Israel Medical Association Journal

Background: Iron deficiency is the most common single cause of anemia worldwide. Treatment consists of improved nutrition along with oral, intramuscular or intravenous iron administration.

Objectives: To describe the efficacy and adverse effects of intravenous iron sucrose therapy in a group of children with iron deficiency anemia who did not respond to oral iron therapy.

Methods: We conducted a prospective investigation of 45 children, aged 11 months to 16 years, whose oral iron therapy had failed. The children attended the Pediatric Ambulatory Care Unit where they received intravenous iron sucrose infusion.

Results: Forty-four of the 45 patients were non-compliant. Nine had Helicobacter pylori gastritis and 16 patients suffered from intestinal malabsorption from different causes. Before treatment, the blood mean hemoglobin concentration was 7.43 g/dl (range 5–10.1 g/dl). Fourteen days after treatment the mean hemoglobin concentration increased to 9.27 g/dl (SD 1.23) and 6 months later to 12.40 g/dl (SD 1.28). One patient demonstrated a severe side effect with temporary and reversible reduced blood pressure during treatment.

Conclusions: These preliminary data suggest that administration of intravenous iron in pediatric patients is well tolerated and has a good clinical result, with minimal adverse reactions.

Background: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and increased dosage is not allowed. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease.

Objectives: To describe our experience with anti-TNF[1] therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results.

Methods: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects.

Results: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n=108), juvenile idiopathic arthritis (n=11), psoriatic arthritis (n=37), ankylosing spondylitis (n=29), adult Still's disease (n=4), overlap disease (RA[2] and scleroderma or polymyositis, n=6), temporal arteritis (n=1), polyarteritis nodosa (n=1), dermatomyositis (n=1), amyloidosis secondary to RA (n=1) and Wegener's granulomatosis (n=1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS[3] and PS[4] patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease.

Conclusion: Our daily practice data are generally in agreement with worldwide experience. The ‘deviations’ might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data.

There has been a paradigm shift in the treatment of rheumatoid arthritis in recent years. Early and aggressive treatment with good control of disease activity has improved the prognosis of the disease, however, there is significant variability in the response of patients to different therapeutic agents. Hence it is essential to find the predictors of response to a drug at baseline so that we can avoid the delay in achieving remission and improve the outcome. Here we review the literature on available predictors for treatment response in general and specifically for methotrexate and biological agents. We also look at specific scores or indices that can help predict the response in individual patients.

Background: In an era of increasing antimicrobial resistance, knowledge of local antimicrobial susceptibility patterns of common uropathogens is essential for prudent empiric therapy of community-acquired urinary tract infections.

Objectives: To define antimicrobial susceptibility of Gram-negative uropathogens in northern Israel over a 10 year period and to compare it with antibiotic-use patterns in the same community.

Methods: We tested the susceptibility of all Gram-negative urinary isolates from outpatients at HaEmek Medical Center over the years 1995, 1999, 2002 and 2005 to common antimicrobial agents. MIC₉₀ of Escherichia coli to some of these agents was determined and antibiotic consumption data over the years 2000–2005 (DDD/1000/day) were obtained.

Results: We observed a rise in susceptibility rates of E. coli to amoxicillin-clavulanate, trimethoprim-sulfamethoxazole and nitrofurantoin and of other Gram-negative isolates to amoxicillin-clavulanate, ceftriaxone and cephalothin. Susceptibility rates of all Gram-negative uropathogens to ciprofloxacin decreased significantly. MIC₉₀ of E. coli for all drugs tested remained stable. There was a significant decrease in the use nitrofurantoin and TMP-SMX[1] and a significant increase in the use of ampicillin, cephalothin and ceftriaxone.

Conclusions: Antibiotic resistance patterns mostly remained unchanged or improved slightly. There was, however, a constant decrease in susceptibility of all Gram-negative uropathogens to ciprofloxacin. Antibiotic use patterns could not explain the changes seen in antibiotic susceptibility patterns.

Background: The extent of medical and financial problems of polypharmacy in the elderly is disturbing, particularly in nursing homes and nursing departments.

Objectives: To improve drug therapy and minimize drug intake in nursing departments.

Methods: We introduced a geriatric-palliative approach and methodology to combat the problem of polypharmacy. The study group comprised 119 disabled patients in six geriatric nursing departments, and the control group 71 patients of comparable age, gender and co-morbidities patients in the same wards. After 12 months, we assessed whether any change in medications affected the death rate, referrals to acute care facility and costs.

Results: A total of 332 different drugs were discontinued in 119 patients (average of 2.8 drugs per patient) and was not associated with significant adverse effects. The overall rate of drug discontinuation failure was 18% of all patients and 10% of all drugs. The 1 year mortality rate was 45% in the control group but only 21% in the study group (P < 0.001, chi-square test). The patients’ annual referral rate to acute care facilities was 30% in the control group but only 11.8% in the study group (P < 0.002). The intervention was associated with a substantial decrease in the cost of drugs.

Conclusions: Application of the geriatric-palliative methodology in the disabled elderly enables simultaneous discontinuation of several medications and yields a number of benefits: reduction in mortality rates and referrals to acute care facilities, lower costs, and improved quality of living.

Background: Mucositis and dermatitis are frequently encountered in patients treated with radiochemotherapy. Dead Sea products that contain minerals and different substances have proved effective in treating various skin diseases.

Objectives: To evaluate the effectiveness of Dead Sea products in reducing acute radiochemotherapy‑induced side effects in patients with head and neck cancer.

Methods: In this phase 2 study we compared the outcomes in 24 treated patients and 30 conventionally treated patients matched for age, tumor site, and type of treatment. The Dead Sea products comprised a mouthwash solution (Lenom®) and a skin cream (Solaris®) used three times daily for 1 week before, during, and up to 2 weeks after completion of radiotherapy. Mucositis and dermatitis were evaluated using common toxicity criteria.

Results: Thirteen treated patients (54%) had grade 1-2 and none had 3-4 mucositis, while 17 controls (57%) had grade 1-2 and 4 (13%) had grade 3-4 mucositis. Thirteen treated patients (54%) had grade 1-2 dermatitis; there was no instance of grade 3-4 dermatitis, while 11 patients in the control group (37%) had grade 1-2 and 5 (17%) had grade 3-4 dermatitis. More patients in the control arm needed a break than the patients in the treatment arm (P = 0.034[T1]).

Conclusions: The two Dead Sea products tested decreased skin and mucosal toxicity in head and neck cancer patients receiving radiochemotherapy.
 

Background: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study.

Objectives: To determine the efficacy and safety of Xolair® as an add-on treatment in patients with severe persistent asthma.

Methods: Asthma patients (age 12–75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair® or placebo for 28 weeks in a double-blind study in two Israeli centers.

Results: Thirty-three patients, 20 females and 13 males, mean age 54 ± 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair® (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction).
Conclusions: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA[1] and inhaled corticosteroids (GINA 2002 step 4), Xolair® is a safe and effective treatment

Background: Hyperglycemia is common among patients admitted to intensive care units, and carries the risk for complications and prolonged ICU[1] stay. With intensive insulin control of blood glucose, morbidity and mortality can be reduced.

Objectives: To determine whether intensive or conventional insulin control of blood glucose in hyperglycemic ICU patients correlated with the prognosis.

Methods: Following admission to the ICU, hyperglycemic patients were randomly assigned to a group treated intensively with insulin targeting glucose at 110–140 mg/dl, or to a conventional insulin therapy group, where glucose, upon exceeding 200 mg/dl, was controlled at 140–200 mg/dl. Rates of morbidity and mortality, hypoglycemic episodes, and insulin dosage were compared.

Results: In the 41 patients treated intensively with insulin the glucose level was 142 ± 14 mg/dl, as compared to 174 ± 20 mg/dl in the 48 patients on conventional insulin treatment. Both groups were similar in age, acute physiology and chronic health evaluation score. Morbidity was also similar, except for increased vascular damage in the conventional treatment group and slightly shorter ICU stay in the intensive therapy group. Both groups had similar in-ICU, in-hospital, and 28 day mortalities, and similar rates of hypoglycemic episodes. The daily dosage of insulin was significantly higher with the conventional treatment (P = 0.004).

Conclusions: Intensive insulin treatment did not affect the mortality or morbidity rates in ICU patients. The increased insulin dosage of conventional insulin treatment was attributable to the group's higher prevalence of diabetes. Future studies should address this bias and determine the optimal glucose target.