ß-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors.

Small molecule neurotensin receptor 1 (NTSR1) agonists have been pursued for more than 40 years as potential therapeutics for psychiatric disorders, including drug addiction. Clinical development of NTSR1 agonists has, however, been precluded by their severe side effects. NTSR1, a G protein-coupled receptor (GPCR), signals through the canonical activation of G proteins and engages ß-arrestins to mediate distinct cellular signaling events. Here, we characterize the allosteric NTSR1 modulator SBI-553. This small molecule not only acts as a ß-arrestin-biased agonist but also extends profound ß-arrestin bias to the endogenous ligand by selectively antagonizing G protein signaling. SBI-553 shows efficacy in animal models of psychostimulant abuse, including cocaine self-administration, without the side effects characteristic of balanced NTSR1 agonism. These findings indicate that NTSR1 G protein and ß-arrestin activation produce discrete and separable physiological effects, thus providing a strategy to develop safer GPCR-targeting therapeutics with more directed pharmacological action.

Primary care provider attitudes about and tendency to use non-recommended surveillance tests after curative breast cancer treatment.

PURPOSE: Little is known about the factors contributing to the receipt of non-recommended surveillance testing among early-stage breast cancer survivors. We assessed primary care providers (PCP) attitudes about and tendency to order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors post-adjuvant chemotherapy. METHODS: A stratified random sample of PCPs identified by early-stage breast cancer survivors were surveyed (N = 518, 61% response rate). PCPs were asked how likely they would be to order bone scans, imaging and/or tumor marker testing using a clinical vignette of an early-stage asymptomatic patient where these tests are non-recommended. A composite tendency to order score was created and categorized by tertiles (low, moderate, high). PCP-reported factors associated with high and moderate tendency to order non-recommended testing (vs. low) were estimated using multivariable, multinomial logistic regression. RESULTS: In this sample, 26% reported a high tendency to order non-recommended surveillance tests during survivorship for early-stage breast cancer survivors. PCPs who identified as family practice physicians and PCPs reporting more confidence in ordering surveillance testing were more likely to report a high tendency to order non-recommended testing (vs. low) ((aOR family practice 2.09, CI 1.2, 3.8; aOR more confidence 1.9, CI 1.1, 3.3). CONCLUSIONS: In this population-based sample of PCPs caring for breast cancer survivors, over a quarter of PCPs reported they would order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors. Efforts to better support PCPs and disseminate information about appropriate surveillance for cancer survivors are warranted.

Benefits and barriers of home blood pressure monitoring in pregnancy: perspectives of obstetric doctors from a Ghanaian tertiary hospital.

BACKGROUND: Delayed diagnosis of preeclampsia contributes to maternal morbidity and mortality. Patient-performed home blood pressure monitoring facilitates more frequent monitoring and earlier diagnosis. However, challenges may exist to implementation in low- and middle income-countries. METHODS: This cross-sectional mixed methods study evaluated obstetric doctors' perspectives on the benefits of and barriers to the implementation of home blood pressure monitoring among pregnant women in Ghana. Participants were doctors providing obstetric care at Korle Bu Teaching Hospital. Electronic surveys were completed by 75 participants (response rate 49.3%), consisting of demographics and questions on attitudes and perceived benefits and challenges of home BP monitoring. Semi-structured interviews were completed by 22 participants to expand on their perspectives. RESULTS: Quantitative and qualitative results converged to highlight that the current state of blood pressure monitoring among pregnant women in Ghana is inadequate. The majority agreed that delayed diagnosis of preeclampsia leads to poor health outcomes in their patients (90.6%, n = 68) and earlier detection would improve outcomes (98.7%, n = 74). Key qualitative benefits to the adoption of home blood pressure monitoring were patient empowerment and trust of diagnosis, more quantity and quality of blood pressure data, and improvement in systems-level efficiency. The most significant barriers were the cost of monitors, lack of a communication system to convey abnormal values, and low health literacy. Overall, doctors felt that most barriers could be overcome with patient education and counseling, and that benefits far outweighed barriers. The majority of doctors (81.3%, n = 61), would use home BP data to inform their clinical decisions and 89% (n = 67) would take immediate action based on elevated home BP values. 91% (n = 68) would recommend home BP monitoring to their pregnant patients. CONCLUSION: Obstetric doctors in Ghana strongly support the implementation of home blood pressure monitoring, would use values to inform their clinical management, and believe it would improve patient outcomes. Addressing the most significant barriers, including cost of blood pressure monitors, lack of a communication system to convey abnormal values, and need for patient education, is essential for successful implementation.

Acceptability of a Text Message-Based Mobile Health Intervention to Promote Physical Activity in Cardiac Rehabilitation Enrollees: A Qualitative Substudy of Participant Perspectives.

BACKGROUND: Mobile health (mHealth) interventions have the potential to deliver longitudinal support to users outside of episodic clinical encounters. We performed a qualitative substudy to assess the acceptability of a text message-based mHealth intervention designed to increase and sustain physical activity in cardiac rehabilitation enrollees. METHODS AND RESULTS: Semistructured interviews were conducted with intervention arm participants of a randomized controlled trial delivered to low- and moderate-risk cardiac rehabilitation enrollees. Interviews explored participants' interaction with the mobile application, reflections on tailored text messages, integration with cardiac rehabilitation, and opportunities for improvement. Transcripts were thematically analyzed using an iteratively developed codebook. Sample size consisted of 17 participants with mean age of 65.7 (SD 8.2) years; 29% were women, 29% had low functional capacity, and 12% were non-White. Four themes emerged from interviews: engagement, health impact, personalization, and future directions. Participants engaged meaningfully with the mHealth intervention, finding it beneficial in promoting increased physical activity. However, participants desired greater personalization to their individual health goals, fitness levels, and real-time environment. Generally, those with lower functional capacity and less experience with exercise were more likely to view the intervention positively. Finally, participants identified future directions for the intervention including better incorporation of exercise physiologists and social support systems. CONCLUSIONS: Cardiac rehabilitation enrollees viewed a text message-based mHealth intervention favorably, suggesting the potentially high usefulness of mHealth technologies in this population. Addressing participant-identified needs on increased user customization and inclusion of clinical and social support is crucial to enhancing the effectiveness of future mHealth interventions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04587882.

Challenges to diagnosing and managing preeclampsia in a low-resource setting: A qualitative study of obstetric provider perspectives from Ghana.

Preeclampsia is a leading cause of global maternal morbidity and mortality. The greatest burden of disease is in low- and middle-income countries where healthcare providers face significant, understudied, challenges to diagnosing and managing preeclampsia. This qualitative study used semi-structured interviews to explore the challenges of diagnosing and managing preeclampsia from the perspectives of obstetric doctors. Participants were doctors who provide obstetric care at the Korle Bu Teaching Hospital, an urban tertiary hospital in Ghana. Purposive sampling identified doctors with meaningful experience in managing patients with preeclampsia. Thematic saturation of data was used to determine sample size. Interviews were audio recorded, transcribed verbatim, coded using an iteratively-developed codebook, and thematically analyzed. Interviews were conducted with 22 participants, consisting of 4 house officers, 6 junior obstetrics/gynecology residents, 8 senior obstetrics/gynecology residents, and 4 obstetrics/gynecology consultants. Doctors identified critical challenges faced at the patient, provider, and systems levels in detecting and managing preeclampsia, each of which mediates the health outcomes of a pregnancy complicated by preeclampsia. Challenges centered around three overarching global themes: (1) low education levels and health literacy among women, (2) insufficient number of healthcare providers highly trained in obstetric care, and (3) inadequate health infrastructure to support critically ill patients with preeclampsia. Recognizing and addressing root challenges to preeclampsia care has great potential to improve outcomes in pregnancies complicated by preeclampsia in low-resource settings.

The effect of parental diabetes prevention program participation on weight loss in dependent children: a prospective cohort study.

INTRODUCTION: Obesity has reached epidemic proportions in children and adolescents in the United States. Children's behaviors are strongly influenced by parental behaviors, and weight loss in parents is positively associated with weight changes in their overweight/obese children. Research is limited on how parents' National Diabetes Prevention Program (DPP) participation affects the health outcomes of their dependent children. Analyzing the impact of parental DPP participation on weight loss in their dependent children may provide valuable insight into an important secondary benefit of DPP participation. METHODS: In this study, we identified 128 adults with prediabetes who were offered the opportunity to participate in a DPP (n = 54 DPP participants and n = 74 DPP non-participants) and who had at least one child 3 to 17 years of age living with them. Age and BMI percentile for dependent children were collected from insurance claims data for 203 children (n = 90 children of DPP participants and n = 113 children of DPP non-participants). Parental practices related to diet and physical activity were assessed by surveys. RESULTS: There were no significant changes in BMI percentiles of overweight or obese children (i.e. BMI percentile ≥ 50%) of DPP participants vs DPP non-participants with prediabetes over one-year. Parents who enrolled and did not enroll in the DPP did not report differences in their parenting practices related to diet and physical activity. DISCUSSION: These results are not consistent with the literature that suggests parent-based interventions may influence their children's weight trajectories. Limitations include small sample size, short time span of intervention, and limited availability of additional health/biographic data on dependent children. Future studies should collect primary outcome data on children, investigate whether there is a minimum duration of parental involvement and level of parental adherence, and assess the effect of parent-child dynamics on child weight trajectories.

Workplace Gender Inequity Is Driven by Broader Societal Inequity: A Qualitative Study of Senior Japanese and American Radiation Oncologists.

PURPOSE: Gender inequity in medicine harms society, and often originates in the context of broader societal discrimination. This study explores the experiences of older women in the radiation oncology specialty in Japan and the United States, with an emphasis on understanding how broader gender inequity affects career trajectory. Radiation oncology is an ideal setting to investigate cross-cultural physician gender equity issues, because few women enter the field despite fewer barriers (eg, frequent emergencies, evening/weekend hours, long procedures) that are commonly cited by women as deterrents in specialty selection. METHODS AND MATERIALS: Between 2012 and 2016, the authors interviewed 14 older women in radiation oncology (department chairs or full professors), with 6 from Japan and 8 from the United States. Multiple analysts identified themes to explore the impact of societal gender inequity on female radiation oncologists' careers. RESULTS: Five themes were identified: (1) childhood gender constructs affect career aspirations, (2) persistent sexism and gender-based workplace challenges affect women's careers, (3) gender inequity in the home affects women's careers, (4) non-gender-related factors intersect to affect women's career satisfaction, and (5) attaining gender equity appears to be even more challenging in Japan compared with the United States. CONCLUSIONS: Female radiation oncologists in 2 of the most technologically advanced countries report that gender discrimination across their lifespans substantially affects career success. Because gender inequality reflects societal injustice and negatively affects scientific progress and patient outcomes, future research should focus on global approaches to address professional and domestic gender constructs that impede women's career progress.

Use and Outcomes of SBRT for Early Stage NSCLC Without Pathologic Confirmation in the Veterans Health Care Administration.

PURPOSE: Stereotactic body radiation therapy (SBRT) use has increased among patients without pathologic confirmation (PC) of lung cancer. Empirical SBRT without PC raises concerns about variation in workup and patient selection, but national trends have not been well described. In this study, we assessed patterns of empirical SBRT use, workup, and causes of death among a large national non-small cell lung cancer (NSCLC) cohort. METHODS AND MATERIALS: We identified 2221 patients treated with SBRT for cT1-T2aN0M0 NSCLC in the Veterans Affairs health care system from 2008 to 2015. We reviewed their pretreatment workup and assessed associations between absence of PC and clinical and demographic factors. We compared causes of death between PC and non-PC groups and used Cox proportional hazards modeling to compare overall survival and lung cancer specific survival (LCSS) between these groups. RESULTS: Treatment without PC varied from 0% to 61% among Veterans Affairs medical centers, with at least 5 cases of stage I NSCLC. Overall, 14.9% of patients were treated without PC and 8.8% did not have a biopsy attempt. Ten percent of facilities were responsible for almost two-thirds (62%) of cases of treatment without PC. Of non-PC patients, 95.5% had positron emission tomography scans, 40.6% had biopsy procedures attempted, and 12.7% underwent endobronchial ultrasound. Non-PC patients were more likely to have cT1 tumors and live outside the histoplasmosis belt. Age, sex, smoking status, and Charlson comorbidity index were similar between groups. Lung cancer was the most common cause of death in both groups. Overall survival was similar between groups, whereas non-PC patients had better LCSS (hazard ratio = 0.77, P = .031). CONCLUSIONS: Empirical SBRT use varied widely among institutions and appropriate radiographic workup was consistently used in this national cohort. Future studies should investigate determinants of variation and reasons for higher LCSS among non-PC patients.

Correction: Evaluating the Feasibility and Acceptability of a Mobile Health-Based Female Community Health Volunteer Program for Hypertension Control in Rural Nepal: Cross-Sectional Study.

[This corrects the article DOI: 10.2196/15419.].

Evaluating the Feasibility and Acceptability of a Mobile Health-Based Female Community Health Volunteer Program for Hypertension Control in Rural Nepal: Cross-Sectional Study.

BACKGROUND: Hypertension is a major modifiable risk factor for cardiovascular disease, the world's leading cause of death. The prevalence of hypertension is disproportionately higher in South Asian countries than in other regions of the world. Screening for hypertension in primary care settings remains a challenge in many South Asian countries, including Nepal. Nepal is located in the Himalayan Mountains region, posing significant geographical challenges for its rural citizens to access primary health care and service delivery. This barrier increases the costs and inconvenience for rural Nepalis to access hypertension screening and treatment. As a result, the prevalence of hypertension in Nepal tripled in the last 25 years to 22.4%-38.6%. Nepal's Ministry of Health and Population relies on female community health volunteers to link health centers and communities to provide basic health services. Over 50,000 of these volunteers in Nepal have received basic health care training and are assigned to take care of maternal and child health. Due to limited health care resources, adopting new methods to control hypertension is an urgent need in Nepal. Several recent studies in Nepal have recommended extending the role of female community health volunteers to include hypertension management through blood pressure monitoring and home-based education. OBJECTIVE: The goal of this study was to assess if a mobile health-based female community health volunteer approach of combining the traditional community health volunteer program with digital technologies would be feasible and acceptable in rural Nepal. METHODS: In this study, we recruited 17 female community health volunteers and extended their role from maternal and child health to hypertension management through screening blood pressures. RESULTS: All 17 female community health volunteers successfully measured 1113 rural Nepalis' blood pressures, identified 169 hypertensive patients, and collected health behaviors data of the 169 hypertensive patients. Among the 169 patients, 70% of them had a mobile phone, and 92% were interested in receiving health-related information via a mobile phone. Among those who were interested in receiving information via a mobile phone, 84% preferred voice calls, and 7% and 1% preferred texting and apps, respectively. CONCLUSIONS: Results from this study indicate that a digital health intervention that leverages feature-phones combined with female community health volunteers may be an acceptable and pragmatic way to implement an evidence-based program to reduce hypertension in rural Nepal.