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עמוד בית Sun, 15.09.19

June 2007


Original Articles
M. Paul, A. Gafter-Gvili, L. Leibovici, J. Bishara, I. Levy, I. Yaniv, I. Shalit Z, Samra, S. Pitlik, H. Konigsberger and M. Weinberger

Background: The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia.

Objectives: To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel.

Methods: We conducted a prospective data collection on all patients with neutropenia (< 500/mm3) and clinically significant bacteremia or fungemia during the period 1988–2004.

Results: Among adults (462 episodes) the most common bloodstream isolate was Esherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3 throughout the study period. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital.
Conclusions: Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients’ risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment

D. Garfinkel, S. Zur-Gil, J. Ben-Israel

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.

 
 

A. Szalat, G. Erez, E. Leitersdorf

Background: The management of aspirin therapy before an invasive procedure poses a frequent clinical dilemma due to uncertainty regarding b[AS1] leeding versus thromboembolic risks associated with continuation or withdrawal of the drug. There is no evidence-based data to refer to.

Objectives: To assess the opinions of internal medicine physicians regarding aspirin therapy prior to an invasive procedure.

Methods: A questionnaire presenting nine hypothetical cases with different combinations of bleeding and thromboembolic risk was given to physicians in an Internal Medicine Division during a personal interview. For each case the participants had to choose between withdrawal of aspirin prior to an invasive procedure, continuation of aspirin, or substitution of low molecular weight heparin for aspirin. Results: Sixty-one physicians participated in the survey. For a patient with low thromboembolic risk, 77% (95% confidence interval 65.3–86.3%), 95% (87.2–98.7%) and 97% (89.6–99.5%) of physicians elected to discontinue aspirin prior to a low, intermediate or high bleeding risk procedure, respectively. For intermediate risk patients, 23% (95% CI[1] 13.7–34.7%), 59% (46.4–70.8%) and 74% (61.7–83.6%) would discontinue aspirin prior to a low, intermediate or high risk procedure, and 5% (95% CI 1.3–12.8%), 23% (13.7–34.7%) and 18% (9.9–29.2%) would substitute LMWH[2] for aspirin. For a patient with high thromboembolic risk, 1.6% (95% CI 0.08–7.8%), 11.5% (5.2–21.4%) and 18% (9.9–29.2%) recommended discontinuing aspirin prior to a low, intermediate or high risk procedure, respectively. In these situations, 18% (95% CI 9.9–29.2%), 53% (40.0–64.7%) and 57% (44.8–69.3%), respectively, would substitute LMWH for aspirin.

Conclusions: The results of the current investigation may help practicing physicians to decide whether to discontinue aspirin therapy prior to invasive procedures. The possible use of LMWH to replace aspirin as suggested here should be further evaluated in a controlled clinical study.

 



 



[2] LMWH = low molecular weight heparin

 [AS1]Is it the appropriate syntax ?


D. Matceyevsky, N. Yaal Hahoshen, A. Vexler, N. Asna, A. Khafif, R. Ben-Yosef

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.
 

R. Gepstein, Z. Arinzon, Y. Folman, S. Shabat, A. Adunsky

Background: Surgery for spinal stenosis is a frequent procedure in elderly patients. Presentation, hospital course and outcome of disease, including pain perception, may vary among patients of different ethnic origin.

Objectives: To evaluate whether differences in various medical indicators can explain differences in pain perception between two ethnic groups

Methods: We conducted a case-control study on the experience of two spinal units treating a mixed Arab and Jewish population, and compared the data on 85 Arab and 189 Jewish patients undergoing spinal lumbar surgery.

Results: Arab patients were younger (P = 0.027), less educated (P < 0.001), had a higher body mass index (P = 0.004) and included a higher proportion of diabetics (P = 0.013). Preoperative pain intensity (P = 0.023) and functional disability (P = 0.005) were more prominent, and factors associated with pre- or postoperative pain perception differed between the two ethnic groups. Despite these differences, results on follow-up were similar with respect to pain perception and level of disability.

Conclusions: A better understanding of ethnic differences is crucial for predicting surgery outcomes.

 
 

A. Basok, M. Vorobiov, B. Rogachev, L. Avnon, D. Tovbin, M. Hausmann, N. Belenko, M. Zlotnik, A. Shnaider

Background: Patients with end-stage renal disease are at high risk of mycobacterial infection.

Objectives: To analyze the difficulties in reaching an accurate diagnosis of tuberculosis in dialysis patients.

Methods: We conducted a retrospective follow-up of patients who attended our peritoneal and hemodialysis units during the 10 year period 1995–2005.

Results: Our dialysis unit diagnosed 10 cases of tuberculosis caused by Mycobacterium tuberculosis and 9 cases of Mycobacterium other than tuberculosis. In the former group, five patients had mycobacterium in the sputum, which was diagnosed by intraabdominal mass biopsy in one, culture of the gastric juices in one, and pleural fluid culture or pleural biopsy in three. One of these patients was suffering from pleural TB[1] as well as Potts disease. Of the patients with Mycobacterium other than tuberculosis, five were diagnosed by sputum cultures, three by urine cultures and one in peritoneal fluid. Differences in treatment and outcome were also reviewed.

Conclusions: The diagnosis of TB in dialysis patients should be approached with a high index of suspicion. It is clear that extensive diagnostic procedures are required to ensure an accurate diagnosis of the disease. Tuberculosis incurs a significant added burden due to the need for isolation of infected patients within the dialysis unit. Treatment of patients with Mycobacterium other than tuberculosis should be addressed individually.






[1] TB = tuberculosis


H. Tandeter, I. Masandilov, I. Kemerly, A. Biderman

Background: Studies have found ethno-cultural disparities in health care delivery in different countries. Minority populations may receive lower standards of care.

Objectives: To test a hypothesis that Jewish Ethiopian women may be receiving less preventive recommendations than other women in Israel.

Methods: A telephone survey was conducted using a structured questionnaire designed specifically for this study in Hebrew, Russian and Amharic (Semitic language of Ethiopia). The study group included 51 post-menopausal women of Ethiopian origin, aged 50–75. The control group included 226 non-Ethiopians matched by age, some of whom were immigrants from the former Soviet Union. The questionnaire dealt with osteoporosis and breast cancer screening and prevention.

Results: All the parameters measured showed that the general population received more preventive treatment than did Jewish Ethiopian women, including manual breast examination, mammography, osteoporosis prevention, bone density scans, and recommendations for a calcium-rich diet, calcium supplementation, hormone replacement therapy, biphosphonates and raloxifen. On a logistic regression model the level of knowledge of the Hebrew language, age, ethnicity and not visiting the gynecologist were significantly related to not having received any preventive medicine recommendations.
Conclusions: Differences in cultural backgrounds and language between physicians and their patients may become barriers in the performance of screening and preventive medicine. Recognizing this potential for inequity and using methods to overcome these barriers may prevent it in the future

S. Flechter, J. Vardi, Y. Finkelstein, L. Pollak

Background: The cognitive impairment (frontal, parietal) in many patients with multiple sclerosis does not correlate with the degree of neurological disability and disease duration. Frontal/prefrontal cognitive impairment requires neuropsychological diagnostic tools.

Objectives: To evaluate the clinical effect of IFNβ-1b[1] (Betaferon®) treatment on cognitive function and event-related potential as compared to the clinical course (EDSS[2]) in MS patients during 1 year of follow-up.

Methods: This prospective open-label design study included 16 consecutive patients with relapsing forms of MS attending the MS outpatient clinic. Mean EDSS score was calculated prior to starting treatment. Parietal lobe event-related potential P300 was elicited using an auditory physical stimulus to an alert subject. Mean P300 amplitude and latency were calculated for the group before treatment. The Wisconsin Card Sorting Test, which measures frontal lobe functions, was performed before the treatment. After 1 year of treatment a second P300 and Wisconsin Card Sorting Test were performed and the mean change between visit 1 and baseline was calculated for each parameter. Correlation between the change in P300 and the Wisconsin Card Sorting Test score at baseline was measured using the paired t-test.

Results: There was a significant reduction in P300 amplitude and latency after 1 year of treatment with IFNβ-1b: from 20.3 ± 8.3 μv to 13.1 ± 10.6 μv (P = 0.026) for amplitude, and from 312.9 ± 15.6 msec to 302.0 ± 17.0 msec (P = 0.002) for latency. The Perseverative Response (raw score) and the Perseverative Response U.S. Census age-matched standard score showed a significant improvement – from 20.7 ± 30.7 to 13.1 ± 10.6 (P = 0.001) and 96.7 ± 15.7 to 100.1 ± 11.1 (P = 0.0025) respectively – after 1 year of treatment. A mild but not significant improvement was observed on the EDSS after 1 year of treatment: 2.9 ± 0.5 to 2.8 ± 1.1.

Conclusions: A cognitive decline in MS patients may have a negative impact on the quality of life, affecting all active daily living domains. IFNβ-1b, a disease-modifying therapy, has demonstrated a positive therapeutic effect on cognitive dysfunction, unrelated to its effect on the EDSS score and course of the disease.






[1] IFNβ = interferon beta

[2] EDSS = Expanded Disability Status Scale


Reviews
A. Gafter-Gvili, M. Paul, A. Fraser, L. Leibovici.
Allergy And Clinical Immunology
Z.M. Sthoeger, A. Eliraz, I. Asher, N. Berkman, D. Elbirt

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







[1] LABA = long-active beta-2 agonists


.T. Handzel, V. Barak, Y. Altman, H. Bibi, M. Lidgi, M. Iancovici-Kidon, D. Yassky, M. Raz

Background: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis. 

 






[1] TB = tuberculosis

[2] IL = interleukin

[3] PPD = purified protein derivative

[4] IFNγ = interferon-gamma

[5] SER = serum

[6] IL-2R = interleukin 2 receptor

[7] NS = non-stimulated


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