[THE INFLUENCE OF NASOTRACHEAL INTUBATION ON NASAL RESISTANCE].

INTRODUCTION: Tracheal intubation is a vital and common procedure during surgical care. The tracheal tube may be inserted orally or trans-nasally. Nasal intubation enables a non-restricted approach for oral and oropharyngeal regions. Thus, nasotracheal intubation is more suitable for surgeries such as uvulopalatopharyngoplasty treating obstructive sleep apnea. Obstructive sleep apnea is an independent risk factor for postoperative cardiorespiratory complications. Thus, meticulous treatment during and post-operatively is needed keeping the upper airway open including the nasal cavity. In several studies, nasotracheal intubation resulted in disruption of the nasal mucosa. OBJECTIVES: The objective of this study is evaluating the developing nasal resistance post nasotracheal intubation and comparing it to nasal resistance post-orotracheal intubation. To our knowledge, this is the first data on nasal obstruction following nasal intubation. METHODS: Forty-four candidates, for elective non-head and neck procedures were randomized into two groups: oral intubation group and nasal intubation group. The nasal resistance of all participants was measured by anterior rhinomanometry upon the recommendation of the standardization committee on objective assessment of the nasal airway. Statistical analysis with paired T test, Chi square and McNemar's test was performed. Statistical significance was evaluated at P≤0.05. RESULTS: There were no differences between the study groups regarding nasal resistance before and after intubation. However, nasotracheal intubation was found to disrupt the normal nasal cycle of the nasal mucosa. CONCLUSIONS: Nasotracheal intubation does not negatively affect nasal resistance in the early postoperative period. DISCUSSION: Nasotracheal intubation does not affect nasal resistance and it seems to be safe for OSA patients. More research has to be conducted to evaluate the nasal resistance in patients who undergo oral and nasal surgeries.

The 'real-life' impact of adding bevacizumab to first-line therapy in metastatic colorectal cancer patients: a large Israeli retrospective cohort study.

BACKGROUND: After a decade of extensive use, the actual contribution of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC) is still unclear. OBJECTIVE: To evaluate 'real-life' outcomes of patients with mCRC before and after the introduction of bevacizumab to standard mCRC first-line practice. METHODS: Using the computerized administrative database of Clalit Health Services' (CHS), Israel's largest health care provider, we retrospectively compared two cohorts (n = 1739): (A) all CHS' patients diagnosed with mCRC between January 2000 and December 2004 that received first-line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced) (n = 1052), and (B) all patients that started first-line irinotecan or oxaliplatin combination chemotherapy together with bevacizumab between September 2006 and December 2009 (after bevacizumab was fully reimbursed in Israel for mCRC first-line therapy) (n = 687). The primary endpoint was overall survival (OS) and secondary endpoints were first-line progression-free survival (PFS) and metastatectomy rates. RESULTS: Median OS was longer in Cohort B than in Cohort A [23.0 months vs.15.0, adjusted hazard ratio (HR), 0.75]. Secondary outcomes were also better; PFS of 14.0 months vs. 9.8 in the earlier period (HR, 0.75) and metastatectomy rate of 8.1% versus 3.9%. The longer OS in Cohort B was preserved even after controlling for latter-line epidermal growth factor receptor (EGFR) inhibitor use (HR = 0.77). CONCLUSION: In this analysis, OS, PFS and metastatectomy rates of first-line treatment of mCRC were significantly higher in the later period of the study. These results, derived from 'real-life' practice, suggest that the use of bevacizumab, among other alterations in the clinical management of mCRC between the two periods, might have had a significant contribution to these outcomes, and may therefore support the current practice of adding bevacizumab to first-line treatment of mCRC.

Factors associated with drug survival of methotrexate and acitretin in patients with psoriasis.

Drug survival has recently become an important clinical issue in psoriasis. However, there has been little research into factors associated with drug survival of methotrexate and acitretin. The aim of this study was to investigate factors associated with drug survival of methotrexate and acitretin treatment for psoriasis. Survival analysis was performed in patients who received methotrexate or acitretin for the treatment of psoriasis, drawn from the Clalit Health Services database. Investigated factors included demographic variables, obesity, metabolic syndrome, psoriatic arthritis, administration route and folic acid supplementation. Among 6,256 patients, factors associated with treatment drop-out were: younger age (p <0.001) and psoriatic arthritis (acitretin p < 0.001). For methotrexate, metabolic syndrome (p = 0.033), intramuscular administration route of injection (p <0.001) and lack of folic acid supplementation (p <0.001) were associated with treatment drop-out. In patients with psoriasis, some ancillary factors may modify the drug survival of acitretin and methotrexate.

Increased prevalence of obstructive lung disease in patients with obstructive sleep apnea.

STUDY PURPOSES: This study aims to determine whether there is an increased prevalence of obstructive lung diseases (OLDs) in patients with obstructive sleep apnea (OSA). We also determined whether among the OLD patients there is a difference in the prevalences of specific chronic disease co-morbidities between patients with and without OSA. METHODS: The prevalences of COPD, asthma, and COPD combined with asthma (ICD-9 coding) were compared between 1,497 adult OSA patients and 1,489 control patients, who were matched for age, gender, geographic location, and primary care physician. The prevalences of specific co-morbidities were measured in the OLD groups between patients with OSA and the matched control group. RESULTS: COPD, asthma, and COPD combined with asthma were found to be more prevalent among OSA patients compared to the matched controls. Prevalences among patients with and without OSA, respectively, were COPD-7.6 and 3.7 % (P<0.0001), asthma-10.4 and 5.1 % (P<0.0001), COPD plus asthma-3.3 and 0.9 % (P<0.0001). The Charlson Comorbidity Index was greater for OSA patients (2.3 ± 0.2) than for controls (1.9 ± 1.8; P<0.0001). These trends held for all severity ranges of OSA. Patients with OSA and COPD were characterized by more severe hypoxia at night compared with the OSA patients without OLD. CONCLUSION: OSA was associated with an increased prevalence of OLDs.

Inflammation and growth in young children with obstructive sleep apnea syndrome before and after adenotonsillectomy.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with growth impairment that usually improves following effective treatment. In this study we investigated the mechanisms underlying the growth processes in young children diagnosed with OSA, before and after adenotonsillectomy (T&A). METHODS: Young children (6-36 months old) were enrolled and evaluated before and several months after T&A surgery for height, weight, circulating high sensitive C-reactive protein (CRP), and insulin-like growth factor 1 (IGF-1) levels. Caloric intake was assessed by a validated Short Food Frequency Questionnaire (SFFQ). RESULTS: Following T&A, children added 4.81 cm and 1.88 kg to their height and weight, respectively (P < 0.001 for both) and had a significant increase in BMI Z score (P = 0.002). Increased caloric intake of 377 kcal/day was noted (P < 0.001), with increased protein and decreased fat intake. The decrease in CRP levels correlated with the increase in body weight in boys (P < 0.05, adjusted for caloric intake). CONCLUSIONS: Adenotonsillectomy results in enhanced somatic growth in young children that correlates with a decrease in systemic inflammation and caloric intake increment. Our findings imply that systemic inflammation may have an important role in this OSA-related morbidity.

Increased Prevalence of Systemic Lupus Erythematosus Comorbidity in Patients With Psoriatic Arthritis: A Population-based Case-control Study.

OBJECTIVE: To assess the prevalence of systemic lupus erythematosus (SLE) in a psoriatic arthritis (PsA) cohort and to compare it to the general population using the database of a large healthcare provider. METHODS: We analyzed the database of a PsA cohort (2002-2017), matched for age and sex, with randomly selected controls for demographics, clinical and laboratory manifestations, and dispensed medications. Statistical analysis used t test and chi-square test as appropriate. In the PsA group, incidence density sampling was performed matching PsA patients without SLE as controls to each case of PsA with SLE by age and follow-up time. Univariable and multivariable conditional logistic regression analyses were used to assess factors affecting SLE development. RESULTS: The PsA and control groups consisted of 4836 and 24,180 subjects, respectively, with a median age of 56 ± 15 years, and of whom 53.8% were female. Eighteen patients (0.37%) in the PsA group and 36 patients (0.15%) in the control group were diagnosed with SLE (P = 0.001). SLE patients without PsA had higher anti-dsDNA and anticardiolipin antibodies. The usage of drugs with known potential to induce SLE was higher in the PsA than in the control group. Older age at PsA diagnosis, shorter PsA duration, and statin treatment were associated with SLE in PsA patients. CONCLUSION: A 2.3-fold increase in the prevalence of SLE in PsA relative to the control group was found. Risk factors for SLE development included older age at PsA diagnosis, shorter PsA duration, and statin treatment. The association between PsA and SLE may affect treatment choices and medication development.

Low socioeconomic status is a risk factor for CPAP acceptance among adult OSAS patients requiring treatment.

STUDY OBJECTIVE: To evaluate whether socioeconomic status (SES) has a role in obstructive sleep apnea syndrome (OSAS) patients' decision to accept continuous positive airway pressure (CPAP) treatment. DESIGN: Cross-sectional study; patients were recruited between March 2007 and December 2007. SETTING: University-affiliated sleep laboratory. PATIENTS: 162 consecutive newly diagnosed (polysomnographically) adult OSAS patients who required CPAP underwent attendant titration and a 2-week adaptation period. RESULTS: 40% (n = 65) of patients who required CPAP therapy accepted this treatment. Patients accepting CPAP were older, had higher apnea-hypopnea index (AHI) and higher income level, and were more likely to sleep in a separate room than patients declining CPAP treatment. More patients who accepted treatment also reported receiving positive information about CPAP treatment from family or friends. Multiple logistic regression (after adjusting for age, body mass index, Epworth Sleepiness Scale, and AHI) revealed that CPAP purchase is determined by: each increased income level category (OR, 95% CI) (2.4; 1.2-4.6), age + 1 year (1.07; 1.01-1.1), AHI ( > or = 35 vs. < 35 events/hr) (4.2, 1.4-12.0), family and/or friends with positive experience of CPAP (2.9, 1.1-7.5), and partner sleeps separately (4.3, 1.4-13.3). CONCLUSIONS: In addition to the already known determinants of CPAP acceptance, patients with low SES are less receptive to CPAP treatment than groups with higher SES. CPAP support and patient education programs should be better tailored for low SES people in order to increase patient treatment initiation and adherence.

[The significance of body posture on breathing abnormalities during sleep: data analysis of 2077 obstructive sleep apnea patients].

The aim of this study was to evaluate demographic and polysomnographic characteristics of positional (PPJ) and non-positional obstructive (NPP) sleep apnea (OSA) patients in 2077 OSA patients diagnosed in our Sleep Disorders Unit during a period of 10 years. An OSA patient is defined as positional if he has twice as many or more breathing abnormalities (apnea and hypopneas) while he sleeps in his supine posture compared to the lateral ones. Of the 2077 OSA patients, 1118 (53.8%) were positional and 959 (46.2%) were non-positional. No age differences were found between these two groups of patients. However, NPP were heavier and thus had a higher BMI than PP. PP had fewer and Less severe breathing abnormalities during sleep compared to NPP and thus, they enjoyed better sleep quality expressed by higher percentages of stage 2, 4 and 3+4 as well as a lower amount of short arousals than NPP. Also, PP patients are less sleepy during daytime hours than NPP. During the Multiple Sleep Latency Test (MSLT), NPP fall asleep faster in every nap than PP patients. No differences between these two patient groups were found for any parameter of Periodic Limb Movement Disorders. AHI and BMI are independently but inversely related to positional dependency. As AHI and BMI increase, the Likelihood to be a positional patient decreases. NPP have breathing abnormalities in the supine and lateral postures, thus, for them without question, CPAP is the treatment of choice. Since avoiding the supine posture during sleep may significantly improve the sleep quality and daytime alertness of many positional patients, it is imperative to carry out a high-quality study to evaluate if this is a real therapeutic alternative for many positional patients.

Cardiac and cardiovascular morbidities in patients with psoriatic arthritis: a population-based case control study.

OBJECTIVE: To assess the prevalence of risk factors associated with cardiovascular disease (CVD) and CVD-related morbidity in a large Middle-Eastern psoriatic arthritis (PsA) cohort. METHOD: A retrospective case control study was conducted using Israel's largest health care provider's patient database from 2000 to 2013. For each patient with PsA, 10 patients with no history of psoriasis or arthritis were matched for age and sex. Analysis of CVD-related risk factors and morbidity included hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus type 2 (DM-2), obesity, smoking, ischemic heart disease (IHD), congestive heart failure (CHF), cerebrovascular accident (CVA), carotid artery disease, peripheral vascular disease (PVD), aortic aneurism, valvular heart disease (VHD), and cardiomyopathy. Statistical analysis was conducted using t test and chi-square tests as appropriate. Univariate and multivariable logistic regression models assessed the association between PsA and CVD-related risk factors and morbidity. RESULTS: Three thousand one hundred sixty-one PsA patients were included, with average age 58 ± 15.0 years, of whom 53.4% were women. Increased prevalence of DM-2, HLD, HTN, and obesity (OR 1.7, 1.5, 1.5, 1.5 respectively) was noted in the PsA group. Increased prevalence of IHD (p < 0.0001), PVD (p < 0.0001), CHF (p = 0.002), VHD (p < 0.0001), and cardiomyopathy (p = 0.006) was found in the PsA group compared to the control group even after adjusting for CVD risk factors. CONCLUSIONS: A high prevalence of CVD-related risk factors and morbidity was found in this Middle Eastern PsA population, in accordance with data from other geographic regions. These results emphasize the importance of clinician awareness of the increased risk for CVD-related complications in PsA patients.

Effectiveness and Safety of Off-Label Dose-Reduced Direct Oral Anticoagulants in Atrial Fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation but may result in serious bleeding complications. Off-label dose-reduced use of DOACs to mitigate bleeding is common in routine clinical practice although data about its consequences on patient outcomes are limited. Therefore, our objective was to evaluate the effectiveness and safety of off-label dose-reduced vs per-label standard-dose DOAC treatment. METHODS: The study cohort included newly diagnosed patients with nonvalvular atrial fibrillation that had initiated DOAC therapy between 2011 and 2017 in Clalit Health Services (Tel Aviv, Israel). Effectiveness was defined as the composite outcome of all-cause mortality, stroke, or myocardial infarction. The safety outcome was defined as bleeding events requiring hospitalization. Patients were followed until March 30, 2018 or until occurrence of an outcome event. Hazard ratios (HR) were adjusted for 21 variables, including comorbidities, concomitant medications, and socioeconomic factors, using multivariate regression. RESULTS: A total of 8425 patients met the study criteria; 5140 (61%) patients were treated with DOACs at per-label dosing and 3285 (39%) patients were treated with off-label dose-reduced DOAC. Off-label dose-reduced treatment was associated with a higher rate of the composite effectiveness outcome: adjusted HR 1.57 (95% confidence interval, 1.34-1.83; P < .001) and a higher rate of bleeding: adjusted HR 1.63 (95% confidence interval, 1.14-2.34; P = .008). CONCLUSIONS: Almost 4 of 10 patients were treated with off-label dose-reduced DOAC, which was associated with reduced effectiveness without a safety benefit. Compliance with per-label dosage may significantly improve outcomes of this population.

The ESMO-Magnitude of Clinical Benefit Scale for novel oncology drugs: correspondence with three years of reimbursement decisions in Israel.

BACKGROUND: The European Society for Medical Oncology published in 2015 its Magnitude of Clinical Benefit Scale (ESMO-MCBS) for cancer medicines. Our objective was to evaluate the association between Israel's national reimbursement decisions regarding novel cancer drugs, prior to the availability of ESMO-MCBS, and the later published ESMO-MCBS scores. RESEARCH DESIGN AND METHODS: ESMO-MCBS scores were obtained retrospectively for the cancer drugs that were candidates for reimbursement in Israel in 2013-2015 and were categorized to 'highest benefit' (ESMO-MCBS 4-5 or A) 'medium benefit' (3 or B) and 'lowest benefit' (0-2 or C). The reimbursement decisions were accessed and compared with the categorized ESMO scores. RESULTS: ESMO-MCBS score was available for 19/22 drugs approved for reimbursement and 15/16 non-approved drugs. 58% of the approved drugs gained a 'highest benefit' score and 37% were 'medium benefit'. 87% of the non-approved drugs had 'lowest benefit' scores. Median score for approved drugs was 4 vs. 1 for the non-approved (p < 0.05). CONCLUSIONS: The Israeli decisions regarding reimbursement of novel cancer drugs, demonstrated concordance with ESMO-MCBS scores. Incorporation of ESMO-MCBS data in reimbursement deliberations could assist in framing the appropriate use of the limited resources to deliver effective and affordable cancer care.

The epidemiology of psoriatic arthritis in Israel - a population-based study.

BACKGROUND: There is limited information on the epidemiology of psoriatic arthritis (PsA) in general and in Middle Eastern populations in particular. The aims of this study were to estimate the prevalence and incidence rates of PsA and their temporal trends in the general population in Israel. METHODS: In this study, a cohort of adult patients with PsA was derived from the database of Clalit Health Services (CHS), Israel's largest health fund, with over 4.4 million members. The crude and age- and sex-standardized prevalence and incidence rates of PsA from 2006 to 2015 in the general population were calculated. The variation in PsA prevalence was assessed in relation to several demographic factors. RESULTS: Among the 2,931,199 individuals aged 18 years and older registered in the CHS database in 2015, 4490 patients had a diagnosis of PsA (322 incident cases), resulting in overall crude prevalence and incidence rates of 0.153% (95% CI 0.149%, 0.158%) and 10.9 (95% CI 9.8, 12.3) per 100,000 population, respectively. The reported prevalence of PsA in Israel has doubled between 2006 and 2015 (from 0.073% to 0.153%). In contrast, the global incidence rate remained stable, with a gradual increase in incidence among individuals aged 51 to 70 years. PsA is associated with Jewish ethnicity, high socioeconomic status, and higher body mass index. CONCLUSIONS: The prevalence and incidence of PsA in Israel are within the range of previous estimates from Southern European populations. An increase in the reported prevalence of PsA was observed over the past decade in the general population in Israel.

Gender differences in morbidity and health care utilization among adult obstructive sleep apnea patients.

STUDY OBJECTIVE: To explore gender differences in morbidity and total health care utilization 5 years prior to diagnosis of obstructive sleep apnea (OSA). DESIGN: Case-control study; patients were recruited between January 2001 and April 2003. SETTING: Two university-affiliated sleep laboratories. PATIENTS: 289 women (22-81 years) with OSA were matched with 289 men with OSA for age, body mass index (BMI), and apnea-hypopnea index (AHI). All OSA patients were matched 1:1 with healthy controls by age, geographic area, and primary physician. MEASUREMENTS AND RESULTS: Women with OSA compared to men with OSA have lower perceived health status and Functional Outcomes of Sleep Questionnaire score (54.5% vs. 28.4%, P <0.05 and 67.5+/-21.4 vs. 76+/-20.1, P <0.05, respectively). Compared to men with OSA, women with OSA have higher risk of hypothyroidism (OR 4.7; 95% CI, 2.3-10) and arthropathy (OR 1.6, 95% CI, 1.1-2.2) and lower risk for CVD (OR 0.7; 95% CI, 0.5-0.91). Compared to controls, both women and men with OSA had 1.8 times higher 5-year total costs (P <0.0001). Compared to men with OSA, expenditures for women with OSA are 1.3 times higher (P <0.0001). The multiple logistic regression (adjusting for BMI, AHI) revealed that age (OR 1.04; 95% CI, 1.01-1.07), antipsychotic and anxiolytic drugs (OR 2.3; 95% CI, 1.2-4.4), and asthma (OR 2.4; 95% CI, 1.1-5.6) are independent determinants for "most costly" OSA women. CONCLUSION: Compared to men with similar OSA severity, women are heavier users of health care resources. Low FOSQ score and poor perceived health status in addition to overuse of psychoactive drugs are associated with high health care utilization among women with OSA.

Endocrine Comorbidities in Patients with Psoriatic Arthritis: A Population-based Case-controlled Study.

OBJECTIVE: To investigate endocrine comorbidities in patients with psoriatic arthritis (PsA). METHODS: A retrospective, cross-sectional study was performed with the database of Clalit Health Services, the largest healthcare provider in Israel, between 2002 and 2014. Patients with PsA were identified and matched by age and sex to healthy controls. The following morbidities were analyzed: hypo/hyperthyroidism, hypo/hyperparathyroidism, hyperprolactinemia, Cushing disease, Addison disease, diabetes insipidus, diabetes mellitus (DM), pituitary adenoma, acromegaly, and osteoporosis. Descriptive statistics were applied. The associations between PsA and endocrine comorbidities were analyzed by univariable and multivariable analysis. RESULTS: The study included 3161 patients with PsA, 53.4% women, mean age 58.4 ± 15.4 years, and 31,610 controls. Comparative analyses yielded higher proportion of hypothyroidism (12.7% vs 8.6%, p < 0.0001), Cushing disease (0.3% vs 0.1%, p < 0.0001), osteoporosis (13.2% vs 9.1%, p < 0.0001), and DM (27.9% vs 20.7%, p < 0.0001) in the PsA group compared with the control group. In the multivariable regression analysis, the following diseases were more frequent in the PsA group: hypothyroidism (OR 1.61, 95% CI 1.47-1.81), DM (OR 1.35, 95% CI 1.18-1.42), Cushing disease (OR 3.96, 95% CI 1.67-9.43), and osteoporosis (OR 1.56, 95% CI 1.37-1.78). CONCLUSION: PsA is associated with a high frequency of hypothyroidism, osteoporosis, DM, and Cushing disease. Awareness of these comorbidities may help physicians provide the optimal medical care to patients with PsA.

Low socioeconomic status is a risk factor for cardiovascular disease among adult obstructive sleep apnea syndrome patients requiring treatment.

STUDY OBJECTIVE: To evaluate the possible role of low socioeconomic status (SES) as a risk factor for cardiovascular disease (CVD) among obstructive sleep apnea syndrome (OSAS) patients requiring treatment. DESIGN: Polysomnographic and demographic characteristics and associated morbidity were measured in 686 prospectively recruited adult OSAS patients from two regions in Israel. SETTING: Two university-affiliated sleep laboratories. MEASUREMENTS AND RESULTS: The multiple logistic regression (after adjusting for gender, body mass index [BMI], and smoking) revealed that the following are independent determinants for CVD in OSAS patients requiring treatment: each decrease in income level category (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1 to 1.7), age > or = 1 year (OR, 1.07; 95% CI, 1.04 to 1.1), hypertension (OR, 2.0; 95% CI, 1.3 to 3.1), and hyperlipidemia (OR, 3.7; 95% CI, 2.4 to 5.8); area under the receiver operating characteristic (ROC) = 81.9%. The multivariate determinants describing the low-SES OSAS patients included: minorities and immigrants combined (OR, 6.0; 95% CI, 2.9 to 12), female gender (OR, 2.4; 95% CI, 1.6 to 3.9), increased BMI (OR, 1.9; 95% CI, 1.3 to 2.9), unmarried status (OR, 1.9; 95% CI, 1.2 to 3.1), and years of education (> or = 1 year) [OR, 0.8; 95% CI, 0.7 to 0.8]; area under the ROC = 78.1%. CONCLUSION: In addition to the already known traditional risk factors, low SES was found to be a novel independent risk factor for CVD among adult OSAS patients requiring treatment.

Gastrointestinal comorbidities in patients with psoriatic arthritis.

Comorbidities associated with psoriatic arthritis (PsA) include cardiovascular diseases, diabetes mellitus, and obesity. This study evaluated the association between PsA and common gastrointestinal (GI) diseases. A retrospective study was performed in Israel's largest health care provider database between 2002 and 2013. 3161 PsA patients were matched for age and sex with 31610 randomly selected patients. We searched these patients' records for the presence of peptic ulcer disease (PUD), reflux esophagitis, Crohn's disease, ulcerative colitis, irritable bowel syndrome (IBS) and celiac disease. T-test was used to compare continuous variables and a Chi-square test was used for categorical variables. Multivariate logistic regression models were used to assess the association between PsA and GI comorbidities. PsA was associated with Crohn's disease (OR 2.4, 95 %CI: 1.75-3.32, p < 0.0001), ulcerative colitis (OR 2.1, 95 %CI: 1.33-3.26, p = 0.001), reflux esophagitis (OR 1.6, 95 %CI: 1.44-1.78, p < 0.0001), PUD (OR 1.5, 95 %CI: 1.31-1.63, p < 0.0001) and IBS (OR 1.4, 95 %CI: 1.01-1.86, p = 0.045). After controlling for known risk factors, the association remained significant between PsA and Crohn's disease (OR 2.2, 95 %CI: 1.59-3.03, p < 0.0001), ulcerative colitis (OR 1.9, 95 %CI: 1.21-3.00, p = 0.005), reflux esophagitis (OR 1.5, 95 %CI: 1.31-1.63, p < 0.0001), and PUD (OR 1.3, 95 %CI: 1.12-1.47, p < 0.0001). No significant association was found between PsA and celiac disease. In the current study PsA was associated with gastrointestinal morbidities including Crohn's disease, ulcerative colitis, PUD and IBS. Physicians treating patients with PsA should be aware of these associations.

Determinants affecting health-care utilization in obstructive sleep apnea syndrome patients.

STUDY OBJECTIVE: To investigate determinants of health-care utilization in patients with obstructive sleep apnea syndrome (OSAS). DESIGN: Case-control prospective study with OSAS patients and a control group. We compared 218 patients with OSAS to those of age-, gender-, geographically-, and family physician-matched control subjects from the general population, matched 1:1 (chi2 = 0.999). PARTICIPANTS: All participants were members of Clalit Health Care Services, a health maintenance organization in the southern region of Israel. All OSAS patients underwent nocturnal polysomnography studies. Indexes of health-care utilization 2 years prior to the polysomnography were analyzed. MEASUREMENTS AND RESULTS: Health-care utilization was 1.7-fold higher (p < 0.001) in the OSAS patients due to more hospitalization days (p < 0.001), consultations (p < 0.001), and cost for drugs (p < 0.05), particularly those for the cardiovascular system. In comparison to men, women consumed significantly more health-care resources (p < 0.001). OSAS patients < or = 65 of age years consumed 2.2-fold more health-care resources than control subjects (p < 0.001). Polysomnography findings and OSAS severity and body mass index (BMI) did not predict health-care utilization, using multivariate logistic regression analysis. Age > 65 (odds ratio [OR], 2.2; p < 0.04) and female gender (OR, 2.0; p < 0.05) were the leading elements predicting the most costly OSAS patients. Arbitrarily dividing the OSAS group by cost of health-care utilization, the upper 25% (n = 55) of patients who were the "most costly" consumed sevenfold more health-care resources than the lower 75% of the patients. This was due to higher comorbidity, ie, 10 to 30% more hypertension, ischemic heart disease, diabetes mellitus, and pulmonary disease. CONCLUSIONS: OSAS patients are heavy users of health-care resources. Age > 65 years and female gender were the leading elements predicting the most costly OSAS patients, and not necessarily patients with a high BMI and classic OSAS severity indexes.

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study.

BACKGROUND: The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice. METHODS: All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services' (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model. RESULTS: 64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5-16.5) vs. 31.0 for TBP (95% CI: 20.6-41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40-0.99, P = 0.045]. CONCLUSION: In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.

Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500,000 Person-year Study.

IMPORTANCE: The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. OBJECTIVE: To describe the risk for HZ in patients with psoriasis and its relation to treatment. DESIGN, SETTING, AND PARTICIPANTS: A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95,941 patients with psoriasis in the analysis, with 522,616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. MAIN OUTCOMES AND MEASURES: Incidence of HZ associated with systemic therapies. RESULTS: In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). CONCLUSIONS AND RELEVANCE: Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.

Defensive medicine among obstetricians and gynecologists in tertiary hospitals.

OBJECTIVE: To describe the daily work practice under the threat of defensive medicine among obstetricians and gynecologists. STUDY DESIGN: A prospective cross-sectional survey of obstetricians and gynecologists working at tertiary medical centers in Israel. RESULTS: Among the 117 obstetricians and gynecologists who participated in the survey, representing 10% of the obstetricians and gynecologists registered by the Israel Medical Association, 113 (97%) felt that their daily work practice is influenced by concern about being sued for medical negligence and not only by genuine medical considerations. As a result, 102 (87%) physicians are more likely to offer the cesarean section option, even in the absence of a clear medical indication, 70 (60%) follow court rulings concerning medical practices, and 85 (73%) physicians mentioned that discussions about medical negligence court rulings are included in their departments' meetings. CONCLUSIONS: Defensive medicine is a well-embedded phenomenon affecting the medical decision process of obstetricians and gynecologists.