Study designs for clinical trials applied to personalised medicine: a scoping review.

OBJECTIVE: Personalised medicine (PM) allows treating patients based on their individual demographic, genomic or biological characteristics for tailoring the 'right treatment for the right person at the right time'. Robust methodology is required for PM clinical trials, to correctly identify groups of participants and treatments. As an initial step for the development of new recommendations on trial designs for PM, we aimed to present an overview of the study designs that have been used in this field. DESIGN: Scoping review. METHODS: We searched (April 2020) PubMed, Embase and the Cochrane Library for all reports in English, French, German, Italian and Spanish, describing study designs for clinical trials applied to PM. Study selection and data extraction were performed in duplicate resolving disagreements by consensus or by involving a third expert reviewer. We extracted information on the characteristics of trial designs and examples of current applications of these approaches. The extracted information was used to generate a new classification of trial designs for PM. RESULTS: We identified 21 trial designs, 10 subtypes and 30 variations of trial designs applied to PM, which we classified into four core categories (namely, Master protocol, Randomise-all, Biomarker strategy and Enrichment). We found 131 clinical trials using these designs, of which the great majority were master protocols (86/131, 65.6%). Most of the trials were phase II studies (75/131, 57.2%) in the field of oncology (113/131, 86.3%). We identified 34 main features of trial designs regarding different aspects (eg, framework, control group, randomisation). The four core categories and 34 features were merged into a double-entry table to create a new classification of trial designs for PM. CONCLUSIONS: A variety of trial designs exists and is applied to PM. A new classification of trial designs is proposed to help readers to navigate the complex field of PM clinical trials.

Cost-effectiveness of multicomponent interventions in type 2 diabetes mellitus in a cluster randomised controlled trial: the INDICA study.

OBJECTIVE: To analyse the cost-effectiveness of multicomponent interventions designed to improve outcomes in type 2 diabetes mellitus (T2DM) in primary care in the Canary Islands, Spain, within the INDICA randomised clinical trial, from the public health system perspective. DESIGN: An economic evaluation was conducted for the within-trial period (2 years) comparing the four arms of the INDICA study. SETTING: Primary care in the Canary Islands, Spain. PARTICIPANTS: 2334 patients with T2DM without complications were included. INTERVENTIONS: Interventions for patients (PTI), for primary care professionals (PFI), for both (combined intervention arm for patients and professionals, CBI) and usual care (UC) as a control group. OUTCOMES: The main outcome was the incremental cost per quality-adjusted life-years (QALY). Only the intervention and the healthcare costs were included. ANALYSIS: Multilevel models were used to estimate results, and to measure the size and significance of incremental changes. Missed values were treated by means of multiple imputations procedure. RESULTS: There were no differences between arms in terms of costs (p=0.093), while some differences were observed in terms of QALYs after 2 years of follow-up (p=0.028). PFI and CBI arms were dominated by the other two arms, PTI and UC. The differences between the PTI and the UC arms were very small in terms of QALYs, but significant in terms of healthcare costs (p=0.045). The total cost of the PTI arm (€2571, 95% CI €2317 to €2826) was lower than the cost in the UC arm (€2750, 95% CI €2506 to €2995), but this difference did not reach statistical significance. Base case estimates of the incremental cost per QALY indicate that the PTI strategy was the cost-effective option. CONCLUSIONS: The INDICA intervention designed for patients with T2DM and families is likely to be cost-effective from the public healthcare perspective. A cost-effectiveness model should explore this in the long term. TRIAL REGISTRATION NUMBER: NCT01657227.

Patient-reported outcome measures for knowledge transfer and behaviour modification interventions in type 2 diabetes-the INDICA study: a multiarm cluster randomised controlled trial.

OBJECTIVE: This study assesses the effectiveness of different interventions of knowledge transfer and behaviour modification to improve type 2 diabetes mellitus patients' (T2DM) reported outcomes measures (PROMs) in the long-term. Design: open, community-based pragmatic, multicentre, controlled trial with random allocation by clusters to usual care (UC) or to one of the three interventions. PARTICIPANTS: A total of 2334 patients with uncomplicated T2DM and 211 healthcare professionals were included of 32 primary care centres. SETTING: Primary Care Centers in Canary Islands (Spain). INTERVENTION: The intervention for patients (PTI) included an educational group programme, logs and a web-based platform for monitoring and automated short message service (SMS). The intervention for professionals (PFI) included an educational programme, a decision support tool embedded into the electronic clinical record and periodic feedback about patients' results. A third group received both PTI and PFI (combined intervention, CBI). OUTCOME MEASURE: Cognitive-attitudinal, behavioural, affective and health-related quality of life (HQoL) variables. RESULTS: Compared with UC at 24 months, the PTI group significantly improved knowledge (p=0.005), self-empowerment (p=0.002), adherence to dietary recommendations (p<0.001) and distress (p=0.01). The PFI group improved at 24 months in distress (p=0.03) and at 12 months there were improvements in depression (p=0.003), anxiety (p=0.05), HQoL (p=0.005) and self-empowerment (p<0.001). The CBI group improved at 24 months in self-empowerment (p=0.008) and adherence to dietary recommendations (p=0.004) and at 12 months in knowledge (p=0.008), depression (p=0.006), anxiety (p=0.003), distress (p=0.01), HQoL (p<0.001) and neuropathic symptoms (p=0.02). Statistically significant improvements were also observed at 24 months in the proportion of patients who quit smoking for PTI and CBI (41.5% in PTI and 42.3% in CBI vs 21.2% in the UC group). CONCLUSIONS: Assessed interventions to improve PROMs in T2DM attain effectiveness for knowledge, self-empowerment, distress, diet adherence and tobacco cessation. PTI produced the most lasting benefits. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01657227 (6 August 2012) https://clinicaltrials.gov/ct2/show/NCT01657227.

Biopharmaceutical Study of Triamcinolone Acetonide Semisolid Formulations for Sublingual and Buccal Administration.

The mouth can be affected by important inflammatory processes resulting from localized or systemic diseases such as diabetes, AIDS and leukemia, among others, and are manifested in various types of buccal sores typically presenting pain. This work focuses on the design, formulation, and characterization of four semisolid formulations for oral mucosa in order to symptomatically treat these painful processes. The formulations have two active pharmaceutical ingredients, triamcinolone acetonide (TA) and lidocaine hydrochloride (LIDO). The formula also contains, as an excipient, Orabase®, which is a protective, hydrophobic, and anhydrous adhesive vehicle, used to retain or facilitate the application of active pharmaceutical ingredients to the oral mucosa. After designing the formulations, an analytical method for TA was validated using HPLC so as to achieve reliable analytical results. Franz-type diffusion cells were used to perform drug release studies using synthetic membrane, and permeation studies using buccal mucosa, estimating the amount and rate of TA permeated across the tissue. Additionally, sublingual permeation studies were carried out to evaluate a scenario of a continuous contact of the tongue with the applied formulation. Permeation fluxes and the amount of TA retained within sublingual mucosa were similar to those in buccal mucosa, also implying anti-inflammatory activity in the part of the tongue that is in direct contact with the formulation. In addition, the dynamic conditions of the mouth were recreated in terms of the presence of phosphate buffered saline, constant movement of the tongue, pH, and temperature, using dissolution equipment. The amount of TA released into the phosphate buffered saline in dynamic conditions (subject to being ingested) is well below the normal oral doses of TA, for which the formulation can be considered safe. The formulations applied to buccal or sublingual mucosas under dynamic conditions permit the successful retention of TA within either tissue, where it exerts anti-inflammatory activity. The four formulations studied show a pseudoplastic and thixotropic behavior, ideal for topical application. These results evidence the potential of these topical formulations in the treatment of inflammatory processes in the buccal mucosa.

Systematic review and meta-analysis of endovenous cyanoacrylate adhesive ablation for incompetent saphenous veins.

OBJECTIVE: The objective of this study was to assess the effectiveness, safety, and quality of care afforded by cyanoacrylate ablation (CA) vs existing options in treating great saphenous vein incompetence. METHODS: We conducted a systematic review; used the Grading of Recommendations Assessment, Development, and Evaluation framework; assessed the quality of randomized clinical trials using the Cochrane risk of bias tool; and performed a meta-analysis on the available comparative measurements. RESULTS: Three comparative studies, two randomized controlled trials and one observational study comprising 1057 participants, were included for effectiveness assessment purposes. The safety assessment also included 10 case series. Available evidence allowed comparison of CA with radiofrequency ablation (RFA) and endovenous laser ablation (EVLA) but not with other treatments. The comparative effectiveness analysis showed that whereas all three treatments reduced disease severity, none was significantly better than any other in terms of effectiveness. In terms of safety, however, CA devices gave rise to fewer adverse events and less severity at 12 months of follow-up than did EVLA or RFA. Other important advantages of CA over EVLA or RFA were linked to quality of care; patients reported less pain during intervention with CA than with RFA or EVLA devices and registered shorter intervention and recovery times. Furthermore, tumescent anesthesia and compression bandages were not necessary, making this technique more comfortable for the patients than endothermal techniques. CONCLUSIONS: Compared with EVLA and RFA, CA treatments yield comparable effectiveness outcomes and lead to less frequent and fewer mild adverse events, without difference in major adverse events. Furthermore, CA devices have advantages in terms of quality of care indicators, such as pain during intervention, treatment and recovery times, lower use of anesthesia, and zero use of compression bandages after treatment.

Improved synthesis and characterization of cholesteryl oleate-loaded cationic solid lipid nanoparticles with high transfection efficiency for gene therapy applications.

The development of new nanoparticle formulations that are capable of high transfection efficiency without toxicity is essential to provide new tools for gene therapy. However, the issues of complex, poorly reproducible manufacturing methods, and low efficiencies during in vivo testing have prevented translation to the clinic. We have previously reported the use of cholesteryl oleate as a novel excipient for solid lipid nanoparticles (SLNs) for the development of highly efficient and nontoxic nucleic acid delivery carriers. Here, we performed an extensive characterization of this novel formulation to make the scale up under Good Manufacturing Practice (GMP) possible. We also describe the complete physicochemical and biological characterization of cholesteryl oleate-loaded SLNs to ensure the reproducibility of this formula and the preservation of its characteristics before and after the lyophilization process. We defined the best manufacturing method and studied the influence of some parameters on the obtained nanoparticles using the Quality by Design (ICH Q8) guideline to obtain cholesteryl oleate-loaded SLNs that remain stable during storage and guarantee in vitro nucleic acid delivery efficacy. Our results indicate that this improved formulation is suitable for gene therapy with the possibility of scale-up the manufacturing of nanoparticles under GMP conditions.

Optimization of the Cohesion Index in the SeDeM Diagram Expert System and application of SeDeM Diagram: An improved methodology to determine the Cohesion Index.

In this study, we suggest optimizing the methodology to determine the Cohesion Index (Icd) in order to avoid mistaken characterizations due to powder bulk density. For this purpose, five different excipients, with different bulk densities and of different chemical nature, were compressed at different heights. Their compression and their tablet characterization enable establishing a powder weight for compression in accordance with its bulk density. Therefore, the resulting tablet will have a height within a defined range of heights where it has no critical effects on its hardness. Then, the impact of this optimization is shown in a formula development, one of the main SeDeM's applications. A mathematical equation was used to calculate the theoretical amount of excipient to formulate the API according to both methodologies. The compression results demonstrate that the characterization with the NM-Icd is more accurate than the previous one while preserving its simplicity.

Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy.

BACKGROUND: Cationic solid lipid nanoparticles (SLNs) have been given considerable attention for therapeutic nucleic acid delivery owing to their advantages over viral and other nanoparticle delivery systems. However, poor delivery efficiency and complex formulations hinder the clinical translation of SLNs. AIM: The aim of this study was to formulate and characterize SLNs incorporating the cholesterol derivative cholesteryl oleate to produce SLN-nucleic acid complexes with reduced cytotoxicity and more efficient cellular uptake. METHODS: Five cholesteryl oleate-containing formulations were prepared. Laser diffraction and laser Doppler microelectrophoresis were used to evaluate particle size and zeta potential, respectively. Nanoparticle morphology was analyzed using electron microscopy. Cytotoxicity and cellular uptake of lipoplexes were evaluated using flow cytometry and fluorescence microscopy. The gene inhibition capacity of the lipoplexes was assessed using siRNAs to block constitutive luciferase expression. RESULTS: We obtained nanoparticles with a mean diameter of approximately 150-200 nm in size and zeta potential values of 25-40 mV. SLN formulations with intermediate concentrations of cholesteryl oleate exhibited good stability and spherical structures with no aggregation. No cell toxicity of any reference SLN was observed. Finally, cellular uptake experiments with DNA-and RNA-SLNs were performed to select one reference with superior transient transfection efficiency that significantly decreased gene activity upon siRNA complexation. CONCLUSION: The results indicate that cholesteryl oleate-loaded SLNs are a safe and effective platform for nonviral nucleic acid delivery.

Osmolality predictive models of different polymers as tools in parenteral and ophthalmic formulation development.

During the development of parenteral dosage forms, different physicochemical studies are required to ensure stable, effective and safe formulations. The osmolality of this kind of dosage forms should bear a close similarity to the body fluids to prevent local irritation, pain or even more significant side effects like endothelial damage. The osmotic studies performed in Polyethylene glycol 400 (PEG 400), Polyethylene glycol 4000 (PEG 4000), Poloxamer 407 (P407), Sodium Hyaluronate (SH), Chondroitin Sulphate Sodium (CS), Cremophor RH 40 (CRE40) and Polyvinyl alcohol (PVA) aqueous solutions, showed that the theoretical determination of the osmolality based on their molecular weight as the only determinant factor did not agree with the values obtained by the measurement of colligative properties such as the freezing point depression. The data obtained from this study and its analysis, provided predictive equations that can be used as tools in the primary development to estimate formulation's osmolality at different concentrations; and its evolution over a period at the hypothetical worst-case scenario of storage temperature.

Development and validation of a risk stratification model for prediction of disability and hospitalisation in patients with heart failure: a study protocol.

BACKGROUND: Chronic heart failure (CHF) reduces quality of life and causes hospitalisation and death. Identifying predictive factors of such events may help change the natural history of this condition. AIM: To develop and validate a stratification system for classifying patients with CHF, according to their degree of disability and need for hospitalisation due to any unscheduled cause, over a period of 1 year. METHODS AND ANALYSIS: Prospective, concurrent, cohort-type study in two towns in the Madrid autonomous region having a combined population of 1 32 851. The study will include patients aged over 18 years who meet the following diagnostic criteria: symptoms and typical signs of CHF (Framingham criteria) and left ventricular ejection fraction (EF)<50% or structural cardiac lesion and/or diastolic dysfunction in the presence of preserved EF (EF>50%).Outcome variables will be(a) Disability, as measured by the WHO Disability Assessment Schedule V.2.0 Questionnaire, and (b) unscheduled hospitalisations. The estimated sample size is 557 patients, 371 for predictive model development (development cohort) and 186 for validation purposes (validation cohort). Predictive models of disability or hospitalisation will be constructed using logistic regression techniques. The resulting model(s) will be validated by estimating the probability of outcomes of interest for each individual included in the validation cohort. ETHICS AND DISSEMINATION: The study protocol has been approved by the Clinical Research Ethics Committee of La Princesa University Teaching Hospital (PI-705). All results will be published in a peer-reviewed journal and shared with the medical community at conferences and scientific meetings.

Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration.

The search for new formulations of anaesthetic agents that allow a localized administration and provide a prolonged effect is of great interest in the multimodal management of postoperative pain. The pre-formulation and characterization of a lidocaine and dexamethasone thermosensitive and bioadhesive long-acting gel for intraperitoneal administration was done as a tool in the management of pain in abdominal surgeries. The pre-formulation process was conducted by a systematic variation of the concentration of the different polymers, until setting it, in a suitable concentration that allowed an adequate gelation temperature. The poloxamer 407 (P407) was used as the main polymer; hydroxypropyl methylcellulose (HPMC) as the bioadhesive agent and polyvinyl pyrrolidone (PVP) to adjust the gelation temperature and physicochemical properties. The formulations were characterized by gelation temperature, pH, viscosity at 25°C and 37°C, gelation time, density and osmolality. Gelation temperature was decreased when increasing the concentration of hydroxypropyl methylcellulose and poloxamer 407, this effect was also observed when adding lidocaine hydrochloride and dexamethasone sodium phosphate to the formulations. The gelation temperature did not have statistically significant relation with the PVP concentration (P-value of 0.6797), even though, there is a tendency in the gelation temperature by varying it. Between the developed formulations, the 12.5/3.3/0.4% (P407/HPMC/PVP) formulation presents an appropriate gelation temperature, a suitable viscosity for administration by syringe, an adequate and stable pH and osmolality to prevent tissue damage and a correct gelation time that allowed the formation of a prolonged release implant.

Establishment of criteria for the selection and adaptation of objectives and indicators in ISO9001: 2008 quality system in a university pharmaceutical pilot plant / Establecimiento de criterios para la selección y adaptación de objetivos e indicadores en un sistema de calidad ISO9001:2008 en una planta piloto farmacéutica universitaria

Aims: The aim of this work is the correct establishment and follow-up of quality objectives and indicators as the cornerstones of a quality assurance system, in this case focused on ISO9001. Materials and methods: In this work, the authors present the criteria that, in their view, an organization must follow for a better selection and adaptation of the ISO9001:2008 quality system objectives and indicators applied to a university pharmaceutical pilot plant. The evolution of errors in setting objectives and indicators is assessed. Results: Based on the experience of several years at the SDM (Service of Development of Medicines) at the Faculty of Pharmacy of the University of Barcelona, the results show that the establishing of appropriate objectives and indicators is not an easy task. A careful selection of both objectives and indicators must be a compulsory step prior to the establishment of a robust, reliable quality assurance system through years. Conclusions: Experience over time proves to be a powerful tool to end up selecting the right quality objectives and indicators for such quality system. Since this task is not always easy to carry out, is necessary to set a selection of criteria in order to obtain useful information that contributes to the continuous improvement of the quality system

Objetivos: El objetivo de este trabajo es el correcto establecimiento y seguimiento de los objetivos de calidad y sus indicadores, como pilar fundamental de un sistema de garantía de calidad, en este caso centrado en ISO9001. Material y métodos: En este trabajo, los autores presentan los criterios que, a su juicio, una organización debe seguir para una mejor selección y adaptación de objetivos e indicadores en el marco de la norma de calidad ISO9001:2008, aplicada a una planta piloto farmacéutica universitaria. Se realiza una evaluación de los errores en el establecimiento de objetivos e indicadores. Resultados: En base a la experiencia de varios años en SDM (Servicio de Desarrollo del Medicamento) en la Facultad de Farmacia de la Universidad de Barcelona, los resultados muestran que el establecimiento de objetivos e indicadores apropiados no resulta una tarea sencilla. Una cuidadosa selección tanto de objetivos como de indicadores debe ser un paso obligado para el establecimiento de un sistema de aseguramiento de calidad robusto y fiable a lo largo del tiempo. Conclusiones: El aprendizaje basado en la experiencia de años demuestra ser una herramienta poderosa para acabar seleccionando los objetivos e indicadores correctos que se adapten al sistema de calidad en cuestión. Dado que este hecho no siempre resulta fácil, es necesario establecer unos criterios con el objetivo de obtener información útil que contribuya a la mejora continua del sistema de calidad (AU)

Heart failure in primary care: co-morbidity and utilization of health care resources.

BACKGROUND: In order to ensure proper management of primary care (PC) services, the efficiency of the health professionals tasked with such services must be known. Patients with heart failure (HF) are characterized by advanced age, high co-morbidity and high resource utilization. OBJECTIVE: To ascertain PC resource utilization by HF patients and variability in the management of such patients by GPs. METHODS: Descriptive, cross-sectional study targeting a population attended by 129 GPs over the course of 1 year. All patients with diagnosis of HF in their clinical histories were included, classified using the Adjusted Clinical Group system and then grouped into six resource utilization bands (RUBs). Resource utilization and Efficiency Index were both calculated. RESULTS: One hundred per cent of patients with HF were ranked in RUBs 3, 4 and 5. The highest GP visit rate was 20 and the lowest in excess of 10 visits per year. Prescription drug costs for these patients ranged from €885 to €1422 per patient per year. Health professional efficiency varied notably, even after adjustment for co-morbidity (Efficiency Index Variation Ratio of 28.27 for visits and 404.29 for prescription drug cost). CONCLUSIONS: Patients with HF register a high utilization of resources, and there is great variability in the management of such patients by health professionals, which cannot be accounted for by the degree of case complexity.

Comorbidity in patients with chronic obstructive pulmonary disease in family practice: a cross sectional study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequent and often coexists with other diseases. The aim of this study was to quantify the prevalence of COPD and related chronic comorbidity among patients aged over 40 years visiting family practices in an area of Madrid. METHODS: An observational, descriptive, cross-sectional study was conducted in a health area of the Madrid Autonomous Region (Comunidad Autónoma de Madrid). The practice population totalled 198,670 persons attended by 129 Family Physicians (FPs), and the study population was made up of persons over the age of 40 years drawn from this practice population. Patients were deemed to have COPD if this diagnosis appeared on their clinical histories. Prevalence of COPD; prevalence of a further 25 chronic diseases in patients with COPD; and standardised prevalence ratios, were calculated. RESULTS: Prevalence of COPD in family medicine was 3.2% (95% CI 3.0-3.3) overall, 5.3% among men and 1.4% among women; 90% of patients presented with comorbidity, with a mean of 4 ± 2.04 chronic diseases per patient, with the most prevalent related diseases being arterial hypertension (52%), disorders of lipid metabolism (34%), obesity (25%), diabetes (20%) and arrhythmia (15%). After controlling for age and sex, the observed prevalence of the following ten chronic diseases was higher than expected: heart failure; chronic liver disease; asthma; generalised artherosclerosis; osteoporosis; ischaemic heart disease; thyroid disease; anxiety/depression; arrhythmia; and obesity. CONCLUSIONS: Patients with COPD, who are frequent in family practice, have a complex profile and pose a clinical and organisational challenge to FPs.

Disability transitions after 30 months in three community-dwelling diagnostic groups in Spain.

BACKGROUND: Little is known about changes in disability over time among community-dwelling patients. Accordingly, this study sought to assess medium-term disability transitions. PATIENTS AND METHODS: 300 chronic obstructive pulmonary disease (COPD), chronic heart failure and stroke patients living at home in Madrid were selected from general practitioner lists. In 2009, disability was assessed after a mean of 30 months using the World Health Organisation (WHO) Disability Assessment Schedule 2.0 (WHODAS 2.0). Follow-up was completed using death registries. Losses to follow-up were due to: death, 56; institutionalisation, 9; non-location, 18; and non-participation, 17. Changes in WHODAS 2.0 scores and life status were described and analysed using Cox and multinomial regression. Disability at end of follow-up was imputed for 56 deceased and 44 surviving patients. RESULTS: Mean disability scores for 200 surviving patients at end of follow-up were similar to baseline scores for the whole group, higher than their own baseline scores, and rose by 16.3% when imputed values were added. The strongest Cox predictors of death were: age over 84 years, adjusted hazard ratios with 95%CI 8.18 (3.06-21.85); severe/complete vs. no/mild disability, 5.18 (0.68-39.48); and stroke compared to COPD, 1.40 (0.67-2.91). Non-participants and institutionalised patients had higher proportions with severe/complete baseline disability. A one-point change in baseline WHODAS 2.0 score predicted independent increases in risk of 12% (8%-15%) for severe/complete disability or death. CONCLUSIONS: A considerably high proportion of community-dwelling patients diagnosed with COPD, CHF and stroke undergo medium-term changes in disability or vital status. The main features of the emerging pattern for this group appear to be as follows: approximately two-thirds of patients continue living at home with moderately reduced functional status; 1/3 die or worsen to severe/complete disability; and 1/10 improve. Baseline disability scores, age and diagnosis are associated with disability and death in the medium term.

Comorbidity patterns in patients with chronic diseases in general practice.

INTRODUCTION: Healthcare management is oriented toward single diseases, yet multimorbidity is nevertheless the rule and there is a tendency for certain diseases to occur in clusters. This study sought to identify comorbidity patterns in patients with chronic diseases, by reference to number of comorbidities, age and sex, in a population receiving medical care from 129 general practitioners in Spain, in 2007. METHODS: A cross-sectional study was conducted in a health-area setting of the Madrid Autonomous Region (Comunidad Autónoma), covering a population of 198,670 individuals aged over 14 years. Multiple correspondences were analyzed to identify the clustering patterns of the conditions targeted. RESULTS: Forty-two percent (95% confidence interval [CI]: 41.8-42.2) of the registered population had at least one chronic condition. In all, 24.5% (95% CI: 24.3-24.6) of the population presented with multimorbidity. In the correspondence analysis, 98.3% of the total information was accounted for by three dimensions. The following four, age- and sex-related comorbidity patterns were identified: pattern B, showing a high comorbidity rate; pattern C, showing a low comorbidity rate; and two patterns, A and D, showing intermediate comorbidity rates. CONCLUSIONS: Four comorbidity patterns could be identified which grouped diseases as follows: one showing diseases with a high comorbidity burden; one showing diseases with a low comorbidity burden; and two showing diseases with an intermediate comorbidity burden.

Evaluation of a telemedicine service for the secondary prevention of coronary artery disease.

PURPOSE: Efficient ways are needed to implement the secondary prevention (SP) of coronary heart disease. Because few studies have investigated Web-based SP programs, our aim was to determine the usefulness of a new Web-based telemonitoring system, connecting patients provided with self-measurement devices and care managers via mobile phone text messages, as a tool for SP. METHODS: A single-blind, randomized controlled, clinical trial of 203 acute coronary syndrome (ACS) survivors, was conducted at a hospital in Madrid, Spain. All patients received lifestyle counseling and usual-care treatment. Patients in the telemonitoring group (TMG) sent, through mobile phones, weight, heart rate, and blood pressure (BP) weekly, and capillary plasma lipid profile and glucose monthly. A cardiologist accessed these data through a Web interface and sent recommendations via short message service. Main outcome measures were BP, body mass index (BMI), smoking status, low-density lipoprotein-cholesterol (LDL-c), and glycated hemoglobin A1c (HbA1c). RESULTS: At 12-month followup, TMG patients were more likely (RR = 1.4; 95% CI = 1.1-1.7) to experience improvement in cardiovascular risk factors profile than control patients (69.6% vs 50.5%, P = .010). More TMG patients achieved treatment goals for BP (62.1% vs 42.9%, P = .012) and HbA1c (86.4% vs 54.2%, P = .018), with no differences in smoking cessation or LDL-c. Body mass index was significantly lower in TMG (-0.77 kg/m² vs +0.29 kg/m², P = .005). CONCLUSIONS: A telemonitoring program, via mobile phone messages, appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention, especially for overweight patients.

ICF disability measured by WHO-DAS II in three community diagnostic groups in Madrid, Spain.

OBJECTIVE: The planning, provision and monitoring of medical and support services for patient groups with chronic ailments may require disability assessment and registration. The purpose of this study was to assess disability in three groups of patients with chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) or stroke. METHODS: Convenience samples of consecutive patients diagnosed with COPD (102), CHF (99), and stroke (99) were taken from 1,053 primary care users in the southern area of the autonomous region of Madrid. The patients were informed of the study and were assessed in their homes by trained field workers using the World Health Organization Disability Assessment Schedule II (WHO-DAS II). RESULTS: None of the groups had patients with extreme disability on their global WHO-DAS II scores. The prevalence of severe disability differed among the groups and was highest for stroke and CHF (33.33% and 29.29%, respectively) and lowest for COPD (14.71%). The three groups shared two similar traits, namely, a higher prevalence of disability among women than men, and a specific pattern by domain, with the highest prevalence of severe/extreme limitations being found in household life activities and mobility. Severe restrictions in Social Participation were more frequent in patients with stroke and CHF. The group with moderate disability according to the global WHODAS II score (n=94) showed a high prevalence of severe limitations in mobility, life activities and self-care. CONCLUSIONS: Disability among non-institutionalized persons with COPD, CHF and stroke is frequent and shows gender- and domain-related patterns similar to those described in a population-based study performed using the WHO-DAS II in elderly persons in Spain. ICF-validated disability categories could be useful in epidemiological surveys, individual assessments and primary care data monitoring systems.

ICF disability measured by WHO-DAS II in three community diagnostic groups in Madrid, Spain / Discapacidad CIF, según WHODAS-2, en tres grupos diagnósticos de atención primaria en un Área de Salud del sur de Madrid, España

Objective: The planning, provision and monitoring of medical and support services for patient groups with chronic ailments may require disability assessment and registration. The purpose of this study was to assess disability in three groups of patients with chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) or stroke. Methods: Convenience samples of consecutive patients diagnosed with COPD (102), CHF (99), and stroke (99) were taken from 1,053 primary care users in the southern area of the autonomous region of Madrid. The patients were informed of the study and were assessed in their homes by trained field workers using the World Health Organization Disability Assessment Schedule II (WHO-DAS II). Results: None of the groups had patients with extreme disability on their global WHO-DAS II scores. The prevalence of severe disability differed among the groups and was highest for stroke and CHF (33.33% and 29.29%, respectively) and lowest for COPD (14.71%). The three groups shared two similar traits, namely, a higher prevalence of disability among women than men, and a specific pattern by domain, with the highest prevalence of severe/extreme limitations being found in household life activities and mobility. Severe restrictions in Social Participation were more frequent in patients with stroke and CHF. The group with moderate disability according to the global WHODAS II score (n=94) showed a high prevalence of severe limitations in mobility, life activities and self-care. Conclusions: Disability among non-institutionalized persons with COPD, CHF and stroke is frequent and shows gender- and domain-related patterns similar to those described in a population-based study performed using the WHO-DAS II in elderly persons in Spain. ICF-validated disability categories could be useful in epidemiological surveys, individual assessments and primary care data monitoring systems (AU)

Objetivo: La planificación, prestación y monitorización de servicios sociales y sanitarios a pacientes con trastornos crónicos puede requerir evaluación y registro de su discapacidad. El objetivo de este estudio fue evaluar la discapacidad de tres grupos de pacientes con enfermedad pulmonar obstructiva crónica (EPOC), insuficiencia cardiaca congestiva (ICC) o ictus. Métodos: Pacientes con EPOC (102), ICC (99) e ictus (99), vistos consecutivamente, identificados de una lista de 1053 usuarios de atención primaria en el sur de la Comunidad Autónoma de Madrid, España. Tras ser informados, fueron evaluados en sus casas por entrevistadores entrenados utilizando WHODAS-2. Resultados: No hubo casos de discapacidad extrema, pero las tres poblaciones mostraron prevalencias de discapacidad grave según WHODAS-2 total, más altas en ictus e ICC (33,33% y 29,29%, respectivamente) y menores en EPOC (14,71%). Los grupos compartían un patrón de discapacidad más alta en mujeres y otro específico por dominios, con prevalencias más altas de discapacidad grave/extrema en actividades domésticas y movilidad. La participación social estaba más restringida en ictus e ICC. El grupo con discapacidad moderada en WHODAS-2 global (94 enfermos) mostraba prevalencias altas de discapacidad grave en movilidad, actividades diarias domésticas y autocuidado. Conclusiones: La discapacidad en personas no institucionalizadas con EPOC, ICC e ictus es frecuente, con patrones por sexo y dominio similares a los descritos en España con WHODAS-2 en un estudio poblacional de personas de edad avanzada. Las categorías CIF de discapacidad podrían utilizarse en encuestas epidemiológicas y evaluaciones individuales, así como en sistemas de información orientados a la monitorización de la discapacidad en atención primaria (AU)

Heart failure in the family practice: a study of the prevalence and co-morbidity.

BACKGROUND: Heart failure (HF) is a health problem that particularly affects the elderly population. Its onset is associated with other chronic diseases, a circumstance that makes it a challenge for health care services. The aim of this study is to quantify the prevalence of HF in family medicine offices and describe the chronic co-morbidity associated with it. METHODS: A cross-sectional, observational descriptive study set in a health area of the Community of Madrid, Spain. The study was carried out in a population of 198,670 individuals over 14 years of age, attended to by 129 specialists in family medicine. The patient was considered to have HF when this diagnosis (ICPC code K77) appeared in his or her electronic medical record. The prevalence of HF was quantified and its association with another 25 chronic diseases was analysed. RESULTS: The prevalence of HF was 6.9‰, 7.9‰ among women and 5.9‰ among men. Patients with HF had a high rate of chronic co-morbidity, with an average of 5.2 + 2.1 chronic diseases. Only 3% of the patients present with isolated HF and >60% have four or more additional chronic problems. Hypertension, cardiac arrhythmias, hyperlipidaemia, obesity and diabetes mellitus are the chronic diseases most frequently detected in HF patients. CONCLUSION: Patients with HF frequently visit the offices of family physicians, presenting with a high rate of cardiac and non-cardiac co-morbidity that proves to be a challenge on the clinical level and in terms of the organization of health care services.