Natan Kahan | Tel Aviv University (original) (raw)

Papers by Natan Kahan

Journal of Managed Care Pharmacy, Jun 1, 2010

• Off-label medication use is common and permitted in the United States and Israel but may not be... more • Off-label medication use is common and permitted in the United States and Israel but may not be evidence based. • Since drug use evaluation (DUE) studies are generally motivated by cost or safety concerns, there is a paucity of information on off-label use of inexpensive drugs. • Unapproved, off-label use of drugs is not identified in managed care plans in the absence of a prior authorization (PA) requirement.

PubMed, Aug 1, 2013

Background: After a new formulation of levothyroxine was distributed in Israel, side effects were... more Background: After a new formulation of levothyroxine was distributed in Israel, side effects were reported to the Ministry of Health generating extensive media coverage. The purpose of this study was to determine whether the new formulation was associated with a change in thyroid-stimulating hormone (TSH) levels of treated patients and to evaluate the effect of the extensive media coverage on the incidence of laboratory test performance. Study design: Retrospective-cohort and crosssectional analysis. Methods: All patients from the Leumit Health Services of Israel treated with levothyroxine between October 2009 and February 2012 were included in the study. A retrospective cohort was constructed of patients treated and maintained within the desired target range (0.35-5 mIU/L) from January to July 2010. A longitudinal analysis was conducted to calculate the monthly distribution of TSH levels from laboratory tests during routine care over 26 months. Data were stratified by cohort and noncohort patients. Results: Data were captured for 18,106 levothyroxine-treated patients; 1140 were included into the retrospective cohort. In both subpopulations a sharp rise in the number of tests performed monthly is observed at the peak of media coverage during October and November 2011. In the retrospective cohort the proportion of TSH results within target range fell to a low of 67.5% during December 2011, with 25.3% between 5.01 and 20 mIU/L. Results>20 mIU/L then peaked at 3.8% indicating an increase in patients who stopped taking levothyroxine. Conclusions: These results demonstrate the power of mass media to influence patient behavior and to foment a public health scare.

Allergy and Asthma Proceedings, Jul 1, 2019

Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly und... more Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly understood. Objective: To identify clinical and laboratory attributes of patients that may be predictive of OmR in CSU. Methods: We conducted a retrospective observational study by using an electronic patient record data base of patients with severe CSU refractory to a fourfold H 1-antihistamine dose, treated with omalizumab 300 mg every 4 weeks for at least 24 weeks. Complete response (CR) was defined as the reduction of baseline urticaria activity score by Ն 90%, partial response (PR) by Ն 30% to Ͻ90%, and OmR by Ͻ30% at 24 weeks. The patient characteristics of the CR, PR, and OmR groups were compared. Results: Sixty-three patients (58.9%) had a complete remission at 24 weeks of omalizumab therapy, and 16 patients (14.9%) had OmR. The patients who were OmR were characterized by a higher rate of arterial hypertension 7 (43.8%), higher mean Ϯ standard deviation (SD) high-sensitivity C-reactive protein (hs-CRP) level (10.3 Ϯ 8.2 mg/L), mean Ϯ SD white blood cell (WBC) count (9.1 Ϯ 2.8 ϫ 10 3 cells/mL), and higher mean Ϯ SD C3 level (164.3 Ϯ 45.4 mg/dL) at baseline than the patients

British Journal of Clinical Pharmacology, Nov 9, 2011

, the month before the policy change, to 494 the following January, rising again to 651 during Ja... more , 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 limitedduration strategy for reduction of prescription of relatively expensive drugs.

Allergy and Asthma Proceedings, 2021

Background: Biomarkers of resistance to H1-antihistamines (AH) and omalizumab in chronic spontane... more Background: Biomarkers of resistance to H1-antihistamines (AH) and omalizumab in chronic spontaneous urticaria (CSU) are still a matter of debate. Objective: To identify clinical and laboratory attributes of the patient that may be predictive of AH and omalizumab resistance in CSU. Methods: We conducted a retrospective observational study by using the electronic patient record data base of patients with CSU and of sex- and age-matched controls. Patients with CSU were divided into three study groups: the CSU group, patients who responded to AHs; the antihistamine-resistant CSU (AH-CSU) group, patients refractory to a fourfold AH dose; and the control group, composed of a random sample of age- and sex-matched subjects, with a case-control ratio of 1:2. The patients in the AH-CSU group treated with omalizumab were compared according to the response or resistance to omalizumab. Results: A total of 106 subjects in the AH-CSU group, 483 in the CSU group, and 1198 in the control group were compared. Both AH-CSU (112.7 ± 43.1 kU/mL) and CSU (129.5 ± 52.4 kU/mL) groups were associated with higher plasma total IgE levels than control group (103.2 ± 49.5 kU/mL; p < 0.001). The AH-CSU group was characterized by a higher plasma high-sensitivity C-reactive protein level (6.4 ± 3.7 mg/L) than the CSU group (4.3 ± 1.4 mg/L; p < 0.001) and the control group (3.1 ± 1.8 mg/L; p < 0.001). The AH-CSU and CSU groups were characterized by a lower mean ± standard deviation basophil counts (0.18 ± 0.16 cells ×109/L and 0.19 ± 0.11 cells ×109/L, respectively) than the control group (0.22 ± 0.09 cells ×109/L; p < 0.001). The mean platelet volume was higher in the AH-CSU group (11.2 ± 0.3 fL) than in the CSU group (11.1 ± 0.4 fL; p = 0.002) and in the control group (10.3 ± 0.4 fL; p < 0.001). There were no significant differences in the mean levels of lymphocytes, monocytes, eosinophils, basophils, and platelets, and the rates of eosinopenia and basopenia between the patients in the AH-CSU group who responded to and those who were resistant to omalizumab. Conclusion: This study provided additional data of interest to examine the pathophysiologic role of low-grade inflammation and basopenia in patients with CSU and resistant to AHs and omalizumab.

The American Journal of Managed Care, Feb 1, 2005

Allergy and asthma proceedings, 2017

There are no published large-scale epidemiologic studies regarding the prevalence of skin disease... more 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. 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...

American Journal of Managed Care, 2005

To identify cases of inappropriate physician prescribing in a managed care setting in Israel that... more To identify cases of inappropriate physician prescribing in a managed care setting in Israel that may have resulted from misuse of magnetic-stripe membership cards. Retrospective drug utilization analysis of electronic patient prescription data. In a managed care setting involving approximately 1000 physicians who issue approximately 1.4 million prescriptions annually, the rate of prescription of sex-specific drugs to patients of the opposite sex for which the drugs are indicated was evaluated for 2003. The categories of drugs included in the analysis were drugs for the treatment of benign prostatic hyperplasia or erectile dysfunction that were prescribed to women, as well as oral contraceptives, vaginal pessaries, hormone therapy, or raloxifene hydrochloride prescribed to men. Throughout the study year, 193 different physicians wrote 341 prescriptions that matched the drug inclusion criteria for 210 different patients. The most frequently observed scenario involved the prescription...

Allergy and Asthma Proceedings, 2021

Background: Biomarkers of resistance to H1-antihistamines (AH) and omalizumab in chronic spontane... more Background: Biomarkers of resistance to H1-antihistamines (AH) and omalizumab in chronic spontaneous urticaria (CSU) are still a matter of debate. Objective: To identify clinical and laboratory attributes of the patient that may be predictive of AH and omalizumab resistance in CSU. Methods: We conducted a retrospective observational study by using the electronic patient record data base of patients with CSU and of sex- and age-matched controls. Patients with CSU were divided into three study groups: the CSU group, patients who responded to AHs; the antihistamine-resistant CSU (AH-CSU) group, patients refractory to a fourfold AH dose; and the control group, composed of a random sample of age- and sex-matched subjects, with a case-control ratio of 1:2. The patients in the AH-CSU group treated with omalizumab were compared according to the response or resistance to omalizumab. Results: A total of 106 subjects in the AH-CSU group, 483 in the CSU group, and 1198 in the control group were...

Allergy and Asthma Proceedings, 2019

Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly und... more Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly understood. Objective: To identify clinical and laboratory attributes of patients that may be predictive of OmR in CSU. Methods: We conducted a retrospective observational study by using an electronic patient record data base of patients with severe CSU refractory to a fourfold H1-antihistamine dose, treated with omalizumab 300 mg every 4 weeks for at least 24 weeks. Complete response (CR) was defined as the reduction of baseline urticaria activity score by ≥ 90%, partial response (PR) by ≥ 30% to <90%, and OmR by <30% at 24 weeks. The patient characteristics of the CR, PR, and OmR groups were compared. Results: Sixty-three patients (58.9%) had a complete remission at 24 weeks of omalizumab therapy, and 16 patients (14.9%) had OmR. The patients who were OmR were characterized by a higher rate of arterial hypertension 7 (43.8%), higher mean ± standard deviation (SD) high-sensitivity C-reactive protein (hs-CRP) level (10.3 ± 8.2 mg/L), mean ± SD white blood cell (WBC) count (9.1 ± 2.8 × 10³ cells/mL), and higher mean ± SD C3 level (164.3 ± 45.4 mg/dL) at baseline than the patients with CR (arterial hypertension, 9 [13.1%], p = 0.009; mean ± SD hs-CRP, 3.4 ± 10.1, p = 0.014; mean ± SD WBC count, 6.5 ± 3.8 × 10³ cells/mL, p = 0.012; and mean ± SD C3 level, 121.8 ± 42.1 m/dL, p < 0.001). In multivariable analysis adjusted for age, sex, and body mass index, OmR was associated with an hs-CRP level of >3.0 mg/L (odds ratio 1.94 [95% confidence interval, 1.28-3.15], p = 0.009) and with C3 > 160 mg/dL (odds ratio 1.54 [95% confidence interval, 1.05-2.36], p = .017). Conclusion: Obesity, arterial hypertension, high plasma C3 level, and high-CRP level were associated with OmR in severe CSU.

British Journal of Medicine and Medical Research, 2013

Aims: In a previous study (2004) we explored the clinical and microbiological aspects of bloodstr... more Aims: In a previous study (2004) we explored the clinical and microbiological aspects of bloodstream infections (BSI) in a multilevel geriatric hospital, and concluded that follow up and monitoring of these parameters is warranted. The purpose of this new study is to evaluate the current BSI status and compare these data to those obtained previously. Study Design and Methodology: We implemented the methodology developed for the initial study. Clinical features, microbiological characteristics and outcome of BSI over the year 2009 were investigated. Results: The rate of positive blood cultures was similar (10% versus 12%). The rate of BSI was 1.35 per 1000 patients in 2004 and 1.7 per 1000 in 2009. The mortality rate at 2 weeks decreased significantly (from 42% to 22.5%, p=.001). The most common isolate was Escherichia coli in both studies, followed by Proteus mirabilis. Interestingly, antibiotic susceptibility of common pathogens between 2004 and 2009 remained unchanged in 40% while increasing in 32% of cases.

Allergy and Asthma Proceedings, 2015

Despite the established association between chronic idiopathic/spontaneous urticaria (CIU) and pr... more 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 Sjögren&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome (SS)-A 52 antibodies (Ab) (7.7% versus 2.4%; p = 0.008), SS-A 60 Ab (11% versus 2.8%; p = &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and SS-B Ab (14.3% versus 3.2%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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.

Value in Health, 2009

To review the PRO end-points appearing in the product labels of pain treatments with a particular... more To review the PRO end-points appearing in the product labels of pain treatments with a particular focus on products approved both in the United States (US) and in Europe. METHODS: Pain treatments approved in the US since 1998 and in Europe through the centralized procedure established in 1995, and including PRO evaluations in the approved labeling were identifi ed from the PROLabels database. PROLabels is a unique on-line tool providing information on the products for which the FDA and/or the EMEA have granted PRO labeling claims. For the products approved by both agencies, we will compare the PRO endpoints appearing in the approved labeling and also analyze the PRO studies submitted by the sponsor. RESULTS: Overall, 26 products indicated for the treatment of pain were identifi ed, accounting for 16 different molecules and ten different indications. Various methods were used to measure pain (VAS, Likert scales). Of these 26 drugs, only two showed evidence of treatment effi cacy using additional PRO endpoints (function and patient satisfaction). The PRO appearing in the approved labeling are rather consistent between both regulatory agencies. Information on additional PRO endpoints that were assessed in the clinical studies submitted by the sponsors but were not accepted in the approved labeling was available for nine out of the 26 dossiers. The concepts assessed were health-related quality of life, psychological functioning, physical functioning (including interference with sleep) and patient global impression. A focus was made on the different reasons of rejection of the most recent claims, in the light of the current PRO guidances published by both regulatory agencies. CONCLUSIONS: Overall, only a few pain treatments include other PRO endpoints in addition to pain in their labeling. An interesting fi nding is the similarity between the American and the European PRO claims for pain therapies.

American health & drug benefits, 2016

BACKGROUND Prior authorization (PA) is a management technique that has been implemented to manage... more BACKGROUND Prior authorization (PA) is a management technique that has been implemented to manage the utilization of expensive drugs and to improve the precision of drug prescribing. PA requirements may incentivize physicians to document adverse effects, sometimes falsely, to meet the eligibility requirements. OBJECTIVES To identify documentation patterns that may facilitate the quantitative analysis of physician gaming and underreporting behaviors associated with the prescribing of angiotensin-converting enzyme (ACE) inhibitors in a primary care setting, and to evaluate the effect of a PA requirement on the documentation of adverse events as a way to receive approval for more expensive drugs. METHODS We conducted a retrospective analysis of physician electronic reporting of adverse effects associated with ACE inhibitors before and after the revocation of a PA requirement for angiotensin receptor blockers (ARBs) between 2004 and 2013 in an Israeli HMO. The data were stratified into ...

The American journal of managed care, 2013

BACKGROUND After a new formulation of levothyroxine was distributed in Israel, side effects were ... more BACKGROUND After a new formulation of levothyroxine was distributed in Israel, side effects were reported to the Ministry of Health generating extensive media coverage. The purpose of this study was to determine whether the new formulation was associated with a change in thyroid-stimulating hormone (TSH) levels of treated patients and to evaluate the effect of the extensive media coverage on the incidence of laboratory test performance. STUDY DESIGN Retrospective-cohort and crosssectional analysis. METHODS All patients from the Leumit Health Services of Israel treated with levothyroxine between October 2009 and February 2012 were included in the study. A retrospective cohort was constructed of patients treated and maintained within the desired target range (0.35-5 mIU/L) from January to July 2010. A longitudinal analysis was conducted to calculate the monthly distribution of TSH levels from laboratory tests during routine care over 26 months. Data were stratified by cohort and nonco...

En la comunidad biomedica se acepta actualmente que las presentaciones sean precedidas por una de... more En la comunidad biomedica se acepta actualmente que las presentaciones sean precedidas por una declaracion en la que los investigadores senalan no tener conflictos de intereses que declarar. En concordancia con esta practica, yo por la presente declaro, segun mi leal saber y entender que yo no tengo lazos con la familia del Dr. Ernesto Kahan. Yo encuentro muy apropiado introducir este articulo editorial con esta declaracion, dado que exactamente con esas palabras (aunque en hebreo) inicie mi carrera como investigador cuando someti esa declaracion a la Autoridad de Investigacion de la Universidad Hebrea de Jerusalen para recibir la aprobacion de tener al Dr. Kahan como uno de mis tutores de doctorado (PhD).

Audiology and Neurotology

Objectives: Autoimmune inner ear disease (AIED) is a distinct clinical entity from sudden sensori... more Objectives: Autoimmune inner ear disease (AIED) is a distinct clinical entity from sudden sensorineural hearing loss. The purpose of this study was to investigate the clinical characteristics of AIED in patients with selective IgA deficiency (sIgAD). Materials and Methods: This retrospective observational study was based on data from the Leumit Healthcare Services database in Israel. We searched all subjects aged ≥12 years who had undergone serum total IgA measurements during 2004–2014 for any reason. The sIgAD patients included all subjects with serum IgA of ≤7 mg/dL (0.07 g/L). A control group was randomly sampled from the full study population (n ≈ 730,000) with a case-control ratio of 10 controls for each case (1:10). Results: Among 347 subjects with sIgAD, we identified 9 patients with concomitant AIED (sIgAD + AIED group). This group was characterized by a higher prevalence of allergic diseases (8 patients; 88.9%) than sIgAD patients without AEID (sIgAD + AIED group; 153 patie...

Clinical and experimental immunology, Jan 8, 2016

Selective IgA deficiency (IgAD) is the most common primary immunodeficiency in the Western world.... more Selective IgA deficiency (IgAD) is the most common primary immunodeficiency in the Western world. The aim of the study was to investigate the prevalence and clinical characteristics of Helicobacter pylori (H. pylori) infected dyspeptic patients with IgAD. Case samples were drawn from all subjects ≥ 12 years of age (n = 104729), who that had undergone serum total IgA measurements during 2004 - 2014 years for any reason at Leumit Healthcare Services (Israel) and had serum total IgA <0.07 g/L. The control group was comprised of a random sample of remaining patients with a case-control ratio ten controls for each case. The dyspeptic diseases were identified and retrieved from Leumit Health Care Services electronic database using specific ICD-9-CM diagnostic codes. Case group included 347 subjects and Control group 3470 subjects. There were no significant difference in the prevalence of patients with dyspepsia (84 (24.2%) vs 821 (23.6%) for cases and controls, respectively). Additiona...

BACKGROUND Ethnicity has been associated with variance in warfarin treatment regimens in various ... more BACKGROUND Ethnicity has been associated with variance in warfarin treatment regimens in various settings. OBJECTIVES To determine whether ethnicity is associated with variance in patient management in Israel. METHODS Data were extracted from the electronic patient records of Clalit Health Services clinics in the Sharon Shomron region. The study group comprised all patients treated with warfarin who performed international normalized ratio tests for at least 6 months in 2003. The proportion of tests of each patient within the target range was calculated, as was the crude average rates and 95% confidence intervals for Jewish and Arab patients. The data were then stratified by patient's gender and age, specialty of the attending physician, and the country where the physician studied medicine. RESULTS We identified 2749 Jews and 293 Arabs who met the inclusion criteria of the study. The crude average rate of patients' INR tests within the target range was 62.3% among Jews (95% ...

Allergy and asthma proceedings, 2018

Epidemiologic studies report that alopecia areata (AA) is related to various atopic and autoimmun... more 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. 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. 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 o...

Journal of Managed Care Pharmacy, Jun 1, 2010

• Off-label medication use is common and permitted in the United States and Israel but may not be... more • Off-label medication use is common and permitted in the United States and Israel but may not be evidence based. • Since drug use evaluation (DUE) studies are generally motivated by cost or safety concerns, there is a paucity of information on off-label use of inexpensive drugs. • Unapproved, off-label use of drugs is not identified in managed care plans in the absence of a prior authorization (PA) requirement.

PubMed, Aug 1, 2013

Background: After a new formulation of levothyroxine was distributed in Israel, side effects were... more Background: After a new formulation of levothyroxine was distributed in Israel, side effects were reported to the Ministry of Health generating extensive media coverage. The purpose of this study was to determine whether the new formulation was associated with a change in thyroid-stimulating hormone (TSH) levels of treated patients and to evaluate the effect of the extensive media coverage on the incidence of laboratory test performance. Study design: Retrospective-cohort and crosssectional analysis. Methods: All patients from the Leumit Health Services of Israel treated with levothyroxine between October 2009 and February 2012 were included in the study. A retrospective cohort was constructed of patients treated and maintained within the desired target range (0.35-5 mIU/L) from January to July 2010. A longitudinal analysis was conducted to calculate the monthly distribution of TSH levels from laboratory tests during routine care over 26 months. Data were stratified by cohort and noncohort patients. Results: Data were captured for 18,106 levothyroxine-treated patients; 1140 were included into the retrospective cohort. In both subpopulations a sharp rise in the number of tests performed monthly is observed at the peak of media coverage during October and November 2011. In the retrospective cohort the proportion of TSH results within target range fell to a low of 67.5% during December 2011, with 25.3% between 5.01 and 20 mIU/L. Results>20 mIU/L then peaked at 3.8% indicating an increase in patients who stopped taking levothyroxine. Conclusions: These results demonstrate the power of mass media to influence patient behavior and to foment a public health scare.

Allergy and Asthma Proceedings, Jul 1, 2019

Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly und... more Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly understood. Objective: To identify clinical and laboratory attributes of patients that may be predictive of OmR in CSU. Methods: We conducted a retrospective observational study by using an electronic patient record data base of patients with severe CSU refractory to a fourfold H 1-antihistamine dose, treated with omalizumab 300 mg every 4 weeks for at least 24 weeks. Complete response (CR) was defined as the reduction of baseline urticaria activity score by Ն 90%, partial response (PR) by Ն 30% to Ͻ90%, and OmR by Ͻ30% at 24 weeks. The patient characteristics of the CR, PR, and OmR groups were compared. Results: Sixty-three patients (58.9%) had a complete remission at 24 weeks of omalizumab therapy, and 16 patients (14.9%) had OmR. The patients who were OmR were characterized by a higher rate of arterial hypertension 7 (43.8%), higher mean Ϯ standard deviation (SD) high-sensitivity C-reactive protein (hs-CRP) level (10.3 Ϯ 8.2 mg/L), mean Ϯ SD white blood cell (WBC) count (9.1 Ϯ 2.8 ϫ 10 3 cells/mL), and higher mean Ϯ SD C3 level (164.3 Ϯ 45.4 mg/dL) at baseline than the patients

British Journal of Clinical Pharmacology, Nov 9, 2011

, the month before the policy change, to 494 the following January, rising again to 651 during Ja... more , 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 limitedduration strategy for reduction of prescription of relatively expensive drugs.

Allergy and Asthma Proceedings, 2021

Background: Biomarkers of resistance to H1-antihistamines (AH) and omalizumab in chronic spontane... more Background: Biomarkers of resistance to H1-antihistamines (AH) and omalizumab in chronic spontaneous urticaria (CSU) are still a matter of debate. Objective: To identify clinical and laboratory attributes of the patient that may be predictive of AH and omalizumab resistance in CSU. Methods: We conducted a retrospective observational study by using the electronic patient record data base of patients with CSU and of sex- and age-matched controls. Patients with CSU were divided into three study groups: the CSU group, patients who responded to AHs; the antihistamine-resistant CSU (AH-CSU) group, patients refractory to a fourfold AH dose; and the control group, composed of a random sample of age- and sex-matched subjects, with a case-control ratio of 1:2. The patients in the AH-CSU group treated with omalizumab were compared according to the response or resistance to omalizumab. Results: A total of 106 subjects in the AH-CSU group, 483 in the CSU group, and 1198 in the control group were compared. Both AH-CSU (112.7 ± 43.1 kU/mL) and CSU (129.5 ± 52.4 kU/mL) groups were associated with higher plasma total IgE levels than control group (103.2 ± 49.5 kU/mL; p &lt; 0.001). The AH-CSU group was characterized by a higher plasma high-sensitivity C-reactive protein level (6.4 ± 3.7 mg/L) than the CSU group (4.3 ± 1.4 mg/L; p &lt; 0.001) and the control group (3.1 ± 1.8 mg/L; p &lt; 0.001). The AH-CSU and CSU groups were characterized by a lower mean ± standard deviation basophil counts (0.18 ± 0.16 cells ×109/L and 0.19 ± 0.11 cells ×109/L, respectively) than the control group (0.22 ± 0.09 cells ×109/L; p &lt; 0.001). The mean platelet volume was higher in the AH-CSU group (11.2 ± 0.3 fL) than in the CSU group (11.1 ± 0.4 fL; p = 0.002) and in the control group (10.3 ± 0.4 fL; p &lt; 0.001). There were no significant differences in the mean levels of lymphocytes, monocytes, eosinophils, basophils, and platelets, and the rates of eosinopenia and basopenia between the patients in the AH-CSU group who responded to and those who were resistant to omalizumab. Conclusion: This study provided additional data of interest to examine the pathophysiologic role of low-grade inflammation and basopenia in patients with CSU and resistant to AHs and omalizumab.

The American Journal of Managed Care, Feb 1, 2005

Allergy and asthma proceedings, 2017

There are no published large-scale epidemiologic studies regarding the prevalence of skin disease... more 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. 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...

American Journal of Managed Care, 2005

To identify cases of inappropriate physician prescribing in a managed care setting in Israel that... more To identify cases of inappropriate physician prescribing in a managed care setting in Israel that may have resulted from misuse of magnetic-stripe membership cards. Retrospective drug utilization analysis of electronic patient prescription data. In a managed care setting involving approximately 1000 physicians who issue approximately 1.4 million prescriptions annually, the rate of prescription of sex-specific drugs to patients of the opposite sex for which the drugs are indicated was evaluated for 2003. The categories of drugs included in the analysis were drugs for the treatment of benign prostatic hyperplasia or erectile dysfunction that were prescribed to women, as well as oral contraceptives, vaginal pessaries, hormone therapy, or raloxifene hydrochloride prescribed to men. Throughout the study year, 193 different physicians wrote 341 prescriptions that matched the drug inclusion criteria for 210 different patients. The most frequently observed scenario involved the prescription...

Allergy and Asthma Proceedings, 2021

Background: Biomarkers of resistance to H1-antihistamines (AH) and omalizumab in chronic spontane... more Background: Biomarkers of resistance to H1-antihistamines (AH) and omalizumab in chronic spontaneous urticaria (CSU) are still a matter of debate. Objective: To identify clinical and laboratory attributes of the patient that may be predictive of AH and omalizumab resistance in CSU. Methods: We conducted a retrospective observational study by using the electronic patient record data base of patients with CSU and of sex- and age-matched controls. Patients with CSU were divided into three study groups: the CSU group, patients who responded to AHs; the antihistamine-resistant CSU (AH-CSU) group, patients refractory to a fourfold AH dose; and the control group, composed of a random sample of age- and sex-matched subjects, with a case-control ratio of 1:2. The patients in the AH-CSU group treated with omalizumab were compared according to the response or resistance to omalizumab. Results: A total of 106 subjects in the AH-CSU group, 483 in the CSU group, and 1198 in the control group were...

Allergy and Asthma Proceedings, 2019

Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly und... more Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly understood. Objective: To identify clinical and laboratory attributes of patients that may be predictive of OmR in CSU. Methods: We conducted a retrospective observational study by using an electronic patient record data base of patients with severe CSU refractory to a fourfold H1-antihistamine dose, treated with omalizumab 300 mg every 4 weeks for at least 24 weeks. Complete response (CR) was defined as the reduction of baseline urticaria activity score by ≥ 90%, partial response (PR) by ≥ 30% to <90%, and OmR by <30% at 24 weeks. The patient characteristics of the CR, PR, and OmR groups were compared. Results: Sixty-three patients (58.9%) had a complete remission at 24 weeks of omalizumab therapy, and 16 patients (14.9%) had OmR. The patients who were OmR were characterized by a higher rate of arterial hypertension 7 (43.8%), higher mean ± standard deviation (SD) high-sensitivity C-reactive protein (hs-CRP) level (10.3 ± 8.2 mg/L), mean ± SD white blood cell (WBC) count (9.1 ± 2.8 × 10³ cells/mL), and higher mean ± SD C3 level (164.3 ± 45.4 mg/dL) at baseline than the patients with CR (arterial hypertension, 9 [13.1%], p = 0.009; mean ± SD hs-CRP, 3.4 ± 10.1, p = 0.014; mean ± SD WBC count, 6.5 ± 3.8 × 10³ cells/mL, p = 0.012; and mean ± SD C3 level, 121.8 ± 42.1 m/dL, p < 0.001). In multivariable analysis adjusted for age, sex, and body mass index, OmR was associated with an hs-CRP level of >3.0 mg/L (odds ratio 1.94 [95% confidence interval, 1.28-3.15], p = 0.009) and with C3 > 160 mg/dL (odds ratio 1.54 [95% confidence interval, 1.05-2.36], p = .017). Conclusion: Obesity, arterial hypertension, high plasma C3 level, and high-CRP level were associated with OmR in severe CSU.

British Journal of Medicine and Medical Research, 2013

Aims: In a previous study (2004) we explored the clinical and microbiological aspects of bloodstr... more Aims: In a previous study (2004) we explored the clinical and microbiological aspects of bloodstream infections (BSI) in a multilevel geriatric hospital, and concluded that follow up and monitoring of these parameters is warranted. The purpose of this new study is to evaluate the current BSI status and compare these data to those obtained previously. Study Design and Methodology: We implemented the methodology developed for the initial study. Clinical features, microbiological characteristics and outcome of BSI over the year 2009 were investigated. Results: The rate of positive blood cultures was similar (10% versus 12%). The rate of BSI was 1.35 per 1000 patients in 2004 and 1.7 per 1000 in 2009. The mortality rate at 2 weeks decreased significantly (from 42% to 22.5%, p=.001). The most common isolate was Escherichia coli in both studies, followed by Proteus mirabilis. Interestingly, antibiotic susceptibility of common pathogens between 2004 and 2009 remained unchanged in 40% while increasing in 32% of cases.

Allergy and Asthma Proceedings, 2015

Despite the established association between chronic idiopathic/spontaneous urticaria (CIU) and pr... more 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 Sjögren&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome (SS)-A 52 antibodies (Ab) (7.7% versus 2.4%; p = 0.008), SS-A 60 Ab (11% versus 2.8%; p = &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and SS-B Ab (14.3% versus 3.2%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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.

Value in Health, 2009

To review the PRO end-points appearing in the product labels of pain treatments with a particular... more To review the PRO end-points appearing in the product labels of pain treatments with a particular focus on products approved both in the United States (US) and in Europe. METHODS: Pain treatments approved in the US since 1998 and in Europe through the centralized procedure established in 1995, and including PRO evaluations in the approved labeling were identifi ed from the PROLabels database. PROLabels is a unique on-line tool providing information on the products for which the FDA and/or the EMEA have granted PRO labeling claims. For the products approved by both agencies, we will compare the PRO endpoints appearing in the approved labeling and also analyze the PRO studies submitted by the sponsor. RESULTS: Overall, 26 products indicated for the treatment of pain were identifi ed, accounting for 16 different molecules and ten different indications. Various methods were used to measure pain (VAS, Likert scales). Of these 26 drugs, only two showed evidence of treatment effi cacy using additional PRO endpoints (function and patient satisfaction). The PRO appearing in the approved labeling are rather consistent between both regulatory agencies. Information on additional PRO endpoints that were assessed in the clinical studies submitted by the sponsors but were not accepted in the approved labeling was available for nine out of the 26 dossiers. The concepts assessed were health-related quality of life, psychological functioning, physical functioning (including interference with sleep) and patient global impression. A focus was made on the different reasons of rejection of the most recent claims, in the light of the current PRO guidances published by both regulatory agencies. CONCLUSIONS: Overall, only a few pain treatments include other PRO endpoints in addition to pain in their labeling. An interesting fi nding is the similarity between the American and the European PRO claims for pain therapies.

American health & drug benefits, 2016

BACKGROUND Prior authorization (PA) is a management technique that has been implemented to manage... more BACKGROUND Prior authorization (PA) is a management technique that has been implemented to manage the utilization of expensive drugs and to improve the precision of drug prescribing. PA requirements may incentivize physicians to document adverse effects, sometimes falsely, to meet the eligibility requirements. OBJECTIVES To identify documentation patterns that may facilitate the quantitative analysis of physician gaming and underreporting behaviors associated with the prescribing of angiotensin-converting enzyme (ACE) inhibitors in a primary care setting, and to evaluate the effect of a PA requirement on the documentation of adverse events as a way to receive approval for more expensive drugs. METHODS We conducted a retrospective analysis of physician electronic reporting of adverse effects associated with ACE inhibitors before and after the revocation of a PA requirement for angiotensin receptor blockers (ARBs) between 2004 and 2013 in an Israeli HMO. The data were stratified into ...

The American journal of managed care, 2013

BACKGROUND After a new formulation of levothyroxine was distributed in Israel, side effects were ... more BACKGROUND After a new formulation of levothyroxine was distributed in Israel, side effects were reported to the Ministry of Health generating extensive media coverage. The purpose of this study was to determine whether the new formulation was associated with a change in thyroid-stimulating hormone (TSH) levels of treated patients and to evaluate the effect of the extensive media coverage on the incidence of laboratory test performance. STUDY DESIGN Retrospective-cohort and crosssectional analysis. METHODS All patients from the Leumit Health Services of Israel treated with levothyroxine between October 2009 and February 2012 were included in the study. A retrospective cohort was constructed of patients treated and maintained within the desired target range (0.35-5 mIU/L) from January to July 2010. A longitudinal analysis was conducted to calculate the monthly distribution of TSH levels from laboratory tests during routine care over 26 months. Data were stratified by cohort and nonco...

En la comunidad biomedica se acepta actualmente que las presentaciones sean precedidas por una de... more En la comunidad biomedica se acepta actualmente que las presentaciones sean precedidas por una declaracion en la que los investigadores senalan no tener conflictos de intereses que declarar. En concordancia con esta practica, yo por la presente declaro, segun mi leal saber y entender que yo no tengo lazos con la familia del Dr. Ernesto Kahan. Yo encuentro muy apropiado introducir este articulo editorial con esta declaracion, dado que exactamente con esas palabras (aunque en hebreo) inicie mi carrera como investigador cuando someti esa declaracion a la Autoridad de Investigacion de la Universidad Hebrea de Jerusalen para recibir la aprobacion de tener al Dr. Kahan como uno de mis tutores de doctorado (PhD).

Audiology and Neurotology

Objectives: Autoimmune inner ear disease (AIED) is a distinct clinical entity from sudden sensori... more Objectives: Autoimmune inner ear disease (AIED) is a distinct clinical entity from sudden sensorineural hearing loss. The purpose of this study was to investigate the clinical characteristics of AIED in patients with selective IgA deficiency (sIgAD). Materials and Methods: This retrospective observational study was based on data from the Leumit Healthcare Services database in Israel. We searched all subjects aged ≥12 years who had undergone serum total IgA measurements during 2004–2014 for any reason. The sIgAD patients included all subjects with serum IgA of ≤7 mg/dL (0.07 g/L). A control group was randomly sampled from the full study population (n ≈ 730,000) with a case-control ratio of 10 controls for each case (1:10). Results: Among 347 subjects with sIgAD, we identified 9 patients with concomitant AIED (sIgAD + AIED group). This group was characterized by a higher prevalence of allergic diseases (8 patients; 88.9%) than sIgAD patients without AEID (sIgAD + AIED group; 153 patie...

Clinical and experimental immunology, Jan 8, 2016

Selective IgA deficiency (IgAD) is the most common primary immunodeficiency in the Western world.... more Selective IgA deficiency (IgAD) is the most common primary immunodeficiency in the Western world. The aim of the study was to investigate the prevalence and clinical characteristics of Helicobacter pylori (H. pylori) infected dyspeptic patients with IgAD. Case samples were drawn from all subjects ≥ 12 years of age (n = 104729), who that had undergone serum total IgA measurements during 2004 - 2014 years for any reason at Leumit Healthcare Services (Israel) and had serum total IgA <0.07 g/L. The control group was comprised of a random sample of remaining patients with a case-control ratio ten controls for each case. The dyspeptic diseases were identified and retrieved from Leumit Health Care Services electronic database using specific ICD-9-CM diagnostic codes. Case group included 347 subjects and Control group 3470 subjects. There were no significant difference in the prevalence of patients with dyspepsia (84 (24.2%) vs 821 (23.6%) for cases and controls, respectively). Additiona...

BACKGROUND Ethnicity has been associated with variance in warfarin treatment regimens in various ... more BACKGROUND Ethnicity has been associated with variance in warfarin treatment regimens in various settings. OBJECTIVES To determine whether ethnicity is associated with variance in patient management in Israel. METHODS Data were extracted from the electronic patient records of Clalit Health Services clinics in the Sharon Shomron region. The study group comprised all patients treated with warfarin who performed international normalized ratio tests for at least 6 months in 2003. The proportion of tests of each patient within the target range was calculated, as was the crude average rates and 95% confidence intervals for Jewish and Arab patients. The data were then stratified by patient's gender and age, specialty of the attending physician, and the country where the physician studied medicine. RESULTS We identified 2749 Jews and 293 Arabs who met the inclusion criteria of the study. The crude average rate of patients' INR tests within the target range was 62.3% among Jews (95% ...

Allergy and asthma proceedings, 2018

Epidemiologic studies report that alopecia areata (AA) is related to various atopic and autoimmun... more 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. 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. 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 o...