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1.
Cochrane Database Syst Rev ; 5: CD013029, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-34097768

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of blindness in high-income countries. The majority of cases of AMD are of the non-exudative type. Experts have proposed photobiomodulation (PBM) therapy as a non-invasive procedure to restore mitochondrial function, upregulate cytoprotective factors and prevent apoptotic cell death in retinal tissue affected by AMD. OBJECTIVES: To assess the effectiveness and safety of PBM compared to standard care, no treatment or sham treatment for people with non-exudative AMD. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 5, 2020), Ovid MEDLINE, Embase, ISRCTN, ClinicalTrials.gov and the WHO ICTRP to 11 May 2020 with no language restrictions. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) on participants receiving any type of PBM therapy for non-exudative AMD compared to standard care, sham treatment or no treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We considered the following outcome measures at 12 months: best-corrected visual acuity (BCVA) ; contrast sensitivity; near vision; low luminance density score; reading speed; vision-related quality of life score; and adverse events such as progression of AMD and conversion to exudative AMD. We graded the certainty of the evidence using GRADE. MAIN RESULTS: We included two published RCTs from single centres in the UK and Canada, which recruited 60 participants (60 eyes) and 30 participants (46 eyes) respectively. Participants in these trials were people with non-exudative AMD with Age-Related Eye Disease Study (AREDS) categories 2 to 4. One study compared single wavelength PBM with no treatment. This study was at risk of performance bias because the study was not masked, and there was attrition bias. One study compared multi-wavelength PBM with sham treatment and conflicts of interest were reported by study investigators. We also identified three eligible ongoing RCTs from searching the clinical trials database. When comparing PBM with sham treatment or no treatment for non-exudative AMD, there was no evidence of any meaningful clinical difference in BCVA at 12 months (mean difference (MD) 0.02 logMAR, 95% confidence interval (CI) -0.02 to 0.05; 2 RCTs, 90 eyes; low-certainty evidence). One study comparing multi-wavelength PBM with sham treatment showed an improvement in contrast sensitivity at Level E (18 cycles/degree) at 12 months (MD 0.29 LogCS, 95% CI 0.23 to 0.35; 1 RCT, 46 eyes; low-certainty evidence). Visual function and health-related quality of life scores were comparable between single wavelength PBM and no treatment groups at 12 months (VFQ-48 score MD 0.43, 95% CI -0.17 to 1.03; P = 0.16; 1 RCT, 47 eyes; low-certainty evidence). When comparing PBM with sham treatment or no treatment for non-exudative AMD, there was no evidence of any meaningful clinical difference in conversion to exudative AMD (risk ratio (RR) 0.97, 95% CI 0.17 to 5.44; 2 RCTs, 96 eyes; very low-certainty evidence) at 12 months. There was inconclusive evidence that single wavelength PBM prevents the progression of AMD (RR 0.79, 95% CI 0.41 to 1.53; P = 0.48; 1 RCT, 50 eyes; low-certainty evidence). Disease progression was defined as the development of advanced AMD or significant increase in drusen volume. No included study reported near vision, low luminance vision or reading speed outcomes. AUTHORS' CONCLUSIONS: Currently there remains uncertainty whether PBM treatment is beneficial in slowing progression of non-exudative macular degeneration. There is a need for further well-designed controlled trials assessing dosimetry, powered for both effectiveness and safety outcomes. Consideration should be given to the adoption of agreed clinical outcome measures and patient-based outcome measures for AMD.


Assuntos
Terapia com Luz de Baixa Intensidade/métodos , Degeneração Macular/radioterapia , Viés , Intervalos de Confiança , Sensibilidades de Contraste , Progressão da Doença , Humanos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde , Placebos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Acuidade Visual
2.
Medicine (Baltimore) ; 100(22): e26190, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087885

RESUMO

BACKGROUND: Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to evaluate the efficacy and safety of adalimumab in patients with moderate-to-severe HS. METHODS: We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Pooled estimates, namely standardized mean difference (SMD) and relative risk (RR), were calculated using random-effect model with trial sequential analysis. Small study effects were examined using the Doi plot. Certainty of evidence (CoE) was assessed using "The Grading of Recommendations Assessment, Development, and Evaluation" approach, and number-needed-to-treat (NNT) was calculated. RESULTS: Five randomized controlled trials, involving 1014 patients, were included. We performed subgroup analysis of adalimumab administered subcutaneously both weekly and every other week. Adalimumab administered weekly was associated with better clinical response achievement (RR 1.76, 95% confidence interval [95% CI] 1.35-2.29; trial sequential analysis TSA-adjusted CI 1.01-3.08; CoE: low; NNT = 5) and a significant improvement in modified Sartorius score (SMD = -0.45, 95% CI = -0.76 to -0.13; CoE: very low; NNT = 10) and dermatology life quality index (DLQI) (SMD -0.47, 95% CI -0.61 to -0.32; CoE: low; NNT = 10). Nevertheless, adalimumab administered every other week showed an improvement only in modified Sartorius score. The pooled RRs of adverse events in both groups revealed no statistical significance when compared with the placebo. CONCLUSIONS: Adalimumab administered weekly resulted in not only better clinical responses than placebo but also significantly improved disease severity and quality of life of patients with moderate-to-severe HS. Our study provides supporting evidence to the current guidelines and aids decision-making in the application of adalimumab in HS management.


Assuntos
Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hidradenite Supurativa/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Casos e Controles , Hidradenite Supurativa/psicologia , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Placebos/administração & dosagem , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico
3.
Medicine (Baltimore) ; 100(22): e26211, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087896

RESUMO

BACKGROUND: Riociguat is a novel soluble guanylate cyclase stimulator, and has been widely used for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH). Some studies found that riociguat had better effects on CTEPH and proved to be safe, but the results were not utterly consistent. Therefore, the purpose of this study was to comprehensively evaluate the efficacy and safety of riociguat in the treatment of CTEPH. METHODS: Randomized controlled trials on riociguat for the treatment of CTEPH were searched through such electronic databases as PubMed, Embase, Cochrane Library, Web of Science, China national knowledge internet, and Wanfang. The outcomes included exercise capacity, pulmonary hemodynamics, and side effects. The fixed-effects or random-effects models were used to analyze the pooled data, and heterogeneity was assessed by the I2 test. RESULTS: Four studies involving 520 patients were included in this meta-analysis. Compared with the placebo group, riociguat significantly improved the hemodynamic indexes and increased 6-min walking distance (P < .0001, standardized mean difference (SMD) = -0.24, 95%CI -0.35 to -0.12; P < .00001, SMD = 0.52, 95%CI 0.33 to 0.71), and decreased the Borg dyspnea score (P = .002, SMD = -0.31, 95%CI -0.51 to -0.12). In addition, riociguat could also significantly reduce the living with pulmonary hypertension scores and increase the EQ-5D scores (P = .01, SMD=-0.23, 95%CI -0.42 to -0.05; P < .00001, SMD = 0.47, 95%CI 0.27 to 0.66), but there was no significant difference in the change level of N-terminal pro-hormone B-type natriuretic peptide in patients with riociguat (P = .20, SMD = -0.24, 95%CI -0.61 to -0.13). The common adverse events of riociguat were dyspepsia and peripheral edema, and no other serious adverse reactions were observed. CONCLUSIONS: We confirmed that riociguat had better therapeutic effects in improving the hemodynamic parameters and exercise capacity in patients with CTEPH without inducing serious adverse events. This will provide a reasonable medication regimen for the treatment of CTEPH.


Assuntos
Ativadores de Enzimas/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Embolia Pulmonar/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Estudos de Casos e Controles , China/epidemiologia , Doença Crônica , Gerenciamento de Dados , Ativadores de Enzimas/administração & dosagem , Ativadores de Enzimas/efeitos adversos , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Hipertensão Arterial Pulmonar/complicações , Embolia Pulmonar/complicações , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Guanilil Ciclase Solúvel/efeitos dos fármacos , Resultado do Tratamento
4.
Nat Commun ; 12(1): 3427, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103518

RESUMO

Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.


Assuntos
Peptídeos/química , Peptídeos/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Sequência de Aminoácidos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Endocitose/efeitos dos fármacos , Determinação de Ponto Final , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Ácidos Oleicos/química , Peptídeos/farmacologia , Placebos , Conformação Proteica , Espectroscopia de Prótons por Ressonância Magnética , Termodinâmica , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
5.
Cochrane Database Syst Rev ; 5: CD011169, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973648

RESUMO

BACKGROUND: Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. This chronic and recurring condition occurs in women of reproductive age. It is a common cause of pain or infertility and can cause non-specific symptoms such as lower back pain, dyspareunia (pain during or after intercourse), and dysmenorrhoea (menstrual pain). Endometriosis is an oestrogen-dependent disease. Medical treatment aims to relieve symptoms and shrink lesions by suppressing the normal menstrual cycle. In this review, we consider medication specifically aiming to modulate oestrogen receptors as an alternative method of treatment. OBJECTIVES: To evaluate the effectiveness and safety of selective oestrogen receptor modulators (SERMs) in the management of endometriosis. SEARCH METHODS: We searched for trials in the following databases (from their inception to 28 May 2020): Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Studies (CRS Online), MEDLINE, Embase, CINAHL, PsycINFO, and registers of ongoing trials. In addition, we searched all reference lists of included trials, and we contacted experts in the field, in an attempt to locate trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing selective oestrogen receptor modulators (SERMs) with placebo, no treatment, other medical treatment, or surgery for endometriosis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Two review authors independently selected trials for inclusion, assessed risk of bias, and extracted data using data extraction forms. We used risk ratios (RRs) with 95% confidence intervals (CIs) for reporting dichotomous data. Primary review outcomes were relief of pelvic pain and adverse events. Secondary outcomes included quality of life, recurrence rate, and economic and fertility outcomes. MAIN RESULTS: We included only one RCT, which included 93 women, comparing the SERM raloxifene with placebo in biopsy-proven endometriosis. All women first underwent complete surgical excision of all lesions. Evidence was of very low quality: the main limitation was imprecision - with very sparse data from only one small study, which included only women after surgical treatment. Relief of pelvic pain The included study did not specifically measure the primary outcome of pain relief. Study authors reported that time to return of pelvic pain (defined as two months of pain equal to or more severe than pain at study entry) was more rapid in the raloxifene group (P = 0.03). Adverse events The included study reported adverse events such as pelvic pain, ovarian cyst, headache, migraine, and depression. We are uncertain whether raloxifene improves the incidence of pelvic pain (RR 1.25, 95% CI 0.63 to 2.45), ovarian cysts (RR 1.57, 95% CI 0.55 to 4.43), headache (RR 1.09, 95% CI 0.49 to 2.43), migraine (RR 0.73, 95% CI 0.28 to 1.95), depression (RR 1.96, 95% CI 0.63 to 6.06), or other adverse events (RR 0.08, 95% CI 0.00 to 1.30) (all: 1 study, n = 93; very low-quality evidence). Quality of life The study described a statistically significant difference in mental health quality of life (QoL) by 12 months, in favour of placebo treatment (mean difference 11.1, 95% CI 0.01 to 21.19). Other QoL data did not differ between groups but were not reported in detail. Recurrence rate, fertility, and economic outcomes We are uncertain whether raloxifene improves the recurrence rate of endometriosis, proven by biopsy, when compared to placebo (RR 1.20, 95% CI 0.66 to 2.21; 1 study, n = 93; very low-quality evidence). This suggests that if 28% of women taking placebo have biopsy-proven recurrence of endometriosis, between 19% and 62% of those taking raloxifene will do so. These outcomes are prone to bias, as not all women had an actual second laparoscopy. Recurrence based on symptoms (non-menstrual pain, dysmenorrhoea, or dyspareunia) was described; in these cases, symptoms improved after use of raloxifene as well as after use of placebo. The included study did not report data on economic outcomes. No comparative data were available on pregnancy, as the study included only women who agreed to postpone pregnancy until after the study endpoint; the few pregnancies that did occur were uneventful but were regarded as an adverse event.  AUTHORS' CONCLUSIONS: Based on a single, small RCT and incomplete data, we are uncertain of the effects of SERMs on pain relief in surgically treated patients with endometriosis. The included study was stopped prematurely because of higher pain scores among women who took SERMs when compared to scores among those receiving placebo. Further research is needed to fully evaluate the role of SERMs in endometriosis.


Assuntos
Endometriose/tratamento farmacológico , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Dismenorreia/etiologia , Dispareunia/etiologia , Endometriose/complicações , Endometriose/cirurgia , Feminino , Humanos , Dor Pélvica/tratamento farmacológico , Placebos/uso terapêutico
6.
Cochrane Database Syst Rev ; 5: CD003336, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34002371

RESUMO

BACKGROUND: People with chronic heart failure (HF) are at risk of thromboembolic events, including stroke, pulmonary embolism, and peripheral arterial embolism; coronary ischaemic events also contribute to the progression of HF. The use of long-term oral anticoagulation is established in certain populations, including people with HF and atrial fibrillation (AF), but there is wide variation in the indications and use of oral anticoagulation in the broader HF population. OBJECTIVES: To determine whether long-term oral anticoagulation reduces total deaths and stroke in people with heart failure in sinus rhythm. SEARCH METHODS: We updated the searches in CENTRAL, MEDLINE, and Embase in March 2020. We screened reference lists of papers and abstracts from national and international cardiovascular meetings to identify unpublished studies. We contacted relevant authors to obtain further data. We did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing oral anticoagulants with placebo or no treatment in adults with HF, with treatment duration of at least one month. We made inclusion decisions in duplicate, and resolved any disagreements between review authors by discussion, or a third party. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, and assessed the risks and benefits of antithrombotic therapy by calculating odds ratio (OR), accompanied by the 95% confidence intervals (CI). MAIN RESULTS: We identified three RCTs (5498 participants). One RCT compared warfarin, aspirin, and no antithrombotic therapy, the second compared warfarin with placebo in participants with idiopathic dilated cardiomyopathy, and the third compared rivaroxaban with placebo in participants with HF and coronary artery disease. We pooled data from the studies that compared warfarin with a placebo or no treatment. We are uncertain if there is an effect on all-cause death (OR 0.66, 95% CI 0.36 to 1.18; 2 studies, 324 participants; low-certainty evidence); warfarin may increase the risk of major bleeding events (OR 5.98, 95% CI 1.71 to 20.93, NNTH 17). 2 studies, 324 participants; low-certainty evidence). None of the studies reported stroke as an individual outcome. Rivaroxaban makes little to no difference to all-cause death compared with placebo (OR 0.99, 95% CI 0.87 to 1.13; 1 study, 5022 participants; high-certainty evidence). Rivaroxaban probably reduces the risk of stroke compared to placebo (OR 0.67, 95% CI 0.47 to 0.95; NNTB 101; 1 study, 5022 participants; moderate-certainty evidence), and probably increases the risk of major bleeding events (OR 1.65, 95% CI 1.17 to 2.33; NNTH 79; 1 study, 5008 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Based on the three RCTs, there is no evidence that oral anticoagulant therapy modifies mortality in people with HF in sinus rhythm. The evidence is uncertain if warfarin has any effect on all-cause death compared to placebo or no treatment, but it may increase the risk of major bleeding events. There is no evidence of a difference in the effect of rivaroxaban on all-cause death compared to placebo. It probably reduces the risk of stroke, but probably increases the risk of major bleedings. The available evidence does not support the routine use of anticoagulation in people with HF who remain in sinus rhythm.


Assuntos
Anticoagulantes/uso terapêutico , Cardiomiopatia Dilatada/complicações , Insuficiência Cardíaca/complicações , Tromboembolia/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Aspirina/uso terapêutico , Doença Crônica , Insuficiência Cardíaca/mortalidade , Frequência Cardíaca , Hemorragia/induzido quimicamente , Humanos , Efeito Placebo , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/etiologia , Tromboembolia/mortalidade , Varfarina/efeitos adversos , Varfarina/uso terapêutico
7.
Cochrane Database Syst Rev ; 5: CD012714, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34031871

RESUMO

BACKGROUND: Idiopathic hypersomnia is a disorder of excessive daytime sleepiness, often accompanied by long sleep times or pronounced difficulty in awakening, in the absence of a known cause. The optimal treatment strategy for idiopathic hypersomnia is currently unknown. OBJECTIVES: To assess the effects of medications for daytime sleepiness and related symptoms in individuals with idiopathic hypersomnia and, in particular, whether medications may: 1. reduce subjective measures of sleepiness; 2. reduce objective measures of sleepiness; 3. reduce symptoms of cognitive dysfunction; 4. improve quality of life; and 5. be associated with adverse events. SEARCH METHODS: We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended. SELECTION CRITERIA: Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials. MAIN RESULTS: We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two pharmaceutical company-sponsored trials compared modafinil with placebo, involving 102 participants, nearly all of whom had idiopathic hypersomnia without long sleep time. Modafinil significantly improved self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence). Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence). Ratings of exhaustion and effectiveness/performance were improved with modafinil compared to placebo in one study. Number of naps per week was no different between modafinil and placebo across two studies. Participants receiving modafinil experienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of sleepiness included 10 participants with idiopathic hypersomnia, with or without long sleep time, and compared clarithromycin to placebo. We only included the subset of trial data for those participants with idiopathic hypersomnia, per our protocol. There were no significant differences between clarithromycin and placebo for the Epworth Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects. AUTHORS' CONCLUSIONS: Modafinil is effective for the treatment of several aspects of idiopathic hypersomnia symptomatology, based on studies predominantly including participants with idiopathic hypersomnia without long sleep times, with low risk of bias, and evidence certainty ranging from high to low. There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia. There is a clear need for additional studies testing interventions for the treatment of idiopathic hypersomnia.


Assuntos
Claritromicina/uso terapêutico , Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico , Hipersonia Idiopática/complicações , Modafinila/uso terapêutico , Promotores da Vigília/uso terapêutico , Viés , Distúrbios do Sono por Sonolência Excessiva/etiologia , Humanos , Placebos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Vigília
8.
Cochrane Database Syst Rev ; 5: CD009289, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34033120

RESUMO

BACKGROUND: Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used. OBJECTIVES: To evaluate the benefits and harms of topical azole treatments for otomycosis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution). A. Topical azoles versus placebo None of the studies assessed this comparison. B. Topical azoles versus no treatment None of the studies assessed this comparison. C. One type of topical azole versus another type of topical azole i) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole) Three studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles. One study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence). Clotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence). ii) Bifonazole cream versus bifonazole solution One study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence). AUTHORS' CONCLUSIONS: We found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.


Assuntos
Antifúngicos/administração & dosagem , Otomicose/tratamento farmacológico , Administração Tópica , Adulto , Antifúngicos/efeitos adversos , Viés , Criança , Clotrimazol/administração & dosagem , Clotrimazol/efeitos adversos , Cicloeptanos/administração & dosagem , Cicloeptanos/efeitos adversos , Fluconazol/administração & dosagem , Fluconazol/efeitos adversos , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Miconazol/administração & dosagem , Miconazol/efeitos adversos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Biomed Res Int ; 2021: 6693221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954198

RESUMO

Background: Although video-assisted thoracoscopy has a smaller incision than traditional surgery, the postoperative pain is still severe. Ultrasound-guided pectoral nerve block (PECS) II is a new technique that can reduce pain in patients, and it had not been reported in the analgesia after thoracoscopic lobectomy. Methods: 40 patients scheduled for thoracoscopic lobectomy were randomly divided into two groups. Patients in the PECS II group received 0.5% ropivacaine 25 ml before the general anesthesia, while patients in the placebo group received 0.9% saline. Thirty minutes after the block was performed, a pin-prick test was used to analyze the sense of pain of T2-T6 segments. The primary endpoint was the total consumption of fentanyl. Data were collected in the postanesthesia care unit (PACU) and in the ward within 24 hours after operation. Results: The total consumption of fentanyl and the consumption of fentanyl in the intravenous analgesia pump within 24 hours after the operation were significantly lower in the PECS II group compared to the placebo group (p < 0.05). The implementation rate of rescue analgesia during operation and in PACU in the PECS II group was significantly lower than that in the placebo group (p < 0.05). The numerical rating scale (NRS) in 1 and 4 h after operation was lower in the PECS II group (p < 0.05). Mean arterial pressure (MAP) and heart rate (HR) of the PECS II group at chest entering (T1) were significantly lower than those in the placebo group (p < 0.05). Conclusion: Preconditioning of PECS II can stabilize the intraoperative circulation and significantly reduce pain and the consumption of opioids after operation.


Assuntos
Pulmão/cirurgia , Bloqueio Nervoso , Dor Pós-Operatória/prevenção & controle , Nervos Torácicos/cirurgia , Toracoscopia/efeitos adversos , Analgesia , Pressão Arterial , Método Duplo-Cego , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Placebos
10.
Cochrane Database Syst Rev ; 5: CD007144, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942281

RESUMO

BACKGROUND: This is an updated version of the Cochrane review previously published in 2016. There is considerable disagreement about the risk of recurrence following a first unprovoked epileptic seizure. A decision about whether to start antiepileptic drug treatment following a first seizure should be informed by information on the size of any reduction in risk of future seizures, the impact on long-term seizure remission, and the risk of adverse effects. OBJECTIVES: To review the probability of seizure recurrence, seizure remission, mortality, and adverse effects of antiepileptic drug (AED) treatment given immediately after the first seizure compared to controls (placebo, deferred treatment, or no treatment) in children and adults. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to May 24, 2019) on 28 May 2019. There were no language restrictions. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised or quasi-randomised, controlled trials from Embase, ClinicalTrials.gov and the World Health Organisation International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that could be blinded or unblinded. People of any age with a first unprovoked seizure of any type. Included studies compared participants receiving immediate antiepileptic treatment versus those receiving deferred treatment, those assigned to placebo, and those untreated. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies identified by the search strategy for inclusion in the review and extracted data. The certainty of the evidence for the outcomes was classified in four categories according to the GRADE approach. Dichotomous outcomes were expressed as Risk Ratios (RR) with 95% confidence intervals (CI). Time-to-event outcomes were expressed as Hazard Ratios (HR) with 95% CI. Only one trial used a double-blind design, and the two largest studies were unblinded. Most of the recurrences were generalised tonic-clonic seizures, a major type of seizures that is easily recognised, which should reduce the risk of outcome reporting bias. MAIN RESULTS: After exclusion of irrelevant papers, six studies (eleven reports) were selected for inclusion. Individual participant data were available from the two largest studies for meta-analysis. Selection bias and attrition bias could not be excluded within the four smaller studies, but the two largest studies reported attrition rates and adequate methods of randomisation and allocation concealment. Only one small trial used a double-blind design and the other trials were unblinded; however, most of the recurrences were generalised tonic-clonic seizures, a type of seizure that is easily recognisable. Compared to controls, participants randomised to immediate treatment had a lower probability of relapse at one year (RR 0.49, 95% CI 0.42 to 0.58; 6 studies, 1634 participants; high-certainty evidence), at five years (RR 0.78; 95% CI 0.68 to 0.89; 2 studies, 1212 participants; high-certainty evidence) and a higher probability of an immediate five-year remission (RR 1.25; 95% CI 1.02 to 1.54; 2 studies, 1212 participants; high-certainty evidence). However, there was no difference between immediate treatment and control in terms of five-year remission at any time (RR 1.02, 95% CI 0.87 to 1.21; 2 studies, 1212 participants; high-certainty evidence). Antiepileptic drugs did not affect overall mortality after a first seizure (RR 1.16; 95% CI 0.69 to 1.95; 2 studies, 1212 participants; high-certainty evidence). Compared to deferred treatment, treatment of the first seizure was associated with a significantly higher risk of adverse events (RR 1.49, 95% CI 1.23 to 1.79; 2 studies, 1212 participants; moderate-certainty evidence). We assessed the certainty of the evidence as moderate to low for the association of higher risk of adverse events when treatment of the first seizure was compared to no treatment or placebo, (RR 14.50, 95% CI 1.93 to 108.76; 1 study; 118 participants) and (RR 4.91, 95% CI 1.10 to 21.93; 1 study, 228 participants) respectively. AUTHORS' CONCLUSIONS: Treatment of the first unprovoked seizure reduces the risk of a subsequent seizure but does not affect the proportion of patients in remission in the long term. Antiepileptic drugs are associated with adverse events, and there is no evidence that they reduce mortality. In light of this review, the decision to start antiepileptic drug treatment following a first unprovoked seizure should be individualised and based on patient preference, clinical, legal, and sociocultural factors.


Assuntos
Anticonvulsivantes/uso terapêutico , Convulsões/tratamento farmacológico , Tempo para o Tratamento , Adulto , Anticonvulsivantes/efeitos adversos , Viés , Criança , Feminino , Humanos , Masculino , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão , Risco , Prevenção Secundária , Convulsões/complicações , Convulsões/mortalidade , Fatores de Tempo , Conduta Expectante
11.
Medicine (Baltimore) ; 100(20): e25740, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011032

RESUMO

INTRODUCTION: The efficacy of gabapentin for pain management of arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of gabapentin versus placebo on the postoperative pain intensity of arthroscopy. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through April 2020 for randomized controlled trials assessing the effect of gabapentin versus placebo on pain control of arthroscopy. This meta-analysis is performed using the random-effect model. RESULTS: Five randomized controlled trials are included in the meta-analysis. Overall, compared with control group for arthroscopy, gabapentin remarkably decreases pain scores at 24 hour (standard mean difference [SMD]=-0.68; 95% confidence interval [CI]=-1.15 to -0.02; P = .21), analgesic consumption (SMD = -18.24; 95% CI=-24.61 to -11.88; P < .00001), nausea and vomiting (OR = 0.42; 95% CI = 0.21 to 0.84; P = .01), but has no obvious influence on pain scores at 6 h (SMD = -1.30; 95% CI = -2.92 to 0.31; P = .11) or dizziness (OR = 1.12; 95% CI = 0.56 to 2.24; P = .75). CONCLUSIONS: Gabapentin is effective for pain control after arthroscopy.


Assuntos
Artroscopia/efeitos adversos , Gabapentina/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/epidemiologia , Gabapentina/efeitos adversos , Humanos , Manejo da Dor/efeitos adversos , Medição da Dor/estatística & dados numéricos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Placebos/administração & dosagem , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
12.
Nutrients ; 13(5)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922493

RESUMO

BACKGROUND: Tart Montmorency cherries (MC) have been shown to be rich in anthocyanins and other phytochemicals known to have anti-inflammatory properties and influence pathways that might improve cardiometabolic health. However, there is limited evidence for the longer-term use of tart cherries on these indices. The aim of the current study was to investigate the influence of MC concentrate on cardiometabolic health indices following a 3-month supplementation period. METHODS: Fifty middle-aged adults (34 males and 16 females; mean ± SD age: 48 ± 6 years and BMI: 27.6 ± 3.7 kg/m2) completed a randomised, placebo-controlled parallel study in which they either received MC or an isocaloric placebo. Participants drank 30 mL of their allocated treatment twice per day for 3 months. Vascular function (blood pressure [BP], heart rate [HR], pulse wave velocity and analysis [PWV/A], and flow mediated dilation [FMD]) as well as indices of metabolic health (insulin, glucose, lipid profiles, and high sensitivity C reactive protein) were measured following an overnight fast before and after the 3 months. RESULTS: No effect of the intervention between the groups was observed for vascular function or metabolic health variables following the intervention (p > 0.05). However, MC concentrate was shown to be safe and well-tolerated and, importantly, did not have any deleterious effects on these outcomes. In conclusion, MC has no influence on cardiometabolic indices in middle-aged adults.


Assuntos
Fatores de Risco Cardiometabólico , Suplementos Nutricionais , Prunus/química , Adulto , Pressão Sanguínea , Composição Corporal , Dieta , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos
13.
Nat Commun ; 12(1): 2078, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824310

RESUMO

Multiple sclerosis (MS) can be divided into four phenotypes based on clinical evolution. The pathophysiological boundaries of these phenotypes are unclear, limiting treatment stratification. Machine learning can identify groups with similar features using multidimensional data. Here, to classify MS subtypes based on pathological features, we apply unsupervised machine learning to brain MRI scans acquired in previously published studies. We use a training dataset from 6322 MS patients to define MRI-based subtypes and an independent cohort of 3068 patients for validation. Based on the earliest abnormalities, we define MS subtypes as cortex-led, normal-appearing white matter-led, and lesion-led. People with the lesion-led subtype have the highest risk of confirmed disability progression (CDP) and the highest relapse rate. People with the lesion-led MS subtype show positive treatment response in selected clinical trials. Our findings suggest that MRI-based subtypes predict MS disability progression and response to treatment and may be used to define groups of patients in interventional trials.


Assuntos
Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/diagnóstico , Aprendizado de Máquina não Supervisionado , Adulto , Bases de Dados como Assunto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Reprodutibilidade dos Testes
14.
Nutrients ; 13(4)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917503

RESUMO

BACKGROUND: Dietary supplements have been proposed to help manage blood cholesterol, including red yeast rice (RYR) extracts, plant sterols and stanols, beta-glucans, and some probiotics. This study was conducted to evaluate the efficacy of RYR (containing 10 mg of monacolin K) combined with 109 CFU of three Lactoplantibacillus plantarum strains (CECT7527, CECT7528, and CECT7529). METHODS: A 12-week randomized, double-blinded, placebo-controlled clinical trial was conducted. In total, 39 adult patients were enrolled, having total cholesterol (TC) ≥200 mg/dL, and being statin-naïve or having recently stopped statin treatment because of intolerance. Active product or placebo were taken once daily, and subjects were evaluated at baseline, 6, and 12 weeks. RESULTS: Study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81% in active vs. 22% in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups and standard error of the mean = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively) upon adjusting for the baseline imbalance in hypercholesterolemia treatment. No adverse effects were noted during the study. CONCLUSION: This combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.


Assuntos
LDL-Colesterol/sangue , Suplementos Nutricionais , Hipercolesterolemia/dietoterapia , Lactobacillaceae , Lovastatina/administração & dosagem , Probióticos/administração & dosagem , Adulto , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Resultado do Tratamento
15.
Nutrients ; 13(4)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921293

RESUMO

The aims of this observational "proof-of-concept" study were to analyze the clinical/psychological characteristics and gut microbiota/mycobiota composition of individuals with suspected non-celiac gluten/wheat sensitivity (NCGS/WS) according to responses to the double-blind-placebo-controlled (DBPC) crossover gluten challenge test. Fifty individuals with suspected NCGS/WS were subjected to the DBPC challenge test; anthropometric measurements, psychometric questionnaires, and fecal samples were collected. Twenty-seven (54%) participants were gluten responsive (NCGS), and 23 were placebo responsive, with an order effect. NCGS individuals displayed a significantly lower risk of eating disorders and a higher mental health score when compared to placebo-responsive participants, confirmed by multiple logistic regression analyses (OR = 0.87; 95% CI 0.76-0.98, p = 0.021, and OR = 1.30; 95% CI 1.06-1.59, p = 0.009, respectively). Principal coordinate analyses based on microbiota composition showed a separation by the DBPC response (p = 0.039). For Bacteroides (p = 0.05) and Parabacteroides (p = 0.007), the frequency of amplicon sequence variants was lower, and that for Blautia (p = 0.009) and Streptococcus (p = 0.004) was higher in NCGS individuals at multiple regression analyses. No difference in the mycobiota composition was detected between the groups. In conclusion, almost half of the individuals with suspected gluten sensitivity reported symptoms with placebo; they showed lower mental health scores, increased risk for eating disorders, and a different gut microbiota composition.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Microbioma Gastrointestinal/imunologia , Glutens/administração & dosagem , Micobioma/imunologia , Hipersensibilidade a Trigo/diagnóstico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Fezes/microbiologia , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/imunologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Glutens/imunologia , Humanos , Testes Imunológicos/métodos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Placebos/administração & dosagem , Estudo de Prova de Conceito , Psicometria , Medição de Risco , Fatores de Risco , Autorrelato , Hipersensibilidade a Trigo/imunologia , Hipersensibilidade a Trigo/psicologia
16.
Cochrane Database Syst Rev ; 4: CD012789, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33849080

RESUMO

BACKGROUND: Trigger finger is a common hand condition that occurs when movement of a finger flexor tendon through the first annular (A1) pulley is impaired by degeneration, inflammation, and swelling. This causes pain and restricted movement of the affected finger. Non-surgical treatment options include activity modification, oral and topical non-steroidal anti-inflammatory drugs (NSAIDs), splinting, and local injections with anti-inflammatory drugs. OBJECTIVES: To review the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) versus placebo, glucocorticoids, or different NSAIDs administered by the same route for trigger finger. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, CNKI (China National Knowledge Infrastructure), ProQuest Dissertations and Theses, www.ClinicalTrials.gov, and the WHO trials portal until 30 September 2020. We applied no language or publication status restrictions. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and quasi-randomised trials of adult participants with trigger finger that compared NSAIDs administered topically, orally, or by injection versus placebo, glucocorticoid, or different NSAIDs administered by the same route. DATA COLLECTION AND ANALYSIS: Two or more review authors independently screened the reports, extracted data, and assessed risk of bias and GRADE certainty of evidence. The seven major outcomes were resolution of trigger finger symptoms, persistent moderate or severe symptoms, recurrence of symptoms, total active range of finger motion, residual pain, patient satisfaction, and adverse events. Treatment effects were reported as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS: Two RCTs conducted in an outpatient hospital setting were included (231 adult participants, mean age 58.6 years, 60% female, 95% to 100% moderate to severe disease). Both studies compared a single injection of a non-selective NSAID (12.5 mg diclofenac or 15.0 mg ketorolac) given at lower than normal doses with a single injection of a glucocorticoid (triamcinolone 20 mg or 5 mg), with maximum follow-up duration of 12 weeks or 24 weeks. In both studies, we detected risk of attrition and performance bias. One study also had risk of selection bias. The effects of treatment were sensitive to assumptions about missing outcomes. All seven outcomes were reported in one study, and five in the other. NSAID injection may offer little to no benefit over glucocorticoid injection, based on low- to very low-certainty evidence from two trials. Evidence was downgraded for bias and imprecision. There may be little to no difference between groups in resolution of symptoms at 12 to 24 weeks (34% with NSAIDs, 41% with glucocorticoids; absolute effect 7% lower, 95% confidence interval (CI) 16% lower to 5% higher; 2 studies, 231 participants; RR 0.83, 95% CI 0.62 to 1.11; low-certainty evidence). The rate of persistent moderate to severe symptoms may be higher at 12 to 24 weeks in the NSAIDs group (28%) compared to the glucocorticoid group (14%) (absolute effect 14% higher, 95% CI 2% to 33% higher; 2 studies, 231 participants; RR 2.03, 95% CI 1.19 to 3.46; low-certainty evidence). We are uncertain whether NSAIDs result in fewer recurrences at 12 to 24 weeks (1%) compared to glucocorticoid (21%) (absolute effect 20% lower, 95% CI 21% to 13% lower; 2 studies, 231 participants; RR 0.07, 95% CI 0.01 to 0.38; very low-certainty evidence). There may be little to no difference between groups in mean total active motion at 24 weeks (235 degrees with NSAIDs, 240 degrees with glucocorticoid) (absolute effect 5% lower, 95% CI 34.54% lower to 24.54% higher; 1 study, 99 participants; MD -5.00, 95% CI -34.54 to 24.54; low-certainty evidence). There may be little to no difference between groups in residual pain at 12 to 24 weeks (20% with NSAIDs, 24% with glucocorticoid) (absolute effect 4% lower, 95% CI 11% lower to 7% higher; 2 studies, 231 participants; RR 0.84, 95% CI 0.54 to 1.31; low-certainty evidence). There may be little to no difference between groups in participant-reported treatment success at 24 weeks (64% with NSAIDs, 68% with glucocorticoid) (absolute effect 4% lower, 95% CI 18% lower to 15% higher; 1 study, 121 participants; RR 0.95, 95% CI 0.74 to 1.23; low-certainty evidence). We are uncertain whether NSAID injection has an effect on adverse events at 12 to 24 weeks (1% with NSAIDs, 1% with glucocorticoid) (absolute effect 0% difference, 95% CI 2% lower to 3% higher; 2 studies, 231 participants; RR 2.00, 95% CI 0.19 to 21.42; very low-certainty evidence). AUTHORS' CONCLUSIONS: For adults with trigger finger, by 24 weeks' follow-up, results from two trials show that compared to glucocorticoid injection, NSAID injection offered little to no benefit in the treatment of trigger finger. Specifically, there was no difference in resolution, symptoms, recurrence, total active motion, residual pain, participant-reported treatment success, or adverse events.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/uso terapêutico , Cetorolaco/uso terapêutico , Dedo em Gatilho/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Viés , Diclofenaco/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Cetorolaco/administração & dosagem , Masculino , Pessoa de Meia-Idade , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Triancinolona/administração & dosagem , Triancinolona/uso terapêutico
17.
Cochrane Database Syst Rev ; 4: CD008605, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33851429

RESUMO

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.  OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment. SEARCH METHODS: We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature. SELECTION CRITERIA: We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence. MAIN RESULTS: The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported. AUTHORS' CONCLUSIONS: Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.


Assuntos
Agonistas de Dopamina/uso terapêutico , Fertilização In Vitro , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Aborto Espontâneo/prevenção & controle , Administração Oral , Aminoquinolinas/uso terapêutico , Bromocriptina/uso terapêutico , Cabergolina/uso terapêutico , Agonistas de Dopamina/administração & dosagem , Ergolinas/uso terapêutico , Feminino , Humanos , Nascido Vivo/epidemiologia , Síndrome de Hiperestimulação Ovariana/epidemiologia , Placebos/uso terapêutico , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Injeções de Esperma Intracitoplásmicas
18.
Cochrane Database Syst Rev ; 4: CD009951, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33870484

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. This is an update of a review last published in 2014. OBJECTIVES: To systematically assess the effects of probiotic supplements used either alone or in combination with pharmacological and non-pharmacological interventions on the prevention of GDM. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (20 March 2020), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and cluster-randomised trials comparing the use of probiotic supplementation with either placebo or diet for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies were not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results were only included if study authors confirmed that data in the abstract came from the final analysis. Otherwise, the abstract was left awaiting classification. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included studies. Data were checked for accuracy. MAIN RESULTS: In this update, we included seven trials with 1647 participants. Two studies were in overweight and obese women, two in obese women and three did not exclude women based on their weight. All included studies compared probiotics with placebo. The included studies were at low risk of bias overall except for one study that had an unclear risk of bias. We excluded two studies, eight studies were ongoing and three studies are awaiting classification. Six included studies with 1440 participants evaluated the risk of GDM. It is uncertain if probiotics have any effect on the risk of GDM compared to placebo (mean risk ratio (RR) 0.80, 95% confidence interval (CI) 0.54 to 1.20; 6 studies, 1440 women; low-certainty evidence). The evidence was low certainty due to substantial heterogeneity and wide CIs that included both appreciable benefit and appreciable harm. Probiotics increase the risk of pre-eclampsia compared to placebo (RR 1.85, 95% CI 1.04 to 3.29; 4 studies, 955 women; high-certainty evidence) and may increase the risk of hypertensive disorders of pregnancy (RR 1.39, 95% CI 0.96 to 2.01, 4 studies, 955 women), although the CIs for hypertensive disorders of pregnancy also indicated probiotics may have no effect. There were few differences between groups for other primary outcomes. Probiotics make little to no difference in the risk of caesarean section (RR 1.00, 95% CI 0.86 to 1.17; 6 studies, 1520 women; high-certainty evidence), and probably make little to no difference in maternal weight gain during pregnancy (MD 0.30 kg, 95% CI -0.67 to 1.26; 4 studies, 853 women; moderate-certainty evidence). Probiotics probably make little to no difference in the incidence of large-for-gestational age infants (RR 0.99, 95% CI 0.72 to 1.36; 4 studies, 919 infants; moderate-certainty evidence) and may make little to no difference in neonatal adiposity (2 studies, 320 infants; data not pooled; low-certainty evidence). One study reported adiposity as fat mass (MD -0.04 kg, 95% CI -0.12 to 0.04), and one study reported adiposity as percentage fat (MD -0.10%, 95% CI -1.19 to 0.99). We do not know the effect of probiotics on perinatal mortality (RR 0.33, 95% CI 0.01 to 8.02; 3 studies, 709 infants; low-certainty evidence), a composite measure of neonatal morbidity (RR 0.69, 95% CI 0.36 to 1.35; 2 studies, 623 infants; low-certainty evidence), or neonatal hypoglycaemia (mean RR 1.15, 95% CI 0.69 to 1.92; 2 studies, 586 infants; low-certainty evidence). No included studies reported on perineal trauma, postnatal depression, maternal and infant development of diabetes or neurosensory disability. AUTHORS' CONCLUSIONS: Low-certainty evidence from six trials has not clearly identified the effect of probiotics on the risk of GDM. However, high-certainty evidence suggests there is an increased risk of pre-eclampsia with probiotic administration. There were no other clear differences between probiotics and placebo among the other primary outcomes. The certainty of evidence for this review's primary outcomes ranged from low to high, with downgrading due to concerns about substantial heterogeneity between studies, wide CIs and low event rates. Given the risk of harm and little observed benefit, we urge caution in using probiotics during pregnancy. The apparent effect of probiotics on pre-eclampsia warrants particular consideration. Eight studies are currently ongoing, and we suggest that these studies take particular care in follow-up and examination of the effect on pre-eclampsia and hypertensive disorders of pregnancy. In addition, the underlying potential physiology of the relationship between probiotics and pre-eclampsia risk should be considered.


Assuntos
Diabetes Gestacional/prevenção & controle , Pré-Eclâmpsia/etiologia , Probióticos/uso terapêutico , Viés , Cesárea/estatística & dados numéricos , Feminino , Humanos , Obesidade , Sobrepeso , Placebos/uso terapêutico , Gravidez , Probióticos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Cochrane Database Syst Rev ; 4: CD012654, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871063

RESUMO

BACKGROUND: Dietary supplements with ginseng, or ginseng alone, are widely used for a broad range of conditions, including erectile dysfunction. Ginseng is particularly popular in Asian countries. Individual studies assessing its effects are mostly small, of uneven methodological quality and have unclear results. OBJECTIVES: To assess the effects of ginseng on erectile dysfunction. SEARCH METHODS: We conducted systematic searches on multiple electronic databases, including CENTRAL, MEDLINE, Embase, CINAHL, AMED, and loco-regional databases of east Asia, from their inceptions to 30 January 2021 without restrictions on language and publication status. Handsearches included conference proceedings. SELECTION CRITERIA: We included randomized or quasi-randomized controlled trials that evaluated the use of any type of ginseng as a treatment for erectile dysfunction compared to placebo or conventional treatment. DATA COLLECTION AND ANALYSIS: Two authors independently classified studies and three authors independently extracted data and assessed risk of bias in the included studies. We rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: We included nine studies with 587 men with mild to moderate erectile dysfunction, aged from 20 to 70 years old. The studies all compared ginseng to placebo. We found only short-term follow-up data (up to 12 weeks).  Primary outcomes Ginseng appears to have a trivial effect on erectile dysfunction when compared to placebo based on the Erectile Function Domain of the International Index of Erectile Function (IIEF)-15 instrument (scale: 1 to 30, higher scores imply better function; mean difference [MD] 3.52, 95% confidence interval [CI] 1.79 to 5.25; I² = 0%; 3 studies; low certainty evidence) assuming a minimal clinically important difference (MCID) of 4.  Ginseng probably also has a trivial effect on erectile function when compared to placebo based on the IIEF-5 instrument (scale: 1 to 25, higher scores imply better function; MD 2.39, 95% CI 0.89 to 3.88; I² = 0%; 3 studies; moderate certainty evidence) assuming a MCID of 5. Ginseng may have little to no effect on adverse events compared to placebo (risk ratio [RR] 1.45, 95% CI 0.69 to 3.03; I² = 0%; 7 studies; low certainty evidence). Based on 86 adverse events per 1000 men in the placebo group, this would correspond to 39 more adverse events per 1000 (95% CI 27 fewer to 174 more). Secondary outcomes Ginseng may improve men's self-reported ability to have intercourse (RR 2.55, 95% CI 1.76 to 3.69; I² = 23%; 6 studies; low certainty evidence). Based on 207 per 1000 men self-reporting the ability to have intercourse in the placebo group, this would correspond to 321 more men (95% CI 158 more to 558 more) per 1000 self-reporting the ability to have intercourse. Ginseng may have a trivial effect on men's satisfaction with intercourse based on the Intercourse Satisfaction Domain of the IIEF-15 (scale: 0 to 15, higher scores imply greater satisfaction; MD 1.19, 95% CI 0.41 to 1.97; I²=0%; 3 studies; low certainty evidence) based on a MCID of 25% improvement from baseline. It may also have a trivial effect on men's satisfaction with intercourse based on item 5 of the IIEF-5 (scale: 0 to 5, higher scores imply more satisfaction; MD 0.60, 95% CI 0.02 to 1.18; 1 study; low certainty evidence) based on a MCID of 25% improvement from baseline. No study reported quality of life as an outcome. We found no trial evidence to inform comparisons to other treatments for erectile dysfunction, such as phosphodiesterase-5 inhibitors. We were unable to conduct any predefined subgroup analyses. AUTHORS' CONCLUSIONS: Based on mostly low certainty evidence, ginseng may only have trivial effects on erectile function or satisfaction with intercourse compared to placebo when assessed using validated instruments. Ginseng may improve men's self-reported ability to have intercourse. It may have little to no effect on adverse events. We found no trial evidence comparing ginseng to other agents with a more established role in treating erectile dysfunction, such as phosphodiesterase-5 inhibitors.


Assuntos
Disfunção Erétil/tratamento farmacológico , Panax , Fitoterapia/métodos , Adulto , Idoso , Coito , Intervalos de Confiança , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
20.
Cochrane Database Syst Rev ; 4: CD011535, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871055

RESUMO

BACKGROUND: Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. OBJECTIVES: To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS: For this living systematic review we updated our searches of the following databases monthly to September 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched two trials registers to the same date. We checked the reference lists of included studies and relevant systematic reviews for further references to eligible RCTs. SELECTION CRITERIA: Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate-to-severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate-to-severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse events (SAEs) at induction phase. We did not evaluate differences in specific adverse events. DATA COLLECTION AND ANALYSIS: Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse events). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes and all comparisons, according to CINeMA, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer on treatment hierarchy: 0% (treatment is the worst for effectiveness or safety) to 100% (treatment is the best for effectiveness or safety). MAIN RESULTS: We included 158 studies (18 new studies for the update) in our review (57,831 randomised participants, 67.2% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (58%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 20 treatments. In all, 133 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (53/158) as being at high risk of bias; 25 were at an unclear risk, and 80 at low risk. Most studies (123/158) declared funding by a pharmaceutical company, and 22 studies did not report their source of funding. Network meta-analysis at class level showed that all of the interventions (non-biological systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in reaching PASI 90. At class level, in reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the non-biological systemic agents. At drug level, infliximab, ixekizumab, secukinumab, brodalumab, risankizumab and guselkumab were significantly more effective in reaching PASI 90 than ustekinumab and three anti-TNF alpha agents: adalimumab, certolizumab, and etanercept. Ustekinumab and adalimumab were significantly more effective in reaching PASI 90 than etanercept; ustekinumab was more effective than certolizumab, and the clinical effectiveness of ustekinumab and adalimumab was similar. There was no significant difference between tofacitinib or apremilast and three non-biological drugs: fumaric acid esters (FAEs), ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab, and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness of these drugs was similar, except for ixekizumab which had a better chance of reaching PASI 90 compared with secukinumab, guselkumab and brodalumab. The clinical effectiveness of these seven drugs was: infliximab (versus placebo): risk ratio (RR) 50.29, 95% confidence interval (CI) 20.96 to 120.67, SUCRA = 93.6; high-certainty evidence; ixekizumab (versus placebo): RR 32.48, 95% CI 27.13 to 38.87; SUCRA = 90.5; high-certainty evidence; risankizumab (versus placebo): RR 28.76, 95% CI 23.96 to 34.54; SUCRA = 84.6; high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86; SUCRA = 81.4; high-certainty evidence; secukinumab (versus placebo): RR 25.79, 95% CI 21.61 to 30.78; SUCRA = 76.2; high-certainty evidence; guselkumab (versus placebo): RR 25.52, 95% CI 21.25 to 30.64; SUCRA = 75; high-certainty evidence; and brodalumab (versus placebo): RR 23.55, 95% CI 19.48 to 28.48; SUCRA = 68.4; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as mirikizumab, tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to moderate certainty for all the comparisons. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS: Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab and brodalumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly-reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the evidence for all the interventions was of low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials directly comparing active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between non-biological systemic agents and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Doença Crônica , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metanálise em Rede , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
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