Incidence and management of patients with methotrexate delayed elimination in the clinical practice: A Delphi study.

INTRODUCTION: High-dose methotrexate (HDMTX) is administered for the treatment of some cancers. HDMTX is usually safe but may crystallize in renal tubules causing acute kidney injury (AKI). Consequently, MTX elimination is delayed, resulting in a severe and life-threatening condition. No studies have been published about the impact of MTX toxicity in Spain. This study aims to estimate the incidence and management of MTX delayed elimination and toxicity. METHODS: A two-round Delphi study was performed to reach consensus between 10 medical experts on haemato-oncology and paediatric oncology with experience in the management of HDMTX treated patients from leading Spanish hospitals. An online questionnaire was developed based on national and international guidelines and previous evidence regarding HDMTX-related toxicity. Consensus was established at 80% agreement. Median and interquartile ranges were calculated, and incidence data were extrapolated to the Spanish general population. RESULTS: Out of 1.475 patients estimated to receive HDMTX treatment annually in Spain, 27.5% present MTX delayed elimination and 11.6% develop HDMTX-induced AKI (35.4% with severe systemic toxicities (>grade 3) and 18.8% develop chronic renal disease). Mortality is estimated in 4.2%. Immuno-enzymatic assay is used in most of the hospitals (90%) for MTX serum level monitoring. All experts use increased supportive care and high leucovorin as first-line treatment. Available treatments in experts' hospitals in case toxicity persists are haemodialysis (90% of hospitals), glucarpidase (60%) and hemofiltration (50%). Most prevalent non-renal systemic toxicities are haematologic and mucositis (21-40% of patients). Patients with HDMTX-induced AKI require from intensive care (5% of patients), more than 3 sessions and 4 days of dialysis, and about 8.5 days of hospitalization (non-ICU patients) and 12 days in case of patients requiring ICU. CONCLUSIONS: These results are the first evidence regarding HDMTX-induced AKI in Spain. Incidence and mortality results are in line with previous studies. Clinical management is based on preventive measures and the treatment depend on the availability in the hospital. The need for effective, safe and rapid treatment for the reduction of MTX toxic levels and the improvement of monitoring methods were noted by experts as urgent needs. Further observational studies to validate these results would be needed.

Feasibility study to characterize price and reimbursement decision-making criteria for the inclusion of new drugs in the Spanish National Health System: the cefiderocol example.

OBJECTIVES: The reimbursement of medicines by the Spanish National Health System (NHS) is based on a set of criteria included in the Royal Legislative Decree 1/2015 (RDL 1/2015). The Interministerial Committee on Pricing of Medicines and Healthcare Products (CIPM) is responsible for the final price and reimbursement (P&R) decision, including on its resolutions the criteria listed in the law by which the reimbursement of a drug is approved or denied. Nevertheless, the information behind its reasoning is not provided. The present study aims to characterize the P&R criteria of the RDL 1/2015 through criteria definitions from other countries to improve the P&R evaluation in Spain. RESULTS: A multidisciplinary experts panel with relevant experience in drug evaluation and decision making at national, regional, and local level in Spain was selected for this study. A literature review to characterize the criteria listed in the RDL 1/2015 was performed based on the most relevant and recognized Health Technology Assessment (HTA) agencies in Europe, UK, and Canada. Eventually, a feasibility study was performed to evaluate the novel drug cefiderocol using the characterized criteria, including a reflective discussion of the results. CONCLUSIONS: Consensus was reached among the multidisciplinary experts on the characterization of the criteria set by the law. The feasibility of their application to a new drug was exploratory, notwithstanding it showed the potential to improve the transparency as well as to offer a more structured rationale for the CIPM to evaluate the inclusion of new drugs in the Spanish NHS.

Patient involvement in reflective multicriteria decision analysis to assist decision making in oncology.

OBJECTIVES: Patient involvement in drug evaluation decision making is increasing. The aim of the current study was to develop a multi-criteria decision analysis (MCDA) framework that would enable the inclusion of the patient perspective in the selection of appropriate criteria for MCDAs being used in the value assessments of oncologic drugs. METHODS: A literature review was conducted to identify and define criteria used in drug assessments from patient perspectives. The Evidence and Value: Impact on Decision Making methodology was used to develop a MCDA framework. Identified criteria were discussed by a sample of oncology patient association representatives who decided which criteria were important from patient perspectives. Selected criteria were rated by importance. The preliminary MCDA framework was tested through the assessment of a hypothetical oncology treatment. A discussion was carried out to agree on a final pilot MCDA framework. RESULTS: Twenty-two criteria were extracted from the literature review. After criteria discussion, sixteen criteria remained. The most important criteria were comparative patient reported outcomes (PRO), comparative efficacy and disease severity. After the discussion generated by the scoring of the hypothetical oncology treatment, the final pilot MCDA framework included seven quantitative criteria ("disease severity", "unmet needs", "comparative efficacy / effectiveness", "comparative safety / tolerability", "comparative PROs", "contribution of oncological innovation") and one contextual criterion ("population priorities and access"). CONCLUSIONS: The present study developed a pilot reflective MCDA framework that could increase patient's capability to participate in the decision-making process by providing systematic drug assessments from the patient perspective.

MULTI-CRITERIA DECISION ANALYSIS AS A DECISION-SUPPORT TOOL FOR DRUG EVALUATION: A PILOT STUDY IN A PHARMACY AND THERAPEUTICS COMMITTEE SETTING.

OBJECTIVES: The aim of this study was to develop and to assess a specific Multi-Criteria Decision Analysis (MCDA) framework to evaluate new drugs in an hospital pharmacy and therapeutics committee (P&TC) setting. METHODS: A pilot criteria framework was developed based on the EVIDEM (Evidence and Value: Impact on DEcisionMaking) framework, together with other relevant criteria, and assessed by a group of P&TC's members. The weighting of included criteria was done using a 5-point weighting technique. Two drugs were chosen by evaluation: an orphan-drug for Gaucher disease, and a nonorphan drug for the treatment of inflammatory bowel disease. Evidence matrices were developed, and value contribution of each drug was evaluated by P&TC's members. An agreed final framework was obtained through a discussion between the P&TC's members. RESULTS: After criteria assessment, the pilot framework included eight quantitative criteria: "disease severity," "unmet needs," "comparative efficacy/effectiveness," "comparative safety/tolerability," "comparative patient-reported outcomes," "comparative cost consequences-cost of treatment," "comparative cost consequences-other medical costs," and "quality of evidence"; and one contextual criterion: "opportunity costs and affordability." The most valued criteria were: "comparative safety/tolerability," "disease severity," and "comparative efficacy/effectiveness." When assessing the drugs most valued characteristics of the MCDA were the possibility that all team may contribute to drug assessment by means of scoring the matrices and the discussion to reach a consensus in drug positioning and value decision making. CONCLUSIONS: The reflective MCDA would integrate quantitative and qualitative criteria relevant for a P&TC setting, allowing reflective discussions based on the criteria weighting score.

Appraising the holistic value of Lenvatinib for radio-iodine refractory differentiated thyroid cancer: A multi-country study applying pragmatic MCDA.

BACKGROUND: The objective of the study was to reveal through pragmatic MCDA (EVIDEM) the contribution of a broad range of criteria to the value of the orphan drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC) in country-specific contexts. METHODS: The study was designed to enable comprehensive appraisal (12 quantitative, 7 qualitative criteria) in the current disease context (watchful waiting, sorafenib) of France, Italy and Spain. Data on the value of lenvatinib was collected from diverse stakeholders during country-specific panels and included: criteria weights (individual and social values); performance scores (judgments on evidence-collected through MCDA systematic review); qualitative impacts of contextual criteria; and verbal and written insights structured by criteria. The value contribution of each criterion was calculated and uncertainty explored. RESULTS: Comparative effectiveness, Quality of evidence (Spain and Italy) and Disease severity (France) received the greatest weights. Four criteria contributed most to the value of lenvatinib, reflecting its superior Comparative effectiveness (16-22% of value), the severity of RR-DTC (16-22%), significant unmet needs (14-21%) and robust evidence (14-20%). Contributions varied by comparator, country and individuals, highlighting the importance of context and consultation. Results were reproducible at the group level. Impacts of contextual criteria varied across countries reflecting different health systems and cultural backgrounds. The MCDA process promoted sharing stakeholders' knowledge on lenvatinib and insights on context. CONCLUSIONS: The value of lenvatinib was consistently positive across diverse therapeutic contexts. MCDA identified the aspects contributing most to value, revealed rich contextual insights, and helped participants express and explicitly tackle ethical trade-offs inherent to balanced appraisal and decisionmaking.

Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly.

PURPOSE: Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease-related symptoms or patient's perceived quality of life. We developed and validated a tool to measure disease activity in acromegaly to support decision-making in clinical practice. METHODS: An international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Subsequently, a panel of 21 renowned endocrinologists at pituitary centers (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. RESULTS: From expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumor status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumor status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumor size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. CONCLUSION: The validation study underlined IGF-I and tumor status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. An Acromegaly Disease Activity Tool (ACRODAT) is in development that might assist clinicians towards a more holistic approach to patient management in acromegaly.

DRUG EVALUATION AND DECISION MAKING IN CATALONIA: DEVELOPMENT AND VALIDATION OF A METHODOLOGICAL FRAMEWORK BASED ON MULTI-CRITERIA DECISION ANALYSIS (MCDA) FOR ORPHAN DRUGS.

OBJECTIVES: The aim of this study was to adapt and assess the value of a Multi-Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of Orphan drugs in Catalonia (Catalan Health Service). METHODS: The standard evaluation and decision-making procedures of CatSalut were compared with the EVIDEM methodology and contents. The EVIDEM framework was adapted to the Catalan context, focusing on the evaluation of Orphan drugs (PASFTAC program), during a Workshop with sixteen PASFTAC members. The criteria weighting was done using two different techniques (nonhierarchical and hierarchical). Reliability was assessed by re-test. RESULTS: The EVIDEM framework and methodology was found useful and feasible for Orphan drugs evaluation and decision making in Catalonia. All the criteria considered for the development of the CatSalut Technical Reports and decision making were considered in the framework. Nevertheless, the framework could improve the reporting of some of these criteria (i.e., "unmet needs" or "nonmedical costs"). Some Contextual criteria were removed (i.e., "Mandate and scope of healthcare system", "Environmental impact") or adapted ("population priorities and access") for CatSalut purposes. Independently of the weighting technique considered, the most important evaluation criteria identified for orphan drugs were: "disease severity", "unmet needs" and "comparative effectiveness", while the "size of the population" had the lowest relevance for decision making. Test-retest analysis showed weight consistency among techniques, supporting reliability overtime. CONCLUSIONS: MCDA (EVIDEM framework) could be a useful tool to complement the current evaluation methods of CatSalut, contributing to standardization and pragmatism, providing a method to tackle ethical dilemmas and facilitating discussions related to decision making.

Quality of Life in Acromegaly.

Available disease-specific questionnaires like the Acromegaly Quality of Life questionnaire have confirmed that quality of life (QoL) is impaired in acromegaly, especially in active disease. Successful therapy improves QoL, but it may not normalize completely even after endocrine cure; furthermore, there is not always a correlation between growth hormone (GH) and insulin-like growth factor 1 and subjective health perception of QoL. Appearance is the dimension most affected and has the highest impact on the patient's QoL. Worse QoL is associated with the presence of musculoskeletal pain, headache (if only medical therapy, not surgery, has been provided), having required treatment with radiotherapy, being older, of female gender, with a longer disease duration, coexisting diabetes mellitus, a higher BMI or becoming GH deficient after treatment for acromegaly.

Pancreatic polypeptide is recognized by two hydrophobic domains of the human Y4 receptor binding pocket.

Structural characterization of the human Y4 receptor (hY4R) interaction with human pancreatic polypeptide (hPP) is crucial, not only for understanding its biological function but also for testing treatment strategies for obesity that target this interaction. Here, the interaction of receptor mutants with pancreatic polypeptide analogs was studied through double-cycle mutagenesis. To guide mutagenesis and interpret results, a three-dimensional comparative model of the hY4R-hPP complex was constructed based on all available class A G protein-coupled receptor crystal structures and refined using experimental data. Our study reveals that residues of the hPP and the hY4R form a complex network consisting of ionic interactions, hydrophobic interactions, and hydrogen binding. Residues Tyr(2.64), Asp(2.68), Asn(6.55), Asn(7.32), and Phe(7.35) of Y4R are found to be important in receptor activation by hPP. Specifically, Tyr(2.64) interacts with Tyr(27) of hPP through hydrophobic contacts. Asn(7.32) is affected by modifications on position Arg(33) of hPP, suggesting a hydrogen bond between these two residues. Likewise, we find that Phe(7.35) is affected by modifications of hPP at positions 33 and 36, indicating interactions between these three amino acids. Taken together, we demonstrate that the top of transmembrane helix 2 (TM2) and the top of transmembrane helices 6 and 7 (TM6-TM7) form the core of the peptide binding pocket. These findings will contribute to the rational design of ligands that bind the receptor more effectively to produce an enhanced agonistic or antagonistic effect.

In vitro modification of substituted cysteines as tool to study receptor functionality and structure-activity relationships.

Mutagenic investigations of expressed membrane proteins are routine, but the variety of modifications is limited by the twenty canonical amino acids. We describe an easy and effective cysteine substitution mutagenesis method to modify and investigate distinct amino acids in vitro. The approach combines the substituted cysteine accessibility method (SCAM) with a functional signal transduction readout system using different thiol-specific reagents. We applied this approach to the prolactin-releasing peptide receptor (PrRPR) to facilitate biochemical structure-activity relationship studies of eight crucial positions. Especially for D(6.59)C, the treatment with the positively charged methanethiosulfonate (MTS) ethylammonium led to an induced basal activity, whereas the coupling of the negatively charged MTS ethylsulfonate nearly reconstituted full activity, obviously by mimicking the wild-type charged side chain. At E(5.26)C, W(5.28)C, Y(5.38)C, and Q(7.35)C, accessibility was observed but hindered transfer into the active receptor conformation. Accordingly, the combination of SCAM and signaling assay is feasible and can be adapted to other G-protein-coupled receptors (GPCRs). This method circumvents the laborious way of inserting non-proteinogenic amino acids to investigate activity and ligand binding, with rising numbers of MTS reagents allowing selective side chain modification. This method pinpoints to residues being accessible but also presents potential molecular positions to investigate the global conformation.

Development of a new tool for assessing health-related quality of life in patients with primary hyperparathyroidism.

BACKGROUND: Several studies in recent years have evaluated Health Related Quality of Life (HRQoL) of patients with primary hyperparathyroidism (PHPT). No disease specific questionnaires are available to assess the impact of the disease. The aim of this research is to describe the development of a new disease specific Quality of Life (QoL) questionnaire for use specifically with PHPT patients. METHODS: A conceptual model was developed describing the impact of the disease and its symptoms on QoL domains. A literature review was conducted to identify the most relevant domains. A focus group with experts was used to validate the domains; 24 patients were also interviewed to complement the information from the patient's perspective. A content analysis of the interviews was performed to identify items related with the impact of the disease, leading to PHPQoL-V.1 which was presented to a sample of 67 patients. Reliability was assessed by Cronbach's coefficient alpha and item-total score correlations. Validity was assessed by a factor analysis performed to determine the number of domains. Rasch analysis was carried out in order to refine the questionnaire items. RESULTS: 259 items were extracted from the interviews that were subsequently reduced to 34 items. Cronbach's coefficient alpha was 0.92. The factor analysis extracted two domains (physical and emotional). After Rasch analysis the questionnaire PHPQoL-V.2 kept 16 items (9 physical and 7 emotional). The questionnaire was developed in a Spanish population and the final version was translated to English through translation and back-translation. CONCLUSION: The first disease specific HRQoL questionnaire for PHPT patients (PHPQoL-16) has been developed. Validation studies designed to assess measurement properties of this tool are currently underway.

ODs with a positive TPR conclusion, not subject to a conditional approval, and approved without requering a pass would be more likely to be reimbursed in Spain.

BACKGROUND: The present study aims to assess clinical and regulatory variables that would influence pricing and reimbursement (P&R) decisions for Orphan Drugs (ODs) in Spain. ODs approved by the European Commission (EC) between 2006 and 2021 were classified according to their P&R status in Spain: approved, undergoing decision and rejected. A statistical analysis was carried out to assess the potential association between clinical and regulatory variables and P&R decision of ODs in Spain: therapeutic area, rarity of disease, existence of alternative therapies, availability of survival-related outcomes, safety profile, type of population, conditional approval status granted by the European Medicines Agency (EMA) and a positive Therapeutic Positioning Report (TPR) opinion. RESULTS: 111 ODs have been approved by the EC and have obtained marketing authorisation in Spain between 2006 and 2021. Out of the 111 ODs, 57 (51.4%) were reimbursed, 24 (21.6%) were undergoing decision and 30 (27%) were rejected. According to the statistical analysis, ODs with a positive TPR conclusion (p-value < 0.01), not subject to a conditional approval by the EMA (p-value < 0.05) and approved without the obligation to conduct a post-authorisation safety study (PASS) (p-value < 0.05), were statistically significant, and therefore, would be more likely to obtain P&R approval in Spain. CONCLUSIONS: This study shows that the TPR plays a key role in the P&R process in Spain and highlights that traditional evaluation tools, such us safety and efficacy, were the main drivers of P&R decisions for ODs. A positive conclusion of the TPR, non-conditional approval by the EMA and no obligation for a PASS seems to favourably affect P&R decisions in Spain.

Use of hospital resources in ICU inpatients with infections caused by carbapenem-resistant Gram-negative bacteria: A real clinical practice-based study in Spain.

INTRODUCTION: Carbapenem-resistant Gram-negative bacteria (CRGN) are an urgent public health threat because of the limited treatment options, its rapid spreading and high clinical impact and mortality rates. However, the burden and the use of resources of these infections have not been investigated. The aim of the current study is to understand the use of resources associated to the clinical management of CRGN infections in real clinical practice conditions. METHODS: An observational retrospective chart review study was performed. Data regarding patient demographics, clinical management and use of resources associated to hospitalization were retrieved from clinical charts of ICU inpatients with a confirmed CRGN infection. Three reference Spanish hospitals were selected according to their patient volume and geographical coverage. Descriptive analyses of the clinical management and the use of resources and its cost were performed and then total costs by type of resource were calculated. RESULTS: A total of 130 patients were included in the study. The higher number of patients (n=43; 33%) were between 61 and 70 years old. Ninety-four (72%) patients were male and 115 (88%) suffered from comorbidities. The mean total cost associated to the resources used in patients with CRGN infections hospitalized in ICU was 96,878€ per patient. These total costs included 84,140€ of total hospital stay, 11,021€ of treatments (558€ of antibiotics; 10,463€ of other treatments) and 1717€ costs of diagnostic tests. CONCLUSIONS: CRGN infection causes a high use of hospital resources, being the length of stay either in hospital wards or ICU the driver of the total costs. Diagnostic tests and treatments, including antibiotics, represent the lowest part of the use of resources and costs (13% of total costs).

Is the CAT questionnaire sensitive to changes in health status in patients with severe COPD exacerbations?

The COPD Assessment Test (CAT) was validated in English showing good psychometric properties. The objective of this study is to assess the capacity of the CAT to detect changes in health status in patients experiencing COPD exacerbations (ECOPD) and to further explore the validity of the Spanish version. An observational study was conducted in 49 Spanish centres. Patients hospitalised because of ECOPD (n = 224) completed the CAT, the St. George's Respiratory Questionnaire-adapted for COPD (SGRQ-C) and the London Chest Activities of Daily Living (LCADL) questionnaire during the first 48 hours of admission and 4 ± 1 weeks after discharge. Stable patients (n = 153) also completed these at recruitment and 4 ± 1 weeks later. Over 90% of patients were male. The CAT discriminated between stable and ECOPD patients (15.8 vs 22.4, p < 0.01), as well as between patients with different levels of airflow limitation and dyspnea (MRC scale). The CAT proved sensitive to change; change in mean score was 8.9 points (effect size (ES), 0.90) in ECOPD patients reporting their health state as "much better" after discharge, 4.8 points in those reporting "quite a lot better" (ES = 0.63), and 4.6 points in those reporting "slightly better" (ES = 0.59). Cronbach's alpha and Intraclass Correlation Coefficient were 0.86 and 0.83, respectively. It correlated with both the SGRQ (r = 0.82; p < 0.01) and the LCADL (r = 0.63; p < 0.01). Change in CAT correlated well with Δ SGRQ (r = 0.63; p < 0.01). The CAT showed to be sensitive to the change in health status associated with ECOPD. We also provide evidence of the validity of the Spanish version.

Contribution of cabotegravir + rilpivirine long-acting for the treatment of HIV-1 infection.

OBJECTIVE: To determine the value contribution of cabotegravir + rilpivirine, the first injectable every two months long-acting antiretroviral  regimen, using multi-criteria decision analysis. METHOD: The study was developed in two phases. After a small pilot, a field  ork study with a larger number of multidisciplinary experts was carried out.  Seven single-tablet regimens, currently recommended by the GeSIDA  guidelines, were selected as comparators. EVIDEM methodology was followed,  with a framework composed by 12 quantitative and 5 contextual criteria. Mean  and standard deviations were calculated for quantitative criteria (1 to 5 scale;  comparative criteria -5 to +5), whereas qualitative criteria were analyzed as  percentages of experts that considered a positive, neutral or negative impact  for the National Health System. RESULTS: 35 experts participated in the study. Human immunodeficiency virus- 1 infection was considered severe (mean ± standard deviation: 3.0 ± 1.0),  with moderate size of affected population (2.7 ± 1.2) and unmet needs (2.8 ±  1.0). Minimal differences were found in comparative efficacy/effectiveness (0.1  ± 0.5), safety/tolerability (-0.5 ± 0.7), and cost criteria: cost of the  intervention (0.5 ± 2.0), other medical costs (0.2 ± 1.8) and non- medical/indirect costs (0.5 ± 1.6). Experts perceived an improvement with  cabotegravir + rilpivirine long-acting, compared  to current daily oral single-tablet regimens, in patient-reported outcomes (2.7 ± 1.4). Therapeutic benefit  of the long-acting regimen was considered moderate-to-high (3.5 ± 1.2).  Experts considered the evidence provided by cabotegravir + rilpivirine long- actingrobust (4.3 ± 0.8), with elevated consensus on its future  recommendation in guidelines (3.2 ± 1.0). In contextual criteria, most experts  considered positive the impact on population priorities and access (91%),  common goal and specific interests (63%) and political, historical, and cultural  context criteria (60%). Impact was neutral in system capacity and appropriate  use (40%), and opportunity costs and affordability criteria (51%). Result of the  weighted global value contribution of cabotegravir + rilpivirine long-acting  was 0.34 (-1 to +1 scale), with Patient Reported Outcomes comparative  criterion bringing the highest added value. CONCLUSIONS: Cabotegravir + rilpivirine long-acting provides added value  contribution to human immunodeficiency virus-1 management in Spain  compared to daily oral single-tablet regimens. Patient Reported Outcomes and  therapeutic benefit of cabotegravir + rilpivirine long-acting were highly valued  by experts, as the expected benefit in adherence and stigma-related issues  would improve overall quality of life for people living with human  immunodeficiency virus-1.

OBJETIVO: Determinar la contribución de valor de cabotegravir + rilpivirina, el  primer tratamiento antirretroviral inyectable de acción prolongada, utilizando  metodología de análisis de decisión multicriterio.Método: El estudio se desarrolló en dos fases: una prueba piloto y una fase de  extensión, con un grupo multidisciplinar más grande. Se seleccionaron siete regímenes de comprimido único orales diarios  recomendados en las guías GeSIDA como comparadores. Se utilizó el marco  EVIDEM, compuesto por 12 criterios cuantitativos y 5 contextuales. Los  criterios cuantitativos se analizaron calculando la media y desviación estándar,  y los cualitativos se analizaron mediante el porcentaje de expertos que  consideraron el impacto positivo, neutro o negativo para el Sistema Nacional de Salud. RESULTADOS: Un total de 35 expertos participaron en el estudio. La infección  por virus de la inmunodeficiencia humana 1 se consideró grave (media ±  desviación estándar: 3,0 ± 1,0), con un tamaño de población afectada (2,7 ±  1,2) y unas necesidades no cubiertas (2,8 ± 1,0) moderadas. Las diferencias  fueron mínimas en los criterios comparativos de eficacia/efectividad (0,1 ±  0,5), seguridad/tolerabilidad (­0,5 ± 0,7) y coste: coste del tratamiento (0,5 ±  2,0), otros costes médicos (0,2 ± 1,8) y costes no-médicos/indirectos (0,5  ± 1,6). Los expertos observaron una emtrimejora con cabotegravir + rilpivirina  de acción prolongada en los resultados reportados por los pacientes  (2,7 ± 1,4). El beneficio terapéutico (3,5 ± 1,2) se consideró moderado-alto.  La evidencia de cabotegravir + rilpivirina de acción prolongada fue considerada  robusta (4,3 ± 0,8), con elevado consenso sobre su futura  recomendación en las guías (3,2 ± 1,0). En los criterios contextuales, el  impacto fue positivo en los criterios de prioridades de acceso (91%), objetivo  común (63%) y contexto político (60%). El impacto fue neutro en la capacidad  del sistema (40%) y los costes de oportunidad (51%). El resultado  promedio de la contribución del valor global de cabotegravir + rilpivirina de  acción prolongada fue de 0,34 (escala de ­1 a +1), siendo el criterio de  resultados reportados por el paciente el que proporcionó la mayor contribución de valor (0,04). CONCLUSIONES: Cabotegravir + rilpivirina de acción prolongada aporta un valor  añadido en el manejo del virus de la inmunodeficiencia humana 1 en  España en comparación con los regímenes de comprimido único utilizados  actualmente. Los expertos valoraron positivamente los resultados reportados  por los pacientes y el beneficio terapéutico de cabotegravir + rilpivirina de  acción prolongada, considerando que el beneficio esperado en la adherencia y  los problemas relacionados con el estigma produciría una mejora en la calidad  de vida de las personas con virus de la inmunodeficiencia humana 1.

The development and roll-out of a new hydrocoele surgery facility assessment tool for the elimination of lymphatic filariasis.

A hydrocoele surgery facility assessment tool (HSFAT) was developed to assess the readiness of hydrocoele surgery services in health facilities prior to implementation of hydrocoele surgical campaigns for the elimination of lymphatic filariasis (LF). A first version of the tool was piloted in Bangladesh, Malawi and Nepal in 2019, then, following feedback from country programme managers, a second version of the tool was rolled out across countries implementing hydrocoele surgery in the Accelerating the Control of Neglected Tropical Diseases (Ascend) West and Central Africa Programme, including Benin, Burkina Faso, Ghana, Guinea, Niger and Nigeria. The HSFAT assessed facilities across 10 domains: background information, essential amenities, emergency patient transfer, laboratory capacity, surgical procedures and trained staff, infection prevention, non-disposable basic equipment, disposable basic equipment, essential medicines and current hydrocoele practices. The HSFAT results highlight key areas for improvement in different countries and can be used to develop a quality improvement plan, which may include actions with agreed deadlines to improve the readiness and quality of hydrocoele surgery services provided by the health facility, prior to implementation of surgical campaigns and assist country programmes to achieve the dossier requirements set out by the World Health Organization for the elimination of LF.

Using HAQ-DI to estimate HUI-3 and EQ-5D utility values for patients with rheumatoid arthritis in Spain.

BACKGROUND/OBJECTIVE: Utility values are not usually assessed in clinical trials and do not allow cost-utility analysis to be performed with the data collected. The aim of this study was to derive relation functions so that Health Assessment Questionnaire - Disability Index (HAQ-DI) scores could be used to estimate Health Utilities Index - 3 (HUI-3) and EQ-5D utility values for patients with rheumatoid arthritis (RA). METHODS: An observational, cross-sectional, naturalistic, multicentre study was conducted. A total of 244 patients aged 18 years or older, with RA according to American College of Rheumatology diagnostic criteria, were recruited. Sociodemographic and clinical variables were recorded and patients completed three generic HRQoL questionnaires: the HAQ-DI, the HUI-3, and the EQ-5D. Two linear regression models were used to predict HUI-3 and EQ-5D utility values as functions of HAQ-DI scores, age, and gender. RESULTS: Patient mean age was 57.8 years old (standard deviation [SD], 13.3 years); 75.8% of the patients were women and 95.9% were white. Mean disease duration was 10.8 years (SD, 9 years). Patient distribution according to HAQ-DI severity was as follows: HAQ-DI < 0.5, 29%; 0.5 ≤ HAQ-DI < 1.1, 28%; 1.1 ≤ HAQ-DI < 1.6, 16%,1.6 ≤ HAQ-DI < 2.1, 15%; and HAQ-DI ≥ 2.1, 12%. HAQ-DI and EQ-5D mean scores were 1.02 (SD, 0.78) and 63.1 (SD, 20.3), respectively. Mean utility values for HUI-3 and time trade-off (TTO) were 0.75 (SD, 0.21) and 0.65 (SD, 0.3), respectively. The equations converting HAQ-DI scores to utilities were HUI-3 = 0.9527 - (0.2018 × HAQ-DI) +ε (R(2)=0.56), and TTO = 0.9567 - (0.309 × HAQ-DI) + ε (R(2)=0.54). Error distribution was non-normal. Age and gender were found to have no bearing on the utility functions. CONCLUSIONS: HAQ-DI scores can be used to estimate HUI-3 and EQ-5D utility values for patients with RA in data obtained from studies where utility values have not been collected.

Development and validation of the SEC-QOL questionnaire in women using contraceptive methods.

OBJECTIVES: Develop and validate a Spanish society of contraception quality-of-life (SEC-QOL) questionnaire to assess the impact of contraceptive methods on the health-related quality of life (HRQOL) of women. METHODS: SEC-QOL was developed following a standardized procedure including review of the literature, interviews with contraception users, and the administration of a pilot questionnaire to 187 women. SEC-QOL consists of 19 items and includes five dimensions. To validate the questionnaire, a multicenter, observational, prospective study was conducted in Spain. The following three study groups were defined: group A (n = 129) comprised women using effective contraceptive methods; group B (n = 251), comprised women about to start using an effective method; and group C (n = 73) comprised women using no or poorly effective contraception. All women attended baseline and final visits (4 ± 1 months). Participants completed the SEC-QOL, psychological well-being index, EuroQol five-dimensional questionnaire, and perceived health state questionnaires. RESULTS: At baseline, women from group A had a better HRQOL in all SEC-QOL dimensions, except for breast symptoms. Heavier menstrual bleeding, more androgenic and breast symptoms, menstrual pain, and not using hormonal contraceptive methods were associated with lower HRQOL. SEC-QOL scores showed moderate correlations to psychological well-being index and slightly lower correlation to EuroQol five-dimensional questionnaire scores. At follow-up, HRQOL had improved in all groups; most markedly in group B, which obtained an average effect size of 0.59. The minimum important difference was established as a 3.4-point change in the global SEC-QOL score. SEC-QOL obtained a Cronbach's α of 0.88 and an intraclass correlation coefficient of 0.82. CONCLUSIONS: SEC-QOL is a valid, reliable, and sensitive to change questionnaire for use in daily clinical practice and future research projects on contraception.

Determining the burden of infectious diseases caused by carbapenem-resistant gram-negative bacteria in Spain.

OBJECTIVE: To estimate the burden of nosocomial infections induced by carbapenem resistant Gram-negative (CRGN) pathogens in Spain, focusing on both the clinical and economic impact. METHODS: The burden of disease was estimated using data from 2017 according to the availability of data sources. The impact, both clinical and economic, of the most frequent CRGN nosocomial infections (those produced by Klebsiella pneumoniae, Pseudomonasaeruginosa and Acinetobacter baumannii) was analysed. Incidence and mortality of CRGN nosocomial infections were estimated, as well as the direct and indirect costs produced by this health problem. RESULTS: Approximately 376,346 patients are believed to have suffered a nosocomial infection in Spain in 2017; 3.2% of them due to CRGN bacilli. Infections by carbapenem-resistant P. aeruginosa produced the highest mortality rates (2578 deaths) when compared with A. baumannii (1571) and K. pneumoniae (415). Total economic costs of CRGN nosocomial infections in Spain were estimated to be €472 million in 2017, with 83% of the total cost caused by direct costs. CONCLUSION: CRGN nosocomial infections have a high clinical impact on patients' lives, high mortality rates, and represent one of the hospitalisation episodes with the most associated costs. Efforts should be focussed to implement preventive policies in order to avoid infections due to CRGN pathogens and the resulting burden, and to reduce direct costs due to morbimortality, specifically in those infections produced by P. aeruginosa.

Validation of the AF-QoL, a disease-specific quality of life questionnaire for patients with atrial fibrillation.

AIMS: To assess the performance of AF-QoL, a quality of life questionnaire for patients with atrial fibrillation (AF). METHODS AND RESULTS: Observational, prospective, multicentre study in 29 Spanish centres. Three patients' groups were identified at baseline visit: AF patients receiving a new therapeutic intervention according to physician criteria (intervention group); AF clinically stable patients according to physician evaluation (clinically stable group); and patients in a stable condition for more than 1 year after a myocardial infarction (control group). All patients were > or = 18 years. Follow-up visit was at 1 month (clinically stable group) and 3 +/- 1 months (intervention group). Sociodemographic and clinical information was gathered. AF-QoL, SF-36, and patient self-perception of general health status were administered. A total of 417 patients was included. Mean (SD) age was 61.2 (12.4), 31.4% women. AF-QoL mean overall score in AF patients (43.6) was lower (worse health-related quality of life, HRQoL) than in the control group (51.7) (P < 0.05). At baseline, patients with higher frequency of symptoms (P < 0.05) and worse NYHA functional class (P < 0.01) reported lower AF-QoL scores. AF-QoL and SF-36 correlated in all of their domains (r = 0.14-0.8, P < 0.01). AF-QoL showed good internal consistency (0.92) and test-retest reliability (0.86). CONCLUSION: AF-QoL is a valid and reliable HRQoL measure. Further investigation is recommended before using it in clinical practice.