Effect of Donor Sex on Recipient Mortality in Transfusion.

BACKGROUND: Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited. METHODS: In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group. RESULTS: A total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], -0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06). CONCLUSIONS: This trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.).

Psychometric Evaluation of the Multidimensional Scale-Uremic Pruritus in Dialysis Patients (UP-Dial): Comparison in Hemodialysis and Peritoneal Dialysis Patients with Chronic Pruritus.

BACKGROUND: High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. OBJECTIVES: To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uremic Pruritus in Dialysis (UP-Dial) 14-item, by comparing hemodialysis and peritoneal dialysis modality. METHODS: This validation study used data from the Thai Renal Outcomes Research-Uremic Pruritus, a prospective, multicenter, longitudinal study. Data for this study were collected from February 1, 2019, to May 31, 2022. The adult sample of 226 hemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across hemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73 to 0.74) with global itching, a positively moderate correlation (0.33 to 0.58) with DLQI, PSQI, global fatigue, SSS-8, and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation: 0.84 to 0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05). CONCLUSIONS: The findings reaffirm good measurement properties of the UP-Dial 14-items in hemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.

Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Associations of preoperative anaemia with healthcare resource use and outcomes after colorectal surgery: a population-based cohort study.

BACKGROUND: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. METHODS: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged ≥18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin <130 g L-1 in males; <120 g L-1 in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. RESULTS: We included 54,286 patients, with mean 65.3 (range 18-102) years of age and 49.0% females, among which 21 264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04-1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04-4.66), MAEs (OR 1.14, 95% CI 1.03-1.27), LOS (RoM 1.08, 95% CI 1.07-1.10), and readmissions (OR 1.16, 95% CI 1.08-1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95-0.96). CONCLUSIONS: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

Indefinite Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Cost-Effectiveness Study.

BACKGROUND: Clinical practice guidelines recommend indefinite anticoagulation for a first unprovoked venous thromboembolism (VTE). OBJECTIVE: To estimate the benefit-harm tradeoffs of indefinite anticoagulation in patients with a first unprovoked VTE. DESIGN: Markov modeling study. DATA SOURCES: Systematic reviews and meta-analyses for the long-term risks and case-fatality rates of recurrent VTE and major bleeding. Published literature for costs, quality of life, and other clinical events. TARGET POPULATION: Patients with a first unprovoked VTE who have completed 3 to 6 months of initial anticoagulant treatment. TIME HORIZON: Lifetime. PERSPECTIVE: Canadian health care public payer. INTERVENTION: Indefinite anticoagulation with direct oral anticoagulants. OUTCOME MEASURES: Recurrent VTE events, major bleeding events, costs in 2022 Canadian dollars (CAD), and quality-adjusted life-years (QALYs). RESULTS OF BASE-CASE ANALYSIS: When compared with discontinuing anticoagulation after initial treatment in a hypothetical cohort of 1000 patients aged 55 years, indefinite anticoagulation prevented 368 recurrent VTE events, which included 14 fatal pulmonary emboli, but induced an additional 114 major bleeding events, which included 30 intracranial hemorrhages and 11 deaths from bleeding. Indefinite anticoagulation cost CAD $16 014 more per person and did not increase QALYs (-0.075 per person). RESULTS OF SENSITIVITY ANALYSIS: Model results were most sensitive to the case-fatality rate of major bleeding and the annual risk for major bleeding during extended anticoagulation. LIMITATION: The model assumed that risks for recurrent VTE and major bleeding measured in clinical trials at 1 year remained constant during extended anticoagulation. CONCLUSION: Clinicians should use shared decision making to incorporate individual patient preferences and values when considering treatment duration for unprovoked VTE. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders.

Turmeric has been gaining popularity as a treatment option for digestive disorders, although a rigorous synthesis of efficacy has not been conducted. This study aimed to summarize the evidence for the efficacy and safety of turmeric in the treatment of digestive disorders, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), dyspepsia, gastroesophageal reflux disease, and peptic ulcers. Literature searches were conducted in Medline, EMBASE, AMED, the Cochrane Central Register of Control Trials, and Dissertation Abstracts from inception to November 15, 2021. Dual independent screening of citations and full texts was conducted and studies meeting inclusion criteria were retained: randomized controlled trials (RCT) and comparative observational studies evaluating turmeric use in people of any age with one of the digestive disorders of interest. Extraction of relevant data and risk of bias assessments were performed by two reviewers independently. Meta-analysis was not conducted due to high heterogeneity. From 1136 citations screened, 26 eligible studies were retained. Most studies were assessed to have a high risk of bias, and many had methodological limitations. Descriptive summaries suggest that turmeric is safe, with possible efficacy in patients with IBD or IBS, but its effects were inconsistent for other conditions. The efficacy of turmeric in digestive disorders remains unclear due to the high risk of bias and methodological limitations of the included studies. Future studies should be designed to include larger sample sizes, use rigorous statistical methods, employ core outcome sets, and adhere to reporting guidance for RCTs of herbal interventions to facilitate more meaningful comparisons and robust conclusions.

Clustering of Health Behaviors in Canadians: A Multiple Behavior Analysis of Data from the Canadian Longitudinal Study on Aging.

BACKGROUND: Health behaviors such as physical inactivity, unhealthy eating, smoking tobacco, and alcohol use are each leading risk factors for non-communicable chronic disease. Better understanding which behaviors tend to co-occur (i.e., cluster together) and co-vary (i.e., are correlated) may provide novel opportunities to develop more comprehensive interventions to promote multiple health behavior change. However, whether co-occurrence or co-variation-based approaches are better suited for this task remains relatively unknown. PURPOSE: To compare the utility of co-occurrence vs. co-variation-based approaches for understanding the interconnectedness between multiple health-impacting behaviors. METHODS: Using baseline and follow-up data (N = 40,268) from the Canadian Longitudinal Study of Aging, we examined the co-occurrence and co-variation of health behaviors. We used cluster analysis to group individuals based on their behavioral tendencies across multiple behaviors and to examine how these clusters are associated with demographic characteristics and health indicators. We compared outputs from cluster analysis to behavioral correlations and compared regression analyses of clusters and individual behaviors predicting future health outcomes. RESULTS: Seven clusters were identified, with clusters differentiated by six of the seven health behaviors included in the analysis. Sociodemographic characteristics varied across several clusters. Correlations between behaviors were generally small. In regression analyses individual behaviors accounted for more variance in health outcomes than clusters. CONCLUSIONS: Co-occurrence-based approaches may be more suitable for identifying sub-groups for intervention targeting while co-variation approaches are more suitable for building an understanding of the relationships between health behaviors.

Health behaviors such as physical inactivity, unhealthy eating, smoking tobacco, and alcohol use are each leading risk factors for non-communicable chronic disease. A better understanding of which behavioral combinations people engage in, and which behaviors are associated with each other, may provide new insights to support the development of interventions to promote multiple health behavior change. Using data with two time points (N = 40,268) from the Canadian Longitudinal Study of Aging, we grouped people into clusters based on their health behaviors and examined how these clusters are associated with demographic characteristics and health indicators. Seven clusters were identified with sociodemographic patterns evident across several clusters. Correlations between behaviors were generally small. We compared whether individual health behaviors, or groupings of people based on their health behaviors, were better predictors of future health outcomes. Individual behaviors were slightly better predictors of future health outcomes than clusters.

Pandemic Effect on Healthcare Use and Death in Adults with Epilepsy: A Population Study.

OBJECTIVES: We conducted a population-based study using Ontario health administrative data to describe trends in healthcare utilization and mortality in adults with epilepsy during the first pandemic year (March 2020-March 2021) compared to historical data (2016-2019). We also investigated if changes in outpatient visits and diagnostic testing during the first pandemic year were associated with increased risk for hospitalizations, emergency department (ED) visits, or death. METHODS: Projected monthly visit rates (per 100,000 people) for outpatient visits, electroencephalography, magnetic resonance, computed tomography, all-cause ED visits, hospitalizations, and mortality were calculated based on historical data by fitting monthly time series autoregressive integrated moving-average models. Two-way interactions were calculated using Quasi-Poisson models. RESULTS: In adults with epilepsy during the first quarter of the pandemic, we demonstrated a reduction in all-cause outpatient visits, diagnostic testing, ED visits and hospitalizations, and a temporary increase in mortality (observed rates of 355.8 vs projected 308.8, 95% CI: 276.3-345.1). By the end of the year, outpatient visits increased (85,535.4 vs 76,620.6, 95% CI: 71,546.9-82,059.4), and most of the diagnostic test rates returned to the projected. The increase in the rate of all-cause mortality during the pandemic, compared to pre-pandemic, was greater during months with the lower frequency of diagnostic tests than months with higher frequency (interaction p-values <.0001). CONCLUSION: We described the impact of the pandemic on healthcare utilization and mortality in adults with epilepsy during the first year. We demonstrated that access to relevant diagnostic testing is likely important for this population while planning restrictions on non-urgent health services.

The co-development of a linguistic and culturally tailored tele-retinopathy screening intervention for immigrants living with diabetes from China and African-Caribbean countries in Ottawa, Canada.

BACKGROUND: Diabetic retinopathy is a sight-threatening ocular complication of diabetes. Screening is an effective way to reduce severe complications, but screening attendance rates are often low, particularly for newcomers and immigrants to Canada and people from cultural and linguistic minority groups. Building on previous work, in partnership with patient and health system stakeholders, we co-developed a linguistically and culturally tailored tele-retinopathy screening intervention for people living with diabetes who recently immigrated to Canada from either China or African-Caribbean countries. METHODS: Following an environmental scan of diabetes eye care pathways in Ottawa, we conducted co-development workshops using a nominal group technique to create and prioritize personas of individuals requiring screening and identify barriers to screening that each persona may face. Next, we used the Theoretical Domains Framework to categorize the barriers/enablers and then mapped these categories to potential evidence-informed behaviour change techniques. Finally with these techniques in mind, participants prioritized strategies and channels of delivery, developed intervention content, and clarified actions required by different actors to overcome anticipated intervention delivery barriers. RESULTS: We carried out iterative co-development workshops with Mandarin and French-speaking individuals living with diabetes (i.e., patients in the community) who immigrated to Canada from China and African-Caribbean countries (n = 13), patient partners (n = 7), and health system partners (n = 6) recruited from community health centres in Ottawa. Patients in the community co-development workshops were conducted in Mandarin or French. Together, we prioritized five barriers to attending diabetic retinopathy screening: language (TDF Domains: skills, social influences), retinopathy familiarity (knowledge, beliefs about consequences), physician barriers regarding communication for screening (social influences), lack of publicity about screening (knowledge, environmental context and resources), and fitting screening around other activities (environmental context and resources). The resulting intervention included the following behaviour change techniques to address prioritized local barriers: information about health consequence, providing instructions on how to attend screening, prompts/cues, adding objects to the environment, social support, and restructuring the social environment. Operationalized delivery channels incorporated language support, pre-booking screening and sending reminders, social support via social media and community champions, and providing using flyers and videos as delivery channels. CONCLUSION: Working with intervention users and stakeholders, we co-developed a culturally and linguistically relevant tele-retinopathy intervention to address barriers to attending diabetic retinopathy screening and increase uptake among two under-served groups.

Length of initial prescription at hospital discharge and long-term medication adherence for elderly, post-myocardial infarction patients: a population-based interrupted time series study.

BACKGROUND: Preliminary evidence suggests that providing longer duration prescriptions at discharge may improve long-term adherence to secondary preventative cardiac medications among post-myocardial infarction (MI) patients. We implemented and assessed the effects of two hospital-based interventions-(1) standardized prolonged discharge prescription forms (90-day supply with 3 repeats for recommended cardiac medications) plus education and (2) education only-on long-term cardiac medication adherence among elderly patients post-MI. METHODS: We conducted an interrupted time series study of all post-MI patients aged 65-104 years in Ontario, Canada, discharged from hospital between September 2015 and August 2018 with ≥ 1 dispensation(s) for a statin, beta blocker, angiotensin system inhibitor, and/or secondary antiplatelet within 7 days post-discharge. The standardized prolonged discharge prescription forms plus education and education-only interventions were implemented at 2 (1,414 patients) and 4 (926 patients) non-randomly selected hospitals in September 2017 for 12 months, with all other Ontario hospitals (n = 143; 18,556 patients) comprising an external control group. The primary outcome, long-term cardiac medication adherence, was defined at the patient-level as an average proportion of days covered (over 1-year post-discharge) ≥ 80% across cardiac medication classes dispensed at their index fill. Primary outcome data were aggregated within hospital groups (intervention 1, 2, or control) to monthly proportions and independently analyzed using segmented regression to evaluate intervention effects. A process evaluation was conducted to assess intervention fidelity. RESULTS: At 12 months post-implementation, there was no statistically significant effect on long-term cardiac medication adherence for either intervention-standardized prolonged discharge prescription forms plus education (5.4%; 95% CI - 6.4%, 17.2%) or education only (1.0%; 95% CI - 28.6%, 30.6%)-over and above the counterfactual trend; similarly, no change was observed in the control group (- 0.3%; 95% CI - 3.6%, 3.1%). During the intervention period, only 10.8% of patients in the intervention groups received ≥ 90 days, on average, for cardiac medications at their index fill. CONCLUSIONS: Recognizing intervention fidelity was low at the pharmacy level, and no statistically significant post-implementation differences in adherence were found, the trends in this study-coupled with other published retrospective analyses of administrative data-support further evaluation of this simple intervention to improve long-term adherence to cardiac medications. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03257579 , registered June 16, 2017 Protocol available at: https://pubmed.ncbi.nlm.nih.gov/33146624/ .

Outcomes of Patients Undergoing Elective Bowel Resection Before and After Implementation of an Anemia Screening and Treatment Program.

BACKGROUND: Patients with anemia undergoing elective colorectal cancer surgery are known to have significantly higher rates of postoperative complications and worse outcomes. OBJECTIVE: This study aimed to improve rates of anemia screening and treatment in patients undergoing elective colon and rectal resections through a quality improvement initiative. DESIGN: We compared a historical cohort of patients before implementation of our anemia screening and treatment quality improvement program to a prospective cohort after implementation. SETTINGS: This study was conducted at a tertiary care hospital. PATIENTS: This study included all adult patients with a new diagnosis of colon or rectal cancer without evidence of metastatic disease between 2017 and 2019. INTERVENTIONS: The interventions include the anemia screening and treatment quality improvement program. MAIN OUTCOME MEASURES: The primary outcome was hospital cost per admission. RESULTS: This study includes a total of 84 patients who underwent elective colon or rectal resection before implementation of our anemia quality improvement project and 88 patients who underwent surgery after. In the preimplementation cohort 44 of 84 patients (55.9%) were anemic compared to 47 of 99 patients (54.7%) in the postimplementation cohort. Rates of screening (25%-86.4%) and treatment (27.8%- 63.8%) were significantly increased in the postimplementation cohort. Mean total cost per admission was significantly decreased in the postimplementation cohort (mean cost $16,827 vs $25,796; p = 0.004); this significant reduction was observed even after adjusting for relevant confounding factors (ratio of means: 0.74; 95% CI, 0.65-0.85). The mechanistic link between treatment of anemia and reductions in cost remains unknown. No significant difference was found in rates of blood transfusion, complications, or mortality between the groups. LIMITATIONS: The study limitation includes before-after design subjected to selection and temporal biases. CONCLUSIONS: We demonstrate the successful implementation of an anemia screening and treatment program. This program was associated with significantly reduced cost per admission. This work demonstrates possible value and benefits of implementation of an anemia screening and treatment program. See Video Abstract at http://links.lww.com/DCR/C15 .RESULTADOS DE LOS PACIENTES SOMETIDOS A RESECCIÓN INTESTINAL ELECTIVA ANTES Y DESPUÉS DE LA IMPLEMENTACIÓN DE UN PROGRAMA DE DETECCIÓN Y TRATAMIENTO DE ANEMIA. ANTECEDENTES: Se sabe que los pacientes anémicos que se someten a una cirugía electiva de cáncer colorrectal tienen tasas significativamente más altas de complicaciones posoperatorias y peores resultados. OBJETIVO: Mejorar las tasas de detección y tratamiento de la anemia en pacientes sometidos a resecciones electivas de colon y recto a través de una iniciativa de mejora de calidad. DISEO: Comparamos una cohorte histórica de pacientes antes de la implementación de nuestro programa de detección de anemia y mejora de la calidad del tratamiento con una cohorte prospectiva después de la implementación. ENTORNO CLINICO: Hospital de atención terciaria. PACIENTES: Todos los pacientes adultos con un nuevo diagnóstico de cáncer de colon o recto sin evidencia de enfermedad metastásica entre 2017 y 2019. INTERVENCIONES: Detección de anemia y programa de mejora de la calidad del tratamiento. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue el costo hospitalario por ingreso. RESULTADOS: Un total de 84 pacientes se sometieron a resección electiva de colon o recto antes de la implementación de nuestro proyecto de mejora de calidad de la anemia y 88 pacientes se sometieron a cirugía después. En la cohorte previa a la implementación, 44/84 (55,9 %) presentaban anemia en comparación con 47/99 (54,7 %) en la cohorte posterior a la implementación. Las tasas de detección (25 % a 86,4 %) y tratamiento (27,8 % a 63,8 %) aumentaron significativamente en la cohorte posterior a la implementación. El costo total medio por admisión se redujo significativamente en la cohorte posterior a la implementación (costo medio $16 827 vs. $25 796, p = 0,004); esta reducción significativa se observó incluso después de ajustar los factores de confusión relevantes (proporción de medias: 0,74, IC del 95 %: 0,65 a 0,85). El vínculo mecánico entre el tratamiento de la anemia y la reducción de costos sigue siendo desconocido. No hubo diferencias significativas en las tasas de transfusión de sangre, complicaciones o mortalidad entre los grupos. LIMITACIONES: El diseño de antes y después está sujeto a sesgos temporales y de selección. CONCLUSIONES: Demostramos la implementación exitosa de un programa de detección y tratamiento de anemia. Este programa se asoció con un costo por admisión significativamente reducido. Este trabajo demuestra el valor y los beneficios posibles de la implementación de un programa de detección y tratamiento de la anemia. Consulte Video Resumen en http://links.lww.com/DCR/C15 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Effects of acute and preventive therapies for episodic and chronic cluster headache: A scoping review of the literature.

BACKGROUND: Cluster headache is the most common primary headache disorder of the trigeminal autonomic cephalalgias, and it is highly disabling. OBJECTIVE: We undertake a scoping review to characterize therapies to prevent and acutely treat cluster headache, characterize trial methodology utilized in studies, and recommend future trial "good practices." We also assess homogeneity of studies and feasibility for future network meta-analyses (NMAs) to compare acute and preventive treatments for cluster headache. METHODS: A priori protocol for this scoping review was registered and available on Open Science Forum. We sought studies that enrolled adult patients with cluster headache as identified by accepted diagnostic criteria. Both randomized controlled trials (RCTs) and observational studies (with a control group) were included. The interventions of interest were medications, procedures, devices, surgeries, and behavioral/psychological interventions, whereas comparators of interest were placebo, sham, or other active treatments. Outcomes were predefined; however, we did not exclude studies lacking these outcomes. A systemic search was conducted in Ovid Medline, Embase, and Cochrane. We performed a targeted search for conference abstracts from journals prominent in the field. RESULTS: We identified 56 studies: 45 RCTs, four studies only available in clinical trial registries, and seven observational studies. Of the 45 RCTs, 20 focused on acute therapies and 25 on preventive therapies. Overall, we determined that it is feasible to pursue a NMA for acute therapy focusing on 15 or 30-min headache reduction for acute trials, as we identified 11 trials in the combined population of patients with either episodic or chronic cluster headache (2 trials in populations with chronic cluster headache were also found). For preventive therapy of cluster headache, we identified trials with common outcomes that may be considered for NMA, however, as these trials had differences in treatment effect modifiers that could not be corrected, NMAs appear infeasible for this indication. We identified new studies looking at noninvasive vagal nerve stimulation, sphenopalatine ganglion stimulation, prednisone, and oxygen published since the most recent systematic review in the field, although these acute treatments were previously identified as effective. However, for calcitonin gene-related peptide (CGRP) monoclonal antibodies, galcanezumab demonstrated effectiveness in episodic cluster headache, but a lack of effectiveness in chronic cluster headache, and fremanezumab was not effective for episodic nor chronic cluster headache. This finding highlights that CGRP monoclonal antibodies may not show a class effect in cluster headache prevention and need to be considered individually. CONCLUSIONS: We describe the treatment landscape of cluster headache for both acute and preventive treatments. Last, we present the NMAs we will undertake in acute therapies of cluster headache.

Network meta-analysis of therapies for cluster headache: Effects of acute therapies for episodic and chronic cluster.

OBJECTIVE: We used network meta-analysis (NMA) to characterize the relative effectiveness and harms of acute treatment options for cluster headache. BACKGROUND: There are few evidence-based acute treatments available for cluster headache. As most treatments were compared only against placebos in clinical trials, few head-to-head comparisons of treatments are available. METHODS: An a priori registered scoping review was performed to identify randomized controlled trials evaluating treatments in adult patients (>18 years old) with cluster headache per accepted diagnostic criteria. Bayesian NMAs were performed to compare treatments in terms of headache relief at 15 or 30 min, and also the occurrence of adverse events. We report odds ratios (ORs) of relative treatment effects along with corresponding 95% credible intervals (CrIs), as well as measures of treatment ranking. RESULTS: A total of 13 randomized controlled trials informed NMAs. We found high flow oxygen to be the most effective therapy for headache response at 15 and 30 min (OR 9.0, 95% CrI 5.3 to 15.9 vs. placebo), with injectable sumatriptan demonstrating the next highest effect (OR 6.4, 95% CrI 3.75 to 11.1 vs. placebo). High flow oxygen was also more effective than low flow oxygen (OR 2.55, 95% CrI 1.13 to 5.8), nasal spray zolmitriptan (OR 3.75, 95% CrI 1.72 to 8.4), octreotide (OR 4.5, 95% CrI 1.64 to 12.5), and non-invasive vagal nerve stimulation (nVNS; OR 5.2, 95% CrI 2.29 to 11.9). Sumatriptan injectable was also effective for headache relief and was found to be better than nasal spray zolmitriptan (OR 2.67, 95% CrI 1.21 to 5.9), octreotide (OR 3.20, 95% CrI 1.17 to 8.8), and nVNS (OR 3.69, 95% CrI 1.63 to 8.4). Octreotide (OR 4.1, 95% CrI 1.71 to 10.5) and sumatriptan (OR 2.40, 95% CrI 1.39 to 4.2) were associated with greater risk of adverse events compared to placebo, while other treatments did not demonstrate increased risk. When focusing on patients with episodic cluster headache, nVNS was significantly better than placebo (OR 4.9, 95% CrI 1.89 to 14.1). CONCLUSIONS: Our findings suggest that high flow oxygen is more efficacious when compared to low flow oxygen for headache relief. When low flow oxygen fails in patients who can tolerate oxygen, increased flow rates should be tried. Additionally, high flow oxygen is likely more effective than zolmitriptan nasal spray, nVNS, and octreotide. Sumatriptan injectable is more likely to be effective when compared to zolmitriptan nasal spray, octreotide, and nVNS.

Cost-effectiveness of integrated disease management for high risk, exacerbation prone, patients with chronic obstructive pulmonary disease in a primary care setting.

BACKGROUND: We evaluate the cost-effectiveness of the 'Best Care' integrated disease management (IDM) program for high risk, exacerbation prone, patients with chronic obstructive pulmonary disease (COPD) compared to usual care (UC) within a primary care setting from the perspective of a publicly funded health system (i.e., Ontario, Canada). METHODS: We conducted a model-based, cost-utility analysis using a Markov model with expected values of costs and outcomes derived from a Monte-Carlo Simulation with 5000 replications. The target population included patients started in GOLD II with a starting age of 68 years in the trial-based analysis. Key input parameters were based on a randomized control trial of 143 patients (i.e., UC (n = 73) versus IDM program (n = 70)). Results were shown as incremental cost per quality-adjusted life year (QALY) gained. RESULTS: The IDM program for high risk, exacerbation prone, patients is dominant in comparison with the UC group. After one year, the IDM program demonstrated cost savings and improved QALYs (i.e., UC was dominated by IDM) with a positive net-benefit of $5360 (95% CI: ($5175, $5546) based on a willingness to pay of $50,000 (CAN) per QALY. CONCLUSIONS: This study demonstrates that the IDM intervention for patients with COPD in a primary care setting is cost-effective in comparison to the standard of care. By demonstrating the cost-effectiveness of IDM, we confirm that investment in the delivery of evidence based best practices in primary care delivers better patient outcomes at a lower cost than UC.

Cost-effectiveness of direct surgery versus preoperative octreotide therapy for growth-hormone secreting pituitary adenomas.

PURPOSE: The objective of this study was to compare the cost-effectiveness of preoperative octreotide therapy followed by surgery versus the standard treatment modality for growth-hormone secreting pituitary adenomas, direct surgery (that is, surgery without preoperative treatment) from a public third-party payer perspective. METHODS: We developed an individual-level state-transition microsimulation model to simulate costs and outcomes associated with preoperative octreotide therapy followed by surgery and direct surgery for patients with growth-hormone secreting pituitary adenomas. Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs [2020 United States (US) Dollars], quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, direct surgery was found to be the dominant strategy as it yielded lower costs and greater health effects (QALYs) compared to preoperative octreotide strategy in the second-order Monte Carlo microsimulation. The ICER was most sensitive to probability of remission following primary therapy and duration of preoperative octreotide therapy. Accounting for joint parameter uncertainty, direct surgery had a higher probability of demonstrating a cost-effective profile compared to preoperative octreotide treatment at 77% compared to 23%, respectively. CONCLUSIONS: Using standard benchmarks for cost-effectiveness in the US ($100,000/QALY), preoperative octreotide therapy followed by surgery may not be cost-effective compared to direct surgery for patients with growth-hormone secreting pituitary adenomas but the result is highly sensitive to initial treatment failure and duration of preoperative treatment.

A Systematic Review of the Cost of Chronic Pelvic Pain in Women.

OBJECTIVE: To systematically summarize the evidence on costs related to chronic pelvic pain (CPP) for women. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane Library) were searched for English and French articles published from 1990 to January 2021 STUDY SELECTION: Of 1304 articles screened, 67 were screened in full-text form, and a total of 13 articles were included in the final analysis. Articles included involved cost studies that estimated hospital or health system costs for pelvic pain, dysmenorrhea, dyspareunia, endometriosis with pain, interstitial cystitis, or painful bladder syndrome. DATA EXTRACTION AND SYNTHESIS: A standardized form was created to extract study setting, design, and population; patient demographics; study duration; and reported costs of CPP components and amounts. Two independent reviewers completed the data extraction, and discrepancies were resolved through discussion with a third reviewer. CONCLUSION: Estimated health care costs ranged from US$1367 to US$7043 per woman per year. Prescription costs ranged from US$193 to US$2457 per woman per year. Indirect costs ranged from US$4216 to US$12 789 per woman per year. Combined costs ranged from US$1820 to US$20 898 per woman per year. The yearly costs of CPP varied according to country; yearly costs were estimated to be $2.8 billion, ¥191,680 to ¥246,488, and $16 970 to $20 898 per woman per year in the United Sates, Japan, and Australia, respectively. The literature suggests that CPP represents a considerable economic burden on women and health care systems internationally, with indirect costs contributing a significant portion of total costs.

Economic feasibility of a novel tool to assist extubation decision-making: an early health economic modeling.

OBJECTIVES: To estimate the minimum percent change in failed extubation to make a tool designed to reduce extubation failure (Extubation Advisor [EA]) economically viable. METHODS: We conducted an early return on investment (ROI) analysis using data from intubated intensive care unit (ICU) patients at a large Canadian tertiary care hospital. We obtained input parameters from the hospital database and published literature. We ran generalized linear models to estimate the attributable length of stay, total hospital cost, and time to subsequent extubation attempt following failure. We developed a Markov model to estimate the expected ROI and performed probabilistic sensitivity analyses to assess the robustness of findings. Costs were presented in 2020 Canadian dollars (C$). RESULTS: The model estimated a 1 percent reduction in failed extubation could save the hospital C$289 per intubated patient (95 percent CI: 197, 459). A large center seeing 2,500 intubated ICU patients per year could save C$723,124/year/percent reduction in failed extubation. At the current annual price of C$164,221, the EA tool must reduce extubation failure by at least 0.24 percent (95 percent CI: .14, .41) to make the tool cost-effective at our site. CONCLUSIONS: Clinical decision-support tools like the EA may play an important role in reducing healthcare costs by reducing the rate of extubation failure, a costly event in the ICU.

Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Systematic Review and Meta-analysis.

BACKGROUND: The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. PURPOSE: To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. STUDY SELECTION: Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment. DATA EXTRACTION: Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies. DATA SYNTHESIS: Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person-years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs. LIMITATION: Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs. CONCLUSION: In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).

Leveraging financial incentives and behavioural economics to engage physicians in achieving quality-improvement process measures.

BACKGROUND: Dedicated quality-improvement (QI) initiatives within health care systems are of clear benefit, and physicians respond to financial incentivization. The Canadian health care system often lacks this lever, and many financially incentivized QI programs rely on traditional economic principles. We describe our evaluation of financial incentivization for the implementation of QI process metrics in a department of surgery at a Canadian academic hospital system and its impact over a 4-year period. METHODS: Quality-improvement processes informed by extant QI incentivization literature and guided by the principles of behavioural economics were implemented within our institution's Department of Surgery. Disbursement of supplemental government funding was modified to be contingent on the ability of divisions within the department to meet predefined QI metrics, including regular multidisciplinary meetings, morbidity and mortality rounds with documented feedback of systemic issues to division members, reviews of adverse events, and implementation of annual patient experience projects. We evaluated the effect of the QI processes from 2015/16 to 2018/19. RESULTS: There was a significant increase in the number of divisions that satisfied all the QI metrics over the study period, from 2 (28%) in 2015/16, to 5 (71%) in 2016/17, to 7 (100.0%) in 2017/18 and 2018/19 (p < 0.01). The application of behavioural economics principles, such as reward versus penalty payoff, loss aversion, payment separation, aligning of values, and relative social ranking, was important to the outcome of the study. CONCLUSION: Incentivizing QI activities in the Canadian health care system is possible and led to improvement in QI processes as a whole in our department. This paper lays out a method of financial reimbursement to facilitate engagement of physicians and establishment of a foundation of important QI processes and measures within a department.

Long-term Health Outcomes and Health System Costs Associated With Surgical Site Infections: A Retrospective Cohort Study.

OBJECTIVES: To examine the association between surgical site infections (SSIs) and hospital readmissions and all-cause mortality, and to estimate the attributable health care costs of SSIs 1 year following surgery. BACKGROUND: SSIs are a common postoperative complication; the long-term impact of SSI on health outcomes and costs has not been formally evaluated. METHODS: This retrospective cohort study included all adult patients who underwent surgery at the 1202-bed teaching hospital in Ottawa, Ontario, Canada, and were included in the National Surgical Quality Improvement Program database between 2010 and 2015. The study exposure was postoperative SSI. The study outcomes included hospital readmission, all-cause mortality, and health care costs at 1 year (primary) and at 30 days and 90 days (secondary) following surgery. RESULTS: We identified 14,351 patients, including 795 patients with SSIs. Our multivariable analyses that accounted for competing risks demonstrated that at 1-year following the index date, superficial and deep/organ space SSIs were significantly associated with an increase in hospital readmission [hazard ratio (HR) = 1.63, 95% confidence interval (95% CI) 1.39-1.92 and HR = 3.49, (95% CI 2.76-4.17, respectively) and all-cause mortality (HR = 1.35, 95% CI 1.10-1.98 and HR = 2.21, 95% CI 1.44-2.78, respectively]. At 1 year after surgery, patients with superficial and deep/organ space SSIs incurred higher health care costs C$20,648 (95% CI) C$16,980- C$24,112and C$53,075 (95% CI) C$44,628- C$60,936), than non-SSI patients. CONCLUSION: SSIs, especially deep/organ space SSI, contribute to adverse health outcomes and health care costs across the entire year after surgery. Our findings highlight the importance of effective prevention/monitoring strategies targeting both short- and long-term consequences of SSI.