International survey on invasive lobular breast cancer identifies priority research questions.

There is growing awareness of the unique etiology, biology, and clinical presentation of invasive lobular breast cancer (ILC), but additional research is needed to ensure translation of findings into management and treatment guidelines. We conducted a survey with input from breast cancer physicians, laboratory-based researchers, and patients to analyze the current understanding of ILC, and identify consensus research questions. 1774 participants from 66 countries respondents self-identified as clinicians (N = 413), researchers (N = 376), and breast cancer patients and advocates (N = 1120), with some belonging to more than one category. The majority of physicians reported being very/extremely (41%) to moderately (42%) confident in describing the differences between ILC and invasive breast cancer of no special type (NST). Knowledge of histology was seen as important (73%) and as affecting treatment decisions (51%), and most agreed that refining treatment guidelines would be valuable (76%). 85% of clinicians have never powered a clinical trial to allow subset analysis for histological subtypes, but the majority would consider it, and would participate in an ILC clinical trials consortium. The majority of laboratory researchers, reported being and very/extremely (48%) to moderately (29%) confident in describing differences between ILC and NST. They reported that ILCs are inadequately presented in large genomic data sets, and that ILC models are insufficient. The majority have adequate access to tissue or blood from patients with ILC. The majority of patients and advocates (52%) thought that their health care providers did not sufficiently explain the unique features of ILC. They identified improvement of ILC screening/early detection, and identification of better imaging tools as top research priorities. In contrast, both researchers and clinicians identified understanding of endocrine resistance and identifying novel drugs that can be tested in clinical trials as top research priority. In summary, we have gathered information from an international community of physicians, researchers, and patients/advocates that we expect will lay the foundation for a community-informed collaborative research agenda, with the goal of improving management and personalizing treatment for patients with ILC.

Disaggregation of Green Space Access, Walkability, and Behavioral Risk Factor Data for Precise Estimation of Local Population Characteristics.

BACKGROUND: Social and Environmental Determinants of Health (SEDH) provide us with a conceptual framework to gain insights into possible associations among different human behaviors and the corresponding health outcomes that take place often in and around complex built environments. Developing better built environments requires an understanding of those aspects of a community that are most likely to have a measurable impact on the target SEDH. Yet data on local characteristics at suitable spatial scales are often unavailable. We aim to address this issue by application of different data disaggregation methods. METHODS: We applied different approaches to data disaggregation to obtain small area estimates of key behavioral risk factors, as well as geospatial measures of green space access and walkability for each zip code of Allegheny County in southwestern Pennsylvania. RESULTS: Tables and maps of local characteristics revealed their overall spatial distribution along with disparities therein across the county. While the top ranked zip codes by behavioral estimates generally have higher than the county's median individual income, this does not lead them to have higher than its median green space access or walkability. CONCLUSION: We demonstrated the utility of data disaggregation for addressing complex questions involving community-specific behavioral attributes and built environments with precision and rigor, which is especially useful for a diverse population. Thus, different types of data, when comparable at a common local scale, can provide key integrative insights for researchers and policymakers.

Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

OBJECTIVE: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. METHODS: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. RESULTS: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). CONCLUSION: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Release of reclassified VUS results of now deceased patients to family members: Practices and opinions.

Variants of uncertain significance (VUS) are commonly identified in genetic testing. The rate at which a VUS is reclassified depends on multiple factors. However, as the amount of time it might take for a VUS to be reclassified varies, some patients with a VUS genetic testing result might have passed away before the VUS is reclassified. A VUS that is reclassified after the patient's death has clinical implications for the deceased patient's family members. The disclosure of reclassified VUS results for a deceased patient has complex legal and ethical implications. There are no established guidelines on how the reclassified VUS result for a deceased patient should be disclosed to at-risk relatives. An online survey was sent to members of the National Society of Genetic Counselors (NSGCs) to elicit practices and opinions regarding this issue. A total of 153 (4%) NSGC members completed the survey. Thirty-seven (24.2%) respondents reported having received a reclassified VUS for a deceased patient. Respondents were more likely to attempt disclosure if the variant was reclassified as pathogenic (93.5%) versus benign (76.5%), although the difference did not reach statistical significance (p = 0.06). Respondents more often reported the impact on family members (85.5%) than the decedent's right to privacy (15.0%) as extremely important when considering disclosure to family members. A legal mechanism to allow disclosure to relatives was supported by 70.6% of respondents and 97.4% felt the issue was important enough to pursue if such a process was in place. Only 9.8% of respondents supported a legal requirement of consent before disclosing to family members when a VUS is reclassified after the patient has passed away. Our results indicate that there is no consensus for how these results should be handled and a mechanism for disclosure of reclassified results to family members is supported.

Barriers to Care Among Glaucoma Patients With a Missed Appointment and Interest in a Navigator Program.

PRCIS: Most glaucoma patients with missed appointments report barriers to care and social risk factors. One third expressed interest in engaging with a patient navigator program. Most expressed interest in rescheduling. PURPOSE: The purpose of this study was to identify barriers to care among glaucoma patients with missed appointments and to assess their interest in a patient navigator program. MATERIAL AND METHODS: A cross-sectional study involving adult glaucoma patients from an academic eye center who missed their scheduled appointment between April 18 and July 25, 2022. Participants were surveyed about reasons for missed appointments, barriers to care, social risk factors, and interest in consulting with our patient navigator program. RESULTS: Of 172 patients with a missed glaucoma appointment, 73% (126/172) were contacted, and 40% (51/126) of those completed the survey. Participant age averaged 67±14 years, half were female (25/51, 49%), and most identified as Black (27/51, 53%) or White (21/51, 40%). Barriers to seeing a doctor including difficulty scheduling appointments (13/51, 26%), transportation (12/51, 24%), and cost or insurance barriers (8/51, 16%). Twenty-eight (55%) respondents reported at least one social risk factor. A positive association was found between having at least one risk factor and expressing interest in consulting our patient navigator (odds ratio=6.7, P =0.009). Overall, a third of respondents expressed interest in engaging with our patient navigator program (17/51, 33%). Two thirds of participants reported awareness of missed appointments (34/51, 67%), of whom 35% (12/34) reported having already rescheduled, 41% (14/34) expressed interest in rescheduling, and 24% (8/34) did not wish to return. CONCLUSIONS: Glaucoma patients with missed appointments report barriers to care and face social risk factors. Telephone outreach may help to re-engage them with care, and patients expressed interest in a patient navigator program to address social needs.

Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

Work Attendance with Acute Respiratory Illness Before and During COVID-19 Pandemic, United States, 2018-2022.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

Medications for opioid use disorder in rural primary care practices: Patient and provider experiences.

INTRODUCTION: The opioid epidemic has exacted a significant toll in rural areas, yet adoption of medications for opioid use disorder (MOUD) lags. The Rural Access to Medication Assisted Treatment in Pennsylvania (RAMP) Project facilitated adoption of MOUD in rural primary care clinics. The purpose of this study was to gain a better understanding of the barriers and facilitators operating at multiple levels to access or provide MOUD in rural Pennsylvania. METHODS: In total, the study conducted 35 semi-structured interviews with MOUD patients and MOUD providers participating in RAMP. Qualitative analysis incorporated both deductive and inductive approaches. The study team coded interviews and performed thematic analysis. Using a modified social-ecological framework, themes from the qualitative interviews are organized in five nested levels: individual, interpersonal, health care setting, community, and public policy. RESULTS: Patients and providers agreed on many barriers (e.g., lack of providers, lack of transportation, insufficient rapport and trust in patient-provider relationship, and cost, etc.); however, their interpretation of the barrier, or indicated solution, diverged in meaningful ways. Patients described their experiences in broad terms pointing to the social determinants of health, as they highlighted their lives outside of the therapeutic encounter in the clinic. Providers focused on their professional roles, responsibilities, and operations within the primary care setting. CONCLUSIONS: Providers may want to discuss barriers to treatment related to social determinants of health with patients, and pursue partnerships with organizations that seek to address those barriers. The findings from these interviews point to potential opportunities to enhance patient experience, increase access to and optimize processes for MOUD in rural areas, and reduce stigma against people with opioid use disorder (OUD) in the wider community.

Strategies to recruit rural primary care providers to implement a medication for opioid use disorder (MOUD) focused integrated care model.

Background: Access to providers and programs that provide medications for opioid use disorder (MOUD) remains a systemic barrier for patients with opioid use disorder (OUD), particularly if they live in rural areas. The Rural Access to Medication Assisted Treatment (MAT) in Pennsylvania Project (Project RAMP) addressed this problem with a multisystem partnership that recruited, trained, and supported rural primary care providers to provide MOUD and implement an integrated care model (ICM) for patients with OUD. Given the demonstrated efficacy of Project RAMP, this article summarizes our recruitment strategies, including feasibility concerns for further expansion into other regions. Methods: The approach for recruiting implementation sites included two phases: partner outreach and site identification. Once recruited, the Systems Transformation Framework guided planning and implementation activities. Recruitment and implementation activities were assessed with implementation trackers and evaluated by providers via key informant interviews (KIIs). Results: Project RAMP recruited 26 primary care practices from 13 counties, including nine health systems and two private practice groups-exceeding the original target of 24 sites. There was a median of 49 days from first contact to project onboarding. A total of 108 primary care practices spanning 22 health systems declined participation. Findings from the KIIs highlighted the value of engaging PCPs by connecting to a shared vision (i.e., improving the quality of patient care) as well as addressing perceived participation barriers (e.g., offering concierge technical assistance to address lack of training or resources). Conclusion: Findings highlight how successful recruitment activities should leverage the support of health system leadership. Findings also emphasize that aiding recruitment and engagement efforts successfully addressed prescribers' perceived barriers to providing MOUD as well as facilitating better communication among administrators, PCPs, behavioral health professionals, care managers, and patients.Plain Language Summary: Opioid use disorder (OUD) is one of the leading causes of preventable illness and death. The standard of care for OUD is the provision of medications for opioid use disorder (MOUD) and the application of an integrative integrated care model (ICM) where behavioral health is blended with specialized medical services. Unfortunately, access to providers and healthcare facilities that provide MOUD or apply an ICM remains a systemic barrier for patients with OUD, particularly if they live in rural areas. Although there is no one-size-fits-all approach to implementing MOUD in primary care, findings from Project The Rural Access to Medication Assisted Treatment (MAT) in Pennsylvania Project (Project RAMP) highlight strategies that may improve future MOUD and ICM implementation efforts in similar rural contexts. Specifically, future efforts to increase MOUD capacity by recruiting new providers should be prepared to leverage health system leadership, address provider barriers via training and expert consultation, and facilitate connections to local behavioral health providers. This approach may be helpful to others recruiting health systems and primary care practices to implement new care models to use MOUD in treating patients with OUD.

Role of Perceived Physical and Mental Fatigability Severity on Prospective, Recurrent, and Injurious Fall Risk in Older Men.

BACKGROUND: Falls occur annually in 25% of adults aged ≥65 years. Fall-related injuries are increasing, highlighting the need to identify modifiable risk factors. METHODS: Role of fatigability on prospective, recurrent, and injurious fall risk was examined in 1 740 men aged 77-101 years in the Osteoporotic Fractures in Men Study. The 10-item Pittsburgh Fatigability Scale measured perceived physical and mental fatigability (0-50/subscale) at Year 14 (2014-16); established cut-points identified men with more severe perceived physical (≥15, 55.7%), more severe mental (≥13, 23.7%) fatigability, or having both (22.8%). Prospective, recurrent (≥2), and injurious falls were captured by triannual questionnaires ≥1 year after fatigability assessment; risk of any fall was estimated with Poisson generalized estimating equations, and likelihood of recurrent/injurious falls with logistic regression. Models adjusted for age, health conditions, and other confounders. RESULTS: Men with more severe physical fatigability had a 20% (p = .03) increased fall risk compared with men with less physical fatigability, with increased odds of recurrent and injurious falls, 37% (p = .04) and 35% (p = .035), respectively. Men with both more severe physical and mental fatigability had a 24% increased risk of a prospective fall (p = .026), and 44% (p = .045) increased odds of recurrent falling compared with men with less severe physical and mental fatigability. Mental fatigability alone was not associated with fall risk. Additional adjustment for previous fall history attenuated associations. CONCLUSIONS: More severe fatigability may be an early indicator to identify men at high risk for falls. Our findings warrant replication in women, as they have higher rates of fatigability and prospective falls.