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Sarah Dahlberg,1 Ellen T Chang,1 Sheila R Weiss,1 Pamela Dopart,1 Errol Gould,2 Mary E Ritchey3 1Exponent, Inc, Menlo Park, CA, 94025, USA; 2Currax Pharmaceuticals LLC., Brentwood, TN, 37027, USA; 3Med Tech Epi, LLC., Philadelphia, PA, 19147, USACorrespondence: Errol Gould, Currax Pharmaceuticals LLC, 155 Franklin Road, Suite 450, Brentwood, TN, 37027, USA, Email egould@curraxpharma.comAbstract: Naltrexone/Bupropion extended release (ER; Contrave) is an extended-release, fixed-dose combination medication of naltrexone (8 mg) and bupropion (90 mg) for patients with obesity or overweight with at least one weight-related comorbidity. Obese and overweight patients with or without comorbidities are at increased cardiovascular (CV) risk. Due to the increased CV risk profile in this patient population, this systematic literature review was conducted to assess human studies reporting major adverse CV events (MACE) and other CV events. A priori eligibility criteria included clinical studies (randomized and observational) published from January 1, 2012, to September 30, 2021, with data comparing users of naltrexone/bupropion ER, naltrexone with bupropion, bupropion without naltrexone, or naltrexone without bupropion versus comparator groups (placebo or other treatments), and with sufficient information to determine the frequency of MACE or other CV adverse events by treatment group. Among 2539 English-language articles identified, 70 articles met the eligibility criteria: seven studies of naltrexone/bupropion ER or naltrexone with bupropion, 32 studies of bupropion, and 31 studies of naltrexone. No studies reported an increased risk of MACE among users of naltrexone/bupropion ER, naltrexone with bupropion, or bupropion or naltrexone individually compared with nonusers. One-half of the available studies (n = 35) reported no (zero) CV events and the other half (n = 35) reported that a non-zero frequency of CV events occurred. Four studies reported data on MACE, including three studies of bupropion and one study of naltrexone/bupropion ER. For composite MACE and its components, the difference in proportions between naltrexone/bupropion ER-, bupropion-, or naltrexone-treated patients compared with active comparators or placebo-treated patients did not exceed 2.5%. In conclusion, the available human evidence does not indicate an increased risk of CV events or MACE following use of naltrexone/bupropion ER, naltrexone with bupropion, or the individual components.Keywords: MACE, obese, overweight, cardiovascular risk

Gaurav Nigam,1 Macario Camacho,2 Edward T Chang,2 Muhammad Riaz3 1Division of Sleep Medicine, Clay County Hospital, Flora, IL, 2Division of Otolaryngology, Sleep Surgery and Sleep Medicine, Tripler Army Medical Center, Honolulu, HI, 3Division of Sleep Medicine, Astria Health Center, Grandview, WA, USA Abstract: Kidney disorders have been associated with a variety of sleep-related disorders. Therefore, researchers are placing greater emphasis on finding the role of chronic kidney disease (CKD) in the development of obstructive sleep apnea and restless legs syndrome. Unfortunately, the presence of other sleep-related disorders with CKDs and non-CKDs has not been investigated with the same clinical rigor. Recent studies have revealed that myriad of sleep disorders are associated with CKDs. Furthermore, there are a few non-CKD-related disorders that are associated with sleep disorders. In this narrative review, we provide a balanced view of the spectrum of sleep disorders (as identified in International Classification of Sleep disorders-3) related to different types of renal disorders prominently including but not exclusively limited to CKD. Keywords: kidney disease, sleep disorders, obstructive sleep apnea, parasomnias, restless legs syndrome, chronic kidney disease, insomnia

PurposeFor classical Hodgkin lymphoma (HL), migrant studies could elucidate contributions of environmental factors (including Epstein-Barr virus (EBV)) to the lower rates in non-whites. Given the well-described etiologic complexity of HL, this research requires a large, immigrant population, such as California Hispanics.MethodsWith 1988-2004 California Cancer Registry data (2,595 Hispanic, 8,637 white HL cases) and tumor cell EBV status on a subset (218 Hispanics, 656 whites), we calculated ethnicity- and nativity-specific HL incidence rates simultaneously by age, sex, and histologic subtype, and tumor cell EBV prevalence.ResultsCompared with white rates, Hispanic HL rates were lower overall (70 %) and for nodular sclerosis HL, particularly among young adults (60-65 % for females). However, they were higher among children (200 %) and older adults, and for mixed cellularity HL. Compared with rates in foreign-born Hispanics, rates in US-born Hispanics were higher among young adults (>threefold in females), lower for children and adults over age 70, and consistently intermediate compared with rates in whites. EBV tumor prevalence was 67, 32, and 23 % among foreign-born Hispanics, US-born Hispanics, and whites, respectively, although with variation by age, sex, and histology.ConclusionsFindings strongly implicate environmental influences, such as nativity-related sociodemographic differences, on HL occurrence. In addition, lower young adult rates and higher EBV prevalence in US-born Hispanics than in whites raise questions about the duration/extent of environmental change for affecting HL rates and also point to ethnic differences in genetic susceptibility. Lesser variation in mixed cellularity HL rates and greater variation in rates for females across groups suggest less modifiable factors interacting with environmental influences.

Family history of haematopoietic malignancies appears to be a risk factor for non-Hodgkin's lymphoma (NHL), but whether risk varies by family member's gender is unclear. Among 121 216 women participating in the prospective California Teachers Study, NHL risk varied by type of haematopoietic malignancy and gender of the relative.

Although advanced parental age at one's birth has been associated with increased risk of breast and prostate cancers, few studies have examined its effect on adult-onset sporadic hematologic malignancies. The authors examined the association of parents' ages at women's births with risk of hematologic malignancies among 110,999 eligible women aged 22-84 years recruited into the prospective California Teachers Study. Between 1995 and 2007, 819 women without a family history of hematologic malignancies were diagnosed with incident lymphoma, leukemia (primarily acute myeloid leukemia), or multiple myeloma. Multivariable-adjusted Cox proportional hazards models provided estimates of relative risks and 95% confidence intervals. Paternal age was positively associated with non-Hodgkin lymphoma after adjustment for race and birth order (relative risk for age > or =40 vs. <25 years = 1.51, 95% confidence interval: 1.08, 2.13; P-trend = 0.01). Further adjustment for maternal age did not materially alter the association. By contrast, the elevated non-Hodgkin lymphoma risk associated with advanced maternal age (> or =40 years) became null when paternal age was included in the statistical model. No association was observed for acute myeloid leukemia or multiple myeloma. Advanced paternal age may play a role in non-Hodgkin lymphoma etiology. Potential etiologic mechanisms include de novo gene mutations, aberrant paternal gene imprinting, or telomere/telomerase biology. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The annual Hepatitis B Prevention and Education Symposium aims to develop partnerships between non-Western and Western health care providers to prevent chronic hepatitis B virus (HBV) infection and death from liver cancer among Asians and Pacific Islanders (APIs). DESIGN: Each year from 2004 through 2007, we partnered with professional, academic, and community-based organizations to organize an educational symposium for Traditional Chinese Medicine practitioners and acupuncturists in California. Participants completed pre- and postsymposium surveys assessing knowledge about HBV and liver cancer. SETTING: The symposia were held in San Francisco, Los Angeles, and Stanford, California. SUBJECTS: Over 1000 participants attended the four symposia combined; most were born in Asia. INTERVENTION: Symposium activities included educational lectures and games, presentation of a physician's guide to HBV management, and case studies. OUTCOME MEASURES: Chi-square tests were used to compare the proportion of correct responses to each knowledge-based question, as well as the total number of correct responses, before and after the symposium. RESULTS: Knowledge about HBV and liver cancer was low prior to the symposium. The proportion of correct responses to the most commonly mistaken questions increased significantly at the conclusion of each symposium. The total number of correct responses rose from below 60% to above 75% each year. CONCLUSIONS: Similar educational symposia targeting health care providers who serve API patients can improve HBV and liver cancer awareness and prevention throughout the API community. [ABSTRACT FROM AUTHOR]

As has happened to many other islands, the Penghu Archipelago has, over the years, fallen gradually into decline due to shrinking revenues from the fishing industry. Making matters worse, in spite of abundant natural resources and many governmental subsidization programs, the adverse winter weather and many other weaknesses have slowed down the transformation of this area's economic base from fisheries to tourism. A Strength, Weakness, Opportunities and Threats (SWOT) analysis is applied in this paper to systematically portray the strengths, weaknesses, opportunities and threats involved in redeveloping this area. Governmental actions, including fishery resource rejuvenation projects, infrastructure investment initiatives, composite tourism programs, tax exemptions and attempts to establish the islands as a casino gaming area are evaluated. Scenarios concerning uncertainties and their impacts for potential investors are also elaborated on. [ABSTRACT FROM AUTHOR]

This study examines globalization of television broadcasting through the experiences of the world's leading broadcasters in Asia from the 1990s. Using a historical research method to chronicle the evolution of programming strategies of global television broadcasters, this study addresses the following research questions: to what degree have global television broadcasters changed their programming to adapt to local needs and preferences in Asia; and the implications of the evolution of programming strategies of global television broadcasters in Asia have on the understanding of globalization of television broadcasting. This study finds that STAR TV, MTV Asia, ESPN Star Sports, and CNBC are leaders in programming localization.

This research is aimed at exploring the professional practice and decision-making considerations of the expert producer in the digital media design field based upon the theory of Benchmarking. The methods are adapted to this research including in-depth interview and participant observation under the naturalistic paradigm. The questions to be answered including: the considerations of taking projects and developing products; the problems to be resolved while the projects going; the interaction among the team members, clients, and customers; the characteristics of a successful digital media producer, etc. The accomplishment of this research is expected to reach several contributions: to synthesize the best practice in the field of digital media design; to shorten the gap between the school and the industry; to facilitate the cooperation between academic and practical fields; to improve the current status of information communication education; to develop a localized theoretical foundation for the information communication education. [ABSTRACT FROM AUTHOR]

A suitable reference gene is an important prerequisite for guarantying accurate and reliable results in qPCR analysis. Celery is one of the representative vegetable in Apiaceae and is widely cultivated and consumed in the world. However, no reports have been previously published concerning reference genes in celery. In this study, the expression stabilities of nine candidate reference genes in leaf blade and petiole at different development stages were evaluated using three statistics algorithms geNorm, NormFinder, and BestKeeper. Our results showed that TUB-B, TUB-A, and UBC were the most reference genes among all tested samples. GAPDH represented the maximum stability for most individual sample, while the UBQ displayed the minimum stability. To further validate the stability of reference genes, the expression pattern of AgAP2-2 was calculated by using the selected genes for normalization. In addition, the expression patterns of several development-related genes were studied using the selected reference gene. Our results will be beneficial for further studies on gene transcription in celery.

Describes a method for combinatorial screening of potential catalyst precursors. Testing of the method by screening for novel catalysts for Hydrogenation of carbon dioxide; Photograph of the apparatus for high-pressure catalyst screening.

Objectives. We estimated trends in breast cancer incidence rates for specific Asian populations in California to determine if disparities exist by immigrant status and age. Methods. To calculate rates by ethnicity and immigrant status, we obtained data for 1998 through 2004 cancer diagnoses from the California Cancer Registry and imputed immigrant status from Social Security Numbers for the 26% of cases with missing birthplace information. Population estimates were obtained from the 1990 and 2000 US Censuses. Results. Breast cancer rates were higher among US- than among foreign-born Chinese (incidence rate ratio [IRR] = 1.84; 95% confidence interval [CI] = 1.72, 1.96) and Filipina women (IRR = 1.32; 95% CI = 1.20, 1.44), but similar between US- and foreign-born Japanese women. US-born Chinese and Filipina women who were younger than 55 years had higher rates than did White women of the same age. Rates increased over time in most groups, as high as 4% per year among foreign-born Korean and US-born Filipina women. From 2000DS2004, the rate among US-born Filipina women exceeded that of White women. Conclusions. These findings challenge the notion that breast cancer rates are uniformly low across Asians and therefore suggest a need for increased awareness, targeted cancer control, and research to better understand underlying factors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous epidemiological studies of the relation between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) have been inconsistent, probably because of small sample sizes of individual studies that result from stratification by NHL subtype and type of alcoholic beverage. We aimed to assess the role of alcohol consumption in NHL with sufficient sample size to analyse by both type of alcoholic beverage and disease subtype. METHODS: We obtained original data from nine case-control studies from the USA, UK, Sweden, and Italy in the International Lymphoma Epidemiology Consortium (InterLymph), yielding a pooled study population of 15 175 individuals (6492 cases and 8683 controls). We derived odds ratios (OR) and 95% CI from unconditional logistic regression models, controlling for study centre and other confounding factors. Heterogeneity between studies was assessed by comparison of results from joint fixed-effects logistic regression and two-stage random-effects logistic regression, and by calculation of Wald chi(2) statistics. FINDINGS: People who drank alcohol had a lower risk of NHL than did non-drinkers (OR 0.83 [95% CI 0.76-0.89]). Compared with non-drinkers, risk estimates were lower for current drinkers than for former drinkers (0.73 [0.64-0.84] vs 0.95 [0.80-1.14]), but risk did not decrease with increasing alcohol consumption. The protective effect of alcohol did not vary by beverage type, but did change with NHL subtype. The lowest risk estimates were recorded for Burkitt's lymphoma (0.51 [0.33-0.77]). INTERPRETATION: People who drink alcoholic beverages might have a lower risk of NHL than those who do not, and this risk might vary by NHL subtype. Further study designs are needed to determine whether confounding lifestyle factors or immunomodulatory effects of alcohol explain this association. [ABSTRACT FROM AUTHOR]

Background: The Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act expanded access to independent community providers outside the Veterans Health Administration (VA). Little is known how quality, costs, and outcomes of primary care received in the community compare to that of the VA., Objective: To compare quality, costs, and outcomes of community and VA-provided primary care for patients with diabetes over a 12-month episode., Design: A cross-sectional study using VA administrative data and community care claims. Adjusted analyses were conducted using inverse probability weighted regression adjustment to balance patient characteristics., Participants: Veterans with diabetes receiving primary care in the VA or community., Main Measures: Quality measures included receipt of hemoglobin A1C tests, eye exams, microalbumin urine tests, and flu shots. Outcomes were measured by hospitalizations for an ambulatory care sensitive condition (ACSC). Costs were measured for VA and community outpatient care, inpatient care, and prescription drugs., Key Results: There were 652,648 VA patients and 3650 community care patients. VA patients were less likely to be White, had shorter mean drive time to VA primary care, and were less likely to be rural than community care patients. In adjusted analyses, community care patients had significantly lower probability of receiving a hemoglobin A1C test, eye exam, microalbumin urine test, and flu shot compared to the VA group. There was no difference in probability of an ACSC hospitalization. Community care patients had higher mean total costs ($1741 [95% CI, $431, $3052]), driven by higher inpatient and prescription drug costs but lower emergency care costs than VA patients., Conclusion: Patients receiving community primary care had worse diabetes quality and higher costs than patients receiving VA primary care. There was no difference in health outcomes. Care provided by an integrated delivery system may have advantages in quality and value., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Many healthcare systems have implemented intensive outpatient primary care programs with the hopes of reducing healthcare costs., Objective: The Veterans Health Administration (VHA) piloted primary care intensive management (PIM) for patients at high risk for hospitalization or death, or "high-risk." We evaluated whether a referral model would decrease high-risk patient costs., Design: Retrospective cohort study using a quasi-experimental design comparing 456 high-risk patients referred to PIM from October 2017 to September 2018 to 415 high-risk patients matched on propensity score., Participants: Veterans in the top 10th percentile of risk for 90-day hospitalization or death and recent hospitalization or emergency department (ED) visit., Intervention: PIM consisted of interdisciplinary teams that performed comprehensive assessments, intensive case management, and care coordination services., Main Outcomes and Measures: Change in VHA and non-VHA outpatient utilization, inpatient admissions, and costs 12 months pre- and post-index date., Key Results: Of the 456 patients referred to PIM, 301 (66%) enrolled. High-risk patients referred to PIM had a marginal reduction in ED visits (- 0.7; [95% CI - 1.50 to 0.08]; p = 0.08) compared to propensity-matched high-risk patients; overall outpatient costs were similar. High-risk patients referred to PIM had similar number of medical/surgical hospitalizations (- 0.2; [95% CI, - 0.6 to 0.16]; p = 0.2), significant increases in length of stay (6.36; [CI, - 0.01 to 12.72]; p = 0.05), and higher inpatient costs ($22,628, [CI, $3587 to $41,669]; p = 0.02) than those not referred to PIM., Conclusions and Relevance: VHA intensive outpatient primary care was associated with higher costs. Referral to intensive case management programs targets the most complex patients and may lead to increased utilization and costs, particularly in an integrated healthcare setting with robust patient-centered medical homes., Trial Registration: PIM 2.0: Patient Aligned Care Team (PACT) Intensive Management (PIM) Project (PIM2). NCT04521816. https://clinicaltrials.gov/study/NCT04521816., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Patients with significant multimorbidity and other factors that make healthcare challenging to access and coordinate are at high risk for poor health outcomes. Although most (93%) of Veterans' Health Administration (VHA) patients at high risk for hospitalization or death ("high-risk Veterans") are primarily managed by primary care teams, few of these teams have implemented evidence-based practices (EBPs) known to improve outcomes for the high-risk patient population's complex healthcare issues. Effective implementation strategies could increase adoption of these EBPs in primary care; however, the most effective implementation strategies to increase evidence-based care for high-risk patients are unknown. The high-RIsk VETerans (RIVET) Quality Enhancement Research Initiative (QUERI) will compare two variants of Evidence-Based Quality Improvement (EBQI) strategies to implement two distinct EBPs for high-risk Veterans: individual coaching (EBQI-IC; tailored training with individual implementation sites to meet site-specific needs) versus learning collaborative (EBQI-LC; implementation sites trained in groups to encourage collaboration among sites). One EBP, Comprehensive Assessment and Care Planning (CACP), guides teams in addressing patients' cognitive, functional, and social needs through a comprehensive care plan. The other EBP, Medication Adherence Assessment (MAA), addresses common challenges to medication adherence using a patient-centered approach., Methods: We will recruit and randomize 16 sites to either EBQI-IC or EBQI-LC to implement one of the EBPs, chosen by the site. Each site will have a site champion (front-line staff) who will participate in 18 months of EBQI facilitation., Analysis: We will use a mixed-methods type 3 hybrid Effectiveness-Implementation trial to test EBQI-IC versus EBQI-LC versus usual care using a Concurrent Stepped Wedge design. We will use the Practical, Robust Implementation and Sustainability Model (PRISM) framework to compare and evaluate Reach, Effectiveness, Adoption, Implementation, and costs. We will then assess the maintenance/sustainment and spread of both EBPs in primary care after the 18-month implementation period. Our primary outcome will be Reach, measured by the percentage of eligible high-risk patients who received the EBP., Discussion: Our study will identify which implementation strategy is most effective overall, and under various contexts, accounting for unique barriers, facilitators, EBP characteristics, and adaptations. Ultimately this study will identify ways for primary care clinics and teams to choose implementation strategies that can improve care and outcomes for patients with complex healthcare needs., Trial Registration: ClinicalTrials.gov, NCT05050643. Registered September 9th, 2021, https://clinicaltrials.gov/study/NCT05050643 PROTOCOL VERSION: This protocol is Version 1.0 which was created on 6/3/2020., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Medications to treat opioid use disorder (MOUD) such as buprenorphine/naloxone can effectively treat OUD and reduce opioid-related mortality, but they remain underutilized, especially in non-substance use disorder settings such as primary care (PC)., Objective: To uncover the factors that can facilitate successful prescribing of MOUD and uptake/acceptance of MOUD by patients in PC settings in the Veterans Health Administration., Design: Semi-structured qualitative telephone interviews with 77 providers (e.g., primary care providers, hospitalists, nurses, addiction psychiatrists) and 22 Veteran patients with experience taking MOUD. Interviews were recorded, transcribed, and analyzed thematically using a combination a priori/inductive approach., Key Results: Providers and patients shared their general perceptions and experiences with MOUD, including high satisfaction with buprenorphine/naloxone with few side effects and caveats, although some patients reported drawbacks to methadone. Both providers and patients supported the idea of prescribing MOUD in PC settings to prioritize patient comfort and convenience. Providers described individual-level barriers (e.g., time, stigma, perceptions of difficulty level), structural-level barriers (e.g., pharmacy not having medications ready, space for inductions), and organizational-level barriers (e.g., inadequate staff support, lack of nursing protocols) to PC providers prescribing MOUD. Facilitators centered on education and knowledge enhancement, workflow and practice support, patient engagement and patient-provider communication, and leadership and organizational support. The most common barrier faced by patients to starting MOUD was apprehensions about pain, while facilitators focused on personal motivation, encouragement from others, education about MOUD, and optimally timed provider communication strategies., Conclusions: These findings can help improve provider-, clinic-, and system-level supports for MOUD prescribing across multiple settings, as well as foster communication strategies that can increase patient acceptance of MOUD. They also point to how interprofessional collaboration across service lines and leadership support can facilitate MOUD prescribing among non-addiction providers., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: People with serious mental illness (SMI) have low rates of primary care (PC) use and die years prematurely, mostly because of medical illnesses such as cardiovascular disease or cancer. To meet the needs of these individuals, a novel, specialized patient-centered medical home with care coordination ("SMI PACT") was developed and implemented in PC. This study qualitatively examined patients' experiences with this innovative care model., Method: After implementation of the medical home in 2018, one-on-one semistructured interviews were conducted with 28 patients (32% women, 43% Black, and 25% Hispanic). Interviews were professionally transcribed and coded prior to thematic analysis., Results: Patients overwhelmingly described positive experiences with SMI PACT because of the qualities of interpersonal communication displayed by SMI PACT staff (e.g., nonjudgment, good listening, patience), structural features of the SMI PACT collaborative care model (e.g., frequent follow-up communication), and other unique aspects of the SMI PACT model tailored for SMI, such as easy-to-understand language. For these reasons, most patients expressed a desire to continue care in SMI PACT. Patients also self-reported improved engagement with their healthcare and self-management of diet, exercise, blood pressure, and diabetes control as a result of SMI PACT participation., Discussion: Patients enrolled in a specialized PC medical home identified clinician characteristics and behaviors that informed an overwhelmingly positive impression of the program model. Their experiences can guide dissemination of specialized PC models and integrated services for people with SMI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Late-stage cancer incidence has been proposed as an early surrogate for mortality in randomized controlled trials (RCTs) of cancer screening; however, its validity has not been systematically evaluated across screening RCTs of different cancers., Methods: We conducted a meta-regression analysis of cancer screening RCTs that reported both late-stage cancer incidence and cancer mortality. Based on a systematic literature review, we included 33 RCTs of screening programs targeting seven cancer types, including lung ( n  = 12), colorectal ( n  = 8), breast ( n  = 5), and prostate ( n  = 4), among others. We regressed the relative reduction of cancer mortality on the relative reduction of late-stage cancer incidence, inversely weighted for each RCT by the variance of estimated mortality reduction., Results: Across cancer types, the relative reduction of late-stage cancer incidence was linearly associated with the relative reduction of cancer mortality. Specifically, we observed this association for lung ( R 2  = 0.79 and 0.996 in three recent large trials), breast ( R 2  = 0.94), prostate ( R 2  = 0.98), and colorectal cancer ( R 2  = 0.75 for stage III/IV cancers and 0.93 for stage IV cancers). Trials with a 20% or greater reduction in late-stage cancers were more likely to achieve a significant reduction in cancer mortality. Our results also showed that no reduction of late-stage cancer incidence was associated with no or minimal reduction in cancer mortality., Conclusions: Meta-regression of historical screening RCTs showed a strong linear association between reductions in late-stage cancer incidence and cancer mortality., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JYD, ETC, CAC, EAH, and NZ are employees of GRAIL, LLC, and report other support from GRAIL, LLC, during the conduct of the study. In addition, EAH has multiple patents in the field of cancer detection pending to GRAIL, LLC. EGL reports receiving consulting fees from GRAIL, LLC.

Purpose: The population with serious mental illness has high risk for hospitalization or death due to unhealthy behaviors and inadequate medical care, though the level of risk varies substantially. Programs that integrate medical and psychiatric services improve outcomes but are challenging to implement and access is limited. It would be useful to know whether benefits are confined to patients with specific levels of risk., Methods: In a population with serious mental illness and increased risk for hospitalization or death, a specialized medical home integrated services and improved treatment and outcomes. Treatment quality, chronic illness care, care experience, symptoms, and quality of life were assessed for a median of 385 days. Analyses examine whether improvements varied by baseline level of patient risk., Results: Patients with greater risk were more likely to be older, more cognitively impaired, and have worse mental health. Integrated services increased appropriate screening for body mass index, lipids, and glucose, but increases did not differ significantly by level of risk. Integrated services also improved chronic illness care, care experience, mental health-related quality of life, and psychotic symptoms. There were also no significant differences by risk level., Conclusions: There were benefits from integration of primary care and psychiatric care at all levels of increased risk, including those with extremely high risk above the 95th percentile. When developing integrated care programs, patients should be considered at all levels of risk, not only those who are the healthiest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

People with serious mental illness (SMI) have lower rates of use of preventative medical services and higher rates of mortality compared to the general population. Research shows that specialized primary care medical homes improve the health care of patients with SMI and are feasible to implement, safe, and more effective than usual care. However, specialized medical homes remain uncommon and model dissemination limited. As part of a controlled trial assessing an SMI-specialized medical home, we examined clinician and administrator perspectives regarding specialized versus mainstream primary care and identified ways to enhance the scale-up of a specialized primary care model for future dissemination. We conducted semistructured interviews with clinicians and administrators at three sites prior to the implementation of an SMI-specialized primary care medical home ( n = 26) and at 1-year follow-up ( n = 24); one site implemented the intervention, and two sites served as controls. Interviews captured service design features that affected the quality of care provided; contextual factors that supported or impeded medical home implementation; and knowledge, attitudes, and behaviors regarding the care of patients with SMI. Interviews were transcribed and coded. Clinicians and administrators described SMI-specialized primary care medical homes as advancing care coordination and outcomes for patients with SMI. Stakeholders identified elements of a specialized medical home that they viewed as superior to usual care, including having a holistic picture of patients' needs and greater care coordination. However, to enable scale-up, efforts are needed to increase staffing on care teams, develop robust clinician onboarding or training, and ensure close coordination with mental health care providers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Purpose: Understanding how stage at cancer diagnosis influences cause of death, an endpoint that is not susceptible to lead-time bias, can inform population-level outcomes of cancer screening., Methods: Using data from 17 US Surveillance, Epidemiology, and End Results registries for 1,154,515 persons aged 50-84 years at cancer diagnosis in 2006-2010, we evaluated proportional causes of death by cancer type and uniformly classified stage, following or extrapolating all patients until death through 2020., Results: Most cancer patients diagnosed at stages I-II did not go on to die from their index cancer, whereas most patients diagnosed at stage IV did. For patients diagnosed with any cancer at stages I-II, an estimated 26% of deaths were due to the index cancer, 63% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. In contrast, for patients diagnosed with any stage IV cancer, 85% of deaths were attributed to the index cancer, with 13% non-cancer and 2% non-index-cancer deaths. Index cancer mortality from stages I-II cancer was proportionally lowest for thyroid, melanoma, uterus, prostate, and breast, and highest for pancreas, liver, esophagus, lung, and stomach., Conclusion: Across all cancer types, the percentage of patients who went on to die from their cancer was over three times greater when the cancer was diagnosed at stage IV than stages I-II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier detection is likely to improve outcomes across cancer types, including those currently unscreened., (© 2024. The Author(s).)

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cure fraction-the proportion of persons considered cured of cancer after long-term follow-up-reflects the total impact of cancer control strategies, including screening, without lead-time bias. Previous studies have not reported stage-stratified cure fraction across the spectrum of cancer types., Methods: Using a mixture cure model, we estimated cure fraction across stages for 21 cancer types and additional subtypes. Cause-specific survival for 2.4 million incident cancers came from 17 US Surveillance, Epidemiology, and End Results registries for adults 40 to 84 years at diagnosis in 2006 to 2015, followed through 2020., Results: Across cancer types, a substantial cure fraction was evident at early stages, followed by either a sharp drop from stages III to IV or a steady decline from stages I to IV. For example, estimated cure fractions for colorectal cancer at stages I, II, III, and IV were 62% (95% confidence interval: 59%-66%), 61% (58%-65%), 58% (57%-59%), and 7% (7%-7%), respectively. Corresponding estimates for gallbladder cancer were 50% (46%-54%), 24% (22%-27%), 22% (19%-25%), and 2% (2%-3%). Differences in 5-year cause-specific survival between early-stage and stage IV cancers were highly correlated with between-stage differences in cure fraction, indicating that survival gaps by stage are persistent and not due to lead-time bias., Conclusions: A considerable fraction of cancer is amenable to cure at early stages, but not after metastasis., Impact: These results emphasize the potential for early detection of numerous cancers, including those with no current screening modalities, to reduce cancer death., (©2023 The Authors; Published by the American Association for Cancer Research.)

Objective: Chronic pain disproportionately affects medically and psychosocially complex patients, many of whom are at high risk of hospitalisation. Pain prevalence among high-risk patients, however, is unknown, and pain is seldom a focus for improving high-risk patient outcomes. Our objective is to (1) evaluate pain frequency in a high-risk patient population and (2) identify intensive management (IM) programme features that patients and providers perceive as important for promoting patient-centred pain care within primary care (PC)-based IM., Design: Secondary observational analysis of quantitative and qualitative evaluation data from a multisite randomised PC-based IM programme for high-risk patients., Setting: Five integrated local Veterans Affairs (VA) healthcare systems within distinct VA administrative regions., Participants: Staff and high-risk PC patients in the VA., Intervention: A multisite randomised PC-based IM programme for high-risk patients., Outcome Measures: (a) Pain prevalence based on VA electronic administrative data and (b) transcripts of interviews with IM staff and patients that mentioned pain., Results: Most (70%, 2593/3723) high-risk patients had at least moderate pain. Over one-third (38%, 40/104) of the interviewees mentioned pain or pain care. There were 89 pain-related comments addressing IM impacts on pain care within the 40 interview transcripts. Patient-identified themes were that IM improved communication and responsiveness to pain. PC provider-identified themes were that IM improved workload and access to expertise. IM team member-identified themes were that IM improved pain care coordination, facilitated non-opioid pain management options and mitigated provider compassion fatigue. No negative IM impacts on pain care were mentioned., Conclusions: Pain is common among high-risk patients. Future IM evaluations should consider including a focus on pain and pain care, with attention to impacts on patients, PC providers and IM teams., Competing Interests: Competing interests: We have read and understand the BMJ policy on competing interest and all authors have completed the ICMJE COI disclosure form. To the best of our knowledge, all authors report no competing interests, financial or other, that exist, apart from one author who reported receiving personal fees from Behavioral Health Services, Inc, outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Although pulmonary rehabilitation and regular exercise have improved negative emotions and cognitive capacity within cases of chronic obstructive pulmonary disease (COPD), influence by exercise training upon different cognitive and memory functions in COPD is still controversial. This investigation aimed to assess whether cognitive performance and mental health are affected by the benefits of exercise training within cases of COPD., Materials and Methods: This pilot investigation included thirty-three patients with Global Initiative for Chronic Obstructive Lung Disease stage ≥B. Based on the subjects' rights, all included patients could choose to join either the exercise group or the control group, according to their free will. Twelve patients were assigned to receive exercise treatment over a 2-month period, while the remaining 16 patients were assigned to the control group. Cognitive capacity outcomes were measured using the Wechsler Memory Scale-III Word List Test, Stroop task, and psychomotor vigilance task (PVT). Mood states were assessed through the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI)., Results: Most cases demonstrated major improvement for BDI and BAI scorings post-60-day therapy. During PVT, the omission rate decreased, while the hit rate increased, indicating an improvement in attention performance. Furthermore, this investigation found a significant increase in immediate verbal and recognition memory for word-list test. However, no major performance shifts were found on Stroop analysis., Conclusion: This investigation demonstrated that a 2-month exercise training program resulted in significant improvement in negative emotions, immediate memory, recognition memory, and attention., Competing Interests: Dr. En-Ting Chang, an editorial board member at Tzu Chi Medical Journal, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper., (Copyright: © 2023 Tzu Chi Medical Journal.)

Background: Many healthcare systems seek to improve care for complex high-risk patients, but engaging such patients to actively participate in their healthcare can be challenging., Objective: To identify and describe types of patient engagement strategies reported as successfully deployed by providers/teams and experienced by patients in a Veterans Health Administration (VA) intensive primary care (IPC) pilot program., Methods: We conducted semi-structured qualitative telephone interviews with 29 VA IPC staff (e.g., physicians, nurses, psychologists) and 51 patients who had at least four IPC team encounters. Interviews were recorded, transcribed, and analyzed thematically using a combination a priori/inductive approach., Results: The engagement strategies successfully deployed by the IPC providers/teams could be considered either more "facilitative," i.e., facilitated by and dependent on staff actions, or more "self-sustaining," i.e., taught to patients, thus cultivating their ongoing patient self-care. Facilitative strategies revolved around enhancing patient access and coordination of care, trust-building, and addressing social determinants of health. Self-sustaining strategies were oriented around patient empowerment and education, caregiver and/or community support, and boundaries and responsibilities. When patients described their experiences with the "facilitative" strategies, many discussed positive proximal outcomes (e.g., increased access to healthcare providers). Self-sustaining strategies led to positive (self-reported) longer-term clinical outcomes, such as behavior change., Conclusion: We identified two categories of strategies for successfully engaging complex, high-risk patients: facilitative and self-sustaining. Intensive primary care program leaders may consider thoughtfully building "self-sustaining" engagement strategies into program development. Future research can confirm their effectiveness in improving health outcomes., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC) carcinogenesis has not previously been investigated., Methods: We characterized the oral salivary fungal mycobiome in 476 untreated incident NPC patients and 537 population-based controls using fungal internal transcribed spacer (ITS)-2 sequencing. The relationship between oral fungal mycobiome and the risk of NPC was assessed through bioinformatic and biostatistical analyses., Findings: We found that lower fungal alpha diversity was associated with an increased odds of NPC [lower vs. higher: observed features (adjusted odds ratio [OR] = 5.81, 95% confidence interval [CI] = 3.60-9.38); Simpson diversity (1.53, 1.03-2.29); Shannon diversity (2.03, 1.35-3.04)]. We also observed a significant difference in global fungal community patterns between cases and controls based on Bray-Curtis dissimilarity (P < 0.001). Carriage of oral fungal species, specifically, Saccharomyces cerevisiae, Candida tropicalis, Lodderomyces elongisporus, Candida albicans, and Fusarium poae, was associated with significantly higher odds of NPC, with ORs ranging from 1.56 to 4.66. Individuals with both low fungal and low bacterial alpha diversity had a profoundly elevated risk of NPC., Interpretation: Our results suggest that dysbiosis in the oral mycobiome, characterized by a loss of fungal community diversity and overgrowth of several fungal organisms, is associated with a substantially increased risk of NPC., Funding: This work was funded by the US National Institutes of Health, the Swedish Research Council, the High-level Talents Research Start-up Project of Fujian Medical University, and the China Scholarship Council., Competing Interests: Declaration of interests E.C. is an employee of GRAIL, LLC, which played no role in the development of this manuscript. The other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study suggests the blood pressure-lowering effects of potassium-enriched salt substitutes may reduce cardiovascular morbidity and mortality.

The current paradigm of carcinogenesis as a cellular evolutionary process driven by mutations of a few critical driver genes has immediate logical implications for the epidemiology of cancer. These include the impact of age on cancer risk, the role played by inherited tumor predisposition syndromes, and the interaction of genetics and environmental exposures on cancer risk. In this paper, we explore the following logical epidemiological consequences of carcinogenesis as a clonal process of mutation accumulation, with special emphasis on asbestos-related cancers, specifically malignant mesothelioma:1 All cancers, including mesothelioma, can and do occur spontaneously, i.e., in the absence of exposure to any environmental carcinogens. 2. Age is an important determinant of cancer risk, with or without exposure to environmental carcinogens. 3. Genetic tumor predisposition syndromes, such as the BAP1 syndrome, increase enormously the risk of cancer even in the absence of exposure to environmental carcinogens. We illustrate these concepts by applying a multistage clonal expansion model to U.S. Surveillance, Epidemiology, and End Results cancer registry data for pleural and peritoneal malignant mesotheliomas in 1975-2018., Competing Interests: Declaration of competing interest Exponent is an international consulting company. SM has served as a consulting and testifying expert in asbestos and talc litigation. EC has served as a consulting and testifying expert in talc litigation. EGL has no competing interests. This work received no funding and the authors received no compensation for this work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A concern of reverse causation exists about the association between nasopharyngeal carcinoma (NPC) prognosis and body mass index (BMI) at diagnosis, while the prognostic impact of BMI measured years before diagnosis is unknown. Therefore, we investigated associations of prediagnosis and pretreatment BMI and body shape on NPC mortality. From a population-based patient cohort in southern China between 2010 and 2013, we included 2526 incident NPC cases with prospective follow-up through 2018. We assessed the associations of BMI and body shape at age 20 years, 10 years before diagnosis, and at diagnosis with NPC mortality, combining strategies of stratification and statistical adjustment to minimize reverse causation. We observed 25% lower all-cause mortality (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.64-0.89) and 25% lower NPC-specific mortality (HR 0.75, 95% CI: 0.61-0.91) among overweight vs normal-weight NPC cases at diagnosis. Lean body shapes 1 and 2 at diagnosis were associated with 68% and 23% higher all-cause mortality, respectively, compared to normal body shape 3. No effect modification by cancer stage was detected for associations with all-cause or NPC-specific mortality. Associations with BMI and body shape 10 years before diagnosis were similar but attenuated, while body size and shape at age 20 were not associated with mortality. Being overweight at diagnosis decreased mortality, and thinner body shape increased mortality, compared to normal weight/body shape. These associations may be due to poorer nutrition and treatment intolerance, resulting in treatment discontinuation and worse survival outcomes., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: We aim to clarify the controversial associations between EBV-related antibodies and gastric cancer risk., Methods: We analysed the associations between serological Epstein-Barr nuclear antigen 1 immunoglobulin A (EBNA1-IgA) and viral capsid antigen immunoglobulin A (VCA-IgA) by enzyme-linked immunosorbent assay and the risk of gastric cancer in a nested case-control study originated from a population-based nasopharyngeal carcinoma (NPC) screening cohort in Zhongshan, a city of southern China, including 18 gastric cancer cases and 444 controls. Conditional logistic regression was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs)., Results: All the sera of cases were sampled before diagnosis and the median time interval was 3.04 (range: 0.04, 7.59) years. Both increased relative optical density (rOD) values of EBNA1-IgA and VCA-IgA were associated with higher risks of gastric cancer with age adjusted ORs of 1.99 (95%CI: 1.07, 3.70) and 2.64 (95%CI: 1.33, 5.23), respectively. Each participant was further classified as high or medium/low risk based on a combination of two anti-EBV antibody levels. Participants in the high-risk group had substantially higher odds of developing gastric cancer than that in the medium/low risk group with an age adjusted OR of 6.53 (95%CI: 1.69, 25.26)., Conclusions: Our research reveals positive associations between EBNA1-IgA and VCA-IgA and gastric cancer risk in southern China. We thus postulate that EBNA1-IgA and VCA-IgA might appear to be potential biomarkers for gastric cancer. More research to further validate the results among diverse populations and investigate its underlying biological mechanism is needed., (© 2023. The Author(s).)

Background: Primary care intensive management programs utilize interdisciplinary care teams to comprehensively meet the complex care needs of patients at high risk for hospitalization. The mixed evidence on the effectiveness of these programs focuses on average treatment effects that may mask heterogeneous treatment effects (HTEs) among subgroups of patients. We test for HTEs by patients' demographic, economic, and social characteristics., Methods: Retrospective analysis of a VA randomized quality improvement trial. 3995 primary care patients at high risk for hospitalization were randomized to primary care intensive management (n = 1761) or usual primary care (n = 1731). We estimated HTEs on ED and hospital utilization one year after randomization using model-based recursive partitioning and a pre-versus post-with control group framework. Splitting variables included administratively collected demographic characteristics, travel distance, copay exemption, risk score for future hospitalizations, history of hospital discharge against medical advice, homelessness, and multiple residence ZIP codes., Results: There were no average or heterogeneous treatment effects of intensive management one year after enrollment. The recursive partitioning algorithm identified variation in effects by risk score, homelessness, and whether the patient had multiple residences in a year. Within each distinct subgroup, the effect of intensive management was not statistically significant., Conclusions: Primary care intensive management did not affect acute care use of high-risk patients on average or differentially for patients defined by various demographic, economic, and social characteristics., Implications: Reducing acute care use for high-risk patients is complex, and more work is required to identify patients positioned to benefit from intensive management programs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)