Quality of life and cost-effectiveness of convalescent plasma compared to standard care for hospitalized COVID-19 patients in the CONCOR-1 trial.

BACKGROUND: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings. METHODS: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population. RESULTS: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078. DISCUSSION: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19.

Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major hepatic resections (PRICE-2): study protocol for a phase 3 randomized controlled trial.

INTRODUCTION: Blood loss and red blood cell (RBC) transfusion in liver surgery are areas of concern for surgeons, anesthesiologists, and patients alike. While various methods are employed to reduce surgical blood loss, the evidence base surrounding each intervention is limited. Hypovolemic phlebotomy, the removal of whole blood from the patient without volume replacement during liver transection, has been strongly associated with decreased bleeding and RBC transfusion in observational studies. This trial aims to investigate whether hypovolemic phlebotomy is superior to usual care in reducing RBC transfusions in liver resection. METHODS: This study is a double-blind multicenter randomized controlled trial. Adult patients undergoing major hepatic resections for any indication will be randomly allocated in a 1:1 ratio to either hypovolemic phlebotomy and usual care or usual care alone. Exclusion criteria will be minor resections, preoperative hemoglobin <100g/L, renal insufficiency, and other contraindication to hypovolemic phlebotomy. The primary outcome will be the proportion of patients receiving at least one allogeneic RBC transfusion unit within 30 days of the onset of surgery. Secondary outcomes will include transfusion of other allogeneic blood products, blood loss, morbidity, mortality, and intraoperative physiologic parameters. The surgical team will be blinded to the intervention. Randomization will occur on the morning of surgery. The sample size will comprise 440 patients. Enrolment will occur at four Canadian academic liver surgery centers over a 4-year period. Ethics approval will be obtained at participating sites before enrolment. DISCUSSION: The results of this randomized control trial will provide high-quality evidence regarding the use of hypovolemic phlebotomy in major liver resection and its effects on RBC transfusion. If proven to be effective, this intervention could become standard of care in liver operations internationally and become incorporated within perioperative patient blood management programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03651154 . Registered on August 29 2018.

Economic Evaluation of In-Hospital Clinical Practices in Acute Injury Care: A Systematic Review.

OBJECTIVES: Underuse of high-value clinical practices and overuse of low-value practices are major sources of inefficiencies in modern healthcare systems. To achieve value-based care, guidelines and recommendations should target both underuse and overuse and be supported by evidence from economic evaluations. We aimed to conduct a systematic review of the economic value of in-hospital clinical practices in acute injury care to advance knowledge on value-based care in this patient population. METHODS: Pairs of independent reviewers systematically searched MEDLINE, Embase, Web of Science, and Cochrane Central Register for full economic evaluations of in-hospital clinical practices in acute trauma care published from 2009 to 2019 (last updated on June 17, 2020). Results were converted into incremental net monetary benefit and were summarized with forest plots. The protocol was registered with PROSPERO (CRD42020164494). RESULTS: Of 33 910 unique citations, 75 studies met our inclusion criteria. We identified 62 cost-utility, 8 cost-effectiveness, and 5 cost-minimization studies. Values of incremental net monetary benefit ranged from international dollars -467 000 to international dollars 194 000. Of 114 clinical interventions evaluated (vs comparators), 56 were cost-effective. We identified 15 cost-effective interventions in emergency medicine, 6 in critical care medicine, and 35 in orthopedic medicine. A total of 58 studies were classified as high quality and 17 as moderate quality. From studies with a high level of evidence (randomized controlled trials), 4 interventions were clearly dominant and 8 were dominated. CONCLUSIONS: This research advances knowledge on value-based care for injury admissions. Results suggest that almost half of clinical interventions in acute injury care that have been studied may not be cost-effective.

Economic evaluation of intrahospital clinical practices in injury care: protocol for a 10-year systematic review.

INTRODUCTION: Underuse of high-value clinical practices and overuse of low-value practices are major sources of inefficiencies in modern healthcare systems. Injuries are second only to cardiovascular disease in terms of acute care costs but data on the economic impact of clinical practices for injury admissions are lacking. This study aims to summarise evidence on the economic value of intrahospital clinical practices for injury care. METHODS AND ANALYSIS: We will perform a systematic review to identify research articles in economic evaluation of intrahospital clinical practices in acute injury care. We will search MEDLINE and databases such as Embase, Web of Science, NHS Economic Evaluation Database, Cochrane CENTRAL, BIOSIS and CINAHL for randomised or non-randomised controlled trials and observational studies using a combination of keywords and controlled vocabulary. We will consider the following outcomes relative to economic evaluations: incremental cost-effectiveness ratio, incremental cost-utility ratio, incremental net health benefit, incremental net monetary benefit (iNMB) and incremental cost-benefit ratio. Pairs of independent reviewers will evaluate studies that meet eligibility criteria and extract data from included articles using an electronic data extraction form. All outcomes will be converted into iNMB. We will report iNMB for practices classified by type of practice (hospitalisation, consultation, diagnostic, therapeutic-surgical, therapeutic-drugs, therapeutic-other). Results obtained with a ceiling ratio of $50 000 per quality-adjusted life year gained for identified clinical practices will be summarised by charting forest plots. In line with Cochrane recommendations for systematic reviews of economic evaluations, meta-analyses will not be conducted. ETHICS AND DISSEMINATION: Ethics approval is not required as original data will not be collected. This study will summarise existing evidence on the economic value of clinical practices in injury care. Results will be used to advance knowledge on value-based care for injury admissions and will be disseminated through a peer-reviewed article, international scientific meetings and clinical and healthcare quality associations.

Predicting the need for supportive services after discharged from hospital: a systematic review.

BACKGROUND: Some patients admitted to acute care hospital require supportive services after discharge. The objective of our review was to identify models and variables that predict the need for supportive services after discharge from acute care hospital. METHODS: We performed a systematic review searching the MEDLINE, CINAHL, EMBASE, and COCHRANE databases from inception to May 1st 2017. We selected studies that derived and validated a prediction model for the need for supportive services after hospital discharge for patients admitted non-electively to a medical ward. We extracted cohort characteristics, model characteristics and variables screened and included in final predictive models. Risk of bias was assessed using the Quality in Prognostic Studies tool. RESULTS: Our search identified 3362 unique references. Full text review identified 6 models. Models had good discrimination in derivation (c-statistics > 0.75) and validation (c-statistics > 0.70) cohorts. There was high quality evidence that age, impaired physical function, disabilities in performing activities of daily living, absence of an informal care giver and frailty predict the need for supportive services after discharge. Stroke was the only unique diagnosis with at least moderate evidence of an independent effect on the outcome. No models were externally validated, and all were at moderate or higher risk of bias. CONCLUSIONS: Deficits in physical function and activities of daily living, age, absence of an informal care giver and frailty have the strongest evidence as determinants of the need for support services after hospital discharge. TRIAL REGISTRATION: This review was registered with PROSPERO #CRD42016037144.

Potential organ donor identification and system accountability: expert guidance from a Canadian consensus conference.

PURPOSE: Deceased donation rates in Canada remain below the predicted potential and lag behind leading countries. Missing a potential donor leads to preventable death and disability of transplant candidates and increased healthcare costs. METHODS: Stakeholders were invited to a national consensus conference on improving deceased organ donor identification and referral (ID&R) and healthcare system accountability. In advance, participants received evidence-based, background documents addressing death audits, clinical triggers, required referral legislation, ethics, clinical pathways, and donation standards. At the conference, expert presentations and summaries of background information prepared by the Steering Committee informed group discussions of the preset questions. The conference's themes were: 1) expectations of potential donors, recipients and their families; 2) donor ID&R: clinical and legal perspectives; 3) enhancing accountability: gaps and solutions; and 4) enhancing accountability: quality/safety organizations. RESULTS: Thirty-seven consensus statements were generated. At the healthcare professional (HCP) level, key statements include: 1) donation be consistently addressed as part of end-of-life care but only after a decision to withdraw life-sustaining treatment; 2) HCP know how and when to identify and refer potential donors; and 3) transplant candidates be informed of local allocation guidelines and performance. At the healthcare system level, key statements include: 1) national adoption of clinical criteria to trigger ID&R; 2) dedicated resources to match donation activities, including transfer of a potential donor; 3) performance measurement through death audits; 4) reporting and investigation of missed donation opportunities (MDO); 5) recognition of top performers; and 6) missed donor ID&R be considered a preventable and critical safety incident. CONCLUSION: Our consensus statements establish HCP and healthcare system responsibilities regarding potential organ donor ID&R and include the tracking, reviewing and elimination of MDO through system-wide death audits. Once implemented, these consensus statements will help honour patients' wishes to donate, improve service to potential transplant recipients, and support HCPs in fulfilling their ethical and legal responsibilitites. Next steps include implementation, assessment of their impact on donation rates, and investigation of new evidence-based targets for system improvement.

RéSUMé: OBJECTIF: Au Canada, les dons des personnes décédées restent inférieurs aux possibilités prédites et loin derrière les pays les plus performants. Le manque de donneurs potentiels aboutit à des décès évitables, à l'invalidité des candidats à la transplantation et à des coûts de soins de santé plus élevés. MéTHODES: Les principaux acteurs ont été invités à une conférence de consensus nationale sur l'amélioration de l'identification et de l'orientation des donneurs d'organes décédés (ID&R ­Identification and referral) et sur la responsabilité du système de santé. Les participants ont reçu à l'avance des documents basés sur des données probantes qui abordaient l'audit des décès, les facteurs cliniques identifiants, la législation requise pour l'orientation, l'éthique, les cheminements cliniques et les normes de dons. Au cours de la conférence, les présentations d'experts et des résumés de l'information de fond préparés par le Comité de pilotage ont alimenté les discussions de groupe sur les questions préparées. Les thèmes de la conférence étaient les suivants : 1) attentes des donneurs potentiels, des receveurs et de leurs familles; 2) identification et orientation des donneurs : points de vue cliniques et légaux; 3) amélioration de la responsabilité : lacunes et solutions; et 4) amélioration de la responsabilité : organisations de la qualité/sécurité. RéSULTATS: Trente-sept énoncés de consensus ont été générés. Au niveau des professionnels de santé, les principaux énoncés sont les suivants : 1) que le don soit constamment abordé dans le cadre des soins de fin de vie, mais seulement après avoir pris la décision d'arrêter les traitements de maintien de vie; 2) les professionnels de santé ont le savoir-faire pour identifier et orienter les donneurs potentiels; et 3) les candidats à la transplantation doivent être informés des lignes directrices locales sur les attributions et sa performance. Au niveau du système de soins de santé, les principaux énoncés sont les suivants : 1) l'adoption au niveau national de critères cliniques déclenchant l'identification et l'orientation des donneurs; 2) des ressources dédiées aux activités d'appariement des dons, y compris au transfert des donneurs potentiels; 3) des mesures de performance par des audits des décès; 4) la déclaration et des investigations sur les opportunités de dons manqués; 5) la reconnaissance des plus performants; et 6) l'identification et l'orientation manquées de donneurs doivent être considérées comme un incident évitable et critique. CONCLUSION: Nos énoncés de consensus établissent les responsabilités des professionnels de santé et du système de soins pour ce qui concerne l'identification et l'orientation des donneurs potentiels d'organes; ils incluent le suivi, l'analyse et l'élimination des dons manqués via une vérification des causes de décès dans tout le système. Une fois mis en œuvre, ces énoncés de consensus contribueront à honorer les souhaits des patients en matière de dons, améliorer les services apportés aux receveurs potentiels de greffes et soutenir les professionnels de santé dans l'accomplissement de leurs obligations éthiques et légales. Les étapes suivantes incluront la mise en œuvre, l'évaluation de leur impact sur les taux de dons et la recherche de nouvelles cibles basées sur des données probantes pour améliorer le système.

Risk assessment tools to predict location of discharge and need for supportive services for medical patients after discharge from hospital: a systematic review protocol.

BACKGROUND: Patients who are discharged from hospital after an acute medical illness often have impaired function that prevents them from returning to their previous place of residence. Assessing each patient's post-discharge needs takes time and resources but is important in order to reduce unplanned readmissions and adverse events post-discharge. METHODS/DESIGN: We will conduct a systematic review to synthesize the evidence on prognostic models and their reported accuracy in predicting the location of discharge after a medical admission to an acute care hospital. We will perform searches in MEDLINE, EMBASE, CINAHL, and COCHRANE databases. Pre-defined study, population, and model characteristics will be reported. We will write a narrative summary of included studies. Methodological quality of the studies will be assessed using the QUIPS tool, and the quality of evidence will be evaluated using the GRADE tool. DISCUSSION: Early and accurate assessment of patient needs for supportive services after discharge has the potential to improve patient outcomes and health system efficiency. This systematic review will identify factors that can accurately predict location of discharge using existing tools and identify priority knowledge gaps to inform future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037144.

Clinical practice guidelines and consensus statements in oncology--an assessment of their methodological quality.

BACKGROUND: Consensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine's standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents. METHODS: Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine's standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents. FINDINGS: Thirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored consistently lower than the others over both domains. No journals adhered to all the items related to the transparency of document development. One journal's consensus statements endorsed a product made by the sponsoring pharmaceutical company in 64% of cases. CONCLUSION: Guidance documents are an essential part of oncology care and should be subjected to a rigorous and validated development process. Consensus statements had lower methodological quality than clinical practice guidelines using AGREE II. At a minimum, journals should ensure that that all consensus statements and clinical practice guidelines adhere to AGREE II criteria. Journals should consider explicitly requiring guidelines to declare pharmaceutical company sponsorship and to identify the sponsor's product to enhance transparency.