A novel method for measuring the burden of breast cancer in neighborhoods.

Community-based breast cancer prevention efforts often focus on women who live in the same neighborhoods, as they tend to have similar demographic characteristics, health behaviors, and environmental exposures; yet little research describes methods of selecting neighborhoods of focus for community-based cancer prevention interventions. Studies frequently use demographics from census data, or single breast cancer outcomes (e.g., mortality, morbidity) in order to choose neighborhoods of focus for breast cancer interventions, which may not be optimal. This study presents a novel method for measuring the burden of breast cancer among neighborhoods that could be used for selecting neighborhoods of focus. In this study, we 1) calculate a metric composed of multiple breast cancer outcomes to describe the burden of breast cancer in census tracts Philadelphia, PA, USA; 2) map the neighborhoods with the greatest breast cancer burden; and 3) compare census tracts with the highest burden of breast cancer to those with demographics sometimes used for geo-based prioritization, i.e., race and income. The results of our study showed that race or income may not be appropriate proxies for neighborhood breast cancer burden; comparing the breast cancer burden with demographics at the census tract level, we found few overlaps with the highest percentage African American or the lowest median incomes. Agencies implementing community-based breast cancer interventions should consider this method to inform the selection of neighborhoods for breast cancer prevention interventions, including education, screening, and treatment.

Estimating Eligibility for Lung Cancer Screening by Neighborhood in Philadelphia Using Previous and Current USPSTF Guidelines.

The National Lung Screening Trial established the benefits of low-dose computed tomography for lung cancer screening (LCS) to identify lung cancer at earlier stages. In February 2021, the US Preventive Services Task Force (USPSTF) revised the eligibility recommendations to increase the number of high-risk individuals eligible for LCS and, in effect, expand screening eligibility for vulnerable populations. One strategy for facilitating LCS is to implement targeted screening in geographic areas with the greatest need. In Philadelphia, although neighborhood smoking rates have been defined, it is not known which neighborhoods have the greatest number of people eligible for LCS. In this study, the authors estimate eligibility for LCS within Philadelphia neighborhoods using both previous and current USPSTF guidelines. They used the Public Health Management Corporation's Household Health Survey from 2010, 2012, and 2015 to identify the number of people within ever-smoker groups (current every day, current occasional, and former smokers) by neighborhood in Philadelphia. Using the 2015 National Health Interview Survey (NHIS) Cancer Supplement, they identified the percentages within ever-smoker groups that were LCS eligible using the previous and current USPSTF guidelines. Finally, they applied the percentages eligible for the ever-smoker groups from the NHIS to the numbers in these groups within Philadelphia neighborhoods. They found that the number of Philadelphians eligible for LCS increased from 41,946 to 89,231 after the revised USPSTF guidelines. The current USPSTF guidelines increased eligibility for LCS within all Philadelphia neighborhoods, with the greatest increases in the River Wards planning district. Local providers should use these results to prioritize LCS services within neighborhoods with greatest eligibility.

A platform for oncogenomic reporting and interpretation.

Manual interpretation of variants remains rate limiting in precision oncology. The increasing scale and complexity of molecular data generated from comprehensive sequencing of cancer samples requires advanced interpretative platforms as precision oncology expands beyond individual patients to entire populations. To address this unmet need, we introduce a Platform for Oncogenomic Reporting and Interpretation (PORI), comprising an analytic framework that facilitates the interpretation and reporting of somatic variants in cancer. PORI integrates reporting and graph knowledge base tools combined with support for manual curation at the reporting stage. PORI represents an open-source platform alternative to commercial reporting solutions suitable for comprehensive genomic data sets in precision oncology. We demonstrate the utility of PORI by matching 9,961 pan-cancer genome atlas tumours to the graph knowledge base, calculating therapeutically informative alterations, and making available reports describing select individual samples.

Corticotropin-Releasing Hormone from the Pontine Micturition Center Plays an Inhibitory Role in Micturition.

Lower urinary tract or voiding disorders are prevalent across all ages and affect >40% of adults over 40 years old, leading to decreased quality of life and high health care costs. The pontine micturition center (PMC; i.e., Barrington's nucleus) contains a large population of neurons that localize the stress-related neuropeptide, corticotropin-releasing hormone (CRH) and project to neurons in the spinal cord to regulate micturition. How the PMC and CRH-expressing neurons in the PMC control volitional micturition is of critical importance for human voiding disorders. To investigate the specific role of CRH in the PMC, neurons in the PMC-expressing CRH were optogenetically activated during in vivo cystometry in unanesthetized mice of either sex. Optogenetic activation of CRH-PMC neurons led to increased intermicturition interval and voided volume, similar to the altered voiding phenotype produced by social stress. Female mice showed a significantly more pronounced phenotype change compared with male mice. These effects were eliminated by CRH-receptor 1 antagonist pretreatment. Optogenetic inhibition of CRH-PMC neurons led to an altered voiding phenotype characterized by more frequent voids and smaller voided volumes. Last, in a cyclophosphamide cystitis model of bladder overactivity, optogenetic activation of CRH-PMC neurons returned the voiding pattern to normal. Collectively, our findings demonstrate that CRH from PMC spinal-projecting neurons has an inhibitory function on micturition and is a potential therapeutic target for human disease states, such as voiding postponement, urinary retention, and underactive or overactive bladder.SIGNIFICANCE STATEMENT The pontine micturition center (PMC), which is a major regulator of volitional micturition, is neurochemically heterogeneous, and excitatory neurotransmission derived from PMC neurons is thought to mediate the micturition reflex. In the present study, using optogenetic manipulation of CRH-containing neurons in double-transgenic mice, we demonstrate that CRH, which is prominent in PMC-spinal projections, has an inhibitory function on volitional micturition. Moreover, engaging this inhibitory function of CRH can ameliorate bladder hyperexcitability induced by cyclophosphamide in a model of cystitis. The data underscore CRH as a novel target for the treatment of voiding dysfunctions, which are highly prevalent disease processes in children and adults.

Spontaneous neoplasia in captive syngnathid species: A retrospective case series (2003-2014) and literature review.

Syngnathidae (seahorses, pipefish and seadragons) are charismatic species commonly kept in commercial aquaria, but published literature on syngnathid diseases is limited and immunohistochemical techniques not routinely employed. A retrospective review of 2,541 syngnathid submissions received between March 2003 and October 2016 identified 18 neoplasms including germ cell tumours, exocrine pancreatic and intestinal carcinomas, chromatophoromas, and single cases of lymphoma, thyroid and renal carcinoma, swim bladder and pituitary adenoma. Big-bellied seahorses accounted for 19% of submissions, but 50% of neoplasms were diagnosed in this species. This study includes the first reported cases of germ cell tumours, chromatophoroma, thyroid carcinoma and pituitary adenoma in Syngnathidae and the first reports of neoplasia in pipefish species. Out of nine commercial antibodies trialled for immunohistochemical characterization of neoplastic tissue, only pan-cytokeratin proved cross-reactive. Electron microscopy was performed in four cases. Tumours should be considered as differential diagnosis in cases with buoyancy issues, debilitated or emaciated animals, and may predispose to secondary infections. This study highlights the value of histopathological disease surveillance for commercial aquarium settings.

Overdose Risk Associated with Opioid Use upon Hospital Discharge in Veterans Health Administration Surgical Patients.

OBJECTIVE: To determine an association between opioid use upon hospital discharge (ongoing and newly started) in surgical patients and risks of opioid overdose and delirium for the first year. DESIGN: Retrospective, cohort study. SETTING: Population-level study of Veterans Health Administration patients. SUBJECTS: All Veterans Health Administration patients (N = 64,391) who underwent surgery in 2011, discharged after one or more days, and without a diagnosis of opioid overdose or delirium from 90 days before admission through 30 days postdischarge (to account for additional opioid dosing in the context of chronic use). METHODS: Patients' opioid use was categorized as 1) no opioids, 2) tramadol only, 3) short-acting only, 4) long-acting only, 5) short- and long-acting. We calculated unadjusted incidence rates and the incidence rate ratio (IRR) for opioid overdose and drug delirium for two time intervals: postdischarge days 0-30 and days 31-365. We then modeled outcomes of opioid overdose and delirium for postdischarge days 31-365 using a multivariable extended Cox regression model. Sensitivity analysis examined risk factors for overdose for postdischarge days 0-30. RESULTS: Incidence of overdose was 11-fold greater from postdischarge days 0-30 than days 31-365: 26.3 events/person-year (N = 68) vs 2.4 events/person-year (N = 476; IRR = 10.80, 95% confidence interval [CI] = 8.37-13.92). Higher-intensity opioid use was associated with increasing risk of overdose for the year after surgery, with the highest risk for the short- and long-acting group (hazard ratio = 4.84, 95% CI = 3.28-7.14). Delirium (IRR = 10.66, 95% CI = 7.96-14.29) was also associated with higher opioid intensity. CONCLUSIONS: Surgical patients should be treated with the lowest effective intensity of opioids and be monitored to prevent opioid-related adverse events.

Patient and provider perspectives on the development of personalized medicine: a mixed-methods approach.

While genetic testing gains adoption in specialty services such as oncology, neurology, and cardiology, use of genetic and genomic testing has yet to be adopted as widely in primary care. The purpose of this study is to identify and compare patient and primary care provider (PCP) expectations of genetics services in primary care. Patient and PCP perspectives were assessed through a mixed-method approach combining an online survey and semi-structured interviews in a primary care department of a large academic medical institution. A convenience sample of 100 adult primary care patients and 26 PCPs was gathered. The survey and interview questions focused on perceptions of genetic testing, experience with genetic testing, and expectations of genetic services in primary care. Patients felt that their PCP was knowledgeable about genetic testing and expected their PCP to be the first to recognize a need for genetic testing based on family history. Nonetheless, patients reported that PCPs rarely used family history information to discuss genetic risks or order testing. In contrast, PCPs felt uncertain about the clinical utility and scientific value of genetic testing. PCPs were concerned that genetic testing could cause anxiety, frustration, discrimination, and reduced insurability, and that there was unequal access to testing. PCPs described themselves as being "gatekeepers" to genetic testing but did not feel confident or have the desire to become experts in genetic testing. However, PCPs were open to increasing their working knowledge of genetic testing. Within this academic medical center, there is a gap between what patients expect and what primary care providers feel they are adequately prepared to provide in terms of genetic testing services.

Primary Care-Based Skin Cancer Screening in a Veterans Affairs Health Care System.

Importance: Skin cancer screening may improve melanoma outcomes and keratinocyte carcinoma morbidity, but little is known about the feasibility of skin cancer training and clinical skin examination (CSE) by primary care practitioners (PCPs) in large health care systems. Objective: To assess the association of skin cancer training and screening by PCPs with dermatology referral patterns and rates of skin biopsies. Design, Setting, and Participants: In this pilot interventional study performed at the Veterans Affairs Palo Alto Health Care System, patients 35 years or older scheduled for an annual health habits screen in the PCP general medicine clinics were studied. Interventions: Six PCPs underwent Internet Curriculum for Melanoma Early Detection (INFORMED) training in May 2015, and 5 screened patients during the following 14 months. Main Outcomes and Measures: Proportion of dermatology referrals, subsequent skin biopsies, and PCP diagnostic accuracy for skin cancer or precancer compared with dermatologist diagnosis were assessed in screened patients 14 months before the intervention (February 18, 2014, through April 30, 2015) and after the intervention (June 18, 2015, through August 30, 2016). Results: Among 258 patients offered screening (median age, 70 years; age range, 35-94 years; 255 [98.8%] male), 189 (73.3%) received CSE and 69 (26.7%) declined. A total of 62 of 189 patients (32.8%) were referred to a dermatologist after intervention: 33 (53.2%) for presumptive skin cancers and 15 (24.2%) for precancers. Nine of 50 patients (18.0%) evaluated in dermatology clinic underwent biopsy to exclude skin cancer. Correct diagnoses were made by PCPs in 13 of 38 patients (34.2%; 4 of 27 patients [14.8%] diagnosed with skin cancers and 5 of 11 patients [45.5%] diagnosed with actinic keratoses). Comparison of all outpatient visits for the 5 main participating PCPs before vs after intervention revealed no significant differences in dermatology referrals overall and those for presumptive skin cancer or actinic keratoses, skin biopsies, or PCP diagnostic accuracy with the exception of significantly fewer postintervention dermatology referrals that lacked specific diagnoses (25 [1.0%] vs 10 [0.4%], P = .01). Conclusions and Relevance: This pilot study suggests that PCP-based skin cancer training and screening are feasible and have the potential to improve PCP diagnostic accuracy without increasing specialty referrals or skin biopsies. Additional studies comparing screening rates, specialty referrals, and patient outcomes in trained vs untrained PCPs are needed before screening is widely implemented in large health care systems in the United States.

Time-to-Cessation of Postoperative Opioids: A Population-Level Analysis of the Veterans Affairs Health Care System.

OBJECTIVE: This study aims to determine 1) the epidemiology of perioperative opioid use; and 2) the association between patterns of preoperative opioid use and time-to-cessation of postoperative opioids. DESIGN: Retrospective, cohort study. SETTING: National, population-level study of Veterans Healthcare Administration (VHA) electronic clinical data. SUBJECTS: All VHA patients (n = 64,391) who underwent surgery in 2011, discharged after stays of ≥1 day, and receiving ≥1 opioid prescription within 90 days of discharge. METHODS: Patients' preoperative opioid use were categorized as 1) no opioids, 2) tramadol only, 3) short-acting (SA) acute/intermittent (≤ 90 days fill), 4) SA chronic (> 90 days fill), or 5) any long-acting (LA). After defining cessation as 90 consecutive, opioid-free days, the authors calculated time-to-opioid-cessation (in days), from day 1 to day 365, after hospital discharge. The authors developed extended Cox regression models with a priori identified predictors. Sensitivity analyses used alternative cessation definitions (30 or 180 consecutive days). RESULTS: Almost 60% of the patients received preoperative opioids: tramadol (7.5%), SA acute/intermittent (24.1%), SA chronic (17.5%), and LA (5.2%). For patients opioid-free preoperatively, median time-to-cessation of opioids postoperatively was 15 days. The SA acute/intermittent cohort (HR =1.96; 95% CI =1.92-2.00) had greater risk for prolonged time-to-cessation than those opioid-free (reference), but lower risk than those taking tramadol only, SA chronic (HR = 9.09; 95% CI = 8.33-9.09), or LA opioids (HR = 9.09; 95% CI = 8.33-10.00). Diagnoses of chronic pain, substance-use, or affective disorders were weaker positive predictors. Sensitivity analyses maintained findings. CONCLUSION: Greater preoperative levels of opioid use were associated with progressively longer time-to-cessation postoperatively.

Sex differences in chronic pain management practices for patients receiving opioids from the Veterans Health Administration.

BACKGROUND: Women experience chronic pain and use pain-related health care at higher rates than men. It is not known whether the pain-related health care female veterans receive is consistent with clinical practice guideline recommendations or whether receipt of this care differs between men and women. OBJECTIVE: The aim of this study was to identify whether sex differences in chronic pain management care exist for patients served by the Veterans Health Administration (VHA). DESIGN: Data on patient demographics, diagnostic criteria, and health care utilization were extracted from VHA administrative databases for fiscal year 2010 (FY10). PATIENTS: Patients in this study included all VHA patients (excluding metastatic cancer patients) who received more than 90 days of a short-acting opioid medication or a long-acting opioid medication prescription in FY10 study. MEASURES: Multilevel logistic regressions were conducted to identify sex differences in receipt of guideline-recommended chronic pain management. RESULTS: A total of 480,809 patients met inclusion criteria. Female patients were more likely to receive most measures of guideline-recommended care for chronic pain including mental health assessments, psychotherapy, rehabilitation therapy, and pharmacy reconciliation. However, women were more likely to receive concurrent sedative prescriptions, which is inconsistent with guideline recommendations. Most of the observed sex differences persisted after controlling for key demographic and diagnostic differences. CONCLUSIONS: Findings suggest that female VHA patients are more likely to receive an array of pain management practices than male patients, including both contraindicated and recommended polypharmacy. Quality improvement efforts to address underutilization of mental health and rehabilitative services for pain by male patients and polypharmacy in female patients should be considered.