Natan R. Kahan

Empiric Treatment of Uncomplicated Urinary Tract Infection with Fluoroquinolones in Older Women in Israel: Another Lost Treatment Option?

Background: Current guidelines for the treatment of uncomplicated urinary tract infection (UTI) in women recommend empiric therapy with antibiotics for which local resistance rates do not exceed 10–20%. We hypothesized that resistance rates of Escherichia coli to fluoroquinolones may have surpassed this level in older women in the Israeli community setting. Objectives: To identify age groups of women in which fluoroquinolones may no longer be appropriate for empiric treatment of UTI. Methods: Resistance rates for ofloxacin were calculated for all cases of uncomplicated UTI diagnosed during the first 5 months of 2005 in a managed care organization (MCO) in Israel, in community-dwelling women aged 41–75 years. The women were without risk factors for fluoroquinolone resistance. Uncomplicated UTI was diagnosed with a urine culture positive for E. coli. The data set was stratified for age, using 5 year intervals, and stratum-specific resistance rates (% and 95% CI) were calculated. These data were analyzed to identify age groups in which resistance rates have surpassed 10%. Results: The data from 1291 urine cultures were included. The crude resistance rate to ofloxacin was 8.7% (95% CI 7.4 to 10.2). Resistance was lowest among the youngest (aged 41–50 y) women (3.2%; 95% CI 1.11 to 5.18), approached 10% in women aged 51–55 years (7.1%; 95% CI 3.4 to 10.9), and reached 19.86% (95% CI 13.2 to 26.5) among the oldest women (aged 56–75 y). Conclusions: Physicians who opt to treat UTI in postmenopausal women empirically should consider prescribing drugs other than fluoroquinolones. Concomitant longitudinal surveillance of both antibiotic utilization patterns and uropathogen resistance rates should become routine practice in this managed-care organization.

Longer than recommended empiric antibiotic treatment of urinary tract infection in women: an avoidable waste of money

Context:  Current Israeli guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommend nitrofurantoin for 5 days. Some physicians nevertheless opt for ofloxacin, which should be prescribed for 3 days according to universally accepted guidelines.

Altered thermoregulation in ambulatory schizophrenia patients: A naturalistic study

Background. Schizophrenia patients may exhibit alterations in core/body temperature. Hence, we intended to examine the potential existence of thermoregulatory abnormalities in ambulatory schizophrenia patients. Methods. Anonymous electronic patient record data of the Leumit Health Fund (Israel) were screened for all schizophrenia patients who have no other apparent chronic co-morbidity (mental or non-mental) and had their oral temperature assessed during routine follow-ups (Schiz-rFUs) or for various transitory infectious/inflammatory processes (Schiz-Infect) during the years 1999–2005 (n = 535). The comparison group consisted of a comparable sample (n = 560) of healthy subjects (Control-rFUs and Control-Infect). Results. The sub-group of Schiz-rFUs (n = 216) exhibited significantly lower mean oral temperature compared to the matched group of Control-rFUs (n = 140) (36.72±0.54 vs. 36.94±0.64°C, respectively; P<0.05). There was no significant difference in mean oral temperatures between the Schiz-Infect (n = 319) and the Control-Infect (n = 420) (37.32±0.92 vs. 37.28±0.98°C, respectively; NS). Conclusions. Ambulatory schizophrenia patients without a concomitant infectious/inflammatory process exhibit altered thermoregulation manifested by a substantial (about 0.2°C) and significantly lower oral temperature compared to healthy comparison subjects as well as a potential exaggerated increase in oral temperature during transitory infectious/inflammatory processes. The relevance of these phenomena to the pathophysiology of schizophrenia as well as the potential immune-mediated pathologies in schizophrenia merit further investigation.

Empiric treatment of uncomplicated UTI in women: wasting money when more is not better

Context:  Trimethoprim–sulfamethoxazole (TMP–SMX) and nitrofurantoin were until recently the two drugs recommended in clinical guidelines in Israel for empiric treatment of uncomplicated urinary tract infection (UTI) in women.

Modifying prescribing behaviour of angiotensin receptor blockers by selectively rescinding managerial prior authorization requirements for losartan

AIMS To evaluate whether rescinding the prior authorization (PA) requirement (managerial pre-approval) for losartan in an health maintenance organization (HMO) could reduce prescribing of the more expensive angiotensin receptor blockers (ARBs). METHODS HMO physicians were notified that losartan would no longer require PA, and appropriate changes were made to the electronic prescribing computer program. The monthly distribution by drug of the number of prescriptions for ARBs dispensed for new patients was calculated before and after the policy change from data captured from electronic records. The proportion of patients (percentage and 95% confidence interval) treated with losartan who met the criteria for treatment with ARBs (hypertension or cardiac insufficiency in patients who have developed adverse effects in response to angiotensin-converting enzyme inhibitors or macroproteinuria) during the first month after the PA requirement was rescinded was calculated. RESULTS The total number of PA requests for ARBs declined by 48.6% from 961 in December 2008, the month before the policy change, to 494 the following January, rising again to 651 during January 2010. Prescription incidence changed from 121 to 255 patients treated per month (114% increase) for losartan, from 15 to 16 (6.7% increase) for candesartan, and from 89 to 71 (20.2% decrease) for valsartan. The duration of effect for decrease in ARB requests for the more expensive drugs was approximately 1 year. Only 23.3% (95% confidence interval 18.1-28.4) of patients receiving losartan met the criteria for receiving ARBs. CONCLUSIONS Rescinding the PA requirement for this drug alone was an effective limited-duration strategy for reduction of prescription of relatively expensive drugs.

The tools of an evidence-based culture: implementing clinical-practice guidelines in an Israeli HMO.

Purpose Although clinical-practice guidelines (CPGs) are implemented on the assumption that they will improve the quality, efficiency, and consistency of health care, they generally have limited effect in changing physicians’ behavior. The purpose of this study was to design and implement an effective program for formulating, promulgating, and implementing CPGs to foster the development of an evidence-based culture in an Israeli HMO. Method The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns, updating CPGs, collecting MDs’ input via focus groups and quantitative surveys, and conducting a randomized controlled trial of a two-stage, multipronged intervention. The test case for this study was the development, dissemination, and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women. Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented, both individually and combined, to improve physicians’ rates of prescribing the first-line drug, nitrofurantoin, and, in the absence of nitrofurantoin, adhering to the recommended duration of three days of treatment with ofloxacin. Results The tools and data-generating capabilities designed and constructed in Stage I of the project were integral components of all subsequent stages of the program. Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4% (95% CI = 16.7, 22.1). Conclusions This study provides a template for introducing the component of experimentation essential for cultivating an evidence-based culture. This process, composed of collaborative efforts between academic institutions and a managed care organization, may be beneficial to other health care systems.

Clinical-laboratory characteristics of ANA-positive chronic idiopathic urticaria.

Despite the established association between chronic idiopathic/spontaneous urticaria (CIU) and presence of antinuclear antibodies (ANAs), the prevalence of autoimmune comorbidities in this population has not been analyzed. Here, we aim to identify clinical and laboratory manifestations associated with ANA-positive CIU. ANA-positive patients were identified via electronic data capture from the electronic patient record database of Leumit Health care Services (LHS) of Israel. Patient characteristics, medical histories, and details of diagnostic workup, medical treatment, and follow-up were retrieved by performing a chart review of electronic patient records (EPRs). The prevalence of target diseases among ANA(+) CIU(+), ANA(+) CIU(-), and ANA(-) CIU(+) patients was calculated. A total of 91 ANA(+) CIU(+), 3131 ANA(+) CIU(-), and 478 ANA(-) CIU(+) patients were identified. The ANA(+) CIU(+) group was characterized by higher prevalence of Sjögrens syndrome (SS)-A 52 antibodies (Ab) (7.7% versus 2.4%; p = 0.008), SS-A 60 Ab (11% versus 2.8%; p = < 0.001), and SS-B Ab (14.3% versus 3.2%; p < 0.001), compared with ANA(-) CIU(+) group. Additionally, ANA(+) CIU(+) patients were more likely to be diagnosed with thyroid autoimmune diseases, higher C-reactive protein (6.4 ± 10.3 versus 4.1 ± 8.8 mg/L; p = 0.027), and more profound basopenia (0.04 ± 0.09 versus 0.15 ± 0.11 cell/mm(3); p < 0.001) than ANA(-) CIU patients. More ANA(+) CIU(+) patients were resistant to four-fold standard licensed doses of antihistamines than ANA(-) CIU(+) patients [11 (12.1%) versus 29 (6.1%); p = 0.046]. ANA-positive CIU is characterized by higher prevalence of SS-A 52, SS-A 60, and SS-B antibodies and poorer clinical response to antihistamine medications.

Association of alopecia areata with atopic dermatitis and chronic spontaneous urticaria

BACKGROUND Epidemiologic studies report that alopecia areata (AA) is related to various atopic and autoimmune diseases. The purpose of this study was to identify clinical characteristics and the prevalence of comorbid conditions in Israeli patients with AA. METHODS This retrospective, matched, case-control study was based on data from an electronic patient record data base. The patients with an electronically documented diagnosis of AA were included in the AA group. The control group was randomly sampled from the remaining subjects, with a case-to-control ratio of two controls for each case. Comorbidity was compared between the study groups. RESULTS A total of 1751 subjects (49.4% men and 50.6% women), ages 34.9 ± 17.8 years old, were identified. The control group consisted of 3502 age- and sex-matched subjects. The AA group was characterized by a higher blood eosinophil count (0.39 ± 0.12 cells/mm3) than the control group (0.31 ± 0.14 cells/mm3; p < 0.001). In the AA group, there was a higher prevalence of allergic rhinitis (odds ratio [OR] 2.15 [1.85-2.49]; p < 0.001), asthma (OR 1.57 [1.28-1.93]; p < 0.001), atopic dermatitis (AD) (OR 4.17 [3.18-5.47]; p < 0.001), and food allergy (OR 2.79 [1.58-4.91]; p < 0.001) than in the control group. The prevalence of organ-specific and systemic autoimmune diseases was significantly higher in the AA group than in the control group, with the OR of having any autoimmune disease calculated to be 4.72 (3.99-5.57; p < 0.001). The OR of having chronic spontaneous urticaria (CSU) with AA was 6.15 (4.06-9.32; p < 0.001). In patients with concomitant AA and CSU, allergic rhinitis and AD were more prevalent than in patients with CSU in the control group. CONCLUSION An estimated prevalence of AA among an Israeli population was ∼0.8%. The novel finding of our study was the high prevalence of food allergy and CSU in patients with AA.

Prevalence of dermatologic diseases among patients with selective immunoglobulin A deficiency.

BACKGROUND There are no published large-scale epidemiologic studies regarding the prevalence of skin diseases in patients with selective immunoglobulin A (IgA) deficiency (sIgAD). The purpose of this study was to investigate the prevalence of dermatological diseases in patients with sIgAD. METHODS This retrospective matched case-control study was based on data from the Leumit Healthcare Services data base (approximately 725,000 residents of Israel), which was searched for all subjects aged ≥12 years who had undergone serum total IgA measurements during 2004-14 for any reason. The case group included subjects with sIgAD. The control A group was randomly sampled from those subjects in whom an IgA was drawn (n ≈ 725,000), with a ratio of 10 controls for every case (1:10). The control A group was randomly sampled from those subjects in whom an IgA was drawn (n = 104,729) and the control B group was randomly sampled from the full study population (n ≈ 725,000), with a ratio of 10 controls for every case (1:10). Comorbidity was compared between the study groups. RESULTS The sIgAD group was characterized: 1) By a higher prevalence of atopic dermatitis (AD) (16 [4.6 %]) than the control A group (76 [2.1 %]; p = 0.004 and the control B group (64 [1.9 %]; p = 0.002). 2) By higher prevalence of acne (69 [19.9 %]) than the control A group (516 [13.8 %]; p = 0.013) and control B group (494 [14.2 %]; p < 0.001). 3) By higher rate of chronic spontaneous urticaria (CSU) (17 [4.9 %)] than in the control A group (31 [0.9 %], with odds ratio 5.54 [3.04-10.13]; p < 0.001) and the control B group (28 [0.8 %]; p < 0.001). CONCLUSIONS sIgAD is characterized by a higher prevalence of AD, CSU and acne.