CREST-UK: Real-world effectiveness, safety and outpatient delivery of CPX-351 for first-line treatment of newly diagnosed therapy-related AML and AML with myelodysplasia-related changes in the UK.

Favourable outcomes with CPX-351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60-75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX-351 Real-World Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan-Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2-15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX-351 identified in CREST-UK. Patients treated with CPX-351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST-UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX-351 in routine clinical practice in the UK.

Complicated carbapenem-resistant infections: a treatment pathway analysis in Italian sites.

INTRODUCTION: Efforts to curb a growing prevalence of carbapenem resistance are prominent worldwide and especially in countries where high levels of carbapenem resistance are reported, such as Italy. Complicated infections, including complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), are often caused by carbapenem-resistant Gram-negative (CRGN) bacteria and as such, these infection sites and their causative bacteria are important areas of focus for healthcare practitioners seeking to follow good antimicrobial stewardship practices. The aim of this study was to assess the clinical management and associated clinical and economic outcomes of patients with cUTI, cIAI, and HABP/VABP resulting from CRGN bacteria in Italy. METHODS: We first conducted a hospital survey focusing on Gram-negative infections and their antibacterial susceptibility profile in four participating Italian hospitals. The second part of the study involved a non-interventional, retrospective single cohort chart review of 100 patients with cUTI, cIAI, or HABP/VABP caused by CRGN bacteria, in which patient characteristics, index hospitalization characteristics, infection characteristics, patient outcomes, treatment pathways, and healthcare resource use were assessed. RESULTS: The hospital survey demonstrated carbapenem resistance in approximately 17% of complicated infections, mostly associated with Acinetobacter baumannii. The non-interventional, retrospective cohort component showed that complicated CRGN infections were hospital- or healthcare-acquired in 99.0% of cases and were most often caused by Klebsiella pneumoniae (66.0%). Despite the carbapenem-resistant nature of the included infections, carbapenems were used in 19.0% of patients as empirical therapy, in 43.0% as late empirical (i.e. immediately before receipt of susceptibility test results), and in 64.0% as targeted therapy (post-susceptibility test result receipt). Colistin was used in 61.0% of patients after susceptibility results were available. High clinical and economic burden was evident, with the average length of hospital stay being greater than 50 days, clinical cure achievement in only 43.0% of patients, and an overall mortality rate of 65.0% by the end of the follow-up period. CONCLUSION: Our results reflect the considerable burden associated with complicated CRGN infections in Italy and the limitations in current treatment strategies. Our study pinpoints potential areas for improvement. For example, regular and detailed local surveillance and state of the art microbial diagnostic capabilities might aid and hasten clinical decision-making and facilitate improved antimicrobial stewardship when treating complex CRGN infections. New therapeutic options which more appropriately address CRGN infections may assist in improving outcomes which are important to both patients and healthcare providers.

Patrones de tratamiento biológico en pacientes con enfermedades articulares inflamatorias. Estudio retrospectivo de 4 años de seguimiento / Biological treatment patterns in patients with inflammatory joint diseases. Retrospective study with 4 years follow-up

OBJETIVO: Describir el manejo terapéutico de la artritis reumatoide (AR), la artritis psoriásica (Aps) y la espondilitis anquilosante (EA) en pacientes que inician tratamiento con agentes biológicos. MATERIALES Y MÉTODOS: Estudio observacional, retrospectivo, longitudinal en 33 hospitales españoles. Se incluyeron pacientes con AR, Aps y EA que iniciaron tratamiento con agentes biológicos entre septiembre de 2009 y agosto de 2010, con un seguimiento de más de 3 años. Se analizaron las características clínico-demográficas, los fármacos, la supervivencia de la terapia biológica y las causas de cambio o interrupción. RESULTADOS: Se incluyeron 463 pacientes (183 AR, 119 Aps y 161 EA) con un seguimiento medio de 3,8 años. Al final del seguimiento una elevada proporción continuaba con el primer biológico prescrito (41,0% de AR, 59,7% de Aps y 51,6% de EA), precisando ajustes de dosis el 31,1%, 47,9% y 42,9% de pacientes con AR, Aps y EA, respectivamente. Hubo interrupción temporal en el 8,2%, 8,4% y 15,5% de los pacientes y se precisó cambio de biológico en el 37,7%, 26,1% y 24,2%. La interrupción definitiva ocurrió en el 13,1%, 5,9% y 8,7% de pacientes con AR, Aps y EA, respectivamente. El tiempo medio de cambio o interrupción fue de 30,1 meses para la AR y de 35,7 meses para la Aps y la EA. CONCLUSIONES: Nuestros resultados sugieren que, en la práctica, la mitad de los pacientes con AR y 2/3 con Aps o EA continúan con el primer biológico, pero con frecuentes ajustes de tratamiento

OBJECTIVES: To describe the therapeutic management of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) in patients initiating treatment with biological agents. MATERIALS AND METHODS: Observational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analyzed. RESULTS: Four hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS. CONCLUSIONS: Our results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments

Biological Treatment Patterns in Patients with Inflammatory Joint Diseases. Retrospective Study with 4 Years Follow-up. / Patrones de tratamiento biológico en pacientes con enfermedades articulares inflamatorias. Estudio retrospectivo de 4 años de seguimiento.

OBJECTIVES: To describe the therapeutic management of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) in patients initiating treatment with biological agents. MATERIALS AND METHODS: Observational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analyzed. RESULTS: Four hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS. CONCLUSIONS: Our results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments.

Evolution of overactive bladder symptoms in genital prolapse surgery / Evolución de los síntomas de vejiga hiperactiva tras la cirugía de prolapso genital

Objective: In the present study, we evaluated the development of symptoms of overactive bladder in women undergoing surgery for pelvic organ prolapse. Material and methods: We performed an epidemiological, longitudinal, prospective study involving 39 gynecological centers in Spain. The study population included women with symptomatic pelvic organ prolapse who were candidates for vaginal surgery. Patients attended a baseline visit (before surgery) and another visit 1 year after surgery. Pelvic organ prolapse was graded according to the Baden-Walker classification and the Pelvic Organ Prolapse Questionnaire. Urgency, urge incontinence, frequency, and nocturia were evaluated separately. Patients filled out the Epidemiology of Prolapse and Incontinence Questionnaire and the International Consultation on Incontinence Questionnaire. Results: The final sample included 360 women (319 were evaluable at the postsurgery visit). At baseline 58.3%, 38.3%, and 47.2% of women reported urgency, urge urinary incontinence, and frequency, respectively, whereas after surgery these symptoms were reported by 34.5%, 17.2%, and 19.7% (p < 0.001). The percentage of patients reporting nocturia also decreased after surgery from 59.4% to 56.4%, although the difference was not statistically significant. Furthermore, 19.8%, 9.8%, and 7.6% of patients, respectively, reported de novo urgency, urge urinary incontinence, and frequency after surgery. Patients with persistence of postsurgical urge urinary incontinence had significantly higher scores in the International Consultation on Incontinence Questionnaire at baseline. Conclusions: In general, a reduction in overactive bladder symptoms was observed in women undergoing surgical treatment for pelvic organ prolapse

Objetivo: el presente estudio pretende evaluar la evolución de síntomas de vejiga hiperactiva en mujeres intervenidas de prolapso de órganos pélvicos. Material y métodos: estudio epidemiológico, longitudinal, prospectivo, en 39 servicios de ginecología de España, que incluyó mujeres con prolapso de órganos pélvicos sintomático candidatas a cirugía de prolapso por vía vaginal. Se realizó una visita previa y una de seguimiento al año de la cirugía. Se evaluó el prolapso de órganos pélvicos mediante la clasificación de Baden y el cuestionario de prolapso de órganos pélvicos. Las pacientes cumplimentaron el cuestionario de epidemiología de prolapso e incontinencia y el de incontinencia urinaria. Se evaluaron los síntomas de urgencia, incontinencia urinaria de urgencia, frecuencia y nocturia. Resultados: se incluyeron 360 mujeres (319 evaluables en la revisión poscirugía). En la evaluación basal el 58,3%, 38,3% y 47,2% de las mujeres refirieron urgencia, incontinencia urinaria de urgencia y frecuencia, mientras que en la visita poscirugía únicamente el 34,5%, 17,2% y 19,7% las presentaban (p < 0,001). El porcentaje de pacientes que presentaban nocturia también se redujo, del 59,4% al 56,4%, aunque no de forma estadísticamente significativa. Un 19,8%, 9,8% y 7,6% de las pacientes presentaron urgencia, incontinencia urinaria de urgencia y frecuencia de novo tras la cirugía, respectivamente. Las pacientes con persistencia de incontinencia urinaria de urgencia poscirugía presentaron puntuaciones significativamente más elevadas en el cuestionario de incontinencia urinaria en la visita basal. Conclusiones: en general, se observa una reducción de los síntomas de vejiga hiperactiva en mujeres sometidas a cirugía de prolapso de órganos pélvicos

Healthcare resource utilization and cost among males with lower urinary tract symptoms with a predominant storage component in Spain: The epidemiological, cross-sectional MERCURY study.

AIMS: To assess the relationship between storage-predominant LUTS and healthcare resource consumption and cost among males in Spain. METHODS: In this non-interventional, cross-sectional study, urologists enrolled males with storage-predominant LUTS and recorded the consumption of healthcare resources (medical visits, diagnostic tests/monitoring, treatment, and hospitalizations) within the previous 6 months. The cost of healthcare resources was calculated from unit costs extracted from a Spanish eHealth database. Severity of LUTS was assessed by the Bladder Self-Assessment Questionnaire (BSAQ) and patients were stratified by symptom score (<6 or ≥6) to assess the relationship between LUTS severity and healthcare resource consumption and cost. RESULTS: Among 610 enrolled patients (BSAQ symptom score <6, n = 191; BSAQ symptom score ≥6, n = 419), the majority (87.7%) consumed healthcare resources during the previous 6 months in the form of medical visits (86.2%), diagnostic tests/monitoring (83.4%), and treatment (85.9%). Patients with BSAQ symptom scores ≥6 used more healthcare resources compared with patients with BSAQ symptom scores <6. The most common treatments for LUTS were α-blockers used as monotherapy (n = 229 [37.5%]) or in combination with antimuscarinics (n = 227 [37.2%]). The estimated median annual cost was €1070 per patient, consisting of diagnostic tests/monitoring (54.6%), medical visits (20.5%), and treatment (29.6%), and was higher in patients with BSAQ symptom score ≥6 (€1127) than in patients with BSAQ symptom score <6 (€920; P < 0.001). CONCLUSIONS: More severe LUTS are associated with higher healthcare consumption and cost. These findings highlight the importance of symptom management in LUTS patients to help minimize healthcare consumption and cost.

Mapping AcroQoL scores to EQ-5D to obtain utility values for patients with acromegaly.

AIMS: To estimate a preference-based single index for the disease-specific instrument (AcroQoL) by mapping it onto the EQ-5D to assist in future economic evaluations. MATERIALS AND METHODS: A sample of 245 acromegaly patients with AcroQoL and EQ-5D scores was obtained from three previously published European studies. The sample was split into two: one sub-sample to construct the model (algorithm construction sample, n = 184), and the other one to confirm it (validation sample, n = 61). Various multiple regression models including two-part model, tobit model, and generalized additive models were tested and/or evaluated for predictive ability, consistency of estimated coefficients, normality of prediction errors, and simplicity. RESULTS: Across these studies, mean age was 50-60 years and the proportion of males was 36-59%. At overall level the percentage of patients with controlled disease was 37.4%. Mean (SD) scores for AcroQoL Global Score and EQ-5D utility were 62.3 (18.5) and 0.71 (0.28), respectively. The best model for predicting EQ-5D was a generalized regression model that included the Physical Dimension summary score and categories from questions 9 and 14 as independent variables (Adj. R2 = 0.56, with mean absolute error of 0.0128 in the confirmatory sample). Observed and predicted utilities were strongly correlated (Spearman r = 0.73, p < .001) and paired t-Student test revealed non-significant differences between means (p > .05). Estimated utility scores showed a minimum error of ≤10% in 45% of patients; however, error increased in patients with an observed utility score under 0.2. The model's predictive ability was confirmed in the validation cohort. LIMITATIONS AND CONCLUSIONS: A mapping algorithm was developed for mapping of AcroQoL to EQ-5D, using patient level data from three previously published studies, and including validation in the confirmatory sub-sample. Mean (SD) utilities index in this study population was estimated as 0.71 (0.28). Additional research may be needed to test this mapping algorithm in other acromegaly populations.

Characteristics of COPD patients initiating treatment with aclidinium or tiotropium in primary care in Catalonia: a population-based study.

OBJECTIVE: To describe and compare demographic and clinical profile of patients newly initiated on aclidinium (ACL) or tiotropium (TIO) and identify factors associated with newly initiated ACL in real-life clinical practice during 2013 in Catalonia. DESIGN: We performed a population-based, retrospective, observational study with data obtained from the Information System for Research Development in Primary Care, a population database that contains information of 5.8 million inhabitants (more than 80% of the Catalan population). Patients over 40 years old, with a recorded diagnosis of COPD and newly initiated treatment with either ACL or TIO during the study period (January to December 2013), were selected. A descriptive analysis of demographic and clinical characteristics was performed, and treatment adherence was also assessed for both cohorts. RESULTS: A total of 8,863 individuals were identified, 4,293 initiated with ACL and 4,570 with TIO. They had a mean age of 69.4 years (standard deviation: 11.3), a median COPD duration of 3 years (interquartile range: 0-8), and 71% were males. Patients treated with ACL were older, with more respiratory comorbidities, a longer time since COPD diagnosis, worse forced expiratory volume in 1 second (% predicted), and with a higher rate of exacerbations during the previous year compared with TIO. It was found that 41.3% of patients with ACL and 62.3% of patients with TIO had no previous COPD treatment. Inhaled corticosteroid and long-acting ß2-agonist were the most frequent concomitant medications (32.9% and 32.6%, respectively). Approximately 75% of patients were persistent with ACL or TIO at 3 months from the beginning of treatment, and more than 50% of patients remained persistent at 9 months. CONCLUSION: Patients initiated with ACL had more severe COPD and were taking more concomitant respiratory medications than patients initiated with TIO. ACL was more frequently initiated as part of triple therapy, while TIO was more frequently initiated as monotherapy.

Conjoint analysis to understand preferences of patients with multiple sclerosis for disease-modifying therapy attributes in Spain: a cross-sectional observational study.

OBJECTIVE: To assess patients' preferences for a range of disease-modifying therapy (DMT) attributes in multiple sclerosis (MS). DESIGN: A cross-sectional observational study. SETTING: The data reported were from 17 MS units throughout Spain. PARTICIPANTS: Adult patients with relapsing-remitting MS. MAIN OUTCOME: A conjoint analysis was applied to assess preferences. A total of 221 patients completed a survey with 10 hypothetical DMT profiles developed using an orthogonal design and rating preferences from 1 (most acceptable) to 10 (least acceptable). Medication attributes included preventing relapse, preventing disease progression, side effect risk, route and frequency of administration. RESULTS: Patients placed the greatest relative importance on the side effect risk domain (32.9%), followed by route of administration (26.1%), frequency of administration (22.7%), prevention of disease progression (10.0%) and prevention of relapse (8.3%). These results were independent of the Expanded Disability Status Scale score. The importance assigned to side effect risk was highest for patients with a recent diagnosis. Patients who had previously received more than one DMT gave a higher importance to relapse rate reduction than patients receiving their first DMT. CONCLUSIONS: Patient DMT preferences were mainly driven by risk minimisation, route of administration and treatment schedule. The risk-benefit spectrum of available DMT for MS is becoming increasingly complicated. Understanding which treatment characteristics are meaningful to patients may help to tailor information for them and facilitate shared decision-making in clinical practice.

Mapping CushingQoL scores onto SF-6D utility values in patients with Cushing's syndrome.

OBJECTIVES: To construct a prediction model of preference-adjusted health status (SF-6D) for Cushing's syndrome using a disease-specific health-related quality of life (HRQOL) measure (CushingQoL). METHODS: Data were obtained from the original multicenter, multinational study to validate the CushingQoL questionnaire. HRQOL was measured using the CushingQoL and the SF-36 questionnaires. SF-6D scores were calculated from responses on the SF-36. Sociodemographic and clinical data were also collected. Various predictive models were tested and the final one was selected on the basis of four criteria: explanatory power, consistency of estimated coefficients, normality of prediction errors, and parsimony. RESULTS: For the mapping analysis, data were available from 116 of the 125 patients included in the original validation study. Mean (SD) age was 45.3 (13.1) years and the sample was predominantly (83 %) female. Patients had a mean (SD) CushingQoL score of 52.9 (21.9), whereas the SF-6D (derived from SF-36) was skewed towards better health with a mean of 0.71 (median 0.74) on a scale of -0.704 to 1. Of the various models tested, a model which included the intercept (0.61), CushingQoL overall score, level one in CushingQoL item 2 (always have pain preventing me from leading a normal life), and level one in CushingQoL item 10 (my illness always affects my everyday activities) best met the four criteria for model selection. The model had an adjusted R (2) of 0.60 and a root mean square error of 0.084. CONCLUSIONS: Although the mapping function finally selected appears to be able to accurately map CushingQoL scores onto SF-6D outcomes at the group level, further testing is required to validate the model in independent patient samples.

Results of a 2-year retrospective cohort study of newly prescribed triptan users in European nationwide practice databases.

OBJECTIVE: This study was conducted to characterize prescription refill patterns for triptans among European patients with new prescriptions of triptans. BACKGROUND: Persistency with prescriptions of triptan monotherapy for migraine headache among newly prescribed users in European primary-care practices has not been well described. METHODS: Using electronic medical databases in the UK (N = 3618), France (N = 2051) and Germany (N = 954), we conducted a retrospective cohort analysis to identify refill patterns over 2 years among migraineurs receiving new prescriptions of triptan monotherapy in 2006. RESULTS: Of all patients, >33% of migraineurs with new triptan prescriptions received ≥1 refill of their index triptan prescriptions (UK, 44.3%; France, 34.2%; Germany, 37.7%). More than 50% never received index-triptan refill prescriptions (UK, 55.7%; France, 65.8%; Germany, 63.3%). Small proportions of patients (<7.0%) switched to alternative triptans, and even fewer switched to different prescription-medication classes (UK and Germany, 2.3%; France, 4.0%). More than 48% of patients received no further prescriptions for migraine after index prescriptions (UK, 48.5%; France, 54.9%; Germany, 54.7%). After the second year, >83.0% of patients in each country had no further prescriptions for migraine medications, <14.0% remained persistent with index prescriptions, <4.0% switched to other triptans, and <3.0% switched to alternative medication classes. CONCLUSIONS: In migraine patients who received new prescriptions of triptan monotherapy from their primary-care physicians, poor triptan prescription refill frequency was observed in Europe. Although consistent with potential clinical challenges in migraine management, our findings should be interpreted with caution given certain inherent limitations associated with the database study design. Further research is warranted to confirm our findings and to identify reasons for, or predictors of, triptan discontinuation.

Validation of a new tool to assess health-related quality of life in psoriasis: the PSO-LIFE questionnaire.

BACKGROUND: Several questionnaires have been used to measure health related quality of life (HRQoL) in patients with psoriasis, few have been adapted for use in Spain; none of them was developed specifically for the Spanish population. The purpose of the study was to validate and assess the sensitivity to change of a new questionnaire to measure HRQOL in patients with psoriasis (PSO-LIFE). METHODS: Observational, prospective, multicenter study performed in centers around Spain. Patients with active or inactive psoriasis completed the PSO-LIFE together with other Dermatology Quality of Life Index (DLQI) and Psoriasis Disability Index (PDI). A control group of patients with urticaria or atopic dermatitis was also included. Internal consistency and test-retest reliability of the PSO-LIFE were assessed by calculating Cronbach's alpha and Intraclass Correlation Coefficient (ICC). Validity was assessed by examining factorial structure, the capacity to discriminate between groups, and correlations with other measures. Sensitivity to change was measured using effect sizes. RESULTS: The final sample included for analysis consisted of 304 patients and 56 controls. Mean (SD) age of psoriasis patients was 45.3 (14.5) years compared to 38.8 (14) years for controls (p < 0.01). Cronbach's alpha for the PSO-LIFE was 0.95 and test-retest reliability using the ICC was 0.98. Factor analysis showed the questionnaire to be unidimensional. Mean (SD) PSO-LIFE scores differed between patients with psoriasis and controls (64.9 [22.5] vs 69.4 [17.3]; p < 0.05), between those with active and inactive disease (57.4 [20.4] vs 76.4 [20.6]; p < 0.01), and between those with visible and non-visible lesions (63.0 [21.9] vs. 74.8 [23.9]; p < 0.01). The correlation between PSO-LIFE and PASI scores was moderate (r = -0.43) while correlations with DLQI and PDI dimensions ranged from moderate to high (between 0.4 and 0.8). Effect size on the PSO-LIFE in patients reporting 'much improved' health status at study completion was 1.01 (large effect size). CONCLUSIONS: The present results provide substantial support for the reliability, validity, and responsiveness of the PSO-LIFE questionnaire in the population for which it was designed.

Cost of clinical management of acromegaly in Spain.

INTRODUCTION AND BACKGROUND: The cost of the therapeutic management of acromegaly depends on the selection of resources used, surgery and/or pharmacological treatment, by the specialist responsible for treatment, related to the characteristics of the patient and tumour. The objective of this work is to evaluate these costs for an illness that is rare but that is associated with a high morbidity in the context of routine clinical practice. METHODS: This was an epidemiological, prospective, naturalistic, multicentre study in Spain, in which 38 endocrinologists participated. Adult patients with acromegaly and a pituitary microadenoma or macroadenoma were included in the study. Patients were assigned, according to first-line treatment, to the following two groups: surgery first-line group (surgery in the 6 months before inclusion or during the follow-up period) and pharmaceutical first-line group (treatment with somatostatin analogues [SAs] for at least 6 months and with or without surgery after starting treatment with SAs). Data were collected during routine visits made during a follow-up period of 2 years. All resources were estimated at 2009 prices (€) and adjusted according to the Spanish consumer price index in 2010. RESULTS: Seventy-four patients were included, the majority of them with macroadenoma (70%). Eighty-eight percent of patients were treated surgically (76% as a first-line treatment), while 12% of patients received only SAs. Treatment with SAs was used at some point in the study by 85% of patients. The mean annual total cost of acromegaly is €9668 per patient (€9223 for the surgery group and €11,054 for the pharmaceutical group). Seventy-one percent of the direct cost of the disease corresponds to treatment with SAs. The cost of a patient treated only with surgery is €2501 on an annual basis, versus €9745 for a patient receiving only pharmacological treatment. In cases where a combination of both types of treatment is required, the annual total cost ranges from €10,866 to €12,364. CONCLUSION: The annual direct cost per patients of acromegaly in Spain is €9668. Even though surgery is the preferred option for treatment for a great number of patients, SAs must be added to the treatment regimen of the majority of such patients. The costs associated with this treatment are greater than the cost of treatment with SAs alone.

Impact of upper digestive symptoms in patients with irritable bowel syndrome.

BACKGROUND: Functional digestive disorders constitute a sizable proportion of gastroenterology and primary healthcare consultations, and have a negative impact on health-related quality of life. Dyspepsia and heartburn are often associated with irritable bowel syndrome (IBS); however, the incidence of these symptoms and their effect on IBS patients have not been evaluated. AIM: To investigate the clinical, psychological and health-related quality of life impact of upper digestive symptoms on IBS patients. METHODS: A prospective, observational, multicentered study was conducted in Spain: 517 IBS patients (Rome II criteria), grouped according to predominant symptoms of constipation (IBS-C), diarrhea (IBS-D) or alternating bowel habit (IBS-A) and 84 controls without IBS were recruited. Upper digestive symptoms were recorded in a 30-day diary. Health-related quality of life was evaluated by Irritable Bowel Syndrome Quality of Life and Euro-Quality of Life Five-Dimension Questionnaires; psychological well-being was evaluated by the Psychological General Well-Being Index. RESULTS: IBS patients had greater frequencies of upper digestive symptoms (72.3 vs. 6.0%), dyspepsia (21.1 vs. 4.8%) and heartburn (40.0 vs. 13.1%) (all P < 0.05) than controls. Prevalence of upper digestive symptoms was lower in patients with IBS-D than in those with IBS-C or IBS-A (P < 0.05). Health-related quality of life and psychological status were significantly worse in IBS patients with upper digestive symptoms than in those without. CONCLUSIONS: Upper digestive symptoms, frequently present in IBS patients, impair health-related quality of life and psychological status. This effect is greater in patients with IBS-C and IBS-A than in those with IBS-D. These data emphasize the importance of evaluating the presence of upper digestive symptoms in IBS patients.

Bayesian regression models for cost-effectiveness analysis.

Recent studies have shown how cost-effectiveness analysis can be undertaken in a regression framework. This contribution explores the use of practical regression models for estimating cost-effectiveness from a Bayesian perspective. Two different Bayesian models are described. The first considers the outcome measure to be a quantitative variable. In the second model the individual outcome measure is a binary variable with value 1 if any objective has been achieved. We describe the implementation of the model using data from a trial that compares two highly active antiretroviral therapies in HIV asymptomatic patients. Data on direct cost and data effectiveness (percentage of patients with undetectable viral load and quality of life) were recorded. If we consider the quality of life as an effectiveness measure, the new treatment is preferred for a willingness to pay more than Euro 142.3 for an increase in the quality of life. For illustrative purposes, if we compare the results with an analogous model that does not include covariates, the critical value becomes Euro 247.4. For the binary measure of effectiveness the control treatment dominates the new treatment.

Clinical patterns over time in irritable bowel syndrome: symptom instability and severity variability.

OBJECTIVES: The clinical course of irritable bowel syndrome (IBS) remains poorly known. In 209 IBS patients meeting Rome II criteria (137 females and 72 males) we evaluated: (1). changes in frequency and intensity of abdominal pain/discomfort, abnormal number of bowel movements, loose or watery stools, defecatory urgency, hard or lumpy stools, straining during bowel movements, and feeling of incomplete evacuation); (2). use of resources, HRQoL, and psychological well being. METHODS: Observational, prospective, multicenter study. Symptoms were registered in a diary over two 28-day periods with an interval of 4 wk; direct resource use and indirect costs were noted weekly. Three HRQoL questionnaires were administered. RESULTS: High-intensity symptoms were present on more than 50% of the days. Sixty-one percent were classified in the same IBS subtype on both occasions (kappa= 0.48), while 49% had the same symptom predominance and intensity (kappa= 0.40). The greatest instability was observed among diarrhea (D-IBS) and constipation (C-IBS) subtypes: only 46% and 51% remained in the same pattern with a tendency to shift to alternating diarrhea/constipation subtype (A-IBS); however, practically no patient changed from D-IBS to C-IBS, or vice versa. The most reliable symptom characteristic was frequency, followed by intensity and number of episodes. Symptom frequency and intensity were directly related to resource use and HRQoL impairment. CONCLUSIONS: IBS symptoms are instable over time and variables in intensity. Many patients with D-IBS or C-IBS move to A-IBS; however, shift from D-IBS to C-IBS, or vice versa, is very infrequent.

Splitting irritable bowel syndrome: from original Rome to Rome II criteria.

OBJECTIVES: Diagnosis of irritable bowel syndrome (IBS) and other functional bowel disorders (FBD) is based on symptom evaluation. Clinical criteria have changed over time, yielding different proportions of subjects fulfilling diagnostic requirements. According to new diagnostic criteria (Rome II), subjects considered some years ago to have IBS no longer do so. The aim of this article is to evaluate how patients diagnosed as having IBS according to original Rome criteria have been split, and to which clinical diagnosis they belong today. METHODS: Two hundred and eleven subjects meeting original Rome IBS diagnostic criteria were studied: 65 also met Rome II criteria while 146 did not. Subjects were extracted from an epidemiological survey, using home-based personal interviews, on 2000 subjects randomly selected as representative of the Spanish population. Clinical complaints, personal well-being, resource utilization, and health-related quality of life (HRQOL) were compared. RESULTS: Of the subjects meeting original Rome but not Rome II criteria, the present diagnosis should be: 40%"minor" IBS (IBS symptoms of less than 12 wk duration), 37% functional constipation, 12% alternating bowel habit, 7% functional diarrhea, 3% functional abdominal bloating, and 1% unspecified functional bowel disorder (FBD). Thus, 52 subjects (36%) should not be diagnosed with IBS because they really had other FBD, 59 (40%) because of symptoms consistent with IBD diagnosis but not the required duration or frequency, and 35 (24%) because of symptoms consistent with some other FBD diagnosis but not meeting the required duration. Clinical complaints, personal well-being, resource utilization, and HRQOL were more severely affected in IBS than in other FBD as a group, and in "major" rather than in "minor" forms. CONCLUSIONS: Many subjects meeting original Rome criteria for IBS do not meet Rome II criteria: approximately one quarter of subjects do not have sufficient symptom duration or frequency to be diagnosed with IBS and almost half are now considered as having other ("major" or "minor") FBD.

Health-related quality of life in HIV patients switching to twice-daily indinavir/ritonavir regimen or continuing with three-times-daily indinavir-based therapy.

OBJECTIVE: To evaluate health-related quality of life (HRQoL) changes in patients treated with indinavir three-times daily after switching to a twice-daily indinavir/ritonavir regimen or continuing with the same regimen. METHODS: Patients on HAART including indinavir three-times-daily with undetectable viral load were randomly assigned to continue with this therapy or to change to a twice-daily indinavir/ritonavir (800/100 mg) regimen. The Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire was used as the HRQoL measure. RESULTS: A total of 118 patients participated in the study, of which 59 (50%) were randomly assigned to continue with the three-times-daily regimen. Patients had a mean age of 39 years and 80% of them were male. At baseline, subjects included in the three-times-daily group presented a significantly greater number of symptoms than subjects in the twice-daily group, but no statistically significant differences were observed in MOS-HIV scores between the groups. In the intention-to-treat (ITT) analysis, a reduction in HRQoL scores was observed in both groups, which was greater in the twice-daily group. In the per protocol analysis, reduction of HRQoL was minimal. CONCLUSIONS: A HRQoL deterioration, greater in the twice-daily group, was observed in this study in the ITT analysis, while HRQoL remained stable in both groups in patients who continued with and tolerated the allocated regimen.

Irritable bowel syndrome subtypes according to bowel habit: revisiting the alternating subtype.

BACKGROUND: Disturbed bowel habit, diarrhoea or constipation is a key manifestation of irritable bowel syndrome (IBS). In some patients, diarrhoea and constipation alternate, giving rise to the so-called alternating subtype. AIMS: To assess IBS subtype breakdown (constipation (C-IBS), diarrhoea (D-IBS) or alternating (A-IBS)) according to the Rome II criteria and patients' self-assessment, the predominance in the alternating subtype (i.e. constipation, diarrhoea or neither), and the medical and personal impact, including health-related quality of life (HRQoL), of the different IBS subtypes. SUBJECTS AND METHODS: Two thousand individuals selected randomly to represent the general population were classified as potential IBS subjects (n = 281) or as non-potential IBS subjects (n = 1719) according to a validated questionnaire. Bowel habit classification was determined using the Rome II IBS supportive symptoms. RESULTS: Among 201 subjects meeting the Rome I criteria, 15% presented with D-IBS, 44% presented with C-IBS, 19% presented with A-IBS, and 22% presented with normal bowel habit. Among the 63 subjects meeting the Rome II criteria, 23% presented with A-IBS. According to the subjects' self-assessment, of those meeting the Rome I criteria, 16% considered themselves to have D-IBS, 66% to have C-IBS and 18% to have A-IBS. In subjects meeting the Rome II criteria, 24% considered themselves to have A-IBS. Among those classified with A-IBS by the Rome II criteria, most considered themselves to be constipated. Regardless of the subtype self-classification, most subjects reported a normal frequency of bowel movements. Clinical manifestations in A-IBS were very similar to those of C-IBS but with the added presence of defecatory urgency. Abdominal discomfort/pain and frequency of visits to physicians were greater in the A-IBS subtype than in the other two IBS subtypes. HRQoL was affected similarly in all IBS subtypes. CONCLUSIONS: Approximately one-quarter of subjects with IBS belong to the A-IBS subtype by the Rome II criteria, although the majority consider themselves to be constipated; indeed, clinical manifestations are more akin to the C-IBS subtype than to the D-IBS subtype. Abdominal discomfort/pain and frequency of visits to physicians are greater in the A-IBS subtype than in the other two IBS subtypes, while HRQoL is impaired similarly.