The costs and outcomes of paediatric tuberculosis treatment at primary healthcare clinics in Johannesburg, South Africa

Background. Little up-to-date information is available about the costs of providing drug-susceptible tuberculosis (DS-TB) treatment to paediatric patients in South Africa (SA), nor have actual costs incurred at clinics been compared with costs expected from guidelines.Objectives. To estimate actual and guideline treatment costs by means of a retrospective cohort analysis.Methods. We report patient characteristics, outcomes and treatment costs from a retrospective cohort of paediatric and adolescent (<18 years) DS-TB patients registered for treatment from 1 April 2011 to 31 March 2013 at three primary healthcare clinics in Johannesburg, SA. Actual treatment costs in 2015 SA rands and US dollars were estimated from the provider perspective using a standard bottom-up microcosting approach and compared with an estimate of guideline costs.Results. We enrolled 88 DS-TB patients (median age 4 years (interquartile range 1.0 - 9.5), 44.3% female, 22.7% HIV co-infected, 92.0% pulmonary TB). Treatment success was high (89.8%; 13.6% cured, 76.1% completed treatment), and the mean (standard deviation (SD)) cost per patient with treatment success was ZAR1 820/USD143 (ZAR593/USD46), comprising fixed costs (44.0%), outpatient visits (30.7%), medication (19.3%) and laboratory investigations (6.0%). This was 17% more than the mean (SD) cost estimated by applying treatment guidelines (ZAR1 553/USD122 (ZAR1 620/USD127)), with differences due mainly to higher laboratory costs and more outpatient visits taking place than were recommended in national guidelines.Conclusions. These results are the first reported estimates of paediatric DS-TB treatment costs in SA and show the potential cost savings of closer adherence to national treatment guidelines. The findings were robust in sensitivity analyses and are lower than previous cost estimates in adults.

Outcomes of treatment of drug-susceptible tuberculosis at public sector primary healthcare clinics in Johannesburg, South Africa: A retrospective cohort study

Background. Despite the large number of tuberculosis (TB) patients treated in South Africa (SA), there are few descriptions in the published literature of drug-susceptible TB patient characteristics, mode of diagnosis or treatment outcomes in routine public sector treatment programmes.Objective. To enhance the evidence base for public sector TB treatment service delivery, we reported the characteristics of and outcomes for a retrospective cohort of adult TB patients at public sector clinics in the Johannesburg Metropolitan Municipality (JHB), SA.Methods. We collected medical record data for a retrospective cohort of adult (≥18 years) TB patients registered between 1 April 2011 and 31 March 2012 at three public sector clinics in JHB. Data were abstracted from National TB Programme clinic cards and the TB case registers routinely maintained at study sites. We report patient characteristics, mode of diagnosis, mode of treatment supervision, treatment characteristics, HIV status and treatment outcomes for this cohort.Results. A total of 544 patients were enrolled in the cohort. Most (86%) were new TB cases, 81% had pulmonary TB, 58% were smear-positive at treatment initiation and 71% were HIV co-infected. Among 495 patients with treatment outcomes reported, 80% (n=394) had successful outcomes, 11% (n=55) were lost to follow-up, 8% (n=40) died and 1% (n=6) failed treatment.Conclusions.Primary healthcare clinics in JHB are achieving relatively high rates of success in treating drug-susceptible TB. Missing laboratory results were common, including follow-up smears, cultures and drug susceptibility tests, making it difficult to assess adherence to guidelines and leaving scope for substantial improvements in record-keeping at the clinics involved.

Antibiotic Review Kit for Hospitals (ARK-Hospital): study protocol for a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: To ensure patients continue to get early access to antibiotics at admission, while also safely reducing antibiotic use in hospitals, one needs to target the continued need for antibiotics as more diagnostic information becomes available. UK Department of Health guidance promotes an initiative called 'Start Smart then Focus': early effective antibiotics followed by active 'review and revision' 24-72 h later. However in 2017, < 10% of antibiotic prescriptions were discontinued at review, despite studies suggesting that 20-30% of prescriptions could be stopped safely. METHODS/DESIGN: Antibiotic Review Kit for Hospitals (ARK-Hospital) is a complex 'review and revise' behavioural intervention targeting healthcare professionals involved in antibiotic prescribing or administration in inpatients admitted to acute/general medicine (the largest consumers of non-prophylactic antibiotics in hospitals). The primary study objective is to evaluate whether ARK-Hospital can safely reduce the total antibiotic burden in acute/general medical inpatients by at least 15%. The primary hypotheses are therefore that the introduction of the behavioural intervention will be non-inferior in terms of 30-day mortality post-admission (relative margin 5%) for an acute/general medical inpatient, and superior in terms of defined daily doses of antibiotics per acute/general medical admission (co-primary outcomes). The unit of observation is a hospital organisation, a single hospital or group of hospitals organised with one executive board and governance framework (National Health Service trusts in England; health boards in Northern Ireland, Wales and Scotland). The study comprises a feasibility study in one organisation (phase I), an internal pilot trial in three organisations (phase II) and a cluster (organisation)-randomised stepped-wedge trial (phase III) targeting a minimum of 36 organisations in total. Randomisation will occur over 18 months from November 2017 with a further 12 months follow-up to assess sustainability. The behavioural intervention will be delivered to healthcare professionals involved in antibiotic prescribing or administration in adult inpatients admitted to acute/general medicine. Outcomes will be assessed in adult inpatients admitted to acute/general medicine, collected through routine electronic health records in all patients. DISCUSSION: ARK-Hospital aims to provide a feasible, sustainable and generalisable mechanism for increasing antibiotic stopping in patients who no longer need to receive them at 'review and revise'. TRIAL REGISTRATION: ISRCTN Current Controlled Trials, ISRCTN12674243 . Registered on 10 April 2017

Systematic review of wastewater surveillance of antimicrobial resistance in human populations

Objectives: We systematically reviewed studies using wastewater for AMR surveillance in human populations, to determine: (i) evidence of concordance between wastewater-human AMR prevalence estimates, and (ii) methodological approaches which optimised identifying such an association, and which could be recommended as standard. We used Lin’s concordance correlation coefficient (CCC) to quantify concordance between AMR prevalence estimates in wastewater and human compartments (where CCC = 1 reflects perfect concordance), and logistic regression to identify study features (e.g. sampling methods) associated with high agreement studies (defined as >70% of within-study wastewater-human AMR prevalence comparisons within ±10%). Results: Of 8,867 records and 441 full-text methods reviewed, 33 studies were included. AMR prevalence data was extractable from 24 studies conducting phenotypic-only (n = 7), genotypic-only (n = 1) or combined (n = 16) AMR detection. Overall concordance of wastewater-human AMR prevalence estimates was reasonably high for both phenotypic (CCC = 0.85 [95% CI 0.8–0.89]) and genotypic approaches (CCC = 0.88 (95% CI 0.84–0.9)) despite diverse study designs, bacterial species investigated and phenotypic/genotypic targets. No significant relationships between methodological approaches and high agreement studies were identified using logistic regression; however, this was limited by inconsistent reporting of study features, significant heterogeneity in approaches and limited sample size. Based on a secondary, descriptive synthesis, studies conducting composite sampling of wastewater influent, longitudinal sampling >12 months, and time-/location-matched sampling of wastewater and human compartments generally had higher agreement. Conclusion: Wastewater-based surveillance of AMR appears promising, with high overall concordance between wastewater and human AMR prevalence estimates in studies irrespective of heterogenous approaches. However, our review suggests future work would benefit from: time-/location-matched sampling of wastewater and human populations, composite sampling of influent, and sampling >12 months for longitudinal studies. Further research and clear and consistent reporting of study methods is required to identify optimal practice

The Prevalence of the Term Subluxation in Chiropractic Degree Program Curricula Throughout the World

Background: The subluxation construct generates debate within and outside the profession. The International Chiropractic Education Collaboration, comprised of 10 chiropractic programs outside of North America, stated they will only teach subluxation in a historical context. This research sought to determine how many chiropractic institutions worldwide still use the term in their curricula and to expand upon the previous work of Mirtz & and Perle. Methods: Forty-six chiropractic programs, 18 United States (US) and 28 non-US, were identified from the World Federation of Chiropractic Educational Institutions list. Websites were searched by multiple researchers for curricular information September 2016–September 2017. Some data were not available on line, so email requests were made for additional information. Two institutions provided additional information. The total number of mentions of subluxation in course titles, technique course (Tech) descriptions, principles and practice (PP) descriptions, and other course descriptions were reported separately for US and non-US institutions. Means for each category were calculated. The number of course titles and descriptions using subluxation was divided by the total number of courses for each institution and reported as percentages. Results: Means for use of subluxation by US institutions were: Total course titles = .44; Tech = 3.83; PP = 1.50; other = 1.16. For non-US institutions, means were: Total course titles = .07; Tech = .27; PP = .44; other = 0. The mean total number of mentions was 6.94 in US vs. 0.83 in non-US institutions. Similarly, the mean course descriptions was 6.50 in US vs. 0.72 in non-US institutions. Conclusions: The term subluxation was found in all but two US course catalogues. The use of subluxation in US courses rose from a mean of 5.53 in 2011 to 6.50 in 2017. US institutions use the term significantly more frequently than non-US. Possible reasons for this were discussed. Unscientific terms and concepts should have no place in modern education, except perhaps in historical context. Unless these outdated concepts are rejected, the chiropractic profession and individual chiropractors will likely continue to face difficulties integrating with established health care systems and attaining cultural authority as experts in conservative neuro-musculoskeletal health care.https://doi.org/10.1186/s12998-018-0191-

Review of methods used by chiropractors to determine the site for applying manipulation

Background: With the development of increasing evidence for the use of manipulation in the management of musculoskeletal conditions, there is growing interest in identifying the appropriate indications for care. Recently, attempts have been made to develop clinical prediction rules, however the validity of these clinical prediction rules remains unclear and their impact on care delivery has yet to be established. The current study was designed to evaluate the literature on the validity and reliability of the more common methods used by doctors of chiropractic to inform the choice of the site at which to apply spinal manipulation. Methods: Structured searches were conducted in Medline, PubMed, CINAHL and ICL, supported by hand searches of archives, to identify studies of the diagnostic reliability and validity of common methods used to identify the site of treatment application. To be included, studies were to present original data from studies of human subjects and be designed to address the region or location of care delivery. Only English language manuscripts from peer-reviewed journals were included. The quality of evidence was ranked using QUADAS for validity and QAREL for reliability, as appropriate. Data were extracted and synthesized, and were evaluated in terms of strength of evidence and the degree to which the evidence was favourable for clinical use of the method under investigation. Results: A total of 2594 titles were screened from which 201 articles met all inclusion criteria. The spectrum of manuscript quality was quite broad, as was the degree to which the evidence favoured clinical application of the diagnostic methods reviewed. The most convincing favourable evidence was for methods which confirmed or provoked pain at a specific spinal segmental level or region. There was also high quality evidence supporting the use, with limitations, of static and motion palpation, and measures of leg length inequality. Evidence of mixed quality supported the use, with limitations, of postural evaluation. The evidence was unclear on the applicability of measures of stiffness and the use of spinal x-rays. The evidence was of mixed quality, but unfavourable for the use of manual muscle testing, skin conductance, surface electromyography and skin temperature measurement. Conclusions: A considerable range of methods is in use for determining where in the spine to administer spinal manipulation. The currently published evidence falls across a spectrum ranging from strongly favourable to strongly unfavourable in regard to using these methods. In general, the stronger and more favourable evidence is for those procedures which take a direct measure of the presumptive site of care– methods involving pain provocation upon palpation or localized tissue examination. Procedures which involve some indirect assessment for identifying the manipulable lesion of the spine–such as skin conductance or thermography–tend not to be supported by the available evidence.https://doi.org/10.1186/2045-709X-21-3

Completeness of reporting and risks of overstating impact in cluster randomised trials : a systematic review

Acknowledgments We received no funding specifically for this systematic review. ELT is funded in part by awards R01-AI141444 from the National Institute of Allergy and Infectious Diseases and R01-MH120649 from the US National Institute of Mental Health; both Institutes are part of the National Institutes of Health (NIH). JAG and ACP's support of this project was made possible (in part) by grant number UL1TR002553 from the National Center for Advancing Translational Sciences of the NIH, and the NIH Roadmap for Medical Research. JEM is supported by an Australian National Health and Medical Research Council Career Development Fellowship (APP1143429). SN was supported by an award that is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, and part of the EDCTP2 programme supported by the European Union (grant reference MR/R010161/1). ABF acknowledges funding support from the National Health and Medical Research Council of Australia (grant ID 1183303). KH is funded by a National Institute for Health Research Senior Research Fellowship SRF-2017-10-002. The contents of the research included in this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of any of the funders. The research contributed by all authors of this manuscript are independent of their funders. Specifically, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We wish to thank the three reviewers for their insightful comments and constructive feedback.Peer reviewedPublisher PD

Antibiotic review kit for hospitals (ARK-Hospital): a stepped wedge cluster randomised controlled trial

Background: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotics. There is limited evidence on how to support this. We evaluated a multifaceted behaviour change intervention (ARK) designed to reduce antibiotic use among adult acute/medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. Methods: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of 39 hospitals in 7 calendar-time blocks in the United Kingdom (25/September/2017-01/July/2019). Randomised implementation date was concealed until 12 weeks before implementation, when local preparations were designed to start. Co-primary outcomes were monthly antibiotic defined-daily-doses (DDD) per adult acute/medical admission (hospital-level, superiority) and all-cause 30-day mortality (patient-level, non-inferiority, margin 5%). Sites were eligible if they admitted non-elective medical patients, could identify an intervention “champion”, and provide study data. Sites were followed for at least 14 months. Intervention effects were assessed using interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed using meta-regression. Trial registration: ISRCTN12674243. Findings: Adjusted estimates showed reductions in total antibiotic DDDs per acute/medical admission (-4.8% per year, 95% CI: -9.1%,-0.2%) following the intervention. Among 7,160,421 acute/medical admissions, there were trends towards -2.7% (95% CI: -5.7%,+0.3%) immediate and +3.0% (95% CI: -0.1%,+6.2%) sustained changes in adjusted 30-day mortality. Site-specific mortality trends were unrelated to the site-specific magnitude of antibiotic reduction (Spearman’s ρ=0.011, p=0.949). Whilst 90-day mortality odds appeared to increase (+3.9%, 95% CI: +0.5%,+7.4%), this was attenuated excluding admissions after COVID-19 onset (+3.2%, 95% CI:-1.5%,+8.2%). There was no evidence of intervention effects on length-of-stay (p>0.4). Interpretation: The weak, inconsistent intervention effects on mortality are likely explained by the post-implementation onset of the COVID-19 pandemic. The ARK intervention resulted in sustained, safe reductions in antibiotic use among adult acute/medical inpatients. Funding: NIHR Programme Grants for Applied Research, RP-PG-0514-20015.</p

The costs and outcomes of paediatric tuberculosis treatment at primary healthcare clinics in Johannesburg South Africa

Background. Little up-to-date information is available about the costs of providing drug-susceptible tuberculosis (DS-TB) treatment to paediatric patients in South Africa (SA), nor have actual costs incurred at clinics been compared with costs expected from guidelines.Objectives. To estimate actual and guideline treatment costs by means of a retrospective cohort analysis.Methods. We report patient characteristics, outcomes and treatment costs from a retrospective cohort of paediatric and adolescent (&lt;18 years) DS-TB patients registered for treatment from 1 April 2011 to 31 March 2013 at three primary healthcare clinics in Johannesburg, SA. Actual treatment costs in 2015 SA rands and US dollars were estimated from the provider perspective using a standard bottom-up microcosting approach and compared with an estimate of guideline costs.Results. We enrolled 88 DS-TB patients (median age 4 years (interquartile range 1.0 - 9.5), 44.3% female, 22.7% HIV co-infected, 92.0% pulmonary TB). Treatment success was high (89.8%; 13.6% cured, 76.1% completed treatment), and the mean (standard deviation (SD)) cost per patient with treatment success was ZAR1 820/USD143 (ZAR593/USD46), comprising fixed costs (44.0%), outpatient visits (30.7%), medication (19.3%) and laboratory investigations (6.0%). This was 17% more than the mean (SD) cost estimated by applying treatment guidelines (ZAR1 553/USD122 (ZAR1 620/USD127)), with differences due mainly to higher laboratory costs and more outpatient visits taking place than were recommended in national guidelines.Conclusions. These results are the first reported estimates of paediatric DS-TB treatment costs in SA and show the potential cost savings of closer adherence to national treatment guidelines. The findings were robust in sensitivity analyses and are lower than previous cost estimates in adults.Â