Lessons Learned From Clinical Studies in Centronuclear Myopathies: The Patient Perspective-A Qualitative Study.

BACKGROUND: Since 2014, several clinical studies focusing on centronuclear myopathies have been conducted, including a prospective natural history study, a gene transfer clinical trial and a clinical trial using an antisense oligonucleotide. Dedicated patient organizations have played an important role in this process. The experience of members of these organizations, either as a study participant, parent or as a patient organization member communicating with the sponsors are potentially very informative for future trial design. METHODS: We investigated the burden of and the lessons learned from the first natural history studies and clinical trials from a patient perspective using a qualitative approach. We arranged 4 focus groups with a total of 37 participants from 3 large international patient organizations: ZNM-ZusammenStark!, the Myotubular Trust, and the MTM-CNM Family Connection. 4 themes, based on a systematic literature search were discussed: Expectations and preparation, Clinical study participation, Communication and Recommendations for future clinical trials. The focus group recordings were transcribed, anonymized, and uploaded to Atlas-ti version 8.1 software. The data were analyzed using a thematic content analysis. RESULTS: Overall, participants were realistic in their expectations, hoping for small improvements of function and quality of life. The realization that trial participation does not equate to a treatment was challenging. Participating in a clinical study had a huge impact on many aspects of daily life, both for patients and their immediate families. First-hand insights into the burden of the design and its possible effect on performance were provided, resulting in numerous compelling recommendations for future clinical studies. Furthermore, participants stressed the importance of clear communication, which was considered to be especially vital in cases of severe adverse events. Finally, while patients were understanding of the importance of adhering to the regulations of good clinical practice, they indicated that they would strongly appreciate a greater understanding and/or acknowledgment of the patient perspective and a reflection of this perspective in future clinical trial design. CONCLUSION: The acknowledgment and inclusion of patients' perspectives and efficient and effective communication is expected to improve patient recruitment and retention in future clinical studies, as well as more accurate assessment of the patient performance related to suitable planning of the study visits.

Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement.

Importance: Among all US women, breast cancer is the second most common cancer and the second most common cause of cancer death. In 2023, an estimated 43 170 women died of breast cancer. Non-Hispanic White women have the highest incidence of breast cancer and non-Hispanic Black women have the highest mortality rate. Objective: The USPSTF commissioned a systematic review to evaluate the comparative effectiveness of different mammography-based breast cancer screening strategies by age to start and stop screening, screening interval, modality, use of supplemental imaging, or personalization of screening for breast cancer on the incidence of and progression to advanced breast cancer, breast cancer morbidity, and breast cancer-specific or all-cause mortality, and collaborative modeling studies to complement the evidence from the review. Population: Cisgender women and all other persons assigned female at birth aged 40 years or older at average risk of breast cancer. Evidence Assessment: The USPSTF concludes with moderate certainty that biennial screening mammography in women aged 40 to 74 years has a moderate net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of screening mammography in women 75 years or older and the balance of benefits and harms of supplemental screening for breast cancer with breast ultrasound or magnetic resonance imaging (MRI), regardless of breast density. Recommendation: The USPSTF recommends biennial screening mammography for women aged 40 to 74 years. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of supplemental screening for breast cancer using breast ultrasonography or MRI in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement).

The experience of clinical study and trial participation in rare diseases: A scoping review of centronuclear myopathy and other neuromuscular disorders.

The design of a clinical trial for a rare disease can be challenging. An optimal study design is required to effectively study the clinical outcomes for possible therapies for these types of disorders. Understanding the study participants' experiences as well as barriers and facilitators of participation are important to optimize future research and to inform clinical trial management. Centronuclear myopathies (CNMs) including X-linked myotubular myopathy (XLMTM) are a group of rare congenital myopathies for which there is no cure currently. Since 2014, a number of natural history studies and clinical trials have been conducted in CNMs. Two trials have been prematurely terminated because of severe adverse events. Since no research has been conducted regarding trial experience in CNM, we performed a scoping literature research on clinical trial experience of patients with neuromuscular disorders in general. The most common barriers to trial participation of patients comprise concerns about potential harmful effects, opportunity loss and the expected burden on daily life. The most common facilitators were an expected benefit on the disease course, altruism and collateral benefit. While several results are in line with trial experiences of other types of patients, for example oncological patients, distinctions can be made for patients with CNM and other neuromuscular disorders. However, the limited availability of relevant literature suggests that future (qualitative) research should focus on trial experiences in CNM patients.

Germline Testing in Patients With Breast Cancer: ASCO-Society of Surgical Oncology Guideline.

PURPOSE: To develop recommendations for germline mutation testing for patients with breast cancer. METHODS: An ASCO-Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process. RESULTS: Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations. RECOMMENDATIONS: BRCA1/2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1/2 testing, regardless of family history. BRCA1/2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1/2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history.Additional information is available at www.asco.org/breast-cancer-guidelines.

Advancing Health Equity: The Role of a Community-Academic-Public Health-Practice (CAPP) Partnership in Addressing COVID-19 Disparities in Louisiana.

We assessed the impact of an innovative Louisiana community-academic-public health-practice (CAPP) partnership in addressing COVID-19-associated Black-White vaccination disparities over 19 months. Initially (April 2021), the cumulative vaccinations for Black versus White Louisianans were 54 542 per 100 000 versus 62 435 per 100 000, respectively. By October 2022, cumulative vaccinations for Black versus White Louisianans were 142 437 per 100 000 versus 132 488 per 100 000, respectively. The vaccination equity score increased from 908 out of 1000 in April 2021 to 942 out of 1000 in October 2022. CAPP partnership efforts contributed to addressing initial Black-White COVID-19 vaccination disparities. (Am J Public Health. 2024;114(S1):S55-S58. https://doi.org/10.2105/AJPH.2023.307509).

Strategies for developing a successful career in academic medicine.

Academic medicine provides physicians an opportunity for long-term career satisfaction and fulfillment. However, despite the potential for great reward, academic careers can be challenging. To better define approaches to successfully navigate academic medicine, the Southern Society for Clinical Investigation sponsored a workshop titled 'Successful Careers in Academic Medicine' during the 2023 Southern Regional Meeting held in New Orleans; the critical elements of which are highlighted in the following summary. Participants discussed the benefits of an academic career, summarized strategies for negotiating a job, listed critical tools for career development, and discussed key concepts about planning and navigating the academic medicine promotion process. The information provides a roadmap for physicians to develop successful careers in academic medicine.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.

Health-care Worker Engagement in Federally Qualified Health Centers and Associations with Confidence in Making Health-care Recommendations: Evidence from the Louisiana Community Engagement Alliance.

Throughout the coronavirus disease 2019 (COVID-19) pandemic, there have been numerous demands on primary care practices and providers affecting work engagement and burnout, which can affect health-care delivery and patient outcomes. We determined potentially modifiable factors associated with work engagement among employees of federally qualified health centers (FQHCs) throughout Louisiana. Resilient coping, spirituality, and social support were associated with being engaged at work. FQHC employees perceiving a more chaotic work environment and those with depressive or anxiety symptoms were less likely to be engaged at work. Being engaged was associated with confidence in COVID-19 vaccine recommendation for adults.

COVID-19 vaccination likelihood among federally qualified health center patients: Lessons learned for future health crises.

BACKGROUND: To prepare for rollout of a COVID-19 vaccine in fall 2020, there was an urgent need to understand barriers to ensuring equitable access and addressing vaccine skepticism and resistance. This study aimed to understand the association between trusted sources of COVID-19 information and likelihood of vaccination during that time, focusing on lessons learned to prepare for future public health crises. METHODS: From December 2020-March 2021, we surveyed a probability-based, cross-sectional sample of 955 patients across seven federally qualified health centers (FQHCs) serving predominantly low-income, Black and White populations in southeastern Louisiana. Vaccination likelihood was measured on a 7-point scale; "very likely to vaccinate" was defined as score=7. Trust in healthcare provider was measured with a single survey item. High trust in personal contacts, government, and media, respectively, were defined as the highest tertiles of summative scores of trust items. Weighted multivariable logistic regression estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for being very likely to vaccinate. RESULTS: Participants were 56% Black, 64% women, mean age 44.6 years; 33% were very likely to vaccinate. High trust in healthcare provider (aOR=4.14, 95% CI 2.26-7.57) and government sources (aOR=3.23, 95% CI 1.98-5.28) were associated with being very likely to vaccinate. CONCLUSIONS: During initial COVID-19 vaccination rollout, trust in healthcare providers and government sources of COVID-19 information was associated with likelihood to vaccinate in FQHC patients. To inform public health planning for future crises, we highlight lessons learned for translating community-relevant insights into direct action to reach those most impacted.

Clinical trial participation among underserved communities: Insights from the Louisiana Community Engagement Alliance.

BACKGROUND: Diverse, equitable and inclusive participation in clinical research is needed to ensure evidence-based clinical practice and lessen disparities in health outcomes. Yet, clinical trial participation remains critically low in minoritized communities, particularly among Blacks. The Louisiana Community Engagement Alliance against COVID-19 Disparities (LA-CEAL) was launched in response to the disproportionate impact of COVID-19 on Black Louisianans to understand community barriers and preferences and increase inclusive participation in research. This study aims to understand perceptions regarding COVID-19 trial participation among underrepresented Louisianans. METHODS: A rapid assessment integrating cross-sectional, surveys among federally qualified health center (FQHC) patients and community residents, and focus group discussions (FGDs) from community representatives was conducted in 2020-2021. Factors and perceptions underlying trial participation were identified using logistic regression models and thematic analyses, respectively. RESULTS: Quantitative findings (FQHC: N=908, mean age=46.6 years, 66.4% Black; community: N=504, mean age=54.2 years, 93.7% Black) indicated that 0.9% and 3.6%, respectively, ever participated in a COVID-19 trial. Doctors/Healthcare providers were most trusted (FQHC=55.1%; community=59.3%) sources of information about trials. Advancing age was associated with increased odds of being very willing to participate (ORFQHC=1.03, 95% CI 1.02-1.05; ORCommunity=1.02, 95% CI 1.00-1.04). Qualitative data (6 FGDs, 29 attendees) revealed limited awareness, experimentation/exploitation-based fears, and minimal racial/ethnic representation among trialists as barriers to participation. CONCLUSION: COVID-19 trial participation rates were low in our sample. Altruism was a key facilitator to participation; fear, mistrust, and low awareness were predominant barriers. Community-centered approaches, engaging informed providers and trusted community members, may facilitate inclusive trial participation.

Clinical outcomes of adjuvant taxane plus anthracycline versus taxane-based chemotherapy regimens in older adults with node-positive, triple-negative breast cancer: A SEER-Medicare study.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer associated with an aggressive clinical course. Adjuvant chemotherapy reduces the risk of recurrence and improves survival in patients with node-positive TNBC. The benefit of anthracycline plus taxane (ATAX) regimens compared with non-anthracycline-containing, taxane-based regimens (TAX) in older women with node-positive TNBC is not well characterised. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 1106 women with node-positive TNBC diagnosed at age 66 years and older between 2010 and 2015. We compared patient clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs). Kaplan-Meier survival curves were generated to estimate 3-year overall survival (OS) and cancer-specific survival (CSS). Cox proportional hazard models were used to analyse OS and CSS while controlling for patient and tumour characteristics. RESULTS: Of the 1106 patients in our cohort, 767 (69.3%) received adjuvant chemotherapy with ATAX (364/767, 47.5%), TAX (297/767, 39%) or other regimens (106/767, 13.8%). Independent predictors of which patients were more likely to receive ATAX versus TAX included more extensive nodal involvement (≥4), age, marital/partner status and non-cardiac comorbidities. There was a statistically significant improvement in 3-year CSS (81.8% versus 71.4%) and OS (70.7% versus 51.3%) with the use of any chemotherapy in our cohort (P < 0.01). Three-year CSS and OS for patients who received ATAX versus TAX were similar at 82.8% versus 83.7% (P = 0.80) and 74.2% versus 72.7% (P = 0.79), respectively. There was a trend towards improved CSS and OS in patients with four or more positive lymph nodes who received ATAX versus TAX (hazard ratio 0.66, 95% CI: 0.36-1.23, P = 0.19 and hazard ratio 0.68, 95% CI: 0.41-1.14, P = 0.14, respectively). CONCLUSION: Among older women with node-positive TNBC, a majority of patients received adjuvant chemotherapy, which was associated with an improvement in CSS and OS. When compared with TAX chemotherapy, there was a trend towards better outcomes with ATAX for patients with ≥4 nodes.

Defining Meaningful Change in Antihypertensive Medication Adherence in Adults with Established Hypertension: Implications for Clinical Practice.

Uncontrolled hypertension and low antihypertensive medication adherence remain significant clinical challenges. There is a critical need to detect meaningful change in adherence in clinical settings. The authors determined that a ≥2-point change in the 4-item Krousel-Wood Medication Adherence Scale score represents meaningful change in antihypertensive medication adherence. Among a sample of participants in an ongoing clinical trial, 5.9% experienced a decline in adherence, which was associated with higher blood pressure (BP) and a higher prevalence of uncontrolled BP at 6 months. Meaningful change in medication adherence behavior may be key in managing hypertension to improve BP control and health outcomes.

Changes in Blood Pressure Outcomes Among Hypertensive Individuals During the COVID-19 Pandemic: A Time Series Analysis in Three US Healthcare Organizations.

BACKGROUND: The COVID-19 pandemic may have negatively affected medical care for and self-management of chronic hypertension. We sought to examine the impact of the pandemic on blood pressure (BP) among individuals with hypertension. METHODS: Using an interrupted time series analysis, we compared the level and trend (slope) of BP outcomes before the public health emergency declaration (prepandemic period: August 2018 through January 2020) versus after the stay-at-home orders (pandemic period: April 2020 through November 2020) among adults with hypertension followed at 3 large health systems (n=137 593). Outcomes include systolic and diastolic BP recorded in electronic health records and the proportion of individuals with BP <140/90 mm Hg. RESULTS: The number of BP measurements substantially dropped early in the pandemic and then gradually increased. During the pandemic period, systolic and diastolic BP increased by 1.79 mm Hg (95% CI, 1.57-2.01; P<0.001) and 1.30 mm Hg (95% CI, 1.18-1.42; P<0.001), respectively, compared with the prepandemic period. Similarly, the proportion of patients with controlled BP decreased by 3.43 percentage points (95% CI, -3.97 to -2.90; P<0.001). A trend showing increasing control in the prepandemic period (+3.19 percentage points per year [95% CI, +2.96 to +3.42]; P<0.001) flattened during the pandemic period (+0.27 percentage points per year [95% CI, -0.81 to -1.37]; P=0.62). CONCLUSIONS: The first 8 months of the pandemic were associated with worsening BP outcomes among individuals with hypertension. Opportunities to ensure ongoing access to health care with telemedicine and home BP monitoring may mitigate adverse impacts on BP control for future disasters/emergencies.

Electronic health strategies to improve medication adherence in patients with cardiometabolic disease: current status and future directions.

PURPOSE OF REVIEW: Enabled by widespread technological advancements, electronic health (eHealth) strategies have expanded rapidly over the last decade, presenting opportunities to support self-management including medication adherence for cardiometabolic disease control. eHealth can minimize access barriers to medications, enable timely assessment and shared decision-making, and provide medication reminders and health data feedback. This review summarizes current evidence for effectiveness of eHealth strategies for improving medication adherence in patients with hypertension, type 2 diabetes, and/or hyperlipidemia, and identifies priorities for future research. RECENT FINDINGS: Current research supports the effectiveness of eHealth strategies to improve medication adherence and clinical outcomes for cardiometabolic disease. Although patient acceptability of eHealth strategies is generally high, engagement may decline over time. In addition, differences in effectiveness across intervention characteristics and sociodemographic groups are understudied, limiting generalizability and tailoring of interventions to local health system resources, culture, and patient needs or preferences. SUMMARY: eHealth is a promising tool for addressing low medication adherence. Further work incorporating rigorous evaluation, assessment of patient engagement over time and effectiveness of intervention characteristics and components, and a health equity lens addressing eHealth use in vulnerable groups will increase understanding of the full potential of eHealth for improving medication adherence in diverse patients with cardiometabolic disease.

Weekly vs Every-3-Week Carboplatin with Weekly Paclitaxel in Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: A Retrospective Analysis.

Background: Adding carboplatin to weekly paclitaxel as part of neoadjuvant chemotherapy (NACT) for stage II-III triple negative breast cancer (TNBC) has been shown to significantly increase the pathologic complete response (pCR) rate. Hematologic toxicities associated with every 3-week dosing of carboplatin have led some oncologists to explore weekly dosing as an alternative, but there are little published data comparing the two dosing schedules. Methods: We performed a retrospective analysis of patients who received paclitaxel and carboplatin, usually followed by AC, as initial NACT for TNBC at two academic cancer centers between 2008 and 2018 for whom pathologic results and post-operative follow-up were available. We recorded pCR, defined as ypT0/isN0, treatment delivery and disease-free survival, censored as of the patient's last follow-up visit. Results: A total of 76 patients were identified (median age 49 years). A total of 47 received weekly carboplatin, of whom 83% received at least 11 of 12 planned doses, and 29 received every 3-week carboplatin, of whom 90% received all 4 planned doses. pCR rates were similar, 53% with weekly and 55% with every 3-week carboplatin dosing. At median follow-up of 18 months (range <1-118), 93% of patients who achieved pCR were alive and free from recurrence, compared to 74% of those who did not. Conclusion: pCR rates were similar between patients receiving weekly or every 3-week carboplatin and were similar to those reported in prior trials with carboplatin. These data suggest that providers can choose either weekly or every 3-week carboplatin dosing without compromising the likelihood of achieving pCR.