Assessing and Addressing the Determinants of Appalachian Population Health: A Scoping Review.

Introduction: Residents of Appalachia experience elevated rates of morbidity and mortality compared to national averages, and these disparities are associated with inequitable exposures to various determinants of population health. Social and environmental determinants of health are a useful lens through which to develop and evaluate programs to mitigate regional health disparities.

Methods: This 2023 scoping review was conducted of studies linking determinants of Appalachian health with leading causes of regional mortality and morbidity.

Promoting sustainable responses to the US opioid epidemic with community-academic partnerships: qualitative outcomes from a statewide program.

Background: Drug overdose deaths in the United States have continued to increase at an alarming rate. The Substance Abuse and Mental Health Services Administration (SAMHSA) distributed more than $7 billion between January 2016 and June 2020 to address the drug overdose crisis. The funds support evidence-based responses, including medications for opioid use disorder, and other prevention, treatment and recovery activities.

A Formative Evaluation of Two FASD Prevention Communication Strategies.

Aims: To evaluate the feasibility, acceptability and effectiveness of placing FASD prevention messages in the women's restrooms of establishments serving alcohol in Alaska and the Yukon, regions with high rates of FASD.

Methods: Our team placed an FASD educational poster, and posters affixed to a pregnancy test dispenser, in women's restrooms of bars and restaurants. We compared drinking behaviors and knowledge and beliefs about FASD among participants at baseline and at follow-up.

Implementation of Care Management: An Analysis of Recent AHRQ Research.

Care management (CM) is a promising team-based, patient-centered approach "designed to assist patients and their support systems in managing medical conditions more effectively." As little is known about its implementation, this article describes CM implementation and associated lessons from 12 Agency for Healthcare Research and Quality-sponsored projects. Two rounds of data collection resulted in project-specific narratives that were analyzed using an iterative approach analogous to framework analysis.

Plk1 inhibition causes post-mitotic DNA damage and senescence in a range of human tumor cell lines.

Plk1 is a checkpoint protein whose role spans all of mitosis and includes DNA repair, and is highly conserved in eukaryotes from yeast to man. Consistent with this wide array of functions for Plk1, the cellular consequences of Plk1 disruption are diverse, spanning delays in mitotic entry, mitotic spindle abnormalities, and transient mitotic arrest leading to mitotic slippage and failures in cytokinesis. In this work, we present the in vitro and in vivo consequences of Plk1 inhibition in cancer cells using potent, selective small-molecule Plk1 inhibitors and Plk1 genetic knock-down approaches.

Medical home implementation and trends in diabetes quality measures for AN/AI primary care patients.

Aims: Patient-centered medical home (PCMH) principles including provider continuity, coordination of care, and advanced access align with healthcare needs of patients with Type II diabetes mellitus (DM-II). We investigate changes in trend for DM-II quality indicators after PCMH implementation at Southcentral Foundation, a tribal health organization in Alaska.

Methods: Monthly rates of DM-II incidence, hemoglobin A1c (HbA1c) measurements, and service utilization were calculated from electronic health records from 1996 to 2009.

Initial findings from the implementation of a community-based sentinel surveillance system to assess the health effects of climate change in Alaska.

Background: This report describes the results of a study to determine whether a community-based sentinel surveillance system can be developed and implemented to assess the health effects of climate change, and to contribute to local discussions to mitigate these health effects. The purpose of this report is to describe the process and outcomes of this innovative approach to identifying priority areas for adaptation investment. This report can be used to assist local, state and federal governments in determining how to develop actions and policies to promote adaptation to climate change.

Assessing the social and physical determinants of circumpolar population health.

Introduction: Systematic reviews of the social and physical determinants of health provide metrics for evaluation of programs to mitigate health disparities. Previous meta-analyses of the population health literature have identified several proximate social and physical determinants of population health in the circumpolar north including addiction, environmental exposures, diet/nutrition and global climate change. Proximate health determinants are most amenable to early detection and modification or mitigation through disease prevention or health promotion interventions.

Tribal implementation of a patient-centred medical home model in Alaska accompanied by decreased hospital use.

Background: Between 1995 and 1998, tribally owned Southcentral Foundation (SCF) incrementally assumed responsibility from the Indian Health Service (IHS) for primary care services on the Alaska Native Medical Center (ANMC) campus in Anchorage, Alaska. In 1999, SCF began implementing components of a Patient-Centered Medical Home (PCMH) model to improve access and continuity of care.

Objective: To evaluate hospitalisation trends before, during and after PCMH implementation.

Context matters: the experience of 14 research teams in systematically reporting contextual factors important for practice change.

Purpose: We aimed to advance the internal and external validity of research by sharing our empirical experience and recommendations for systematically reporting contextual factors.

Methods: Fourteen teams conducting research on primary care practice transformation retrospectively considered contextual factors important to interpreting their findings (internal validity) and transporting or reinventing their findings in other settings/situations (external validity). Each team provided a table or list of important contextual factors and interpretive text included as appendices to the articles in this supplement.

Process and outcomes of patient-centered medical care with Alaska Native people at Southcentral Foundation.

Purpose: This study describes key elements of the transition to a patient-centered medical home (PCMH) model at Southcentral Foundation (SCF), a tribally owned and managed primary care system, and evaluates changes in emergency care use for any reason, for asthma, and for unintentional injuries, during and after the transition.

Methods: We conducted a time series analyses of emergency care use from medical record data. We also conducted 45 individual, in-depth interviews with PCMH patients (customer-owners), primary care clinicians, health system employees, and tribal leaders.

Demographic and contextual factors associated with inhalant use among youth in rural Alaska.

Background: Abuse of harmful legal products that can be inhaled or ingested is a serious and growing problem in many rural Alaskan communities, and particularly so among preteens.

Methods: This study analyses data collected during baseline measurements of a 5-year NIH/NIDA-funded study entitled A Community Trial to Prevent Youth's Abuse of Harmful Legal Products in Alaska. Youth in 8 communities located throughout the state participated in a survey during the fall of 2009 to measure the prevalence and availability of harmful legal products (n=697).

Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905).

This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice.

Genome-wide siRNA screen for modulators of cell death induced by proteasome inhibitor bortezomib.

Multiple pathways have been proposed to explain how proteasome inhibition induces cell death, but mechanisms remain unclear. To approach this issue, we performed a genome-wide siRNA screen to evaluate the genetic determinants that confer sensitivity to bortezomib (Velcade (R); PS-341). This screen identified 100 genes whose knockdown affected lethality to bortezomib and to a structurally diverse set of other proteasome inhibitors.

Promoting prostate-specific antigen informed decision-making. Evaluating two community-level interventions.

Background: Most medical associations recommend that patients make informed decisions about whether to be screened for prostate cancer with the prostate-specific antigen (PSA) test. Studies assessing how to promote PSA informed decision-making (IDM) have been conducted almost exclusively in healthcare settings; there is a need for similar research in community settings.

Methods: This paper describes the results of a 5-year study (2002--2007) in which two community-level interventions were developed, implemented, and evaluated in matched upper- and lower-SES comparison communities in Greensboro and Wilmington, North Carolina.

American Joint Committee on Cancer clinical stage as a selection criterion for sentinel lymph node biopsy in thin melanoma.

Background: A significant proportion of newly diagnosed melanomas are thin lesions (< or = 1.00 mm). Because tumor thickness correlates with the risk for nodal metastases, sentinel lymph node (SLN) biopsy in this subset is controversial.

Response of combination platinum and gemcitabine chemotherapy for recurrent epithelial ovarian carcinoma.

Objective: It has been postulated that gemcitabine inhibits DNA repair, and platinum resistance is due to increased DNA repair activity. The addition of gemcitabine to platinum-based agents may have synergistic tumoricidal activity.

Methods: Retrospective chart review of all patients with recurrent, persistent, or progressive fallopian tube or ovarian carcinoma treated with a platinum-based compound and gemcitabine from 2001 to present was performed.

The prognostic significance of margin width for extremity and trunk sarcoma.

Background And Objectives: To evaluate the significance of resection margin for soft tissue sarcoma (STS), we determined local recurrence-free interval (LRFI), distant metastases-free interval (DMFI), and overall survival (OS) for primary extremity and truncal STS with clear margins (> or =10 mm), close margins (1-9 mm), and positive margins (0 mm).

Methods: Patients were evaluated via review of charts and tumor specimens.

Results: Among 111 patients, tumors were predominantly high grade (86%), > or =5 cm (76%), and deep (81%).

Evaluation of urinary plasminogen activator, its receptor, matrix metalloproteinase-9, and von Willebrand factor in pancreatic cancer.

Purpose: Pancreatic cancer remains a devastating problem with the majority of patients succumbing to death from this disease. A hallmark of pancreatic cancer is the loss of basement membrane that may be attributed to the action of urinary plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9). These enzymes are also implicated in angiogenesis.

Effect of stereotactic core needle biopsy on pathologic measurement of tumor size of T1 invasive breast carcinomas presenting as mammographic masses.

Background: Stereotactic core needle biopsy (SCNB) may change the size of the tumor defined pathologically at excision. This may alter tumor stage and affect recommendations for adjuvant systemic therapy. This study evaluated the effect of SCNB on assessment of pathologic tumor size and staging for invasive breast carcinomas presenting as mammographic masses.

The impact of pre-therapy extraperitoneal surgical staging on the evaluation and treatment of patients with locally advanced cervical cancer.

Objective: The use of extraperitoneal surgical staging prior to treatment in patients with bulky or locally advanced cervical cancer allows the detection and treatment of disease beyond the standard pelvic radiation fields. This study was conducted to evaluate the impact of extraperitoneal surgical staging in the treatment and outcome of patients with locally advanced cervical cancer.

Methods: 51 patients with locally advanced cervical cancer treated between 1985 and 1998 were retrospectively reviewed.

Pulmonary resection in metastatic uterine and cervical malignancies.

Objective: Although thoracotomy for removal of pulmonary metastasis is well documented in a wide variety of solid tumors, data are sparse regarding management of patients with gynecologic malignancies metastatic to the lung.

Methods: We retrospectively reviewed the Roswell Park Cancer Institute experience between 1982 and 1999. Of 82 eligible patients with gynecologic tumors metastatic and confined to the lung, 25 underwent pulmonary resection.

Pericardial catheter sclerosis versus surgical procedures for pericardial effusions in cancer patients.

Background: Approximately 21% of patients with advanced malignancies have cardiac or pericardial involvement with tumor. Controversy exists regarding the optimal approach to the pericardial space when hemodynamic compromise due to effusions occurs.

Methods: A six-year retrospective review of 59 cancer patients with pericardial effusions.

Soluble 2-substituted aminopyrido[2,3-d]pyrimidin-7-yl ureas. Structure-activity relationships against selected tyrosine kinases and exploration of in vitro and in vivo anticancer activity.

In continuing our search for medicinal agents to treat proliferative diseases, we have discovered 2-substituted aminopyrido[2,3-d]pyrimidin-7-yl ureas as a novel class of soluble, potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. From the lead structure 1, several series of analogues were made that examined the C-6 aryl substituent, a variety of water solublizing substitutents at the C-2 position, and urea or other acyl functionality at the N-7 position.