Cost-effectiveness of antenatal multiple micronutrients and balanced energy protein supplementation compared to iron and folic acid supplementation in India, Pakistan, Mali, and Tanzania: A dynamic microsimulation study.

BACKGROUND: Malnutrition among women of childbearing age is especially prevalent in Asia and sub-Saharan Africa and can be harmful to the fetus during pregnancy. In the most recently available Demographic and Health Survey (DHS), approximately 10% to 20% of pregnant women in India, Pakistan, Mali, and Tanzania were undernourished (body mass index [BMI] <18.5 kg/m2), and according to the Global Burden of Disease (GBD) 2017 study, approximately 20% of babies were born with low birth weight (LBW; <2,500 g) in India, Pakistan, and Mali and 8% in Tanzania. Supplementing pregnant women with micro and macronutrients during the antenatal period can improve birth outcomes. Recently, the World Health Organization (WHO) recommended antenatal multiple micronutrient supplementation (MMS) that includes iron and folic acid (IFA) in the context of rigorous research. Additionally, WHO recommends balanced energy protein (BEP) for undernourished populations. However, few studies have compared the cost-effectiveness of different supplementation regimens. We compared the cost-effectiveness of MMS and BEP with IFA to quantify their benefits in 4 countries with considerable prevalence of maternal undernutrition. METHODS AND FINDINGS: Using nationally representative estimates from the 2017 GBD study, we conducted an individual-based dynamic microsimulation of population cohorts from birth to 2 years of age in India, Pakistan, Mali, and Tanzania. We modeled the effect of maternal nutritional supplementation on infant birth weight, stunting and wasting using effect sizes from Cochrane systematic reviews and published literature. We used a payer's perspective and obtained costs of supplementation per pregnancy from the published literature. We compared disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs) in a baseline scenario with existing antenatal IFA coverage with scenarios where 90% of antenatal care (ANC) attendees receive either universal MMS, universal BEP, or MMS + targeted BEP (women with prepregnancy BMI <18.5 kg/m2 receive BEP containing MMS while women with BMI ≥18.5 kg/m2 receive MMS). We obtained 95% uncertainty intervals (UIs) for all outputs to represent parameter and stochastic uncertainty across 100 iterations of model runs. ICERs for all scenarios were lowest in Pakistan and greatest in Tanzania, in line with the baseline trend in prevalence of and attributable burden to LBW. MMS + targeted BEP averts more DALYs than universal MMS alone while remaining cost-effective. ICERs for universal MMS compared to baseline IFA were $52 (95% UI: $28 to $78) for Pakistan, $72 (95% UI: $37 to $118) for Mali, $70 (95% UI: $43 to $104) for India, and $253 (95% UI: $112 to $481) for Tanzania. ICERs for MMS + targeted BEP compared to baseline IFA were $54 (95% UI: $32 to $77) for Pakistan, $73 (95% UI: $40 to $104) for Mali, $83 (95% UI: $58 to $111) for India, and $245 (95% UI: $127 to $405) for Tanzania. Study limitations include generalizing experimental findings from the literature to our populations of interest and using population-level input parameters that may not reflect the heterogeneity of subpopulations. Additionally, our microsimulation fuses multiple sources of data and may be limited by data quality and availability. CONCLUSIONS: In this study, we observed that MMS + targeted BEP averts more DALYs and remains cost-effective compared to universal MMS. As countries consider using MMS in alignment with recent WHO guidelines, offering targeted BEP is a cost-effective strategy that can be considered concurrently to maximize benefits and synergize program implementation.

Characteristics of Cost-effectiveness Studies for Oncology Drugs Approved in the United States From 2015-2020.

Importance: Increasingly, cost-effectiveness analyses are being done to determine the value of rapidly increasing oncology drugs; however, this assumes that these analyses are unbiased. Objective: To analyze the characteristics of cost-effectiveness studies and to determine characteristics associated with whether an oncology drug is found to be cost-effective. Design, Setting, and Participants: This retrospective cross-sectional study included 254 cost-effectiveness analyses for 116 oncology drugs that were approved by the US Food and Drug Administration from 2015 to 2020. Exposures: Each drug was analyzed for the incremental cost-effectiveness ratio per quality-adjusted life year, the funding of the study, the authors' conflict of interest, the threshold of willingness-to-pay, from what country's perspective the analysis was done, and whether a National Institute for Health and Care Excellence cost-effectiveness analysis had been done. Main Outcomes and Measures: The main outcome was the odds of a study concluding that a drug was cost-effective. Results: There were 116 drug approvals with 254 studies and country perspectives. Of the country perspectives, 132 (52%) were from the US. Forty-seven of 78 drugs with cost-effective studies had been shown to improve overall survival, whereas 15 of 38 of drugs without a cost-effectiveness study had been shown to improve overall survival. Having a study funded by a pharmaceutical company was associated with higher odds of a study concluding that a drug was cost-effective than studies without funding (odds ratio, 41.36; 95% CI, 11.86-262.23). Conclusions and Relevance: In this cross-sectional study, pharmaceutical funding was associated with greater odds that an oncology drug would be found to be cost-effective. These findings suggest that simply disclosing potential conflict of interest is inadequate. We encourage cost-effectiveness analyses by independent groups.

Epidemiological Analysis of 37,424 Carotid Artery Stenosis Intervention Procedures During 11 Years in the Public Health System in Brazil: Stenting has Been More Common Than Endarterectomy.

BACKGROUND: Stroke is a leading cause of death worldwide, with carotid atherosclerosis accounting for 10-20% of cases. In Brazil, the Public Health System provides care for roughly two-thirds of the population. No studies, however, have analysed large-scale results of carotid bifurcation surgery in Brazil. METHODS: This study aimed to describe rates of carotid artery stenting (CAS) and carotid endarterectomy (CEA) performed between 2008 and 2019 in the country through web scraping of publicly available databases. RESULTS: Between 2008 and 2019, 37,424 carotid bifurcation revascularization procedures were performed, of which 22,578 were CAS (60.34%) and 14,846 (39.66%) were CEA. There were 620 in-hospital deaths (1.66%), 336 after CAS (1.48%) and 284 after CEA (1.92%) (P = 0.032). Governmental reimbursement was US$ 77,216,298.85 (79.31% of all reimbursement) for CAS procedures and US$ 20,143,009.63 (20.69%) for CEA procedures. The average cost per procedure for CAS (US$ 3,062.98) was higher than that for CEA (US$ 1,430.33) (P = 0.008). CONCLUSIONS: In Brazil, the frequency of CAS largely surpassed that of CEA. In-hospital mortality rates of CAS were significantly lower than those of CEA, although both had mortality rates within the acceptable rates as dictated by literature. The cost of CAS, however, was significantly higher. This is a pioneering analysis of carotid artery disease management in Brazil that provides, for the first time, preliminary insight into the fact that the low adoption of CEA in the country is in opposition to countries where utilization rates are higher for CEA than for CAS.

When More Is Better: Underused Advanced Imaging Exams That Can Improve Outcomes and Reduce Cost of Care.

Appropriate use of resources is a tenet of care transformation efforts, with a national campaign to reduce low-value imaging. The next level of performance improvement is to bolster evidence-based screening, imaging surveillance, and diagnostic innovation, which can avert more costly, higher-risk elements of unnecessary care like emergent interventions. Clinical scenarios in which underused advanced imaging can improve outcomes and reduce total cost of care are reviewed, including abdominal aortic aneurysm surveillance, coronary artery disease diagnosis, and renal mass characterization. Reliable abdominal aortic aneurysm surveillance imaging reduces emergency surgery and can be driven by radiologists incorporating best practice standardized recommendations in imaging interpretations. Coronary computed tomography angiography in patients with stable and unstable chest pain can reduce downstream resource use while improving outcomes. Preoperative 99mTc-sestamibi single-photon emission computed tomography (SPECT) reliably distinguishes oncocytoma from renal cell carcinoma to obviate unnecessary nephrectomy. As technological advances in diagnostic, molecular, and interventional radiology improve our ability to detect and cure disease, analyses of cost effectiveness will be critical to radiology leadership and sustainability in the transition to a value-based reimbursement model.

Factors Associated With Progression to Surgical Intervention for Lumbar Disc Herniation in the Military Health System.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To determine surgery-free survival of patients receiving conservative management of lumbar disc herniation (LDH) in the military healthcare system (MHS) and risk factors for surgical intervention. SUMMARY OF BACKGROUND DATA: Radiculopathy from LDH is a major cause of morbidity and cost. METHODS: The Military Data Repository was queried for all patients diagnosed with LDH from FY2011-2018; the earliest such diagnosis in a military treatment facility (MTF) was kept for each patient as the initial diagnosis. Follow-up time to surgical intervention was defined as the time from diagnosis to first encounter for lumbar microdiscectomy or lumbar decompression in either a MTF or in the civilian sector. The Military Data Repository was also queried for history of tobacco use at any time during MHS care, age at the time of diagnosis, sex, MHS beneficiary category, and diagnosing facility characteristics. Multivariable Cox proportional hazards models were used to evaluate the associations of patient and diagnosing facility characteristics with time to surgical intervention. RESULTS: A total of 84,985 MHS beneficiaries including 62,771 active duty service members were diagnosed with LDH in a MTF during the 8-year study period. A total of 10,532 (12.4%) MHS beneficiaries, including 7650 (10.9%) active duty, failed conservative management onto surgical intervention with lumbar microdiscectomy or lumbar decompression. Median follow-up time of the cohort was 5.2 (interquartile range 2.6, 7.5) years. Among all healthcare beneficiaries, several patient-level (younger age, male sex, and history of tobacco use) and facility-level characteristics (hospital vs. clinic and surgical care vs. primary care clinic) were independently associated with higher risk of surgical intervention. CONCLUSION: LDH compromises military readiness and negatively impacts healthcare costs. MHS beneficiaries with LDH have a good prognosis with approximately 88% of patients successfully completing conservative management. However, strategies to improve outcomes of conservative management in LDH should address risks associated with both patient and facility characteristics.Level of Evidence: 4.

Artificial intelligence in colonoscopy - Now on the market. What's next?

Adoption of artificial intelligence (AI) in clinical medicine is revolutionizing daily practice. In the field of colonoscopy, major endoscopy manufacturers have already launched their own AI products on the market with regulatory approval in Europe and Asia. This commercialization is strongly supported by positive evidence that has been recently established through rigorously designed prospective trials and randomized controlled trials. According to some of the trials, AI tools possibly increase the adenoma detection rate by roughly 50% and contribute to a 7-20% reduction of colonoscopy-related costs. Given that reliable evidence is emerging, together with active commercialization, this seems to be a good time for us to review and discuss the current status of AI in colonoscopy from a clinical perspective. In this review, we introduce the advantages and possible drawbacks of AI tools and explore their future potential including the possibility of obtaining reimbursement.

Evaluation of Benefit and Cost Utility of Immediate Postanesthesia Care Unit Radiographs to Predict Airway Compromise After Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective review. OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure that may be complicated by airway compromise postoperatively. This life-threatening complication may necessitate reintubation and reoperation. We evaluated the cost utility of conventional postoperative x-ray. SUMMARY OF BACKGROUND DATA: Studies have demonstrated minimal benefit in obtaining an x-ray on postoperative day 1, but there is some utility of postanesthesia care unit (PACU) x-rays for predicting the likelihood of reoperation. METHODS: We retrospectively reviewed the records of consecutive patients who underwent ACDF between September 2013 and February 2017. Patients were dichotomized into those who received PACU x-rays and those who did not (control group). Primary outcomes were reoperation, reintubation, mortality, and health care costs. RESULTS: Eight-hundred and fifteen patients were included in our analysis: 558 had PACU x-rays; 257 did not. In those who received PACU x-rays, mean age was 53.7 ±â€Š11.3 years, mean levels operated on were 2.0 ±â€Š0.79, and mean body mass index (BMI) was 30.3 ±â€Š6.9. In those who did not, mean age was 51.8 ±â€Š10.9 years, mean levels operated on were 1.48 ±â€Š0.65, and mean BMI was 29.9 ±â€Š6.3. Complications in the PACU x-ray group were reintubation-0.4%, reoperation-0.7%, and death-0.3% (due to prevertebral swelling causing airway compromise). Complications in the control group were reintubation-0.4%, reoperation-0.8%, and death-0. There were no differences between groups with respect to reoperation (P = 0.92), reintubation (P = 0.94), or mortality (P = 0.49). The mean per-patient cost was significantly higher (P = 0.009) in those who received PACU x-rays, $1031.76 ±â€Š948.67, versus those in the control group, $700.26 ±â€Š634.48. Mean length of stay was significantly longer in those who had PACU x-rays (P = 0.01). CONCLUSION: Although there were no differences in reoperation, reintubation, or mortality, there was a significantly higher cost for care and hospitalization in those who received PACU x-rays. Further studies are warranted to validate the results of the presented study.Level of Evidence: 3.

Cost-effectiveness of Population-Wide Genomic Screening for Hereditary Breast and Ovarian Cancer in the United States.

Importance: Genomic screening for hereditary breast and ovarian cancer (HBOC) in unselected women offers an opportunity to prevent cancer morbidity and mortality, but the potential clinical impact and cost-effectiveness of such screening have not been well studied. Objective: To estimate the lifetime incremental incidence of HBOC and the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of HBOC genomic screening in an unselected population vs family history-based testing. Design, Setting, and Participants: In this study conducted from October 27, 2017, to May 3, 2020, a decision analytic Markov model was developed that included health states for precancer, for risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), for earlier- and later-stage HBOC, after cancer, and for death. A complimentary cascade testing module was also developed to estimate outcomes in first-degree relatives. Age-specific RRM and RRSO uptake probabilities were estimated from the Geisinger MyCode Community Health Initiative and published sources. Parameters including RRM and RRSO effectiveness, variant-specific cancer risk, costs, and utilities were derived from published sources. Sensitivity and scenario analyses were conducted to evaluate model assumptions and uncertainty. Main Outcomes and Measures: Lifetime cancer incidence, QALYs, life-years, and direct medical costs for genomic screening in an unselected population vs family history-based testing only were calculated. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in cost between strategies divided by the difference in QALYs between strategies. Earlier-stage and later-stage cancer cases prevented and total cancer cases prevented were also calculated. Results: The model found that population screening of 30-year-old women was associated with 75 (95% credible range [CR], 60-90) fewer overall cancer cases and 288 QALYs (95% CR, 212-373 QALYs) gained per 100 000 women screened, at an incremental cost of $25 million (95% CR, $21 millon to $30 million) vs family history-based testing; the ICER was $87 700 (78% probability of being cost-effective at a threshold of $100 000 per QALY). In contrast, population screening of 45-year-old women was associated with 24 (95% CR, 18-29) fewer cancer cases and 97 QALYs (95% CR, 66-130 QALYs) gained per 100 000 women screened, at an incremental cost of $26 million (95% CR, $22 million to $30 million); the ICER was $268 200 (0% probability of being cost-effective at a threshold of $100 000 per QALY). A scenario analysis without cascade testing increased the ICER to $92 600 for 30-year-old women and $354 500 for 45-year-old women. A scenario analysis assuming a 5% absolute decrease in mammography screening in women without a variant was associated with the potential for net harm (-90 QALYs per 100 000 women screened; 95% CR, -180 to 10 QALYs). Conclusions and Relevance: The results of this study suggest that population HBOC screening may be cost-effective among younger women but not among older women. Cascade testing of first-degree relatives added a modest improvement in clinical and economic value. The potential for harm conferred by inappropriate reduction in mammography among noncarriers should be quantified.

Endoscopic full-thickness resection and its treatment alternatives in difficult-to-treat lesions of the lower gastrointestinal tract: a cost-effectiveness analysis.

OBJECTIVE: Endoscopic full-thickness resection (EFTR) has shown efficacy and safety in the colorectum. The aim of this analysis was to investigate whether EFTR is cost-effective in comparison with surgical and endoscopic treatment alternatives. DESIGN: Real data from the study cohort of the prospective, single-arm WALL RESECT study were used. A simulated comparison arm was created based on a survey that included suggested treatment alternatives to EFTR of the respective lesions. Treatment costs and reimbursement were calculated in euro according to the coding rules of 2017 and 2019 (EFTR). R0 resection rate was used as a measure of effectiveness. To assess cost-effectiveness, the average cost-effectiveness ratio (ACER) and the incremental cost-effectiveness ratio (ICER) were determined. Calculations were made both from the perspective of the care provider as well as of the payer. RESULTS: The cost per case was €2852.20 for the EFTR group, €1712 for the standard endoscopic resection (SER) group, €8895 for the surgical resection group and €5828 for the pooled alternative treatment to EFTR. From the perspective of the care provider, the ACER (mean cost per R0 resection) was €3708.98 for EFTR, €3115.10 for SER, €8924.05 for surgical treatment and €7169.30 for all pooled and weighted alternatives to EFTR. The ICER (additional cost per R0 resection compared with EFTR) was €5196.47 for SER, €26 533.13 for surgical resection and €67 768.62 for the pooled rate of alternatives. Results from the perspective of the payer were similar. CONCLUSION: EFTR is cost-effective in comparison with surgical and endoscopic treatment alternatives in the colorectum.

Changes in Cost-Effectiveness for Chronic Hepatitis C Virus Pharmacotherapy: The Case for Continuous Cost-Effectiveness Analyses.

BACKGROUND: Cost-effectiveness evaluations for hepatitis C virus (HCV) treatments have been published frequently, but new products with significant cost and effectiveness differences make these analyses obsolete. How valuable are economic models for a fixed time period in a dynamic market? OBJECTIVE: To estimate the cost-effectiveness of the best available HCV treatment at different points in time, using the same comparator to demonstrate how rapid innovation in a disease area influences economic outcomes. METHODS: A Markov model was used to calculate the cost-effectiveness of treatment in 2010, 2012, 2014, 2016, and 2018 compared with a standard comparator (no treatment) from the payer perspective. Expected drug costs and treatment effectiveness estimates for sustained virologic response (SVR) were calculated using recommended regimens for each of the 6 HCV genotypes at each time point and distribution of genotypes in the United States. Patients entered the model with different stages of fibrosis. Utility estimates for each health state were used to calculate quality-adjusted life-years (QALYs) earned at each cycle. Incremental cost-effectiveness ratios were reported for each year to compare the "treatment versus no treatment" decision at that time. RESULTS: No HCV treatment resulted in a gain of 11.54 QALYs over a 20-year time horizon at a cost of $42,938. Costs for treated groups were $69,075, $123,267, $125,431, $86,782, and $56,470 for the 2010, 2012, 2014, 2016, and 2018 scenarios, respectively. QALYs gained for treated groups were 12.90, 12.97, 13.34, 13.39, and 13.46 for the 2010, 2012, 2014, 2016, and 2018 scenarios, respectively. The incremental cost-effectiveness ratios in each year compared with no treatment were $19,218 per QALY, $56,104 per QALY, $45,829 per QALY, $23,699 per QALY, and $7,048 per QALY. CONCLUSIONS: Treatment effectiveness for HCV has increased steadily, while treatment costs increased substantially from 2010-2014 before decreasing to its lowest point in 2018. Thus, the dynamic nature of innovation creates the need for iterative cost-effectiveness analyses. DISCLOSURES: No outside funding supported this study. Mattingly reports unrelated consulting from the National Health Council, Bristol Myers Squibb, G&W Laboratories, Allergy and Asthma Foundation of American, and the Massachusetts Health Policy Commission. Love reports an unrelated research grant from the American Cancer Society.

Real-World Clinical and Economic Outcomes Associated with Palbociclib for HR-Positive/HER2 Negative Metastatic Breast Cancer: A Commentary.

Despite the achieved advancement in pharmacological cancer treatments, the majority of postmenopausal women with hormone receptor-positive metastatic breast cancer (mBC) will experience disease progression. Research into alternative therapies with improved efficacy and reduced side effects has led to the development of a new class of oral anticancer medications, the cyclin-dependent kinase (CDK) 4/6 inhibitors, which include palbociclib, ribociclib, and abemaciclib. Nonetheless, there is growing evidence that the effectiveness of oral anticancer medications is sub-optimal, being influenced by low adherence, sociodemographic factors, and adverse effect profiles. In addition, there is a disconnect between the high price tags of CDK 4/6 inhibitors and their observed effectiveness, raising questions about their value. Currently, the existing knowledge base on the effectiveness and cost-effectiveness of newer oral anticancer medications in understudied populations with possible health disparities is scant. This commentary discusses what is known about palbociclib's clinical effectiveness, safety, and adherence and suggests the need for further studies of real-world effectiveness and cost-effectiveness to help establish the value of newer oncologic drugs, such as palbociclib. DISCLOSURES: No funding supported the writing of this article. The authors have nothing to disclose.

Cost-Effectiveness Analysis of Xpert MTB/RIF for Multi-Outcomes of Patients With Presumptive Pulmonary Tuberculosis in Thailand.

OBJECTIVES: The cost-effectiveness of screening adult patients for pulmonary tuberculosis is not clear. As such, this study aims to identify the cost-effectiveness between the Xpert MTB/RIF assay and the sputum acid-fast bacilli (AFB) smear. Multi-outcomes were correct diagnosis, time to achieve correct diagnosis, and gain in quality-adjusted life-years (QALYs). METHODS: A decision tree model was constructed to reveal a possible clinical pathway of tuberculosis diagnosis. The researchers used a clinical study to establish the probability of all clinical pathways for input into this model. The sample size was calculated following the correct diagnosis. Participants were randomly divided into 2 groups. A structural questionnaire and the Thai version of quality of life (EQ-5D-5L) were used for interviewing. RESULTS: The results showed that the time to achieve the correct diagnosis for the group using Xpert MTB/RIF was shorter than that for the group using the sputum AFB smear. Both the correct diagnosis and QALYs of the base case analysis presented the Xpert MTB/RIF method as dominant. A Monte Carlo model, which analyzed the Xpert MTB/RIF method, revealed that the average number of patients who were correctly diagnosed was 673, the QALYs were 945.85 years, and the total cost was $143 110.64. For the sputum AFB smear method, the average number who received a correct diagnosis was 592, the QALYs were 940.40 years, and the total cost was $196 666.84. Probabilistic and one-way sensitivity analysis confirmed that the Xpert MTB/RIF remained dominant. CONCLUSIONS: These results provide useful information for the National Strategic Plan to screen all adult patients for pulmonary tuberculosis.

Implementation of a pharmacogenomic program in a Brazilian public institution.

This narrative review describes implementation, current status and perspectives of a pharmacogenomic (PGx) program at the Brazilian National Cancer Institute (INCA), targeting the cancer chemotherapeutic drugs - fluoropyrimidines, irinotecan and thiopurines. This initiative, designed as a research project, was supported by a grant from the Brazilian Ministry of Health. A dedicated task force developed standard operational procedures from recruitment of patients to creating PGx reports with dosing recommendations, which were successfully applied to test 100 gastrointestinal cancer INCA outpatients and 162 acute lymphoblastic leukemia pediatric patients from INCA and seven other hospitals. The program has been subsequently expanded to include gastrointestinal cancer patients from three additional cancer treatment centers. We anticipate implementation of routine pre-emptive PGx testing at INCA but acknowledge challenges associated with this transition, such as continuous financing support, availability of trained personnel, adoption of the PGx-informed prescription by the clinical staff and, ultimately, evidence of cost-effectiveness.

Cytoreductive surgery (CRS) with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) versus standard of care (SoC) in people with peritoneal metastases from colorectal, ovarian or gastric origin: protocol for a systematic review and individual participant data (IPD) meta-analyses of effectiveness and cost-effectiveness.

INTRODUCTION: There is uncertainty about whether cytoreductive surgery (CRS)+hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared with standard of care (SoC) in people with peritoneal metastases who can withstand major surgery. PRIMARY OBJECTIVES: To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis. SECONDARY OBJECTIVES: To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services perspective using a model-based cost-utility analysis. METHODS AND ANALYSIS: We will perform a systematic review of literature by updating the searches from MEDLINE, Embase, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of intervention and control, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications and resource utilisation data. Using IPD, we will perform a two-step IPD, that is, calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses, meta-regression and sensitivity analyses. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting. ETHICS AND DISSEMINATION: This project was approved by the UCL Research Ethics Committee (Ethics number: 16023/001). We aim to present the findings at appropriate international meetings and publish the review, irrespective of the findings, in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019130504.

Assessing the value for money of an integrated health and wellbeing service in the UK.

Lay health workers have been utilized to deliver health promotion programmes in a variety of settings. However, few studies have sought to determine whether these programmes represent value for money, particularly in a UK context. The present study involved an economic evaluation of Wellbeing for Life, an integrated health and wellbeing service in northern England. The service combined one-to-one interventions delivered by lay health workers (known as health trainers), group wellbeing interventions, volunteering opportunities and other community development activities. Value for money was assessed using an established economic model developed with input from a panel of commissioners and providers, and the main data source was the national health trainer data collection and reporting system. Between June 2015 and January 2017, behaviour change outcomes (i.e. whether client goals in relation to diet, physical activity, smoking or other behaviours, had been achieved) were recorded for 2433 of the 3179 individuals who accessed one-to-one interventions. The level of achievement observed gave an estimated total health gain of 287.7 quality-adjusted life years (QALYs). In addition, there were 4669 health-promoting events, five asset mapping projects and 1595 occurrences of signposting to other services. Combining the value of individual behaviour change with the value of these additional activities gave an overall net cost per QALY gained of £3900 and a total estimated societal value of at least £3.45 for every £1 spent on the service. These results suggest that the Wellbeing for Life service offered good value for money. Further research is needed to systematically and comprehensively determine the societal value of similar holistic, asset-based and lay-led approaches.

Emergent and Urgent Craniotomies in Pediatric Patients: Resource Utilization and Cost Analysis.

BACKGROUND: Pediatric neurosurgeons are occasionally tasked with performing surgery expeditiously to preserve a child's neurologic faculties and life. OBJECTIVE: This study examines the etiologies, outcomes, and costs for urgent or emergent craniotomies at a Level I Pediatric Trauma center over a 7-year time period. METHODS: A retrospective review was conducted for each patient who underwent an emergent or urgent craniotomy within 24 hours of presentation between January 2010 and April 2017. Demographic, clinical, and surgical details were recorded for a total of 48 variables. Any readmission within 90 days was analyzed. Hospital charges for each admission and readmission were collected and adjusted for inflation to October 2018 values. RESULTS: Among the 223 children who underwent urgent or emergent craniotomies, the majority were admitted for traumatic injuries (n = 163, 73.1%). The most common traumatic mechanism was fall (n = 51, 22.9%), and the most common non-traumatic cause was tumor (n = 21, 9.4%). Overall, craniotomies were typically performed for hematoma evacuation of one type or combination (n = 115, 51.6%) during off-peak times (n = 178, 79.8%). Seventy-seven (34.5%) subjects experienced 1 or more postoperative events, 22 of whom returned to the operating room. There were 13 (5.8%) and 33 (14.8%) readmissions within 30 days and 90 days of discharge, respectively. Non-trauma patients (compared with trauma patients) and polytrauma (compared with isolated head injury) had greater healthcare needs, resulting in higher charges. CONCLUSION: Most urgent or emergent pediatric craniotomies were performed for the treatment of traumatic injuries involving hematoma evacuation, but non-traumatic patients were more complex requiring greater resources.

Clinical outcomes and cost-effectiveness analysis for the treatment of basilar tip aneurysms.

BACKGROUND: Endovascular treatment of basilar tip aneurysms is less invasive than microsurgical clipping, but requires closer follow-up. OBJECTIVE: To characterize the additional costs associated with endovascular treatment of basilar tip aneurysms rather than microsurgical clipping. MATERIALS AND METHODS: We obtained clinical records and billing information for 141 basilar tip aneurysms treated with clip ligation (n=48) or endovascular embolization (n=93). Costs included direct and indirect costs associated with index hospitalization, as well as re-treatments, follow-up visits, imaging studies, rehabilitation, and disability. Effectiveness of treatment was quantified by converting functional outcomes (modified Rankin Scale (mRS) score) into quality-adjusted life-years (QALYs). Cost-effectiveness was performed using cost/QALY ratios. RESULTS: Average index hospitalization costs were significantly higher for patients with unruptured aneurysms treated with clip ligation ($71 400 ± $47 100) compared with coil embolization ($33 500 ± $22 600), balloon-assisted coiling ($26 200 ± $11 600), and stent-assisted coiling ($38 500 ± $20 900). Multivariate predictors for higher index hospitalization cost included vasospasm requiring endovascular intervention, placement of a ventriculoperitoneal shunt, longer length of stay, larger aneurysm neck and width, higher Hunt-Hess grade, and treatment-associated complications. At 1 year, endovascular treatment was associated with lower cost/QALY than clip ligation in unruptured aneurysms ($52 000/QALY vs $137 000/QALY, respectively, p=0.006), but comparable rates in ruptured aneurysms ($193 000/QALY vs $233 000/QALY, p=0.277). Multivariate predictors for higher cost/QALY included worse mRS score at discharge, procedural complications, and larger aneurysm width. CONCLUSIONS: Coil embolization of basilar tip aneurysms is associated with a lower cost/QALY. This effect is sustained during follow-up. Clinical condition at discharge is the most significant predictor of overall cost/QALY at 1 year.

Effectiveness and cost-effectiveness of incentives as a tool for prevention of non-communicable diseases: A systematic review.

The rising epidemic of non-communicable diseases (NCDs) poses substantial health and economic challenges to both individuals and society. Application of incentive-based strategies based on traditional and behavioural economic theory has emerged as a potential strategy to address rising rates of NCDs. Yet, whether or not incentives truly represent a promising strategy for addressing NCDs has not been systematically addressed nor is it clear whether certain behavioural economic strategies outperform others or simply offering a cash-based incentive for meeting a goal. In this systematic review we aim to determine whether there is an evidence base for any of these strategies. Forty-eight published randomized controlled trials (70 contrasts) evaluating the effectiveness of incentive-based strategies for improvements in NCD risk-factors were reviewed. Our primary conclusion is that there is a lack of compelling evidence that incentives of any form represent a compelling NCD reduction strategy. More evidence for long-term effectiveness and cost-effectiveness is needed to justify third party funding of any incentive based strategy.

Reducing Phlebotomy Utilization With Education and Changes to Computerized Provider Order Entry.

INTRODUCTION: Daily phlebotomy is often a standard procedure in hospitalized patients. Recently, this practice has begun receiving attention as a potential target for efforts focused on eliminating overuse. Several organizations have published their efforts in this arena. Interventions have included education, feedback, and changes to computerized provider order entry (CPOE) but have yielded mixed results. METHODS: A quality improvement initiative to reduce the utilization of daily phlebotomy was conducted at a 505-bed Academic Medical Center. This project involved a combination of educational interventions and changes to CPOE. The primary end point evaluated was the daily performance of complete blood counts (CBCs) and basic metabolic profiles (BMPs) on medical and surgery units relative to the corresponding hospital census. RESULTS: Over the course of this project from August 1, 2013, to September 23, 2016, there was a 15.2% reduction in CBCs (p < .001 for linear trend) and 13.1% reduction in BMPs. DISCUSSION: Our results suggest that layering multimodal interventions that involve both "hard-wired" changes to CPOE and education and performance feedback can result in decreased utilization of phlebotomy.

Anticipated Rates and Costs of Guideline-Concordant Preoperative Stress Testing.

BACKGROUND: Current guidelines recommend that patients have preoperative assessment of cardiac risk and functional status, and that patients at "elevated" cardiac risk with poor or unknown functional status be referred for preoperative stress testing. Little is known about current rates of testing or resultant medical costs. We set out to estimate the expected rates of preoperative stress testing and resultant costs if physicians in the United States were to follow current guidelines and to investigate differences that would arise from 2 risk prediction methods included in current guidelines. METHODS: We applied 2 risk prediction tools (Revised Cardiac Risk Index and Myocardial Infarction or Cardiac Arrest) included in current American College of Cardiology/American Heart Association guidelines to a multicenter prospective registry of patients undergoing surgery in the United States in 2009. We then calculated expected rates of preoperative cardiac stress testing if physicians were to follow American College of Cardiology/American Heart Association guidelines, expected nationwide direct medical expenditures that would result (in 2017 US dollars), and agreement beyond chance between the 2 risk prediction tools. RESULTS: Current guidelines recommend considerable spending on preoperative stress testing. Guideline-recommended spending would differ substantially depending on the risk prediction tool used and the reliability of the functional status assessment. Rates of testing and resultant spending are likely much greater among patients at "elevated" risk, compared with patients at "low" risk. Two guideline-recommended risk assessment tools, Revised Cardiac Risk Index and Myocardial Infarction or Cardiac Arrest, have poor agreement beyond chance across the currently recommended risk threshold. CONCLUSIONS: Preoperative stress testing is likely a considerable source of medical spending, despite unproven benefit. Which perioperative risk assessment tool clinicians should use, what risk thresholds are appropriate for patient selection, and the reliability of the functional status assessment all warrant further attention.