Clinical efficacy and safety of compound Congrong Yizhi Capsules on Alzheimer's disease in mainland China: A systematic review with trial sequential analysis and GRADE assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a degenerative disease of the central nervous system (CNS) with insidious onset. AD is also the most common cause of dementia. Compound Congrong Yizhi Capsules (CCYC), a traditional Chinese medicine compound developed by the team of Beijing University of Chinese Medicine, has been widely used to treat AD. AIM OF THIS STUDY: To systematically evaluate the clinical efficacy and safety of CCYC for AD by meta-analysis, Trial Sequential Analysis (TSA) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. METHODS: This study was registered at PROSPERO (CRD42022295496). Randomized controlled trials (RCTs) of CCYC as the treatment for AD published before December 1, 2021 were retrieved from 4 Chinses databases, 4 English databases and 2 clinical trials registration systems. RevMan 5.4 and STATA 17.0 was used to conduct the meta-analysis of the included studies, the quality of outcomes was rated by the GRADE system, the TSA was conducted by TSA 0.9.5.10 software. RESULTS: Seven studies were included, and the total sample size was 746. Meta-analysis showed that 6 months of treatment with CCYC plus conventional western medicine treatments (CTs) improved MMSE scores compared with CTs alone (WMD: 4.32, 95% CI: 3.23, 5.42), and TSA confirmed that more trials in the future will not reverse the result. Among which, CCYC combined with donepezil can significantly improve MMSE scores (WMD: 3.54, 95% CI: 2.86, 4.22). CCYC combined with olanzapine also showed good effect on both MMSE (WMD: 6.49, 95% CI: 5.54, 7.44) and ADL scores (WMD: 5.23, 95% CI: 4.63, 5.83). No serious adverse events were reported. The strengths of the evidences above are MODERATE. CONCLUSION: CCYC combined with cognition-modifying western medicine can improve cognitive function, mental behavioural symptoms, and activities of daily living in AD patients with good safety.

The use of GRADE approach in Cochrane reviews of TCM was insufficient: a cross-sectional survey.

OBJECTIVE: To conduct a cross-sectional survey on the application status of the Grades of Recommendations Assessment Development and Evaluation (GRADE) in Cochrane systematic reviews (CSRs) of traditional Chinese medicine (TCM). STUDY DESIGN AND SETTING: We searched CSRs of TCM from the inception to December 2020 in the Cochrane Library database. General characteristics and details of GRADE were extracted. RESULTS: Among 226 CSRs of TCM, 86 (38.05%) involving 711 outcomes used GRADE to rate the certainty of evidence. Topics mainly focused on genitourinary diseases (17.44%), diseases of the musculoskeletal system or connective tissue (11.63%), and diseases of the nervous system (10.47%). Only 15.89% of the outcomes reported high or moderate certainty of evidence. Acupuncture was the most common intervention. There were no significant differences in evidence certainty between acupuncture and non-acupuncture, between TCM alone and integrated Chinese and western medicine, or between Chinese patent medicines and non-Chinese patent medicines (P > 0.05). Among 1 273 instances of downgrading, 44.62% were due to the risk of bias and 40.14% due to imprecision. CONCLUSION: Overall, GRADE approach is not widely used in CSRs of TCM. The certainty of evidence is generally low to very low, mainly because of the serious risk of bias and imprecision.

Lineamientos para el uso de terapias pulpares en dientes primarios con pulpas no-vitales / Diretriz sobre o uso de terapia pulpar devitalizada para dentes decíduos / Guidelines for the use of pulp therapy in primary teeth with non-vital pulps

Objetivo: Presentar lineamientos basados en evidencia para el tratamiento de pulpas no vitales debidas a caries profundas o traumatismos en dientes primarios. Métodos: el Grupo de Trabajo de la Academia Americana de Odontología Pediátrica AAPD realizó una revisión sistemática/meta-análisis de estudios acerca de terapia para pulpa no vital en dientes primarios, producto de caries o trauma, usando el enfoque GRADE para determinar el nivel de certeza de la evidencia para recomendaciones clínicas. Resultados: La determinación de GRADE fue de elevada a muy baja. Al comparar dientes con o sin resorción radicular, el éxito de la pulpectomía fue mayor (p<0,001) en los que no presentaban resorción radicular antes del tratamiento. El éxito de las pulpototmías obturadas con ZO/yodoformo/HC EndoflasTM(Laboratorios Sanlor, Cali, Colombia) y ZOE (óxido de zinc con eugenol) no fue diferente al yodoformo(yodoformo + hidróxido de calcio, VitapexTM o MetapexTM) después de 18 meses (p= 0,55); sin embargo el éxito de ZO/iodoformo/HC y ZOE fue cercano al 90% mientras que el del yodoformo fue 71% o menor. El análisis de red demostró que ZO/iodoformo/HC y ZOE son mejores que yodoformo. ELRP fue mejor que pulpectomía (p<0,001) en dientes con resorción radicular previa al tratamiento, pero la pulpectomía fue superior si las raíces estaban íntegras (p= 0,09). La instrumentación de los conductos radiculares fue significativamente más rápida (p<0,001) que la instrumentación manual, pero la calidad de la obturación no presentó diferencia (p= 0,09) y ambas técnicas presentaron éxito similar. El análisis de red clasificó al ZO/iodoformo/HC como mejor, ZOE en segundo lugar, y yodoformo en último lugar a los 18 meses. La tasa de éxito no fue impactada por el método de obturación, método de determinación de la longitud radicular, tipo de diente, número de citas, agentes de irrigación, remoción de la capa de desechos dentinarios o momento/tipo de restauración definitiva. Conclusiones: La tasa de éxito a 18 meses para pulpectomías demuestran que ZO/iodoformo/HC y ZOE son superiores al yodoformo. Las indicaciones de ELRP están limitadas a dientes con resorción radicular y requiere la realización de un seguimiento cercano.

Objetivo: Apresentar uma orientação baseada em evidência para terapias pulpar não vitais de cárie profundas ou trauma em dentes deciduos. Métodos: Um grupo de trabalho da AAPD realizou uma revisão/análise sistemática para estudos não vitais de dentes deciduos resultantes de trauma ou cárie e utilizou a abordagem GRADE para avaliar o nível de certeza de evidência para recomendações clínicas. Resultados: O GRADE foi avaliado de nível alto à muito baixo. Comparando os dentes com/sem reabsorção radicular, o sucesso da pulpectomia foi melhor (p<0,001) naqueles sem reabsorção radicular pré-operatória. OZ/iodofórmio/HC (óxido de zinco + iodofórmio + hidróxido de cálcio; EndoflasTM) e OZE (óxido de zinco e eugenol) o sucesso da pulpectomia não diferiu do iodofórmio (iodofórmio + hidróxido de cálcio; VitapexTM, MetapexTM) (p= 0,55) após 18 meses; contudo, as taxas de sucesso de OZ/iodofórmio/HC e OZE permaneceram perto de 90% enquanto que o iodofórmio foi de 71% ou menos. As taxas de análise da rede mostraram que o OZ/iodofórmio/HC e OZE era melhor do que o iodofórmio. LERT foi melhor (p<0,001) do que a pulpectomia nos dentes com reabsorção radicular pré-operatória, mas os resultados da pulpectomia foram melhores (p= 0,.09) se as raízes estivessem intactas. A instrumentação rotatória dos canais radiculares foi significativamente mais rápida (p<0,001) do que manual, mas a qualidade do preenchimento não diferiu (p= 0.09) e ambos tiveram sucesso comparável. A análise de rede classificou OZ/iodofórmio/HC como o melhor, OZE segundo, e iodofórmio como o mais baixo aos 18 meses. As taxas de sucesso não foram influenciadas pelo método de obturação ou determinação do comprimento da raiz, tipo de dente, número de visitas, irrigantes, remoção da lama dentinária, ou tempo/tipo de restauração final. Conclusões: As taxas de sucesso da pulpectomia de 18 meses favoreceram pulpectomias com OZ/iodofórmio/HC e OZE sobre iodofórmio. O LERT demonstrou indicação limitada para dentes com raízes reabsorvidas e requer um acompanhamento assíduo.

Abstract: Purpose: To present an evidence-based guideline for non-vital pulp therapies due to deep caries or trauma in primary teeth. Methods: The authors, working with the American Academy of Pediatric Dentistry, conducted a systematic review/meta-analysis for studies on non-vital primary teeth resulting from trauma or caries and used the GRADE approach to assess level of certainty of evidence for clinical recommendations. Results: GRADE was assessed from high to very low. Comparing teeth with/without root resorption, pulpectomy success was better (P<0.001) in those without preoperative root resorption. Zinc oxide plus iodoform plus calcium hydroxide ([ZO/iodoform/CH]; EndoflasTM) and zinc oxide and eugenol (ZOE) pulpectomy success did not differ from iodoform (iodoform plus calcium hydroxide; VitapexTM, MetapexTM) (P=0.55) after 18-months; however, ZO/iodoform/CH and ZOE success rates remained near 90 percent while iodoform was 71 percent or less. Network analysis ratings showed ZO/iodoform/CH and ZOE better than iodoform. Lesion sterilization tissue repair (LSTR) was better (P<0.001) than pulpectomy in teeth with preoperative root resorption, but pulpectomy results were better (P=0.09) if roots were intact. Rotary instrumentation of root canals was significantly faster (P<0.001) than manual, but the quality of fill did not differ (P=0.09) and both had comparable success. Network analysis ranked ZO/iodoform/CH the best, ZOE second, and iodoform lowest at 18 months. Success rates were not impacted by method of obturation or root length determination, type of tooth, number of visits, irrigants, smear layer removal, or timing/type of final restoration. Conclusions: Pulpectomy 18-month success rates supported ZO/iodoform/CH and ZOE pulpectomy over iodoform.

Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs.

BACKGROUND: The associations between vitamin D and coronavirus disease 2019 (COVID-19) infection and clinical outcomes are controversial. The efficacy of vitamin D supplementation in COVID-19 is also not clear. METHODS: We identified relevant cohort studies that assessed the relationship between vitamin D, COVID-19 infection and associated death and randomized controlled trials (RCTs) that reported vitamin D supplementation on the outcomes in patients with COVID-19 by searching the PubMed, EMBASE, and medRxiv databases up to June 5th, 2021. Evidence quality levels and recommendations were assessed using the GRADE system. RESULTS: Eleven cohort studies with 536,105 patients and two RCTs were identified. Vitamin D deficiency (< 20 ng/ml) or insufficiency (< 30 ng/ml) was not associated with an significant increased risk of COVID-19 infection (OR for < 20 ng/ml: 1.61, 95% CI: 0.92-2.80, I2 = 92%) or in-hospital death (OR for < 20 ng/ml: 2.18, 95% CI: 0.91-5.26, I2 = 72%; OR for < 30 ng/ml: 3.07, 95% CI: 0.64-14.78, I2 = 66%). Each 10 ng/ml increase in serum vitamin D was not associated with a significant decreased risk of COVID-19 infection (OR: 0.92, 95% CI: 0.79-1.08, I2 = 98%) or death (OR: 0.65, 95% CI: 0.40-1.06, I2 = 79%). The overall quality of evidence (GRADE) for COVID-19 infection and associated death was very low. Vitamin D supplements did not significantly decrease death (OR: 0.57, I2 = 64%) or ICU admission (OR: 0.14, I2 = 90%) in patients with COVID-19. The level of evidence as qualified using GRADE was low. CONCLUSIONS: Current evidence suggested that vitamin D deficiency or insufficiency was not significantly linked to susceptibility to COVID-19 infection or its associated death. Vitamin D supplements did not significantly improve clinical outcomes in patients with COVID-19. The overall GRADE evidence quality was low, we suggest that vitamin D supplementation was not recommended for patients with COVID-19.

Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence. METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations. RESULTS: The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(9):1895-1945.

Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the referral of adults with obstructive sleep apnea (OSA) for surgical consultation. METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of upper airway sleep apnea surgery or bariatric surgery to no treatment as well as studies that reported on patient-important and physiologic outcomes pre- and postoperatively. Statistical analyses were performed to determine the clinical significance of using surgery to treat obstructive sleep apnea in adults. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for making recommendations. RESULTS: The literature search resulted in 274 studies that provided data suitable for statistical analyses. The analyses demonstrated that surgery as a rescue therapy results in a clinically significant reduction in excessive sleepiness, snoring, blood pressure (BP), apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index (ODI); an increase in lowest oxygen saturation (LSAT) and sleep quality; and an improvement in quality of life in adults with OSA who are intolerant or unaccepting of positive airway pressure (PAP) therapy. The analyses demonstrated that surgery as an adjunctive therapy results in a clinically significant reduction in optimal PAP pressure and improvement in PAP adherence in adults with OSA who are intolerant or unaccepting of PAP due to side effects associated with high pressure requirements. The analyses also demonstrated that surgery as an initial treatment results in a clinically significant reduction in AHI/RDI, sleepiness, snoring, BP, and ODI and an increase in LSAT in adults with OSA and major anatomical obstruction. Analysis of bariatric surgery data showed a clinically significant reduction in BP, AHI/RDI, sleepiness, snoring, optimal PAP level, BMI, and ODI and an increase in LSAT in adults with OSA and obesity. Analyses of very limited evidence suggested that upper airway surgery does not result in a clinically significant increase in risk of serious persistent adverse events and suggested that bariatric surgery may result in a clinically significant risk of iron malabsorption that may be managed with iron supplements. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12):2507-2531.

Efectos de la suplementación con vitamina D en el control del asma en pacientes adultos: una revisión sistemática / Effects of vitamin D supplementation on asthma control in adult patients: a systematic review

INTRODUCCIÓN: El asma es una enfermedad crónica inflamatoria de la vía aérea e inmunomediada en su patogénesis. La vitamina D es un inmunomodulador que regula el perfil secretor de citoquinas, entre otras funciones celulares. Una asociación entre la suficiencia de vitamina D y mejoría en la función pulmonar, control de asma y número de exacerbaciones se ha propuesto en adultos, importante dada la elevada prevalencia de insuficiencia de vitamina D globalmente. OBJETIVO: Conocer los efectos de la suplementación con vitamina D en el control del asma en adultos. MÉTODOS: Se realizó una revisión sistemática de la literatura a través de una búsqueda en la base de datos PubMed y EMBASE. Los desenlaces primarios fueron cambios en VEF1, control sintomático, frecuencia de exacerbaciones, además de eventos adversos y FEM como desenlaces secundarios. La calidad de evidencia de los desenlaces fue evaluada a través del modelo GRADE. RESULTADOS: Siete estudios fueron seleccionados después de remover duplicados y aplicar los criterios de inclusión y exclusión, con calidad de evidencia muy baja aplicando sistema GRADE. DISCUSIÓN: No se encontraron diferencias estadísticamente significativas tras la suplementación con vitamina D en los desenlaces evaluados en general, pero dada la calidad de evidencia muy baja y que no se reportaron efectos adversos serios, es necesario tomar cautelosamente estos resultados. Asímismo no se puede descartar la utilidad de esta terapia como tratamiento auxiliar a los pacientes asmáticos con este déficit vitamínico.

BACKGROUND: Asthma is an airway chronic disease, with an important inflammatory component within its pathogenesis, driven by a dysregulated immune response. Vitamin D is an immunomodulator that regulates cell proliferation, differentiation and cytokine secretion profile. An association between vitamin D sufficiency and improvement in pulmonary function, asthma control and a decrease in exacerbations have been proposed in the adult population, which falls into importance given the high prevalence of vitamin D insufficiency globally. OBJECTIVE: To know vitamin D supplementation effects in asthma control in adults. METHODS: Through a PubMed and EMBASE database search, a systematic review of the literature was conducted. Primary outcomes were: changes in FEV1, symptomatic control, exacerbation frequency and PEF and adverse events as secondary outcomes. Outcome evidence quality assessment was made using the GRADE model. Results: Seven studies were selected after taking out duplicates, applying inclusion and exclusion criteria. In all cases, evidence quality assessed by the GRADE system yielded very low quality. CONCLUSIONS: No statistically significant differences were found after vitamin D supplementation in the overall evaluated outcomes. Nonetheless, a cautious interpretation of studies is mandatory, because evidence quality was very low and no serious adverse events were reported. Hence this treatment usefulness as an ancillary therapy for vitamin D deficient asthmatic patients cannot be dismissed.

Offloader knee braces for knee osteoarthritis. / Uso de órtesis de rodilla con refuerzo en descarga en artrosis de rodilla.

INTRODUCTION: Knee osteoarthritis is a relevant health problem given its high prevalence and associated disability. Within the non-pharmacological management alternatives, the use of offloader knee braces has been proposed, however, there is no consensus in the literature regarding its indication. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified 14 systematic reviews including nine studies overall, all of which were randomized trials. We conclude that the use of offloader knee braces in patients with knee osteoarthritis probably increases physical function through walking distance. However, its use may make little or no difference to physical function measured with the Hospital for Special Surgery Knee score, it may slightly worsen the quality of life and increase adverse events, but the certainty of the evidence is low. In addition, we are uncertain whether the use of offloader knee braces reduces pain as the certainty of the evidence has been assessed as very low.

INTRODUCCIÓN: La artrosis de rodilla es una enfermedad degenerativa que constituye un problema de salud relevante dada su alta prevalencia y discapacidad asociada. Dentro de las alternativas de manejo no farmacológico se ha planteado el uso de órtesis de rodilla, sin embargo no existe consenso en la literatura respecto a su utilidad. 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, analizamos los datos de los estudios primarios, realizamos un metanálisis, preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos 14 revisiones sistemáticas que en conjunto incluyeron nueve estudios primarios, de los cuales, todos corresponden a ensayos aleatorizados. Concluimos que el uso de órtesis de rodilla con refuerzo en descarga en pacientes con artrosis de rodilla probablemente aumenta la funcionalidad medida a través de la distancia caminada. Sin embargo, podría resultar en poca o nula diferencia sobre la funcionalidad evaluada con Hospital for Special Surgery Knee score, podría empeorar levemente la calidad de vida y aumentar los efectos adversos, pero la certeza de la evidencia es baja. Además, no es posible establecer con claridad si el uso de órtesis de rodilla disminuye el dolor dado que la certeza de la evidencia fue evaluada como muy baja.

[How to interpret the certainty of evidence based on GRADE (Grading of Recommendations, Assessment, Development and Evaluation)]. / Wie sich die Vertrauenswürdigkeit von Evidenz anhand von GRADE ("grading of recommendations, assessment, development and evaluation") interpretieren lässt.

BACKGROUND: GRADE (Grading of Recommendations, Assessment, Development and Evaluation) is a widely used approach in the fields of medicine and public health to assess the outcome-specific certainty of the evidence in systematic reviews. OBJECTIVES: To make the GRADE approach comprehensible in order to facilitate the reading, understanding and interpretation of GRADE assessments in systematic reviews. MATERIALS AND METHODS: Presentation of the procedure of the GRADE approach using the example of a Cochrane review on selenium supplements in the prevention of prostate cancer. RESULTS: GRADE provides criteria for rating the certainty of evidence. GRADE's approach to rating the certainty of the evidence is based on a four-level system (high, moderate, low, very low). The GRADE approach classifies bodies of randomized controlled trials as initially starting at high certainty and bodies of observational studies at initially starting at low certainty. By assessing the five domains (risk for bias, inconsistency, indirectness, insufficient precision and publication bias), certainty can be rated down or, in the case of large effects, existing dose-response relationships or plausible confounders, rated up. CONCLUSIONS: GRADE is a consistent and transparent approach for rating the certainty of a body of evidence by offering explicit key questions.

Clinical evidence and GRADE assessment for breviscapine injection (DengZhanHuaSu) in patients with acute cerebral infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Breviscapine injections (DengZhanHuaSu, DZHS) is a famous Chinese patent medicine authorized by China Food and Drug Administration, which is widely used to treat acute cerebral infarction (ACI) in China. AIM OF THE STUDY: In the present study, meta-analysis has been performed in determining the efficacy and safety of DZHS combined with conventional treatment (CT) for ACI and GRADE assessment. MATERIALS AND METHODS: Randomized controlled trials (RCTs) testing the use of DZHS for treating ACI were screened by searching the databases of the Cochrane Library, PubMed, Embase, and Web of Science as well as four Chinese databases. Meta-analysis was carried out with RevMan 5.3 and Stata 16.0 software. The quality of research evidence was assessed by the GRADEprofiler (GRADEpro version: 3.6). RESULTS: Forty-three studies (n = 4618) were included. When compared to the control groups, the total effective rate of the national institutes of health stroke scale (NIHSS) was higher in the experimental group with DZHS (RR = 1.23, 95% CI = 1.19 to 1.28, P < 0.001; RR = 1.29, 95% CI = 1.21 to 1.38, P < 0.001); clinical symptoms and signs were improved in the experimental group with DZHS (RR = 1.17, 95% CI = 1.10 to 1.24, P < 0.001; RR = 1.25, 95% CI = 1.11 to 1.42, P < 0.001); the incidence of adverse reactions was reduced in the experimental group with DZHS (RR = 0.50, 95% CI = 0.26 to 0.98, P = 0.044); and the NIHSS score was decreased in the experimental group with DZHS (WMD = -3.30, 95% CI = -3.86 to -2.73, P < 0.001). CONCLUSIONS: DZHS combined with CT is conditionally recommended to improve the total effective rate of the NIHSS, clinical symptoms, and neurological deficits and reduce the incidence of adverse reactions, and no serious adverse reactions were noted. The GRADE assessment indicates that the overall certainty quality of evidence is low. Further large-scale, well-designed and high-quality RCTs are needed to confirm the positive results. PROSPERO registration No. CRD42019128856.

Fitoterápicos como adjuvante à raspagem e alisamento radicular (RAR) para tratamento não cirúrgico de periodontite em adulto: revisão sistemática de ensaios clínicos randomizados / Herbal as an adjunct to scaling and root planing (SRP) in nonsurgical in adult periodontitis treatment: a systematic review of randomized controlled trials

A doença periodontal é a infecção crônica mais prevalente em adultos. A gengivite é a forma mais comum desta doença afetando cerca de 50 a 90% dos adultos no mundo, enquanto que a periodontite pode ser a evolução do cenário e danos que causam a gengivite e afeta 56,7% da população em geral. Os fitoterápicos podem ser uma alternativa promissora na busca de tratamento adjuvante à raspagem e alisamento radicular (RAR) para a periodontite. O objetivo deste trabalho foi avaliar os efeitos dos fitoterápicos (e.g., romã, camomila, capim-limão) como adjuvantes à raspagem e alisamento radicular (RAR) quando comparados à pelo menos um dos seguintes tratamentos: padrão, ou seja, RAR isolado (tratamento padrão); RAR em combinação com tratamento antisséptico clorexidina; RAR em combinação com antibióticos sistêmicos; modulação da resposta do hospedeiro com ou sem medicamentos ativo; enxaguatório antimicrobiano; placebo isolado; placebo associado à RAR; nenhuma intervenção; ou outro tipo de terapia complementar e alternativa (e.g., acupuntura, homeopatia) para o tratamento não cirúrgico de pacientes com periodontite. Foi realizada uma revisão sistem tica de ensaios cl nicos randomizados (ECRs) e/ou quase-randomizados. Os estudos foram obtidos das seguintes bases de dados eletrônicas: MEDLINE, EMBASE, CENTRAL, LILACS e ISI Web of Science. A data da última busca foi em 26 de março de 2019. Revisores independentemente selecionaram e extraíram os dados dos estudos incluídos, e avaliaram o risco de viés dos mesmos. Usamos a abordagem GRADE para avaliar a certeza geral das evidências por desfecho avaliado. Um total de 32 estudos envolvendo 1.225 pacientes foram incluídos na revisão. Resultados provenientes de cinco ECRs com um total de 166 pacientes demonstraram uma diferença estatisticamente significante à favor dos fitoterápicos como adjuvantes à RAR quando comparado ao tratamento padrão (i.e., RAR isolado) na redução da profundidade de sondagem (Diferença de média (DM) -0,51, 95% Intervalo de confiança (IC) -0,78 a -0,23, p = 0,0003; I2 =38%, p = 0,17); entretanto não houve diferença estatisticamente significante entre o grupo de fitoterápico adjuvantes à RAR e o tratamento clorexidina associada à RAR no que concerne ao mesmo desfecho (DM -0,03, 95% IC -0,16 a 0,10, p = 0,65; I2 =0%, p = 0,61; dois estudos, n = 50 pacientes). Além disso, resultados provenientes de apenas um estudo com um total de 37 pacientes demonstraram uma diferença à favor do tratamento padrão (i.e., RAR isolado) quando comparado ao extrato de gel de semente de linhaça como adjuvante à RAR no aumento de nível de inserção clínica (DM -0,99, 95% IC - 1,68 a -0,30, p = 0,005, I2 =não aplicável); entretanto não houve diferença entre o grupo de fitoterápico adjuvante à RAR e o tratamento clorexidina em associação à RAR em relação ao mesmo desfecho (DM -0,12, 95% IC -0,78 a 0,54, p = 0,73; I 2 =19%, p = 0,27; dois estudos, n = 72 pacientes). Não houve diferença estatisticamente significante referente ao desfecho porcentagem de sangramento à sondagem em nenhum dos subgrupos seguintes avaliados: placebo em associação à RAR (DM -1,67, 95% IC -4,82 a 1,48, p = 0,30; I2 =0%, p = 0,79, três estudos, n = 88 pacientes) e clorexidina isolada (DM -0,33, 95% IC -7,02 a 6,36, p = 0,92; I2 =não aplicável, um estudo, n = 34 pacientes). Ainda referente à porcentagem de sangramento à sondagem, mas como variável dicotômica, foi observada uma diferença à favor do gel de mangostão como adjuvante à RAR quando comparado ao tratamento padrão (i.e., RAR isolado) (Risco relativo (RR) 0,72, 95% IC 0,52 a 0,99, p = 0,05; I2 = não aplicável, um estudo, n = 69). No que concerne ao desfecho índice gengival, a clorexidina em combinação à RAR apresentou-se mais efetiva quando comparada ao extrato de camomila (DM 0,07, 95% IC 0,02 a 0,13, p = 0,009; I2 =0%, p = 0,51, três estudos, n = 91 pacientes). No que concerne ao extrato de romã, não foi encontrada diferença quando comparada ao tratamento clorexidina em associação à RAR (DM 0,03, 95% IC -0,22 a 0,28, p = 0,83; I2 =46%, p = 0,16, três estudos, n = 91 pacientes). Foi encontrada uma diferença estatisticamente significante à favor dos fitoterápicos como adjuvantes à RAR quando comparado ao placebo em associação à RAR ainda em se tratando da redução do índice gengival (DM -0,35, 95% IC -0,47 a -0,22, p < 0,00001; I2 =19%, p = 0,29, quatro estudos, n = 259 pacientes). Em relação à redução do índice de placa, houve uma diferença à favor dos fitoterápicos como adjuvantes à RAR quando comparado ao tratamento clorexidina em combinação à RAR (DM -0,13, 95% IC -0,17 a -0,09, p < 0,00001; I 2 =não aplicável, um estudo, n = 30 pacientes), entretanto quando comparado ao placebo em associação à RAR este apresentou maior índice de redução de placa versus os fitoterápicos como adjuvantes à RAR (DM 0,73, 95% IC 0,04 a 1,43, p = 0,04; I2 =97%, p < 0,00001, três estudos, n = 217 pacientes). Entre os estudos elegíveis, não houve evidências relatadas sobre perda dentária e perda óssea, bem como, efeitos adversos, qualidade de vida, e mau hálito. Há baixa certeza das evidências, entretanto, que demonstram a efetividade dos fitoterápicos como adjuvantes à RAR quando comparados ao tratamento com clorexidina em combinação à RAR na redução do índice de placa em pacientes com periodontite. Além disso, há baixa certeza das evidências sugerindo que o fitoterápico como adjuvante à RAR não é inferior à clorexidina associada à RAR em relação aos seguintes desfechos clínicos: profundidade de sondagem e índice gengival em pacientes com periodontite. Da mesma forma, há muito baixa certeza das evidências sugerindo que o fitoterápico como adjuvante à RAR não é inferior à clorexidina associada à RAR em relação os desfecho clínico nível de inserção clínica em pacientes com periodontite. Futuros ensaios clínicos devem avaliar o perfil segurança entre os fitoterápicos e a clorexidina ambos como adjuvantes à RAR, bem como, seus efeitos a longo prazo(AU)

Periodontal disease is a more prevalent chronic infection disease in adults. Gingivitis is the most common form of this disease affecting about 50 to 90% of adults worldwide, while periodontitis may be the evolution of the scenario and damage that causes gingivitis and affects 56.7% of the general population. Herbal medicine may be a promising alternative in seeking adjunctive treatment to scaling and root planing (SRP) for periodontitis. The aim of this review was to evaluate the effects of herbal medicine (e.g., pomegranate, chamomile, lemon grass) as adjuvant to scaling and root planing (SRP) with at least one of the following treatment: SRP only (standard of care, SoC); SRP with antiseptic treatment chlorhexidine; SRP in combination with systemic antibiotics; modulation of host response with or without active drugs, antimicrobial rinsing, placebo, no intervention, other complementary therapy and alternative (eg, acupuncture, homeopathy), for non-surgical treatment of patients with periodontitis. A systematic review of randomized controlled trials (RCTs) and / or quasi-randomized trials was performed. The studies were obtained from the following electronic databases: MEDLINE, EMBASE, CENTRAL, LILACS and ISI Web of Science. The date of the last search was March 26, 2019. Reviewers independently selected and extracted data from included studies, and assessed their risk of bias. We use the GRADE approach to evaluate the overall certainty of evidence by outcomes. A total of 32 studies including 1,225 patients were included in this review. Results from five RCTs with a total of 166 patients showed a statistically significant difference in favor of herbal medicine as adjunct to SRP when compared to SoC in reducing probing depth (Mean Difference (MD) -0.51, 95% Confidence Interval (CI) - 0.78 to -0.23, p = 0.0003; I2 = 38%, p = 0.17); however, there was no difference between the herbal medicine as adjuvant to SRP and the SRP-associated chlorhexidine regarding the same outcome (MD -0.03, 95% CI -0.16 to 0.10, p = 0.65; I 2 = 0%, p = 0.61; two studies, n = 50 patients). Furthermore, results from only one study with a total of 37 patients showed a difference in favor of SoC when compared to flaxseed gel extract as an adjunct to SRP in increasing clinical insertion level (MD 0.99, 95% CI -1.68 to -0.30, p = 0.005; I 2 = not applicable); however there was no difference between the herbal medicine as adjuvant to SRP and the SRPassociated chlorhexidine regarding the same outcome (MD -0.12, 95% CI -0.78 to 0.54 , p = 0.73; I2 = 19%, p = 0.27; two studies, n = 72 patients). There was no difference regarding percentage of bleeding on probing in any of the following evaluated subgroups: placebo in association with SRP (MD -1.67, 95% CI -4.82 to 1.48, p = 0.30; I2 = 0%, p = 0.79, three studies, n = 88 patients) and chlorhexidine alone (MD -0.33, 95% CI -7.02 to 6.36, p = 0.92; I2 = not applicable, one study, n = 34 patients). However, still referring to the percentage of bleeding on probing, but as a dichotomous variable, a difference was observed in favor of mangosteen gel as an adjunct to SRP when compared to SoC (Relative Risk (RR) 0.72 95% CI 0.52 to 0.99, p = 0.05; I 2 = not applicable, one study, n = 69). Regarding gingival index, the SRP-associated chlorhexidine was more effective when compared to chamomile extract (MD 0.07, 95% CI 0.02 to 0,13, p = 0.00; I 2 = 0%, p = 0.51, three studies, n = 91 patients). However, with regards pomegranate extract there was no difference when compared to the SRP-associated chlorhexidine (MD 0.03, 95% CI -0.22 to 0.28, p = 0.83; I 2 = 46%, p = 0.16, three studies, n = 91 patients). Moreover, a statistically significant difference was found in favor of herbal medicine as adjunct to SRP when compared to placebo in association with SRP also in relation to the reduction of gingival index (MD -0.35, 95% CI -0.47 to -0.22), p <0.00001; I2 = 19%, p = 0.29, four studies, n = 259 patients). Regarding the reduction in plaque index, there was a difference in favor of herbal medicine as adjunct to SRP when compared to the SRP-associated chlorhexidine (MD -0.13, 95% CI -0.17 to -0.09, p <0 , 00001; I2 = not applicable, one study, n = 30 patients) and also when compared to placebo in combination with SRP (MD 0.73, 95% CI 0.04 to 1.43, p = 0.04; I2 = 97%, p <0.00001, three studies, n = 217 patients). Among the eligible studies, there was no reported of both tooth and bone loss as well as adverse effects, quality of life, and bad breath. There is low certainty evidence, however, that demonstrates the effectiveness of herbal medicine as adjunct to SRP compared to the SRP-associated chlorhexidine in reducing plaque index in patients with chronic periodontitis. Furthermore, there is low certainty evidence suggesting that herbal medicine as an adjunct to SRP is not inferior to chlorhexidine associated with SRP with regards to the following clinical outcomes: probing depth and reducing gingival index in patients with periodontitis. Similarly, there is very little certainty of evidence suggesting that herbal medicine as an adjunct to SRP is not inferior to chlorhexidine associated with SRP in relation to clinical outcome clinical insertion level in patients with periodontitis. Future clinical trials should evaluate the safety profile between herbal medicine and chlorhexidine both as adjunct to SRP as well as its long-term effects(AU)

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

Light therapies for acne: abridged Cochrane systematic review including GRADE assessments.

We undertook a Cochrane review of randomized controlled trials (RCTs) evaluating the effects of light-based interventions for acne vulgaris. We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and grey literature sources (September 2015). We used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach to assess the quality of evidence (QoE). We included 71 RCTs (4211 participants, median sample size 31). Results from a single study (n = 266, low QoE) showed little or no difference in effectiveness on participants' assessment of improvement between 20% aminolaevulinic acid (ALA) photodynamic therapy (PDT), activated by blue light, vs. vehicle plus blue light, whereas another study (n = 180) comparing ALA-PDT (red light) concentrations showed that 20% ALA-PDT was no more effective than 15% ALA-PDT but better than 10% and 5% ALA-PDT. Pooled data from three studies (n = 360, moderate QoE) showed that methyl aminolaevulinate PDT, activated by red light, had a similar effect on changes in lesion counts vs. placebo cream with red light. Several studies compared yellow light with placebo or no treatment, infrared light with no treatment, gold microparticle suspension with vehicle and clindamycin/benzoyl peroxide (C/BPO) combined with pulsed dye laser with C/BPO alone. None of these showed any clinically significant effects. Most studies reported adverse effects, but inadequately, with scarring reported as absent, and blistering only in studies on intense pulsed light, infrared light and PDT (very low QoE). Carefully planned studies, using standardized outcome measures and common acne treatments as comparators, are needed.

Guía de práctica clínica para el manejo de pacientes con angina estable: guía en versión extensa / Clinical practice guide for the management of patients with stable angina: extensive version guide

Este documento abarcar el manejo del paciente con angina estable.

Guía de práctica clínica sobre la depresión mayor en la infancia y adolescencia: actualización / Clinical practice guide on major depression in childhood and adolescence: update

Objetivos: Mejorar la atención sanitaria prestada a los niños y adolescentes con depresión en el ámbito de la atención primaria y especializada. Ofrecer recomendaciones al profesional sanitario para la atención de estos pacientes. Desarrollar indicadores de evaluación de la calidad asistencial. Ayudar a los pacientes y a sus familiares a la toma de decisiones informada y a la mejora de la comunicación entre los pacientes y los profesionales. No se abordan otros servicios, como los sociales, educacionales o de tiempo libre. Aspectos contemplados Las áreas clínicas que contempla la guía son: - Criterios diagnósticos y caracterización de la depresión infanto-juvenil. - Factores de riesgo y de protección. - Evaluación. - Perspectivas de pacientes y familiares. - Cribado en atención primaria. - Opciones de tratamiento de la depresión: - Tratamiento psicológico (modalidades, numero de sesiones, duración). - Manejo farmacológico (indicación, dosis, duración, cese, efectos secundarios, toxicidad y ausencia de respuesta a la medicación). - Tratamiento combinado. - Prevención de recaídas/recurrencia. - Estrategias para la depresión que no responde al tratamiento. - Tratamiento de la depresión mayor con síntomas psicóticos. - Otras alternativas terapéuticas: ejercicio físico, intervenciones online y terapias alternativas. - El consentimiento informado desde el punto de vista legal en España. - Algoritmo terapéutico: criterios de derivación y manejo según gravedad. Aspectos no abordados en la GPC 1) Los trastornos distímico, bipolar, ni el adaptativo. 2) La prevención primaria de la depresión en la infancia y adolescencia. 3) La prevención de la conducta suicida, debido a que este aspecto se recoge en la GPC de Prevención y Tratamiento de la Conducta Suicida del Programa de GPC en el SNS, en su apartado especifico sobre infancia y adolescencia.

Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on noninvasive treatment of low back pain. METHODS: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials and systematic reviews published through April 2015 on noninvasive pharmacologic and nonpharmacologic treatments for low back pain. Updated searches were performed through November 2016. Clinical outcomes evaluated included reduction or elimination of low back pain, improvement in back-specific and overall function, improvement in health-related quality of life, reduction in work disability and return to work, global improvement, number of back pain episodes or time between episodes, patient satisfaction, and adverse effects. TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute, subacute, or chronic low back pain. RECOMMENDATION 1: Given that most patients with acute or subacute low back pain improve over time regardless of treatment, clinicians and patients should select nonpharmacologic treatment with superficial heat (moderate-quality evidence), massage, acupuncture, or spinal manipulation (low-quality evidence). If pharmacologic treatment is desired, clinicians and patients should select nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants (moderate-quality evidence). (Grade: strong recommendation). RECOMMENDATION 2: For patients with chronic low back pain, clinicians and patients should initially select nonpharmacologic treatment with exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction (moderate-quality evidence), tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation (low-quality evidence). (Grade: strong recommendation). RECOMMENDATION 3: In patients with chronic low back pain who have had an inadequate response to nonpharmacologic therapy, clinicians and patients should consider pharmacologic treatment with nonsteroidal anti-inflammatory drugs as first-line therapy, or tramadol or duloxetine as second-line therapy. Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. (Grade: weak recommendation, moderate-quality evidence).

The Treatment of Neck Pain-Associated Disorders and Whiplash-Associated Disorders: A Clinical Practice Guideline

OBJECTIVE: The objective was to develop a clinical practice guideline on the management of neck pain-associated disorders (NADs) and whiplash-associated disorders (WADs). This guideline replaces 2 prior chiropractic guidelines on NADs and WADs. METHODS: Pertinent systematic reviews on 6 topic areas (education, multimodal care, exercise, work disability, manual therapy, passive modalities) were assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and data extracted from admissible randomized controlled trials. We incorporated risk of bias scores in the Grading of Recommendations Assessment, Development, and Evaluation. Evidence profiles were used to summarize judgments of the evidence quality, detail relative and absolute effects, and link recommendations to the supporting evidence. The guideline panel considered the balance of desirable and undesirable consequences. Consensus was achieved using a modified Delphi. The guideline was peer reviewed by a 10-member multidisciplinary (medical and chiropractic) external committee. RESULTS: For recent-onset (0-3 months) neck pain, we suggest offering multimodal care; manipulation or mobilization; range-of-motion home exercise, or multimodal manual therapy (for grades I-II NAD); supervised graded strengthening exercise (grade III NAD); and multimodal care (grade III WAD). For persistent (>3 months) neck pain, we suggest offering multimodal care or stress self-management; manipulation with soft tissue therapy; high-dose massage; supervised group exercise; supervised yoga; supervised strengthening exercises or home exercises (grades I-II NAD); multimodal care or practitioner's advice (grades I-III NAD); and supervised exercise with advice or advice alone (grades I-II WAD). For workers with persistent neck and shoulder pain, evidence supports mixed supervised and unsupervised high-intensity strength training or advice alone (grades I-III NAD). CONCLUSIONS: A multimodal approach including manual therapy, self-management advice, and exercise is an effective treatment strategy for both recent-onset and persistent neck pain

Treatment of adult patients with schizophrenia and complex mental health needs: a national clinical guideline

BACKGROUND AND AIM: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key issues. METHODS: Systematic literature searches were performed stepwise for each review question to identify relevant guidelines, systematic reviews/meta-analyses, and randomized controlled trials. The quality of the body of evidence for each review question was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Clinical recommendations were developed on the basis of the evidence, assessment of the risk-benefit ratio, and perceived patient preferences. RESULTS: Based on the identified evidence, a guideline development group (GDG) recommended that the following interventions should be offered routinely: antipsychotic maintenance therapy, family intervention and assertive community treatment. The following interventions should be considered: long-acting injectable antipsychotics, neurocognitive training, social cognitive training, cognitive behavioural therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence was available, the GDG agreed on a good practice recommendation. CONCLUSIONS: The implementation of this guideline in daily clinical practice can facilitate good treatment outcomes within the population of patients with schizophrenia and complex mental health needs. The guideline does not cover all available interventions and should be used in conjunction with other relevant guidelines.(AU)

ESPEN guidelines on nutrition in dementia

BACKGROUND: Older people suffering from dementia are at increased risk of malnutrition due to various nutritional problems, and the question arises which interventions are effective in maintaining adequate nutritional intake and nutritional status in the course of the disease. It is of further interest whether supplementation of energy and/or specific nutrients is able to prevent further cognitive decline or even correct cognitive impairment, and in which situations artificial nutritional support is justified. OBJECTIVE: It is the purpose of these guidelines to cover these issues with evidence-based recommendations. METHODS: The guidelines were developed by an international multidisciplinary working group in accordance with officially accepted standards. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds and accepted in an online survey among ESPEN members. RESULTS: 26 recommendations for nutritional care of older persons with dementia are given. In every person with dementia, screening for malnutrition and close monitoring of body weight are recommended. In all stages of the disease, oral nutrition may be supported by provision of adequate, attractive food in a pleasant environment, by adequate nursing support and elimination of potential causes of malnutrition. Supplementation of single nutrients is not recommended unless there is a sign of deficiency. Oral nutritional supplements are recommended to improve nutritional status but not to correct cognitive impairment or prevent cognitive decline. Artificial nutrition is suggested in patients with mild or moderate dementia for a limited period of time to overcome a crisis situation with markedly insufficient oral intake, if low nutritional intake is predominantly caused by a potentially reversible condition, but not in patients with severe dementia or in the terminal phase of life. CONCLUSION: Nutritional care and support should be an integral part of dementia management. In all stages of the disease, the decision for or against nutritional interventions should be made on an individual basis after carefully balancing expected benefit and potential burden, taking the (assumed) patient will and general prognosis into account.(AU)

Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (aswpd), delayed sleep-wake phase disorder (dswpd), non-24-hour sleep-wake rhythm disorder (n24swd), and irregular sleep-wake rhythm disorder (iswrd): an update for 2015

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.