A Generic Method and Implementation to Evaluate and Improve Data Quality in Distributed Research Networks.

BACKGROUND: With the increasing personalization of clinical therapies, translational research is evermore dependent on multisite research cooperations to obtain sufficient data and biomaterial. Distributed research networks rely on the availability of high-quality data stored in local databases operated by their member institutions. However, reusing data documented by independent health providers for the purpose of care, rather than research ("secondary use"), reveal a high variability in terms of data formats, as well as poor data quality, across network sites. OBJECTIVES: The aim of this work is the provision of a process for the assessment of data quality with regard to completeness and syntactic accuracy across independently operated data warehouses using common definitions stored in a central (network-wide) metadata repository (MDR). METHODS: For assessment of data quality across multiple sites, we employ a framework of so-called bridgeheads. These are federated data warehouses, which allow the sites to participate in a research network. A central MDR is used to store the definitions of the commonly agreed data elements and their permissible values. RESULTS: We present the design for a generator of quality reports within a bridgehead, allowing the validation of data in the local data warehouse against a research network's central MDR. A standardized quality report can be produced at each network site, providing a means to compare data quality across sites, as well as to channel feedback to the local data source systems, and local documentation personnel. A reference implementation for this concept has been successfully utilized at 10 sites across the German Cancer Consortium. CONCLUSIONS: We have shown that comparable data quality assessment across different partners of a distributed research network is feasible when a central metadata repository is combined with locally installed assessment processes. To achieve this, we designed a quality report and the process for generating such a report. The final step was the implementation in a German research network.

Medium term effects of physical conditioning on breath-hold diving performance.

The current study aimed to analyze the effects of physical conditioning inclusion on apnea performance after a 22-week structured apnea training program. Twenty-nine male breath-hold divers participated and were allocated into: (1) cross-training in apnea and physical activity (CT; n = 10); (2) apnea training only (AT; n = 10); and control group (CG; n = 9). Measures were static apnea (STA), dynamic with fins (DYN) and dynamic no fins (DNF) performance, body composition, hemoglobin, vital capacity (VC), maximal aerobic capacity (VO2max), resting metabolic rate, oxygen saturation, and pulse during a static apnea in dry conditions at baseline and after the intervention. Total performance, referred as POINTS (constructed from the variables STA, DNF and DYN) was used as a global performance variable on apnea indoor diving. + 30, +26 vs. + 4 average POINTS of difference after-before training for CT, AT and CG respectively were found. After a discriminant analysis, CT appears to be the most appropriate for DNF performance. The post-hoc analysis determined that the CT was the only group in which the difference of means was significant before and after training for the VC (p < 0.01) and VO2max (p < 0.05) variables. Inclusion of physical activity in apnea training increased VC and VO2max in breath hold divers; divers who followed a mixed training, physical training and hypoxic training, achieved increased DNF performance.

The Burden of Diagnosed and Undiagnosed Diabetes in Native Hawaiian and Asian American Hospitalized Patients.

AIMS: Little is known about diabetes in hospitalized Native Hawaiians and Asian Americans. We determined the burden of diabetes (both diagnosed and undiagnosed) among hospitalized Native Hawaiian, Asian (Filipino, Chinese, Japanese), and White patients. METHODS: Diagnosed diabetes was determined from discharge data from a major medical center in Hawai'i during 2007-2008. Potentially undiagnosed diabetes was determined by Hemoglobin A1c ≥6.5% or glucose ≥200 mg/dl values for those without diagnosed diabetes. Multivariable log-binomial models predicted diabetes (potentially undiagnosed and diagnosed, separately) controlling for socio-demographic factors. RESULTS: Of 17,828 hospitalized patients, 3.4% had potentially undiagnosed diabetes and 30.5% had diagnosed diabetes. In multivariable models compared to Whites, Native Hawaiian and all Asian subgroups had significantly higher percentages of diagnosed diabetes, but not of potentially undiagnosed diabetes. Potentially undiagnosed diabetes was associated with significantly more hospitalizations during the study period compared to both those without diabetes and those with diagnosed diabetes. In all racial/ethnic groups, those with potentially undiagnosed diabetes also had the longest length of stay and were more likely to die during the hospitalization. CONCLUSIONS: Hospitalized Native Hawaiians (41%) and Asian subgroups had significantly higher overall diabetes burdens compared to Whites (23%). Potentially undiagnosed diabetes was associated with poor outcomes. Hospitalized patients, irrespective of race/ethnicity, may require more effective inpatient identification and management of previously undiagnosed diabetes to improve clinical outcomes.

Deciphering the GPER/GPR30-agonist and antagonists interactions using molecular modeling studies, molecular dynamics, and docking simulations.

The G-protein coupled estrogen receptor 1 GPER/GPR30 is a transmembrane seven-helix (7TM) receptor involved in the growth and proliferation of breast cancer. Due to the absence of a crystal structure of GPER/GPR30, in this work, molecular modeling studies have been carried out to build a three-dimensional structure, which was subsequently refined by molecular dynamics (MD) simulations (up to 120 ns). Furthermore, we explored GPER/GPR30's molecular recognition properties by using reported agonist ligands (G1, estradiol (E2), tamoxifen, and fulvestrant) and the antagonist ligands (G15 and G36) in subsequent docking studies. Our results identified the E2 binding site on GPER/GPR30, as well as other receptor cavities for accepting large volume ligands, through GPER/GPR30 π-π, hydrophobic, and hydrogen bond interactions. Snapshots of the MD trajectory at 14 and 70 ns showed almost identical binding motifs for G1 and G15. It was also observed that C107 interacts with the acetyl oxygen of G1 (at 14 ns) and that at 70 ns the residue E275 interacts with the acetyl group and with the oxygen from the other agonist whereas the isopropyl group of G36 is oriented toward Met141, suggesting that both C107 and E275 could be involved in the protein activation. This contribution suggest that GPER1 has great structural changes which explain its great capacity to accept diverse ligands, and also, the same ligand could be recognized in different binding pose according to GPER structural conformations.

Intervención en ancianos con multimorbilidad y polimedicados: resultados en la prescripción y en la calidad de vida / Intervention in elderly patients with multiple morbidities and multiple medications: results of the prescription and the quality of life

Objetivo. Evaluar el efecto de una intervención a través de los criterios de STOPP/START y el algoritmo de Garfinkel sobre la prescripción y la calidad de vida relacionada con la salud (CVRS) en ancianos polimedicados con multimorbilidad. Material y método. Estudio de intervención antes-después en 381 pacientes mayores de 67 años polimedicados de 71 médicos de atención primaria. Intervención: se formó a los médicos en los criterios de STOPP/START y en el algoritmo de Garfinkel. Cada médico revisó todos los medicamentos de sus enfermos seleccionados, posteriormente los citó a una primera consulta para realizarles una valoración clínica, modificarles el tratamiento según los criterios y medirles la CVRS mediante el cuestionario Short-Form Health Survey-V2 (SF-12). A los 2 meses, en una segunda consulta, se les realizó una nueva valoración clínica y se midió la CVRS. Las dimensiones de la CVRS entre la primera y la segunda consulta fueron comparadas con la «t» de Student pareada. Resultados. La intervención supuso la retirada de 1,5 fármacos de promedio por enfermo. Se modificó la dosis en el 4% de fármacos; al 8,9% de los pacientes se les prescribió un fármaco nuevo. Los AINE, fármacos psicoactivos e inhibidores de la bomba de protones fueron los más modificados. Mejoraron significativamente (p < 0,05) la función social y el componente sumario físico de la CVRS tras la intervención. Conclusión. La intervención mediante el algoritmo de Garfinkel y los criterios de STOPP/START conllevó una mejora de la CVRS y redujo el número de fármacos prescritos (AU)

Objective. To evaluate the effect of an intervention using STOPP/START criteria and the Garfinkel algorithm on prescription and the health-related quality of life (HRQoL) in elderly patients with multimorbidity and prescribed multiple medications. Material and method. A before-after intervention study on 381 patients over 67 years old and prescribed multiple medications by 71 Primary Care doctors. Intervention: The doctors were trained in the STOPP / START criteria and Garfinkel algorithm. Each doctor then reviewed all the drugs of their selected patients and then made appointments with them for an initial medical consultation and clinical assessment. Treatment was modified according to the criteria and the HRQoL measured using the SF-12 questionnaire. Two months later, in a second medical consultation, a new clinical assessment was made and the HRQoL was measured. The dimensions of the HRQoL between the first and the second consultation were compared using the paired Student-t test. Results. The intervention involved the removal of a mean of 1.5 drugs per patient. The dose was modified in 4% of drugs, and 8.9% of patients were prescribed a new drug. Non-Steroidal Anti-inflammatory drugs (NSAID), psychoactive drugs and proton pump inhibitors were the most modified. Social Function and Physical Component Summary of the HRQOL improved significantly (P < .05) after intervention. Conclusion. The intervention using the Garfinkel algorithm and STOPP -START criteria improved HRQoL and reduced the number of prescribed drugs (AU)

[Intervention in elderly patients with multiple morbidities and multiple medications: results of the prescription and the quality of life]. / Intervención en ancianos con multimorbilidad y polimedicados: resultados en la prescripción y en la calidad de vida.

OBJECTIVE: To evaluate the effect of an intervention using STOPP/START criteria and the Garfinkel algorithm on prescription and the health-related quality of life (HRQoL) in elderly patients with multimorbidity and prescribed multiple medications. MATERIAL AND METHOD: A before-after intervention study on 381 patients over 67 years old and prescribed multiple medications by 71 Primary Care doctors. INTERVENTION: The doctors were trained in the STOPP / START criteria and Garfinkel algorithm. Each doctor then reviewed all the drugs of their selected patients and then made appointments with them for an initial medical consultation and clinical assessment. Treatment was modified according to the criteria and the HRQoL measured using the SF-12 questionnaire. Two months later, in a second medical consultation, a new clinical assessment was made and the HRQoL was measured. The dimensions of the HRQoL between the first and the second consultation were compared using the paired Student-t test. RESULTS: The intervention involved the removal of a mean of 1.5 drugs per patient. The dose was modified in 4% of drugs, and 8.9% of patients were prescribed a new drug. Non-Steroidal Anti-inflammatory drugs (NSAID), psychoactive drugs and proton pump inhibitors were the most modified. Social Function and Physical Component Summary of the HRQOL improved significantly (P<.05) after intervention. CONCLUSION: The intervention using the Garfinkel algorithm and STOPP -START criteria improved HRQoL and reduced the number of prescribed drugs.

Improved protease stability of the antimicrobial peptide Pin2 substituted with D-amino acids.

Cationic antimicrobial peptides (AMPs) have attracted a great interest as novel class of antibiotics that might help in the treatment of infectious diseases caused by pathogenic bacteria. However, some AMPs with high antimicrobial activities are also highly hemolytic and subject to proteolytic degradation from human and bacterial proteases that limit their pharmaceutical uses. In this work a D-diastereomer of Pandinin 2, D-Pin2, was constructed to observe if it maintained antimicrobial activity in the same range as the parental one, but with the purpose of reducing its hemolytic activity to human erythrocytes and improving its ability to resist proteolytic cleavage. Although, the hydrophobic and secondary structure characteristics of L- and D-Pin2 were to some extent similar, an important reduction in D-Pin2 hemolytic activity (30-40 %) was achieved compared to that of L-Pin2 over human erythrocytes. Furthermore, D-Pin2 had an antimicrobial activity with a MIC value of 12.5 µM towards Staphylococcus aureus, Escherichia coli, Streptococcus agalactiae and two strains of Pseudomonas aeruginosa in agar diffusion assays, but it was half less potent than that of L-Pin2. Nevertheless, the antimicrobial activity of D-Pin2 was equally effective as that of L-Pin2 in microdilution assays. Yet, when D- and L-Pin2 were incubated with trypsin, elastase and whole human serum, only D-Pin2 kept its antimicrobial activity towards all bacteria, but in diluted human serum, L- and D-Pin2 maintained similar peptide stability. Finally, when L- and D-Pin2 were incubated with proteases from P. aeruginosa DFU3 culture, a clinical isolated strain, D-Pin2 kept its antibiotic activity while L-Pin2 was not effective.

[The appropriate use of pharmacological treatment in patients with chronic heart failure. A perspective from Primary Care]. / Grado de adecuación del tratamiento farmacológico en pacientes con insuficiencia cardíaca crónica. Visión desde atención primaria.

INTRODUCTION AND OBJECTIVE: The appropriate use of pharmacological treatment according to the indications in Clinical Guidelines reduces morbidity and mortality in patients with chronic heart failure (CHF). There are numerous studies regarding this in the hospital environment, but there are few studies done in Primary Care. The objective of this study is to evaluate the degree of compliance by Primary Care doctors to the Clinical Guidelines of the European Society of Cardiology in patients with CHF. METHODS: A descriptive, observational study on the use of indication-prescription drugs was conducted. POPULATION AND SAMPLE: Primary Care teams of the Leon Health Area (9 urban and 19 rural). The study population included patients with a diagnosis of New York Heart Association (NYHA) Grade II-IV chronic heart failure, from a register of 2047 with chronic heart failure patients treated by 97 Primary Care doctors. A proportional representative random sample of 474 patients from the urban and rural areas was studied. MAIN MEASUREMENTS: Adherence to the drugs recommended in the Clinical Guidelines was evaluated using two indicators; one overall, and another for drugs with a higher level of evidence (A1: angiotensin converting enzyme inhibitors-angiotensin II receptor antagonists [ACE-I/ARA-II], ß-blockers [BB] and spironolactone). RESULTS: A total of 456 patients were studied, with a mean age of 78.4 years, and 53.1% females. Arterial hypertension (AHT) and ischaemic heart disease were present in 64.7% of patients. The mean comorbidity rate, excluding CHF, was 2.9. Around 40% were diagnosed a NYHA Grade 11-1V. The overall compliance rate (diuretics, ACE-I/ARA-II, ß-blockers, spironolactone, digoxin, and oral anticoagulants) and rate of adherence to evidence-based ones was 55.2% and 44.6%, respectively. There was low compliance by 39.5%, and only 12.9% of patients showed perfect compliance with the drugs with a higher level of evidence, while to be less than 70 years-old, a history of ischaemia, AHT, and a hospital admission, were variables associated with better adherence to treatment. CONCLUSION: There is a low use of the drugs recommended by the Clinical Guidelines for heart failure, particularly of those with better evidence for reducing morbidity and mortality.

Grado de adecuación del tratamiento farmacológico en pacientes con insuficiencia cardíaca crónica. Visión desde atención primaria / The appropriate use of pharmacological treatment in patients with chronic heart failure. A perspective from Primary Care

Introducción y objetivo. La adecuación del tratamiento farmacológico a las indicaciones de las guías clínicas reduce la morbimortalidad en enfermos con insuficiencia cardíaca crónica (ICC). Numerosos estudios informan sobre esta adecuación en el ámbito hospitalario, mientras que en atención primaria son escasos. El objetivo es evaluar el grado de adecuación a la guía clínica de la Sociedad Europea de Cardiología en la ICC en los pacientes de médicos de atención primaria. Métodos. Diseño observacional descriptivo, de utilización de medicamentos, tipo indicación-prescripción. Población y muestra: equipos de atención primaria del Área Sanitaria de León (9 urbanos y 19 rurales). La población de estudio está formada por los pacientes con un diagnóstico de insuficiencia cardíaca crónica en grado II-IV de la New York Heart Association (NYHA), de un registro de 2.047 con insuficiencia cardíaca crónica, pertenecientes a 97 médicos de atención primaria. Mediante un muestreo aleatorio se seleccionaron 474 enfermos con afijación proporcional a los estratos rural y urbano. Mediciones principales: se evalúa la adherencia a los fármacos recomendados en la guía clínica mediante 2 indicadores, uno global y otro para fármacos con mayor grado de evidencia (A1: inhibidores de la enzima conversora de angiotensina/antagonistas de los receptores de angiotensina II [IECA/ARA-II], β-bloqueantes [BB] y espironolactona). Resultados. Se estudian 456 enfermos, con una edad promedio de 78,4 años, de los cuales son mujeres el 53,1%. La hipertensión arterial (HTA) y la isquemia cardíaca causan el 64,7%. La comorbilidad promedio, excluyendo la ICC, fue de 2,9. El 40,4% están en grado III-IV de la NYHA. El Índice de Adherencia Global (diuréticos, IECA/ARA-II, β-bloqueantes, espironolactona, digoxina y anticoagulantes orales) y el de Adherencia a la Evidencia A1 (IECA/ARA-II, BB y espironolactona) fueron del 55,2 y del 44,6%, respectivamente. El 39,5% tiene una baja adherencia, solo el 12,9% de los pacientes exhiben una perfecta adherencia a los medicamentos con el mejor grado de evidencia, mientras que tener menos de 70 años, los antecedentes de isquemia, HTA e ingreso hospitalario son variables asociadas a mejor adherencia. Conclusión. Existe una infrautilización de medicamentos recomendados por la guía clínica para la insuficiencia cardíaca, sobre todo de aquellos con mejores evidencias para reducir la morbimortalidad (AU)

Introduction and objective. The appropriate use of pharmacological treatment according to the indications in Clinical Guidelines reduces morbidity and mortality in patients with chronic heart failure (CHF). There are numerous studies regarding this in the hospital environment, but there are few studies done in Primary Care. The objective of this study is to evaluate the degree of compliance by Primary Care doctors to the Clinical Guidelines of the European Society of Cardiology in patients with CHF. Methods. A descriptive, observational study on the use of indication-prescription drugs was conducted. Population and sample: Primary Care teams of the Leon Health Area (9 urban and 19 rural). The study population included patients with a diagnosis of New York Heart Association (NYHA) Grade II-IV chronic heart failure, from a register of 2047 with chronic heart failure patients treated by 97 Primary Care doctors. A proportional representative random sample of 474 patients from the urban and rural areas was studied. Main measurements: Adherence to the drugs recommended in the Clinical Guidelines was evaluated using two indicators; one overall, and another for drugs with a higher level of evidence (A1: angiotensin converting enzyme inhibitors-angiotensin II receptor antagonists [ACE-I/ARA-II], β-blockers [BB] and spironolactone). Results. A total of 456 patients were studied, with a mean age of 78.4 years, and 53.1% females. Arterial hypertension (AHT) and ischaemic heart disease were present in 64.7% of patients. The mean comorbidity rate, excluding CHF, was 2.9. Around 40% were diagnosed a NYHA Grade 11-1V. The overall compliance rate (diuretics, ACE-I/ARA-II, β-blockers, spironolactone, digoxin, and oral anticoagulants) and rate of adherence to evidence-based ones was 55.2% and 44.6%, respectively. There was low compliance by 39.5%, and only 12.9% of patients showed perfect compliance with the drugs with a higher level of evidence, while to be less than 70 years-old, a history of ischaemia, AHT, and a hospital admission, were variables associated with better adherence to treatment. Conclusion. There is a low use of the drugs recommended by the Clinical Guidelines for heart failure, particularly of those with better evidence for reducing morbidity and mortality (AU)

Factores asociados a la variabilidad en la utilización de recursos en la consulta de los médicos de atención primaria / Factors associated with variability in the use of resources in primary care clinics

Objetivo. Analizar los factores que influyen en la utilización de recursos en la consulta de los médicos de atención primaria. Métodos. Estudio transversal. Las fuentes de datos fueron el sistema de información Medora-CyL de atención primaria, la tarjeta sanitaria para los denominadores y el registro de personal para variables relativas al médico. Los indicadores de derivaciones al especialista, peticiones al laboratorio, pruebas radiológicas y prescripción de recetas fueron ajustadas para la edad, utilizando como población de referencia la del área. Se realizó un análisis bivariante y multivariante. Resultados. Ser médico fijo, especialista en Medicina Familiar y Comunitaria (MFyC) y trabajar en medio urbano se asocia a una mayor utilización de recursos. Existe alta correlación entre las derivaciones al especialista con solicitudes al laboratorio, pruebas radiológicas, prescripción de recetas y distancia al centro de especialidades (r comprendidos entre 0,28 y 0,84). El ajuste mediante regresión multivariante determinó que los médicos más derivadores, solicitan más pruebas a laboratorio, más radiografías y prescriben más recetas. Ser especialista en MFyC y urbano permanecen como variables asociadas a mayor utilización de pruebas radiológicas y mayor prescripción, pero menor derivación al especialista. La variabilidad explicada va desde un 48% en la prescripción de recetas hasta un 80% en las peticiones a laboratorio. Conclusiones. Cuanto más se deriva al especialista, más peticiones se realizan al laboratorio más radiografías se solicitan y más recetas se prescriben. Los factores implicados son en su mayoría intrínsecos a la práctica del profesional(AU)

Objective. To analyse the factors that influence the use of resources by general practitioners. Methods. Cross-sectional study. The source of data was the General Practitioner's Management Information System Medora-CyL, the personal medical card database for the calculation of denominators, and the registry of personnel for variables related to doctors. The indicators for referrals to specialists, laboratory tests, X-ray requests and the issuing of prescriptions were adjusted for the age, taking the population of the area as a reference. Bivariate and multivariate analyses were performed. Results. Being a permanent general practitioner, specialist in Family and Community Medicine and to work in an urban environment was associated with a greater use of resources. There was a high correlation between referrals to specialists and laboratory requests, radiology tests, prescriptions and distance from the specialist centre (coefficient r between 0.28 and 0.84). Multivariate regression adjustment showed that the general practitioners who made more specialist referrals, also requested further laboratory tests, more X-rays and prescribed more. Being family doctor and working in urban areas remained associated with greater use of X-rays tests and more prescriptions but fewer referrals to specialists. The variability explained ranges from 48% on prescriptions and up to 80% on requests to the laboratory. Conclusion. The more referrals to specialists, the more requests are made to the laboratory, more X-rays are requested and more prescriptions are prescribed. Factors involved are largely intrinsic to the professional practice(AU)