Background The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. Methods We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. Results Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points (90% confidence interval [CI], −4.9 to 2.2; 95% CI, −5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P = 0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). Conclusions Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927.)

Macroeconomic and renal service factors are more often associated with RRT incidence rates than measured demographic or general population health status factors.

BackgroundThe past decades have seen rapid advances in the treatment of rheumatoid arthritis (RA). In particular, the introduction of biologic and targeted synthetic disease-modifying antirheumatic drugs have improved clinical outcomes and reconfigured traditional RA cost compositions.ObjectivesTo map the existing evidence concerning cost of illness of RA, as the treatment pathway evolves in the biologic era, and examine how costs have been measured and estimated, in order to assemble and appropriately interpret available data.MethodsSystematic review of studies that estimated the costs of patients with RA. Multiple electronic databases were searched to identify studies published between 2000 and 2019. The reported total costs and cost components were evaluated according to the study and population characteristics. The Cochran-Armitage test was used to determine statistically significant trends in increasing or decreasing proportions over time.ResultsOverall, 72 studies were included. Drug costs compromised the main component (up to 87%) of direct costs with an increasing trajectory over time, although not statistically significant. The proportion of costs for hospitalisation showed a statistically significant decrease chronologically (p=0.044). Indirect costs, primarily associated with absenteeism and work disability accounted for 39% to 86% of total costs. The reported indirect costs are highly sensitive to the approach to estimation.ConclusionsA decreasing trend in inpatient costs chronologically suggested a cost shift in other components of direct costs. Indirect costs still contributed a considerable proportion of total costs, with work disability being the main cost component. Economic analyses that do not incorporate or appropriately measure indirect costs will underestimate the full economic impact of RA.

Background In England, the provision of early supported discharge is recommended as part of an evidence-based stroke care pathway. Objectives To investigate the effectiveness of early supported discharge services when implemented at scale in practice and to understand how the context within which these services operate influences their implementation and effectiveness. Design A mixed-methods study using a realist evaluation approach and two interlinking work packages was undertaken. Three programme theories were tested to investigate the adoption of evidence-based core components, differences in urban and rural settings, and communication processes. Setting and interventions Early supported discharge services across a large geographical area of England, covering the West and East Midlands, the East of England and the North of England. Participants Work package 1: historical prospective patient data from the Sentinel Stroke National Audit Programme collected by early supported discharge and hospital teams. Work package 2: NHS staff (n = 117) and patients (n = 30) from six purposely selected early supported discharge services. Data and main outcome Work package 1: a 17-item early supported discharge consensus score measured the adherence to evidence-based core components defined in an international consensus document. The effectiveness of early supported discharge was measured with process and patient outcomes and costs. Work package 2: semistructured interviews and focus groups with NHS staff and patients were undertaken to investigate the contextual determinants of early supported discharge effectiveness. Results A variety of early supported discharge service models had been adopted, as reflected by the variability in the early supported discharge consensus score. A one-unit increase in early supported discharge consensus score was significantly associated with a more responsive early supported discharge service and increased treatment intensity. There was no association with stroke survivor outcome. Patients who received early supported discharge in their stroke care pathway spent, on average, 1 day longer in hospital than those who did not receive early supported discharge. The most rural services had the highest service costs per patient. NHS staff identified core evidence-based components (e.g. eligibility criteria, co-ordinated multidisciplinary team and regular weekly multidisciplinary team meetings) as central to the effectiveness of early supported discharge. Mechanisms thought to streamline discharge and help teams to meet their responsiveness targets included having access to a social worker and the quality of communications and transitions across services. The role of rehabilitation assistants and an interdisciplinary approach were facilitators of delivering an intensive service. The rurality of early supported discharge services, especially when coupled with capacity issues and increased travel times to visit patients, could influence the intensity of rehabilitation provision and teams’ flexibility to adjust to patients’ needs. This required organising multidisciplinary teams and meetings around the local geography. Findings also highlighted the importance of good leadership and communication. Early supported discharge staff highlighted the need for collaborative and trusting relationships with patients and carers and stroke unit staff, as well as across the wider stroke care pathway. Limitations Work package 1: possible influence of unobserved variables and we were unable to determine the effect of early supported discharge on patient outcomes. Work package 2: the pragmatic approach led to ‘theoretical nuggets’ rather than an overarching higher-level theory. Conclusions The realist evaluation methodology allowed us to address the complexity of early supported discharge delivery in real-world settings. The findings highlighted the importance of context and contextual features and mechanisms that need to be either addressed or capitalised on to improve effectiveness. Trial registration Current Controlled Trials ISRCTN15568163. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 9, No. 22. See the NIHR Journals Library website for further project information.

Background Following the initial identification of the 2019 coronavirus disease (covid-19), the subsequent months saw substantial increases in published biomedical research. Concerns have been raised in both scientific and lay press around the quality of some of this research. We assessed clinical research from major clinical journals, comparing methodological and reporting quality of covid-19 papers published in the first wave (here defined as December 2019 to May 2020 inclusive) of the viral pandemic with non-covid papers published at the same time. Methods We reviewed research publications (print and online) from The BMJ, Journal of the American Medical Association (JAMA), The Lancet, and New England Journal of Medicine, from first publication of a covid-19 research paper (February 2020) to May 2020 inclusive. Paired reviewers were randomly allocated to extract data on methodological quality (risk of bias) and reporting quality (adherence to reporting guidance) from each paper using validated assessment tools. A random 10% of papers were assessed by a third, independent rater. Overall methodological quality for each paper was rated high, low or unclear. Reporting quality was described as percentage of total items reported. Results From 168 research papers, 165 were eligible, including 54 (33%) papers with a covid-19 focus. For methodological quality, 18 (33%) covid-19 papers and 83 (73%) non-covid papers were rated as low risk of bias, OR 6.32 (95%CI 2.85 to 14.00). The difference in quality was maintained after adjusting for publication date, results, funding, study design, journal and raters (OR 6.09 (95%CI 2.09 to 17.72)). For reporting quality, adherence to reporting guidelines was poorer for covid-19 papers, mean percentage of total items reported 72% (95%CI:66 to 77) for covid-19 papers and 84% (95%CI:81 to 87) for non-covid. Conclusions Across various measures, we have demonstrated that covid-19 research from the first wave of the pandemic was potentially of lower quality than contemporaneous non-covid research. While some differences may be an inevitable consequence of conducting research during a viral pandemic, poor reporting should not be accepted.