Identification of the most relevant aspects of spinal muscular atrophy (SMA) with impact on the quality of life of SMA patients and their caregivers: the PROfuture project, a qualitative study.

BACKGROUND: SMA is a hereditary neuromuscular disease that causes progressive muscle weakness and atrophy. Several studies have shown that the burden of SMA is very high at many levels. Functional assessment tools currently used do not completely address the impact of the disease in patients' life. The objective of this qualitative study was to identify aspects of SMA that are relevant to patients and to design items useful for assessment purposes. RESULTS: Five focus group sessions were run during an annual SMA families meeting in Madrid, Spain. Focus groups were composed by parents of SMA type I children, sitter children type II-III, parents of sitter children type II-III, adult patients, and parents of walker children. Two trained facilitators conducted the focus groups using a semi-structured guideline to cover previously agreed topics based on the input of a Scientific and Patient Advisory Committee. The guideline was adapted for the different groups. According to what was communicated by participants, SMA entails a high burden of disease for both patients and their parents. Burden was perceived in physical, psychological, and social areas. Patient's physical domain was the most relevant for participants, especially for parents of non-ambulant children, followed by limitations of motor scales to capture all changes, parents psychological burden, treatment expectations and patient's psychological burden. Ten domains were the main areas identified as impacted by the disease: mobility and independence, fatigue and fatigability, infections and hospital consultations, scoliosis and contractures, vulnerability, pain, feeding, time spent in care, breathing, and sleep and rest. CONCLUSIONS: This study confirms the necessity of evaluating other aspects of the disease that are not assessed in the functional motor scale. Measures of other aspects of the disease, such as pain, fatigue, feeding, should be also considered. A patient-reported outcomes instrument measuring such aspects in a valid and reliable way would be very useful. This study generated a list of new items relevant to be systematically measured in the assessment of the impact of SMA on the patients' everyday life.

Preferences for neuromyelitis optica spectrum disorder treatments: A conjoint analysis with neurologists in Spain.

BACKGROUND: The treatment landscape for neuromyelitis optica spectrum disorder (NMOSD) has changed in recent years with the approval of therapies with different efficacy, safety and administration profiles. OBJECTIVE: The aim of this study was to assess neurologists' preferences for different NMOSD treatment attributes using conjoint analysis (CA). METHODS: We conducted an online, non-interventional, cross-sectional study in collaboration with the Spanish Society of Neurology. Our CA assessed five drugs' attributes: prevention of relapse, prevention of disability accumulation, safety risk, management during pregnancy, and route and frequency of administration. Participants were presented with eight hypothetical treatment scenarios to rank based on their preferences from the most preferred to the least. An ordinary least squares method was selected to estimate weighted preferences. RESULTS: A total of 104 neurologists were included. Mean age (standard deviation-SD) was 37.7 (10.3) years, 52.9 % were male, and median time (interquartile range) of experience managing NMOSD was 5.0 (2.9, 10.8) years. Neurologists placed the greatest importance on efficacy attributes, time to relapse (44.1 %) being the most important, followed by preventing disability accumulation (36.8 %). In contrast, route and frequency of administration (4.6 %) was the least important characteristic. Participants who prioritised efficacy attributes felt more comfortable in decision-making, had fewer past experiences of care-related regret and a lower attitude to risk taking than their counterparts. CONCLUSION: Neurologists' treatment preferences in NMOSD were mainly driven by efficacy attributes. These results may be useful to design policy decisions and treatment guidelines for this condition.

Therapeutic inertia in the management of neuromyelitis optica spectrum disorder.

Introduction and objective: Limited information is available on how neurologists make therapeutic decisions in neuromyelitis optica spectrum disorder (NMOSD), especially when new treatments with different mechanisms of action, administration, and safety profile are being approved. Decision-making can be complex under this uncertainty and may lead to therapeutic inertia (TI), which refers to lack of treatment initiation or intensification when therapeutic goals are not met. The study aim was to assess neurologists' TI in NMOSD. Methods: An online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists answered a survey composed of demographic characteristics, professional background, and behavioral traits. TI was defined as the lack of initiation or intensification with high-efficacy treatments when there is evidence of disease activity and was assessed through five NMOSD aquaporin-4 positive (AQP4+) simulated case scenarios. A multivariate logistic regression analysis was used to determine the association between neurologists' characteristics and TI. Results: A total of 78 neurologists were included (median interquartile range [IQR] age: 36.0 [29.0-46.0] years, 55.1% male, median [IQR] experience managing demyelinating conditions was 5.2 [3.0-11.1] years). The majority of participants were general neurologists (59.0%) attending a median (IQR) of 5.0 NMOSD patients (3.0-12.0) annually. Thirty participants (38.5%) were classified as having TI. Working in a low complexity hospital and giving high importance to patient's tolerability/safety when choosing a treatment were predictors of TI. Conclusion: TI is a common phenomenon among neurologists managing NMOSD AQP4+. Identifying TI and implementing specific intervention strategies may be critical to improving therapeutic decisions and patient care.

Design and Validation of a Clinical Outcome Measure for Adolescents and Adult Patients with Spinal Muscular Atrophy: SMA Life Study Protocol.

INTRODUCTION: The objective of this study is to develop a clinical tool for the evaluation and follow-up of adolescent and adult patients with 5q spinal muscular atrophy (SMA) and to design its validation. METHODS: This prospective, non-interventional study will be carried out at five centres in Spain and will include patients aged 16 years or older with a confirmed diagnosis of 5q SMA (biallelic mutation of the survival motor neuron 1 [SMN1] gene). A panel of experts made up of neurologists, physiatrists and Spanish patients' association (FundAME), participated in the design of the clinical tool. Physicians will administer the tool at three time points (baseline, 12 months and 24 months). Additionally, data from other questionnaires and scales will be collected. Once recruitment is achieved, an interim statistical analysis will be performed to assess its psychometric properties by applying Rasch analysis and classical statistical tests. RESULTS: The tool will consist of up to 53 items to assess functional status from a clinical perspective in seven key dimensions (bulbar, respiratory, axial, lower, upper, fatigability and other symptoms), which will be collected together with objective clinical measures (body mass index, forced vital capacity, pinch strength and 6-minute walk test). CONCLUSIONS: The validation of this tool will facilitate the clinical evaluation of adult and adolescent patients with SMA and the quantification of their response to new treatments in both clinical practice and research.

Attitudes of Neurologists Toward the Use of Biomarkers in the Diagnosis of Early Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) biomarkers reflect key elements of pathophysiology and improve the diagnostic process. However, their use in routine clinical practice is still limited. OBJECTIVE: We aimed to assess neurologists' barriers and enablers to early AD diagnosis using core AD biomarkers. METHODS: We conducted an online study in collaboration with the Spanish Society of Neurology. Neurologists answered a survey exploring their attitudes towards AD diagnosis using biomarkers in mild cognitive impairment (MCI) or mild AD dementia. Multivariate logistic regression analyses were conducted to determine the association between neurologists' characteristics and diagnostic attitudes. RESULTS: We included 188 neurologists with a mean age (SD) of 40.6 (11.3) years, 52.7% male. Most participants had access to AD biomarkers, mainly in cerebrospinal fluid (CSF) (89.9%,#x0025;, n = 169). The majority of participants (95.2%,#x0025;, n = 179) considered CSF biomarkers useful for an etiological diagnosis in MCI. However, 85.6% of respondents (n = 161) used them in less than 60% of their MCI patients in routine clinical practice. Facilitating patients and their families to plan for the future was the most frequent enabler for the use of biomarkers. Short consultation time and practicalities associated with the programming of a lumbar puncture were the most common barriers. A younger neurologist age (p = 0.010) and a higher number of patients managed weekly (p = 0.036) were positively associated with the use of biomarkers. CONCLUSION: Most neurologists had a favorable attitude to the use of biomarkers, especially in MCI patients. Improvements in resources and consultation time may increase their use in routine clinical practice.

Geographical differences in the use of oral corticosteroids in patients with severe asthma in Spain: heat map based on existing databases analyses.

BACKGROUND: Although there are currently alternative treatments to the long-term use of oral corticosteroids (OCS) in severe asthma, recent studies show excessive use depending on geography and differences in medical practice. The objective of the study was to describe the differences in OCS use for severe asthma across the Spanish geography. METHODS: This is a real-world study using existing databases (year 2019): longitudinal patient database (EMR), based on electronic medical records, and database of pharmacological consumption (Sell-in) in basic healthcare areas. With EMR, the percentage of OCS prescriptions corresponding to patients with severe asthma (ICD-9 "asthma" and prescription of biological treatment and/or high dose of inhaled corticosteroids/long-acting inhaled ß2 agonists) was calculated. This percentage was transferred to the OCS consumption of each basic healthcare area as reported in the Sell-in database and a national heat map was created. The estimation of OCS use in patients with severe asthma per 100,000 inhabitants for each region was calculated by grouping basic healthcare areas and the mean OCS use per patient for different regions in Spain was also estimated. RESULTS: Patients with severe asthma in Spain were mostly female (69.6%), with a mean age (SD) of 57.6 years (18.01). Median time (Pc25-Pc75) since asthma diagnosis was 83.1 months (34.65-131.56). Of all patients with OCS prescriptions in 2019 identified in EMR, 4.4% corresponded to patients with severe asthma. Regions with the highest OCS use were Asturias, Andalucía, and Galicia, whereas those with the lowest use were Navarra, Baleares, Madrid and País Vasco. The mean OCS use per patient with severe asthma in 2019 throughout Spain was 1099.85 mg per patient, ranging from 782.99 mg in Navarra to 1432.64 in Asturias. CONCLUSIONS: There are geographical differences between Spanish regions with respect to the use of OCS in patients with severe asthma. The national mean consumption of OCS per patient with severe asthma and year is above the limits that indicate good asthma control.

Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study.

INTRODUCTION: Outcome measures traditionally used in spinal muscular atrophy (SMA) clinical trials are inadequate to assess the full range of disease severity. The aim of this study was to assess the psychometric properties of a set of existing questionnaires and new items, gathering information on the impact of SMA from the patient and caregiver perspectives. METHODS: This was a multicenter, prospective, noninterventional study including patients with a confirmed diagnosis of 5q-autosomal-recessive SMA aged 8 years and above, or their parents (if aged between 2 and 8 years). The set of outcome measurements included the SMA Independence Scale (SMAIS) patient and caregiver versions, the Neuro-QoL Fatigue Computer Adaptive Test (CAT), the Neuro-QoL Pain Short Form-Pediatric Pain, the PROMIS adult Pain Interference CAT, and new items developed by Fundación Atrofia Muscular España: perceived fatigability, breathing and voice, sleep and rest, and vulnerability. Reliability, construct validity, discriminant validity, and sensitivity to change (4 months from baseline) were measured. RESULTS: A total of 113 patients were included (59.3% 2-17 years old, 59.3% male, and 50.4% with SMA type II). Patients required moderate assistance [mean patient and caregiver SMAIS (SD) scores were 31.1 (12.8) and 7.6 (11.1), respectively]. Perceived fatigability was the most impacted domain, followed by vulnerability. Cronbach's alpha coefficient for perceived fatigability, breathing and voice, and vulnerability total scores were 0.92, 0.88, and 0.85, respectively. The exploratory factor analysis identified the main factors considered in the design, except in the sleep and rest domain. All questionnaires were able to discriminate between the Clinical Global Impression-Severity scores and SMA types. Sensitivity to change was only found for the SMAIS caregiver version and vulnerability items. CONCLUSIONS: This set of outcome measures showed adequate reliability, construct validity, and discriminant validity and may constitute a valuable option to measure symptom severity in patients with SMA.

Epidemiology of atrial fibrillation-related ischemic stroke and its association with DOAC uptake in Spain: first national population-based study 2005 to 2018.

INTRODUCTION AND OBJECTIVES: The incidence and prevalence of atrial fibrillation (AF), a major risk factor for stroke, has increased substantially in the past few years. However, several studies have reported a decline in AF-related stroke rates associated with higher uptake of direct oral anticoagulants (DOACs). This ecological study evaluated the association between DOAC uptake in Spain and the incidence rate (IR) of AF-related ischemic stroke. METHODS: Data were obtained from the Registry of Activity of Specialized Healthcare of the Spanish Ministry of Health (RAE-MDS). AF-related ischemic strokes were identified using International Classification of Diseases codes. IR were age-standardized and adjusted to the 2013 European standard population. Poisson regression models were used to identify the association between DOAC uptake and AF-related ischemic stroke in patients aged ≥ 65 years. RESULTS: Before the use of DOACs, the adjusted IR of AF-related ischemic stroke increased steadily from 2005 (IR=2.20 per 100 000 person/y) to 2012 (IR=2.67). Upon DOAC uptake in Spain from 2012 onwards for AF-related ischemic stroke prevention, the IR remained constant or decreased slightly (IR in 2018=2.66). Poisson regression showed that DOAC uptake was a significant predictor for the rate of AF-related ischemic stroke in patients older than 65 years (IRR=0.995; 95%CI, 0.995-0.996). CONCLUSIONS: This study shows an association between DOAC use and a reduced incidence of AF-related ischemic stroke. While this association is based on aggregate data and cannot demonstrate causality, these findings suggest that higher DOAC uptake could improve health outcomes in AF patients in Spain.

Unmet Needs in the Osteoarthritis Chronic Moderate to Severe Pain Management in Spain: A Real Word Data Study.

INTRODUCTION: Patients with moderate or severe pain due to osteoarthritis (OAP) usually undergo pharmacological treatment with NSAIDs and/or opioids. Many of them do not get adequate pain relief because of intolerances, contraindications and the ineffectiveness of these treatments. The main objective of the present study was to quantify the group of OAP patients who are inadequately treated for their pain in routine clinical practice in Spain and to describe the prescription flow of these patients. METHODS: This was a non-interventional, retrospective cohort study conducted using the IQVIA's electronic medical records database in Spain. Patients with osteoarthritis (OA), aged ≥ 15 years and receiving any pain treatment during 12 out of 24 months between 1 October 2017 and 30 September 2019 were studied. Assumptions were made to identify patients with contraindication or intolerance to NSAIDs or opioids and those who failed NSAID or opioid therapy. RESULTS: Out of 136,556 patients with OA, 29,886 had moderate-to-severe pain, which extrapolated to the general population in Spain represents 1,541,286 OAP patients. Mean age (SD) of OAP patients was 75 (12.8) years, and 73.8% were female; 52.8% were treated with NSAIDs and/or weak opioids. There were were 16,748 OAP patients (56.08%) (extrapolated figure 838,620) with one or more conditions associated with being inadequately treated (contraindication, intolerance or failed NSAID and/or opioid therapy). In most OAP patients (91%) pain treatment was initiated by the general practitioner (GP) alone. Considering overall successive therapy lines, after the first prescription, pain drugs were prescribed by a GP in 61% of the cases, by a specialist in 20% and by both in 18%. CONCLUSION: More than half of the patients with OA in Spain have unsatisfactory pain control. Pain drugs are mainly prescribed by GPs, and specialists (traumatologists, rheumatologists, physiatrists and pain management specialists) are not very involved in the management of OAP patients.

Design of a Non-Interventional Study to Validate a Set of Patient- and Caregiver-Oriented Measurements to Assess Health Outcomes in Spinal Muscular Atrophy (SMA-TOOL Study).

INTRODUCTION: There is a need to optimize the current clinical outcome measures in spinal muscular atrophy (SMA) incorporating patients' and caregivers' perspectives. The aim of this study is to evaluate the psychometric properties (validity, reliability and sensitivity to change) of a set of existing questionnaires and newly created items grouped in a "toolbox" to assess the impact of SMA on the physical, psychological and activities of daily living domains of the patient's life. METHODS: This non-interventional, prospective study will be conducted at 12 neuromuscular clinics specialized in the management of patients with SMA in Spain. An expert panel of pediatric and adult neurologists, rehabilitation physicians, and a patient representative participated in the study design and selected key disease dimensions to explore and their respective measurements: mobility-independence, fatigue and endurance, pain, fatigability, breathing and voice, sleep and rest, and vulnerability. Patients aged 2 years or older with a confirmed diagnosis of 5q-autosomal recessive SMA (genetic confirmation of homozygous deletion or heterozygosity predictive of loss of function of the SMN1 gene) will be recruited. PLANNED OUTCOMES: The development of robust outcome measures in collaboration with the patient community is essential to determine what is meaningful to patients and their caregivers. This study will provide us with a comprehensive set of tools to better capture the course of the disease and the response to treatments.

The cost-effectiveness of isavuconazole compared to voriconazole, the standard of care in the treatment of patients with invasive mould diseases, prior to differential pathogen diagnosis in Spain.

BACKGROUND: Invasive mould diseases are associated with high morbidity, mortality and economic impact. Its treatment is often started prior to differential pathogen diagnosis. Isavuconazole is approved for treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM) when amphotericin-B is not indicated. OBJECTIVES: To estimate the cost-effectiveness of isavuconazole vs voriconazole for the treatment of adult patients with possible IA prior to differential pathogen diagnosis, in Spain. METHODS: A decision tree analysis was performed using the Spanish Healthcare System perspective. Among all patients with possible IA, it was considered that 7.81% actually had IM. Costs for laboratory analysis, management of adverse events, hospitalisation and drugs per patient, deaths and long-term effects in life years (LYs) and quality-adjusted LYs (QALYs) were considered. Efficacy data were obtained from clinical trials and utilities from the literature. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: In patients with possible IA and when compared to voricanozole, isavuconazole showed an incremental cost of 4758.53€, besides an incremental effectiveness of +0.49 LYs and +0.41 QALYs per patient. The Incremental Cost Effectiveness Ratio was 9622.52€ per LY gained and 11,734.79€ per QALY gained. The higher cost of isavuconazole was due to drug acquisition. Main parameters influencing results were mortality, treatment duration and hospitalisation days. The PSA results showed that isavuconazole has a probability of being cost-effective of 67.34%, being dominant in 24.00% of cases. CONCLUSIONS: Isavuconazole is a cost-effective treatment compared to voriconazole for patients with possible IA for a willingness to pay threshold of 25,000€ per additional QALY.

Spanish validation of a specific measure to assess work-related problems in people with multiple sclerosis: The Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23).

INTRODUCTION: Unemployment is a significant problem for people with multiple sclerosis (MS). The MS Work Difficulties Questionnaire (MSWDQ-23) is a self-report tool to assess work-related problems in people with MS across three domains: physical, psychological/cognitive, and external barriers. The aim of this study was to assess the psychometric properties of the Spanish version of the MSWDQ-23. METHODS: A multicentre, non-interventional, cross-sectional study in adult patients with relapsing-remitting multiple sclerosis (RRMS) or primary progressive (PPMS) multiple sclerosis (McDonald 2010 criteria) was conducted. Socio-demographic and clinical characteristics as well as health-related quality of life using the 29-item Multiple Sclerosis Impact Scale (MSIS-29) were collected. RESULTS: A total of 201 subjects were studied (mean age: 43.9 years, 60% female, 86% with RRMS). Median Expanded Disability Status Scale (EDSS) (score: 2.0 [IQR: 1.0-3.5]). The employment rate was 47.3% (n = 95). The MSWDQ-23 was feasible (90% response rate), with high internal consistency and test-retest reliability (Cronbach's alpha = 0.94 and intraclass correlation coefficient-ICC > 0.87). MSWDQ-23 scores significantly and positively correlated with EDSS and both MSIS-29 physical and psychological subscales scores, showing an adequate convergent validity. Regarding construct validity, scores of patients with PPMS were higher than those of patients with RRMS, reaching statistically significance in MSWDQ-23 physical barriers domain and total scores. CONCLUSION: The Spanish version of the MSWDQ-23 shows appropriate feasibility, reliability, and discriminative performance as a patient-reported outcome. MSWDQ-23 may be a valuable addition to measure the impact of a comprehensive spectrum of difficulties experienced by people with MS in the workplace.

Beliefs, Barriers, and Preferences of European Overweight Women to Adopt a Healthier Lifestyle in Pregnancy to Minimize Risk of Developing Gestational Diabetes Mellitus: An Explorative Study.

INTRODUCTION: We explored beliefs, perceived barriers, and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future lifestyle interventions in the prevention of gestational diabetes mellitus. METHODS: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI ≥ 25 kg/m2). In three European countries 21 interviews were conducted, followed by 71 questionnaires in six other European countries. Content analysis and descriptive and chi-square statistics were applied (p < 0.05). RESULTS: Women preferred to obtain detailed information about their personal risk. The health of their baby was a major motivating factor. Perceived barriers for physical activity included pregnancy-specific issues such as tiredness and experiencing physical complaints. Insufficient time was a barrier more frequently reported by women with children. Abstaining from snacking was identified as a challenge for the majority of women, especially for those without children. Women preferred to obtain support from their partner, as well as health professionals and valued flexible lifestyle programs. CONCLUSIONS: Healthcare professionals need to inform overweight pregnant women about their personal risk, discuss lifestyle modification, and assist in weight management. Lifestyle programs should be tailored to the individual, taking into account barriers experienced by overweight first-time mothers and multipara women.

Physical activity, depressed mood and pregnancy worries in European obese pregnant women: results from the DALI study.

BACKGROUND: The purpose of this study was to examine the association between mental health status (i.e. depressed mood and pregnancy-related worries) and objectively measured physical activity levels in obese pregnant women from seven European countries. METHODS: Baseline data from the vitamin D and lifestyle intervention for the prevention of gestational diabetes mellitus (DALI) study were used. Time spent in moderate-to-vigorous physical activity (MVPA) and sedentary behaviour was measured with accelerometers. Depressed mood was measured with the WHO well-being index (WHO-5) and pregnancy-related worries with the Cambridge Worry Scale (CWS). In addition, socio-demographic characteristics, lifestyle factors, and perceptions and attitude regarding weight management and physical activity were measured. Linear regression analyses were performed to assess the association of mental health status with MVPA and sedentary behaviour. RESULTS: A total of 98 obese pregnant women from Austria, Belgium, Ireland, Italy, Poland, Spain and the Netherlands were included. Women had a mean age of 31.6 ± 5.8 years, a pre-pregnancy BMI of 34.1 ± 4.3 kg/m(2), and were on average 15.4 ± 2.8 weeks pregnant. WHO-5 scores indicative of depressed mood (<50) were reported by 27.1 % of the women and most frequently endorsed pregnancy-related worries pertained to own and the baby's health. Women with good well-being spent 85% more time in MVPA compared to women with a depressed mood (P = 0.03). No differences in MVPA levels were found for women with no, some, or many pregnancy worries. Depressed mood and pregnancy-related worries were not associated with sedentary behaviour. CONCLUSIONS: These findings suggest that in pregnant women who are obese, a depressed mood, but not pregnancy-related worries, may be associated with less physical activity. The combined risk of poor mental health and low physical activity levels makes women vulnerable for pregnancy complications. Whether a depressed mood may be a barrier for improving physical activity warrants further study.

Results From a European Multicenter Randomized Trial of Physical Activity and/or Healthy Eating to Reduce the Risk of Gestational Diabetes Mellitus: The DALI Lifestyle Pilot.

OBJECTIVE: Ways to prevent gestational diabetes mellitus (GDM) remain unproven. We compared the impact of three lifestyle interventions (healthy eating [HE], physical activity [PA], and both HE and PA [HE+PA]) on GDM risk in a pilot multicenter randomized trial. RESEARCH DESIGN AND METHODS: Pregnant women at risk for GDM (BMI ≥29 kg/m2) from nine European countries were invited to undertake a 75-g oral glucose tolerance test before 20 weeks' gestation. Those without GDM were randomized to HE, PA, or HE+PA. Women received five face-to-face and four optional telephone coaching sessions, based on the principles of motivational interviewing. A gestational weight gain (GWG) <5 kg was targeted. Coaches received standardized training and an intervention toolkit. Primary outcome measures were GWG, fasting glucose, and insulin sensitivity (HOMA) at 35-37 weeks. RESULTS: Among the 150 trial participants, 32% developed GDM by 35-37 weeks and 20% achieved GWG <5 kg. HE women had less GWG (-2.6 kg [95% CI -4.9, -0.2]; P = 0.03) and lower fasting glucose (-0.3 mmol/L [-0.4, -0.1]; P = 0.01) than those in the PA group at 24-28 weeks. HOMA was comparable. No significant differences between HE+PA and the other groups were observed. CONCLUSIONS: An antenatal HE intervention is associated with less GWG and lower fasting glucose compared with PA alone. These findings require a larger trial for confirmation but support the use of early HE interventions in obese pregnant women.

The 3-day bladder diary is a feasible, reliable and valid tool to evaluate the lower urinary tract symptoms in women.

AIMS: To evaluate the feasibility (% of completion), reliability (test-retest and inter-observer) and validity (convergent vs. questionnaires and vs. urodynamic study-UDS) of the 3-day bladder diary (3dBD) in women with lower urinary tract symptoms (LUTS). METHODS: Epidemiological, descriptive, cross-sectional and prospective study. Fourteen Functional Urology and Urodynamic Units participated. One hundred thirty-six women with mean age (SD) 55.2 (13.8) years with LUTS, without bladder catheterization and who were able to fill in the 3dBD were included. An UDS was performed. They filled in the 3dBD in two times separated by 15 days (test and retest), the International Consultation on Incontinence-Short Form (ICIQ-UI SF) and the Bladder Control Self-Assessment Questionnaire (BSAQ). RESULTS: One hundred ten women completed 3dBD for test and retest. Feasibility: each 3dBD has 42 variables, 77.2% women completed 80%. Test-retest reliability: there were not differences in the proportion of patients classified as positive for each symptom (urgency: P = 0.3173; incontinence: P = 1; nocturia: P = 0.0522; frequency: P = 0.4386). The Intraclass Correlation Coefficient (ICC) ranged from 0.67 to 0.92, except for night time VVmax which was lower (0.54). Inter-observer reliability: ICC ranged from 0.64 to 0.99, except for day time VVmax (0.29) and the number of urgency episodes (0.45). VALIDITY: Spearman correlation coefficients for ICIQ-UI SF and BSAQ ranged from 0.4 to 0.6 (P < 0.0001) and for UDS were lower (P < 0.05). CONCLUSIONS: The 3dBD showed good feasibility, reliability and validity to be used in the assessment of LUTS in women.

New oral anticoagulants vs vitamin K antagonists: benefits for health-related quality of life in patients with atrial fibrillation.

New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL.

Pelvic floor symptoms and severity of pelvic organ prolapse in women seeking care for pelvic floor problems.

OBJECTIVE: The aim of the study was to estimate whether POP severity is related to lower urinary tract symptoms (LUTS) and symptoms of sexual difficulties, when evaluated with validated questionnaires. STUDY DESIGN: Multicentric cross-sectional study of 521 women seeking care for PFD in 35 specialized urogynecological clinics. Patients answered the EPIQ to detect symptoms of PFD. The severity of urinary incontinence and the OAB symptoms were measured by ICIQ-UI SF and BSAQ. POP anatomic severity was measured by the anatomic stage of each compartment, determined in pelvic examination in accordance with the IUGA-ICS terminology. A maximum POP stage (M-POP-S) was assigned to each patient: Group A, patients with no POP (stage 0-I); group B, M-POP-S stage II; and group C, M-POP-S stage III-IV. RESULTS: Pelvic examination demonstrated anatomic POP in 224 patients (stage from II to IV). 288 women (56.25%) were classified in group A (no prolapse); 102 (19.92%) group B (stage II); and 122 (28.83%) group C (stage III-IV). Several associations were found between studied variables and M-POP-S (age<55 years, menopause, number of vaginal deliveries, symptom of vaginal bulge, feeling of a bulge makes it difficult to have sexual relations, symptoms of stress urinary incontinence, nocturia and voiding difficulties), but the only variables independently associated were age, symptom of vaginal bulge and difficulty in having sexual relations due to feeling of a bulge. CONCLUSIONS: In patients seeking care for PFD, LUTS are not independently associated to the prolapse stage.

Assessing quality of life in patients with prostate cancer: a systematic and standardized comparison of available instruments.

PURPOSE: The objective was to obtain a standardized evaluation of available prostate cancer-specific quality of life instruments used in patients with early-stage disease. METHODS: We carried out systematic literature reviews in the PubMed database to identify manuscripts which contained information regarding either the development process or metric properties of prostate cancer-specific quality of life instruments. Each instrument was evaluated by two experts, independently, using the Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool. An overall and seven attribute-specific EMPRO scores were calculated (range 0-100, worst to best): measurement model, reliability, validity, responsiveness, interpretability, burden and alternative forms. RESULTS: Eight instruments and 57 manuscripts (2-15 per instrument) were identified. The Expanded Prostate Cancer Index Composite (EPIC) was the best rated (overall EMPRO score 83.1 points). Good results were also obtained by University of California Los Angeles-Prostate Cancer Index (UCLA-PCI), Patient-Oriented Prostate Utility Scale (PORPUS) and Prostate Cancer Quality of Life Instrument (PC-QoL) with 77.3, 70.5 and 64.8 points, respectively. These four instruments passed with distinction the validity and responsiveness evaluation. Insufficient reliability results were observed for UCLA-PCI and PORPUS. CONCLUSIONS: Current evidence supports the choice of EPIC, PORPUS or PC-QoL. Attribute-specific EMPRO results facilitate selecting the adequate instrument for every purpose. For longitudinal studies or clinical trials, where responsiveness is the priority, EPIC or PC-QoL should be considered. We recommend the PORPUS for economic evaluations because it allows cost-utility analysis, and EPIC short versions to minimize administration burden.

DALI: Vitamin D and lifestyle intervention for gestational diabetes mellitus (GDM) prevention: an European multicentre, randomised trial - study protocol.

BACKGROUND: Gestational diabetes mellitus (GDM) is an increasing problem world-wide. Lifestyle interventions and/or vitamin D supplementation might help prevent GDM in some women. METHODS/DESIGN: Pregnant women at risk of GDM (BMI ≥ 29 (kg/m(2))) from 9 European countries will be invited to participate and consent obtained before 19+6 weeks of gestation. After giving informed consent, women without GDM will be included (based on IADPSG criteria: fasting glucose<5.1 mmol; 1 hour glucose <10.0 mmol; 2 hour glucose <8.5 mmol) and randomized to one of the 8 intervention arms using a 2 × (2 × 2) factorial design: (1) healthy eating (HE), 2) physical activity (PA), 3) HE+PA, 4) control, 5) HE+PA+vitamin D, 6) HE+PA+placebo, 7) vitamin D alone, 8) placebo alone), pre-stratified for each site. In total, 880 women will be included with 110 women allocated to each arm. Between entry and 35 weeks of gestation, women allocated to a lifestyle intervention will receive 5 face-to-face, and 4 telephone coaching sessions, based on the principles of motivational interviewing. The lifestyle intervention includes a discussion about the risks of GDM, a weight gain target <5 kg and either 7 healthy eating 'messages' and/or 5 physical activity 'messages' depending on randomization. Fidelity is monitored by the use of a personal digital assistance (PDA) system. Participants randomized to the vitamin D intervention receive either 1600 IU vitamin D or placebo for daily intake until delivery. Data is collected at baseline measurement, at 24-28 weeks, 35-37 weeks of gestation and after delivery. Primary outcome measures are gestational weight gain, fasting glucose and insulin sensitivity, with a range of obstetric secondary outcome measures including birth weight. DISCUSSION: DALI is a unique Europe-wide randomised controlled trial, which will gain insight into preventive measures against the development of GDM in overweight and obese women. TRIAL REGISTRATION: ISRCTN70595832.