IMPORTANCE Harms and benefits of opioids for chronic noncancer pain remain unclear. OBJECTIVE To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain. DATA SOURCES AND STUDY SELECTION The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. DATA EXTRACTION AND SYNTHESIS Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence. MAIN OUTCOMES AND MEASURES The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting. RESULTS Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], −0.69 cm [95% CI, −0.82 to −0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low-to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, −0.60 cm [95% CI, −1.54 to 0.34 cm]; physical functioning: WMD, −0.90 points [95% CI, −2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, −0.13 cm [95% CI, −0.99 to 0.74 cm]; physical functioning: WMD, −5.31 points [95% CI, −13.77 to 3.14 points]), and anticonvulsants (pain: WMD, −0.90 cm [95% CI, −1.65 to −0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, −5.77 to 6.66 points]). CONCLUSIONS AND RELEVANCE In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

We aim to examine the miR-1288 expression in cancer cell lines and a large cohort of patients with colorectal cancer. Two colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The miRNA expressions of miR-1288 were tested on these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). An exogenous miR-1288 (mimic) was used to detect cell proliferation and cell cycle changes in SW480 using MTT calorimetric assay and flow cytometry, respectively. In addition, tissues from 122 patients with surgical resection of colorectum (82 adenocarcinomas, 20 adenomas, and 20 non-neoplastic tissues) were tested for miR-1288 expression by qRT-PCR. The colon cancer cell lines showed reduced expression of miR-1288 compared to normal colonic epithelial cell line. Over expression of miR-1288 in SW480 cell line showed increased cell proliferation and increased G2-M phase cells. In tissues, reduced miR-1288 expression was noted in majority of colorectal adenocarcinoma compared to colorectal adenoma and non-neoplastic tissues. Reduced or absent expression of miR-1288 was noted in 76% (n = 62/82) of the cancers. The expression levels of miR-1288 were higher in distal colorectal adenocarcinomas (P = 0.013) and in cancers of lower T staging (P = 0.033). To conclude, alternation of miR-1288 expression is important in the progression of colorectal cancer. The differential regulation of miR-1288 was found to be related to cancer location and pathological staging in colorectal cancers.

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BackgroundOpioids are prescribed frequently and increasingly for the management of chronic non-cancer pain (CNCP). Current systematic reviews have a number of limitations, leaving uncertainty with regard to the benefits and harms associated with opioid therapy for CNCP. We propose to conduct a systematic review and meta-analysis to summarize the evidence for using opioids in the treatment of CNCP and the risk of associated adverse events.Methods and designEligible trials will include those that randomly allocate patients with CNCP to treatment with any opioid or any non-opioid control group. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to evaluate confidence in the evidence on an outcome-by-outcome basis. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. To ensure interpretability of our results, we will present risk differences and measures of relative effect for all outcomes reported and these will be based on anchor-based minimally important clinical differences, when available. We will conduct a priori defined subgroup analyses consistent with current best practices.DiscussionOur review will evaluate both the effectiveness and the adverse events associated with opioid use for CNCP, evaluate confidence in the evidence using the GRADE approach, and prioritize patient-important outcomes with a focus on functional gains guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with CNCP and identify key areas for future research.Trial registrationOur protocol is registered on PROSPERO (CRD42012003023), http://www.crd.york.ac.uk/PROSPERO.

ObjectiveTo evaluate the effects of denosumab on erosion healing at 2–4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease.MethodsThis was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 months for 24 months. The primary outcome was erosion healing at MCP 2–4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined.ResultsAt 24 months, HR-pQCT images were analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (18% vs 8%, p=0.019) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months.ConclusionAlthough no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months.Trial registration numberNCT03239080.

Objective Anti-melanoma differentiation-associated protein 5 (MDA5) positive dermatomyositis (DM) is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors for mortality and RP-ILD. Methods Anti-MDA5 positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. Results Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed that RP-ILD (HR 9.735, 95%CI 3.905–24.272), age >52 (HR 4.750, 95%CI 1.692–13.333), ferritin level >2800pmol/l (HR 3.042, 95%CI 1.323–6.997) and lactate dehydrogenase (LDH) >400 IU/l (HR 2.290, 95% CI 1.009–5.198) were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years old (HR 2.640, 95%CI 1.277–5.455), LDH >300IU/l (HR3.189, 95%CI 1.469–6.918), fever (HR 1.903, 95% CI: 0.956–3.790) and neutrophil to lymphocyte ratio (NLR) >7.0 (HR 1.967, 95%CI 0.942–4.107). We proposed a prediction model, based on Fever, LDH, Age and White cell count (“FLAW”), to stratify risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75% respectively. Conclusions Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The “FLAW” model maybe useful to predict the development of RP-ILD.

The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has recommended that trialists evaluating treatments for chronic pain should consider reporting 9 patient-important outcome domains. We examined the extent to which clinical trials evaluating the effect of opioids for chronic non-cancer pain (CNCP) report outcome domains recommended by IMMPACT. We systematically searched electronic databases for English-language studies that randomized patients with CNCP to receive an opioid or a non-opioid control. In duplicate and independently, reviewers established the eligibility of each identified study and recorded all reported outcome domains from eligible trials. We conducted a priori regression analyses to explore factors that may be associated with IMMPACT-recommended outcome domains. Among 156 eligible trials, reporting of IMMPACT-recommended outcome domains was highly variable, ranging from 99% for pain to 7% for interpersonal functioning. Recently published trials were more likely to report the effect of treatment on physical functioning, emotional functioning, role functioning, sleep and fatigue, and participant disposition. Trials for which the corresponding author was from North America were more likely to report treatment effects on physical functioning and participant ratings of improvement and satisfaction with treatment. Trials published in higher impact journals were more likely to report treatment effects on emotional function, but less likely to report participant ratings of improvement and satisfaction with treatment. Most IMMPACT domains showed an increased rate of reporting over time, although many patient-important outcome domains remained unreported by over half of all trials evaluating the effects of opioids for CNCP.

Background The aims of the study were to investigate the prevalence of myositis specific autoantibodies (MSAs) and their associated complications in a cohort of patients with idiopathic inflammatory myopathies (IIMs). Methods A total of 201 consecutive patients with IIMs being followed up in the Rheumatology clinics of the participating regional hospitals in Hong Kong from July 2016 to January 2018 were recruited. Clinical characteristics, treatment history and disease complications were documented. Immunoblot assay was used to detect the MSAs. Results Out of the 201 patients, at least one MSA was found in 63.2% of patients. The most common MSAs were the anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) and the antitranscriptional intermediary factor 1-gamma antibody (anti-TIF1-γ Ab) (both 13.9%), followed by anti-Jo-1 antibody (12.4%). Anti-MDA5 Ab was present exclusively in dermatomyositis (DM) and was strongly associated with digital ulcers, the clinically amyopathic phenotype and rapidly progressive interstitial lung disease (RP-ILD). Anti-TIF1γ Ab was strongly associated with refractory rash and malignancy. Multivariate analysis showed that the independent risk factors of RP-ILD included anti-MDA5 Ab (OR 14.5, p=0.001), clinically amyopathic DM (OR 13.9, p=0.015) and history of pulmonary tuberculosis (OR 12.2, p=0.026). Cox regression analysis showed that the independent predictors of malignancy included anti-TIF1γ Ab (HR 3.55, p=0.002), DM (HR 3.82, p=0.009) and family history of cancer (HR 3.40, p=0.038). Conclusions MSA testing enables dividing of patients with IIMs into phenotypically homogenous subgroups and prediction of potentially life-threatening complications. Background Myositis-specific autoantibodies (MSAs) are antibodies which direct against cytoplasmic or nuclear