Cardiovascular events and all-cause mortality in patients with chronic obstructive pulmonary disease using olodaterol and other long-acting beta2-agonists.

PURPOSE: We examined the effect of olodaterol on the risk of myocardial ischaemia, cardiac arrhythmia, and all-cause mortality compared with use of other long-acting beta2-agonists (LABAs). Channelling bias was also explored. METHODS: This Danish population-based cohort study used data linked from registries of hospital diagnoses, outpatient dispensings, and deaths. It included patients (aged ≥40 years) with a diagnosis of chronic obstructive pulmonary disease (COPD) who initiated olodaterol or another LABA. Using matching and propensity score (PS) stratification, we calculated adjusted incidence rate ratios (IRRs) using Poisson regression, followed by several additional analyses to evaluate and control channelling bias. RESULTS: The IRRs of cardiac arrhythmias or myocardial ischaemia among users of olodaterol (n = 14 239) compared to users of other LABAs (n = 51 167) ranged from 0.96 to 1.65 in various analyses, although some estimates had low precision. Initial analysis suggested an increased risk for death with olodaterol compared with other LABAs (IRR, 1.63; 95% CI, 1.44-1.84). Because olodaterol prescribing was associated with COPD severity, the mortality association was attenuated by using different methods of tighter confounding control: the IRRs were 1.26 (95% CI, 0.97-1.64) among LABA-naïve LABA/LAMA users without recent COPD hospitalisation; 1.27 (95% CI, 1.03-1.57) in a population with additional trimming from the tails of the PS distribution; and 1.32 (95% CI, 1.19-1.48) after applying overlap-weights analysis. CONCLUSIONS: Olodaterol users had a similar risk for cardiac arrhythmias or myocardial ischaemia as other LABA users. The observed excess all-cause mortality associated with olodaterol use could be due to uncontrolled channelling bias.

GOLD assessment of COPD severity in the Clinical Practice Research Datalink (CPRD).

PURPOSE: To evaluate availability of spirometry and symptom data in the Clinical Practice Research Datalink (United Kingdom) to assess COPD severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 definition and comparing it with an algorithm used in other studies. METHODS: This was a descriptive, noninterventional, secondary database cohort study of patients with COPD aged 40 years or older, who initiated treatment with specific COPD medications. Patients were classified according to COPD severity (1) in GOLD 2016 "ABCD" categories based on symptoms (Medical Research Council dyspnea grade, COPD Assessment Test, breathlessness), percent predicted FEV1, and exacerbation history and (2) as mild, moderate, severe, or very severe based on treatment and exacerbation history. RESULTS: The study included 63 900 patients with COPD aged 40 years or older that were new users of 1 or more COPD medication of interest. Percent predicted FEV1 was available for 80.9% of patients; symptoms for 75.6% of patients. Classification into GOLD 2016 ABCD categories was possible for 75.6% of the patients. The GOLD 2016 ABCD definition classified more patients under the high-risk categories (22.1%, A; 18.8%, B; 21.3%, C; 37.9%, D) than did the adapted algorithm (7.9%, mild; 48.6%, moderate; 42.1%, severe; 1.4%, very severe). CONCLUSION: Using our adaptation of the GOLD 2016 COPD severity classification, the information in the Clinical Practice Research Datalink allowed us to ascertain COPD severity in approximately 75% of patients with COPD. Algorithms that include medication use tend to misclassify patients with the extreme COPD severity categories.

Factors associated with and impact of pain persistence in Asian patients with depression: a 3-month, prospective observational study.

OBJECTIVE: We investigated the depression outcomes and the factors associated with pain persistence in Asian patients treated for major depressive disorder (MDD). METHODS: This observational study enrolled 909 Asian adult inpatients and outpatients. The presence or absence of painful physical symptoms and severity of depression were assessed at baseline and after three months of treatment. Factors associated with pain persistence and outcome of depression were investigated using regression methods. RESULTS: Of the 909 patients enrolled, 684 were included in the analysis and evaluated at three months. Of them, 335 (49%) had no pain at baseline nor follow up, 198 (29%) at baseline but not at follow up and 151 (22%) in both assessments. Pain more frequently persisted in patients who were divorced/widowed/separated, with >1 comorbidity, aged <40 years, with previous MDD episodes, taking pain medications, and with greater depression severity. At three months, response/remission were 84%/73% in the no pain group, 83%/63% in the remitted pain group and 46%/25% in the persistent pain group (differences all p < .0001; all bivariate comparisons were statistically significant with p < .05 except response between no pain and remitted pain). Persistent pain was also associated with less improvement in quality of life and health state. CONCLUSIONS: Pain should be taken into account when diagnosing MDD and when tailoring therapy.

Baseline Predictors for Success Following Strategy-Based Cognitive Remediation Group Training in Schizophrenia.

Our aim was to examine predictive variables associated with the improvement in cognitive, clinical, and functional outcomes after outpatient participation in REPYFLEC strategy-based Cognitive Remediation (CR) group training. In addition, we investigated which factors might be associated with some long-lasting effects at 6 months' follow-up. Predictors of improvement after CR were studied in a sample of 29 outpatients with schizophrenia. Partial correlations were computed between targeted variables and outcomes of response to explore significant associations. Subsequently, we built linear regression models for each outcome variable and predictors of improvement. The improvement in negative symptoms at posttreatment was linked to faster performance in the Trail Making Test B. Disorganization and cognitive symptoms were related to changes in executive function at follow-up. Lower levels of positive symptoms were related to durable improvements in life skills. Levels of symptoms and cognition were associated with improvements following CR, but the pattern of resulting associations was nonspecific.

Relationship of insight with medication adherence and the impact on outcomes in patients with schizophrenia and bipolar disorder: results from a 1-year European outpatient observational study.

BACKGROUND: Many patients with schizophrenia and bipolar disorder have impaired insight and low medication adherence. The aim of this post hoc analysis was to explore the relationship between insight and medication adherence. METHODS: We included 903 patients with schizophrenia or bipolar disorder who participated in an observational study conducted in Europe on the outcomes of patients treated with two oral formulations of olanzapine over a 1-year period. Evaluations included Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), insight (Scale to Assess Unawareness of Mental Disorder, SUMD) medication adherence (Medication Adherence Rating Scale, MARS), and therapeutic alliance (Working Alliance Inventory, WAI). RESULTS: Medication adherence was higher in bipolar patients (mean MARS score (SD) 6.5 (2.8) versus 5.8 (2.7) in schizophrenia; p < 0.001). Patients with schizophrenia had lower insight (i.e., SUMD item 1, unawareness of mental disorder, mean (SD) of 2.5 (1.3) in schizophrenia versus 1.9 (1.2) in bipolar, p < 0.001). Better insight was associated with higher adherence (Spearman Correlation Coefficient, SCC, ranging from 0.39 to 0.49 for the three SUMD general items, p < 0.0001 in all cases). Higher insight was related to a stronger therapeutic alliance (SCC ranging from 0.38 to 0.48, p < 0.0001). A path analysis revealed a positive impact of insight on adherence and alliance and that stronger alliance was related to lower clinical severity (lower CGI score). CONCLUSION: Insight and adherence were found to be closely related. Insight impacts on the therapeutic alliance with mental health professionals. These factors are associated to treatment outcomes.

Should Unexplained Painful Physical Symptoms be Considered within the Spectrum of Depressive Symptoms?

OBJECTIVE: To examine whether painful physical symptoms (PPS) can be considered within the spectrum of depressive symptoms. METHODS: Data for this post-hoc analysis were taken from a 6-month observational study mostly conducted in East Asia, Mexico, and the Middle East of 1,549 depressed patients without sexual dysfunction at baseline. Both explanatory and confirmatory factor analyses (EFA and CFA) were performed on the combined items of the 16-item Quick Inventory of Depressive Symptomatology Self-Report and the Somatic Symptom Inventory (seven pain-related items only). An additional second-order CFA was also conducted to examine an association between retained factors and the overall "depressive symptoms" factor. In addition, Spearman's correlation was used to assess levels of correlation between retained factors and depression severity as well as quality of life. RESULTS: Both EFA and CFA suggested and validated a four-factor solution, which included a pain factor. The other three factors identified were a mood/cognitive factor, a sleep disturbance factor, and an appetite/weight disturbance factor. All four factors were significantly associated with the overall factor of depression. They were also highly correlated to depression severity and quality of life (p<0.001 for all). The levels of correlations with the pain factor were generally greater than those with the appetite/weight factor and similar to those with the sleep factor. CONCLUSION: It may be reasonable to consider PPS within a broad spectrum of depressive symptoms. At least, they should be routinely assessed in patients with depression. Further research is warranted to validate these preliminary findings.

Empirically driven definitions of "good," "moderate," and "poor" levels of functioning in the treatment of schizophrenia.

PURPOSE: This study used an empirical approach to identify and validate the classification of patients with schizophrenia in "good," "moderate," or "poor" functioning groups based on the assessment of functional measures. METHODS: Using data from a study of schizophrenia outpatients, patients were classified into functional groups using cluster analysis based on the Heinrich-Carpenter Quality of Life Scale (QLS), the 36-item Short-Form Health Survey (SF-36) Mental Component Summary Score, and a productivity measure. A three-cluster solution was chosen. Concurrent, convergent, and discriminant validity were assessed. Criteria for classifying patient functioning as "good," "moderate," or "poor" were established using classification and regression tree analysis. RESULTS: The three clusters consistently differentiated patients on the QLS, SF-36 Mental Component Summary Score, and productivity measure. The clusters also differed on other functional measures and were concordant with previous functional classifications. Concurrent, convergent, and discriminant validity were good. "Good" functioning was identified as a QLS total score ≥ 84.5; "moderate" and "poor" functioning were separated by a cutoff score of 15.5 on the QLS intrapsychic foundation domain. Sensitivity ranged from 86 to 93 % and specificity from 89 to 99 %. CONCLUSIONS: The heterogeneity in functioning of schizophrenia patients can be classified reliably in an empirical manner using specific cutoff scores on commonly used functional measures.

Double J catheter migrated to the bladder and encrusted. Case report and bibliographic review.

OBJECTIVE: Urinary tract obstruction is one of the most prevalent diseases in urology. The handling of it includes conservative (analgesia and fluid therapy) and invasive (urinary diversion) measures. Ureteral stent is the method currently employed for urinary tract diversion. Complications of urinary tract stents maintenance have already been studied and are well known. We report a case of ureteral stent migrated to the bladder, calcified and embedded and we review the existing literature. METHODS: A 28 year-old man with the diagnosis of ureteral stent coiled in bladder and calcified. The patient was successfully operated of suprapubic cystolithotomy. We conducted a Medline search using the terms "ureteral stent "+" embedded stent, "" bladder ureteral stent, "incrusted bladder stent" and "ureteral stent complicactions". RESULTS: He is currently free of disease. We found a total of 45 articles that responded to the search criteria, from which we select the highest citation index. CONCLUSIONS: The use of ureteral stents for urinary diversion of the upper urinary tract is safe and well tolerated but not without complications, that is why we have to raise awareness among patients of the need to undergo periodic inspections and instruct them to possible symptoms and / or signs that may indicate changes in position and / or state of the stent.

Risk Assessment of Acute Myocardial Infarction and Stroke Associated with Long-Acting Muscarinic Antagonists, Alone or in Combination, versus Long-Acting beta2-Agonists.

Background: The long-acting muscarinic antagonist (LAMA) aclidinium was approved in Europe in 2012 to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). A post-authorization safety study was initiated to assess potential cardiovascular risks associated with LAMAs versus long-acting beta2-agonists. Purpose: To estimate incidence rates and adjusted incidence rate ratios (IRRs) for acute myocardial infarction (AMI), stroke, and major adverse cardiac events (MACE) in new users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, long-acting beta-agonists/inhaled corticosteroids (LABA/ICS), and LAMA/LABA compared with initiators of LABA. Patients and Methods: This population-based cohort study included patients with COPD aged ≥40 years initiating COPD medications in the UK Clinical Practice Research Datalink (CPRD) Aurum database from 2012 to 2019. Poisson regression models were used to estimate the IRR for AMI, stroke, and MACE in users of COPD medications versus LABA, adjusting for clinically relevant covariables. Results: The study included 11,121 new users of aclidinium, 4804 of aclidinium/formoterol, 56,198 of tiotropium, 23,856 of other LAMA, 17,450 of LAMA/LABA, 70,289 of LABA/ICS, and 13,716 of LABA. During periods of continuous medication use after initiation (current use), crude incidence rates per 1000 person-years for AMI ranged from 8.7 (aclidinium/formoterol) to 12.4 (LAMA/LABA), for stroke ranged from 4.8 (aclidinium/formoterol) to 7.2 (LAMA/LABA), and for MACE ranged from 13.5 (aclidinium/formoterol) to 19.3 (LAMA/LABA). Using LABA as reference, adjusted IRRs [95% confidence intervals] were close to 1 for all study drugs for AMI (lowest for aclidinium/formoterol, 0.95 [0.60-1.52], and highest for LAMA/LABA, 1.23 [0.91-1.67]), stroke (lowest for aclidinium/formoterol, 0.64 [0.39-1.06], and highest for tiotropium, 1.02 [0.81-1.27] for tiotropium) and for MACE (lowest for aclidinium, 0.93 [0.75-1.16], and highest for LAMA/LABA, 1.24 [0.97-1.59]). Conclusion: Risks of AMI, stroke, and MACE in current users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, LAMA/LABA, or LABA/ICS were similar to the risks among current users of LABA.

Characteristics of New Users of Aclidinium Bromide, Aclidinium/Formoterol, and Other COPD Medications in the United Kingdom, Denmark, and Germany.

BACKGROUND AND OBJECTIVES: Aclidinium bromide was approved in the European Union for the treatment of chronic obstructive pulmonary disease (COPD) in adult patients in 2012 and in a fixed-dose combination with formoterol in 2014. We characterised new users of aclidinium, aclidinium/formoterol and other COPD medications and evaluated off-label prescribing of these medications in three European populations. METHODS: We described demographic characteristics, comorbidities, comedications, COPD severity and off-label prescribing of new users of aclidinium, aclidinium/formoterol and other COPD medications in patients with COPD aged ≥ 40 years in the Clinical Practice Research Datalink (CPRD, UK), Danish National Health Databases, and German Pharmacoepidemiological Research Database (GePaRD) between 2015 and 2017. RESULTS: We included 17,668 new users of aclidinium (CPRD, 4871; Denmark, 2836; GePaRD, 9961) and 14,808 new users of aclidinium/formoterol (CPRD, 2153; Denmark, 2586; GePaRD, 10,069). Study patients were of similar age, except in GePaRD, where users of long-acting beta2-agonists (LABA)/inhaled corticosteroids were younger. Patients had multiple comorbidities and used multiple comedications-most frequently hypertension (50-79%) and short-acting beta2-agonists (26-84%). Aclidinium users in CPRD and long-acting anticholinergics/LABA users in Denmark and GePaRD had the highest frequency of severe/very severe COPD. Off-label prescribing of aclidinium (5.0% [CPRD]-8.9% [Denmark]) and aclidinium/formoterol (2.6% [GePaRD]-3.2% [CPRD]) was low, and the main reason was asthma without a COPD diagnosis. CONCLUSIONS: Aclidinium and aclidinium/formoterol were mostly prescribed according to label, with preference given to older patients with more severe COPD and to patients with a high prevalence of comorbidities and comedication use.

Methodological quality in pharmacogenetic studies with binary assessment of treatment response: a review.

OBJECTIVE: To evaluate the reporting of critical design issues and methods of statistical analysis in pharmacogenetic studies published in the medical literature. STUDY DESIGN AND SETTINGS: Systematic review of 65 original pharmacogenetic studies published in the literature over the last 15 years. RESULTS: The sample size determination and the planned sample size were lacking in 63 papers. The study design characterization was lacking in 43 papers. The number of patients analyzed ranged from 36 to 1400 (median=161 and interquartile range of 119-250). The Pearson's χ2 test and the Fisher's test were the most common forms of analysis. Multiple statistical testing was relevant to 59 papers, but only 11 addressed the issue of multiplicity (Bonferroni correction). Sources of multiplicity were multiple association assessment (45 papers), analysis of both genotype and allelic frequencies (44), and multiple analysis methods (unadjusted and adjusted). Hardy-Weinberg equilibrium was tested in 12 of 45 papers performing allelic analysis and was fully reported in four of them. The results of association analyses were commonly reported as P values but rarely as estimates of an association measure (odds ratio or relative risk) and its accuracy. CONCLUSIONS: These results show that there is considerable room for improvement in the current standards of design, analysis, and reporting of pharmacogenetic research.

Psychometric properties of the IDS-SR30 for the assessment of depressive symptoms in Spanish population.

BACKGROUND: Due to the high prevalence of depression, it is clinically relevant to improve the early identification and assessment of depressive episodes. The main objective of the present study was to examine the psychometric properties of the IDS-SR30 (Self-rated Inventory of Depressive Symptomatology) in a large Spanish sample of depressive patients. METHODS: This prospective, naturalistic, multicenter, nationwide epidemiological study conducted in Spain included 1595 adult patients (65.3% females) with a DSM-IV Major Depressive Disorder (MDD. IDS-SR30 and the Hamilton Depression Rating Scale (HDRS, 21 items)were administered to the sample. Data was collected during 2 routine visits. The second assessment was carried out after 10 ± 2 weeks after first assessment. RESULTS: The IDS-SR30 showed good internal consistency (α = 0.94) and high item total correlations (≥ 0.50) were found in 70% of the items. The convergent validity was 0.85. Results of the principal component analysis (PCA) and confirmatory factor analyses (CFA) showed that a three factor model (labelled mood/cognition, anxiety/somatic and sleep) is adequate for the current sample. CONCLUSIONS: The Spanish version of the IDS-SR30 seems a reliable, valid and useful tool for measuring depression symptomatology in Spanish population.

Clinical and economic consequences of medication non-adherence in the treatment of patients with a manic/mixed episode of bipolar disorder: results from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study.

The aim of the present study was to investigate clinical and economic consequences of medication non-adherence during 21-month follow-up in the treatment of bipolar disorder following a manic or mixed episode. Data were taken from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), which was a prospective, observational study on patient outcomes with a manic/mixed episode in Europe. Physician-rated adherence was dichotomized as adherence/non-adherence at each assessment. Cox proportional hazards models were employed to investigate the impact of non-adherence on remission, recovery, relapse, recurrence, hospitalization and suicide attempts. Costs of medication and resource use in adherent and non-adherent patients during follow-up were estimated with multivariate analyses. Of the 1341 patients analysed, 23.6% were rated non-adherent over 21 months. Non-adherence was significantly associated with decreased likelihood of achieving remission and recovery as well as increased risk of relapse and recurrence as well as hospitalization and suicide attempts. In addition, costs incurred by non-adherent patients during this period were significantly higher than those of adherent patients (£10231 vs £7379, p<0.05). This disparity mainly resulted from differences in inpatient costs (£4796 vs £2150, p<0.05). In conclusion, non-adherence in bipolar patients was associated with poorer long term clinical outcomes that have economic implications for health-care providers.

Giant bladder lithiasis: case report and bibliographic review.

OBJECTIVE: Urinary lithiasis is a very frequent urological disease but bladder lithiasis is very uncommon.Patients usually refer voiding symptoms and hematuria. The diagnosis is made after imaging tests. We report a clinical case describing a giant bladder stone and perform a bibliographic review. METHODS: A 43 year old man with the diagnosis of giant bladder stone (more than 10 cm diameter). We searched Medline using the terms: giant bladder stone, giant bladder lithiasis, bladder lithiasis, giant bladder lithiasis. RESULTS: We made the diagnosis of giant bladder stone after a simple kidney, ureter and bladder (KUB) X Ray. The treatment for this patient was a cystolithotomy. We found more than 230 reports at Medline and chose the most referred ones and the last 10 years reports. CONCLUSIONS: Giant bladder lithiasis is a very rare pathology. The gold standard for diagnosis is cystoscopy but sometimes with a KUB Xray or an ultrasound is enough. Because of its size, cistolitotomy is the correct treatment for giant bladder stone.

Large cell neuroendocrine carcinoma of the urinary bladder. Bibliographic review.

OBJECTIVES: Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is very rare. We intend to update diagnostic criteria, pathologic and immunohistochemical characteristics, prognosis and treatment options. All published articles related with LCNEC of the urinary bladder have been reviewed and a descriptive study has been done. RESULTS: A total of 17 LCNEC of the bladder has been found. The 50% of all LCNEC of the bladder are mixed histological variant. This variant implies a better prognosis than the pure variant. The 70% of LCNEC of the bladder were ≥T3 at the time of diagnosis and the survival rate was 25%, whereas T2 tumors showed a survival rate of 100%. Radical cystectomy with lymphadenectomy combined with chemotherapy can sometimes reduce local and distant recurrence and improve survival of LCNEC of the bladder. CONCLUSIONS: LCNEC of the bladder is a tumor with high rate of local and distant recurrence, as well as low survival, requiring early diagnosis and aggressive combined treatment.

Hyperbaric oxygen therapy for the management of hemorrhagic radio-induced cystitis.

OBJECTIVES: Radio-induced cystitis (RADC) is an inflammatory bladder disease that presents as anemic-hematuria in its most serious form. Classic treatments can not control the disease in the mid-to-long term because they don't treat the pathogenesis of the disease. Thus, we evaluated the effectiveness of hyperbaric oxygen (HBO) therapy as a potential treatment for patients with RADC. METHODS: This prospective study included 38 patients, 21 men and 17 women, mean age of 66.5 years(46-75), who had been subjected to pelvic radiotherapy (RT), with the diagnosis of RADC with or without radio-induced proctitis (RADP), gross hematuria and lower urinary tract symptoms. HBO treatment was applied in a multiplace chamber; patients breathed pure oxygen (100%) at 2-2.5 atmospheres of pressure (ATAs). Patients received an average of 31.2 sessions (10-48 sessions) and the median follow-up period was 56 months (4-72 months). RESULTS: Hematuria was completely resolved in 34 of the 38 patients. After HBO 6 patients required readmission, 5 for anemic hematuria and 1 for acute obstructive pyelonephritis. In general, patients tolerated treatment well; however, one patient experienced barotrauma requiring myringotomy. CONCLUSIONS: HBO can be used to satisfactorily treat RADC, leading to clinical improvements that begin during the initial sessions in the majority of cases, and with a more than acceptable level of patient tolerance.

Hypebaric oxygen treatment in urology.

OBJECTIVES: Hyperbaric oxygen therapy (HBO) has been successfully used in several disorders derived from tissue hypoxia, due to the extra oxygen supply to the tissues it enables. In this manuscript we performed a systematic review including all the existing data published until 2010 about HBO in urologic disorders. METHODS: We performed a Medline search using the terms "hyperbaric oxygen", "radical cystitis", "interstitial cystitis", "hemorrhagic cystitis", "urological/pelvic fistula"and "Fournier's gangrene". The search was restricted to human clinical trials published in any language. RESULTS: We found 56 papers: 1 randomized controlled trial, 7 reviews and 48 case reports; only one of them was a prospective study. A total of 695 patients were included. Just one study used tissue oxygen measurement to define hypoxia. The number of hyperbaric oxygen therapy sessions ranged from 4 to 44 (mean 19.2 sessions/patient). CONCLUSIONS: The level of evidence from most reviewed papers is low because most of them are case series. Nevertheless, results of most of those studies regarding patient management are good or very good. So it seems that HBO can be very useful in urological diseases related to tissue hypoxia.

A Cohort Study to Evaluate the Risk of Hospitalisation for Congestive Heart Failure Associated with the Use of Aclidinium and Other Chronic Obstructive Pulmonary Disease Medications in the UK Clinical Practice Research Datalink.

BACKGROUND: The long-acting anticholinergic (LAMA) aclidinium was approved in Europe in 2012 to relieve symptoms in adults with chronic obstructive pulmonary disease (COPD). A Post-Authorisation Safety Study (PASS) was initiated to assess potential cardiovascular safety concerns for aclidinium. OBJECTIVE: To estimate the adjusted incidence rate ratio (IRR) for hospitalisation for heart failure in patients with COPD who were new users of aclidinium, tiotropium, other LAMA, long-acting beta-agonists/inhaled corticosteroids (LABA/ICS), and LAMA/LABA were compared with initiators of LABA. METHODS: This population-based cohort study included patients with COPD aged ≥40 years initiating COPD medications in the Clinical Practice Research Datalink (CPRD) GOLD in the United Kingdom from 2012 to 2017. Medications were identified via general practice prescriptions. The first-ever hospitalisations for heart failure were identified in the Hospital Episode Statistics, and general practitioner records from the CPRD. Poisson regression models were used to estimate the IRR for hospitalisation for heart failure in users of COPD medications versus LABA, adjusting for clinically relevant covariates. RESULTS: The study included 4350 new users of aclidinium, 23,405 of tiotropium, 6977 of other LAMAs, 3122 of LAMA/LABA, 26,093 of LABA/ICS, and 5678 of LABA. Mean age was 69-70 years across medication groups. Aclidinium users had the highest proportion of severe COPD, and LABA users had the lowest (35% vs 19%, respectively). Crude incidence rates per 1000 person-years for the first-ever hospitalisation for heart failure ranged from 6.9 in LABA to 9.5 in aclidinium. Using LABA as reference, adjusted IRRs (95% confidence interval) for first-ever hospitalisation for heart failure were 0.90 (0.53-1.53) for aclidinium, 1.02 (0.69-1.51) for tiotropium, 0.86 (0.50-1.47) for other LAMAs, 1.09 (0.41-2.92) for LAMA/LABA, and 1.01 (0.69, 1.48) for LABA/ICS. CONCLUSION: The study did not find increased risks of hospitalisations for heart failure in new users of aclidinium, tiotropium, other LAMAs, LAMA/LABA, and LABA/ICS compared with LABA.

The 12-item World Health Organization Disability Assessment Schedule II (WHO-DAS II): a nonparametric item response analysis.

BACKGROUND: Previous studies have analyzed the psychometric properties of the World Health Organization Disability Assessment Schedule II (WHO-DAS II) using classical omnibus measures of scale quality. These analyses are sample dependent and do not model item responses as a function of the underlying trait level. The main objective of this study was to examine the effectiveness of the WHO-DAS II items and their options in discriminating between changes in the underlying disability level by means of item response analyses. We also explored differential item functioning (DIF) in men and women. METHODS: The participants were 3615 adult general practice patients from 17 regions of Spain, with a first diagnosed major depressive episode. The 12-item WHO-DAS II was administered by the general practitioners during the consultation. We used a non-parametric item response method (Kernel-Smoothing) implemented with the TestGraf software to examine the effectiveness of each item (item characteristic curves) and their options (option characteristic curves) in discriminating between changes in the underliying disability level. We examined composite DIF to know whether women had a higher probability than men of endorsing each item. RESULTS: Item response analyses indicated that the twelve items forming the WHO-DAS II perform very well. All items were determined to provide good discrimination across varying standardized levels of the trait. The items also had option characteristic curves that showed good discrimination, given that each increasing option became more likely than the previous as a function of increasing trait level. No gender-related DIF was found on any of the items. CONCLUSIONS: All WHO-DAS II items were very good at assessing overall disability. Our results supported the appropriateness of the weights assigned to response option categories and showed an absence of gender differences in item functioning.

Utility of the twelve-item World Health Organization Disability Assessment Schedule II (WHO-DAS II) for discriminating depression "caseness" and severity in Spanish primary care patients.

PURPOSE: The 12-item WHO-DAS II was developed to assess the activity limitations and participation restrictions experienced by individuals irrespective of medical diagnosis. In this paper we examine the known-groups' validity of the instrument by evaluating its ability to discriminate between patients with/without major depression, patients with depression with/without medical comorbidity, and patients with depression with different depression severity. METHOD: The participants were 3,615 PC patients from 17 regions of Spain, with a first-time diagnosis of major depressive episode according to the general practitioner. The 12-item WHO-DAS II, the PHQ-9, and a chronic medical conditions checklist were administered during the consultation. RESULTS: The statistical analyses indicated that the 12-item WHO-DAS II was able to discriminate between patients with/without depression and between those with different depression severity. The ROC analysis revealed that with a cutoff score >or=50, the instrument correctly classified 70.4% of the sample (area under the ROC curve = .76; sensitivity = 71.4%; specificity = 67.6%). CONCLUSIONS: Overall, our results support the discriminant validity of the 12-item WHO-DAS II for major depression, being quite recommendable its use in epidemiological research.