A systematic review of the economic value proposition for commercially available nonsurgical weight-loss interventions.

OBJECTIVE: The study aim was to review the economic evaluation literature of commercially available and effective nonsurgical weight-loss interventions to investigate whether there is evidence to support claims of cost-effectiveness (i.e., good value for money) or cost savings (i.e., a positive return on investment). METHODS: Relevant databases were systematically reviewed to identify economic evaluations of commercially available weight-loss products and services shown to result in clinically significant weight loss. Five weight-loss medications (orlistat, liraglutide, naltrexone-bupropion, semaglutide, and phentermine-topiramate), two meal replacement programs (Jenny Craig, Optifast), and one behavioral intervention (Weight Watchers [WW]) that met inclusion criteria were identified. After screening, 32 relevant comparisons of cost-effectiveness or cost savings across 20 studies were identified. RESULTS: Ten of twenty pharmaceutical comparisons showed evidence of cost-effectiveness based on established thresholds. Four of twelve nonpharmaceutical comparisons provided evidence of cost-effectiveness, and five made claims of cost savings. However, methodological concerns cast doubt on the robustness of these claims. CONCLUSIONS: Evidence of cost-effectiveness for commercially available, evidence-based, nonsurgical weight-loss interventions is mixed. There is no evidence for cost-saving weight-loss medications and only weak evidence for behavioral and weight-loss interventions. Results provide a call to action to generate more robust evidence of the economic value proposition for these interventions.

Healthcare utilization and costs of singaporean youth with symptoms of depression and anxiety: results from a 2022 web panel.

BACKGROUND: There is evidence that the prevalence of depression and anxiety among youth is increasing and that these factors contribute to high healthcare costs and poor school performance. The goal of this study is to provide up-to-date estimates of the prevalence and economic burden of depression and anxiety among youth in Singapore. METHODS: Using an existing web panel, 991 parents filled out the PHQ-4 screener on behalf of 1,515 youth. 104 of these parents whose children (ages 4 to 21) had symptoms consistent with depression or anxiety filled out a full survey with questions on mental health symptoms, school absences, school performance, and healthcare utilization. The survey was fielded between April and June 2022. Publicly available prices were used to estimate the cost associated with the observed rates of health service use. FINDINGS: Based on parental responses, 11.7% (95% CI:10.2 - 13.5%) of youth had symptoms consistent with depression and 12.8% (95% CI:11.2 - 14.6%) had symptoms consistent with anxiety. In total, 16.2% (95% CI:14.5 - 18.3%) were reported to have symptoms consistent with at least one of these conditions. These youths missed an average of 190 (95% CI: 126-254) hours of school per year due to their mental health conditions and parents reported that school and daily activities performance was significantly degraded. Per capita annual healthcare costs averaged S$10,250 (95% CI: 7,150-13,350), with 64% of youth receiving emergency or inpatient services. In aggregate, annual costs associated with these conditions were estimated to be S$1.2 billion (95% CI:S$1.1bn - S$1.4bn). INTERPRETATION: Even with significant potential for underreporting, these results reveal concerning rates of Singaporean youth with symptoms consistent with depression or anxiety, many of whom remain untreated. Results also reveal the short-term economic burden caused by these symptoms and hint at longer-term consequences resulting from poor school performance. This study should represent a call to action for Singapore to address poor mental health among youth.

Prevalence and economic burden of depression and anxiety symptoms among Singaporean adults: results from a 2022 web panel.

BACKGROUND: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are leading causes of disability and premature mortality. At a global level, over 300 million people are estimated to suffer from major depressive disorders, equivalent to 4·4% of the world's population. Pandemic era stressors have increased rates for depression and anxiety by upwards of 25%. The goal of this study is to estimate the prevalence and economic burden of depression and anxiety symptoms in Singapore after the peak of the COVID-19 pandemic. METHODS: An existing web panel was queried between April 2022 and June 2022. Adult participants aged > 21 years old who screened positive for depression and anxiety symptoms based on the Patient Health Questionnaire-4 (PHQ-4) Screener were eligible for participation. Prevalence estimates were quantified by dividing the number of respondents who screened positive for these symptoms by the total number of respondents. Participants who screened positive were asked about healthcare utilization, days missed from work, and reduced productivity due to these symptoms. These values were then monetized and scaled based on prevalence and population counts to generate per capita and total annual costs. RESULTS: Two thousand three hundred forty-eight respondents filled out the PHQ-4 depression/anxiety screener on behalf of the 5,725 adults living in their households (including respondents themselves). Prevalence estimates were calculated based on the responses recorded for these 5,725 adults. 14.1% adults had symptoms consistent with depression and 15.2% had symptoms consistent with anxiety. In total, 20.0% may experience symptoms consistent with at least one of these two conditions, yet approximately half reported never being formally diagnosed. 350 respondents screened positive for depression or anxiety symptoms and thus were eligible to fill out the healthcare utilization, presenteeism, and absenteeism survey. Direct annual healthcare costs due to depression and anxiety symptoms averaged Singapore dollar (SGD) $1,050 for these respondents. The employed subset (n = 304) missed an extra 17.7 days of work on average per year, which translates to SGD $4,980 per worker. These workers also reported being ~ 40% less productive at work, which equates to SGD $28,720 in economic losses annually. In total, these symptoms caused SGD $15.7 billion in increased costs. Presenteeism accounts for 81.6% of this total (SGD $12.8 billion), absenteeism for 14.2% (SGD $2.3 billion) and healthcare accounts for 4.2% (SGD $0.7 billion). CONCLUSIONS: The health and economic burden associated with depression and anxiety symptoms is large in Singapore, representing 2.9% of Singapore's gross domestic product (GDP). Employers and governments should look to identify effective remediation strategies, including strategies to address the high rates of undiagnosed cases. Increasing psychiatric resources, general practitioner mental health competency, access to peer support, and increased efforts to reduce mental health stigma should be considered to address this growing public health crisis.

Association Between Device Type and Type IIIb Endoleaks Following Thoracic Endovascular Aortic Repair.

OBJECTIVE: Endoleaks following thoracic endovascular aortic repair (TEVAR) can lead to the need for re-intervention and aortic rupture. Given the recent recall of a specific thoracic stent graft type due to concerns about type IIIb endoleak (T3bE), in which blood leaks through the stent graft fabric, the aim was to characterise patterns of T3bEs among available TEVAR devices. METHODS: Reports related to thoracic stent grafts in the Food and Drug Administration's (FDA) Manufacturer and User Facility Device Experience (MAUDE) database between 2010 and 2020 were reviewed. Proportional reporting ratios (PRRs) and chi squared tests were used to assess for the presence of a signal of association between device type and T3bE. A PRR > 2 and chi squared value > 4 with three or more reports overall constituted a signal of association. The institutional database of patients undergoing TEVAR for thoracic aneurysms since 2002 was also queried for T3bE. RESULTS: There were 7 328 MAUDE reports available for analysis. When analysing T3bEs in the MAUDE database, the lowest PRR was 0.36 (95% confidence interval [CI] 0 - 1.03 in Gore CTAG, nine T3bE among 1 328 reports) and the highest was 2.07 (95% CI 1.72 - 2.42 in Medtronic Valiant, 64 T3bE among 2 520 reports). The T3bE chi squared value for Medtronic Valiant was 17.3. The relationship between Medtronic Valiant and T3bE was ascertainable by MAUDE data as early as 2013. Among 542 TEVARs for an aneurysm indication at Duke University Hospital since 2002, there were eight T3bEs - all in devices with sutured on graft material. CONCLUSION: The Medtronic Valiant device met criteria for association with type IIIb endoleaks in the FDA's MAUDE database and met those criteria as early as 2013. A possible relationship between woven graft fabric and T3bEs is supported by the observation that all types of T3bE that occurred among a large number of TEVARs at the institution followed placement of grafts with sutured on woven fabric.

Long-term outcomes of aortic root replacement for endocarditis.

BACKGROUND: Infective endocarditis (IE) involving the aortic valve and root is associated with high risk requiring thoughtful surgical decision-making. The impact of valve and conduit choices and patient factors on long-term outcomes in this patient population is poorly documented. METHODS: From January 1976 to December 2013, 485 patients underwent aortic root and valve replacement at a single institution. Cox's proportional hazard model identified predictors of long-term survival and cumulative incidence functions were compared to assess need for reoperation with death as a competing risk. RESULTS: Median age at time of operation was 56.6 years (interquartile range: 23.1) with the indication for operation being endocarditis in 14.6% (n = 71). Stentless root replacement was used in 70% IE versus 34% non-IE (p < .001). Endocarditis at time of root replacement did not have a significant impact on survival through 15 years (IE: 37.3% vs. non-IE: 42.5%; log-rank; p = .13). After multivariable adjustment, survival was similar between patients with and without endocarditis (hazard ratio: 1.1; 95% confidence interval: [0.77, 1.62]; p = .57). Freedom from reoperation at 15 years did not vary significantly by endocarditis status (IE: 95.9% vs. non-IE: 73.6%; p = .07). Among endocarditis patients, freedom from reoperation at 10 years was similar between homograft and stentless bioprosthetic conduits (95.3% vs. 88.5%; log-rank; K-sample; p = .46). CONCLUSIONS: In a sample with frequent use of stentless prostheses, aortic root replacement for infective endocarditis had acceptable risk and long-term survival similar to root replacement for other indications. In the setting of endocarditis, root replacement with homograft or stentless bioprosthetic root has excellent durability through 15 years.

Synergy between early-incorporation immunotherapy and extracranial radiotherapy in metastatic non-small cell lung cancer.

BACKGROUND: Combining radiotherapy (RT) and immunotherapy (IT) may enhance outcomes for metastatic non-small cell lung cancer (mNSCLC). However, data on the immunomodulatory effects of extracranial RT remains limited. This retrospective database analysis examined real-world practice patterns, predictors of survival, and comparative effectiveness of extracranial radioimmunotherapy (RT + IT) versus early-incorporation immunotherapy (eIT) in patients with mNSCLC. METHODS: Patients diagnosed with mNSCLC between 2004-2016 treated with eIT or RT + IT were identified in the National Cancer Database. Practice patterns were assessed using Cochrane-Armitrage trend test. Cox proportional hazards and Kaplan-Meier method were used to analyze overall survival (OS). Propensity score matching was performed to account for baseline imbalances. Biologically effective doses (BED) were stratified based on the median (39 Gy10). Stereotactic body radiotherapy (SBRT) was defined as above median BED in ≤5 fractions. RESULTS: eIT utilization increased from 0.3% in 2010 to 13.2% in 2016 (P<0.0001). Rates of RT + eIT increased from 38.8% in 2010 to 49.1% in 2016 among those who received eIT (P<0.0001). Compared to eIT alone, RT + eIT demonstrated worse median OS (11.2 vs. 13.2 months) while SBRT + eIT demonstrated improved median OS (25 vs. 13.2 months) (P<0.0001). There were no significant differences in OS based on sequencing of eIT relative to RT (log-rank P=0.4415) or irradiated site (log-rank P=0.1606). On multivariate analysis, factors associated with improved OS included chemotherapy (HR 0.86, P=0.0058), treatment at academic facilities (HR 0.83, P<0.0001), and SBRT (HR 0.60, P=0.0009); after propensity-score multivariate analysis, SBRT alone showed improved OS (HR 0.28, P<0.0001). CONCLUSIONS: Utilization of RT + eIT in mNSCLC is increasing. SBRT + eIT was associated with improved OS on propensity-score matched analysis. There were no significant differences in OS based on RT + eIT sequencing or site irradiated. Whether these observations reflect patient selection or possible immunomodulatory benefits of RT is unclear and warrants further study.

Off-study utilization of experimental therapies: Analysis of GOG249-eligible cohorts using real world data.

OBJECTIVE: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. METHODS: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. RESULTS: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.

International Funding for Global Common Goods for Health: An Analysis Using the Creditor Reporting System and G-FINDER Databases.

West Africa's Ebola epidemic of 2014-2016 exposed, among other problems, the under-funding of transnational global health activities known as global common goods for health (CGH), global functions such as pandemic preparedness and research and development (R&D) for neglected diseases. To mobilize sustainable funding for global CGH, it is critical first to understand existing financing flowing to different types of global CGH. In this study, we estimate trends in international spending for global CGH in 2013, 2015, and 2017, encompassing the era before and after the Ebola epidemic. We use a measure of international funding that combines official development assistance (ODA) for health with additional international spending on R&D for diseases of poverty, a measure called ODA+. We classify ODA+ into funding for three global functions-provision of global public goods, management of cross-border externalities, and fostering of global health leadership and stewardship-and country-specific aid. International funding for global functions increased between 2013 and 2015 by $1.4 billion to a total of $7.3 billion in 2015. It then declined to $7.0 billion in 2017, accounting for 24% of all ODA+ in 2017. These findings provide empirical evidence of the reactive nature of international funders for global CGH. While international funders increased funding for global functions in response to the Ebola outbreak, they failed to sustain that funding. To meet future global health challenges proactively, international funders should allocate more funding for global functions.

Wnt pathway in atypical teratoid rhabdoid tumors.

BACKGROUND: Atypical teratoid rhabdoid tumor (ATRT) is an aggressive pediatric brain tumor with limited therapeutic options. The hypothesis for this study was that the Wnt pathway triggered by the Wnt5B ligand plays an important role in ATRT biology. To address this hypothesis, the role of WNT5B and other Wnt pathway genes was analyzed in ATRT tissues and ATRT primary cell lines. METHODS: Transcriptome-sequencing analyses were performed using nanoString platforms, immunohistochemistry, Western blotting, quantitative reverse transcriptase PCR, immunoprecipitation, short interference RNA studies, cell viability studies, and drug dose response (DDR) assays. RESULTS: Our transcriptome-sequencing results of Wnt pathway genes from ATRT tissues and cell lines indicated that the WNT5B gene is significantly upregulated in ATRT samples compared with nontumor brain samples. These results also indicated a differential expression of both canonical and noncanonical Wnt genes. Imunoprecipitation studies indicated that Wnt5B binds to Frizzled1 and Ryk receptors. Inhibition of WNT5B by short interference RNA decreased the expression of FRIZZLED1 and RYK. Cell viability studies a indicated significant decrease in cell viability by inhibiting Frizzled1 receptor. DDR assays showed promising results with some inhibitors. CONCLUSIONS: These promising therapeutic options will be studied further before starting a translational clinical trial. The success of these options will improve care for these patients.