Janus kinases (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is involved in pathophysiologic cascade of a notable number of rheumatic diseases. The development of JAK inhibitors has expanded treatment choices in rheumatoid arthritis (RA) with a sustained class-effect efficacy. Filgotinib is a novel selective inhibitor of JAK1 isoform licensed for use in RA and ulcerative colitis. In this review we aim to present an analysis of filgotinib\'s efficacy and drug-specific safety warnings. Patients with RA with or without concomitant conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) (naïve or experienced) and those who have failed biologic Disease-Modifying Antirheumatic Drugs (bDMARDs) were examined in randomised clinical trials. Filgotinib was also tested against placebo, methotrexate, or adalimumab. Long-term extension trials provide insights for up to four years of continuous filgotinib administration. Beneficial effects are depicted in both disease activity parameters and quality of life indexes in moderate or severe RA with a longitudinal efficacy. In head-to-head comparison with adalimumab, filgotinib 200 mg was non-inferior. Adverse effects alerts are marked by the elevated risk of infectious adverse effects with the exception of herpes zoster infection, which has a low incidence.

We aimed to evaluate the efficacy of IVIG in the treatment with patients with recurrent spontaneous abortion (RSA).
PubMed, Embase, Web of science, Cochrane library were searched for randomized controlled (RCTs) about effect of IVIG on RSA from inception to August 20, 2021. Values of standardized mean differences (SMD) were determined for continuous outcomes.
A total of 15 articles involving 902 patients were included in meta-analysis. Compared with the control group, IVIG can increase the live birth rate of recurrent spontaneous abortion patients [OR = 3.06, 95%CI (1.23, 7.64, P = .02]. However, recurrent abortion was divided into primary and secondary abortion for subgroup analysis, and there was no statistical difference. Besides, IVIG can also increase the expression in peripheral blood CD3+[OR = .4, 95%CI(-2.47, 3.15, P = .81],CD4+[OR = 1.16, 95%CI(-4.60, 6.93, P = .69], and a decrease in the expression of CD8+[OR = -1.78, 95%CI(-5.30, 1.75, P = .32], but there is no statistical significance.
IVIG can significantly increase the live birth rate of recurrent spontaneous abortion. However, the evidence needs further verification and the curative effect is uncertain. It is necessary to further explore the pathogenesis of recurrent abortion and the mechanism of IVIG in the treatment of recurrent spontaneous abortion. Besides, more high-quality randomized controlled trials suitable for population, race, dosage and timing of IVIG in the treatment of recurrent abortion are needed to confirm its effectiveness, and effective systematic evaluation is also needed to evaluate its use benefit.

UNASSIGNED: Anxiety disorders are highly prevalent and cause significant distress, disability, and cost. Medication adverse effects and interactions increase in mid-life and late-life, highlighting the need for effective non-pharmacological interventions.
UNASSIGNED: We aimed to evaluate the extent of evidence supporting exercise interventions for anxiety and subthreshold anxiety disorders in mid-life and late-life.
UNASSIGNED: Systematic review.
UNASSIGNED: We searched MEDLINE, PsycINFO, Embase, Emcare, Ovid Nursing, CINAHL Plus, Cochrane Library, Health Collection, Humanities & Social Sciences Collection, and https://clinicaltrials.gov databases for trials published January 1994-May 2019. Randomised controlled trials of exercise interventions involving aerobic exercise or resistance training for adults aged 40 years and above with anxiety or subthreshold anxiety disorders in residential or health settings were identified. The primary outcome was change in anxiety. We excluded trials including participants aged below 40 years, participants with diagnosis of separation anxiety, selective mutism, obsessive-compulsive disorder, acute stress disorder and post-traumatic stress disorder, and head-to-head comparisons of interventions. Trial quality was assessed using the Cochrane Risk of Bias Tool and evidence synthesised in narrative form.
UNASSIGNED: Four trials totalling 132 participants met inclusion criteria, although some had methodological limitations. Interventions included a home-based resistance training intervention, supervised group-based aerobic intervention, Tai Chi intervention, and supervised group-based aerobic and strength intervention. Three trials included late-life participants and the fourth mid-life. Three trials demonstrated greater reductions in anxiety in the intervention group compared with control. The fourth trial showed pre-post reductions in anxiety in both groups, with between-group difference not reaching statistical significance.
UNASSIGNED: There is limited supportive evidence suggesting that exercise interventions have potential to be effective, feasible and safe non-pharmacological interventions for anxiety and subthreshold anxiety disorders in mid-life and late-life. The heterogeneity, limited number and high risk of bias of some trials meant that we were not able to conduct a meta-analysis. Tailoring of interventions may improve uptake and reduce dropout. The paucity of research in this area with only four included trials demonstrates the urgent need for future and larger trials to provide proof of concept, data about effective types and doses of exercise interventions, and guidance to community, clinical, and public health services.

Burning mouth syndrome is a chronic condition, which is characterised by a burning sensation or pain in the mucosa of the oral cavity. Treatment options include antidepressants, antipsychotics, anticonvulsants, analgesics, hormone replacement therapies and more recently photobiomodulation. This study aims to perform a systematic review with meta-analysis in order to determine the effect of photobiomodulation on pain relief and the oral health-related quality of life associated with this condition. A bibliographical search of the Pubmed, Embase, Web of Science and Scopus databases was conducted. Only randomised clinical trials were included. Pain and quality of life were calculated as mean difference and pooled at different treatment points (baseline = T0 and final time point = Tf) and laser modality. From a total of 103 records, 7 articles were retrieved for inclusion. PBM group had a greater decrease in pain than control group at Tf with a mean difference =  - 2.536 (IC 95% - 3.662 to - 1.410; I2 = 85.33%, p < 0.001). An improvement in oral health-related quality of life was observed in both groups, although this was more significant in the photobiomodulation group mean difference =  - 5.148 (IC 95% - 8.576 to - 1.719; I2 = 84.91%, p = 0.003). For the red laser, a greater improvement than infrared was observed, in pain, mean difference =  - 2.498 (IC 95% - 3.942 to - 1.053; I2 = 79.93%, p < 0.001), and in quality of life, mean difference =  - 8.144 (IC 95% - 12.082 to - 4.206; I2 = 64.22%, p = 0.027). Photobiomodulation, in particular, red laser protocols, resulted in improvement in pain and in quality of life of burning mouth syndrome patients.

There is substantial variation in how menopausal vasomotor symptoms are reported and measured among intervention studies. This has prevented meaningful comparisons between treatments and limited data synthesis.
To review systematically the outcome reporting and measures used to assess menopausal vasomotor symptoms from randomised controlled trials of treatments.
We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to May 2018.
Randomised controlled trials with a primary outcome of menopausal vasomotor symptoms in women and a sample size of at least 20 women per study arm.
Data about study characteristics, primary vasomotor-related outcomes and methods of measuring them.
The search identified 5591 studies, 214 of which were included. Forty-nine different primary reported outcomes were identified for vasomotor symptoms and 16 different tools had been used to measure these outcomes. The most commonly reported outcomes were frequency (97/214), severity (116/214), and intensity (28/114) of vasomotor symptoms or a composite of these outcomes (68/214). There was little consistency in how the frequency and severity/intensity of vasomotor symptoms were defined.
There is substantial variation in how menopausal vasomotor symptoms have been reported and measured in treatment trials. Future studies should include standardised outcome measures which reflect the priorities of patients, clinicians, and researchers. This is most effectively achieved through the development of a Core Outcome Set. This systematic review is the first step towards development of a Core Outcome Set for menopausal vasomotor symptoms.
Menopausal hot flushes and night sweats have been reported in 49 different ways in clinical research. A core outcome set is urgently required.

BACKGROUND: The prognostic value of the systemic inflammatory response in cancer has been well established in observational studies. This review aims to examine and rationalise the evidence for the role of systemic inflammation based prognostic scores in randomised clinical trials.
METHODS: An extensive literature review using targeted medical subject headings was carried out in the MEDLINE, EMBASE, and CDSR databases until January 2018. Titles were examined for relevance and after exclusions bibliographies were hand searched to identify additional trials.
RESULTS: There were 29 trials containing data on 37,020 patients presented in full paper form and 8 trials containing data on 3805 patients presented in abstract form. Most trials were published within the last three years. Seven trials containing data on 6044 patients were published in 2015. Eight trials containing data on 4384 patients were published in 2016. Twelve trials containing data on 27,228 patients were published in 2017. The majority of trials were in advanced inoperable cancer and colorectal cancer was the most common cancer type with 11 articles containing data on 27,909 patients. The GPS/mGPS was shown to have prognostic value in randomised clinical trials in NSCLC, oesophageal cancer, pancreatic cancer, prostate cancer and breast cancer. The NLR/dNLR was shown to have prognostic value in randomised clinical trials in nasopharyngeal cancer, oesophageal cancer, pancreatic cancer, biliary cancer, prostate cancer and multiple cancer types.
CONCLUSIONS: The prognostic value of systemic inflammation based prognostic scores has been confirmed in multiple trials and should be incorporated into future prospective randomised clinical trials.

BACKGROUND: Evidence-based clinical practice is challenging in all fields, but poses special barriers in the field of rare diseases. The present paper summarises the main barriers faced by clinical research in rare diseases, and highlights opportunities for improvement.
METHODS: Systematic literature searches without meta-analyses and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project.
RESULTS: Barriers specific to rare diseases comprise the difficulty to recruit participants because of rarity, scattering of patients, limited knowledge on natural history of diseases, difficulties to achieve accurate diagnosis and identify patients in health information systems, and difficulties choosing clinically relevant outcomes.
CONCLUSIONS: Evidence-based clinical practice for rare diseases should start by collecting clinical data in databases and registries; defining measurable patient-centred outcomes; and selecting appropriate study designs adapted to small study populations. Rare diseases constitute one of the most paradigmatic fields in which multi-stakeholder engagement, especially from patients, is needed for success. Clinical research infrastructures and expertise networks offer opportunities for establishing evidence-based clinical practice within rare diseases.

To assess the benefits and harms of exercise in patients with depression.
Systematic review DATA SOURCES: Bibliographical databases were searched until 20 June 2017.
Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention.
Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was -0.66 standardised mean difference (SMD) (95% CI -0.86 to -0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into -0.11 SMD (-0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes.
Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes.
The protocol was published in the journal Systematic Reviews: 2015; 4:40.

OBJECTIVE: Is massage therapy effective for people with musculoskeletal disorders compared to any other treatment or no treatment?
METHODS: Systematic review of randomised clinical trials.
METHODS: People with musculoskeletal disorders.
METHODS: Massage therapy (manual manipulation of the soft tissues) as a stand-alone intervention.
RESULTS: The primary outcomes were pain and function.
RESULTS: The 26 eligible randomised trials involved 2565 participants. The mean sample size was 95 participants (range 16 to 579) per study; 10 studies were considered to be at low risk of bias. Overall, low-to-moderate-level evidence indicated that massage reduces pain in the short term compared to no treatment in people with shoulder pain and osteoarthritis of the knee, but not in those with low back pain or neck pain. Furthermore, low-to-moderate-level evidence indicated that massage improves function in the short term compared to no treatment in people with low back pain, knee arthritis or shoulder pain. Low-to-very-low-level evidence from single studies indicated no clear benefits of massage over acupuncture, joint mobilisation, manipulation or relaxation therapy in people with fibromyalgia, low back pain and general musculoskeletal pain.
CONCLUSIONS: Massage therapy, as a stand-alone treatment, reduces pain and improves function compared to no treatment in some musculoskeletal conditions. When massage is compared to another active treatment, no clear benefit was evident.

BACKGROUND: Chinese herbal medicine (CHM) has been increasingly used as an adjuvant treatment for multi-drug resistant tuberculosis (MDR-TB) in China. To inform clinical practice, we performed a systematic review on the beneficial effect and safety of CHM for MDR-TB.
METHODS: We searched six electronic databases for randomised clinical trials (RCTs) of CHM for MDR-TB. We used RevMan 5.2 software for data analyses with effect estimates as risk ratio (RR) with 95% confidence interval (CI).
RESULTS: 30 RCTs involving 3374 participants with MDR-TB were included. The methodological quality was generally poor in terms of risk of bias. Meta-analyses favoured CHM plus chemotherapy on sputum bacteriological conversion rate compared with chemotherapy alone after initiation of treatment (6th mos: RR 1.27, 95% CI 1.14 to 1.41, n = 12; 12th mos: RR 1.30, 95% CI 1.11 to 1.52, n = 6; 18th mos: RR 1.19, 95% CI 1.11 to 1.27, n = 9). Compared with chemotherapy alone, meta-analyses showed benefit from CHM plus chemotherapy on lung lesions resorption rate (6th mos: RR 1.10, 95% CI 0.91 to 1.32, n = 5; 12th mos: RR 1.26, 95% CI 1.10 to 1.45, n = 4; 18th mos: RR 1.19, 95% CI 1.08 to 1.32, n = 7) and cavity closure rate (12th mos: RR 1.48, 95% CI 1.06 to 2.07, n = 2; 18th mos: RR 1.26, 95% CI 1.04 to 1.53, n = 5), relapse rate (RR 0.28, 95% CI 0.16 to 0.50, n = 4), and abnormal liver function (RR 0.56, 95% CI 0.46 to 0.69, n = 14). No serious adverse effects were reported.
CONCLUSIONS: CHM as an adjuvant to anti-TB chemotherapy may have beneficial effect for MDR-TB in terms of bacteriological and radiological outcomes, and is relatively safe. However, due to poor methodological reporting of the included trials, a confirmative conclusion needs to be supported by further robust clinical trials.