Israel Medical Association Journal

The complexity of medical problems is a well-recognized phenomenon. In the presence of economic and cultural restrictions, medical decision-making can be particularly challenging. This paper outlines a system of analysis and decision-making for solving such problems, and briefly describes a case study in which the method was used to analyze the case of antibiotic overprescribing in a large health maintenance organization. The purpose of the study was to determine if a technique for problem-solving in the field of engineering could be applied to the complex problems facing primary care. The method is designated Systematic Inventive Thinking and consists of a three-step procedure: problem reformulation, general search-strategy selection, and an application of idea-provoking techniques. The problem examined is the over-prescribing of antibiotics by general practitioners working in Maccabi Healthcare Services, an HMO[1] serving one and a half million patients in Israel. The group of healthcare professionals involved in the discussions generated 117 ideas for improving antibiotic use. Six of these ideas were then implemented in a national campaign in the winter of 2000/1 and 2001/2. During this period, a significant reduction in per-visit antibiotic purchasing was observed for influenza visits (from 79.2 per 1,000 to 58.1 per 1,000, P < .0001), but not for other categories of visits. The SIT[2] methodology is a useful technique for problem-solving and idea generation within the medical framework.

Background: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke.

Objectives: To assess the feasibility and safety of rt-PA[1] therapy for reperfusion in routine clinical practice in Israel, in a setting of a dedicated stroke unit.

Methods: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography eligible patients were treated with intravenous rt-PA (0.9 mg/kg; maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Re-canalization was assessed by serial transcranial Doppler.

Results: The study group comprised 16 patients, mean age 61 years (range 47–80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6–24). They were treated within a mean door-to-CT time of 39 minutes (range 17–62 min), door-to-drug time 101 minutes (range 72–150), and stroke onset-to-drug time 151 minutes (range 90–180). There was an early improvement within 24 hours (of ≥ 4 points in the NIHSS[2] score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study.

Conclusion: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.

Background: Hypovitaminosis D is an important risk factor for osteoporosis and its complications. Previous studies found that the incidence of hypovitaminosis D among patients in an internal medicine ward reached up to 57%.

Objectives: To determine the prevalence and determinants of hypovitaminosis D among patients in internal medicine wards in a sunny country.

Methods: We measured 25-hydroxyvitamin D, parathyroid hormone and various other laboratory parameters, and assessed the amount of sun exposure, dietary vitamin D intake and other risk factors for hypovitaminosis D in 296 internal medicine inpatients admitted consecutively to the Soroka University Medical Center, which is situated in a sunny region of Israel.

Results: We found hypovitaminosis D (serum 25-HO-D[1] <15 ng/ml) in 77 inpatients (26.27%). The amount of sunlight exposure, serum albumin concentration, being housebound or resident of a nursing home, vitamin D intake, ethnic group, cerebrovascular accident and glucocorticoid therapy were all significantly associated with hypovitaminosis D. Multivariate analysis showed a significant association between hypovitaminosis D and Bedouin origin, sun exposure, vitamin D intake, and stroke. Hypovitaminosis D was also found among inpatients who reported consuming more than the recommended daily amount of vitamin D. Parathyroid hormone levels were significantly higher in patients with 25-OH-D levels below 15 ng/ml. In a subgroup of 74 inpatients under 65 years old with no known risk factors for hypovitaminosis D, we found 20.3% with hypovitaminosis D.

Conclusions: Hypovitaminosis D is common in patients hospitalized in internal medicine wards in our region, including patients with no known risk factors for this condition. Based on our findings, we recommend vitamin D supplementation during hospitalization and upon discharge from general internal medicine wards as a primary or secondary preventive measure.

Background: Pyoderma gangrenosum is an uncommon ulcerative cutaneous condition associated with inflammatory bowel disease. PG[1] occurs rarely in IBD[2] patients and there are insufficient data on the clinical manifestations of this disease with IBD.

Objective: To determine the incidence, clinical manifestations and treatment of PG in patients with IBD and the connection to IBD, its activity and extent.

Methods: All patients hospitalized with IBD at a university hospital during a 20 year period were evaluated for the occurrence of PG.

Results: Of 986 patients hospitalized for IBD 6 suffered from PG (0.6% incidence). Their average age was 37 with equal sex distribution and equal distribution of Crohn’s disease and ulcerative colitis. PG appeared 6.5 years on average after diagnosis of IBD in all patients. The development of PG correlated with significant clinical exacerbation of IBD, the majority having active colitis at the onset of the PG. Extra-intestinal manifestations of IBD occurred in half the patients (sacroiliitis, peripheral arthritis and erythema nodosum). Pathergy was not elicited in any patients. Four patients had multiple skin lesions, frequently on the lower extremities. Diagnosis was made by skin biopsy in four patients. There was little correlation between amelioration of IBD and the skin lesions. Treatment consisted of high dose steroids and immunomodulatory drugs (cyclosporine, azathioprine and dapsone) in conjunction with topical treatment.

Conclusions: PG is a rare extra-intestinal manifestation of IBD that coincides with the exacerbation of the intestinal disease but does not always respond to treatment of the bowel disease.

Background: Increased serum potassium and intraventricular hemorrhage occur frequently in preterm infants.

Objective: To retrospectively analyze data obtained on infants with severe IVH[1] in relation to blood K⁺ concentrations.

Methods: We identified all patients with severe IVH born between July 1997 and July 2000. Each patient was pair-matched with a control infant of the same gestational age (±1 week) without IVH in terms of head ultrasound findings on day 5, and whole blood K⁺ on days 3–5.

Results: There were 24 infants in each group. The IVH group had significantly lower 1 minute Apgar scores and pH and higher blood K⁺ than the control group. Blood pH and K⁺ were inversely correlated. Stepwise regression analysis, taking into account blood pH and 1 minute Apgar score, showed a correlation only between blood K⁺ and IVH status.

Conclusions: Severe IVH is significantly associated with higher blood K⁺ concentrations. A causal relationship cannot be ascertained at this point.

Background: Anemia is a known risk factor for ischemic heart disease. Based on knowledge of the physiologic role of oxygen delivery to the myocardium, anemia may be a cause of more severe cardiovascular diseases or a marker of other processes occurring in the body that induce more severe disease.

Objectives: To investigate the relationship between anemia and the clinical picture of IHD[1], including manifestations, severity and complications.

Methods: The population studied comprised 417 similarly aged patients with IHD and anemia. The patients were categorized into subgroups of IHD according to disease severity: namely, angina pectoris, acute ischemia, acute myocardial infarction, congestive heart failure or cardiac arrhythmias. Two populations served as control groups: patients with anemia but no IHD (C-I) and patients with IHD without anemia (C-II). A standard anemia workup was conducted in all patients with IHD and anemia and a correlation was made between the hematologic parameters and the manifestations and complications of IHD.

Results: The common presenting symptom was chest pain in the study group and in C-II (94% and 86% respectively) and weakness (90%) in C-I. Patients with IHD and anemia tended to suffer from a more advanced degree of IHD (80%) compared to patients with IHD alone who had milder disease (46%). Hematologic values including hemoglobin, mean cell volume, serum iron and total iron binding capacity correlated inversely with disease severity among anemic patients with IHD. There were significant differences between the study group and C-II regarding CHF[2] (31% and 18% respectively) and arrhythmias (41% and 16% respectively). The mortality rate was higher in patients with IHD and anemia than in patients with IHD alone (13% and 4% respectively).

Conclusions: Anemia is a significant risk factor in IHD. It correlates with advanced IHD, CHF, rhythm disturbance and higher mortality rate. An aggressive therapeutic and preventive approach might improve the outcome of this disease.

Background: Genetic hemochromatosis leads to iron overload in many tissues and may lead to liver cirrhosis and hepatocellular carcinoma. Early diagnosis and therapy are crucial. Since 80–100% of hemochromatosis patients of European origin are homozygous for a cysteine to tyrosine exchange in the HFE gene at codon 282, genetic screening might be useful. Representative population studies are needed to evaluate the phenotype of people heterozygous and homozygous for the C282Y mutation.

Objective: To determine the correlation between parameters of iron metabolism and the hemochromatosis genotype in a large population-based study.

Methods: A representative population-based survey, the Diabetomobil study, analyzed 5,083 German probands. Serum transferrin saturation and ferritin levels were determined, and the C282Y mutation of the HFE gene was analyzed by restriction fragment length polymorphism- polymerase chain reaction analysis.

Results: Nine of 373 probands with a transferrin saturation > 55% (2.4%) and none of 264 randomly selected probands with a transferrin saturation £ 55% (0%) were homozygous for the C282Y mutation. Three of the nine homozygous probands had ferritin values less than 250 µg/L. The frequency of the heterozygous genotype was 8.8%, and the percentage of heterozygous probands increased with increasing levels of transferrin saturation.

Conclusion:We propose a population screening strategy with an initial transferrin saturation test, followed by genotyping for the C282Y mutation if the transferrin saturation is above 55%, regardless of the ferritin level. Heterozygous individuals with higher transferrin saturation values may be protected against iron loss but may also be more susceptible for certain liver diseases, depending on the simultaneous prevalence of other diseases.
 

Background: Nasal colonization with methicillin-resistant Staphylococcus aureus in the community is being increasingly reported, but there is a general lack of data on MRSA[1] colonization in children in chronic care institutions and on colonization rates in Israeli children.

Objectives: To define the rate of MRSA nasal colonization in a generally healthy pediatric population in Jerusalem, to compare it with that of children in chronic care institutions, to define risk factors for colonization, and to compare community and hospital-acquired MRSA strains.

Methods: Anterior nares culture for the presence of methicillin-sensitive and methicillin-resistant S. aureus was taken from 831 healthy children attending primary pediatric clinics or emergency department and 118 children hospitalized in three chronic care institutions in Jerusalem.

Results: Of the 831 healthy children, 195 (23.5%) were colonized with S. aureus, as compared to 43 of 118 (36.4%) chronically institutionalized children (P < 0.005). Five of the 195 S. aureus isolates from healthy children (2.6%) were MRSA, as compared to 9 of 43 (21%) from chronically institutionalized children (P < 0.001). Older age and a family member who is a healthcare worker were associated with S. aureus colonization in the population of healthy children, and older age was associated with MRSA colonization in the chronically institutionalized children. The antibiotic susceptibility pattern was similar for both groups, and pulsed field gel electrophoresis of the isolates showed a wide and random distribution in both groups.

Conclusions: MRSA colonization in the studied pediatric community in Jerusalem was very low, whereas that of patients hospitalized in chronic care institutions was significantly higher. In the small number of isolates detected, no significant differences were found in antibiotic susceptibility or PFGE[2] pattern between hospital-acquired and community-acquired strains.

Background: The humanized SCID mouse model is an attractive tool for testing gene therapy to combat human immunodeficiency virus infection in vivo.

Objectives: To devise a more specific gene therapy directed against HIV, replacing the formerly used interferon with either soluble CD4 molecule immunoadhesin (sCD4-IgG) and/or anti-gp41 monoclonal antibody (2F5), or negative transdominants (Tat, Rev).

Methods: Human monocytoid cell line (U937) was transfected with IFNa[1], b or g genes. 3T3 murine fibroblastic cell line was transfected with sCD4-IgG or 2F5, or both genes, and a human T4 cell line (CEM) was grafted to SCID mice. Negative transdominant genes (Tat, Rev or both) were also transduced in CEM T cell line. Animals were then challenged with HIV-1[2]. Viral load was followed.

Results: IFNa or b were potent anti-HIV, reducing viral load in vivo and inhibiting reverse transcriptase activity in human-removed cells from animals. sCD4-IgG immunoadhesin and gp41 monoclonal antibody resulted in a dramatic reduction of HIV-1 cellular and plasmatic viral load in humanized SCID mice. The simultaneous introduction of negative Tat and Rev genes resulted in a synergistic inhibition of HIV-1 replication in vivo.

Conclusions: Despite the marked reduction of HIV-1 propagation by IFN genes or by negative Tat and Rev transdominants, the gene therapy using soluble CD4 immunoadhesin or anti-gp41 was a more efficient preventive treatment against HIV infection.