Year Of Life Research Articles

Cost-effectiveness of atezolizumab plus Bevacizumab as first-line therapy for metastatic renal cell carcinoma

ABSTRACT Objectives Recently, the IMmotion151 trial evaluated the safety and efficacy of atezolizumab plus bevacizumab in metastatic renal cell carcinoma (mRCC) and found that this combination led to longer progression-free survival. However, no studies have evaluated the cost-effectiveness of atezolizumab plus bevacizumab. Methods We constructed a Markov model to evaluate the cost-effectiveness of atezolizumab plus bevacizumab, using costs and utilities from the published studies. We set the willingness-to-pay (WTP) threshold at $150,000. One-way and probabilistic sensitivity analyses were performed to ensure that our results were robust. We performed a threshold analysis to explore a more appropriate price for atezolizumab. Results Our results found that although atezolizumab plus bevacizumab provided more quality-adjusted life years (QALYs), its incremental cost-effectiveness ratio (ICER) was $1,640,532/QALY, well above the WTP threshold. One-way and probabilistic sensitivity analysis results confirmed the robust of this conclusion. Based on the threshold analysis, for atezolizumab plus bevacizumab to be cost-effective, the price of them would need to be reduced by 46.3% or more. Conclusions From the perspective of US payers, atezolizumab plus bevacizumab is not cost-effective for mRCC patients. To make this combination cost-effective in the future, the price of atezolizumab and bevacizumab needs to be reduced.

Hand-Arm Bimanual Intensive Therapy Including Lower Extremities in Infants With Unilateral Cerebral Palsy

ImportanceEarlier detection of cerebral palsy (CP) and the high neuroplastic potential during the first years of life have motivated a search for early interventions to improve children’s long-term motor abilities.ObjectiveTo determine the effectiveness of baby Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) to improve motor function in infants with unilateral CP (UCP).Design, Setting, and ParticipantsThis parallel group, 1:1, randomized clinical trial was conducted between December 1, 2020, and September 9, 2022, in infants recruited through centers specializing in CP treatment and parents’ spontaneous applications. Therapy took place in Brussels, Belgium, from March 8, 2021, through June 17, 2022. Infants were matched in pairs by age and lesion type and randomized to either the treatment or control group. Infants were assessed at baseline (T0) and 1 (T1) and 3 months (T2) follow-up. Inclusion criteria were aged 6 to 18 months at T0 (corrected age if preterm birth), a diagnosis or being at risk of UCP, and the ability to comply with the testing and training procedures. Exclusion criteria were uncontrolled seizures, botulinum toxin injections, orthopedic surgery, or specific intensive therapy within 6 months before and until the end of the study.InterventionInfants in the treatment group received 50 hours of baby HABIT-ILE over 2 weeks, while those in the control group continued their usual motor activities.Main Outcomes and MeasuresThe primary outcome was use of the more affected hand as measured using the Mini-Assisting Hand Assessment (Mini-AHA). Secondary outcomes included Canadian Occupational Performance Measure (COPM) performance and satisfaction scores, Gross Motor Function Measure-66 (GMFM-66) scores, and other motor and functional outcomes. Between-group comparisons were calculated using repeated-measures analysis of variance (2 groups × 3 assessment times). Effect sizes were reported as partial η squared (ηp2) (small, 0.01; medium, 0.06; large, 0.14).ResultsOf the 48 infants entering the study, 46 (mean [SD] age, 13.3 [4.1] months; 27 boys [58%]) were included in the final analyses, with 24 in the treatment group and 22 in the control group. Group × assessment time interactions showed significant improvements that favored the treatment group for the Mini-AHA (mean [SE] difference from T0 to T2, 7.4 [1.4] Mini-AHA units in the treatment group vs 1.9 [1.5] Mini-AHA units in the control group; P = .008; ƞp2 = 0.11) and for both parts of the COPM (mean [SE] difference from T0 to T2, 5.0 [0.4] in the treatment group vs 2.9 [0.4] in the control group; P < .001; ƞp2 = 0.35 for the performance score and 4.4 [0.4] in the treatment group vs 2.1 [0.4] in the control group; P < .001; ƞp2 = 0.33 for the satisfaction score). Although both groups improved in the GMFM-66 (mean [SE] difference from T0 to T2, 6.6% [0.7%] logits in the treatment group vs 5.5% [0.7%] logits in the control group; P < .001; ηp2 = 0.68), there was no significant interaction (P = .43; ηp2 = 0.02).Conclusions and RelevanceThis randomized clinical trial demonstrates the feasibility of delivering 50 hours of HABIT-ILE over a 2-week period in infants with UCP. These findings show that the intervention is effective in improving motor abilities, as revealed by an increase in the use of the more affected hand in bimanual tasks and in enhanced reported functional goal outcomes.Trial RegistrationClinicalTrials.gov Identifier: NCT04698395

Cost-effectiveness analysis of mHealth applications for depression in Germany using a Markov cohort simulation

AbstractRegulated mobile health applications are called digital health applications (“DiGA”) in Germany. To qualify for reimbursement by statutory health insurance companies, DiGA have to prove positive care effects in scientific studies. Since the empirical exploration of DiGA cost-effectiveness remains largely uncharted, this study pioneers the methodology of cohort-based state-transition Markov models to evaluate DiGA for depression. As health states, we define mild, moderate, severe depression, remission and death. Comparing a future scenario where 50% of patients receive supplementary DiGA access with the current standard of care reveals a gain of 0.02 quality-adjusted life years (QALYs) per patient, which comes at additional direct costs of ~1536 EUR per patient over a five-year timeframe. Influencing factors determining DiGA cost-effectiveness are the DiGA cost structure and individual DiGA effectiveness. Under Germany’s existing cost structure, DiGA for depression are yet to demonstrate the ability to generate overall savings in healthcare expenditures.

Projected Cost Savings With Optimal Medication Adherence in Patients With Cardiovascular Disease Requiring Lipid-Lowering Therapy: A Multinational Economic Evaluation Study.

Poor adherence to chronic cardiovascular treatments can impede targeted clinical outcomes. This study estimates the potential benefits of improving adherence among patients with cardiovascular disease requiring secondary prevention in Mexico, Thailand, and China. We performed Markov model simulation for patients with cardiovascular disease in 3 countries from health care and societal perspectives over a lifetime horizon. Two scenarios were compared: (1) optimal adherence based on a meta-analysis of 51 randomized controlled trials and (2) status quo. The association between adherence and cardiovascular disease outcomes derives from a dose-response meta-analysis of 4 051 338 patients. Outcomes include the accumulated number of cardiovascular events and associated costs in 2022 US dollars, life years, and quality-adjusted life years. Optimal adherence could prevent 42 (95% credible interval [CrI], 29-56) cardiovascular events in Mexico, 34 (95% CrI, 24-50) in Thailand, and 63 (95% CrI, 43-89) in China per 1000 patients over a lifetime. Incremental effectiveness per patient was 0.60 (95% CrI, 0.47-0.74) life-years in Mexico, 0.68 (95% CrI, 0.37-0.94) quality-adjusted life years in Thailand, and 0.93 (95% CrI, 0.44-1.27) quality-adjusted life years in China. Cost savings from societal perspective amounted to $412 (95% CrI, $211-$723), $316 (95% CrI, $187-$541), and $700 (95% CrI, $355-$1144) per patient for Mexico, Thailand, and China, respectively. Findings remained cost saving in deterministic and probabilistic sensitivity analyses. Achieving optimal adherence in patients with cardiovascular disease requiring lipid-lowering therapy saves costs and improves health outcomes in Mexico, Thailand, and China. These findings support national health care systems implementing strategies to improve adherence in these countries.

Neuroeducación en el aula

The present study seeks to establish the way in which neuroeducation can be used in classroom activities through a documentary review. Where it was found that early childhood is a fundamental stage of human development and, therefore, the Ministry of Education has given high priority to children from their conception to their first years of life. At this time, the brain undergoes an irreversible transformation. For it to grow and develop, going through sensitive moments for the acquisition of certain specific learning, millions of phenomenal neural connections are created. For this reason, it requires that external stimuli be of high quality, allowing children to live experiences according to each need, using physical resources and multisensory tools. It is crucial to understand that the brain develops properly considering the harmonious interaction between genetics and environmental cues. For this reason, the experiences lived by children are crucial because they allow the brain development process to be adjusted, resulting in positive or negative outcomes depending on whether adults are present in children’s lives.

Cost Effectiveness of Tremelimumab Plus Durvalumab for Unresectable Hepatocellular Carcinoma in the USA.

Treating unresectable hepatocellular carcinoma (uHCC) is challenging. Clinical trials have shown that Single Tremelimumab Regular Interval Durvalumab (STRIDE) offers clinical benefits as a first-line treatment for uHCC, but its cost effectiveness remains unknown in the USA. We aimed to assess the cost effectiveness of STRIDE (tremelimumab plus durvalumab) versus sorafenib and durvalumab monotherapy as the first-line treatment for uHCC in the USA. A partitioned survival model was constructed to assess the cost effectiveness of STRIDE compared to sorafenib and durvalumab monotherapy as the first-line treatment for uHCC from the US societal perspective. The time horizon was 48 months with 1-month cycles. Seven parametric survival functions replicated survival curves from clinical trials, with the best-fitting model used to calculate survival probabilities. Costs, health utilities, and adverse events were included, with quality-adjusted life-years (QALYs) as the primary effectiveness measure. Both costs and effectiveness were discounted at 3%. In the base-case analysis, the incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $150,000 per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to examine the uncertainty of the model. In the base-case analysis, STRIDE was cost effective compared to sorafenib, with an incremental cost-effectiveness ratio of $97,995.51 per QALY gained, based on a willingness-to-pay threshold of $150,000 per QALY gained. However, STRIDE was not cost effective compared to durvalumab monotherapy at the same threshold, with an incremental cost-effectiveness ratio of $754,408.92 per QALY gained. Deterministic sensitivity analyses were consistent with the base-case analysis. A probabilistic sensitivity analysis indicated that STRIDE was more likely to be cost effective than sorafenib and durvalumab monotherapy when the willingness-to-pay exceeded $101,000 and $713,000, respectively. The STRIDE regimen appears to be cost effective compared to sorafenib but not compared to durvalumab for first-line uHCC treatment in the USA. However, durvalumab has not yet been approved for uHCC in the USA. Future research should focus on long-term data and economic evaluations of other recommended biologics.

Evaluation of the osteoarthritis disease burden in China from 1990 to 2021: based on the Global Burden of Disease Study 2021

ObjectiveThis study aims to understand the current status and trend of the disease burden of osteoarthritis (OA) in people over 30 years old in China from 1990 to 2021 and identify the priority population groups, to provide reference data for the prevention and treatment of OA in China.MethodsThe Global Burden of Disease Study 2021 was used to describe the incidence, prevalence, and disability-adjusted life years (DALYs) of OA in adult aged 30 years or older in China by sex and age groups, which was used to analyze the disease burden of OA from 1990 to 2021. The joinpoint regression model and age-period-cohort model were used to characterize the temporal trend.ResultsIn 2021, the number of OA prevalence in China was about 152.85 million, and the number of incidences was about 11.65 million. The age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR) and age-standardized DALYs rate (ASDR) of OA in China are lower than those in developed countries such as Korea, the United States of America and Japan, but higher than those in India. Knee osteoarthritis had the highest ASPR and ASDR. The highest incidence rate was 50–54 years, and the highest prevalence and DALYs rate were in the age group of patients over 95 years old. The incidence rate of women in all age groups is higher than that of men. From 1990 to 2021, the ASIR, ASPR and ASDR of OA in China roughly showed an increasing trend year by year. The age-period-cohort analysis showed that the peak age groups for longitudinal age incidence of OA in China from 1992 to 2021 were 50–54 years and 80–84 years. We found that the OA incidence was highest in the period 2017–2021.ConclusionThe disease burden of OA in those over 30 years old in China from 1990 to 2021 will become more and more serious, and the target population for primary prevention is the female population under 50 years old. The development of a scientific and effective comprehensive prevention and treatment program for OA is imminent.

Projected epidemiological trends and burden of liver cancer by 2040 based on GBD, CI5plus, and WHO data.

Incidence of liver cancer as one of the most common cancers worldwide and become the significant contributor for the mortality among cancer patients. The disease burden, risk factors, and trends in incidence and mortality of liver cancer globally was described subsequently estimated the projections of liver cancer incidence or mortality by 2040. Data regarding age-standardized incidence and mortality rates for liver cancer was obtained from multiple databases, including GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD)-2019. Concentrating on worldwide variations, this thorough analysis offers insights into patterns of incidence and mortality based on gender and age. Our findings encompass significant indicators, including age-standardized rates (ASRs), average annual percentage change (AAPC), and future projections extending up to the year 2040. Liver cancer holds the sixth position in terms of most frequently diagnosed cancers and stands as the sixth leading cause of cancer-related deaths worldwide in 2020, accounting for 905,677 new cases and 782,000 fatalities. Additionally, liver cancer contributed to 12,528,421 age-standardized disability-adjusted life years (DALYs), with an age-standardized DALYs rate of 161.92 in 2019 worldwide. The age-specific incidence rates exhibited significant variations across different regions, showing a fivefold difference in males and females. A significant increase in incidence was observed in North Europe and Asia, while North African countries reported a higher mortality burden (ASR, 10 per 100,000) compared to developed countries. Since last few years, the incidence and mortality rates have increased and attained Annual Average Percentage Change (AAPC) incidence rate of 7.7 (95% CI 3.9-11.6) for men and the highest AAPC mortality rate of 12.2 (95% CI 9.5-15.0) for women. In 2019, Western Europe emerged as the high-risk region for DALYs related to smoking and alcohol consumption, while high-income North America carried a high risk for DALYs associated with a high body-mass index. The projected trend indicates a surge in new liver cancer incident cases, expected to rise from around 905,347 to an estimated 1,392,474 by 2040. This study described the evidence pertinent to higher incidence trends in liver cancer, particularly among both young and older adults, encompassing males and females, as well as those who are HIV-infected and HBsAg positive. A significant rise in the young population poses a significant public health concern that warrants attention from healthcare professionals to prioritize the promotion of health awareness and the development of effective cancer prevention strategies, particularly in many developing countries.

Comparison of clinical outcomes and cost-utility between unilateral biportal endoscopic discectomy and percutaneous endoscopic interlaminar discectomy for single-level lumbar disc herniation: a retrospective matched controlled study.

This study aimed to compare the efficacy and cost-utility of unilateral biportal endoscopy (UBE) versus percutaneous endoscopic interlaminar discectomy (PEID) for the treatment of single-level lumbar disc herniation (LDH). A retrospective analysis was conducted on 99 patients who underwent either UBE (n = 33) or PEID (n = 66) between July 2022 and December 2023 at the Second Xiangya Hospital. Patients were matched 1:2 based on age, sex, and surgery level to ensure comparability. Clinical outcomes were assessed using Visual Analog Scale (VAS), European Quality of Life-5 Dimensions (EQ-5D), and Oswestry Disability Index (ODI) scores, with quality-adjusted life years (QALYs) calculated for cost-utility analysis. Hospitalization costs were analyzed, and the incremental cost-utility ratio (ICER) was determined. Both UBE and PEID groups demonstrated significant postoperative improvements in VAS, EQ-5D, and ODI scores (p < 0.05). The operative time, blood loss and nursing cost were significantly higher for UBE compared to PEID (p < 0.05). UBE has higher gained QALY and overall costs, but the differences are not statistically significant (p = 0.643 for QALY, p = 0.327 for costs). The Incremental Cost-Effectiveness Ratio (ICER) for UBE compared to PEID was calculated to be $354.5 per QALY gained, indicating that for each additional QALY gained through UBE, an additional cost of $354.5 is incurred compared to PEID. In our single-center study conducted in China, both the UBE and PEID procedures have demonstrated comparable short-term efficacy in alleviating pain and improving functional ability in patients with single-level LDH. UBE procedure demonstrates greater cost-utility than the PEID procedure in cost-utility analysis, despite its longer operative time, higher nursing costs and greater blood loss.

Cost-Effectiveness of Computer-Assisted Cognitive Behavioral Therapy for Depression Among Adults in Primary Care.

Approximately 1 in 5 adults are diagnosed with depression in their lifetime. However, less than half receive help from a health professional, with the treatment gap being worse for individuals with socioeconomic disadvantage. Computer-assisted cognitive behavioral therapy (CCBT) is an effective and convenient strategy to treat depression; however, its cost-effectiveness in a sociodemographically diverse population remains unknown. To evaluate the cost-effectiveness of clinician-supported CCBT compared with treatment as usual (TAU) in a primary care population with a substantial number of patients with low income, limited computer or internet access, and lack of college education. This economic evaluation was a randomized clinical trial-based cost-effectiveness analysis. The trial was conducted at the Departments of Family and Geriatric Medicine and Internal Medicine at the University of Louisville. Enrollment occurred from June 24, 2016, to May 13, 2019. Participants had mild to moderate depression and were followed up for 6 months after treatment completion. The last follow-up assessment was conducted on January 30, 2020. Statistical analysis was performed from August 2023 to August 2024. CCBT intervention was provided for 12 weeks and included 9 modules ranging from behavioral activation and cognitive restructuring to relapse prevention strategies, supported by telephonic sessions with a clinician, in addition to TAU, which included standard clinical management in primary care. The primary health outcome was quality-adjusted life years (QALYs), estimated using the Short-Form 12 questionnaire (SF-12). The secondary outcome was treatment response, defined as at least 50% improvement in the Patient Health Questionnaire. The intervention cost included sessions with mental health clinicians and the cost of the CCBT software, plus the cost of loaner computer and internet data plan for low-resource households. An incremental cost-effectiveness ratio (ICER) was computed, while adjusting for baseline scores, age, and sex. The cost-effectiveness acceptability curve presented the probability of CCBT being cost-effective for a range of willingness-to-pay values. Among the 175 primary care patients included in this study, 148 (84.5%) were female; 48 (27.4%) were African American, 2 (1.2%) were American Indian or Alaska Native, 4 (2.5%) were Hispanic, 106 (60.5%) were White, and 15 (8.6%) were multiracial; and the mean (SD) age was 47.03 (13.15) years. CCBT was associated with better quality of life and higher chance of treatment response at the posttreatment and 6-month time points, compared with the TAU group. The ICER for CCBT was $37 295 (95% CI, $22 724-$66 546) per QALY, with a probability of 89.4% of being cost-effective at a willingness-to-pay threshold of $50 000/QALY. The ICER per case of treatment response was $3623 (95% CI, $2617-$5377). In this trial-based economic evaluation, CCBT was found to be cost-effective, compared with TAU, in primary care patients with depression. As this study included individuals with low income and with limited internet access who are underrepresented in cost-effectiveness studies, it has important policy implications for addressing unmet needs in sociodemographically diverse populations.

Cost-effectiveness of high-dose vitamin D supplementation to reduce the occurrence of repeat episodes of pneumonia in children.

Despite the growing evidence on efficacy, little is known regarding the efficiency of Vitamin D supplementation (VDS) to reduce the incidence of repeat episodes of pneumonia in children. This study aimed to determine the cost-utility of VDS to reduce the incidence rate of repeat episodes of pneumonia in children. A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of VDS in a patient aged 2 to 60 months with a clinical diagnosis of community-acquired pneumonia requiring in-hospital management. Multiple sensitivity analyses were conducted to evaluate the robustness of the model. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. The QALYs per person were 0,93 with VDS and 0,92 without VDS. The total costs per person were US$ 1148 for VDS and US$ 1284 without VDS. This position of absolute dominance of VDS makes it unnecessary to estimate the incremental cost-effectiveness ratio. The ICER was sensitive to changes in the relative risk of Vitamin D supplementation. In conclusion, our study shows that VDS is a cost-effective to reduce the incidence rate of repeat episodes of pneumonia in children, from a societal perspective. However, the sensitivity of ICER to relative risk makes it necessary to take the results of this economic evaluation with caution.

Correlations between Sociodemographic Status, Attitude, Cultural Belief, and Family Support towards Complementary Feeding Practices

Introduction: Proper nutrition is crucial during the first two years of life, as this period is a "critical window" for promoting optimal growth, health, and behavioral development. Complementary feeding refers to the introduction of additional foods and liquids when breast milk alone no longer meets an infant's nutritional needs. Providing adequate and appropriate complementary foods, along with proper feeding practices, can help prevent stunting and promote healthy eating habits. Objective: This study aimed to identify the factors correlated with complementary feeding practices (i.e., MDD, MMF, MAD, and SSSFs) among children aged 6–23 months in Surakarta City. Method: This cross-sectional study involved 110 mothers with children aged 6-23 months. Data were collected through questionnaires interviewed directly to the respondents. The variables in this study included the child’s age, the mother’s age, parity, maternal education level, maternal employment status, attitude, cultural beliefs, and family support. Complementary feeding practices were assessed using the composite indicators such as MDD, MMF, MAD, SSSFs as recommended by the WHO. Result: This study identified that child's age (0.012 (OR: 3.71, CI: 1.28-10.75)), mother's age (0.001 (OR: 9.35, CI: 2.06-42.37)), parity (0.003 (OR: 4.16, CI: 1.54-11.21)), mother's education (0.018 (OR: 3.06, CI: 1.18-7.90)), attitude (0.028 (OR: 4.93, CI: 1.05-23.0)), cultural belief (0.000 (OR: 9.00, CI: 2.52-32.0)), and family support (0.000 (OR: 5.39, CI: 2.17-13.35)) were determinant factors of complementary feeding practice. There was no statistically significant correlation between the mother’s employment status and complementary feeding practices. Conclusion: It is essential to educate mothers on the correct timing and process of transitioning to complementary feeding. Nutrition education should aim to enhance and correct knowledge and beliefs about these practices. Mothers should receive practical guidance on making informed decisions, considering factors such as affordability, availability, access, and the preparation of nutrient-dense foods

First Trimester Tetracycline Exposure and Risk of Major Congenital Malformations.

Safety data on tetracycline antibiotic use during pregnancy are limited. To investigate the association between first trimester exposure to tetracyclines and the risk of major congenital malformations (MCMs). This cohort study used data from nationwide registers for singleton infants live-born in Sweden from July 1, 2006, to December 31, 2018, with follow-up through December 2019. Tetracycline-exposed and unexposed infants were matched on propensity scores (ratio 1:10). Data analysis was performed from June 2023 to May 2024. First trimester exposure to tetracyclines determined from maternal prescription fills, compared with no exposure. The primary outcome was any MCM diagnosed in the first year of life; secondary outcomes were 12 major malformation organ system subgroups and 16 individual malformations selected on the basis of prior safety signals and/or fulfillment of prespecified statistical power criteria. Malformations were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes aligned to the European Surveillance of Congenital Anomalies (EUROCAT) classification. Log binomial regression was used to estimate relative risks (RRs) with 95% CIs. From a source cohort of 1 245 889 eligible infants (640 892 male [51.4%]), a propensity score-matched analytical cohort of 69 656 infants (35 903 male [51.5%]) was generated. Of 6340 infants exposed to tetracyclines during the first trimester (3325 male [52.4%]), 252 received a diagnosis of any MCM (39.75 cases per 1000 infants; 95% CI, 35.14-44.93 cases per 1000 infants) compared with 2454 of 63 316 unexposed infants (38.76 cases per 1000 infants; 95% CI, 37.27-40.30 cases per 1000 infants). Tetracycline exposure was not associated with any MCM (RR, 1.03; 95% CI, 0.90-1.16). The RRs for specific tetracycline substances were 1.07 (95% CI, 0.93-1.23) for doxycycline, 0.83 (95% CI, 0.60-1.15) for lymecycline, and 0.78 (95% CI, 0.32-1.92) for tetracycline-oxytetracycline. There was no increased risk for 10 of 12 malformation subgroups or for any of the 16 individual malformations analyzed. The higher RRs in the main analysis for nervous system anomalies (1.92; 95% CI, 0.98-3.78) and eye anomalies (1.76; 95% CI, 1.07-2.91) were attenuated in a sensitivity analysis with follow-up extended to age 3 years (nervous system anomalies, RR, 1.08; 95% CI, 0.52-2.24; eye anomalies, RR, 1.42; 95% CI, 0.88-2.29). In this cohort study, first trimester tetracycline exposure was not associated with increased risks of any MCMs. Additional studies are needed to rule out potential risks owing to power limitations for several MCM subgroups and individual malformations.

The Health and Economic Effects of PCV15 and PCV20 During the First Year of Life in the US

The Health and Economic Effects of PCV15 and PCV20 During the First Year of Life in the US

Trends of extreme hyperbilirubinemia related infant mortality in select European countries (1990-2019).

Limited data exist on population-level mortality outcomes related to extreme neonatal hyperbilirubinemia (EHB) and this study examines trends in annual infant mortality rate (IMR) attributed to hemolytic and perinatal jaundice among Germany, France, Italy, Portugal, Greece and Spain from 1990 to 2019. Data on annual incident cases and disability-adjusted life years were collected from the 2019 Global Burden of Disease study. Live birth cohort data were sourced from UN World Population Prospects. We quantified temporal trends, with relative percent changes. Average annual percent changes (AAPCs) were evaluated using the Joinpoint Regression Program. EHB-related infant mortality decreased from 21.4 (95%CI: 16.1, 27.1) in 1990 to 4.2 (95%CI: 1.9, 7.6) per million live births in 2019. Germany demonstrated lowest AAPC of -3.2% (95% CI: -3.8, -2.5), while Portugal had the highest AAPC of -8.6% (95% CI -11.9, -5.1) in reducing infant mortality due to EHB. There were distinct divergences in the trajectories of declining EHB mortality among the studied countries. This study highlights a significant decline in infant mortality due to extreme hyperbilirubinemia, emphasizing the need for national surveillance and tailored guidelines to prevent bilirubin induced neurological damage. This cross-sectional analysis revealed a marked decline in infant mortality rates attributed to extreme hyperbilirubinemia across the selected European countries. The rates of decline varied significantly between countries, demonstrating notable heterogeneity in mortality trends when stratified by age at death. Implementing data-driven surveillance systems can optimize the alignment of equitable healthcare services, strengthen accountability measures, and identify critical operational inefficiencies. In the European Union, country-specific hyperbilirubinemia guidelines should be reinforced to ensure effective screening and post-discharge follow-up protocols that are tailored to risk burden and available healthcare resources.

Disease burden of Parkinson's disease in Asia and its 34 countries and territories from 1990 to 2021: findings from the Global Burden of Disease Study 2021.

The increasing global population and aging have made Parkinson's disease (PD) a significant public health concern. Comprehensive evaluations of PD burden trends in Asian subregions and countries are lacking. This study investigated PD burden in Asia from 1990 to 2021, categorized by age, sex, and region. Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 were analyzed to assess the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) across five Asian subregions and 34 countries/territories, using join-point regression, decomposition analysis, frontier analysis, and Bayesian models to examine changes, influencing factors, and predict future trends. In 2021, the age-standardized PD incidence and prevalence in Asia were higher than the global average, particularly in East Asia (24.16 and 243.46/100,000, respectively). From 1990 to 2021, the incidence of PD in Asia rose by 198.01%, its prevalence rose by 284.35%, mortality rose by 111.27%, and DALY rose by 144.45%. Males consistently presented a greater PD burden than females did, with a growing sex gap over time. PD burden increased with age, especially among those aged 65 years and older. Population aging was the primary driver of new PD cases, and increasing etiological factors led to more patients. Inequalities in the PD burden have increased between high- and low-income areas, with low-income regions being more affected. By 2036, PD incidence is projected to increase in all subregions except the High-income Asia-Pacific region, with males experiencing a higher rate of increase. The PD burden in Asia has significantly increased over the past three decades, particularly in middle-aged and elderly males, middle- and low-SDI countries, and individuals already suffering from PD. The increasing incidence and aging population necessitate the reallocation of medical resources, improved chronic disease management systems, stronger public health interventions, and sustainable development efforts. Research into etiological factors, pathogenesis, early diagnosis, preventive interventions, and regional management is critical.

Cost-effectiveness analysis of trifluridine/tipiracil combined with bevacizumab vs. monotherapy for third-line treatment of colorectal cancer

BackgroundThe combination of trifluridine/tipiracil (FTD/TPI) and bevacizumab has demonstrated promising efficacy and safety in the treatment of colorectal cancer (CRC). This study aims to evaluate the cost-effectiveness of trifluridine/tipiracil combined with bevacizumab vs. trifluridine/tipiracil monotherapy as a third-line treatment regimen for colorectal cancer within the Chinese healthcare system, providing an economic basis for clinical application.MethodsBased on data from the SUNLIGHT Phase III clinical trial, a dynamic Markov model was constructed with a cycle length of 4 weeks and a simulation duration of 10 years. Direct medical costs and quality-adjusted life years (QALYs) were calculated. The incremental cost-effectiveness ratio (ICER) was compared with the willingness-to-pay threshold (WTP = ¥268,200.00/QALY) to assess the economic viability of the treatment regimen. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to verify the robustness of the model results.ResultsThe cost of trifluridine/tipiracil combined with bevacizumab treatment (¥838,492.74) was higher than that of trifluridine/tipiracil monotherapy (¥357,396.97), with greater health benefits (2.45 QALYs vs. 1.54 QALYs). The ICER was ¥527,577.36/QALY, exceeding the willingness-to-pay threshold. One-way sensitivity analysis indicated that drug costs and utility values during the progression-free period significantly impacted model outputs. Probabilistic sensitivity analysis further confirmed the robustness of the results, showing that at a willingness-to-pay threshold of ¥494,000.00, the probability of the combined treatment being cost-effective was 50%.ConclusionTrifluridine/tipiracil combined with bevacizumab, as a third-line treatment for colorectal cancer, does not have a cost-effectiveness advantage compared to trifluridine/tipiracil monotherapy in economic evaluations.

Cost-effectiveness of Implementing a Genotype-Guided De-Escalation Strategy in Patients with Acute Coronary Syndrome.

A genotype-guided P2Y12-inhibitor de-escalation strategy, switching acute coronary syndrome (ACS) patients without a CYP2C19 loss-of-function allele from ticagrelor or prasugrel to clopidogrel, has shown to reduce bleeding risk without affecting effectivity of therapy by increasing ischemic risk. We estimated the cost-effectiveness of this personalized approach compared to standard dual antiplatelet therapy (DAPT; aspirin plus ticagrelor/prasugrel) in the Netherlands. We developed a one-year decision tree based on results of the FORCE-ACS registry, comparing a cohort of ACS patients who underwent genotyping with a cohort of ACS patients treated with standard DAPT. This was followed by a lifelong Markov model to compare lifetime costs, and quality-adjusted life years (QALYs) for a fictional cohort of 1000 patients. The cost-effectiveness analysis was performed from the perspective of the Dutch healthcare system. A genotype-guided de-escalation strategy led to anincrease of 55.30 QALYs and saved €698,286 compared to standard DAPT based on a lifetime horizon. Probabilistic sensitivity analysis showed that the genotype-guided strategy was cost-saving in 93% and increased QALYs in 86% of simulations. The intervention remained cost-effective in the scenario where prices for all P2Y12-inhibitors were equalized. The genotype-guided strategy remained dominant in various other scenario and sensitivity analyses. A genotype-guided de-escalation strategy in patients with ACS was both cost-saving and yielded higher QALYs compared to standard DAPT, highlighting its potential for implementation in clinical practice. Trial registration: ClinicalTrials.gov identifier: NCT03823547.

OPTIMIZING THE DELIVERY METHOD FOR EXTREMELY PREMATURE BIRTHS

The contemporary classifi cation of premature birth is predicated on the condition of the newborn, encompassing the severity of respiratory disorders, morpho- functional immaturity, prognosis for survival, and long-term consequences. In accordance with these criteria, newborns with a gestational age of up to 28 weeks are classifi ed as extremely premature, given the inherently challenging nature of their weaning process. This article presents the dynamics of early neonatal mortality and lethality indicators in cases of vaginal and abdominal delivery. This article presents an analysis of contemporary global trends in the selection of delivery methods for premature births and extremely premature pregnancies.The aim of the study. To propose a modifi ed approach to the choice of delivery method in pregnant women in the gestational period of 24-28 weeks.Research materials and methods. The analysis was conducted on 350 cases of extremely premature singleton births (within 24-28 weeks) that occurred at the Perinatal Center of Kyiv between 2019 and 2023. A comparison of the early neonatal mortality rate of newborns with a gestational age of 24-28 weeks was conducted, stratifi ed by the method of delivery. The relative risk of mortality during the fi rst seven days and throughout the fi rst year of life, contingent on the method of delivery, was calculated. Furthermore, the frequency of the most common complications of the neonatal period in newborns with extremely low body weight was analyzed, and the relative risk of their development was calculated depending on the method of delivery. The Foster- Stewart test was employed to substantiate the statistical reliability of the obtained results. The two average indicators are then compared with one another using the Student’s test. A value of ≤0.05 indicates statistically signifi cant changes in the indicator’s dynamics. The research was carried out within the framework of the implementation of scientifi c topics of the Department of Obstetrics and Gynecology No. 1 of the Bogomolets National Medical University: Research work «Preservation and restoration of women’s reproductive health in conditions of rapid medical and social changes» implementation period 01.01.2023-12.2024. Research results and their discussion. An analysis of the dynamics of early neonatal mortality in the category of 24-28 gestationalweeks from 2019 to 2023 was conducted, identifying several factors. These included the active implementation of intranatal magnesium therapy and improvements in the quality of neonatal care at the technical level. As evidenced by the data, the rate of early neonatal mortality in very early premature births reached 43.3 % in 2019, declining to 25.5 % by 2022. In the 2019-2020 period, 50 % of neonatal deaths occurring within the fi rst seven days were infants born by caesarean section. The ratio of vaginal births to births by caesarean section in gestational periods up to 28 weeks is approximately 2:1. In addition to the observed reduction in the rate of early neonatal mortality, a two-fold decrease was noted in the rate among children born by caesarean section. The mortality rate of extremely premature infants, despite a gradual decline, remains relatively high, at approximately 34.2 % in 2023. Our fi ndings, based on the expansion of indications for caesarean section rather than its routine use in preterm birth, indicate that the relative risk of neonatal death before seven days for vaginal delivery compared with caesarean section, calculated with a 95 % confi dence interval, was 2.65. Similarly, the calculated riskof mortality during the fi rst year of life is 1.34. With regard to intraventricular hemorrhage, the relative risk was 3.12, indicating that the route of delivery in this cohort of newborns exerts an infl uence on the frequency of the complication. The risk of hemorrhagic syndrome is 0.97, which does not provide suffi cient evidence to suggest that it can be prevented by selecting an abdominal delivery. The proportion of abdominal deliveries at the Perinatal Center has remained relatively stable since the expansion of indications for premature births, with a slight increase from 14.2 % in 2019 to 15.2 % in 2023. This was accomplished through a logical and evidence- based approach to caesarean section in full-term pregnancies.Conclusions. 1.From 2019 to 2023, a notable decline was observed in the incidence of early neonatal mortality (from 43.3 to 23.6 %) and child mortality (from 61.3 % to 34.2 %) among newborns with a gestational age of up to 28 weeks. 2. The incidence of early neonatal mortality up to 28 weeks is lower among newborns delivered by caesarean section than among those delivered vaginally. 3. The optimization of perinatal indicators is contingent upon an individualized approach to the selection of a delivery method for pregnant women with premature rupture of the membranes up to 28 weeks.

Clinical- and Cost-Effectiveness of Liver Disease Staging in Hepatitis C Virus Infection: A Microsimulation Study.

Liver disease assessment is a key aspect of chronic hepatitis C virus (HCV) infection pre-treatment evaluation but guidelines differ on the optimal testing modality given trade-offs in availability and accuracy. We compared clinical outcomes and cost-effectiveness of common fibrosis staging strategies. We simulated adults with chronic HCV receiving care at US health centers through a lifetime microsimulation across five strategies: (1) no staging or treatment (comparator), (2) indirect serum biomarker testing (Fibrosis-4 index [FIB-4]) only, (3) transient elastography (TE) only, (4) staged approach: FIB-4 for all, TE only for intermediate FIB-4 scores (1.45-3.25), and (5) both tests for all. Outcomes included infections cured, cirrhosis cases, liver-related deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We used literature-informed loss to follow-up (LTFU) rates and 2021 Medicaid perspective and costs. FIB-4 alone generated the best clinical outcomes: 87.7% cured, 8.7% developed cirrhosis, and 4.6% had liver-related deaths. TE strategies cured 58.5%-76.6%, 16.8%-29.4% developed cirrhosis, and 11.6%-22.6% had liver-related deaths. All TE strategies yielded worse clinical outcomes at higher costs per QALY than FIB-4 only, which had an ICER of $12 869 per QALY gained compared with no staging or treatment. LTFU drove these findings: TE strategies were only cost-effective with no LTFU. In a point-of-care HCV test-and-treat scenario, treatment without any staging was most clinically and cost-effective. FIB-4 staging alone resulted in optimal clinical outcomes and was cost-effective. Treatment for chronic HCV should not be delayed while awaiting fibrosis staging with TE.