Dosimetric parameters predict radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma patients: A systematic review and meta-analysis.

This systematic review examines the role of dosimetric parameters in predicting temporal lobe necrosis (TLN) risk in nasopharyngeal carcinoma (NPC) patients treated with three-dimensional conformal RT (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). TLN is a serious late complication that can adversely affect the quality of life of NPC patients. Understanding the relationship between dosimetric parameters and TLN can guide treatment planning and minimize radiation-related complications. A comprehensive search identified relevant studies published up to July 2023. Studies reporting on dosimetric parameters and TLN in NPC patients undergoing 3D-CRT, IMRT, and VMAT were included. TLN incidence, follow-up duration, and correlation with dosimetric parameters of the temporal lobe were analyzed. The review included 30 studies with median follow-up durations ranging from 28 to 110 months. The crude incidence of TLN varied from 2.3 % to 47.3 % and the average crude incidence of TLN is approximately 14 %. Dmax and D1cc emerged as potential predictors of TLN in 3D-CRT and IMRT-treated NPC patients. Threshold values of >72 Gy for Dmax and >62 Gy for D1cc were associated with increased TLN risk. However, other factors should also be considered, including host characteristics, tumor-specific features and therapeutic factors. In conclusion, this systematic review highlights the significance of dosimetric parameters, particularly Dmax and D1cc, in predicting TLN risk in NPC patients undergoing 3D-CRT, IMRT, and VMAT. The findings provide valuable insights that can help in developing optimal treatment planning strategies and contribute to the development of clinical guidelines in this field.

Caregiver Perspectives on Barriers and Facilitators to Timely Well-Child Visits for Black Infants.

OBJECTIVES: Missed infant well-child visits (WCV) result in lost opportunities for critical preventive care. Black infants consistently receive less WCV care than other racial groups. We sought to understand barriers and facilitators to timely infant WCV for Black families in the context of COVID-19. METHODS: We conducted 21 semi-structured interviews with caregivers of Medicaid-insured Black children aged 15- to 24-months who attended six or fewer of eight recommended well-child visits within the first 15 months of life. Interviews focused on WCV value, barriers, and facilitators. After developing our initial coding structure through rapid qualitative analysis, we inductively derived the final codebook and themes through line-by-line content analysis. RESULTS: Caregivers attended a mean of 3.53 of eight infant visits. Structural (e.g., transportation) and psychological (e.g., maternal depression) barriers delayed Black infant WCV. Families most frequently valued monitoring development and addressing concerns. Caregivers perceived visits as less urgent when infants seemed healthy or more recently avoided visits due to fears around COVID-19. Long waits and feeling rushed/dismissed were linked to WCV delays; positive provider relationships encouraged WCV attendance. Most caregivers reported reluctance to vaccinate. Vaccine hesitancy contributed to delayed infant WCV. CONCLUSIONS: Caregivers described several factors that impacted WCV attendance for Black infants. Persistent structural and psychological barriers are compounded by perceptions that caregiver time is not respected and by notable vaccine hesitancy. To address these barriers, well-care can meet Black families in their communities, better address caregiver wellbeing, more efficiently use caregiver and provider time, and cultivate partnerships with Black caregivers.

Investing in Child Health Through Alternative Payment Models: Lessons From North Carolina Integrated Care for Kids.

Pediatric value-based payment reform has been hindered by limited return on investment (ROI) for child-focused measures and the accrual of financial benefits to non-health care sectors. States participating in the federally-funded Integrated Care for Kids (InCK) models are required to design child-centered alternative payment models (APMs) for Medicaid-enrolled children. The North Carolina InCK pediatric APM launched in January 2023 and includes innovative measures focused on school readiness and social needs. We interviewed experts at NC Medicaid managed care organizations, NC Medicaid, and actuaries with pediatric value-based payment experience to assess the NC InCK APM design process and develop strategies for future child-focused value-based payment reform. Key principles emerging from conversations included: accounting for payer priorities and readiness to implement measures; impact of data uncertainty on investment in novel measures; misalignment of a short-term ROI framework with whole child health measures; and state levers like mandates and financial incentives to promote implementation.

Axial length elongation profiles from 3 to 6 years in an Asian paediatric population: the Growing Up in Singapore Towards Healthy Outcomes birth cohort study (GUSTO).

AIMS: To determine axial length (AL) elongation profiles in children aged 3-6 years in an Asian population. METHODS: Eligible subjects were recruited from the Growing Up in Singapore Towards Healthy Outcomes birth cohort. AL measurement was performed using IOLMaster (Carl Zeiss Meditec, Jena, Germany) at 3 and 6 years. Anthropometric measurements at birth, cycloplegic refraction at 3 and 6 years, questionnaires on the children's behavioural habits at 2 years and parental spherical equivalent refraction were performed. Multivariable linear regression model with generalised estimating equation was performed to determine factors associated with AL elongation. RESULTS: 273 eyes of 194 children were included. The mean AL increased from 21.72±0.59 mm at 3 years to 22.52±0.66 mm at 6 years (p<0.001). Myopic eyes at 6 years had greater AL elongation (1.02±0.34 mm) compared with emmetropic eyes (0.85±0.25 mm, p=0.008) and hyperopic eyes (0.74±0.16 mm, p<0.001). The 95th percentile limit of AL elongation was 1.59 mm in myopes, 1.34 mm in emmetropes and 1.00 mm in hyperopes. Greater birth weight (per 100 g, ß=0.010, p=0.02) was significantly associated with greater AL elongation from 3 to 6 years, while parental and other behavioural factors assessed at 2 years were not (all p≥0.08). CONCLUSION: In this preschool cohort, AL elongates at an average length of 0.80 mm from 3 to 6 years, with myopes demonstrating the greatest elongation. The differences in 95th percentile limits for AL elongation between myopes, emmetropes and hyperopes can be valuable information in identifying myopia development in preschool children.

Barriers and Facilitators to Implementing Interventions for Reducing Avoidable Hospital Readmission: Systematic Review of Qualitative Studies.

BACKGROUND: Avoidable hospital readmission is a major problem among health systems. Although there are effective peri-discharge interventions for reducing avoidable hospital readmission, successful implementation is challenging. This systematic review of qualitative studies aimed to identify barriers and facilitators to implementing peri-discharge interventions from providers' and service users' perspectives. METHODS: We searched four databases for potentially eligible qualitative studies from databases' inception to March 2020, and updated literature search for studies published between January 2020 to October 2021. Barriers and facilitators to implementing peri-discharge interventions were identified and mapped onto the Consolidated Framework for Implementation Research (CFIR) constructs. Inductive analysis of the CFIR constructs was performed to yield thematic areas that illustrated the relationship between various facilitators and barriers, generating practical insights to key implementation issues. RESULTS: Thirteen qualitative studies were included in this systematic review. Key issues were clustered in the CFIR constructs of Design Quality and Complexity of the intervention, strength of Network and Communication, being responsive to Patient Needs with sufficient Resource support, and External Incentives. The three thematic areas were rationality of the interventions, readiness and effort of multidisciplinary implementation teams, and influence of external stakeholders. Common barriers included (i) limited resources, (ii) poor communication among team members, (iii) incompatibility between the new intervention and existing work routine, (iv) complicated implementation process, (v) low practicality of supporting instruments, and (vi) lack of understanding about the content and effectiveness of the new interventions. Common facilitators were (i) information sharing via regular meetings on implementation issues, (ii) organizational culture that values quality and accountability, (iii) financial penalties for hospitals with high avoidable readmissions rates, (iv) external support offered via quality improvement programs and community resources, and (v) senior leadership support. CONCLUSION: This study synthesized commonly-presenting barriers and facilitators to implementing peri-discharge interventions among different healthcare organizations. Findings may inform development of implementation strategies in different health systems after appropriate tailoring, based on a consensus-based formative research process.

Analysis of North Carolina Medicaid Claims Data to Simulate a Pediatric Accountable Care Organization.

Importance: Despite momentum for pediatric value-based payment models, little is known about tailoring design elements to account for the unique needs and utilization patterns of children and young adults. Objective: To simulate attribution to a hypothetical pediatric accountable care organization (ACO) and describe baseline demographic characteristics, expenditures, and utilization patterns over the subsequent year. Design, Setting, and Participants: This retrospective cohort study used Medicaid claims data for children and young adults aged 1 to 20 years enrolled in North Carolina Medicaid at any time during 2017. Children and young adults receiving at least 50% of their primary care at a large academic medical center (AMC) in 2017 were attributed to the ACO. Data were analyzed from April 2020 to March 2021. Main Outcomes and Measures: Primary outcomes were total cost of care and care utilization during the 2018 performance year. Results: Among 930 266 children and young adults (377 233 children [40.6%] aged 6-12 years; 470 612 [50.6%] female) enrolled in Medicare in North Carolina in 2017, 27 290 children and young adults were attributed to the ACO. A total of 12 306 Black non-Hispanic children and young adults (45.1%), 6308 Hispanic or Latinx children and young adults (23.1%), and 6531 White non-Hispanic children and young adults (23.9%) were included. Most attributed individuals (23 133 individuals [84.7%]) had at least 1 claim in the performance year. The median (IQR) total cost of care in 2018 was $347 ($107-$1123); 272 individuals (1.0%) accounted for nearly half of total costs. Compared with children and young adults in the lowest-cost quartile, those in the highest-cost quartile were more likely to have complex medical conditions (399 individuals [6.9%] vs 3442 individuals [59.5%]) and to live farther from the AMC (median [IQR distance, 6.0 [4.6-20.3] miles vs 13.9 [4.6-30.9] miles). Total cost of care was accrued in home (43%), outpatient specialty (19%), inpatient (14%) and primary (8%) care. More than half of attributed children and young adults received care outside of the ACO; the median (IQR) cost for leaked care was $349 ($130-$1326). The costliest leaked encounters included inpatient, ancillary, and home health care, while the most frequently leaked encounters included behavioral health, emergency, and primary care. Conclusions and Relevance: This cohort study found that while most children attributed to the hypothetical Medicaid pediatric ACO lived locally with few health care encounters, a small group of children with medical complexity traveled long distances for care and used frequent and costly home-based and outpatient specialty care. Leaked care was substantial for all attributed children, with the cost of leaked care being higher than the total cost of care. These pediatric-specific clinical and utilization profiles have implications for future pediatric ACO design choices related to attribution, accounting for children with high costs, and strategies to address leaked care.

The impact of the multi-disciplinary molecular tumour board and integrative next generation sequencing on clinical outcomes in advanced solid tumours.

Background: The integration of next-generation sequencing (NGS) comprehensive gene profiling (CGP) into clinical practice is playing an increasingly important role in oncology. Therefore, the HKU-HKSH Multi-disciplinary Molecular Tumour Board (MTB) was established to advance precision oncology in Hong Kong. A multicenter retrospective study investigated the feasibility of the HKU-HKSH MTB in determining genome-guided therapy for treatment-refractory solid cancers in Hong Kong. Methods: Patients who were presented at the HKU-HKSH MTB between August 2018 and June 2022 were included in this study. The primary study endpoints were the proportion of patients who receive MTB-guided therapy based on genomic analysis and overall survival (OS). Secondary endpoints included the proportion of patients with actionable genomic alterations, objective response rate (ORR), and disease control rate (DCR). The Kaplan-Meier method was used in the survival analyses, and hazard ratios were calculated using univariate Cox regression. Findings: 122 patients were reviewed at the HKU-HKSH MTB, and 63% (n = 77) adopted treatment per the MTB recommendations. These patients achieved a significantly longer median OS than those who did not receive MTB-guided therapy (12.7 months vs. 5.2 months, P = 0.0073). Their ORR and DCR were 29% and 65%, respectively. Interpretation: Our study demonstrated that among patients with heavily pre-treated advanced solid cancers, MTB-guided treatment could positively impact survival outcomes, thus illustrating the applicability of NGS CGPs in real-world clinical practice. Funding: The study was supported by the Li Shu Pui Medical Foundation. Dr Aya El Helali was supported by the Li Shu Pui Medical Foundation Fellowship grant from the Li Shu Pui Medical Foundation. Funders had no role in study design, data collection, data analysis, interpretation, or writing of the report.

Racial/ethnic and sex differences in safety outcomes and atrial fibrillation/atrial flutter-related acute healthcare utilization after catheter ablation of atrial fibrillation.

Background: Catheter ablation is recommended for the treatment of symptomatic atrial fibrillation (AF) refractory to medical therapy. Objective: The study sought to examine racial/ethnic and sex differences in complications and AF/atrial flutter (AFL)-related acute healthcare utilization following catheter ablation for AF. Methods: We performed a retrospective analysis using data from the Centers for Medicare and Medicaid Services Medicare Standard Analytical Files (October 1, 2014, to September 30, 2019) among patients ≥65 years of age with AF who underwent catheter ablation for rhythm control. The risk of any complication within 30 days and AF/AFL-related acute healthcare utilization within 1 year of ablation by race, ethnicity, and sex were assessed using multivariable Cox regression modeling. Results: We identified 95,394 patients for analysis of postablation complications and 68,408 patients for analysis of AF/AFL-related acute healthcare utilization. Both cohorts were ∼95% White and 52% male. Female patients had a slightly elevated risk of complications compared with male patients (adjusted hazard ratio [aHR] 1.07, 95% confidence interval [CI] 1.03-1.12). Black (aHR 0.78, 95% CI 0.77-1.00) and Asian (aHR 0.67, 95% CI 0.50-0.89) patients had lower utilization compared with White patients. Specifically, Asian men (aHR 0.58, 95% CI 0.38-0.91) had lower utilization compared with White men. Conclusion: Differences in safety and healthcare utilization after catheter ablation for AF were observed by race/ethnicity and sex groups. Underrepresented racial and ethnic groups with AF had a lower risk of AF/AFL-related acute healthcare utilization postablation.

Race and Ethnic and Sex Differences in Rhythm Control Treatment of Incident Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with considerable morbidity and mortality. Timely management and treatment is critical in alleviating AF disease burden. Variation in treatment by race and ethnic and sex could lead to inequities in health outcomes. Objective: To identify racial and ethnic and sex differences in rhythm treatment for patients with incident AF. Methods: Using 2010-2019 Optum Clinformatics database, an administrative claims data for commercially insured patients in the United States (US), incident AF patients ≥20 years old who were continuously enrolled 12-months pre- and post-index diagnosis were identified. Rhythm control treatment (ablation, antiarrhythmic drugs [AAD], and cardioversion) for AF were compared by patient race and ethnicity (Asian, Hispanic, Black vs White) and sex (female vs male). Multivariable regression analysis was used to examine the relationship of race and ethnicity and sex with rhythm control AF treatment. Results: A total of 77,932 patients were identified with incident AF. Black and Hispanic female patients had the highest CHA2DS2VASc scores (4.3 ± 1.8) and Elixhauser scores (4.1 ± 2.8 and 4.0 ± 6.7), respectively. Black males were less likely to receive AAD treatment (adjusted odds ratio [aOR] 0.87; 95% confidence interval [CI], 0.79-0.96) or ablation (aOR, 0.72; 95% CI, 0.58-0.90). Compared to White males, all groups had lower likelihood of receiving cardioversion with Asian females having the lowest [aOR, 0.48; 95% CI, (0.37-0.63)]. Conclusion: Black patients were less likely to receive pharmacologic and procedural rhythm control therapies. Further research is needed to understand the drivers of undertreatment among racial and ethnic groups and females with AF.

Contextualizing evidence-based nurse-led interventions for reducing 30-day hospital readmissions using GRADE evidence to decision framework: A Delphi study.

BACKGROUND: High 30-day readmission rates increase hospital costs and negatively impact patient outcomes in many healthcare systems, including Hong Kong. Evidence-based and local adaptable nurse-led interventions have not been established for reducing 30-day hospital readmissions among general medical patients in Hong Kong's public healthcare system. AIMS: The aim of this study was to select and refine evidence-based nurse-led interventions for reducing 30-day hospital readmissions among general medical patients in Hong Kong's public healthcare system using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) framework. METHODS: Eighteen local healthcare stakeholders were recruited to carry out a two-step process. In step 1, stakeholders were invited to prioritize nurse-led interventions which were supported by existing evidence and suggest important combinations of different interventions. For all interventions prioritized in step 1, step 2 involved stakeholders performing a two-round Delphi questionnaire aiming to generate consensus-based interventions appropriate to the local context. GRADE EtD framework was applied to guide the decision-making process, taking into account certainty of evidence, benefits and harms, resource use, equity, acceptability, and feasibility. RESULTS: Four out of eight nurse-led interventions reached a positive consensus with percentage agreement ranging from 70.6% to 82.4%. GRADE EtD criteria ratings showed that over 70% of stakeholders agreed these four interventions were probably acceptable and feasible, though the certainty of evidence was low or moderate. Half of stakeholders believed their desirable effects compared to undesirable effects were large. However, the resources required and how these nurse-led interventions might affect health inequities when implemented were uncertain. Preliminary implementation issues included high complexity of delivering multiple nurse-led intervention components, and challenges of coordinating different involved parties in delivering the interventions. Appropriate resource allocation and training should be provided to address these potential problems, as suggested by stakeholders. LINKING EVIDENCE TO ACTION: Using the GRADE EtD framework, four nurse-led interventions were recommended by healthcare stakeholders as possible strategies for reducing 30-day hospital readmissions among general medical patients in Hong Kong. To address preliminary implementation issues, nurses' role as care coordinators should also be strengthened to ensure smooth delivery of nurse-led intervention components, and to facilitate multidisciplinary collaboration during service delivery.

Changes in the care of acute cerebrovascular and cardiovascular conditions during the first year of the covid-19 pandemic in 746 hospitals in the USA: retrospective analysis.

Objective: To measure the impact of the covid-19 pandemic on admissions to hospital and interventions for acute ischemic stroke and acute myocardial infarction. Design: A retrospective analysis. Setting: 746 qualifying hospitals in the USA from the Premier Healthcare Database. Participants: Patients aged 18 years and older who were admitted to hospital with a primary diagnosis of acute ischemic stroke or acute myocardial infarction between 1 March 2019 and 28 February 2021. Main outcome measures: Relative changes in volumes were assessed for acute ischemic stroke and acute myocardial infarction hospital admissions as well as intravenous thrombolysis, mechanical thrombectomy, and percutaneous coronary intervention (overall and for acute myocardial infarction only) across the first year of the pandemic versus the prior year. Mortality in hospital and length of stay in hospital were also compared across the first year of the pandemic versus the corresponding period the year prior. These metrics were explored across the different pandemic waves. Results: Among 746 qualifying hospitals, admissions to hospital were significantly reduced after the covid-19 pandemic compared with before the pandemic for acute ischemic stroke (-13.59% (95% confidence interval-13.77% to -13.41%) and acute myocardial infarction (-17.20% (-17.39% to -17.01%)), as well as intravenous thrombolysis (-9.47% (-9.99% to -9.02%)), any percutaneous coronary intervention (-17.89% (-18.06% to -17.71%)), and percutaneous coronary intervention for acute myocardial infarction (-14.36% (-14.59% to -14.12%)). During the first year of the pandemic versus the previous year, the odds of mortality in hospital for acute ischemic stroke were 9.00% higher (3.51% v 3.16%; ratio of the means 1.09 (95% confidence interval (1.03 to 1.15); P=0.0013) and for acute myocardial infarction were 18.00% higher (4.81% v 4.29%; ratio of the means 1.18 (1.13 to 1.23); P<0.0001). Conclusions: We observed substantial decreases in admissions to hospital with acute ischemic stroke and acute myocardial infarction, but an increase in mortality in hospital throughout the first year of the pandemic. Public health interventions are needed to prevent these reductions in future pandemics.

Rates and predictors of hospital and emergency department care after catheter ablation of atrial fibrillation.

INTRODUCTION: Although atrial fibrillation (AF) ablation has become increasingly safer, rehospitalization and emergency department (ED) evaluations can occur in the postablation period. Better understanding of the frequency, causes, and predictors for hospitalization and ED evaluation after ablation are needed, particularly as same-day discharge programs expand. METHODS: The Optum Clinformatics database was used to define rates, causes, and predictors of hospital and ED care after AF ablation performed between January 2016 and May 2019. Primary outcomes were all-cause hospital and ED care within 30 days of discharge. Independent predictors of all-cause ED and hospital admissions care were determined via logistic regression. RESULTS: Of the 18 848 patients in this study, the mean age was 67.5 ± 10 years, 37.9% were female, and the mean CHA2 DS2 -VASc score was 3.27 ± 1.84. Within 30 days of AF ablation, 1440 of 18 848 patients (7.6%) required hospital care of which 15% had >1 admission; 7.9% required ED care of which 28.6% had >1 ED visit. The most common reasons for hospital admission (which occurred on average 12.3 days after discharge) were supraventricular tachycardia (SVT) or AF (33.2%), heart failure (12.7%), and infection (12.2%). The most common reasons for ED care were SVT/AF (15.0%), noncardiac chest pain (13.3%), and noninfectious respiratory illness (12.2%). Age, female sex, ablation in an inpatient setting, and co-morbidities were associated with increased risk of rehospitalization. Age, female sex, patient comorbidities, and non-use of direct oral anticoagulation were associated with increased risk of ED visit. CONCLUSION: Approximately 7%-8% of patients require unplanned hospitalization or ED care after AF ablation, most commonly due to SVT/AF. Predictors of unscheduled care include patient age, sex, and several patient comorbidities. This study can inform quality improvement initiatives by identifying common causes for unscheduled care.

Food Insecurity Was Associated With Greater Family Health Care Expenditures In The US, 2016-17.

Food insecurity has been associated with the health care expenditures of individuals, but it can affect the entire family. Evaluating the relationship between food insecurity and family expenditures provides a better understanding of the financial implications of food insecurity interventions. Our primary objective was to evaluate the association between food insecurity in one year (2016) and family health care expenditures-for all members, for children only, and for adults only-in the next year (2017). We also evaluated whether this association varied across types of insurance coverage within families: all private, all public, or mixed (including uninsured). Using nationally representative data, we found that food-insecure families had 20 percent greater total health care expenditures than food-secure families, for an annual difference of $2,456. Food insecurity was associated with greater expenditures across all family insurance patterns, including the 19.1 percent of families with mixed coverage. Our findings suggest that in families with mixed coverage, positive impacts of food insecurity interventions on health care use may accrue to family members other than the targeted beneficiaries and those who have different insurance, benefiting the entire family but potentially discouraging investments on the part of any one payer.

Adolescent and Young Adult Perspectives on Quality and Value in Health Care.

OBJECTIVE: To describe adolescent and young adult (AYA) perspectives on defining quality and value in health care and to gain understanding of their knowledge of value-based payment. METHODS: A text message-based survey was sent to a convenience sample of AYAs aged 14 to 24 in 2019. Participants were asked 4 open-ended questions: 1) how they would define "good health care," 2) what factors to consider in rating doctors, 3) whose opinions should matter most when rating doctors, and 4) the best ways to collect AYA opinions on doctors, and one yes/no question on their awareness of value-based payment. Analyses included descriptive demographic statistics and an inductive thematic approach with multivariable models comparing adolescent (14-18) and young adult (19-24) responses. RESULTS: Response rate was 61.0% (782/1283). Most participants were White (63.3%), female (53.3%), and adolescents (55.6%). Common themes from the first 2 questions included accessibility (specifically affordability), coverage benefits, and care experience (including compassion, respect, and clinical competence). Young adults more commonly mentioned affordability than adolescents (54.4% vs 43.3%, P = .001) and more commonly felt their opinion should matter more than their parents when rating doctors (80.6% vs 62.0%, P < .001). Only 21.0% of AYAs were familiar with the potential value-based link between physician payment and care quality. CONCLUSIONS: When considering quality and value in health care, AYAs expressed their desired agency in rating the quality of their care and clinicians. AYAs' perspectives on health care quality, including the importance of care accessibility and affordability, should be considered when designing youth-centered care delivery and value-based payment models.

A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer.

Background: While the efficacy of immune checkpoint inhibitors (ICIs) is increasingly recognized in advanced gastric cancer (aGC), overall survival (OS) has not been consistently improved across the different randomized controlled trials (RCTs). This meta-analysis aimed to quantify the efficacy and safety of ICI and explore potential predictive tumor tissue biomarkers in aGC. Methods: A random-effect pairwise meta-analysis was used to evaluate the primary outcome of OS. Sensitivity analysis was performed to investigate the effects of ICIs on PD-L1 status, TMB, MSI-H, and the Asian patient population. We extracted the OS Kaplan-Meier curves from the included trials to compare the effect of PD-L1 status on response to ICIs using DigitizeIt 2.5 and Guyot's algorithm. Results: A pairwise meta-analysis of seven RCTs included in this study showed that ICIs were more effective than the comparator in improving OS (pooled HR: 0.84). We demonstrated that PD-1 ICIs were additive when combined with the comparator arm (pooled HR: 0.79). A sensitivity analysis showed that PD-1 ICIs were associated with better OS outcomes in the Asian patient population as monotherapy (pooled HR: 0.66) or in combination with chemotherapy (pooled HR: 0.83). We demonstrated that tumors with PD-L1 ≥1 (P = 0.02) and PD-L1 ≥10 (P = 0.006) derived OS benefit from ICI monotherapy. Equally, MSI-H (P <0.00001) and TMB-high (P <0.0001) tumors derived favorable survival benefits from ICIs. Conclusions and relevance: The results of this meta-analysis suggest that ICIs result in improved OS outcomes in aGC. The benefits varied with different ethnicities, class of ICI, PD-L1 expression, MSI status, and TMB. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42019137829).

Comparing diagnostic performance of Cantonese-Chinese version of Rome IV criteria and a short Reference Standard for functional dyspepsia in China.

INTRODUCTION: Functional dyspepsia (FD) is diagnosed based on self-reported symptoms and negative upper gastrointestinal endoscopic findings. The Rome criteria were not adopted as a diagnostic instrument in clinical guidelines due to their complexity. Different guidelines used relatively simple symptom assessment schemes with contents that vary significantly. A previously evaluated short Reference Standard may serve as a more standardised tool for guidelines. We evaluated its diagnostic accuracy against the Rome IV criteria in a cross-sectional study in Hong Kong. METHODS: A total of 220 dyspeptic patients sampled consecutively from a tertiary hospital and the community completed the Rome IV diagnostic questionnaire, which was translated into Cantonese-Chinese, and the Reference Standard. Sensitivity, specificity, positive and negative likelihood ratios (LRs), and area under the receiver operating characteristics curve (AUC), with 95% confidence intervals (CIs), were calculated. RESULTS: Among the participants, 160 (72.7%) fulfilled the Reference Standard with negative upper gastrointestinal endoscopic results. The Reference Standard identified patients with Rome IV-defined FD with 91.1% (95% CI 82.6%-96.4%) sensitivity and 37.6% (95% CI 29.6%-46.1%) specificity. The positive and negative LRs were 1.46 (95% CI 1.26-1.69) and 0.24 (95% CI 0.11-0.49), respectively. The AUC value was 0.64 (95% CI 0.59-0.69). CONCLUSIONS: The Reference Standard can rule out patients without Rome IV-defined FD. It may be used as an initial screening tool for FD in settings where the use of the Rome IV criteria is impractical. It may also provide a uniform definition and diagnostic rule for future updates of clinical guidelines.

Methodological quality of systematic reviews on treatments for Alzheimer's disease: a cross-sectional study.

BACKGROUND: Carefully conducted systematic reviews (SRs) can provide reliable evidence on the effectiveness of treatment strategies for Alzheimer's disease (AD). Nevertheless, the reliability of SR results can be limited by methodological flaws. This cross-sectional study aimed to examine the methodological quality of SRs on AD treatments, along with potentially relevant factors. METHODS: To identify eligible SRs on AD treatments, four databases including the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, and PsycINFO were searched. The Assessing the Methodological Quality of Systematic Reviews 2 instrument was used for quality appraisal of SRs. Multivariable regression analyses were used to examine factors related to methodological quality. RESULTS: A total of 102 SRs were appraised. Four (3.90%) SRs were considered as high quality; 14 (13.7%), 48 (47.1%), and 36 (35.3%) were as moderate, low, and critically low quality, respectively. The following significant methodological limitations were identified: only 22.5% of SRs registered protocols a priori, 6.9% discussed the rationales of chosen study designs, 21.6% gave a list of excluded studies with reasons, and 23.5% documented funding sources of primary studies. Cochrane SRs (adjusted odds ratio (AOR): 31.9, 95% confidence interval (CI): 3.81-266.9) and SRs of pharmacological treatments (AOR: 3.96, 95%CI: 1.27-12.3) were related to the higher overall methodological quality of SRs. CONCLUSION: Methodological quality of SRs on AD treatments is unsatisfactory, especially among non-Cochrane SRs and SRs of non-pharmacological interventions. Improvement in the following methodological domains requires particular attention due to poor performance: registering and publishing protocols a priori, justifying study design selection, providing a list of excluded studies, and reporting funding sources of primary studies.

Particle beam therapy for nasopharyngeal cancer: A systematic review and meta-analysis.

Background/purpose: A systematic review and meta-analysis were performed to better understand the benefits of particle beam therapy for nasopharyngeal cancer (NPC) treatment. The survival outcomes and toxicity of primary and recurrent NPC patients treated with proton or carbon ion beam therapy were investigated. Method: PubMed, Scopus, and Embase were searched between 1 January 2007 to 3 November 2021. The inclusion and exclusion criteria included studies with either primary or recurrent NPC patients, sample size of ≥10 patients, and proton or carbon ion beam therapy as interventions. Twenty-six eligible studies with a total of 1502 patients were included. We used a random-effect meta-analysis to examine the impact of particle beam therapy on primary NPC patients and qualitatively described the results among recurrent patients. The primary outcome was overall survival (OS), while secondary outcomes included progression-free survival (PFS), local control (LC) and toxicity. Results: The pooled OS at 1-year, 2-year and 3-year and 5-year for primary NPC patients who received particle beam therapy were 96 % (95 % confidence interval (CI) = 92 %-98 %), 93 % (95 % CI = 83 %-97 %), 90 % (95 % CI = 73 %-97 %) and 73 % (95 % CI = 52 %-87 %) respectively. The pooled 1-year and 2-year PFS, and LC for these patients were above 90 %. For locally recurrent NPC patients, the 1-year OS rate ranged from 65 % to 92 %, while the 1-year LC rate ranged from 80 % to 88 %. Both proton and carbon ion beam therapy were generally safe among primary and recurrent patients, with ≥G3 late toxicity rates of 20 % or less. Approximately a 5 % mortality rate was reported among recurrent patients. Conclusions: This systematic review and meta-analysis demonstrated particle beam therapy has great potential in treating NPC, yielding excellent survival outcomes with low toxicity. However, further investigations are needed to assess the long-term outcomes and cost-effectiveness of this newer form of radiotherapy.