Preoperative Anemia Prior to Gynecologic Surgery is Associated with Increased Healthcare Costs.

OBJECTIVE: To compare healthcare utilization costs between anemic and nonanemic patients undergoing elective hysterectomy and myomectomy for benign indications from the date of surgery to 30 days postoperatively. DESIGN: Retrospective population-based cohort study. SETTING: Single-payer publicly funded healthcare system in Ontario, Canada between 2013 and 2020. PARTICIPANTS: Adult women (≥18 years of age) who underwent elective hysterectomy or myomectomy (laparoscopic/laparotomy) for benign indications. INTERVENTIONS: Our exposure of interest was preoperative anemia, defined as the most recent hemoglobin value <12 g/dL on the complete blood count measured before the date of surgery. Our primary outcome was healthcare costs (total and disaggregated) from the perspective of the single-payer publicly funded healthcare system. RESULTS: Of the 59 270 patients in the cohort, 11 802 (19.9%) had preoperative anemia. After propensity matching, standardized differences in all baseline characteristics (N = 10 103 per group) were <0.10. In the matched cohort, the mean total healthcare cost per anemic patient was higher compared to cost per nonanemic patient ($6134.88 ± $2782.38 vs $6009.97 ± $2423.27, p < .001). Anemic patients, compared to nonanemic patients, had a higher mean difference in total healthcare cost of $124.91 per patient (95% CI $53.54-$196.29) translating to an increased cost attributable to anemia of 2.08% (95% CI 0.89%-3.28%, p < .001). In a subgroup analysis of patients undergoing hysterectomy (N = 9041), the cost was also significantly higher for anemic patients (mean difference per patient of $117.67, 95% CI $41.58-$193.75). For those undergoing myomectomy (N = 1062) the difference in cost was not statistically significant (mean difference $186.61, 95% CI -$17.42 to $390.65). CONCLUSION: Preoperative anemia was associated with significantly increased healthcare resource utilization and costs for patients undergoing elective gynecologic surgery. Although the cost difference per case was modest, when extrapolated to the population level, this difference could result in substantially significant cost to the healthcare system, attributable to preoperative anemia.

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.

Rapid antigen-based and rapid molecular tests for the detection of SARS-CoV-2: a rapid review with network meta-analysis of diagnostic test accuracy studies.

BACKGROUND: The global spread of COVID-19 created an explosion in rapid tests with results in < 1 hour, but their relative performance characteristics are not fully understood yet. Our aim was to determine the most sensitive and specific rapid test for the diagnosis of SARS-CoV-2. METHODS: Design: Rapid review and diagnostic test accuracy network meta-analysis (DTA-NMA). ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies assessing rapid antigen and/or rapid molecular test(s) to detect SARS-CoV-2 in participants of any age, suspected or not with SARS-CoV-2 infection. INFORMATION SOURCES: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials, up to September 12, 2021. OUTCOME MEASURES: Sensitivity and specificity of rapid antigen and molecular tests suitable for detecting SARS-CoV-2. Data extraction and risk of bias assessment: Screening of literature search results was conducted by one reviewer; data abstraction was completed by one reviewer and independently verified by a second reviewer. Risk of bias was not assessed in the included studies. DATA SYNTHESIS: Random-effects meta-analysis and DTA-NMA. RESULTS: We included 93 studies (reported in 88 articles) relating to 36 rapid antigen tests in 104,961 participants and 23 rapid molecular tests in 10,449 participants. Overall, rapid antigen tests had a sensitivity of 0.75 (95% confidence interval 0.70-0.79) and specificity of 0.99 (0.98-0.99). Rapid antigen test sensitivity was higher when nasal or combined samples (e.g., combinations of nose, throat, mouth, or saliva samples) were used, but lower when nasopharyngeal samples were used, and in those classified as asymptomatic at the time of testing. Rapid molecular tests may result in fewer false negatives than rapid antigen tests (sensitivity: 0.93, 0.88-0.96; specificity: 0.98, 0.97-0.99). The tests with the highest sensitivity and specificity estimates were the Xpert Xpress rapid molecular test by Cepheid (sensitivity: 0.99, 0.83-1.00; specificity: 0.97, 0.69-1.00) among the 23 commercial rapid molecular tests and the COVID-VIRO test by AAZ-LMB (sensitivity: 0.93, 0.48-0.99; specificity: 0.98, 0.44-1.00) among the 36 rapid antigen tests we examined. CONCLUSIONS: Rapid molecular tests were associated with both high sensitivity and specificity, while rapid antigen tests were mainly associated with high specificity, according to the minimum performance requirements by WHO and Health Canada. Our rapid review was limited to English, peer-reviewed published results of commercial tests, and study risk of bias was not assessed. A full systematic review is required. REVIEW REGISTRATION: PROSPERO CRD42021289712.

Efficacy of sustained knowledge translation (KT) interventions in chronic disease management in older adults: systematic review and meta-analysis of complex interventions.

BACKGROUND: Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. METHODS: Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) including adults (> 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). INFORMATION SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database's inception to March 2020. OUTCOME MEASURES: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. DATA SYNTHESIS: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. RESULTS: We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [- 1.25, 3.47], 14 RCTs, 5876 participants, I2 = 96%; European QOL-5 dimensions: MD 0.01, 95% CI [- 0.01, 0.02], 15 RCTs, 6628 participants, I2 = 25%; St George's Respiratory Questionnaire: MD - 2.12, 95% CI [- 3.72, - 0.51] 44 12 RCTs, 2893 participants, I2 = 44%). KT interventions improved QOC (OR 1.55, 95% CI [1.29, 1.85], 12 RCTS, 5271 participants, I2 = 21%). CONCLUSIONS: KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

Characterizing the cascade of care for hepatitis C virus infection among Status First Nations peoples in Ontario: a retrospective cohort study.

BACKGROUND: As First Nations Peoples are a priority focus of Canada's commitment to eliminating hepatitis C virus (HCV) as a public health threat, understanding individuals' progression from diagnosis to cure can guide prioritization of elimination efforts. We sought to characterize and identify gaps in the HCV care cascade for Status First Nations peoples in Ontario. METHODS: In this retrospective cohort study, a partnership between the Ontario First Nations HIV/AIDS Education Circle and academic researchers, HCV testing records (1999-2018) for Status First Nations peoples in Ontario were linked to health administrative data. We defined the cascade of care as 6 stages, as follows: tested positive for HCV antibody, tested for HCV RNA, tested positive for HCV RNA, HCV genotyped, initiated treatment and achieved sustained viral response (SVR). We mapped the care cascade from 1999 to 2018, and estimated the number and proportion of people at each stage. We stratified analyses by sex, diagnosis date and location of residence. We used Cox regression to analyze the secondary outcomes, namely the associations between undergoing HCV RNA testing and initiating treatment, and demographic and clinical predictors. RESULTS: By Dec. 31, 2018, 4962 people tested positive for HCV antibody. Of those testing positive, 4118 (83.0%) were tested for HCV RNA, with 2480 (60.2%) testing positive. Genotyping was completed in 2374 (95.7%) of those who tested positive for HCV RNA, with 1002 (42.2%) initiating treatment. Nearly 80% (n = 801, 79.9%) of treated people achieved SVR, with 34 (4.2%) experiencing reinfection or relapse. Undergoing testing for HCV RNA was more likely among people in older age categories (within 1 yr of antibody test; adjusted hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.19-1.41, among people aged 41-60 yr; adjusted HR 1.47, 95% CI 1.18-1.81, among people aged > 60 yr), those living in rural areas (adjusted HR 1.20, 95% CI 1.10-1.30), those with an index date after Dec. 31, 2013 (era of treatment with direct-acting antiviral regimens) (adjusted HR 1.99, 95% CI 1.85-2.15) and those with a record of substance use or addictive disorders (> 1 yr after antibody test; adjusted HR 1.38, 95% CI 1.18-1.60). Treatment initiation was more likely among people in older age categories at index date (adjusted HR 1.32, 95% CI 1.15-1.50, among people aged 41-60 yr; adjusted HR 2.62, 95% CI 1.80-3.82, among people aged > 60 yr) and those with a later diagnosis year (adjusted HR 2.71, 95% CI 2.29-3.22). INTERPRETATION: In comparison with HCV testing and diagnosis, a substantial gap in treatment initiation remains among Status First Nations populations in Ontario. Elimination efforts that prioritize linkage to care and integration with harm reduction and substance use services are needed to close gaps in HCV care among First Nations populations in Ontario.

Which interventions for alcohol use should be included in a universal healthcare benefit package? An umbrella review of targeted interventions to address harmful drinking and dependence.

BACKGROUND: This study aimed to identify targeted interventions for the prevention and treatment of harmful alcohol use. Umbrella review methodology was used to summarise the effectiveness across a broad range of interventions, in order to identify which interventions should be considered for inclusion within universal health coverage schemes in low- and middle-income countries. METHODS AND FINDINGS: We included systematic reviews with meta-analysis of randomised controlled trials (RCTs) on targeted interventions addressing alcohol use in harmful drinkers or individuals with alcohol use disorder. We only included outcomes related to alcohol consumption, heavy drinking, binge drinking, abstinence, or alcohol-attributable accident, injury, morbidity or mortality. PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and the International HTA Database were searched from inception to 3 September 2021. Risk of bias of reviews was assessed using the AMSTAR2 tool. After reviewing the abstracts of 9,167 articles, results were summarised narratively and certainty in the body of evidence for each intervention was assessed using GRADE. In total, 86 studies met the inclusion criteria, of which the majority reported outcomes for brief intervention (30 studies) or pharmacological interventions (29 studies). Overall, methodological quality of included studies was low. CONCLUSIONS: For harmful drinking, brief interventions, cognitive behavioural therapy, and motivational interviewing showed a small effect, whereas mentoring in adolescents and children may have a significant long-term effect. For alcohol use disorder, social network approaches and acamprosate showed evidence of a significant and durable effect. More evidence is required on the effectiveness of gamma-hydroxybutyric acid (GHB), nalmefene, and quetiapine, as well as optimal combinations of pharmacological and psychosocial interventions. As an umbrella review, we were unable to identify the extent to which variation between studies stemmed from differences in intervention delivery or variation between country contexts. Further research is required on applicability of findings across settings and best practice for implementation. Funded by the Thai Health Promotion Foundation, grant number 61-00-1812.

Pattern of OPD utilisation during the COVID-19 pandemic under the Universal Coverage Scheme in Thailand: what can 850 million records tell us?

BACKGROUND: Out-patient department (OPD) is a crucial component of the healthcare systems in low- and middle-income countries including Thailand. A considerable impact of coronavirus disease 2019 (COVID-19) pandemic and its control measures, especially the lockdown, on utilisation of OPD services was expected. This study thus aims to estimate the pattern of OPD utilisation during the COVID-19 pandemic in Thailand including overall utilisation and within each sub-groups including diagnostic group, age group, and health region. METHODS: This study was a secondary data analysis of aggregated outpatient data from patients covered under the Universal Coverage Scheme (UCS) in Thailand over a 4-year period (2017-2020). Interrupted time series analyses and segmented Quasi-Poisson regression were used to examine the impact of COVID-19 on the overall OPD utilisation including the impact on each diagnostic group, age groups, health regions, and provinces. RESULTS: Analysis of 845,344,946 OPD visits in this study showed a seasonal pattern and increasing trend in monthly OPD visits before the COVID-19 pandemic. A 28% (rate ratio (RR) 0.718, 95% confidence interval (CI): 0.631-0.819) and 11% (RR 0.890, 95% CI: 0.811-0.977) reduction in OPD visits was observed during the lockdown and post-lockdown periods, respectively, when compared to the pre-lockdown period. Diseases of respiratory system were most affected with a RR of 0.411 (95% CI: 0.320-0.527), while the number of visits for non-communicable diseases (ICD-10: E00-E90, I00-I99) and elderly (> 60 years) dropped slightly. The post-lockdown trend in monthly OPD visits gradually increased to the pre-pandemic levels in most groups. CONCLUSIONS: Thailand's OPD utilisation rate during the COVID-19 lockdown decreased in some diseases, but the service for certain group of patients appeared to remain available. After the COVID-19 lockdown, the rate returned to the pre-pandemic level in a timely manner. Equipped with a knowledge of OPD utilisation pattern during COVID-19 based on a national real-world database could aid with a better preparation of healthcare system for future pandemics.

Can knowledgeable experts assess costs and outcomes as if they were ignorant? An experiment within precision medicine evaluation.

OBJECTIVES: The purpose of this study is to evaluate the validity of the standard approach in expert judgment for evaluating precision medicines, in which experts are required to estimate outcomes as if they did not have access to diagnostic information, whereas in fact, they do. METHODS: Fourteen clinicians participated in an expert judgment task to estimate the cost and medical outcomes of the use of exome sequencing in pediatric patients with intractable epilepsy in Thailand. Experts were randomly assigned to either an "unblind" or "blind" group; the former was provided with the exome sequencing results for each patient case prior to the judgment task, whereas the latter was not provided with the exome sequencing results. Both groups were asked to estimate the outcomes for the counterfactual scenario, in which patients had not been tested by exome sequencing. RESULTS: Our study did not show significant results, possibly due to the small sample size of both participants and case studies. CONCLUSIONS: A comparison of the unblind and blind approach did not show conclusive evidence that there is a difference in outcomes. However, until further evidence suggests otherwise, we recommend the blind approach as preferable when using expert judgment to evaluate precision medicines because this approach is more representative of the counterfactual scenario than the unblind approach.

SLEAP SMART (Sleep Apnea Screening Using Mobile Ambulatory Recorders After TIA/Stroke): A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Poststroke/transient ischemic attack obstructive sleep apnea (OSA) is prevalent, linked with numerous unfavorable health consequences, but remains underdiagnosed. Reasons include patient inconvenience and costs associated with use of in-laboratory polysomnography (iPSG), the current standard tool. Fortunately, home sleep apnea testing (HSAT) can accurately diagnose OSA and is potentially more convenient and cost-effective compared with iPSG. Our objective was to assess whether screening for OSA in patients with stroke/transient ischemic attack using HSAT, compared with standard of care using iPSG, increased diagnosis and treatment of OSA, improved clinical outcomes and patient experiences with sleep testing, and was a cost-effective approach. METHODS: We consecutively recruited 250 patients who had sustained a stroke/transient ischemic attack within the past 6 months. Patients were randomized (1:1) to use of (1) HSAT versus (2) iPSG. Patients completed assessments and questionnaires at baseline and 6-month follow-up appointments. Patients diagnosed with OSA were offered continuous positive airway pressure. The primary outcome was compared between study arms via an intention-to-treat analysis. RESULTS: At 6 months, 94 patients completed HSAT and 71 patients completed iPSG. A significantly greater proportion of patients in the HSAT arm were diagnosed with OSA (48.8% versus 35.2%, P=0.04) compared with the iPSG arm. Furthermore, patients assigned to HSAT, compared with iPSG, were more likely to be prescribed continuous positive airway pressure (40.0% versus 27.2%), report significantly reduced sleepiness, and a greater ability to perform daily activities. Moreover, a significantly greater proportion of patients reported a positive experience with sleep testing in the HSAT arm compared with the iPSG arm (89.4% versus 31.1%). Finally, a cost-effectiveness analysis revealed that HSAT was economically attractive for the detection of OSA compared with iPSG. CONCLUSIONS: In patients with stroke/transient ischemic attack, use of HSAT compared with iPSG increases the rate of OSA diagnosis and treatment, reduces daytime sleepiness, improves functional outcomes and experiences with sleep testing, and could be an economically attractive approach. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02454023.

Multi-use physical activity trails in an urban setting and cardiovascular disease: a difference-in-differences analysis of a natural experiment in Winnipeg, Manitoba, Canada.

OBJECTIVE: To determine if expansion of multi-use physical activity trails in an urban centre is associated with reduced rates of cardiovascular disease (CVD). METHODS: This was a natural experiment with a difference in differences analysis using administrative health records and trail-based cycling data in Winnipeg, Canada. Prior to the intervention, each year, 314,595 (IQR: 309,044 to 319,860) persons over 30 years without CVD were in the comparison group and 37,901 residents (IQR: 37,213 to 38,488) were in the intervention group. Following the intervention, each year, 303,853 (IQR: 302,843 to 304,465) persons were in the comparison group and 35,778 (IQR: 35,551 to 36,053) in the intervention group. The natural experiment was the construction of four multi-use trails, 4-7 km in length, between 2010 and 2012. Intervention and comparison areas were based on buffers of 400 m, 800 m and 1200 m from a new multi-use trail. Bicycle counts were obtained from electromagnetic counters embedded in the trail. The primary outcome was a composite of incident CVD events: CVD-related mortality, ischemic heart disease, cerebrovascular events and congestive heart failure. The secondary outcome was a composite of incident CVD risk factors: hypertension, diabetes and dyslipidemia. RESULTS: Between 2014 and 2018, 1,681,125 cyclists were recorded on the trails, which varied ~ 2.0-fold across the four trails (2358 vs 4264 counts/week in summer months). Between 2000 and 2018, there were 82,632 CVD events and 201,058 CVD risk events. In propensity score matched Poisson regression models, the incident rate ratio (IRR) was 1.06 (95% CI: 0.90 to 1.24) for CVD events and 0.95 (95%CI: 0.88 to 1.02) for CVD risk factors for areas within 400 m of a trail, relative to comparison areas. Sensitivity analyses indicated this effect was greatest among households adjacent to the trail with highest cycling counts (IRR = 0.85; 95% CI: 0.75 to 0.96). CONCLUSIONS: The addition of multi-use trails was not associated with differences in CVD events or CVD risk factors, however the differences in CVD risk may depend on the level of trail use. TRIAL REGISTRATION: Trial registration number: NCT04057417 .

The Effectiveness of 6 versus 12 Months of Dialectical Behavior Therapy for Borderline Personality Disorder: A Noninferiority Randomized Clinical Trial.

INTRODUCTION: Evidence-based psychotherapies for borderline personality disorder (BPD) are lengthy, posing a barrier to their access. Brief psychotherapy may achieve comparable outcomes to long-term psychotherapy for BPD. Evidence is needed regarding the comparative effectiveness of short- versus long-term psychotherapy for BPD. OBJECTIVE: The aim was to determine if 6 months of Dialectical Behavior Therapy (DBT) is noninferior to 12 months of DBT in terms of clinical effectiveness. METHODS: This two-arm, single-blinded, randomized controlled noninferiority trial with suicidal or self-harming patients with BPD was conducted at two sites in Canada. Participants (N = 240, M (SD)age = 28.27 (8.62), 79% females) were randomized to receive either 6 (DBT-6) or 12 months (DBT-12) of comprehensive DBT. Masked assessors obtained measures of clinical effectiveness at baseline and every 3 months, ending at month 24. DBT-6 and DBT-12 were outpatient treatments consisting of weekly individual therapy sessions, weekly DBT skills training group sessions, telephone consultation as needed, and weekly therapist consultation team meetings. RESULTS: The noninferiority hypothesis was supported for the primary outcome, total self-harm (6 months: margin = -1.94, Mdiff [95% CI] = 0.16 [-0.14, 0.46]; 12 months: margin = -1.47, Mdiff [95% CI] = 0.04 [-0.17, 0.23]; 24 months: margin = -1.25, Mdiff [95% CI] = 0.12 [-0.02, 0.36]). Results also supported noninferiority of DBT-6 for general psychopathology and coping skills at 24 months. Furthermore, DBT-6 participants showed more rapid reductions in BPD symptoms and general psychopathology. There were no between-group differences in dropout rates. CONCLUSIONS: The noninferiority of a briefer yet comprehensive treatment for BPD has potential to reduce barriers to treatment access.

Systematic Review on the Cost-Effectiveness of Seasonal Influenza Vaccines in Older Adults.

OBJECTIVES: Older adults are at high risk of influenza-related complications or hospitalization. The purpose of this systematic review is to assess the relative cost-effectiveness of all influenza vaccine options for older adults. METHODS: This systematic review identified economic evaluation studies assessing the cost-effectiveness of influenza vaccines in adults ≥65 years of age from 5 literature databases. Two reviewers independently selected, extracted, and appraised relevant studies using the JBI Critical Appraisal Checklist for Economic Evaluations and Heyland's generalizability checklist. Costs were converted to 2019 Canadian dollars and adjusted for inflation and purchasing power parity. RESULTS: A total of 27 studies were included. There were 18 comparisons of quadrivalent inactivated vaccine (QIV) versus trivalent inactivated vaccine (TIV): 5 showed QIV dominated TIV (ie, lower costs and higher health benefit), and 13 showed the results depended on willingness to pay (WTP). There were 9 comparisons of high-dose TIV (TIV-HD) versus TIV: 5 showed TIV-HD dominated TIV, and 4 showed the results depended on WTP. There were 8 comparisons of adjuvanted TIV (TIV-ADJ) versus TIV: 4 showed TIV-ADJ dominated TIV, and 4 showed the results depended on WTP. There were few pairwise comparisons among QIV, TIV-HD, and TIV-ADJ. CONCLUSIONS: The evidence suggests QIV, TIV-HD, and TIV-ADJ are cost-effective against TIV for a WTP threshold of $50 000 per quality-adjusted life-year. Future studies should include new and existing vaccine options for broad age ranges and use more robust methodologies-such as real-world evaluations or modeling studies accounting for methodological, structural, and parameter uncertainty.

The Cost-Effectiveness of Intermediate-Acting, Long-Acting, Ultralong-Acting, and Biosimilar Insulins for Type 1 Diabetes Mellitus: A Systematic Review.

OBJECTIVES: The incidence of type 1 diabetes mellitus is increasing every year requiring substantial expenditure on treatment and complications. A systematic review was conducted on the cost-effectiveness of insulin formulations, including ultralong-, long-, or intermediate-acting insulin, and their biosimilar insulin equivalents. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, HTA, and NHS EED were searched from inception to June 11, 2021. Cost-effectiveness and cost-utility analyses were included if insulin formulations in adults (≥ 16 years) with type 1 diabetes mellitus were evaluated. Two reviewers independently screened titles, abstracts, and full-text articles, extracted study data, and appraised their quality using the Drummond 10-item checklist. Costs were converted to 2020 US dollars adjusting for inflation and purchasing power parity across currencies. RESULTS: A total of 27 studies were included. Incremental cost-effectiveness ratios ranged widely across the studies. All pairwise comparisons (11 of 11, 100%) found that ultralong-acting insulin was cost-effective compared with other long-acting insulins, including a long-acting biosimilar. Most pairwise comparisons (24 of 27, 89%) concluded that long-acting insulin was cost-effective compared with intermediate-acting insulin. Few studies compared long-acting insulins with one another. CONCLUSIONS: Long-acting insulin may be cost-effective compared with intermediate-acting insulin. Future studies should directly compare biosimilar options and long-acting insulin options and evaluate the long-term consequences of ultralong-acting insulins.

Cancer treatment-related financial toxicity experienced by patients in low- and middle-income countries: a scoping review.

PURPOSE: In the past decade, literature has called attention to financial toxicities experienced by cancer patients. Though studies have addressed research questions in high-income countries, there remains a paucity of in-depth reviews regarding low- and middle-income countries (LMICs). Our scoping review provides an overview of treatment-related financial toxicities experienced by cancer patients in LMICs. METHODS: A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. English peer-reviewed articles that (a) explored patients' experience with financial toxicity due to cancer treatment (b) were specific to LMICs as defined by the World Bank and (c) focused on qualitative data were included. Details regarding participants and main findings were extracted and synthesized. RESULTS: The search yielded 6290 citations, and 42 studies across 3 low-income, 9 lower-middle-income and 8 upper-middle-income countries. Main themes identified included cancer patients encountered various material hardships, managed costs with different coping behaviours and experienced negative psychological responses to their financial burden. Higher levels of financial toxicities were associated with patient characteristics such as lower socio-economic status and lack of insurance, as well as patient outcomes such as lower quality of life. CONCLUSION: Cancer patients in LMIC experience deleterious financial toxicities as a result of treatment. This comprehensive characterization of financial toxicities will better allow health systems to adopt evidence-based mitigation strategies to reduce the financial burden on patients.

What is the value of explicit priority setting for health interventions? A simulation study.

Many countries seek to secure efficiency in health spending through establishing explicit priority setting institutions (PSIs). Since such institutions divert resources from frontline services which benefit patients directly, it is legitimate and reasonable to ask whether they are worth the money. We address this question by comparing, through simulation, the health benefits and costs from implementing two alternative funding approaches - one scenario in which an active PSI enables cost-effectiveness-threshold based funding decisions, and a counterfactual scenario where there is no PSI. We present indicative results for one dataset from the United Kingdom (published in 2015) and one from Malawi (published in 2018), which show that the threshold rule reliably resulted in decreased health system costs, improved health benefits, or both. Our model is implemented in Microsoft Excel and designed to be user-friendly, and both the model and a user guide are made publicly available, in order to enable others to parameterise the model based on the local setting. Although inevitably stylised, we believe that our modelling and results offer a valid perspective on the added value of explicit PSIs.

A model-based study to estimate the health and economic impact of health technology assessment in Thailand.

OBJECTIVES: Health technology assessment (HTA) plays a central role in the coverage and reimbursement decision-making process for public health expenditure in many countries, including Thailand. However, there have been few attempts to quantitatively understand the benefits of using HTA to inform resource allocation decisions. The objective of this research was to simulate the expected net monetary benefit (NMB) from using HTA-based decision criteria compared to a first-come, first-served (FCFS) approach using data from Thailand. METHODS: A previously published simulation model was adapted to the Thai context which aimed to simulate the impact of using different decision-making criteria to adopt or reject health technologies for public reimbursement. Specifically, the simulation model provides a quantitative comparison between an HTA-based funding rule and a counterfactual (FCFS) funding rule to make decisions on which health technologies should be funded. The primary output of the model was the NMB of using HTA-based decision criteria compared to the counterfactual approach. The HTA-based decision rule in the model involved measuring incremental cost-effectiveness ratios against a cost-effectiveness threshold. The counterfactual decision rule was a FCFS (random) selection of health technologies. RESULTS: The HTA-based decision rule was associated with a greater NMB compared to the counterfactual. In the investigated analyses, the NMB ranged from THB24,238 million (USD725 million) to THB759,328 million (USD22,719 million). HTA-based decisions led to fewer costs, superior health outcomes (more quality-adjusted life-years). CONCLUSIONS: The results support the hypothesis that HTA can provide health and economic benefits by improving the efficiency of resource allocation decision making.

How can health technology assessment support our response to public health emergencies?

Public health emergencies (PHEs), such as the COVID-19 crisis, are threats to global health and public order. We recommend that countries bolster their PHE responses by investing in health technology assessment (HTA), defined as a systematic process of gathering pertinent information on and evaluating health technologies from a medical, economic, social and ethical standpoint. We present examples of how HTA organizations in low- and middle-income countries have adapted to supporting PHE-related decisions during COVID-19 and describe the ways HTA can help the response to a PHE. In turn, we advocate for HTA capacity to be further developed globally and for increased institutional acceptance of these methods as a building block for preparedness and response to future PHEs. Finally, the long-term potential of HTA in strengthening health systems and embedding confidence and transparency into scientific policy should be recognized.

Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries.

Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in low- and middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$ 18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average

En general, los programas de control de la hipertensión son costo-eficaces, incluso en los países de ingresos bajos y medios. Aun así, es poco probable que los gobiernos nacionales y la sociedad civil apoyen los programas de control de la hipertensión a menos que se demuestre su valor en términos de beneficios para la salud pública, impacto presupuestario y valor de la inversión para el contexto individual del país. La Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS) implementaron la iniciativa HEARTS, un enfoque mundial estandarizado y simplificado para el control de la hipertensión, que incluye los medicamentos antihipertensivos y los dispositivos de medición de la presión arterial de preferencia. El objetivo de este estudio es informar sobre los estudios en el ámbito de la economía de la salud relativos al costo de las medidas de control de la hipertensión previstas en HEARTS (especialmente, de los medicamentos), la costo-efectividad y el impacto presupuestario, así como describir los modelos matemáticos diseñados para traducir los datos de este programa en un enfoque óptimo para la prestación y el financiamiento de los servicios de atención de la hipertensión, especialmente en países de ingresos medianos y bajos. Los primeros resultados indican que las intervenciones de HEARTS para el control de la hipertensión son de bajo costo o costo-eficaces, que el conjunto de medidas HEARTS es asequible, a un precio que oscila entre US$ 18 y US$ 44 al año por paciente tratado, y que los medicamentos antihipertensivos podrían tener un precio lo suficientemente bajo como para alcanzar un estándar medio mundial de

Geralmente, os programas de controle de hipertensão são custo-efetivos, inclusive em países de baixa e média renda, mas os governos dos países e a sociedade civil provavelmente não apoiarão tais programas a menos que demonstrem valor em termos de benefícios à saúde pública, impacto orçamentário e retorno sobre o investimento no contexto individual do país. A Organização Mundial da Saúde (OMS) e a Organização Pan-Americana da Saúde (OPAS) criaram a Global HEARTS, uma abordagem padrão e simplificada ao controle da hipertensão arterial, que inclui medicamentos anti-hipertensivos preferidos e dispositivos para aferição da pressão arterial preferidos. O objetivo deste estudo é relatar os estudos de economia em saúde que analisaram o custo (especialmente custos de medicamentos), custo-benefício e impacto orçamentário do pacote HEARTS para controle da hipertensão e descrever modelos matemáticos elaborados para traduzir os dados do programa de controle de hipertensão em uma abordagem ideal para a prestação e financiamento de serviços de atenção às pessoas com hipertensão, especialmente em países de baixa e média renda. Os primeiros resultados sugerem que as intervenções HEARTS para controle da hipertensão são de baixo custo ou custo-efetivas, que o pacote HEARTS é acessível (custando de US$ 18 a 44 por pessoa tratada por ano) e que o preço dos medicamentos anti-hipertensivos poderia ser baixo o suficiente para atingir uma média global de

Real-world, population-based cohort study of toxicity and resource utilization of second-line ipilimumab for metastatic melanoma in Ontario, Canada.

Second-line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real-world toxicity of second-line ipilimumab compared to standard second-line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second-line ipilimumab after September 2012 were considered as cases, and those who received second-line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment-related mortality, any-cause hospital visits, ipilimumab-related hospital visits and specialist visits (eg, endocrinologists, ophthalmologists, gastroenterologists, rheumatologists and respirologists), which were captured from up to 30 and/or 90 days after end of second-line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second-line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any-cause (60.1% vs 45.7%; OR = 1.81; P value = .019) and ipilimumab-related (47.2% vs 31.9%; OR = 1.91; P value = .011) hospital visits. Adjusting for different follow-up days, ipilimumab was associated with higher rates of all-cause (RR = 1.56 [95%CI: 1.12-2.16]), and ipilimumab-related (RR = 2.18 [95% CI: 1.45-3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; P value = .04). Compared to historical second-line treatments, second-line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real world.

Assessing the performance of health technology assessment (HTA) agencies: developing a multi-country, multi-stakeholder, and multi-dimensional framework to explore mechanisms of impact.

BACKGROUND: Health technology assessment (HTA) agencies have an important role to play in managing the rising demands on health systems. However, creating and running such agencies potentially diverts resources from frontline services. A large number of studies address the question of 'what is the impact of HTA?'. Several points of heterogeneity in this literature include: purpose of the study, definition of HTA, definition of impact, and scope and rigour of evaluations. Our study seeks to address several limitations in this literature. This study aims to explore the mechanisms of impact of an HTA agency. In doing so, we consider HTA as an institution rather than a knowledge product to build an impact evaluation framework from an international, multi-stakeholder and multi-dimensional perspective. METHODS: We conducted 9 key informant interviews with experts from the international HTA community. We addressed several questions, informed by existing frameworks of impact within the literature, to understand their perspectives on the mechanisms of impact of an HTA agency. We analyse data using logic modelling and impact mapping, as tools to understand and visualise mechanisms of change. FINDINGS: Our impact mapping highlights several distinct, but not necessarily mutually exclusive, mechanisms through which the overall impact of an HTA agency is achieved. These are: the effective conduct of HTA studies; effective use of HTA in agenda-setting and policy formulation processes; effective engagement and external communications; good institutional reputation and fit within the healthcare and policy-making system; effective use of HTA as a tool for the negotiation of health technology prices; and the effective implementation of policy change regarding health technologies. We also identify indicators of these effects. CONCLUSIONS: Our findings and resulting evaluation framework complement and add to existing literature by offering a new perspective on the mechanisms by which HTA agencies generate impact. This new perspective considers HTA as an institution rather than a knowledge product, is international, multi-dimensional, and includes multi-stakeholder views. We hope the analysis will be useful to countries interested in managing HTA performance.