of its pathogenesis has increased considerably. The striking association of the disease with hepatitis C virus infection was initially noted in 1990. Since then, the disease has gained growing attention among investigators involved in the study of autoimmune systemic disorders because it represents one of the most intriguing models of autoimmunity triggered by a virus. Nonetheless, a number of answered questions still remain to be resolved and are reviewed in this article.

Background: Patients who feel involved in their treatment have better outcomes than those who do not.

Objective: To identify determinants of perceived patient involvement in obstetric care.

Methods: A retrospective study was undertaken in 1,452 (83%) of 1,750 women sampled in November 1995 from maternity wards of 14 general hospitals in Israel. A postal and telephone survey using a self-administered questionnaire included the following variables: hospital (identity number), patients' age, self-reported complications, previous deliveries, education, ethnicity, and number of obstetric interventions performed and/or considered. The main outcome measured was the reported involvement in decisions for obstetric interventions.

Results: Reported full involvement varied from 72% for epidural analgesia to 13% for forceps/vacuum extraction. Factor analysis identified two dimensions of perceived involvement: one for routine” interventions (enema, monitor­ing, IV line and episiotomy), which are performed in Israel mostly by midwives, and another for "special" interventions (forceps/vacuum extraction, epidural or other analgesia, and cesarian section) performed by physicians. Logistic regression identified hospitals, younger age, number of interventions, and Arab ethnicity as correlates of a perceived non-involvement in decisions for "special" interventions.

Conclusions: Clinical setting, age and ethnicity affected patient perception of involvement in decisions for obstetric interventions.

Background: Diabetes mellitus is a serious, costly and growing public health problem. Very few studies have been published on the economic impact of diabetes in Israel.

Objective: To estimate health fund expenditures and rates of hospitalization for general conditions among the diabetic population in Israel.

Methods: The total number of hospitalization. All hospitals in Israel were included.

Results: There were 618,317 general admissions for a total of 3,005,288 hospitalization days. Analysis by age revealed that diabetic patients over age 45 represented 18.3% of all admissions and 17.5% of all hospitalization days. The average stay in hospital expenditure of the GSF for general medical conditions among diabetic patients in 1998 was estimated at US $173,455,790, of which 57% accounted for the daily hospitalization cost. Of the total hospital expenditures for that year, 13.3% was allocated to patients with diabetes of whom 96.4% were over 45 years old.

No significant difference was found between males and females.

Conclusion: Hospital expenditures for diabetic people increase with patient age and represent one-fifth of the total health insurance expenditure for the middle-aged and elderly population.

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.

Background: The degree to which serum total cholesterol predicts cariovascular disease is uncertain. While most authors have placed TC among the most powerful risk indicators of CVD, some have claimed that it predicted CVD in women only, or even not at all.

Objective: To determine the predictive value of serum total cholesterol relative to diabetes, smoking, systolic blood pressure and body mass index (kg/m2), for cardiovascular disease mortality in 3,461 occupationally active Israeli males.

Methods: A prospective follow-up was carried out for the years 1987-1998 to determine the effect of age, smoking habits, a history of diabetes, SBP, BMI and TC, at entry, on CVD mortality.

Results: There were 84 CVD deaths during a total of 37,174 person-years follow up. The hazard ratios (95% confidence intervals) for CVD mortality with respect to variables at entry were: diabetes 5.2 (2.1-13.2), age 2.2 (1.7-2.9), smoking 1.3 (1.0-1.8), SBP 1.4 (1.1-2.0), TC 1.5 (1.0-2.1) and BMI 1.2 (0.7-2.2). Among non-obese, non-diabetic, normotensive subjects the hazard ratio of TC adjusted for age and smoking was 1.16 (1.09-1.22) per 10 mg/dl. In the remaining subjects it was 1.04 (0.98-1.12) only. There was a significant interaction between TC and diabetes, hypertension or obesity (P=0.003).

Conclusions: In this population of Israeli males we found an interaction between TC and other risk indicators for CVD. Confirmation is required for the unexpected finding that the predictive value of TC for CVD mortality among non-diabetic, non-obese and normotensive subjects exceeded that among subjects with either of these risk factors.
 

Background: In simultaneous pancreas-kidney transplantation, with both organs coming from the same donor, the addition of a pancreas to the kidney transplant does not jeopardize the kidney allograft outcome despite higher postoperative SPK morbidity. Pancreas allograft outcome has recently improved due to better organ selection and more accurate surgical techniques.

Objective: To demonstrate the positive impact of SPK on kidney allograft outcome versus kidney transplantation alone in insulin-dependent diabetes mellitus patients with end-stage renal failure.

Methods: We performed 39 consecutive SPKs in 14 female and 25 male IDDM patients with renal failure after an average waiting time of 9 months. Multi-organ donor age was 30 years (range 12-53). The kidneys were transplanted in the left retroperitoneal iliac fossa following completion of the pancreas transplantation; kidney cold ischemia time was 16±4 hours. Induction anti-rejection therapy was achieved with polyclonal antithymocytic globulin and methylprednisolone, and maintenance immunosuppression by triple drug therapy (prednisone, cyclosporine or tacrolimus, and azathioprine or mycophenolate mofetil). Infection and rejection were closely monitored.

Results: All kidney allografts produced immediate urinary output following SPK. Two renal grafts had mild function impairment due to acute tubular damage but recovered after a short delay. Three patients died from myocardial infarction, cerebrovascular event and abdominal sepsis on days 1, 32 and 45 respectively (1 year patient survival 92%). An additional kidney allograft was lost due to a renal artery pseudo-aneurysm requiring nephrectomy on day 26. Nineteen patients (49%) had an early rejection of the kidney that was resistant to pulse-steroid therapy in 6. No kidney graft was lost due to rejection. Patients with acute kidney-pancreas rejection episodes suffered from severe infection, which was the main cause of morbidity with a 55% re-admission rate. Complications of the pancreas allograft included graft pancreatitis and sepsis, leading to a poor kidney outcome with sub-optimal kidney function at 1 year. Kidney graft survival at one year was 89% or 95% after censoring the data for patients who died with functioning grafts.

Conclusions: Eligible IDDM patients with advanced diabetic nephropathy should choose SPK over kidney transplantation alone from either a cadaver or a living source.

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SPK= simutaneous pancreas-kidney transplatation

IDDM= insulin-dependent diabetes mellitus

Background: Cigarette smoking is a major contributor to the risk of acute myocardial infarction and the subsequent morbidity and mortality. Physicians can play an important role in smoking cessation among patients with AMI because of their frequent contact with the patient during the event.

Objectives: To study the prevalence of smoking, age, localization of coronary occlusion, mortality and rate of smoking cessation in consecutive patients who were diagnosed with a first AMI in our center in 1989–93.

Methods: The study included 1,510 consecutive patients with first AMI: 973 men (512 smokers, 52.6%) and 537 women (215 smokers, 40%), whose mean age was 64.1±6.7 and 68.6±5.2 years respectively.

Results: The median age at the first AMI in non-smoking and smoking men differed significantly (70.4±6.8 vs. 56.6±6.1 years, P<0.001) while the difference in the women was smaller (70.4±6.9 vs. 66.8±7.2). The proportion of smokers/non-smokers among men was greater at a younger age and decreased proportionally with age. The overall mortality was 11.3% with a significant difference in mortality rate in the younger age groups between smokers and non-smokers (1% vs. 0% in the age group 31–40 years, P<0.05, and 6.1% vs. 0.8% in the 41–50 year age group, P<0.001). Only 62% of the smokers who survived the AMI declared that they had received anti-smoking advice from a physician during hospitalization. The cessation rate in this group was significantly higher than in smokers who had not been cautioned against smoking (56% vs. 18%).

Conclusions: Current smokers sustained their first AMI more than one decade earlier than non-smokers, and the younger smokers had a higher mortality rate. The majority of the smokers who received anti-smoking advice during their hospitalization for AMI quit smoking in the year following the acute event. 

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AMI= acute myocardial infarction

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

Background: Smoking rates have decreased in western countries as well as in Israel during the past 20 years.

Objectives: To estimate current rates of smoking and smoking cessation, and to assess factors associated with smoking and smoking cessation in family practice.

Methods: Prospective face-to-face interviews were conducted with 1,094 subjects, aged 16 years or older, registered in a family practice.

Results: Of all subjects studied, 746 (68.2%) were non-smokers, 237 (21.7%) were current smokers, and 111 (10.1%) had stopped smoking. Overall, 31.8% of the males and 13.8% of the females were current smokers, and 20.1% males and 2.4% females had stopped smoking. Current smoking and smoking cessation rates were significantly and inversely associated with age among males and females. Smoking rates were higher among males and females who were married, had 10-12 years of education, and among males of North African origin and females of Israeli origin. The number of cigarettes smoked per day was associated with smoking and smoking cessation in males, but not in females. The highest rate of quitting occurred among males who smoked 25 cigarettes per day. In a multiple regression analysis, gender and the number of cigarettes smoked per day were the most significant factors that predicted smoking cessation. The most common reason for stopping was the appearance of new signs of illness or the development of a new chronic disease, followed by a physician's recommendation to quit smoking.

Conclusions: Female smokers and male smokers who smoke less than 25 cigarettes per day are the least likely to quit smoking. Future programs should be designed for and targeted at these groups of patients.

Background: Smoking is the most important preventable cause of chronic disease in the western world. Many smokers want to quit, but have difficulty overcoming the addictive effect of nicotine.

Objectives: To assess the quitting rate of smokers who participated in smoking cessation groups and to characterize predictors of success or failure over a 1-3 year follow-up period.

Methods: We studied 89 participants in 7 groups. Questionnaires were completed at baseline and after a follow-up period of 1 to 3 years. Smoking cessation was determined by self-report and a carbon monoxide breath test.

Results: Of the 89 participants in the support groups 76 (85%) were located. An intention-to-treat analysis was done for these participants. At follow-up 25 (33%) were non-smokers. There was a 95% agreement rate between self-report of smoking status and CO breath analysis. There were no differences between quitters and non-quitters in education level, gender, age at initiation of smoking, previous quit attempts, extent of participation in group meetings, concern about gaining weight, Fagerstrom index, or the number of close friends or relatives who smoke. Belief in one's ability to quit, satisfaction with group meetings, and spouse support were significantly associated with success (P<0.01).

Conclusions: The quit rate was 33%. Self-report is a reliable method for assessing smoking status. Smokers' belief in their ability to quit must be reinforced. Spouse participation in some group meetings may be beneficial, as may the involvement of a dietician and an expert on exercise. Follow-up "booster" meetings may also help.

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CO= carbon monoxide

* In partial fulfilment of the requirements for an MD degree.

Background: Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis.  No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects.

Objectives: To describe our clinical experience in culturing and transplanting autologous chondrocytes. 

Methods: Biopsies were obtained from 10 patients, aged 18–45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap.

Results: The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage.

Conclusions: Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.

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ACT = autologous chondrocyte transplantation

Background: Cystic fibrosis is the most common life-limiting autosomal recessive genetic disorder in Caucasians. Typically it is a multisystem disease diagnosed by increased chloride levels on sweat testing, with mortality due mainly to progressive respiratory disease. The clinical spectrum of CF has recently been much expanded.

Genetic testing for mutant CF transmembrane regulator has revealed atypical cases where sweat test results are borderline or normal. In other patients, genetic mutations cannot be identified but abnormal CFTR function is shown using nasal potential difference measurement.

Objectives: To highlight the diagnostic and therapeutic dilemmas in cases of atypical cystic fibrosis.

Methods: We reviewed patients with atypical CF and widely varying phenotype who are managed at Schneider Children’s Medical Center of Israel. 

Results: Two patients had severe lung disease but little expression in other organs. Accurate diagnosis was essential to enable aggressive therapy in a specialized center. Four other patients are in excellent general health but have symptoms limited to male infertility, heat exhaustion, pancreatitis or transient liver dysfunction, while lung disease is minimal. For these patients, careful counseling is needed to avoid unnecessary upheaval, inappropriately aggressive management, and the psychosocial implications of a CF diagnosis. These dilemmas have increased considerably in our center, as in others worldwide.

Conclusion: It is our obligation as clinicians - at the level of both primary physician and referral center - to maintain an ever higher index of suspicion for CF, tempered by a rational program of counseling and management appropriate to the individual.

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CF= cystic fibrosis

CFTR= CF transmembrane regulator