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We report surveillance conducted in 217 pestiferous rodents in Hong Kong for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We did not detect SARS-CoV-2 RNA but identified 1 seropositive rodent, suggesting exposure to a virus antigenically similar to SARS-CoV-2. Potential exposure of urban rodents to SARS-CoV-2 cannot be ruled out.

Abstract While phylogenetic trees and associated data have been getting easier to generate, it has been difficult to reuse, combine, and synthesize the information they provided, because published trees are often only available as image files and associated data are often stored in incompatible formats. To increase the reproducibility and reusability of phylogenetic data, the ggtree object was designed for storing phylogenetic tree and associated data, as well as visualization directives. The ggtree object itself is a graphic object and can be rendered as a static image. More importantly, the input tree and associated data that are used in visualization can be extracted from the graphic object, making it an ideal data structure for publishing tree (image, tree, and data in one single object) and thus enhancing data reuse and analytical reproducibility, as well as facilitating integrative and comparative studies. The ggtree package is freely available at https://www.bioconductor.org/packages/ggtree.

Editorial summary Avian influenza A viruses (AIVs) pose a threat to global health because of their sporadic zoonotic transmission and potential to cause pandemics. Genomic surveillance of AIVs has become a powerful, cost-effective approach for studying virus transmission, evolution, and dissemination, and has the potential to inform outbreak control efforts and policies.

A novel betacoronavirus associated with lethal respiratory and renal complications was recently identified in patients from several countries in the Middle East. We report the deep genome sequencing of the virus directly from a patient’s sputum sample. Our high-throughput sequencing yielded a substantial depth of genome sequence assembly and showed the minority viral variants in the specimen. Detailed phylogenetic analysis of the virus genome (England/Qatar/2012) revealed its close relationship to European bat coronaviruses circulating among the bat species of the Vespertilionidae family. Molecular clock analysis showed that the 2 human infections of this betacoronavirus in June 2012 (EMC/2012) and September 2012 (England/Qatar/2012) share a common virus ancestor most likely considerably before early 2012, suggesting the human diversity is the result of multiple zoonotic events.

Our purpose was to determine if docusate monotherapy is effective in preventing opioid-induced constipation in patients receiving opioids following orthopedic surgery. Our single-center, retrospective, cohort study evaluated 212 orthopedic patients who received opioids between May 1, 2018, and December 31, 2018. All patients were aged 18 years and older, hospitalized for more than 48 hours, and received docusate for primary prevention of constipation post-operatively. The primary outcome was the proportion of patients taking opioid medications who experienced docusate failure, defined as patients who did not have a bowel movement within 5 days of starting docusate after surgery or those patients who required the use of additional laxative agents to produce a bowel movement. After excluding patients which did not meet the inclusion criteria, 79.9% (n = 159/199) experienced docusate treatment failure. Of these patients, 42.8% (68/159) failed to have a bowel movement or had a bowel movement greater than 5 days post-surgery. The remaining 57.2% (91/159) of patients required an additional laxative to produce a bowel movement. Docusate monotherapy was not effective in preventing constipation in patients receiving opioids following elective orthopedic surgery. Based on these findings, we propose utilization of stimulant bowel products with proven efficacy as primary therapy after surgery to prevent constipation. Future multi-centered, randomized controlled trials are necessary to evaluate the differences in efficacy and safety between common bowel regimens in treating opioid-induced constipation in patients who undergo elective orthopedic surgery.

Migratory birds play a major role in spreading influenza viruses over long distances. We report highly pathogenic avian influenza A(H5N6) viruses in migratory and resident ducks in Bangladesh. The viruses were genetically similar to viruses detected in wild birds in China and Mongolia, suggesting migration-associated dissemination of these zoonotic pathogens.

Objective: To 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., Methods: This 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., Results: At 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., Conclusion: Although 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 Number: NCT03239080., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Physical restraints are used liberally in some intensive care units (ICUs) to prevent patient harm from device removal or falls. Although the intention of restraint use is patient safety, their application may inadvertently cause physical or psychological harm. Physical restraints may contribute to post-traumatic stress disorder (PTSD), but there is a paucity of supportive data. Objectives: To investigate the association between physical restraint use and PTSD symptoms in ICU survivors. Secondary objectives were to examine the cognitive and physical outcomes associated with physical restraint use and to assess interventions that may be effective in reducing restraint use. Methods: A systematic review of English language studies in PubMed, Medline, Embase, CINAHL, and CENTRAL between January 1, 1990, to February 8, 2020 was performed. Observational or randomized studies that reported on restraint use and associated outcomes, or interventions to reduce restraint use, in critically ill adult patients were identified. Two independent reviewers completed the review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: We identified 794 articles, of which 37 met inclusion criteria and were included. Thirty of these studies related to patient outcomes including PTSD, delirium, mechanical ventilation hours, and physical injury. Seven related to interventions to reduce physical restraint use. The quality of studies was not high; only four of the included studies were assessed to have a low risk of bias. Three studies found a significant relationship between restraint use and PTSD, but their results could not be pooled for analysis. Pooled data indicated a significant association between physical restraint use and delirium (odds ratio [OR], 11.54; 95% confidence interval [CI], 6.66-20.01; P  < 0.001) and duration of mechanical ventilation (mean difference in days, 3.35; 95% CI, 1.95-4.75; P  < 0.001). We also found that interventions, such as nursing education, may effectively reduce restraint use by approximately 50% (OR, 0.48; 95% CI, 0.32-0.73; P  < 0.001). The impact that a reduction in restraint use may have on associated outcomes was not examined. Conclusions: Physical restraint use may be associated with PTSD in ICU survivors and is associated with delirium and longer duration of mechanical ventilation. Nurse education is likely effective in reducing rates of physical restraint among ICU patients.

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.

Influenza B viruses of both the Yamagata and the Victoria lineages are implicated in a large proportion of the morbidity and mortality associated with influenza outbreaks. In this study, we characterized the full genomes of 53 influenza B viruses isolated during 2012-2015 in three Asian countries: Japan, Myanmar, and Vietnam. Analysis of the hemagglutinin (HA) genes revealed co-circulation of both the Yamagata and Victoria lineages within the same season in these countries. Our analysis revealed, that a large proportion of viruses circulating during 2013-2014 in Japan and Vietnam were mismatched to the vaccine supporting the rationale for using quadrivalent vaccines. Molecular analysis of the neuraminidase (NA) genes did not reveal any of the previously reported substitutions associated with reduced susceptibility to neuraminidase inhibitors (NAIs). However, one isolate from Nagasaki displayed reduced inhibition by NAIs, associated with an NA-M426I substitution (N2-numbering). Phylogenetic analysis of the eight genome segments identified a 6 + 2 reassortant strain belonging to the Victoria lineage that circulated in Japan during the 2013-2014 season. This strain appears to have evolved from a descendent of a B/Brisbane/60/2008-like strain in an intra-lineage reassortment event involving the nucleoprotein (NP) and nonstructural (NS) genes. Therefore, influenza B strains circulating worldwide continue to evolve via complex reassortment events, which contribute to their survival and the emergence of new strains. These findings highlight the need for ongoing genome-wide studies of circulating viruses and assessing the implications of these evolutionary events on the vaccines., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

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: Opioids 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 Design: Eligible 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., Discussion: Our 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 Registration: Our protocol is registered on PROSPERO (CRD42012003023), http://www.crd.york.ac.uk/PROSPERO.