Evaluación de los comparadores empleados en los estudios pivotales de nuevos medicamentos e indicaciones / Assessment of comparators used in pivotal studies of new medicines and indications

Objetivo: En algunos casos, los estudios pivotales para aprobar nuevos medicamentos no emplean el comparador más adecuado. El objetivo es cuantificar este problema analizando los Informes de Posicionamiento Terapéutico (IPT) publicados por el Ministerio de Sanidad español.Métodos: El comparador se clasificó en seis categorías según la adecuación del tratamiento, es decir, si coincidía con el estándar de tratamiento al ser autorizado: A-“inicialmente adecuado”, B-“sin comparador por causa ética”, C-“sin comparador excluyendo los clasificados en B”, D-“inadecuado” y E-“parcialmente subóptimo” (cuando era estándar solo para parte de los pacientes).La variable principal fue la proporción de nuevos fármacos/indicaciones con comparación suficiente (categorías A, B y C) o deficiente (el resto). La información sobre comparadores y tratamiento estándar se extrajo del IPT. Resultados: Se analizaron aleatoriamente 186 IPT con nuevos medicamentos/indicaciones, publicados entre 2013 y 2022. La comparación se consideró suficiente en un 73,7% (IC95 66,9-79,5) de los casos. El 26,3% restante (IC95 20,5-33,1) presentaba comparaciones deficientes en el ensayo pivotal, ya fuera por comparador inadecuado (11,3%), parcialmente subóptimo (5,4%) o ausencia de un estudio comparativo (9,7%). No hubo diferencias en relación con el año de aprobación.Conclusiones: Aproximadamente uno de cada cuatro nuevos medicamentos o indicaciones carece de una comparación suficiente en el momento de empezar a ser utilizado en la práctica clínica. La proporción no mejora a lo largo de los últimos 10 años. Las agencias reguladoras deben ser más exigentes en la selección del comparador para los ensayos clínicos pivotales, por cuestiones éticas y sanitarias. (AU)

Objective: Pivotal studies to approve new medicines often do not use the most appropriate comparator. The objective is to quantify this problem by analysing the Therapeutic Positioning Reports (IPT for its acronym in Spanish) published by the Spanish Health Ministry.Methods: The comparator was classified into six categories, based on the appropriateness of the treatment, i.e. whether it matched the standard of treatment when authorised: A-«initially adequate» (at the start of the study), B-«no comparator for ethical reasons», C-«no comparator -excluding B-«, D-«inadequate» and E-«partially suboptimal» (when it was standard for part of the included patients but not for all of them).The primary endpoint was the proportion of new drugs/indications with sufficient (categories A, B and C) or poor comparator (the rest). Information on comparators and standard treatment was extracted from the IPT. Results: We randomly analysed 186 IPTs with new drugs or indications, published between 2013 and March 2022. Comparability was assessed as sufficient in 73.7% (95%CI 66.9-79.5) of cases. The remaining 26.3% (95%CI 20.5-33.1) had poor comparisons in the pivotal trial, either due to inadequate comparator (11.3%), partially suboptimal (5.4%) or absence of a comparative study excluding ethical justification (9.7%). Conclusions: Approximately one in four new medicines or indications lacks sufficient comparability at the time of entry into clinical practice. The proportion has not improved over the last 10 years. Regulatory agencies need to be more stringent in comparator selection for pivotal clinical trials, for ethical and health reasons. (AU)

Use of wearable biometric monitoring devices to measure outcomes in randomized clinical trials: a methodological systematic review.

BACKGROUND: Wearable biometric monitoring devices (BMDs) have the potential to transform the conduct of randomized controlled trials (RCTs) by shifting the collection of outcome data from single measurements at predefined time points to dense continuous measurements. METHODS: Methodological systematic review to understand how recent RCTs used BMDs to measure outcomes and to describe the reporting of these RCTs. Electronic search was performed in the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE and completed a page-by-page hand search in five leading medical journals between January 1, 2018, and December 31, 2018. Three reviewers independently extracted all primary and secondary outcomes collected using BMDs, and assessed (1) the definitions used to summarize BMD outcome data; (2) whether the validity, reliability, and responsiveness of sensors was reported; (3) the discrepancy with outcomes prespecified in public clinical trial registries; and (4) the methods used to manage missing and incomplete BMD outcome data. RESULTS: Of the 4562 records screened, 75 RCTs were eligible. Among them, 24% tested a pharmacological intervention and 57% used an inertial measurement sensor to measure physical activity. Included trials involved 464 outcomes (average of 6 [SD = 8] outcomes per trial). In total, 35 trials used a BMD to measure a primary outcome. Several issues affected the value and transparency of trials using BMDs to measure outcomes. First, the definition of outcomes used in the trials was highly heterogeneous (e.g., 21 diabetes trials had 266 outcomes and 153 had different unique definitions to measure diabetes control), which limited the combination and comparison of results. Second, information on the validity, reliability, and responsiveness of sensors used was lacking in 74% of trials. Third, half (53%) of the outcomes measured with BMDs had not been prespecified, with a high risk of outcome reporting bias. Finally, reporting on the management of incomplete outcome data (e.g., due to suboptimal compliance with the BMD) was absent in 68% of RCTs. CONCLUSIONS: Use of BMDs to measure outcomes is becoming the norm rather than the exception in many fields. Yet, trialists need to account for several methodological issues when specifying and conducting RCTs using these novel tools.

Adenosina frente a antagonistas de los canales del calcio intravenosos en la taquicardia supraventricular / Adenosine versus intravenous calcium channel antagonists for supraventricular tachycardia

No disponible

Use of daily electronic patient-reported outcome (PRO) diaries in randomized controlled trials for rheumatoid arthritis: rationale and implementation.

BACKGROUND: Rheumatoid arthritis (RA) is associated with significantly diminished health-related quality of life. Patient-reported outcomes (PROs) are considered important in RA; however, some symptoms such as morning joint stiffness (MJS) and fatigue that are considered important by patients are not captured by the American College of Rheumatology "core set" measures for RA trials. The US Food and Drug Administration has endorsed electronic capture of clinical trial data including PROs, and electronic PRO (ePRO) systems may lead to more accurate and complete data capture, improved compliance, and patient acceptance compared with paper-based methods. Our objective was to assess the implementation of ePRO measures of Duration and Severity of MJS, Severity of Worst Tiredness, and Severity of Worst Joint Pain in baricitinib RA-BEAM and RA-BUILD phase 3 randomized clinical trials (RCTs). METHODS: A daily electronic diary (handheld device; Invivodata®, Inc.) was utilized to capture PRO data in the RCTs. Three "reporting window" options were incorporated to accommodate differences in patients' routine daily schedules, and alarms were programmed for each reporting window. Duration of MJS was recorded in "hours and minutes," and Severity of MJS, Worst Tiredness, and Worst Joint Pain were captured on a 0 to 10 rating scale, with a higher score indicating more severe symptoms. The patients and site staff were trained to use the daily electronic diary. RESULTS: Patients with moderately to severely active RA used the daily electronic diary in the RA-BEAM study (N = 1305) and RA-BUILD study (N = 684). The average compliance, calculated as total days completed by patients compared with total days expected to complete the diary, through Week 12 was high (RA-BEAM 94% patients; RA-BUILD 93% patients), potentially attributable to appropriate training, clarity of instructions, simple user interface, and electronic device design. Identified process challenges included non-timely issuance of the device, low battery, inadequate training of patients before data collection, inappropriate diary set-up, and first response entry 1 day after the baseline visit. CONCLUSIONS: High compliance rates support the use of the daily electronic PRO diary in large RCTs. Despite the anticipated issues, the daily electronic diary is expected to reduce recall bias and improve the quality of PRO data collection. TRIAL REGISTRATION: RA-BEAM ( NCT01710358 ) and RA-BUILD ( NCT01721057 ).

Critical appraisal of the recent US FDA approval for earlier DBS intervention.

In November 2015, Medtronic announced the US Food and Drug Administration (FDA) approval for the use of deep brain stimulation (DBS) therapy in people with Parkinson disease (PD) "of at least 4 years duration and with recent onset motor complications, or motor complications of longer-standing duration that are not adequately controlled with medication." The approval was based on data from the EARLYSTIM clinical trial, a randomized, prospective, multicenter, parallel-group clinical trial in Germany and France involving 251 patients with PD. While others have reviewed the application of DBS earlier in the disease course and the results from EARLYSTIM, we focus on the conceptual, scientific, clinical, ethical, and policy issues that arise regarding the recent FDA approval.

The Impact of Spinal Needle Selection on Postdural Puncture Headache: A Meta-Analysis and Metaregression of Randomized Studies.

BACKGROUND AND OBJECTIVES: Potentially broadened indications for spinal anesthesia require increased understanding of the risk factors and prevention measures associated with postdural puncture headache (PDPH). This review is designed to examine the association between spinal needle characteristics and incidence of PDPH. METHODS: Meta-analysis and metaregression was performed on randomized controlled trials to determine the effect of needle design and gauge on the incidence of PDPH after controlling for patient confounders such as age, sex, and year of publication. RESULTS: Fifty-seven randomized controlled trials (n = 16416) were included in our analysis, of which 32 compared pencil-point design with cutting-needle design and 25 compared individual gauges of similar design. Pencil-point design was associated with a statistically significant reduction in incidence of PDPH (risk ratio, 0.41; 95% confidence interval, 0.31-0.54; P < 0.001; I = 29%) compared with cutting needles among studies that assessed both design types. Subgroup analysis among obstetric and nonobstetric procedures yielded similar results. After adjustment for significant covariates, metaregression analysis among all 57 included trials revealed a significant correlation between needle gauge and rate of PDPH among cutting needles (slope = -2.65, P < 0.001), but not pencil-point needles (slope = -0.01, P = 0.819). CONCLUSIONS: Pencil-point needles are associated with significantly lower incidence of PDPH compared with the cutting-needle design. Whereas a significant relationship was noted between needle gauge and PDPH for cutting-needle design, a similar association was not shown for pencil-point needles. Providers may consider selection of larger-caliber pencil-point needle to maximize technical proficiency without expensing increased rates of PDPH.

Tourniquet use in arthroscopic anterior cruciate ligament reconstruction: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: To assess the effects of tourniquet use in arthroscopic anterior cruciate ligament (ACL) reconstruction surgery. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) that compared surgical outcomes following tourniquet use against non-tourniquet use during ACL reconstruction surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE for relevant RCTs. We used the Cochrane Collaboration's tool to assess the risk of bias of included RCTs, and performed a random-effects meta-analysis in calculating the pooled risk estimates. The primary outcomes was postoperative pain measured by visual analogue scale, verbal rating scale, or required morphine dose. The secondary outcomes were blood loss in drainage, operative time, muscle strength, and calf and thigh girth. RESULTS: We included 5 RCTs with 226 participants (116 in the tourniquet group and 110 in the non-tourniquet group). Postoperative pain and morphine doses were not significantly different between the two groups. Compared to the non-tourniquet group, the tourniquet group had a significantly increased blood loss in the drain (mean difference: 94.40 ml; 95% CI 3.65-185.14; P = 0.04). No significant differences in the operative time and muscle strength were found between the two groups. Tourniquet use was associated with a greater decrease in thigh girth but not in calf girth. CONCLUSIONS: The current evidence shows that compared to tourniquet use, ACL reconstruction surgery without tourniquet does not appear to have any major disadvantages and does not prolong operation time. There might be less drain blood loss associated with tourniquet use, though drains are no longer routinely used in ACL reconstruction surgery.

Mobile Device-Based Electronic Data Capture System Used in a Clinical Randomized Controlled Trial: Advantages and Challenges.

BACKGROUND: Electronic data capture (EDC) systems have been widely used in clinical research, but mobile device-based electronic data capture (mEDC) system has not been well evaluated. OBJECTIVE: The aim of our study was to evaluate the feasibility, advantages, and challenges of mEDC in data collection, project management, and telemonitoring in a randomized controlled trial (RCT). METHODS: We developed an mEDC to support an RCT called "Telmisartan and Hydrochlorothiazide Antihypertensive Treatment (THAT)" study, which was a multicenter, double-blinded, RCT, with the purpose of comparing the efficacy of telmisartan and hydrochlorothiazide (HCTZ) monotherapy in high-sodium-intake patients with mild to moderate hypertension during a 60 days follow-up. Semistructured interviews were conducted during and after the trial to evaluate the feasibility, advantage, and challenge of mEDC. Nvivo version 9.0 (QSR International) was used to analyze records of interviews, and a thematic framework method was used to obtain outcomes. RESULTS: The mEDC was successfully used to support the data collection and project management in all the 14 study hospitals. A total of 1333 patients were recruited with support of mEDC, of whom 1037 successfully completed all 4 visits. Across all visits, the average time needed for 141 questions per patient was 53 min, which were acceptable to both doctors and patients. All the interviewees, including 24 doctors, 53 patients, 1 clinical research associate (CRA), 1 project manager (PM), and 1 data manager (DM), expressed their satisfaction to nearly all the functions of the innovative mEDC in randomization, data collection, project management, quality control, and remote monitoring in real time. The average satisfaction score was 9.2 (scale, 0-10). The biggest challenge came from the stability of the mobile or Wi-Fi signal although it was not a problem in THAT study. CONCLUSIONS: The innovative mEDC has many merits and is well acceptable in supporting data collection and project management in a timely manner in clinical trial.

Coiling Is Not Superior to Clipping in Patients with High-Grade Aneurysmal Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis.

BACKGROUND: Outcomes of coiling embolization versus clipping for patients with high-grade aneurysmal subarachnoid hemorrhage (aSAH) have not been previously compared. We reviewed current evidence regarding the safety and efficacy of clipping versus coiling for high-grade aSAH. METHODS: We conducted a meta-analysis of studies that compared clipping with coiling in patients with high-grade aSAH published from January 1999 to February 2016 in Medline, Embase, and Cochrane databases based on PRISMA inclusion and exclusion criteria. Binary outcome comparisons between clipping and coiling were described using odds ratios (ORs). RESULTS: Three randomized controlled trials (RCTs) and 16 observational studies were included. There was no statistical difference in good outcome rates between the clipping and coiling groups (OR, 1.44; 95% confidence interval [CI], 0.97-2.13). Subgroup analysis showed no significant difference between the 2 treatments in non-RCTs (OR, 1.49; 95% CI, 0.95-2.36) and RCTs (OR, 1.15; 95% CI, 0.59-2.25). Coiling was associated with higher mortality (OR, 0.55; 95% CI, 0.41-0.75). Lower mortality was associated with clipping in non-RCTs (OR, 0.54; 95% CI, 0.40-0.74), but there was no difference in the RCTs (OR, 0.79; 95% CI, 0.19-3.39). Coiling was not associated with lower rates of complications including rebleeding (OR, 0.62; 95% CI, 0.30-1.29), ischemic infarct (OR, 0.89; 95% CI, 0.53-1.49), symptomatic vasospasm (OR, 0.76; 95% CI, 0.45-1.29), or shunt-dependent hydrocephalus (OR, 1.33; 95% CI, 0.52-3.40). CONCLUSION: The outcome with coiling is not superior to clipping in patients with high-grade aSAH; moreover, coiling has a greater risk of mortality.

Clinical outcome after surgical clipping or endovascular coiling for cerebral aneurysms: a pragmatic meta-analysis of randomized and non-randomized trials with short- and long-term follow-up.

BACKGROUND: Two randomized trials have evaluated clipping and coiling in patients with ruptured aneurysms. Aggregated evidence for management of ruptured and unruptured aneurysms is missing. OBJECTIVE: To conduct a meta-analysis evaluating clinical outcome after aneurysm treatment. METHODS: PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were searched for studies evaluating aneurysm treatment. The primary outcome measure was an independent clinical outcome (modified Rankin scale 0-2, Glasgow Outcome Scale 4-5, or equivalent). Secondary outcomes were poor outcome and mortality. ORs were calculated on an intention-to-treat basis with 95% CIs. Outcome heterogeneity was evaluated with Cochrane's Q test (significance level cut-off value at <0.10) and I2 (significance cut-off value >50%) with the Mantel-Haenszel method for dichotomous outcomes. A p value <0.05 was regarded as statistically significant. RESULTS: Searches yielded 18 802 articles. All titles were assessed, 403 abstracts were evaluated, and 183 full-text articles were read. One-hundred and fifty articles were qualitatively assessed and 85 articles were included in the meta-analysis. Patients treated with coiling (randomized controlled trials (RCTs)) had higher independent outcome at short-term follow-up (OR=0.67, 95% CI 0.57 to 0.79). Independent outcome was favored for coiling at intermediate and long-term follow-up (RCTs and observational studies combined-OR=0.80, 0.68 to 0.94 and OR=0.81, 0.71 to 0.93, respectively). Independent outcome and lower mortality was favored after coiling in unruptured aneurysms (database registry studies) at short-term follow-up (OR=0.34, 0.29 to 0.41 and OR=1.74, 1.52 to 1.98, respectively). CONCLUSIONS: This meta-analysis evaluating clinical outcome after coiling or clipping for intracranial aneurysms, indicates a higher independent outcome and lower mortality after coiling.

Wearables, Smartphones and Novel Anticoagulants: We Will Treat More Atrial Fibrillation, but Will Patients Be Better Off?

The widespread adoption of medical practices without a firm evidence base is common and the current growing enthusiasm for atrial fibrillation screening offers a real-time example of this phenomenon. Although no randomized trials supporting the utility of screening for atrial fibrillation exist, proponents suggest that such screening should be considered. Atrial fibrillation is a common condition that is often asymptomatic. It is also a condition associated with serious morbidity, primarily resulting from stroke. We practice at a time in which the ability to detect atrial fibrillation is becoming easier and treatments are becoming less onerous. Screening for atrial fibrillation may be beneficial but there is also a reasonable likelihood that its harms will outweigh it benefits. In this article we make the case that adopting this practice prior to data from randomized controlled trial would be a mistake. If screening for atrial fibrillation is adopted without such a robust evidence base we may well later discover that this course of action was wrong.

Beneficios de una intervención educativa en la dieta y en el perfil antropométrico de mujeres con un factor de riesgo cardiovascular / Benefits of an educational intervention on diet and anthropometric profile of women with one cardiovascular risk factor

Fundamento y objetivo: Evaluar si una intervención educativa en mujeres perimenopáusicas con hipertensión, diabetes mellitus y/o dislipidemia sería capaz de mejorar la adherencia a un patrón de dieta mediterráneo y conseguir cambios en parámetros antropométricos. Pacientes: Ensayo clínico aleatorizado de grupos paralelos: 320 mujeres (45-60 años) de 2 servicios de atención primaria urbanos. Variables a estudio: perímetro abdominal y de cadera, índice de masa corporal (IMC), grasa corporal total, visceral y de tronco (medidas con bioimpedancia) y adherencia a dieta mediterránea (cuestionario MEDAS-14). Grupo intervención: 3 talleres interactivos sobre prevención de enfermedad cardiovascular, y grupo control: información por correo. Resultados: Concluyeron el estudio 230 mujeres (113 en el grupo control y 117 en el grupo intervención). Un año después, las diferencias entre grupos fueron significativas en todos los parámetros. En la comparación intragrupos, las mujeres del grupo intervención mantuvieron el IMC y mejoraron la adherencia a la dieta mediterránea. El grupo control aumentó el IMC, el perímetro abdominal y de cadera y los parámetros de grasa (corporal total, visceral y tronco). Conclusiones: Una sencilla intervención educativa en mujeres perimenopáusicas con riesgo cardiovascular puede mejorar sus hábitos saludables (AU)

Background and objective: To assess whether an educational intervention in perimenopausal women with hypertension, diabetes mellitus and/or dyslipidaemia would improve adherence to a Mediterranean diet pattern and achieve changes in anthropometric parameters. Patients: Randomized clinical trial of parallel groups: 320 women (45-60 years) in 2 urban primary care services. Variables studied: hip and waist circumference, body mass index (BMI), total, visceral and trunk fat (bioimpedance measures) and adherence to Mediterranean diet (MEDAS-14 questionnaire). Intervention group: 3 interactive workshops on prevention of cardiovascular disease, and control group: information by post. Results: Two hundred and thirty women completed the study (113 control group and 117 intervention group). The differences between groups were significant in all parameters one year later. In the intragroup comparison, the intervention group maintained their BMI and improved adherence to the Mediterranean diet. The control group increased their BMI, abdominal and hip circumference and fat parameters (total, visceral and trunk fat). Conclusions: A simple educational intervention in perimenopausal women with cardiovascular risk can improve their healthy habits (AU)

ETAP: una escala de tabaquismo para la atención primaria de salud / ETAP: a smoking scale for Primary Health Care

OBJETIVO: Obtener una escala de exposición al tabaco para abordar la deshabituación. DISEÑO: Seguimiento de una cohorte. Validación de una escala. Emplazamiento: Unidad de investigación de atención primaria. Tenerife. PARTICIPANTES: Seis mil setecientos veintinueve participantes de la cohorte «CDC de Canarias». MÉTODOS: Se construyó una escala bajo la hipótesis de que el tiempo de exposición al tabaco es el factor clave para expresar riego acumulado; su validez discriminante fue probada sobre casos prevalentes de infarto agudo de miocardio (IAM) (n = 171) y se obtuvo su mejor punto de corte para cribado preventivo. Se comprobó su validez predictiva con casos incidentes de IAM (n = 46), comparándose el poder predictivo con factores (hipertensión, diabetes, dislipemia) clásicos de riesgo de IAM, incluido el índice años a paquete diario (APD). RESULTADOS: La escala obtenida fue la suma del triple de años que se había fumado, más los expuestos al tabaco en casa y en el trabajo. La frecuencia de IAM aumentó con los valores de la escala, siendo el valor 20 años de exposición el mejor punto de corte para la actuación preventiva puesto que presentó adecuados valores predictivos para el IAM incidente. La escala superó a APD en la predicción del IAM y compitió con los marcadores y factores de riesgo conocidos. CONCLUSIÓN: La escala propuesta permite una medición válida de exposición al tabaco y proporciona un criterio útil y sencillo que puede ayudar a promover una disposición al cambio y realizar una prevención oportuna. Aún requiere probar su validez tomando como referente otros problemas asociados al tabaco

OBJECTIVE: To obtain a scale of tobacco exposure to address smoking cessation. DESIGN: Follow-up of a cohort. Scale validation. SETTING: Primary Care Research Unit. Tenerife. PARTICIPANTS: A total of 6729 participants from the 'CDC de Canarias' cohort. METHODS: A scale was constructed under the assumption that the time of exposure to tobacco is the key factor to express accumulated risk. Discriminant validity was tested on prevalent cases of acute myocardial infarction (AMI; n = 171), and its best cut-off for preventive screening was obtained. Its predictive validity was tested with incident cases of AMI (n = 46), comparing the predictive power with markers (age, sex) and classic risk factors of AMI (hypertension, diabetes, dyslipidaemia), including the pack-years index (PYI). RESULTS: The scale obtained was the sum of three times the years that they had smoked plus years exposed to smoking at home and at work. The frequency of AMI increased with the values of the scale, with the value 20 years of exposure being the most appropriate cut-off for preventive action, as it provided adequate predictive values for incident AMI. The scale surpassed PYI in predicting AMI, and competed with the known markers and risk factors. CONCLUSION: The proposed scale allows a valid measurement of exposure to smoking and provides a useful and simple approach that can help promote a willingness to change, as well as prevention. It still needs to demonstrate its validity, taking as reference other problems associated with smoking

Impacto de una intervención farmacéutica en la prevención de recaídas en depresión en atención primaria / Impact of pharmaceutical intervention in preventing relapses in depression in Primary Care

OBJETIVO: Evaluar el impacto a largo plazo de una intervención farmacéutica (IF) respecto a la atención habitual (AH) en la prevención de recaídas en depresión. DISEÑO: Ensayo clínico aleatorizado (estudio PRODEFAR). Emplazamiento: Atención primaria. PARTICIPANTES: Ciento setenta y nueve pacientes con depresión mayor que inician antidepresivos, de estos, se seleccionaron para este análisis secundario los 113 cuyos síntomas habían remitido (definición principal) a los 6 meses (grupo intervención [GI] = 58; grupo control [GC] = 55). Intervención: Se realizó una entrevista personal en la farmacia comunitaria para mejorar la adhesión terapéutica durante la dispensación de medicación. MEDICIONES PRINCIPALES: Se realizaron 3 mediciones (línea base, 3 y 6 meses). La gravedad de síntomas depresivos (PHQ-9) fue evaluada a los 6 meses y se seleccionaron aquellos pacientes que presentaban remisión. Se revisaron sus historias clínicas para identificar recaídas, mediante 4 indicadores, en los siguientes 12 meses. RESULTADOS: La proporción de recaídas (variable principal) fue menor en el GI respecto al GC a los 18 meses de haber iniciado el tratamiento, pero la diferencia no fue estadísticamente significativa, ni en análisis por intención de tratar (OR = 0,734 [IC 95% 0,273;1,975]) ni en el análisis por protocolo (OR = 0,615 [95% CI 0,183; 2,060]). Todos los análisis de sensibilidad mostraron resultados consistentes. El tamaño de la muestra y la adhesión al protocolo en el GI fueron bajos. CONCLUSIÓN: El GI mostró una tendencia no significativa a presentar un menor número de recaídas. Esto podría relacionarse con la mejora en la adhesión entre los pacientes que recibieron la IF

OBJECTIVE: To evaluate the long-term impact of a brief pharmacist intervention (PI) compared with usual care (UC) on prevention of depression relapse. DESIGN: randomised controlled clinical trial SETTING: Primary Care. PARTICIPANTS: Of the 179 depressed patients initiating antidepressants, the 113 whose clinical symptoms had remitted (main definition) at 6 months assessment were selected for this secondary study (PI = 58; UC = 55). Intervention: PI was an interview to promote medication adherence when patients get antidepressants from pharmacy. MAIN MEASUREMENTS: Baseline, 3 months, and six-months follow-up assessments were made. The severity of depressive symptoms was evaluated with PHQ9. Patients presenting a remission of symptoms were selected. The patient medical records were reviewed to identify a relapse in the following 12 months by using 4 indicators. RESULTS: There was a lower proportion of patients that relapsed in the PI group than in the UC group 18 months after initiation of treatment, but the difference was not statistically significant either in the intent-to-treat analysis (OR = 0.734 [95%CI; 0.273-1.975]) or the per-protocol analysis (OR = 0.615 [95%CI; 0.183 -2.060]). All the sensitivity analyses showed consistent results. The sample size and adherence to the protocol in the intervention group were low. CONCLUSION: PI group showed a non-statistically significant tendency towards presenting fewer relapses. This could be related to the improvement in adherence among patients that received the intervention

Efectividad de la dieta cetogénica en niños con epilepsia refractaria: revisión sistemática / Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review

Introducción. La epilepsia es una patología cerebral que afecta tanto a niños como a adultos. Desde los años veinte, la dieta cetogénica ha ganado prestigio como otra opción de tratamiento en pacientes con epilepsia refractaria. Sujetos y métodos. Se realiza una síntesis de la evidencia a través de una revisión sistemática de ensayos clínicos aleatorizados que hayan comparado una dieta cetogénica sola con otros tipos de dieta para el tratamiento de estos pacientes. Objetivo. Determinar la efectividad de la dieta cetogénica en la disminución de los episodios de convulsiones en pacientes con epilepsia refractaria. La estrategia de búsqueda incluyó ensayos clínicos aleatorizados y ensayos clínicos controlados. Las bases de datos usadas fueron: Medline, LILACS, Central y CINAHL. Resultados. Se obtuvieron seis artículos que cumplían con los criterios de elegibilidad. Conclusiones. Existe evidencia limitada de que la dieta cetogénica en comparación con la dieta de triglicéridos de cadena media es más efectiva en disminuir la frecuencia de las convulsiones. Existe evidencia moderada de que la dieta cetogénica clásica en comparación con la dieta gradual (2,5:1 y 3:1) es más efectiva para disminuir las crisis epilépticas. Existe evidencia moderada de que la dieta cetogénica clásica en comparación con la dieta Atkins es más efectiva para disminuir la frecuencia de convulsiones en tres meses. La decisión de aplicar este tipo de dietas también debe basarse en costes, preferencias y seguridad del tratamiento. Además, debe considerarse la probabilidad de que algunos estudios, por problemas de indización, hayan quedado fuera de la revisión (AU)

Introduction. Epilepsy is a brain disorder that affects both children and adults. From the 1920s the ketogenic diet has gained prestige as another treatment option for patients with refractory epilepsy. Subjects and methods. A summary of the evidence will be made through a systematic review of randomized clinical trials that have compared a single ketogenic diet with other diet for the management of these patients. Aim. To determine the effectiveness of the ketogenic diet in reducing episodes of seizures in patients with refractory epilepsy. The search strategy included randomized controlled trials and controlled clinical trials. Databases used were Medline, LILACS, Central and CINAHL. Results. Six articles that met our elegibility criteria. Conclusions. There is limited evidence that the ketogenic diet compared to the medium-chain triglyceride diet is more effective in reducing the frequency of seizures. There is also moderate evidence that classical ketogenic diet compared to the gradual diet (2.5:1 and 3:1) is more effective in reducing seizures. There is moderate evidence that classical ketogenic diet compared to Atkins diet is more effective in reducing the frequency of seizure. The decision to apply this type of diet should also be based on costs, preferences and safety of treatment. It should also take into account the likelihood that studies have indexing problems have been left out of the review (AU)

Eficacia de los ejercicios excéntricos en tendinopatías rotulianas. Revisión bibliográfica / Effectiveness of eccentric exercise in patellar tendinopathy. Literature review

Introducción: La tendinopatía crónica rotuliana se describe por la aparición de dolor, inflamación y pérdida de la función del tendón rotuliano. Es una patología desarrollada por el uso excesivo en deportes que implican carreras, traumatismos repetitivos y saltos. Objetivos: Evidenciar la eficacia de los ejercicios excéntricos en las tendinopatías rotulianas, analizar algunos de los cambios fisiológicos que se dan en el tendón e intentar determinar un protocolo de ejercicios concreto. Materiales y métodos: Se ha realizado una búsqueda bibliográfica en las bases de datos Cochrane, ScienceDirect, Pubmed, PEDro. Se han encontrado 10 artículos donde se han comparado los ejercicios excéntricos con ondas de choque, ejercicios concéntricos, férula de noche y estiramientos, valorándose la mejora del dolor, la función y la calidad de vida de los pacientes. Resultados: Los ejercicios excéntricos han sido efectivos en el tratamiento de la tendinopatía rotuliana, en comparación con otras terapias como las ondas de choque, estiramientos, férulas de noche, etc. En algunos de éstos artículos se evidencia la eficacia de los ejercicios excéntricos, en otros deja abierta la posibilidad de seguir investigando en la existencia de combinación de varias terapias, pudiendo ser más efectiva y rápida la rehabilitación de esta lesión. Conclusión: Los ejercicios excéntricos son efectivos en la tendinopatía rotuliana, sin embargo no se ha demostrado que sean superiores a otros tratamientos aplicados actualmente. Por otro lado, no se ha podido determinar un protocolo concreto de aplicación de estos ejercicios

Introduction: Chronic patellar tendinopathy is described as the appearance of pain, inflammation and a loss of function of the patellar tendon. It is a pathology that develops through overuse in sports that involve racing, repetitive trauma and jumps. Objectives: Demonstrate the effectiveness of eccentric exercises on patellar tendinopathy, analysing some of the physiological changes that occur to the tendon and attempt to establish a protocol of specific exercises. Materials and methods: A literary search was performed of the Cochrane, ScienceDirect, Pubmed and PEDro databases. 10 articles were found that compared eccentric exercises with shockwaves, concentric exercises, a night-worn splint and stretches, grading improvements in pain, function and the quality of life of the patients. Results: The eccentric exercises were effective in treating patellar tendinopathy in comparison with other therapies such as shockwaves, stretches, night-worn splints, etc. In some of these articles evidence emerged regarding the effectiveness of eccentric exercises, in others the possibility was left open for continued research into the existence of a combination of various therapies, perhaps being the most effective and quick way of recovering from this injury. Conclusion: Eccentric exercises are effective in treating patellar tendinopathy; however, no evidence has shown that they are better than other currently applied treatments. On the other hand, no specific protocol for applying these exercises has been established

Ansiedad social en la adolescencia: factores psicoevolutivos y de contexto familiar / Social anxiety in adolescence: psychoevolutionary and family factors

El estudio sobre los factores de riesgo y protección relacionados con el desarrollo de la ansiedad social en la adolescencia ha avanzado notablemente en las ultimas décadas. Sin embargo, no existe mucha evidencia sobre el papel del contexto familiar y social inmediato. El objetivo de este estudio ha sido analizar el valor predictivo de los estilos educativos, la disciplina parental, la competencia social y la autoestima sobre la ansiedad social adolescente, en función del sexo y de la edad de los jóvenes. La muestra estuvo compuesta por 2060 estudiantes andaluces de Educación Secundaria Obligatoria (52,1% chicos). Se realizaron análisis de regresión múltiple que explicaron entre un 27,7% y un 33,8% de la varianza de la ansiedad social y destacaron su relación positiva con la autoestima negativa, el ajuste normativo y el control parental, y su relación negativa con el ajuste social. Se discute la importancia de trabajar la autoestima y competencia social de los jóvenes, así como de favorecer practicas parentales positivas y adaptadas al nivel evolutivo de los hijos para prevenir el desarrollo la ansiedad social en este periodo

Research on protective or risk factors of social anxiety in adolescence has advanced significantly in last decades. However, there is scarce evidence about the role of family and social context in the development of this problem. The aim of this study was to analyze the predictive value of parenting styles, parental discipline, social competence and self-esteem, in the development of social anxiety during adolescence, taking into account the gender and age of adolescents. The sample consisted of 2060 Andalusian teenagers who were studying Obligatory Secondary Education (52.1% boys). Multiple regression analyses were performed. These analyses explained between 27.7% and 33.8% of the variance of social anxiety and highlighted its positive relationship with negative self-esteem, normative adjustment and parental control, and its negative relationship with social adjustment. These results are discussed emphasizing the importance of focusing on supporting the development of self-esteem and social competence of youths and working with their parents to promote positive parenting practices, adapted to the developmental level of the children, to prevent social anxiety in adolescence

Non-surgical adjunctive interventions for accelerating tooth movement in patients undergoing fixed orthodontic treatment.

BACKGROUND: Accelerating the rate of tooth movement may help to reduce the duration of orthodontic treatment and associated unwanted effects including root resorption and enamel demineralisation. Several methods, including surgical and non-surgical adjuncts, have been advocated to accelerate the rate of tooth movement. Non-surgical techniques include low-intensity laser irradiation, resonance vibration, pulsed electromagnetic fields, electrical currents and pharmacological approaches. OBJECTIVES: To assess the effect of non-surgical adjunctive interventions on the rate of orthodontic tooth movement and the overall duration of treatment. SEARCH METHODS: We searched the following databases on 25 November 2014: the Cochrane Oral Health Group's Trials Register (November 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2014, Issue 10), MEDLINE via OVID (1946 to November 2014), EMBASE via OVID (1980 to November 2014), LILACS via BIREME (1980 to November 2014), metaRegister of Controlled Trials (November 2014), the US National Institutes of Health Trials Register (ClinicalTrials.gov; November 2014) and the WHO International Clinical Trials Registry Platform (November 2014). We checked the reference lists of all trials identified for further studies. There were no restrictions regarding language or date of publication in the searches of the electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people receiving orthodontic treatment using fixed appliances along with non-surgical adjunctive interventions to accelerate tooth movement. We excluded non-parallel design studies (for example, split-mouth) as we regarded them as inappropriate for assessment of the effects of this type of intervention. DATA COLLECTION AND ANALYSIS: Two review authors were responsible for study selection, risk of bias assessment and data extraction; they carried out these tasks independently. Any disagreements were resolved by discussion amongst the review team to reach consensus. The review authors contacted the corresponding authors of trials to obtain missing information and data to allow calculation of mean differences (MD), 95% confidence intervals (CI) or risk ratios (RR) when these were not reported. MAIN RESULTS: We included two studies in this review, which were both assessed as being at high risk of bias. The two studies, involving a total of 111 participants, compared the use of Tooth Masseuse and OrthoAccel with conventional treatment mechanics during orthodontic alignment and canine retraction phases, respectively. Both studies included objective assessment of the amount or rate of tooth movement, but we were not able to meta-analyse this data as they used different outcome measurements at different stages of the orthodontic treatment process. One study measured subjective evaluation of pain and discomfort and the other evaluated adverse effects. The studies did not directly report either the duration of orthodontic treatment or the number of visits during active treatment.Using the Tooth Masseuse with 111 Hz at 0.06 Newtons (N) for 20 minutes daily resulted in greater reduction in irregularity in the lower incisor region over 10 weeks, assessed using Little's Irregularity Index (LII) with a mean difference (MD) of 0.6 mm (95% confidence interval (CI) -0.94 to 2.34) when compared to the control group. Pain and discomfort increased at six to eight hours after arch wire placement and after seven days, with minimal difference between the intervention and control groups. No statistical tests were provided for either variable and the differences between the two groups were not clinically important.Using OrthoAccel with 30 Hz at 0.25 N for 20 minutes daily produced a higher rate of maxillary canine distalisation in comparison to the control group (MD 0.37 mm/month; 95% CI -0.07 to 0.81; P = 0.05). Whilst this difference suggested 50% faster tooth movement using the vibrational appliance, the absolute differences were marginal and deemed clinically unimportant. Similar levels of non-serious adverse effects were reported in the intervention and control groups with a risk ratio of 0.96 (95% CI 0.32 to 2.85).Overall, the quality of the evidence was very low and therefore we cannot rely on the findings. AUTHORS' CONCLUSIONS: There is very little clinical research concerning the effectiveness of non-surgical interventions to accelerate orthodontic treatment. The available evidence is of very low quality and so it is not possible to determine if there is a positive effect of non-surgical adjunctive interventions to accelerate tooth movement. Although there have been claims that there may be a positive effect of light vibrational forces, results of the current studies do not reach either statistical or clinical significance. Further well-designed and rigorous RCTs with longer follow-up periods are required to determine whether non-surgical interventions may result in a clinically important reduction in the duration of orthodontic treatment, without any adverse effects.

Cinética lipídica en el tratamiento antiviral dual en pacientes con hepatitis crónica C / Lipid kinetics during dual antiviral therapy in patients with chronic hepatitis C

Fundamento y objetivo: Valorar el metabolismo basal y cinético de las lipoproteínas durante el primer mes de biterapia en pacientes con hepatitis crónica C genotipo 1 (HCC-1). Pacientes y métodos: Estudio longitudinal, prospectivo, que incluyó 99 pacientes HCC-1 naive, biopsiados y tratados con biterapia. Clasificamos a nuestros pacientes en 5 niveles de exigencia lipídica, según el grado de fibrosis hepática, carga viral basal y ratio de infectividad (cociente entre concentraciones medias de triglicéridos y colesterol unido a lipoproteínas de alta densidad durante el primer mes), estableciendo para cada uno de ellos, durante este período, una concentración media mínima necesaria de colesterol unido a lipoproteínas de baja densidad (colesterol LDL) para que el paciente alcanzara un «metabolismo lipídico favorable» (MLF), y valoramos su relación con las tasas de curación. Resultados: Alcanzaron mayores tasas de curación aquellos pacientes con fibrosis F3-F4 que presentaron mayores concentraciones basales de colesterol LDL, así como aquellos que consiguieron mantener durante el primer mes de biterapia una ratio de infectividad menor de 3,2 y mayores concentraciones medias de colesterol LDL: media (DE) de 100 (23) mg/dl en «curados» frente a 89 (28) mg/dl en «no curados»,odds ratio 1,1, intervalo de confianza del 95% (1,0-1,2) (p < 0,05), siendo más significativas estas diferencias en los genotipos IL-28B-CC (p = 0,013). Aquellos que alcanzaron la respuesta virológica sostenida presentaron mayores tasas de MLF. Conclusiones: No todos los pacientes con HCC-1 van a presentar durante el primer mes de tratamiento una cinética lipídica favorable, siendo necesario para curarse y/o alcanzar un MLF mantener durante este período unas concentraciones plasmáticas medias de colesterol LDL mayores. Aquellos con ausencia de un MLF podrían beneficiarse del uso de estatinas (AU)

Background and objective: We analyzed baseline and kinetic characteristics of lipid metabolism during the first month of bitherapy in patients with chronic hepatitis C genotype 1 (CHC-1). Patients and methods: A longitudinal, prospective study including 99 naïve CHC-1 patients with liver biopsy who were treated with bitherapy. Our patients were assigned to one of 5 different “degrees of lipid requirement” that we established depending on the degree of liver fibrosis, baseline viral load and infectivity ratio (ratio between the median level of triglycerides and high densitity lipoproteins-cholesterol during the first month). The goal was to achieve 'a favorable lipid metabolism' (FLM) by establishing a necessary minimum level of low density lipoproteins (LDL)-cholesterol during this period for each one of them. We also analyzed the relationship with the rate of sustained virological response. Results: Patients with liver fibrosis F3-F4 who had higher baseline levels of LDL-cholesterol achieved higher rates of sustained virological response. Those patients who had a lower value of infectivity ratio and median levels of LDL-cholesterol during the first month of bitherapy also achieved higher rates of sustained virological response: SVR group 100 (23) mg/dl against non-SVR group: 89 (28) mg/dl; odds ratio 1.1; 95% confidence interval (1.0-1.2); P < .05, these differences being more significant for genotype IL-28B-CC (P = .013). Patients with sustained virological response had higher rates of FLM. Conclusions: Not every patient with CHC-1 has the same lipid kinetics during the first month of bitherapy, and it is necessary to achieve a sustained virological response and/or a FLM to keep higher plasma levels of LDL-cholesterol during this period. Those subjects without FLM could benefit from statins (AU)