bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative patient-controlled regional analgesia versus patient-controlled intravenous analgesia for patients with critical limb ischaemia: a study protocol for a randomised controlled trial
Authors: Chen Si , Xu Zhonghuang , Liu Hongju , Zhang Yuelun , Zhang Jiao , Chen Yuexin , Zheng Yuehong , Huang Yuguang 
Published: October 2020

IntroductionBoth regional analgesia and intravenous analgesia are frequently used perioperatively for patients with critical limb ischaemia (CLI). Nevertheless, the comparison of perioperative effect of regional and intravenous analgesia has not yet been thoroughly illustrated. This study will comprehensively compare patient-controlled regional analgesia (PCRA) and patient-controlled intravenous analgesia (PCIA) as two different perioperative analgesia approaches for patients with CLI. It investigates their effects on analgesia, reperfusion and the quality of recovery perioperatively, also aims to provide clinical evidence to those non-surgical patients with non-reconstructable arteries.Methods and analysisThis trial is a randomised, single-centre, open-label, parallel trial with target sample size of 52 in total. Eligible participants will be randomly allocated to the PCRA group (group R) or the PCIA group (group I) after admission. Participants in group R will receive ultrasound-guided subgluteal sciatic catheterisation, followed by continuous PCRA infusion (0.2% ropivacaine 15 mL as loading dose, 8 mL/hour as background with a patient-controlled bolus of 6 mL). Participants in group I will receive PCIA (morphine is given in boluses of 1 mg as needed, background infusion at 1 mg/hour). Data will be collected at baseline (T0), 2 hours before revascularisation treatment (T1) and 2 hours before discharge (T2). The primary outcomes include the Numerical Rating Scale pain score at T1 and T2. The secondary outcomes include the perioperative transcutaneous oxygen pressure, the Tissue Haemoglobin Index, Hospital Anxiety and Depression Scale at T1 and T2; the Patient Global Impression of Change and patient satisfaction at T1 and T2; the perioperative cumulative morphine consumption, the length of postoperative hospital stay and adverse events.Ethics and disseminationThis study received authorisation from the Institutional Review Board of Peking Union Medical College Hospital on 21 March 2017 (approval no. ZS-1289X). Study findings will be disseminated through presentations at scientific conferences or publications in peer-reviewed journals.Trial registration numberChinese Clinical Trial Registry (ChiCTR2000029298).Protocol versionV.4CP.B2 (15 June 2020).
Understanding the importance of non-material factors in retaining community health workers in low-income settings: a qualitative case-study in Ethiopia
Authors: Arora Nikita , Hanson Kara , Spicer Neil , Estifanos Abiy Seifu , Keraga Dorka Woldesenbet , Welearegay Alemtsehay Tewele , Tela Freweini Gebrearegay , Hussen Yemisrach Ahmed , Mandefro Yordanos Semu , Quaife Matthew 
Published: October 2020

ObjectivesThe motivation and retention of community health workers (CHWs) is a challenge and inadequately addressed in research and policy. We sought to identify factors influencing the retention of CHWs in Ethiopia and ways to avert their exit.DesignA qualitative study was undertaken using in-depth interviews with the study participants. Interviews were audio-recorded, and then simultaneously translated into English and transcribed for analysis. Data were analysed in NVivo 12 using an iterative inductive-deductive approach.SettingThe study was conducted in two districts each in the Tigray and Southern Nations, Nationalities and People’s Republic (SNNPR) regions in Ethiopia. Respondents were located in a mix of rural and urban settings.ParticipantsLeavers of health extension worker (HEW) positions (n=20), active HEWs (n=16) and key informants (n=11) in the form of policymakers were interviewed.ResultsWe identified several extrinsic and intrinsic motivational factors affecting the retention and labour market choices of HEWs. While financial incentives in the form of salaries and material incentives in the form of improvements to health facility infrastructure, provision of childcare were reported to be important, non-material factors like HEWs’ self-image, acceptance and validation by the community and their supervisors were found to be critical. A reduction or loss of these non-material factors proved to be the catalyst for many HEWs to leave their jobs.ConclusionOur study contributes new empirical evidence to the global debate on factors influencing the motivation and retention of CHWs, by being the first to include job leavers in the analysis. Our findings suggest that policy interventions that appeal to the social needs of CHWs can prove to be more acceptable and potentially cost-effective in improving their retention in the long run. This is important for government policymakers in resource constrained settings like Ethiopia that rely heavily on lay workers for primary healthcare delivery.
Development and pilot implementation of a standardised trauma documentation form to inform a national trauma registry in a low-resource setting: lessons from Tanzania
Authors: Sawe Hendry R , Reynolds Teri A , Weber Ellen J , Mfinanga Juma A , Coats Timothy J , Wallis Lee A 
Published: October 2020

ObjectivesTrauma registries are an integral part of a well-organised trauma system. Tanzania, like many low and middle-income countries, does not have a trauma registry. We describe the development, structure, implementation and impact of a context appropriate standardised trauma form based on the adaptation of the WHO Data Set for Injury (DSI), for clinical documentation and use in a national trauma registry.SettingOur study was conducted in emergency units of five regional referral hospitals in Tanzania.ProceduresMixed methods participatory action research was employed. After an assessment of baseline trauma documentation, we conducted semi-structured interviews with a purposefully selected sample of 33 healthcare providers from all participating hospitals to understand, develop, pilot and implement a standardised trauma form. We compared the number and types of variables captured before and after the form was implemented.OutcomesChange in proportion of variables of DSI captured after implementation of a standardised trauma documentation form.ResultsPiloting and feedback informed the development of a context appropriate standardised trauma documentation paper form with carbonless copy that could be used as both the clinical chart and data capture. Among 721 patients (seen by 21 clinicians) during the initial 30-day pilot, overall variable capture was 86.4% of required variables. After modifications of the form and training of healthcare providers, the form was implemented for 7 months, during which the capture improved to 96.3% among 6302 patients (seen by 31 clinicians). The providers reported the form was user-friendly, resulted in less time documenting, and served as a guide to managing trauma patients.ConclusionsThe development and implementation of a contextually appropriate, standardised trauma form were successful, yielding increased capture rates of injury variables. This system will facilitate expansion of the trauma registry across the country and inform similar initiatives in Sub-Saharan Africa.
Vedolizumab treatment across antiretroviral treatment interruption in chronic HIV infection: the HAVARTI protocol for a pilot dose-ranging clinical trial to assess safety, tolerance, immunological and virological activity
Authors: McGuinty Michaeline , Angel Jonathan B , Cooper Curtis L , Cowan Juthaporn , MacPherson Paul A , Kumar Ashok , Murthy Sanjay , Sy Richmond , Dennehy Michelle , Tremblay Nancy , Byrareddy Siddappa N , Cameron D William 
Published: October 2020

IntroductionContinuous antiretroviral therapy (ART) suppresses HIV plasma viral load (pVL) to very low levels, which allows for some immune recovery. Discontinuation of ART leads to pVL rebound from reservoirs of persistence and latency, and progressive immunodeficiency. One promising but controversial strategy targeting CD4+ T lymphocytes with a monoclonal antibody (mAb) against α4β7 integrin has shown promise through sustained virological remission of pVL (SVR) in SIV239-infected rhesus macaques. We propose to assess the safety and tolerability of vedolizumab, a licensed humanised mAb against human α4β7 integrin, in healthy HIV-infected adults on ART. This study will also assess, by analytical treatment interruption (ATI), whether vedolizumab treatment can induce SVR beyond ART and vedolizumab treatment.Methods and analysisThe HIV-ART-vedolizumab-ATI (HAVARTI) trial is a single-arm, dose-ranging pilot trial in healthy HIV-positive adult volunteers receiving ART. Twelve consenting persons will be enrolled in sequential groups of 4 to each serial dosing vedolizumab regimen (300 mg, 150 mg, 75 mg). The primary outcomes are: (1) to assess the safety and tolerability of seven serial infusions of vedolizumab at each of three doses; (2) to identify the immunovirological measures, including pVL and T-cell kinetics, that characterise HIV/ART cases before, during, after vedolizumab treatment and ATI; and (3) to seek SVR of pVL after ATI. Secondary outcomes will include immune reconstitution and pVL suppression as well as immune reconstitution and long-term safety following re-initiation of ART in the absence of SVR.Ethics and disseminationThe study protocol was approved by the Ottawa Health Science Network-REB and by the Health Canada Therapeutic Products Directorate. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open access journal within a year of study completion.Trial registration numberClinicalTrials.gov NCT03147859; https://clinicaltrials.gov/ct2/show/NCT03147859
Effects of crowding in the emergency department on the diagnosis and management of suspected acute coronary syndrome using rapid algorithms: an observational study
Authors: Stoyanov Kiril M , Biener Moritz , Hund Hauke , Mueller-Hennessen Matthias , Vafaie Mehrshad , Katus Hugo A , Giannitsis Evangelos 
Published: October 2020

ObjectivesFast diagnostic algorithms using high-sensitivity troponin (hsTn) in suspected acute coronary syndrome (ACS) are regarded as beneficial to expedite diagnosis and safe discharge of patients in crowded emergency departments (ED). This study investigates the effects of crowding on process times related to the diagnostic protocol itself or other time delays, and outcomes.DesignProspective single-centre observational study.SettingED (Germany).ParticipantsFinal study population of 2525 consecutive patients with suspected ACS within 12 months, after exclusion of patients with ST-elevation myocardial infarction, missing blood samples, referral from other hospitals or repeated visits.InterventionsUse of fast algorithms as per 2015 European Society of Cardiology guidelines.Main outcome measuresCrowding was defined as mismatch between patient numbers and monitoring capacities, or mean physician time per case, categorised as normal, high and very high crowding. Outcome measures were length of ED stay, direct discharge from ED, laboratory turn around times (TAT), utilisation of fast algorithms, absolute and relative non-laboratory time, as well as mortality.ResultsCrowding was associated with increased length of ED stay (3.75–4.89 hours, p<0.001). While median TAT of the first hsTnT increased (53–57 min, p<0.001), total TAT of serial hsTnT did not increase significantly with higher crowding (p=0.170). Lower utilisation of fast algorithms (p=0.009) and increase of additional hsTnT measurements after diagnosis (p=0.001) were observed in higher crowding. Most importantly, crowding was significantly associated with prolonged absolute (p<0.001), and particularly relative non-laboratory time (63.3%–71.3%, p<0.001). However, there was no significant effect of crowding on mortality, even after adjustment for relevant clinical variables.ConclusionsProcess times, and particularly non-laboratory times, are prolonged in a crowded ED diminishing some positive effects of fast diagnostic algorithms in suspected ACS. Higher crowding levels were not significantly associated with higher all-cause mortality rates.Trial registration numberNCT03111862.
Emergency department interventions for adult patients with low back pain: a systematic review of randomised controlled trials
Authors: Oliveira Crystian B , Amorim Hugo E , Coombs Danielle M , Richards Bethan , Reedyk Marco , Maher Chris G , Machado Gustavo C 
Published: October 2020

BackgroundMost low back pain trials have limited applicability to the emergency department (ED) because they provide treatment and measure outcomes after discharge from the ED. We investigated the efficacy and safety of pharmacological and non-pharmacological interventions delivered in the ED to patients with non-specific low back pain and/or sciatica on patient-relevant outcomes measured during the emergency visit.MethodsLiterature searches were performed in MEDLINE, EMBASE and CINAHL from inception to week 1 February 2020. We included all randomised controlled trials investigating adult patients (≥18 years) with non-specific low back pain and/or sciatica presenting to ED. The primary outcome of interest was pain intensity. Two reviewers independently screened the full texts, extracted the data and assessed risk of bias of each trial using the Physiotherapy Evidence Database (PEDro) scale. The overall quality of evidence, or certainty, provided by a set of trials evaluating the same treatment was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which considers imprecision, inconsistency, indirectness and bias in the evidence.ResultsFifteen trials (1802 participants) were included with 12 of 15 at low risk of bias (ie, PEDro score >6). Based on results from individual trials and moderate quality evidence, ketoprofen gel was more effective than placebo for non-specific low back pain at 30 min (mean difference (MD) −15.0, 95% confidence interval (CI) −21.0 to −9.0). For those with sciatica (moderate quality evidence), intravenous paracetamol (acetaminophen) (MD −15.7, 95% CI −19.8 to −11.6) and intravenous morphine (MD −11.4, 95% CI −21.6 to −1.2) were both superior to placebo at 30 min. Based on moderate quality of evidence, corticosteroids showed no benefits against placebo at emergency discharge for non-specific low back pain (MD 9.0, 95% CI −0.71 to 18.7) or sciatica (MD −6.8, 95% CI −24.2 to 10.6). There were conflicting results from trials comparing different pharmacological options (moderate quality evidence) or investigating non-pharmacological treatments (low quality evidence).ConclusionKetoprofen gel for non-specific low back pain and intravenous paracetamol or morphine for sciatica were superior to placebo, whereas corticosteroids were ineffective for both conditions. There was conflicting evidence for comparisons of different pharmacological options and those involving non-pharmacological treatments. Additional trials measuring important patient-related outcomes to EDs are needed.
Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer
Authors: Chen Hanyu , Zheng Xiaobin , Zong Xiaoyu , Li Zitong , Li Na , Hur Jinhee , Fritz Cassandra DL , Chapman Jr William , Nickel Katelin B , Tipping Andrew , Colditz Graham A , Giovannucci Edward L , Olsen Margaret A , Fields Ryan C , Cao Yin 
Published: October 2020

ObjectiveFactors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined.DesignWe conducted a nested case–control study among participants aged 18–64 in the IBM MarketScan Commercial Database (2006–2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs.ResultsMetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50–64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (ptrend<0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50–64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09).ConclusionsMetabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.
Safety and clinical activity of intratumoral MEDI9197 alone and in combination with durvalumab and/or palliative radiation therapy in patients with advanced solid tumors
Authors: Siu Lillian , Brody Joshua , Gupta Shilpa , Marabelle Aurélien , Jimeno Antonio , Munster Pamela , Grilley-Olson Juneko , Rook Alain H , Hollebecque Antoine , Wong Rebecca K S , Welsh James W , Wu Yuling , Morehouse Christopher , Hamid Oday , Walcott Farzana , Cooper Zachary A , Kumar Rakesh , Ferté Charles , Hong David S 
Published: October 2020

BackgroundMEDI9197 is an intratumorally administered toll-like receptor 7 and 8 agonist. In mice, MEDI9197 modulated antitumor immune responses, inhibited tumor growth and increased survival. This first-time-in-human, phase 1 study evaluated MEDI9197 with or without the programmed cell death ligand-1 (PD-L1) inhibitor durvalumab and/or palliative radiation therapy (RT) for advanced solid tumors.Patients and methodsEligible patients had at least one cutaneous, subcutaneous, or deep-seated lesion suitable for intratumoral (IT) injection. Dose escalation used a standard 3+3 design. Patients received IT MEDI9197 0.005–0.055 mg with or without RT (part 1), or IT MEDI9197 0.005 or 0.012 mg plus durvalumab 1500 mg intravenous with or without RT (part 3), in 4-week cycles. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics, pharmacodynamics, and objective response based on Response Evaluation Criteria for Solid Tumors version 1.1. Exploratory endpoints included tumor and peripheral biomarkers that correlate with biological activity or predict response.ResultsFrom November 2015 to March 2018, part 1 enrolled 35 patients and part 3 enrolled 17 patients; five in part 1 and 2 in part 3 received RT. The maximum tolerated dose of MEDI9197 monotherapy was 0.037 mg, with dose-limiting toxicity (DLT) of cytokine release syndrome in two patients (one grade 3, one grade 4) and 0.012 mg in combination with durvalumab 1500 mg with DLT of MEDI9197-related hemorrhagic shock in one patient (grade 5) following liver metastasis rupture after two cycles of MEDI9197. Across parts 1 and 3, the most frequent MEDI9197-related adverse events (AEs) of any grade were fever (56%), fatigue (31%), and nausea (21%). The most frequent MEDI9197-related grade ≥3 events were decreased lymphocytes (15%), neutrophils (10%), and white cell counts (10%). MEDI9197 increased tumoral CD8+ and PD-L1+ cells, inducing type 1 and 2 interferons and Th1 response. There were no objective clinical responses; 10 patients in part 1 and 3 patients in part 3 had stable disease ≥8 weeks.ConclusionIT MEDI9197 was feasible for subcutaneous/cutaneous lesions but AEs precluded its use in deep-seated lesions. Although no patients responded, MEDI9197 induced systemic and intratumoral immune activation, indicating potential value in combination regimens in other patient populations.Trial registration numberNCT02556463.
Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis
Authors: Apolo Andrea B , Ellerton John A , Infante Jeffrey R , Agrawal Manish , Gordon Michael S , Aljumaily Raid , Gourdin Theodore , Dirix Luc , Lee Keun-Wook , Taylor Matthew H , Schöffski Patrick , Wang Ding , Ravaud Alain , Manitz Juliane , Pennock Gregory , Ruisi Mary , Gulley James L , Patel Manish R 
Published: October 2020

BackgroundAnti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1). We report ≥2-year follow-up data for avelumab treatment and exploratory subgroup analyses in patients with urothelial carcinoma.MethodsPatients with previously treated advanced/metastatic urothelial carcinoma, pooled from two cohorts of the phase Ib JAVELIN Solid Tumor trial, received avelumab 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity or withdrawal. End points included best overall response and progression-free survival (PFS) per RECIST V.1.1, overall survival (OS) and safety. Post hoc analyses included objective response rates (ORRs) in subgroups defined by established high-risk/poor-prognosis characteristics and association between time to response and outcome.Results249 patients received avelumab; efficacy was assessed in 242 postplatinum patients. Median follow-up was 31.9 months (range 24–43), and median treatment duration was 2.8 months (range 0.5–42.8). The confirmed ORR was 16.5% (95% CI 12.1% to 21.8%; complete response in 4.1% and partial response in 12.4%). Median duration of response was 20.5 months (95% CI 9.7 months to not estimable). Median PFS was 1.6 months (95% CI 1.4 to 2.7 months) and the 12-month PFS rate was 16.8% (95% CI 11.9% to 22.4%). Median OS was 7.0 months (95% CI 5.9 to 8.5 months) and the 24-month OS rate was 20.1% (95% CI 15.2% to 25.4%). In post hoc exploratory analyses, avelumab showed antitumor activity in high-risk subgroups, including elderly patients and those with renal insufficiency or upper tract disease; ORRs were numerically lower in patients with liver metastases or low albumin levels. Objective response achieved by 3 months versus later was associated with longer OS (median not reached (95% CI 18.9 months to not estimable) vs 7.1 months (95% CI 5.2 to 9.0 months)). Safety findings were consistent with previously reported 6-month analyses.ConclusionsAfter ≥2 years of follow-up, avelumab showed prolonged efficacy and acceptable safety in patients with platinum-treated advanced/metastatic urothelial carcinoma, including high-risk subgroups. Survival appeared longer in patients who responded within 3 months. Long-term safety findings were consistent with earlier reports with avelumab treatment in this patient population.