OBJECTIVES: To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS: Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS: This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND: Chronic pain, considered to be pain lasting more than three months, is a common and often difficult to treat condition that can significantly impact upon function and quality of life. Treatment typically includes pharmacological and non-pharmacological approaches. Transcutaneous electrical nerve stimulation (TENS) is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain.
OBJECTIVES: To provide an overview of evidence from Cochrane Reviews of the effectiveness of TENS to reduce pain in adults with chronic pain (excluding headache or migraine).To provide an overview of evidence from Cochrane Reviews of the safety of TENS when used to reduce pain in adults with chronic pain (excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting.To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine) with a view to recommending strategies to reduce any uncertainty.
METHODS: Search methodsWe searched the Cochrane Database of Systematic Reviews (CDSR), in the Cochrane Library, across all years up to Issue 11 of 12, 2018.Selection of reviewsTwo authors independently screened the results of the electronic search by title and abstract against inclusion/exclusion criteria. We included all Cochrane Reviews of randomised controlled trials (RCTs) assessing the effectiveness of TENS in people with chronic pain. We included reviews if they investigated the following: TENS versus sham; TENS versus usual care or no treatment/waiting list control; TENS plus active intervention versus active intervention alone; comparisons between different types of TENS; or TENS delivered using different stimulation parameters.Data extraction and analysisTwo authors independently extracted relevant data, assessed review quality using the AMSTAR checklist and applied GRADE judgements where required to individual reviews. Our primary outcomes included pain intensity and nature/incidence of adverse effects; our secondary outcomes included disability, health-related quality of life, analgesic medication use and participant global impression of change.
MAIN RESULTS: We included nine reviews investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain. One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies. We therefore extracted data from eight reviews which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies.The included reviews followed consistent methods and achieved overall high scores on the AMSTAR checklist. The evidence reported within each review was consistently rated as very low quality. Using review authors' assessment of risk of bias, there were significant methodological limitations in included studies; and for all reviews, sample sizes were consistently small (the majority of studies included fewer than 50 participants per group).Six of the eight reviews presented a narrative synthesis of included studies. Two reviews reported a pooled analysis.Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale (MD -1.58, 95% CI -2.08 to -1.09, P < 0.001, I² = 29%, P = 0.22, 5 studies, 207 participants). However the quality of the evidence was very low due to significant methodological limitations and imprecision. A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention (SMD -0.85, 95% CI -1.36 to -0.34, P = 0.001, I² = 83%, P < 0.001). This pooled analysis was judged as offering very low quality evidence due to significant methodological limitations, large between-trial heterogeneity and imprecision. We considered the approach of combining sham and no intervention data to be problematic since we would predict these different comparisons may be estimating different true effects. All remaining reviews also reported pain intensity as an outcome measure; however the data were presented in narrative review form only.Due to methodological limitation and lack of useable data, we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects, nor for the remaining secondary outcomes: disability, health-related quality of life, analgesic medication use and participant global impression of change for any comparisons.We found the included reviews had a number of inconsistencies when evaluating the evidence from TENS studies. Approaches to assessing risk of bias around the participant, personnel and outcome-assessor blinding were perhaps the most obvious area of difference across included reviews. We also found wide variability in terms of primary and secondary outcome measures, and inclusion/exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions.
AUTHORS' CONCLUSIONS: We found the methodological quality of the reviews was good, but quality of the evidence within them was very low. We were therefore unable to conclude with any confidence that, in people with chronic pain, TENS is harmful, or beneficial for pain control, disability, health-related quality of life, use of pain relieving medicines, or global impression of change. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic pain.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
OBJECTIVES: Massage therapy has been proposed for painful conditions, but it can be difficult to understand the breadth and depth of evidence, as various painful conditions may respond differently to massage. The authors conducted an evidence mapping process and generated an "evidence map" to visually depict the distribution of evidence available for massage and various pain indications to identify gaps in evidence and to inform future research priorities.
DESIGN: The authors searched PubMed, Embase, and Cochrane for systematic reviews reporting pain outcomes for massage therapy. The authors assessed the quality of each review using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) criteria. The authors used a bubble plot to depict the number of included articles, pain indication, effect of massage for pain, and strength of findings for each included systematic review.
RESULTS: The authors identified 49 systematic reviews, of which 32 were considered high quality. Types of pain frequently included in systematic reviews were cancer pain, low back pain, and neck pain. High quality reviews concluded that there was low strength of evidence of potential benefits of massage for labor, shoulder, neck, low back, cancer, arthritis, postoperative, delayed onset muscle soreness, and musculoskeletal pain. Reported attributes of massage interventions include style of massage, provider, co-interventions, duration, and comparators, with 14 high-quality reviews reporting all these attributes in their review.
CONCLUSION: Prior reviews have conclusions of low strength of evidence because few primary studies of large samples with rigorous methods had been conducted, leaving evidence gaps about specific massage type for specific pain. Primary studies often do not provide adequate details of massage therapy provided, limiting the extent to which reviews are able to draw conclusions about characteristics such as provider type.
INTRODUCCIÓN: Se postula que los cannabinoides pudieran tener beneficios en la fibromialgia, sin embargo, su efectividad clínica sigue siendo un tema de discusión. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos quince revisiones sistemáticas que en conjunto incluyen dos ensayos aleatorizados pertinentes. Concluimos que no está claro si los cannabinoides tienen beneficios en la fibromialgia porque la certeza de la evidencia es muy baja. Por otra parte, están asociados a efectos adversos frecuentes.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND: Traditional Chinese medicine (TCM) has been accepted as a complementary therapy for knee osteoarthritis. However, the efficacy and safety of the intervention were still conflicting and uncertain. Meanwhile, the quality of methodology and evidence in the field was unknown.
OBJECTIVE: To summarize the characteristics and critically evaluate the quality of methodology, as well as the evidence of systematic reviews (SRs) on TCM for knee osteoarthritis.
METHODS: Five electronic databases were searched from inception to April 2016. The methodological quality of the included studies was assessed by AMSTAR and ROBIS. The quality of the evidence was determined using the GRADE approach.
RESULTS: Ten SRs were included. The conclusions suggest that TCM provides potential benefits for patients with knee osteoarthritis. These benefits include pain relief, functional improvement, and presence of few adverse events. Limitations of the methodological quality mainly included the lack of a-priori protocol or protocol registration and incomprehensive literature search. A list of excluded studies was also not provided. The overall quality of evidence in the SRs was poor, ranging from "very low" to "low," mainly because of the serious risk of bias of original trials, inconsistencies, and imprecision in the outcomes.
CONCLUSIONS: TCM generally appears to be effective for knee osteoarthritis treatment. However, the evidence is not robust enough because of the methodological flaws in SRs. Hence, these conclusions on available SRs should be treated with caution for clinical practice.
BACKGROUND & AIMS: Musculoskeletal pain, the most common cause of disability globally, is most frequently managed in primary care. People with musculoskeletal pain in different body regions share similar characteristics, prognosis, and may respond to similar treatments. This overview aims to summarise current best evidence on currently available treatment options for the five most common musculoskeletal pain presentations (back, neck, shoulder, knee and multi-site pain) in primary care.
METHODS: A systematic search was conducted. Initial searches identified clinical guidelines, clinical pathways and systematic reviews. Additional searches found recently published trials and those addressing gaps in the evidence base. Data on study populations, interventions, and outcomes of intervention on pain and function were extracted. Quality of systematic reviews was assessed using AMSTAR, and strength of evidence rated using a modified GRADE approach.
RESULTS: Moderate to strong evidence suggests that exercise therapy and psychosocial interventions are effective for relieving pain and improving function for musculoskeletal pain. NSAIDs and opioids reduce pain in the short-term, but the effect size is modest and the potential for adverse effects need careful consideration. Corticosteroid injections were found to be beneficial for short-term pain relief among patients with knee and shoulder pain. However, current evidence remains equivocal on optimal dose, intensity and frequency, or mode of application for most treatment options.
CONCLUSION: This review presents a comprehensive summary and critical assessment of current evidence for the treatment of pain presentations in primary care. The evidence synthesis of interventions for common musculoskeletal pain presentations shows moderate-strong evidence for exercise therapy and psychosocial interventions, with short-term benefits only from pharmacological treatments. Future research into optimal dose and application of the most promising treatments is needed.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
FUNDAMENTOS: La fibromialgia (FM) es un trastorno doloroso crónico y debilitante. La insatisfacción con la medicina convencional puede llevar a las personas con FM a recurrir a la medicina complementaria y alternativa (CAM). Se han publicado dos reseñas anteriores de revisiones sistemáticas de CAM para FM, pero no se evaluó el riesgo de sesgo en el proceso de revisión. MÉTODOS: Se realizaron búsquedas en cinco bases de datos Medline, Embase, AMED (vía OVID), Web of Science y Central desde su inicio hasta diciembre de 2015. Se realizaron búsquedas manuales en las listas de referencias. Teníamos dos objetivos: el primero era proporcionar una síntesis actualizada y rigurosamente conducida de las revisiones sistemáticas de la literatura de la CAM sobre FM; La segunda fue evaluar la calidad de la evidencia de la revisión sistemática disponible utilizando dos herramientas diferentes: AMSTAR (Shea et al., BMC Med Res Methodol 15; 7:10, 2007) y una herramienta desarrollada recientemente ROBIS (Whiting et al., J Clin Epidemiol 69: 225-34, 2016) diseñado específicamente para evaluar el riesgo de sesgo en revisiones sistemáticas. Se consideró cualquier revisión que evaluó una de ocho terapias de CAM para participantes diagnosticados con FM. Los estudios individuales tuvieron que ser ensayos controlados aleatorios donde la intervención fue comparada con placebo, el tratamiento como de costumbre o los controles de lista de espera para ser incluidos. La medida de resultado primaria fue dolor, y la medida de resultado secundaria fue eventos adversos. RESULTADOS: Se identificaron 15 revisiones que cumplieron con los criterios de inclusión. Hubo pruebas de baja calidad que la acupuntura mejora el dolor en comparación con ningún tratamiento o tratamiento estándar, pero buena evidencia de que no es mejor que la acupuntura simulada. La evidencia para la homeopatía, la manipulación espinal y la medicina herbal fue limitada. CONCLUSIONES: En total, cinco evaluaciones tuvieron 6 o más puntajes utilizando la escala AMSTAR y el acuerdo entre evaluadores fue buena (83,6%), mientras que siete evaluaciones lograron un bajo riesgo de sesgo utilizando ROBIS y el acuerdo entre evaluadores fue justo (60,0% ). No se sacaron conclusiones firmes sobre la eficacia de la manipulación espinal o la homeopatía para la FM. Hay evidencia limitada para Capsicum tópico, pero se requiere más investigación. Hay algunas pruebas que apoyan la efectividad de la acupuntura para la FM, pero se necesitan más ensayos de alta calidad para investigar sus beneficios, los daños y los mecanismos de acción, en comparación con ningún tratamiento estándar o estándar. REGISTRO DE REVISIÓN SISTEMÁTICA: PROSPERO CRD42016035846.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
Fundamento: Las terapias de medicina complementaria y alternativa (CAM) pueden ser utilizadas como un enfoque no farmacológico para el manejo del dolor crónico. Mientras cientos de ensayos sobre la modalidad CAM individual se han llevado a cabo, una visión global de sus resultados es actualmente insuficiente para los médicos e investigadores del dolor. Esta revisión general sintetizó la calidad de la evidencia meta-analítica que apoya la eficacia, tolerabilidad y seguridad de las terapias de CAM para el manejo del dolor crónico. MATERIALES Y MÉTODOS: MEDLINE, EMBASE, CINAHL y CENTRAL fueron examinados entre octubre de 1991 y noviembre de 2016. Se evaluaron los ensayos clínicos (aleatorizados y no aleatorios) con metanálisis que investigaban la utilidad de cualquier modalidad de CAM para el dolor crónico. El alivio del dolor después de la intervención fue el principal resultado y los resultados secundarios incluyeron la adherencia de los pacientes y la incidencia de efectos adversos durante el protocolo CAM. RESULTADOS: Se incluyeron 26 revisiones (207 ensayos clínicos,> 12.000 participantes), alrededor de 18 modalidades de CAM, incluidas en productos naturales, prácticas mentales y corporales u otros enfoques de salud complementarios. Se encontró que el cannabis inhalado, las imágenes motoras graduadas y la inyección de Kushen compuesto (una forma de medicina china) eran los más eficaces (con tamaños de efecto moderado a alto y baja heterogeneidad) y tolerables (≥80% de adherencia a los protocolos del estudio) alivio del dolor. Cuando se informó, los efectos adversos relacionados con estas CAM fueron menores. Conclusión: Aunque varios CAM se encontraron eficaces para el alivio del dolor crónico, todavía no está claro cuando estas modalidades son una opción razonable contra o en conjunción con los tratamientos de corriente. En ese sentido, se necesita investigación futura con un claro énfasis en la evaluación concurrente de la eficacia global de la CAM y la adherencia / tolerancia del paciente.
Resultados: De los 2.545 citas identificadas en el título y el nivel abstracto, se incluyeron un total de 156 publicaciones. La mayoría de los ensayos incluyeron pacientes con síntomas de dolor de intensidad al menos moderada (por ejemplo,> 5 en un 0 a 10 puntos, escala de calificación numérica para el dolor). Al otro lado de las intervenciones, la intensidad del dolor fue el resultado más frecuente, seguido de la función de devolución específico. Cuando están presentes, los beneficios observados para el dolor eran por lo general en los pequeños (de 5 a 10 puntos en una escala analógica visual de 0 a 100 puntos o 0,5 a 1,0 puntos en una escala de calificación numérica de 0 a 10 puntos) a moderada (10 a 20 puntos) gama. Efectos sobre la función eran generalmente más pequeñas que efectos sobre el dolor; en algunos casos, hubo efectos positivos sobre el dolor, pero no hay efectos sobre la función, y un menor número de estudios de la función que el dolor medidos. Los beneficios se miden en su mayoría en el seguimiento a corto plazo. Para el dolor lumbar agudo, la evidencia sugiere que los AINE (fuerza de la evidencia [SOE]: bajo a moderado), relajantes musculares esqueléticas (SOE; moderada), opiáceos (SOE; bajo), el ejercicio (SOE; bajo), y el calor superficial ( SOE; moderada) son más eficaces que el placebo, ninguna intervención o la atención habitual, y que el acetaminofén (SOE; baja) y los corticosteroides sistémicos (SOE; bajo) no son más efectivos que el placebo. Para el dolor crónico de espalda, terapias eficaces frente a placebo, el tratamiento simulado, ningún tratamiento, la atención habitual o lista de espera son los AINE, opioides, tramadol, duloxetina, la rehabilitación multidisciplinaria, la acupuntura y el ejercicio (SOE; moderada) y benzodiazepinas, terapias psicológicas, masaje , el yoga, el tai chi y la terapia con láser de bajo nivel (SOE; bajo); manipulación de la columna fue tan efectiva como otras intervenciones activas (SOE; moderada). Pocos ensayos evaluaron la efectividad de los tratamientos para el dolor lumbar radicular, pero la evidencia disponible encontraron que las benzodiazepinas, los corticosteroides, la tracción y la manipulación espinal no eran eficaces o se asociaron con efectos pequeños (SOE; baja). Relativamente pocos ensayos compararon directamente la efectividad de diferentes medicamentos o terapias no farmacológicas diferentes, o se pueden comparar farmacológica versus tratamientos no farmacológicos, y se encuentran por lo general no hay claras diferencias en los efectos. terapias farmacológicas se asociaron con un mayor riesgo de efectos adversos en comparación con el placebo (SOE; baja a moderada). Los ensayos no fueron diseñados o potencia para detectar daños graves de las terapias farmacológicas. Aunque las tasas parecieron ser bajas y no había un mayor riesgo de daños graves en comparación con el placebo, esto no descarta riesgo significativo de algunos tratamientos. Para los tratamientos no farmacológicos, la evaluación de los daños no fue óptima, pero los daños graves que parecía ser rara (SOE; bajo).
OBJECTIVE: To summarize the evidence on the health benefits of tai chi.Sources Of Information: A literature review was conducted on the benefits of tai chi for 25 specific conditions, as well as for general health and fitness, to update a 2014 review of systematic reviews. Systematic reviews and recent clinical trials were assessed and organized into 5 different groups: evidence of benefit as excellent, good, fair, or preliminary, or evidence of no direct benefit.Main Message: During the past 45 years more than 500 trials and 120 systematic reviews have been published on the health benefits of tai chi. Systematic reviews of tai chi for specific conditions indicate excellent evidence of benefit for preventing falls, osteoarthritis, Parkinson disease, rehabilitation for chronic obstructive pulmonary disease, and improving cognitive capacity in older adults. There is good evidence of benefit for depression, cardiac and stroke rehabilitation, and dementia. There is fair evidence of benefit for improving quality of life for cancer patients, fibromyalgia, hypertension, and osteoporosis. Current evidence indicates no direct benefit for diabetes, rheumatoid arthritis, or chronic heart failure. Systematic reviews of general health and fitness benefits show excellent evidence of benefit for improving balance and aerobic capacity in those with poor fitness. There is good evidence for increased strength in the lower limbs. There is fair evidence for increased well-being and improved sleep. There were no studies that found tai chi worsened a condition. A recent systematic review on the safety of tai chi found adverse events were typically minor and primarily musculoskeletal; no intervention-related serious adverse events have been reported.CONCLUSION: There is abundant evidence on the health and fitness effects of tai chi. Based on this, physicians can now offer evidence-based recommendations to their patients, noting that tai chi is still an area of active research, and patients should continue to receive medical follow-up for any clinical conditions.
To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS:
PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS:
Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS:
This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
