[Impacts of Urban Form on Carbon Emissions Under the Goal of Carbon Emission Peak and Carbon Neutrality: A Case Study of the Yangtze River Economic Belt].

Clarifying the mechanism of influence of urban form on carbon emissions is an important prerequisite for achieving urban carbon emission reduction. Taking the Yangtze River Economic Belt as an example, this study elaborated on the general mechanism of urban form on carbon emissions, used multi-source data to quantitatively evaluate the urban form, and explored the impacts of urban form indicators on carbon emissions from 2005 to 2020 at global and sub-regional scales with the help of spatial econometric models and geodetector, respectively. The results showed that:① The carbon emissions of the Yangtze River Economic Belt increased from 2 365.31 Mt to 4 230.67 Mt, but the growth rate gradually decreased. Its spatial distribution pattern was bipolar, with high-value areas mainly distributed in core cities such as Shanghai and Chongqing and low-value areas concentrated in the western regions of Sichuan and Yunnan. ② The area of construction land in the study area expanded over the past 15 years, but the population density of construction land had been decreasing. The degree of urban fragmentation was decreasing, and the difference between cities was also progressively narrowing. The average regularity of urban shape improved, and the compactness increased significantly. ③ All indicators of urban scale had significant positive effects on carbon emissions at the global scale, urban fragmentation had a significant negative effect in 2005, and the effective mesh size (MESH) indicator of urban compactness showed a significant negative correlation with carbon emissions in the study period. ④ Total class area, patch density, and effective mesh size had the most significant impacts on carbon emissions in upstream cities. Effective mesh size, mean perimeter-area ratio, and total class area had higher influences in midstream cities. Effective mesh size, percentage of like adjacencies, and largest patch index were the key factors to promote carbon reduction in downstream cities. Cities in different regions should comprehensively consider the impacts of various urban form indicators on carbon emissions and then optimize their urban form to promote sustainable development.

Immunotherapy utilization patterns in patients with advanced cancer and autoimmune disease.

PURPOSE: Immunotherapy has been shown to improve cancer survival, but there are no consensus guidelines to inform use in patients with both cancer and autoimmune disease (AD). We sought to examine immunotherapy utilization patterns between cancer patients with and without AD. PATIENTS AND METHODS: This retrospective cohort study utilized data from a de-identified nationwide oncology database. Patients diagnosed with advanced melanoma, non-small cell lung cancer, and renal cell carcinoma were included. Outcomes of interest included first-line immunotherapy, overall immunotherapy, and number of immunotherapy cycles. We used logistic and Poisson regression models to examine associations between AD and immunotherapy utilization patterns. RESULTS: A total of 25,076 patients were included (796 with AD). Patients with AD were more likely to be female, White, receive care at academic centers, and have ECOG ≥ 3. Controlling for demographic and clinical variables, AD was associated with lower odds of receiving first-line (odds ratio [OR] = 0.68, 95% confidence interval [CI] 0.56-0.82) and overall (OR = 0.80, 95% CI 0.67-0.94) immunotherapy. Among patients who received at least one cycle of immunotherapy, there was no difference in mean number of cycles received between patients with and without AD (11.3 and 10.5 cycles respectively). The incident rate of immunotherapy cycles received for patients with AD was 1.03 times that of patients without AD (95% CI 1.01-1.06). DISCUSSION: Patients with AD were less likely to receive immunotherapy as first-line and overall therapy for treatment of their advanced cancer. However, among those who did receive at least one cycle of immunotherapy, patients with AD received a similar number of cycles compared to patients without AD. This not only indicates that AD is not an absolute contraindication for immunotherapy in clinical practice but may also demonstrate overall treatment tolerability and net benefit in patients with AD.

Effectiveness and safety of glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes: evidence from a retrospective real-world study.

Introduction: Global phase III clinical trials have shown superior hypoglycemic efficacy to insulin and other oral hypoglycemic agents. However, there is a scarcity of real-world data comparing different glucagon-like peptide 1 receptor agonist (GLP-1RA) directly. This study aimed to assess the safety and effectiveness of various GLP-1RA in treating type 2 diabetes mellitus (T2DM) in a real-world clinical setting and identify predictive factors for favorable treatment outcomes. Methods: This was a retrospective, single-center, real-world study. The changes in HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the percentage of participants who achieved HbA1c of <7%, 7%-8%, and ≥ 8% after GLP-1RA treatment was analyzed. The clinical factors that affect the effectiveness of GLP-1RA were analyzed. Results: At baseline, the 249 participants had a mean baseline HbA1c of 8.7 ± 1.1%. After at least three months of follow-up, the change in HbA1c was -0.89 ± 1.3% from baseline. Dulaglutide exerted a more significant hypoglycemic effect than immediate-release exenatide. The percentage of participants who achieved HbA1c<7% was substantial, from 6.0% at baseline to 28.9%. Average body weight decreased by 2.02 ± 3.8 kg compared to baseline. After GLP-1RA treatment, the reduction in SBP was 2.4 ± 7.1 mmHg from baseline. A shorter duration of diabetes and a higher baseline HbA1c level were more likely to achieve a good response in blood glucose reduction. Conclusions: This study provided real-world evidence showing that GLP-1RA significantly improved HbA1c, body weight, and SBP. The results can inform the decision-making about GLP-1RA treatment in daily clinical practice.

Racial differences in treatment and survival among older patients with multiple myeloma.

BACKGROUND: Treatments for multiple myeloma (MM) have evolved over time and improved MM survival. While racial differences in MM treatment and prognosis between non-Hispanic African American (NHAA) and non-Hispanic White (NHW) patients are well-established, it is unclear whether they have persisted after the introduction of novel agents. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, our study investigated racial difference in the receipt of treatment within 1 year following diagnosis and assessed survival outcomes among Medicare beneficiaries (≥66 years) diagnosed with MM from 2007 to 2017. We applied multivariable Cox proportional hazards models to estimate the association between race and survival and presented hazard ratios (HRs). RESULTS: Of 2094 NHAA and 11,983 NHW older patients with MM, 59.5% and 64.8% received treatment during the first year, respectively. Discrepancy in the proportion of patients receiving treatment between the two groups increased from 2.9% in 2007 to 2009 to 6.9% in 2014-2017. After controlling for relevant factors, patients who received treatment within the first year had lower mortality than those who did not (HR = 0.90, 95% confidence interval [CI]: 0.86-0.94). NHAA patients had a lower probability to receive treatments during the first year than NHW patients (HR = 0.91, 95% CI: 0.85-0.97) but had lower mortality (HR = 0.94, 95% CI: 0.88-1.00). The lower mortality was only observed among patients who received no treatment (HR = 0.84, 95% CI: 0.77-0.93); NHAA and NHW patients who received treatment had similar survival (p = 0.63). CONCLUSIONS: The increasing racial disparity in treatment utilization over time is concerning. Efforts are needed to eliminate the barriers of receiving treatment.

Beneficial Effect of Societal Factors on APOE-ε2 and ε4 Carriers' Brain Health: A Systematic Review.

BACKGROUND: Apolipoprotein-E (APOE) ε4 and ε2 are the most prevalent risk-increasing and risk-reducing genetic predictors of Alzheimer's disease, respectively. However, the extent to which societal factors can reduce the harmful impact of APOE-ε4 and enhance the beneficial impact of APOE-ε2 on brain health has not yet been examined systematically. METHODS: To fill this gap, we conducted a systematic review searching for studies in MEDLINE, Embase, PsycINFO, and Scopus until June 2023, that included: (a) 1 of 5 social determinants of health (SDH) identified by Healthy People 2030, (b) APOE-ε2 or APOE-ε4 allele carriers, (c) cognitive or brain-biomarker outcomes, and (d) studies with an analysis of how APOE-ε2 and/ or APOE-ε4 carriers differ on outcomes when exposed to SDH. RESULTS: From 14 076 articles retrieved, 124 met the inclusion criteria. In most of the studies, exposure to favorable SDH reduced APOE-ε4's detrimental effect and enhanced APOE-ε2's beneficial effect on cognitive and brain-biomarker outcomes (cognition: 70.5%, n: 74/105; brain-biomarkers: 71.4%, n: 20/28). A similar pattern of results emerged in each of the 5 Healthy People 2030 SDH categories, where finishing high school, having resources to satisfy basic needs, less air pollution, less negative external stimuli that can generate stress (eg, negative age stereotypes), and exposure to multiple favorable SDH were associated with better cognitive and brain health among APOE-ε4 and APOE-ε2 carriers. CONCLUSIONS: Societal factors can reduce the harmful impact of APOE-ε4 and enhance the beneficial impact of APOE-ε2 on cognitive outcomes. This suggests that plans to reduce dementia should include community-level policies promoting favorable SDH.

Approaches to developing de novo cancer population models to examine questions about cancer and race in bladder, gastric, and endometrial cancer and multiple myeloma: the Cancer Intervention and Surveillance Modeling Network incubator program.

BACKGROUND: We are developing 10 de novo population-level mathematical models in 4 malignancies (multiple myeloma and bladder, gastric, and uterine cancers). Each of these sites has documented disparities in outcome that are believed to be downstream effects of systemic racism. METHODS: Ten models are being independently developed as part of the Cancer Intervention and Surveillance Modeling Network incubator program. These models simulate trends in cancer incidence, early diagnosis, treatment, and mortality for the general population and are stratified by racial subgroup. Model inputs are based on large population datasets, clinical trials, and observational studies. Some core parameters are shared, and other parameters are model specific. All models are microsimulation models that use self-reported race to stratify model inputs. They can simulate the distribution of relevant risk factors (eg, smoking, obesity) and insurance status (for multiple myeloma and uterine cancer) in US birth cohorts and population. DISCUSSION: The models aim to refine approaches in prevention, detection, and management of 4 cancers given uncertainties and constraints. They will help explore whether the observed racial disparities are explainable by inequities, assess the effects of existing and potential cancer prevention and control policies on health equity and disparities, and identify policies that balance efficiency and fairness in decreasing cancer mortality.

Effect of melting combined with ice recrystallization on porous starch preparation: Pore-forming properties, granular morphology, functionality, and multi-scale structures.

In this work, critical melting (CM) combined with freeze-thawing treatment (FT, freezing at -20 â„ƒ and -80 â„ƒ, respectively) was used to prepare porous starch. The results showed that CM combined with the slow freezing rate (-20 â„ƒ) can prepare porous starch with characteristics of grooves and cavities, while combined with the rapid freezing rate (-80 â„ƒ) can prepare with holes and channels, especially after repeating FT cycles. Compared with the native counterpart, the specific surface area, pore volume, and average diameter of CMFT-prepared porous starch were significantly increased to 4.07 m2/g, 7.29 cm3/g × 10-3, and 3.57 nm, respectively. CMFT significantly increased the thermal stability of starch, in which the To, Tp, and Tc significantly increased from 63.32, 69.62, and 72.90 (native) to ∼69, 72, and 76 °C, respectively. CMFT significantly increased water and oil absorption of porous starch from 91.20 % and 72.00 % (native) up to ∼163 % and 94 %, respectively. Moreover, CMFT-prepared porous starch had a more ordered double-helical structure, which showed in the significantly increased relative crystallinity, semi-crystalline lamellae structure, and the proportion of the double helix structure of starch. The synergistic effect of melting combined with ice recrystallization can be used as an effective way to prepare structure-stabilized porous starch.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

BACKGROUND: Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women. OBJECTIVE: To estimate overdiagnosis associated with breast cancer screening among older women by age. DESIGN: Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age. SETTING: Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program. PATIENTS: Women 70 years and older who had been recently screened. MEASUREMENTS: Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up. RESULTS: This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening. LIMITATIONS: This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram. CONCLUSION: Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question. PRIMARY FUNDING SOURCE: National Cancer Institute.

Relative Burden of Cancer and Noncancer Mortality Among Long-Term Survivors of Breast, Prostate, and Colorectal Cancer in the US.

Importance: Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors. Objective: To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors. Design, Setting, and Participants: This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 years after their initial diagnosis (ie, long-term survivors of cancer). Statistical analysis was conducted from November 2022 to January 2023. Main Outcomes and Measures: Survival time ratios (TRs) were calculated using accelerated failure time models, and the primary outcome of interest examined was death from index cancer vs alternative (nonindex cancer) mortality across breast, prostate, colon, and rectal cancer cohorts. Secondary outcomes included subgroup mortality in cancer-specific risk groups, categorized based on prognostic factors, and proportion of deaths due to cancer-specific vs noncancer-specific causes. Independent variables included age, sex, race and ethnicity, income, residence, stage, grade, estrogen receptor status, progesterone receptor status, prostate-specific antigen level, and Gleason score. Follow-up ended in 2019. Results: The study included 627 702 patients (mean [SD] age, 61.1 [12.3] years; 434 848 women [69.3%]): 364 230 with breast cancer, 118 839 with prostate cancer, and 144 633 with colorectal cancer who survived 5 years or more from an initial diagnosis of early-stage cancer. Factors associated with shorter median cancer-specific survival included stage III disease for breast cancer (TR, 0.54; 95% CI, 0.53-0.55) and colorectal cancer (colon: TR, 0.60; 95% CI, 0.58-0.62; rectal: TR, 0.71; 95% CI, 0.69-0.74), as well as a Gleason score of 8 or higher for prostate cancer (TR, 0.61; 95% CI, 0.58-0.63). For all cancer cohorts, patients at low risk had at least a 3-fold higher noncancer-specific mortality compared with cancer-specific mortality at 10 years of diagnosis. Patients at high risk had a higher cumulative incidence of cancer-specific mortality than noncancer-specific mortality in all cancer cohorts except prostate. Conclusions and Relevance: This study is the first to date to examine competing oncologic and nononcologic risks focusing on long-term adult survivors of cancer. Knowledge of the relative risks facing long-term survivors may help provide pragmatic guidance to patients and clinicians regarding the importance of ongoing primary and oncologic-focused care.

Mortality in the US Populations With Monoclonal Gammopathy of Undetermined Significance.

This cohort study analyzes a nationally representative sample with a screening test for monoclonal gammopathy of undetermined significance (MGUS) to evaluate overall survival of populations with MGUS compared with those without MGUS among the general population in the US.

Cancer cell-autonomous cGAS-STING response confers drug resistance.

The cGAS-STING pathway has long been recognized as playing a crucial role in immune surveillance and tumor suppression. Here, we show that when the pathway is activated in a cancer-cell-autonomous response manner, it confers drug resistance. Targeted or conventional chemotherapy drugs promoted cytosolic DNA accumulation in cancer cells, activating the cGAS-STING pathway and downstream TBK1-IRF3/NF-κB signaling. This cancer cell-intrinsic response enabled the cells to counteract drug stress, allowing treatment resistance to be acquired and maintained. Blockade of stimulator of interferon genes (STING) signaling delayed and overcame resistance in models in vitro and in vivo. This finding uncovers an alternative face of cGAS-STING signaling other than the well-reported modulation of microenvironmental immune cells. It also implies a caution for the combination of STING agonist with targeted or conventional chemotherapy drug treatment, a strategy prevailing in current clinical trials.

Effects of enhanced starch-xanthan gum synergism on their physicochemical properties, functionalities, structural characteristics, and digestibility.

The limited and unstable interactions between potato starch (PS) and xanthan gum (XG) by simple mixing (SM) lead it difficult to induce substantial changes in starchy products. Structural unwinding and rearrangement of PS and XG by critical melting and freeze-thawing (CMFT) were used to promote PS/XG synergism, and the physicochemical, functionalities, and structural properties were investigated. Compared to "Native" and SM, CMFT promoted the formation of large clusters with a rough granular surface and wrapped by a matrix composed of released soluble starches and XG (SEM), thus making the composite more compact to thermal processes, such as the significantly decreased WSI and SP, and increased the melting temperatures. The enhanced synergism of PS/XG after CMFT effectively decreased the breakdown viscosity from ~3600 (Native) to ~300 mPa·s and increased the final viscosity from ~2800 (Native) to ~4800. CMFT significantly increased the functional properties of PS/XG composite, including water/oil absorptions and resistant starch content. CMFT caused the partial melting and loss of large packaged structures in starch (XRD, FTIR, and NMR), and the melting and the loss of crystalline structure controlled at approximately 20 % and 30 %, respectively, are the most effective for promoting PS/XG interaction.

Association of marital/partner status and patient-reported outcomes following myocardial infarction: a systematic review and meta-analysis.

Aims: Little is known about the relationship between marital/partner status and patient-reported outcome measures (PROMs) following myocardial infarction (MI). We conducted a systematic review/meta-analysis and explored potential sex differences. Methods and results: We searched five databases (Medline, Web of Science, Scopus, EMBASE, and PsycINFO) from inception to 27 July 2022. Peer-reviewed studies of MI patients that evaluated marital/partner status as an independent variable and reported its associations with defined PROMs were eligible for inclusion. Results for eligible studies were classified into four pre-specified outcome domains [health-related quality of life (HRQoL), functional status, symptoms, and personal recovery (i.e. self-efficacy, adherence, and purpose/hope)]. Study quality was appraised using Newcastle-Ottawa Scale, and data were synthesized by outcome domains. We conducted subgroup analysis by sex. We included 34 studies (n = 16 712), of which 11 were included in meta-analyses. Being married/partnered was significantly associated with higher HRQoL {six studies [n = 2734]; pooled standardized mean difference, 0.37 [95% confidence interval (CI), 0.12-0.63], I 2 = 51%} but not depression [three studies (n = 2005); pooled odds ratio, 0.72 (95% CI, 0.32-1.64); I 2 = 65%] or self-efficacy [two studies (n = 356); pooled ß, 0.03 (95% CI, -0.09 to 0.14); I 2 = 0%]. The associations of marital/partner status with functional status, personal recovery outcomes, and symptoms of anxiety and fatigue were mixed. Sex differences were not evident due to mixed results from the available studies. Conclusions: Married/partnered MI patients had higher HRQoL than unpartnered patients, but the associations with functional, symptom, and personal recovery outcomes and sex differences were less clear. Our findings inform better methodological approaches and standardized reporting to facilitate future research on these relationships.

Cost-effectiveness of first-line immunotherapies for advanced non-small cell lung cancer.

BACKGROUND: Researchers have not simultaneously compared the cost-effectiveness of six immunotherapies with chemotherapy for advanced non-small cell lung cancer. This study evaluated the cost-effectiveness across different programmed death-ligand 1 (PD-L1) levels. METHODS: A Markov model with lifetime horizon was created for seven regimens: pembrolizumab plus chemotherapy (pembro-chemo), nivolumab plus ipilimumab (nivo-ipi), nivolumab, ipilimumab plus chemotherapy (nivo-ipi-chemo), atezolizumab plus chemotherapy (atezo-chemo), atezolizumab, bevacizumab plus chemotherapy (atezo-beva-chemo), single-agent pembrolizumab, and chemotherapy alone. Input parameters were derived from trial data, a network meta-analysis, and other literature. We conducted the analysis from the perspective of US health care sector. RESULTS: For all patients without considering PD-L1 expression, the incremental cost-effectiveness ratio (ICER) of pembro-chemo versus chemotherapy was $183,299 per quality-adjusted life year (QALY). The preferred regimens based on ICERs differed by PD-L1 levels. For patients with PD-L1 ≥50%, pembrolizumab versus chemotherapy and pembro-chemo versus pembrolizumab resulted in ICERs of $96,189 and $198,913 per QALY, respectively. The other strategies were dominated. For patients with PD-L1 of 1%-49%, the ICER of pembro-chemo comparing to chemotherapy was $218,159 per QALY. The other regimens were dominated by pembro-chemo. For patients with PD-L1 <1%, nivo-ipi versus chemotherapy and nivo-ipi-chemo versus nivo-ipi resulted in ICERs of $161,277 and $881,975 per QALY, and the other regimens were dominated strategies. At the willingness-to-pay threshold of $150,000 per QALY, pembrolizumab had 87% and pembro-chemo had 1% probabilities being cost-effective in patients with PD-L1 ≥50% and 1%-49%, respectively. Nivo-ipi had a 34% probability being cost-effective in patients with PD-L1 <1%. CONCLUSIONS: The PD-L1 level should be incorporated into treatment decision-making. Our findings suggest that first-line pembrolizumab, pembro-chemo, and nivo-ipi are the preferred strategies for patients with PD-L1 ≥50%, 1%-49%, and <1%, respectively.

End-of-life care trajectories among older adults with lung cancer.

INTRODUCTION: Medicare decedents with cancer often receive intensive care during the last month of life; however, little information exists on longer end-of-life care trajectories. MATERIALS AND METHODS: Using SEER-Medicare data, we selected older adults diagnosed with lung cancer between 2008 and 2013 who survived at least six months and died between 2008 and 2014. Each month we assessed claims to assign care categories ordered by intensity as follows: full-month inpatient/skilled nursing facility > cancer-directed therapy (CDT) only > concurrent CDT and symptom management and supportive care services (SMSCS) > SMSCS only > full-month hospice. We assigned each decedent to one of six trajectories: stable hospice, stable SMSCS, stable CDT with or without concurrent SMSCS, decreasing intensity, increasing intensity, and mixed. Multinomial logistic regression estimated associations between socio-demographics, calendar year, and area hospice use rates with end-of-life trajectory. RESULTS: The sample (N = 24,342) was predominantly aged ≥75 years (59.4%) and non-Hispanic White (80.5%); 19.1% lived in healthcare referral regions where ≤50% of cancer decedents received hospice care. Overall, 6.5% were continuously hospice enrolled, 25.6% received SMSCS only, and 29.4% experienced decreasing intensity; 3.9% received CDT or concurrent care, while 8.7% experienced an increase in intensity. Higher healthcare referral region hospice rates were associated with decreasing end-of-life intensity; Black, non-Hispanic decedents had a higher risk of increasing intensity and mixed patterns. DISCUSSION: Among older decedents with lung cancer, 62% had six-month end-of-life trajectories indicating low or decreasing intensity, but few received persistent CDT. Demographic characteristics, including race/ethnicity, and contextual measures, including area hospice use patterns, were associated with end-of-life trajectory.

The association of marital/partner status with patient-reported health outcomes following acute myocardial infarction or stroke: Protocol for a systematic review and meta-analysis.

INTRODUCTION: Marital/Partner support is associated with lower mortality and morbidity following acute myocardial infarction (AMI) and stroke. Despite an increasing focus on the effect of patient-centered factors on health outcomes, little is known about the impact of marital/partner status on patient-reported outcome measures (PROMs). OBJECTIVE: To synthesize evidence of the association between marital/partner status and PROMs after AMI and stroke and to determine whether associations differ by sex. METHODS AND ANALYSIS: We will search MEDLINE (via Ovid), Web of Science Core Collection (as licensed by Yale University), Scopus, EMBASE (via Ovid), and PsycINFO (via Ovid) from inception to July 15, 2022. Two authors will independently screen titles, abstracts, and then full texts as appropriate, extract data, and assess risk of bias. Conflicts will be resolved by discussion with a third reviewer. The primary outcomes will be the associations between marital/partner status and PROMs. An outcome framework was designed to classify PROMs into four domains (health-related quality of life, functional status, symptoms, and personal recovery). Meta-analysis will be conducted if appropriate. Subgroup analysis by sex and meta-regression with a covariate for the proportion of male participants will be performed to explore differences by sex. ETHICS AND DISSEMINATION: This research is exempt from ethics approval because the study will be conducted using published data. We will disseminate the results of the analysis in a related peer-reviewed journal. TRIAL REGISTRATION: PROSPERO registration number: CRD42022295975.

Treatment Sequencing Patterns and Associated Direct Medical Costs of Metastatic Breast Cancer Care in the United States, 2011 to 2021.

Importance: Advances in treatment of metastatic breast cancer (MBC) led to changes in clinical practice and treatment costs in the US over the past decade. There is limited information on current MBC treatment sequences and associated costs by MBC subtype in the US. Objectives: To identify treatment patterns by MBC subtype and associated anticancer and supportive drug costs from health care sector and Medicare perspectives. Design, Setting, and Participants: This economic evaluation analyzed data of patients with MBC obtained from the nationwide Flatiron Health database, an electronic health record-derived, deidentified database with data from community and academic practices across the US from 2011 to 2021. Participants included women aged at least 18 years diagnosed with MBC, who had at least 6 months of follow-up data, known hormone receptor (HR) and human epidermal growth factor receptor 2 (ERBB2) receptor status, and at least 1 documented line of therapy. Patients with documented receipt of clinical study drugs were excluded. Data were analyzed from June 2021 to May 2022. Main Outcomes and Measures: Outcomes of interest were frequency of different drug regimens received as a line of therapy by subtype for the first 5 lines and mean medical costs of documented anticancer treatment and supportive care drugs per patient by MBC subtype and years since metastatic diagnosis, indexed to 2021 US dollars. Results: Among 15 215 patients (10 171 patients [66.85%] with HR-positive and ERBB2-negative MBC; 2785 patients [18.30%] with HR-positive and ERBB2-positive MBC; 802 patients [5.27%] with HR-negative and ERBB2-positive MBC; 1457 patients [9.58%] with triple-negative breast cancer [TNBC]) who met eligibility criteria, 1777 (11.68%) were African American, 363 (2.39%) were Asian, and 9800 (64.41%) were White; the median (range) age was 64 (21-84) years. The mean total per-patient treatment and supportive care drug cost using publicly available Medicare prices was $334 812 for patients with HR-positive and ERBB2-positive MBC, $284 609 for patients with HR-negative and ERBB2-positive MBC, $104 774 for patients with HR-positive and ERBB2-negative MBC, and $54 355 for patients with TNBC. From 2011 to 2019 (most recent complete year 1 data are for patients diagnosed in 2019), annual costs in year 1 increased from $12 986 to $80 563 for ERBB2-negative and HR-positive MBC, $99 997 to $156 712 for ERBB2-positive and HR-positive MBC, and $31 397 to $53 775 for TNBC. Conclusions and Relevance: This economic evaluation found that drug costs related to MBC treatment increased between 2011 and 2021 and differed by tumor subtype. These findings suggest the growing financial burden of MBC treatment in the US and highlights the importance of performing more accurate cost-effectiveness analysis of novel adjuvant therapies that aim to reduce metastatic recurrence rates for early-stage breast cancer.

Evidence-based service delivery interventions for testing, linking, treating, and retaining children and adolescents living with HIV in primary health care settings: Protocol for a systematic review.

BACKGROUND: At the end of 2019, there were about 2.8 million children and adolescents aged 0-19 living with HIV. In contrast to pregnant women and adults, service delivery for children and adolescents living with HIV continues to lag behind with regard to access to care, components of care delivery, treatment options, and clinical and immunologic outcomes. AIM: The aim of this systematic review is to synthesize the evidence on the most effective interventions, models, programs, and strategies to optimize the delivery of services for the testing, linkage, treatment and retention of children and adolescents living with HIV globally. METHODS: This review protocol is registered at PROSPERO with Registration number: CRD42020209553. The systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). We will use a comprehensive search strategy to search several bibliographic databases including MEDLINE, Embase, CINAHL, Cochrane Library, Global Health, and Psycinfo to identify relevant studies published in the last ten years (2010 to 2020). In addition, we will review cited and citing references of included studies. A pair of reviewers will independently screen titles, abstracts and full texts of articles, extract data from articles meeting inclusion criteria and perform quality assessments of the evidence collected. We will conduct a narrative synthesis of our findings, and if there are sufficient clinically similar studies available, we will conduct meta-analysis using a random-effects model. DISCUSSION: This review will provide evidence on service delivery models that have been evaluated in a range of settings to efficiently and effectively locate, link, treat and retain in care, children and adolescents living with HIV. The synthesized evidence will help guide national governments and health care providers in prioritizing and adopting evidence-based service delivery approaches for children and adolescents living with HIV. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020209553.

Perioperative magnetic resonance imaging in breast cancer care: Distinct adoption trajectories among physician patient-sharing networks.

BACKGROUND: Despite no proven benefit in clinical outcomes, perioperative magnetic resonance imaging (MRI) was rapidly adopted into breast cancer care in the 2000's, offering a prime opportunity for assessing factors influencing overutilization of unproven technology. OBJECTIVES: To examine variation among physician patient-sharing networks in their trajectory of adopting perioperative MRI for breast cancer surgery and compare the characteristics of patients, providers, and mastectomy use in physician networks that had different adoption trajectories. METHODS AND FINDINGS: Using the Surveillance, Epidemiology, and End Results-Medicare database in 2004-2009, we identified 147 physician patient-sharing networks (caring for 26,886 patients with stage I-III breast cancer). After adjusting for patient clinical risk factors, we calculated risk-adjusted rate of perioperative MRI use for each physician network in 2004-2005, 2006-2007, and 2008-2009, respectively. Based on the risk-adjusted rate, we identified three distinct trajectories of adopting perioperative MRI among physician networks: 1) low adoption (risk-adjusted rate of perioperative MRI increased from 2.8% in 2004-2005 to 14.8% in 2008-2009), 2) medium adoption (8.8% to 45.1%), and 3) high adoption (33.0% to 71.7%). Physician networks in the higher adoption trajectory tended to have a larger proportion of cancer specialists, more patients with high income, and fewer patients who were Black. After adjusting for patients' clinical risk factors, the proportion of patients undergoing mastectomy decreased from 41.1% in 2004-2005 to 38.5% in 2008-2009 among those in physician networks with low MRI adoption, but increased from 27.0% to 31.4% among those in physician networks with high MRI adoption (p = 0.03 for the interaction term between trajectory group and time). CONCLUSIONS: Physician patient-sharing networks varied in their trajectory of adopting perioperative MRI. These distinct trajectories were associated with the composition of patients and providers in the networks, and had important implications for patterns of mastectomy use.

Primary care physician continuity, survival, and end-of-life care intensity.

OBJECTIVE: To examine the associations of primary care physician (PCP) care continuity with cancer-specific survival and end-of-life care intensity. DATA SOURCES: Surveillance, epidemiology, and end results linked to Medicare claims data from 2001 to 2015. STUDY DESIGN: Cox proportional hazards models with mixed effects and hierarchical generalized logistic models were used to examine the associations of PCP care continuity with cancer-specific survival and end-of-life care intensity, respectively. PCP care continuity, defined as having visited the predominant PCP (who saw the patient most frequently before diagnosis) within 6 months of diagnosis. DATA EXTRACTION METHODS: We identified Medicare patients diagnosed at age 66.5-94 years with stage-III or IV poor-prognosis cancer during 2001-2012 and followed them up until 2015. Patients who died within 6 months after diagnosis were excluded. PRINCIPAL FINDINGS: Primary study cohort consisted of 85,467 patients (median survival 22 months), 71.7% of whom had PCP care continuity. Patients with PCP care continuity tended to be older, married, nonblack, non-Hispanic, and to have fewer comorbid conditions (p < 0.001 for all). Patients with PCP care continuity had lower cancer-specific mortality (adjusted hazard ratio: 0.93; 95% confidence interval [CI]: 0.91 to 0.95; p = 0.001) than did those without PCP care continuity. Findings of the 2001-2003 cohorts (nearly all of whom died by 2015) show no associations of overall end-of-life care intensity measures with PCP care continuity (adjusted marginal effects: 0.005; 95% CI: -0.016 to 0.026; p = 0.264). CONCLUSIONS: Among Medicare beneficiaries with advanced poor-prognosis cancer, PCP continuity was associated with modestly improved survival without raising overall aggressive end-of-life care.