Investigating cortical hypoxia in multiple sclerosis via time-domain near-infrared spectroscopy.

OBJECTIVES: Hypoperfusion and tissue hypoxia have been implicated as contributory mechanisms in the neuropathology of multiple sclerosis (MS). Our objective has been to study cortical oxygenation in vivo in patients with MS and age-matched controls. METHODS: A custom, multiwavelength time-domain near-infrared spectroscopy system was developed for assessing tissue hypoxia from the prefrontal cortex. A cross-sectional case-control study was undertaken assessing patients with secondary progressive MS (SPMS) and age-matched controls. Co-registered magnetic resonance imaging was used to verify the location from which near-infrared spectroscopy data were obtained through Monte Carlo simulations of photon propagation. Additional clinical assessments of MS disease severity were carried out by trained neurologists. Linear mixed effect models were used to compare cortical oxygenation between cases and controls, and against measures of MS severity. RESULTS: Thirty-three patients with secondary progressive MS (median expanded disability status scale 6 [IQR: 5-6.5]; median age 53.0 [IQR: 49-58]) and 20 age-matched controls were recruited. Modeling of photon propagation confirmed spectroscopy data were obtained from the prefrontal cortex. Patients with SPMS had significantly lower cortical hemoglobin oxygenation compared with controls (-6.0% [95% CI: -10.0 to -1.9], P = 0.004). There were no significant associations between cortical oxygenation and MS severity. INTERPRETATION: Using an advanced, multiwavelength time-domain near-infrared spectroscopy system, we demonstrate that patients with SPMS have lower cortical oxygenation compared with controls.

Cost-effectiveness of recombinant influenza vaccine compared with standard dose influenza vaccine in adults 18-64 years of age.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) uses the Evidence to Recommendations Framework that includes cost-effectiveness analyses (CEA) for determining vaccine recommendations. ACIP's preference for protecting adults ≥ 65 years is enhanced vaccines, including recombinant influenza vaccine (RIV4), adjuvanted or high dose influenza vaccine. Less is known about the CEA of enhanced vaccines for younger adults. METHODS: We used decision analysis modeling from a societal perspective to determine the cost-effectiveness, measured in quality adjusted life years (QALYs), of RIV4 compared with standard dose quadrivalent influenza vaccine (SD-IIV4) in adults 18-64 years old. Model inputs included 2018-2020 vaccine effectiveness (VE) estimates based on medical record data from a large local health system, 2019-2020 national vaccination and influenza epidemic parameters, with costs and population distributions fitted to the season. RESULTS: Among adults ages 18-64 years, RIV4 cost $94,186/QALY gained, compared to SD-IIV4. Among those 50-64 years old, RIV4 was relatively more cost-effective ($61,329/QALY gained). Cost-effectiveness estimates for 18-64-year-olds were sensitive to the absolute difference in VE between SD-IIV4 and RIV4, among other parameters. Use of RIV4 in 18-64-year-olds would result in fewer cases (669,984), outpatient visits (261,293), hospitalizations (20,046) and deaths (1,018) annually. The majority (59 %; 597 of 1018) of the decreases in deaths occurred in the 50-64-year-olds. CONCLUSIONS: While RIV4 was effective and cost-effective relative to SD-IIV4 for both 50-64-year-old and 18-64-year-old adults, cost-effectiveness was sensitive to small changes in parameters among 18-64-year-olds. Because substantial public health benefits occur with enhanced vaccines, health systems and policy makers may opt for preferential product use in select age/risk groups (e.g., 50-64 year olds) to maximize their cost-benefit ratios.

Economic evaluation of weight loss and transplantation strategies for kidney transplant candidates with obesity.

Novel antiobesity medications, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), have expanded weight loss (WL) options for kidney transplantation (KT) candidates with obesity beyond lifestyle modifications and bariatric surgery. However, varying effectiveness, risk profiles, and costs make strategy choices challenging. To aid decision-making, we used a Markov model to examine the cost-effectiveness of different WL strategies over a 10-year horizon. A target WL of 15% of total body weight was used for the base case scenario, and we compared these strategies to a "liberal" KT strategy of transplanting candidates with obesity. Outcomes included costs (2023 US dollars), quality-adjusted life years, and incremental cost-effectiveness ratios. In analysis, a liberal KT strategy was favored over lifestyle modifications and GLP-1RAs. Among WL strategies, bariatric surgery was the most effective and cost the least, whereas lifestyle modification had the highest cumulative costs and was the least effective. Compared to liberal KT, bariatric surgery costs $45 859 per quality-adjusted life year gained. GLP-1RAs were favored over bariatric surgery only when drug costs were below $5000 per year (base cost $12 077). In conclusion, for KT candidates with obesity, a liberal KT strategy and bariatric surgery are preferred over lifestyle modifications alone and GLP-1RAs based on outcomes and cost-effectiveness.

Changes in the cost-effectiveness of pneumococcal vaccination and of programs to increase its uptake in U.S. older adults.

BACKGROUND: Multiple factors, such as less complex U.S. adult pneumococcal recommendations that could increase vaccination rates, childhood pneumococcal vaccination indirect effects that decrease adult vaccination impact, and increased vaccine hesitancy (particularly in underserved minorities), could diminish the cost-effectiveness of programs to increase pneumococcal vaccination in older adults. Prior analyses supported the economic favorability of these programs. METHODS: A Markov model compared no vaccination and current recommendations (either 20-valent pneumococcal conjugate vaccine [PCV20] alone or 15-valent pneumococcal conjugate vaccine plus the 23-valent pneumococcal polysaccharide vaccine [PCV15/PPSV23]) without or with programs to increase vaccine uptake in Black and non-Black 65-year-old cohorts. Pre-pandemic population- and serotype-specific pneumococcal disease risk and illness/vaccine costs came from U.S. DATABASES: Program costs were $2.19 per vaccine-eligible person and increased absolute vaccination likelihood by 7.5%. Delphi panel estimates and trial data informed vaccine effectiveness values. Analyses took a healthcare perspective, discounting at 3%/year over a lifetime time horizon. RESULTS: Uptake programs decreased pneumococcal disease overall. In Black cohorts, PCV20 without program cost $216,805 per quality-adjusted life year (QALY) gained compared with no vaccination; incremental cost-effectiveness was $245,546/QALY for PCV20 with program and $425,264/QALY for PCV15/PPSV23 with program. In non-Black cohorts, all strategies cost >$200,000/QALY gained. When considering the potential indirect effects from childhood vaccination, all strategies became less economically attractive. Increased vaccination with less complex strategies had negligible effects. In probabilistic sensitivity analyses, current recommendations with or without programs were unlikely to be favored at thresholds <$200,000/QALY gained. CONCLUSION: Current U.S. pneumococcal vaccination recommendations for older adults were unlikely to be economically reasonable with or without programs to increase vaccine uptake. Alternatives to current pneumococcal vaccines that include pneumococcal serotypes associated with adult disease should be considered.

Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.

Associations of Health Care Utilization and Therapeutic Alliance in Patients with Advanced Cancer.

Introduction: Therapeutic alliance (TA), or the extent to which patients feel a sense of caring and trust with their physician, may have an impact on health care utilization. We sought to determine if TA is associated with: (1) emergency department (ED) visits within 30 days of death and (2) hospice enrollment. Methods and Materials: This is a secondary analysis of data from a randomized clinical trial. We used restricted cubic splines to assess the relationship between TA scores and health care utilization. Results: Six hundred seventy-two patients were enrolled in the study, with 331 (49.3%) dying within 12 months. Patients with higher TA were less likely to have an ED visit in the last 30 days of life, but there was no evidence of a relationship between TA and enrollment in hospice. Conclusions: Higher TA was associated with decreased ED visits within 30 days of death. There was no association between TA and rates of hospice enrollment. Clinical Registration Number: NCT02712229.

Cost-effectiveness of an in-development adult-formulated 21-valent pneumococcal conjugate vaccine in US adults aged 50 years or older.

Indirect effects of childhood pneumococcal conjugate vaccines (PCV) have diminished the cost-effectiveness of current adult vaccine recommendations. An in-development adult-formulated 21-valent pneumococcal conjugate vaccine (PCV21) may play a critical role in reducing pneumococcal illness by targeting a larger number of serotypes responsible for adult pneumococcal infections. This study assesses the cost-effectiveness of PCV21 in US adults aged 50 years or older compared with currently recommended pneumococcal vaccines, from both the societal and healthcare perspectives. A Markov model evaluated the lifetime cost-effectiveness of PCV21 (given at age 50 years only, at ages 50/65 years, and risk-based at ages < 65 years plus age-based at age 65 years) compared to no vaccination and to currently recommended pneumococcal vaccines given either as currently recommended or routinely at ages 50/65 years. The analysis was conducted in hypothetical Black and non-Black cohorts aged 50 years or older, with and without considering childhood pneumococcal vaccination indirect effects. Model parameters were based on US data. Parameter uncertainty was assessed using 1-way and probabilistic sensitivity analyses. From the societal perspective, PCV21 at ages 50/65 years compared to PCV21 at age 50 years cost $7,410 per quality adjusted life year (QALY) gained in Black cohort analyses and $85,696/QALY gained in the non-Black cohort; PCV21 at ages 50/65 years had the most favorable public health outcomes. From the healthcare perspective, compared to no vaccination, PCV21 at age 50 years cost $46,213/QALY gained in the Black cohort and $86,629/QALY in non-Blacks. All other strategies were dominated in both cohorts and from both perspectives. When considering childhood pneumococcal vaccination indirect effects, costs of PCV21 at ages 50/65 years remained less than $140,000/QALY gained from the societal perspective in both populations. PCV21 is potentially cost-effective compared to currently approved pneumococcal vaccines in adults aged 50 years or older from both the societal and healthcare perspectives.

Pneumococcal Vaccination Strategies in 50-Year-Olds to Decrease Racial Disparities: A US Societal Perspective Cost-Effectiveness Analysis.

OBJECTIVES: This study assesses the impact of expanding pneumococcal vaccination to all 50-year-olds to decrease racial disparities by estimating from the societal perspective, the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) and 15-valent conjugate vaccine followed by 23-valent polysaccharide vaccine (PCV15/PPSV23) for 50-year-olds. METHODS: A Markov model compared the cost-effectiveness of PCV20 or PCV15/PPSV23 in all general population 50- and 65-years-olds compared with current US recommendations and with no vaccination in US Black and non-Black cohorts. US data informed model parameters. Pneumococcal disease societal costs were estimated using direct and indirect costs of acute illness and of pneumococcal-related long-term disability and mortality. Hypothetical 50-year-old cohorts were followed over their lifetimes with costs and effectiveness discounted 3% per year. Deterministic and probabilistic sensitivity analyses assessed model uncertainty. RESULTS: In Black cohorts, PCV20 for all at ages 50 and 65 was the least costly strategy and had greater effectiveness than no vaccination and current recommendation strategies, whereas PCV15/PPSV23 at 50 and 65 cost more than $1 million per quality-adjusted life year (QALY) gained compared with PCV20 at 50 and 65. In non-Black cohorts, PCV20 at 50 and 65 cost $62 083/QALY and PCV15/PPSV23 at 50 and 65 cost more than $1 million/QALY with current recommendations, again being more costly and less effective. In probabilistic sensitivity analyses, PCV20 at 50 and 65 was favored in 85.7% (Black) and 61.8% (non-Black) of model iterations at a $100 000/QALY gained willingness-to-pay threshold. CONCLUSIONS: When considering the societal costs of pneumococcal disease, PCV20 at ages 50 and 65 years in the general US population is a potentially economically viable strategy, particularly in Black cohorts.

Tissue Hypoxia and Associated Innate Immune Factors in Experimental Autoimmune Optic Neuritis.

Visual loss in acute optic neuritis is typically attributed to axonal conduction block due to inflammatory demyelination, but the mechanisms remain unclear. Recent research has highlighted tissue hypoxia as an important cause of neurological deficits and tissue damage in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) and, here, we examine whether the optic nerves are hypoxic in experimental optic neuritis induced in Dark Agouti rats. At both the first and second peaks of disease expression, inflamed optic nerves labelled significantly for tissue hypoxia (namely, positive for hypoxia inducible factor-1α (HIF1α) and intravenously administered pimonidazole). Acutely inflamed nerves were also labelled significantly for innate markers of oxidative and nitrative stress and damage, including superoxide, nitric oxide and 3-nitrotyrosine. The density and diameter of capillaries were also increased. We conclude that in acute optic neuritis, the optic nerves are hypoxic and come under oxidative and nitrative stress and damage. Tissue hypoxia can cause mitochondrial failure and thus explains visual loss due to axonal conduction block. Tissue hypoxia can also induce a damaging oxidative and nitrative environment. The findings indicate that treatment to prevent tissue hypoxia in acute optic neuritis may help to restore vision and protect from damaging reactive oxygen and nitrogen species.

Societal Cost of Racial Pneumococcal Disease Disparities in US Adults Aged 50 Years or Older.

OBJECTIVE: This study aimed to estimate the societal cost of racial disparities in pneumococcal disease among US adults aged ≥  50 years. METHODS: In a model-based analysis, societal costs of invasive pneumococcal disease (IPD) and hospitalized nonbacteremic pneumococcal pneumonia (NBP) were estimated using (1) direct medical costs plus indirect costs of acute illness; (2) indirect costs of pneumococcal mortality; and (3) direct and indirect costs of related disability. Disparities costs were calculated as differences in average per-person pneumococcal disease cost between Black and non-Black adults aged ≥  50 years multiplied by the Black population aged ≥  50 years. Costs were in 2019 US dollars (US$), with future costs discounted at 3% per year. RESULTS: Total direct and indirect costs per IPD case were US$186,791 in Black populations and US$182,689 in non-Black populations; total hospitalized NBP costs per case were US$100,632 (Black) and US$96,781 (non-Black). The difference in population per-person total pneumococcal disease costs between Black and non-Black adults was US$47.85. Combined societal costs of disparities for IPD and hospitalized NBP totaled US$673.2 million for Black adults aged ≥  50 years. Disease and disability risks, life expectancy, and case-fatality rates were influential in one-way sensitivity analyses, but the lowest cost across all analyses was US$194 million. The 95% probability range of racial disparity costs were US$227.2-US$1156.9 million in a probabilistic sensitivity analysis. CONCLUSIONS: US societal cost of racial pneumococcal disease disparities in persons aged ≥ 50 years is substantial. Successful pneumococcal vaccination policy and programmatic interventions to mitigate these disparities could decrease costs and improve health.

Hope and illness expectations: A cross-sectional study in patients with advanced cancer.

BACKGROUND: The fear of taking away hope hinders clinicians' willingness to share serious news with patients with advanced disease. Unrealistic illness expectations, on the other hand, can complicate decision making and end-of-life care outcomes. Exploration of the association between hope and illness expectations can support clinicians in better communication with their patients. AIM: The aim of this study was to explore whether realistic illness expectations are associated with reduced hope in people with advanced cancer. DESIGN: This is a cross-sectional secondary analysis of baseline data from a primary palliative care cluster-randomized trial CONNECT (data collected from July 2016 to October 2020). Hope was measured by Herth Hope Index. Illness expectations were measured by assessing patients' understanding of their treatment goals, life expectancy, and terminal illness acknowledgement. Multivariable regression was performed, adjusting for demographical and clinical confounders. SETTING/PARTICIPANTS: Adult patients with advanced solid cancers recruited across 17 oncology clinics. RESULTS: Data from 672 patients were included in the study, with mean age of 69.3 years (±10.2), 53.6% were female. Proportion of patients indicating realistic expectations varied based on which question was asked from 10% to 46%. Median level of hope was 39 (IQR = 36-43). Multivariate non-inferiority regression did not find any significant differences in hope between patients with more and less realistic illness expectations. CONCLUSIONS: Our results suggest that hope can be sustained while holding both realistic and unrealistic illness expectations. Communication about serious news should focus on clarifying the expectations as well as supporting people's hopes.

Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial.

BACKGROUND: Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding. We aimed to compare recombinant VWF with tranexamic acid for reducing heavy menstrual bleeding in patients with von Willebrand disease. METHODS: VWDMin, a phase 3, open-label, randomised crossover trial, was done in 13 haemophilia treatment centres in the USA. Female patients aged 13-45 years with mild or moderate von Willebrand disease, defined as VWF ristocetin cofactor less than 0·50 IU/mL, and heavy menstrual bleeding, defined as a pictorial blood assessment chart (PBAC) score more than 100 in one of the past two cycles were eligible for enrolment. Participants were randomly assigned (1:1) to two consecutive cycles each of intravenous recombinant VWF, 40 IU/kg over 5-10 min on day 1, and oral tranexamic acid 1300 mg three times daily on days 1-5, the order determined by randomisation. The primary outcome was a 40-point reduction in PBAC score by day 5 after two cycles of treatment. Efficacy and safety were analysed in all patients with any post-baseline PBAC scores. The trial was stopped early due to slow recruitment on Feb 15, 2022, by a data safety monitoring board request, and was registered at ClinicalTrials.gov, NCT02606045. FINDINGS: Between Feb 12, 2019, and Nov 16, 2021, 39 patients were enrolled, 36 of whom completed the trial (17 received recombinant VWF then tranexamic acid and 19 received tranexamic acid then recombinant VWF). At the time of this unplanned interim analysis (data cutoff Jan 27, 2022), median follow-up was 23·97 weeks (IQR 21·81-28·14). The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146 [95% CI 117-199] vs 213 [152-298]; adjusted mean treatment difference 46 [95% CI 2-90]; p=0·039). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs zero during recombinant VWF treatment) and other bleeding (four [6%] vs two [3%]). INTERPRETATION: These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience. FUNDING: National Heart Lung Blood Institute (National Institutes of Health).

Cost-effectiveness of an in-development adult-formulated pneumococcal vaccine in older US adults.

INTRODUCTION: CDC pneumococcal vaccination recommendations for older adults now include either 15- or 20-valent pneumococcal conjugate vaccine (PCV15/PCV20). However, an in-development 21-valent vaccine (PCV21), formulated based on adult pneumococcal disease epidemiology, could substantially increase coverage of disease-causing pneumococcal serotypes, particularly in Black older adults, who are at greater risk. The potential public health impact and cost-effectiveness of PCV21 compared to currently recommended vaccines in older adults is unclear. METHODS: A Markov decision model compared current pneumococcal vaccination recommendations to PCV21 use in Black and non-Black 65-year-old cohorts. CDC Active Bacterial Core surveillance data informed population and serotype-specific pneumococcal disease risk. Vaccine effectiveness was estimated using Delphi panel estimates and clinical trial data, with variation in sensitivity analyses. Potential indirect effects on adult disease from PCV15 childhood vaccination were examined. All model parameters were varied individually and collectively in sensitivity analyses. Scenarios with decreased PCV21 effectiveness and potential COVID-19 pandemic effects were also examined. RESULTS: In the Black cohort, the PCV21 strategy cost $88,478 per quality adjusted life-year (QALY) gained without and $97,952/QALY with childhood PCV15 indirect effects. PCV21 in the non-Black cohort cost $127,436/QALY gained without and $141,358/QALY with childhood PCV15 effects. Current recommendation strategies were economically unfavorable, regardless of population or indirect childhood vaccination effects. Results favoring PCV21 use were robust in sensitivity analyses and alternative scenarios. CONCLUSION: An in-development PCV21 vaccine would likely be economically and clinically favorable compared to currently recommended pneumococcal vaccines in older adults. While PCV21 was more favorable in Black cohort analyses, results for both Black and non-Black populations were economically reasonable, highlighting the potential importance of adult-specific pneumococcal vaccine formulations and, pending further investigation, potentially justifying a future general population recommendation for PCV21 use in older adults.

Primary Palliative Care Improves Uptake of Advance Care Planning Among Patients With Advanced Cancers.

BACKGROUND: Palliative care specialists are experts in conducting advance care planning (ACP) but are a limited resource. Oncology nurses often have special relationships with their patients and thus may be poised to provide primary palliative care. We sought to determine the impact of a nurse-led primary palliative care intervention on ACP uptake among patients with advanced cancer. METHODS: We performed a secondary analysis of a cluster randomized controlled trial examining the impact of nurse-based primary palliative care. In the parent trial, patients with advanced cancer received either monthly primary palliative care visits with trained nurses within their cancer center or standard care. Nurses in the intervention arm received special training in ACP. ACP uptake was assessed at enrollment and 3 months later evaluating (1) whether an end-of-life conversation (EOLC) occurred with one's oncologist, and (2) completion of an advance directive (AD). Multivariable logistic regression tested differences in ACP uptake by treatment arm adjusted for age, religious importance, education, time with current oncologist, and performance status. RESULTS: Of 672 patients enrolled, 182/336 (54%) patients in the intervention arm and 196/336 (58%) in the standard care arm lacked an EOLC at baseline and completed the 3-month assessment. Of those, 82/182 (45.1%) patients in the intervention arm and 29/196 (14.8%) in the standard care arm reported having an EOLC at 3 months (adjusted odds ratio, 5.28; 95% CI, 3.10-8.97; P<.001). Similarly, 111/336 (33%) patients in the intervention arm and 105/336 (31%) in the standard care arm lacked an AD at baseline and completed the 3-month assessment. Of those, 48/111 (43.2%) patients in the intervention arm and 19/105 (18.1%) in the standard care arm completed an AD over the study period (adjusted odds ratio, 3.68; 95% CI, 1.89-7.16; P<.001). CONCLUSIONS: Nurse-led primary palliative care increased ACP uptake among patients with advanced cancer. Training oncology nurses embedded within community cancer centers to provide primary palliative care may help improve ACP access.

Cost-effectiveness analysis of tumor molecular testing in stage III endometrial cancer.

BACKGROUND: Standard of care for adjuvant treatment of stage III endometrial cancer includes chemotherapy and radiation. In addition to stage, tumor molecular profiles may predict treatment outcomes, and prospective clinical trials are ongoing. However, tumor molecular testing is costly and time-consuming. Our objective was to evaluate the cost-effectiveness of tumor molecular testing in stage III endometrial cancer. METHODS: A Markov decision model compared two strategies for stage III endometrial cancer: Tumor Molecular Testing (TMT) versus No TMT. TMT included sequential POLE next generation sequencing, mismatch repair immunohistochemistry (IHC), and p53 IHC. POLE-mutated patients were assigned to adjuvant radiation therapy; all others including controls were assigned to adjuvant chemoradiation. First recurrences were treated with 6 cycles of carboplatin and paclitaxel. Second recurrences were treated with pembrolizumab alone for mismatch repair deficient patients and both pembrolizumab and lenvatinib for other patients. Sensitivity analyses were performed to test model robustness. RESULTS: Compared to No TMT, TMT was cost saving with equivalent effectiveness. On one-way sensitivity analysis, TMT remained cost saving over all parameter ranges. TMT was also favored on probabilistic sensitivity analysis in 80% of iterations at a willingness-to-pay threshold of $100,000/quality adjusted life-year (QALY) gained. However, when TMT was compared to mismatch repair IHC alone, TMT cost $182,798/QALY gained. CONCLUSIONS: In this model of patients with stage III endometrial cancer, TMT was cost saving compared to No TMT. However, when compared to mismatch repair IHC alone, TMT was economically unfavorable.

Pediatric intestine transplant cost: Analysis of the Pediatric Health Information System database.

BACKGROUND: We aimed to evaluate costs from transplant to discharge in children who had undergone intestine transplant. METHODS: We performed a cross-sectional observational study of pediatric intestine transplant recipients from 2004 through 2020, utilizing the Pediatric Health Information System database. Standardized costs were applied to all charges and converted to 2021 US dollars. We analyzed the association of cost from transplant to discharge with age, sex, race and ethnicity, length of stay, insurance type, transplant year, short bowel syndrome diagnosis, liver-containing graft, hospitalization status, and immunosuppressive regimen. Predictors with a P value <0.20 in univariable analysis were included in a multivariable model, which was reduced using backwards selection with a P value of 0.05. RESULTS: We identified 376 intestinal transplant recipients across nine centers (median age, 2 years; 44% female). Most patients had short bowel syndrome (294; 78%). The liver was included in 218 transplants (58%). Median posttransplant cost was $263,724 (interquartile range [IQR], $179,564-$384,147), and length of stay was 51.5 days (IQR, 34-77). In the final model, increased cost from transplant to hospital discharge was associated with liver-containing graft (+$31,805; P = 0.028), T-cell-depleting antibody use (+$77,004; P < 0.001), and mycophenolate mofetil use (+$50,514; P = 0.012) while controlling for insurance type and length of stay. A 60-day posttransplant hospital stay would cost an estimated $272,533. CONCLUSIONS: Intestine transplant has high immediate cost and long length of stay that varies by center, graft type, and immunosuppression regimen. Future work will examine the cost-effectiveness of various management strategies before and after transplant.

Program Factors Affecting Weight Loss and Mobility in Older Adults: Evidence From the Mobility and Vitality Lifestyle Program (MOVE UP).

Background. The Mobility and Vitality Lifestyle Program (MOVE UP) is a behavioral weight-management intervention for improving mobility among community-dwelling older adults. We examined program factors that affect implementation outcomes and participant-level health outcomes. Methods. The MOVE UP program was implemented in the greater Pittsburgh area from January 2015 to June 2019 to improve lower extremity performance in community-dwelling older adults who were overweight or obese. Thirty-two sessions were delivered over 13 months. All sessions were designed to be 1-hour in length, on-site, group-based, and led by trained and supported community health workers (CHWs). Participants completed weekly Lifestyle Logs for self-monitoring of body weight, diet, and physical activity. We evaluated the MOVE UP program using the RE-AIM framework, and collected quantitative data at baseline, 5-, 9-, and 13-months. Multilevel linear regression models assessed the impacts of program factors (site, CHW, and participant characteristics) on implementation outcomes and participant-level health outcomes. Results. Twenty-two CHWs delivered MOVE UP program to 303 participants in 26 cohorts. Participants were similar to the target source population in weight but differed in some demographic characteristics. The program was effective for weight loss and lower extremity function in both intervention and maintenance periods (Ps < .01), with an independent effect for Lifestyle Logs submission but not session attendance. Discussion. CHWs were able to deliver a multi-component weight loss intervention effectively in community settings. CHW and site characteristics had independent impacts on participants' adherence. Lifestyle Log submission may be a more potent measure of adherence in weight loss interventions than attendance.