Identifying genes associated with disease outcomes using joint sparse canonical correlation analysis-An application in renal clear cell carcinoma.

Somatic changes like copy number aberrations (CNAs) and epigenetic alterations like methylation have pivotal effects on disease outcomes and prognosis in cancer, by regulating gene expressions, that drive critical biological processes. To identify potential biomarkers and molecular targets and understand how they impact disease outcomes, it is important to identify key groups of CNAs, the associated methylation, and the gene expressions they impact, through a joint integrative analysis. Here, we propose a novel analysis pipeline, the joint sparse canonical correlation analysis (jsCCA), an extension of sCCA, to effectively identify an ensemble of CNAs, methylation sites and gene (expression) components in the context of disease endpoints, especially tumor characteristics. Our approach detects potentially orthogonal gene components that are highly correlated with sets of methylation sites which in turn are correlated with sets of CNA sites. It then identifies the genes within these components that are associated with the outcome. Further, we aggregate the effect of each gene expression set on tumor stage by constructing "gene component scores" and test its interaction with traditional risk factors. Analyzing clinical and genomic data on 515 renal clear cell carcinoma (ccRCC) patients from the TCGA-KIRC, we found eight gene components to be associated with methylation sites, regulated by groups of proximally located CNA sites. Association analysis with tumor stage at diagnosis identified a novel association of expression of ASAH1 gene trans-regulated by methylation of several genes including SIX5 and by CNAs in the 10q25 region including TCF7L2. Further analysis to quantify the overall effect of gene sets on tumor stage, revealed that two of the eight gene components have significant interaction with smoking in relation to tumor stage. These gene components represent distinct biological functions including immune function, inflammatory responses, and hypoxia-regulated pathways. Our findings suggest that jsCCA analysis can identify interpretable and important genes, regulatory structures, and clinically consequential pathways. Such methods are warranted for comprehensive analysis of multimodal data especially in cancer genomics.

Systematic Reviews and Meta-analyses in Regional Anesthesia and Pain Medicine (Part II): Guidelines for Performing the Systematic Review.

In Part I of this series, we provide guidance for preparing a systematic review protocol. In this article, we highlight important steps and supplement with exemplars on conducting and reporting the results of a systematic review. We suggest how authors can manage protocol violations, multiplicity of outcomes and analyses, and heterogeneity. The quality (certainty) of the evidence and strength of recommendations should follow the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. It is our goal that Part II of this series provides valid guidance to authors and peer reviewers who conduct systematic reviews to adhere to important constructs of transparency, structure, reproducibility, and accountability. This will likely result in more rigorous systematic reviews being submitted for publication to the journals like Regional Anesthesia & Pain Medicine and Anesthesia & Analgesia .

Systematic reviews and meta-analyses in regional anesthesia and pain medicine (Part II): guidelines for performing the systematic review.

In Part I of this series, we provide guidance for preparing a systematic review protocol. In this article, we highlight important steps and supplement with exemplars on conducting and reporting the results of a systematic review. We suggest how authors can manage protocol violations, multiplicity of outcomes and analyses, and heterogeneity. The quality (certainty) of the evidence and strength of recommendations should follow the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. It is our goal that Part II of this series provides valid guidance to authors and peer reviewers who conduct systematic reviews to adhere to important constructs of transparency, structure, reproducibility, and accountability. This will likely result in more rigorous systematic reviews being submitted for publication to the journals like Regional Anesthesia & Pain Medicine and Anesthesia & Analgesia.

Model Clinic to Increase Preventive Screenings Among Patients With Physical Disabilities: Protocol for a Mixed Methods Intervention Pilot Study.

BACKGROUND: People with physical disabilities often experience premature multimorbidity and adverse health events. A tailored primary care approach for this vulnerable population that also accounts for social and functional risk factors could promote healthier aging and more equitable health care. OBJECTIVE: This project will evaluate the implementation of a health program designed for people with physical disabilities. The proposed evaluation result is to generate the first best-practice protocol focused specifically on developing primary care to help reduce preventable causes of morbidity and improve functioning among people with physical disabilities. METHODS: We will design and implement a pilot health program for people with physical disabilities at a primary care clinic within Michigan Medicine. The health program for people with physical disabilities will be an integrated intervention involving a tailored best practice alert designed to prompt family medicine providers to screen and monitor for common, preventable health conditions. The program will also collect social and functional status information to determine the patient's need for further care coordination and support. Adult participants from this clinic with identified physical disabilities will be targeted for potential enrollment. To create a quasi-experimental setting, a separate departmental clinic will serve as a control site for comparison purposes. A quantitative analysis to estimate the treatment effect of implementing this health program will be conducted using a difference-in-differences approach. Outcomes of interest will include the use of preventative services (eg, hemoglobin A1c for diabetes screening), social work assistance, and emergency and hospital services. These data will be extracted from electronic health records. Time-invariant covariates, particularly sociodemographic covariates, will be included in the models. A qualitative analysis of patient and health care provider interviews will also be completed to assess the effect of the health program. Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scores will be assessed to both screen for depression and anxiety as well as explore program impacts related to addressing health and functioning needs related to physical disabilities in a primary care setting. These will be summarized through descriptive analyses. RESULTS: This study was funded in September 2018, data collection started in September 2021, and data collection is expected to be concluded in September 2023. CONCLUSIONS: This study is a mixed methods evaluation of the effectiveness of an integrated health program designed for people with physical disabilities, based on a quasi-experimental comparison between an intervention and a control clinic site. The intervention will be considered successful if it leads to improvements in greater use of screening and monitoring for preventable health conditions, increased social worker referrals to assist with health and functioning needs, and improvements in emergency and hospital-based services. The findings will help inform best practices for people with physical disabilities in a primary care setting. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50105.

The Association of Hearing Loss with Hospitalization.

BACKGROUND: Individuals with hearing loss (HL) are at higher risk for hospitalizations, and may be for readmissions, compared with their hearing peers. The objective of this prospective study was to confirm retrospective studies suggesting that HL increases hospital readmissions, and, if confirmed, possible causes for it. METHODS: A prospective cohort study of English-speaking patients >55 years old admitted to general medical and surgical floors at 2 large hospital systems in southeastern Michigan over a 2-year period was conducted. All patients underwent bedside audiometric testing. HL presence and severity were categorized using World Health Organization pure tone assessment parameters. Readmission rates, Charlson comorbidity index, socio-demographic and medical variables were obtained from Epic EMR databases. OUTCOMES: There were 1247 hospitalized patients enrolled. Of these, 76.8% had documented HL of which 50.5% (630) was mild HL and 26.3% (328) moderate or worse HL. Patients with any HL were older and more likely to be non-Hispanic, white, male, and had less education, lower health literacy, more comorbidities, and more difficulty communicating with their doctor. Readmission rates at 30 and 90-days were similar between HL and hearing groups, after adjusting for HL severity, Charlston index, and numerous potential confounders. CONCLUSION: Patients with HL do not seem to have higher rates of hospital readmissions. We did find high frequency of HL in hospitalized patients along with significant communication difficulties that patients had with their clinicians. These findings have implications for measures to improve patient-physician communication, potentially improving long-term health outcomes.

Self-administered acupressure for veterans with chronic back pain: Study design and methodology of a type 1 hybrid effectiveness implementation randomized controlled trial.

BACKGROUND: Chronic low back pain is prevalent and disabling in Veterans, but effective pain management is challenging. Clinical practice guidelines emphasize multimodal pain management including evidence-based complementary and integrative health treatments such as acupressure as a first line of care. Unfortunately, the ability to replicate interventions, cost, resources, and limited access are implementation barriers. Self-administered acupressure has shown positive effects on pain and can be practiced anywhere with little to no side effects. METHODS/DESIGN: The aims of this Type 1 hybrid effectiveness implementation randomized controlled trial are 1) to determine effectiveness of a self-administered acupressure protocol at improving pain interference and secondary outcomes of fatigue, sleep quality, and disability in 300 Veterans with chronic low back pain, and 2) evaluate implementation barriers and facilitators to scale-up acupressure utilization within Veterans Health Administration (VHA). Participants randomized to the intervention will receive instruction on acupressure application using an app that facilitates daily practice for 6 weeks. During weeks 6 through 10, participants will discontinue acupressure to determine sustainability of effects. Participants randomized to waitlist control will continue their usual care for pain management and receive study materials at the end of the study period. Outcomes will be collected at baseline and at 6- and 10-weeks post baseline. The primary outcome is pain interference, measured by the PROMIS pain interference scale. Using established frameworks and a mixed methods approach, we will evaluate intervention implementation. DISCUSSION: If acupressure is effective, we will tailor strategies to support implementation in the VHA based on study findings. TRIAL REGISTRATION NUMBER: NCT05423145.

Comparing Very Low-Carbohydrate vs DASH Diets for Overweight or Obese Adults With Hypertension and Prediabetes or Type 2 Diabetes: A Randomized Trial.

PURPOSE: Adults with a triple multimorbidity (hypertension, prediabetes or type 2 diabetes, and overweight or obesity), are at increased risk of serious health complications, but experts disagree on which dietary patterns and support strategies should be recommended. METHODS: We randomized 94 adults from southeast Michigan with this triple multimorbidity using a 2 × 2 diet-by-support factorial design, comparing a very low-carbohydrate (VLC) diet vs a Dietary Approaches to Stop Hypertension (DASH) diet, as well as comparing results with and without multicomponent extra support (mindful eating, positive emotion regulation, social support, and cooking). RESULTS: Using intention-to-treat analyses, compared with the DASH diet, the VLC diet led to greater improvement in estimated mean systolic blood pressure (-9.77 mm Hg vs -5.18 mm Hg; P = .046), greater improvement in glycated hemoglobin (-0.35% vs -0.14%; P = .034), and greater improvement in weight (-19.14 lb vs -10.34 lb; P = .0003). The addition of extra support did not have a statistically significant effect on outcomes. CONCLUSIONS: For adults with hypertension, prediabetes or type 2 diabetes, and overweight or obesity, the VLC diet resulted in greater improvements in systolic blood pressure, glycemic control, and weight over a 4-month period compared with the DASH diet. These findings suggest that larger trials with longer follow-up are warranted to determine whether the VLC diet might be more beneficial for disease management than the DASH diet for these high-risk adults.

"Three Good Things" Digital Intervention Among Health Care Workers: A Randomized Controlled Trial.

PURPOSE: Positive psychology shows promise in improving positive affect and happiness. We tested a digital version of a positive psychology intervention called Three Good Things (3GT) among health care workers to assess whether gratitude practice improved well-being. METHODS: All members of a large academic medicine department were invited. Participants were randomized to an immediate intervention group or control group (delayed intervention). Participants completed outcome measures surveys (demographics, depression, positive affect, gratitude, and life satisfaction) at baseline, and at 1 month and 3 months post-intervention. Controls completed additional surveys at 4 and 6 months (completion of the delayed intervention). During the intervention, we sent 3 text messages per week asking for 3GT that occurred that day. We used linear mixed models to compare the groups and to look at the effects of department role, sex, age, and time on outcomes. RESULTS: Of 468 eligible individuals, 223 (48%) enrolled and were randomized with high retention through the end of the study. Most (87%) identified as female. For the intervention group, positive affect improved slightly at 1 month, then declined slightly but remained significantly improved at 3 months. Depression, gratitude, and life satisfaction scores showed a similar trend but were not statistically different between groups. CONCLUSIONS: Our research showed adherence to a positive psychology intervention for health care workers created small positive improvements immediately post-intervention but were not sustained. Further work should evaluate whether utilizing different duration or intensity of the intervention improves benefits.

The Prevalence of Periodontitis Among US Adults with Multimorbidity Using NHANES Data 2011-2014.

INTRODUCTION: Often misperceived as solely a dental disease, periodontitis is a chronic condition characterized by inflammation of the support structures of the tooth and associated with chronic systemic inflammation and endothelial dysfunction. Despite affecting almost 40% of US adults 30 years of age or older, periodontitis is rarely considered when quantifying the multimorbidity (the presence of 2 or more chronic conditions in an individual) burden for our patients. Multimorbidity represents a major challenge for primary care and is associated with increasing health care expenditure and increased hospitalizations. We hypothesized that periodontitis was associated with multimorbidity. METHODS: To interrogate our hypothesis, we performed a secondary data analysis of a population-based cross-sectional survey, the NHANES 2011 to 2014 dataset. The study population included US adults aged 30 years or older who underwent a periodontal examination. Prevalence of periodontitis in individuals with and without multimorbidity was calculated using likelihood estimates and adjusting for confounding variables with logistic regression models. RESULTS: Individuals with multimorbidity were more likely than the general population and individuals without multimorbidity to have periodontitis. However, in adjusted analyses, there was no independent association between periodontitis and multimorbidity. Given the absence of an association, we included periodontitis as a qualifying condition for the diagnosis of multimorbidity. As a result, the prevalence of multimorbidity in US adults 30 years and older increased from 54.1% to 65.8%. DISCUSSION: Periodontitis is a highly prevalent, preventable chronic inflammatory condition. It shares many common risk factors with multimorbidity but was not independently associated with multimorbidity in our study. Further research is required to understand these observations and whether treating periodontitis in patients with multimorbidity may improve health care outcomes.

Learning Obstetrical Cervical Exam Skills : Development of a Novel Model to Demystify Blind Procedures.

BACKGROUND AND OBJECTIVES: Obstetric care is a core element in family medicine education. New interns typically learn the sterile cervical exam on the job by examining women in labor. This can be uncomfortable for patients and may increase the risk of infection. Simulated training could minimize these challenges, but manufactured models are expensive and not widely available in residency programs. We sought to evaluate a simple, homemade sewn model using stretchy fabric and pipe cleaners that could improve teaching and acquisition of cervical examination skills and common obstetrical procedures. METHODS: We used the model to teach cervical examination skills to students and new interns and assessed participant satisfaction. We evaluated examination accuracy by grading practice exams on the model before and after a workshop teaching obstetrical procedures including the sterile vaginal exam. We calculated satisfaction using summary statistics. We evaluated pre- and postscores for exam accuracy using paired t tests. RESULTS: Interns demonstrated a significant improvement in cervical exam skills using the model, and participants reported very high satisfaction with the workshop utilizing the model. CONCLUSIONS: We developed a simple, low-cost cervical exam model that was shown to be well-regarded by trainees and could be duplicated by other residency programs. This approach provides a unique and accessible way to offer hands-on simulation during obstetrical training. The model may improve trainees' understanding of the procedures which would lead to better experiences for obstetrical patients.

Sparse canonical correlation to identify breast cancer related genes regulated by copy number aberrations.

BACKGROUND: Copy number aberrations (CNAs) in cancer affect disease outcomes by regulating molecular phenotypes, such as gene expressions, that drive important biological processes. To gain comprehensive insights into molecular biomarkers for cancer, it is critical to identify key groups of CNAs, the associated gene modules, regulatory modules, and their downstream effect on outcomes. METHODS: In this paper, we demonstrate an innovative use of sparse canonical correlation analysis (sCCA) to effectively identify the ensemble of CNAs, and gene modules in the context of binary and censored disease endpoints. Our approach detects potentially orthogonal gene expression modules which are highly correlated with sets of CNA and then identifies the genes within these modules that are associated with the outcome. RESULTS: Analyzing clinical and genomic data on 1,904 breast cancer patients from the METABRIC study, we found 14 gene modules to be regulated by groups of proximally located CNA sites. We validated this finding using an independent set of 1,077 breast invasive carcinoma samples from The Cancer Genome Atlas (TCGA). Our analysis of 7 clinical endpoints identified several novel and interpretable regulatory associations, highlighting the role of CNAs in key biological pathways and processes for breast cancer. Genes significantly associated with the outcomes were enriched for early estrogen response pathway, DNA repair pathways as well as targets of transcription factors such as E2F4, MYC, and ETS1 that have recognized roles in tumor characteristics and survival. Subsequent meta-analysis across the endpoints further identified several genes through the aggregation of weaker associations. CONCLUSIONS: Our findings suggest that sCCA analysis can aggregate weaker associations to identify interpretable and important genes, modules, and clinically consequential pathways.

Grocery Delivery to Support Healthy Weight Gain Among Pregnant Young Women With Low Income: Protocol for a Randomized Controlled Trial.

BACKGROUND: Excessive weight gain during pregnancy is associated with complications for both the mother and her infant including gestational diabetes, hypertensive disorders, operative delivery, and long-term obesity. A healthy diet during pregnancy promotes healthy gestational weight gain and determines fetal epigenetic programming in infants that impacts risk for future chronic disease. OBJECTIVE: This project will examine the impact of grocery delivery during pregnancy on the weight, diet, and health outcomes of young pregnant women and their infants. METHODS: A three-arm randomized controlled trial design will be performed. A total of 855 young pregnant women, aged 14-24 years, from across the state of Michigan will be enrolled and randomized equally into the three study arms. Participants in arm one (control) will receive usual care from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC); arm two will receive WIC plus biweekly grocery delivery; and arm three will receive WIC plus biweekly grocery and unsweetened beverage delivery. Weight will be assessed weekly during pregnancy, and total pregnancy weight gain will be categorized as above, below, or within guidelines. Additionally, dietary intake will be assessed at three time points (baseline, second trimester, and third trimester), and pregnancy outcomes will be extracted from medical records. The appropriateness of pregnancy weight gain, diet quality, and occurrence of poor outcomes will be compared between groups using standard practices for multinomial regression and confounder adjustment. RESULTS: This study was funded in April 2021, data collection started in December 2021, and data collection is expected to be concluded in 2026. CONCLUSIONS: This study will test whether grocery delivery of healthy foods improves weight, diet, and pregnancy outcomes of young moms with low income. The findings will inform policies and practices that promote a healthy diet during pregnancy, which has multigenerational impacts on health. TRIAL REGISTRATION: ClinicalTrials.gov NCT05000645; https://clinicaltrials.gov/ct2/show/NCT05000645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40568.

The Impact of COVID-19 on Postdischarge Outcomes for Dialysis Patients in the United States: Evidence from Medicare Claims Data.

Background: Recent investigations have shown that, on average, patients hospitalized with coronavirus disease 2019 (COVID-19) have a poorer postdischarge prognosis than those hospitalized without COVID-19, but this effect remains unclear among patients with end-stage kidney disease (ESKD) who are on dialysis. Methods: Leveraging a national ESKD patient claims database administered by the US Centers for Medicare and Medicaid Services, we conducted a retrospective cohort study that characterized the effects of in-hospital COVID-19 on all-cause unplanned readmission and death within 30 days of discharge for patients on dialysis. Included in this study were 436,745 live acute-care hospital discharges of 222,154 Medicare beneficiaries on dialysis from 7871 Medicare-certified dialysis facilities between January 1 and October 31, 2020. Adjusting for patient demographics, clinical characteristics, and prevalent comorbidities, we fit facility-stratified Cox cause-specific hazard models with two interval-specific (1-7 and 8-30 days after hospital discharge) effects of in-hospital COVID-19 and effects of prehospitalization COVID-19. Results: The hazard ratios due to in-hospital COVID-19 over the first 7 days after discharge were 95% CI, 1.53 to 1.65 for readmission and 95% CI, 1.38 to 1.70 for death, both with P<0.001. For the remaining 23 days, the hazard ratios were 95% CI, 0.89 to 0.96 and 95% CI, 0.86 to 1.07, with P<0.001 and P=0.50, respectively. Effects of prehospitalization COVID-19 were mostly nonsignificant. Conclusions: In-hospital COVID-19 had an adverse effect on both postdischarge readmission and death over the first week. With the surviving patients having COVID-19 substantially selected from those hospitalized, in-hospital COVID-19 was associated with lower rates of readmission and death starting from the second week.

Concordant physician-patient characteristics lose importance for Arab American women and their healthcare- cross-sectional study.

Background: Arab American women have preferred women physicians of their own culture in the past. The primary aim of this study is to determine the current influence of religion/culture among MENA women and their preferences for physicians of same sex, culture, and religion on the avoidance and uncomfortableness of routine and women's health exams. Methods: A cross sectional community survey including religiosity and the importance of physician matched sex, culture, and religion was completed. Outcome measures were avoidance of a routine physical exam, or a women's health exam because of religious/cultural issues; and the uncomfortableness of the women's health exam. Linear regression modeling was used to evaluate the association between outcomes and potential predictors, with significance assessed using a bootstrap method. Findings: The responses of 97 MENA women 30-65 years old showed that MENA women agreed that they would avoid routine health exams because of religious/cultural issues if their physician was of the same religion or culture as they were (p < 0.001, p < 0.05, respectively) or they had less education (p < 0.05). MENA women also avoided women's health exams due to religious/cultural issues if her physician was of the same religion as she (p < 0.01). Interpretation: MENA women 30-65 years old may no longer be bound to a female physician of their same religion/culture for their health exams.

US women screen at low rates for both cervical and colorectal cancers than a single cancer: a cross-sectional population-based observational study.

Background: Using screen counts, women 50-64 years old have lower cancer screening rates for cervical and colorectal cancers (CRC) than all other age ranges. This paper aims to present woman-centric cervical cancer and CRC screenings to determine the predictor of being up-to-date for both. Methods: We used the Behavioral Risk Factor Surveillance System (BRFSS), an annual survey to guide health policy in the United States, to explore the up-to-date status of dual cervical cancer and CRC screening for women 50-64 years old. We categorized women into four mutually exclusive categories: up-to-date for dual-screening, each single screen, or neither screen. We used multinomial multivariate regression modeling to evaluate the predictors of each category. Results: Among women ages 50-64 years old, dual-screening was reported for 58.2% (57.1-59.4), cervical cancer screening alone (27.1% (26.0-28.2)), CRC screening alone (5.4% (4.9-5.9)), and neither screen (9.3% (8.7-9.9)). Age, race, education, income, and chronic health conditions were significantly associated with dual-screening compared to neither screen. Hispanic women compared to non-Hispanic White women were more likely to be up-to-date with cervical cancer screening than dual-screening (adjusted odds ratio [aOR] = 1.39 (1.10, 1.77)). Compared to younger women, those 60-64 years are significantly more likely to be up-to-date with CRC screening than dual-screening (aOR = 1.75 (1.30, 2.35)). Conclusions: Screening received by each woman shows a much lower rate of dual-screening than prior single cancer screening rates. Addressing dual-screening strategies rather than single cancer screening programs for women 50-64 years may increase both cancer screening rates. Funding: This work was supported by NIH through the Michigan Institute for Clinical and61 Health Research UL1TR002240 and by NCI through The University of Michigan Rogel Cancer62 Center P30CA046592 grants.

Routine screenings for cervical and colorectal cancers save lives by detecting cancers at an early stage when they are more treatable and more likley to cure. Most cancer screening in the United States is focused on single cancer screening programs, often held at community health fairs, pop-up screening vans and other settings, without coordination with the individuals' primary care doctors. This is problematic because the primary care physician cannot counsel if the results are abnormal and advise when the next routine screen is appropriate. This leads to gaps in women not being informed that they are due for routine screening and gaps to act on any abnormal screening results. This is especially problematic for women aged 50 to 64, who are less likely to screen for either cancer alone compared to other age groups. Currently, 86% of women in the United States are up to date with cervical cancer screening, and 64% are up to date with colorectal cancer screening. However, it is not clear how many women in this age group receive both screens, compared to a single screen or neither screen. Harper et al. analyzed data from over 40,000 women aged 50 to 64, collected in a United States health survey in 2018. This study revealed that only 59% of the women reported being up to date with cervical and colorectal cancer screenings. Compared to women who did not screen at all, women completing both screens were more educated, had higher incomes, and were more likely to have other chronic conditions such as arthritis, diabetes, depression and other cancers. These findings reveal that the number of women aged 50 to 64 in the United States, who are up to date with both cancer screenings, is still well below national targets. Harper et al. propose that shifting towards a women-centric focus, with primary care physicians or health care systems responsible for managing screening efforts, could decrease cancer incidence and mortality. In future, self-test kits for both cancers should help encourage more women to have both screens in a comfortable environment. This change in focus will also allow primary care physicians to notify women at appropriate intervals to attend routine screening and immediate follow-ups in the case of abnormal results.

Continuous Glucose Monitoring With Low-Carbohydrate Nutritional Coaching to Improve Type 2 Diabetes Control: Randomized Quality Improvement Program.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a leading cause of morbidity and mortality globally, with adverse health consequences largely related to hyperglycemia. Despite clinical practice guideline recommendations, effective pharmacotherapy, and interventions to support patients and providers, up to 60% of patients diagnosed with T2DM are estimated to have hemoglobin A1c (HbA1c) levels above the recommended targets owing to multilevel barriers hindering optimal glycemic control. OBJECTIVE: The aim of this study is to compare changes in HbA1c levels among patients with suboptimally controlled T2DM who were offered the opportunity to use an intermittently viewed continuous glucose monitor and receive personalized low-carbohydrate nutrition counseling (<100 g/day) versus those who received usual care (UC). METHODS: This was a 12-month, pragmatic, randomized quality improvement program. All adult patients with T2DM who received primary care at a university-affiliated primary care clinic (N=1584) were randomized to either the UC or the enhanced care (EC) group. Within each program arm, we identified individuals with HbA1c >7.5% (58 mmol/mol) who were medically eligible for tighter glycemic control, and we defined these subgroups as UC-high risk (UC-HR) or EC-HR. UC-HR participants (n=197) received routine primary care. EC-HR participants (n=185) were invited to use an intermittently viewed continuous glucose monitor and receive low-carbohydrate nutrition counseling. The primary outcome was mean change in HbA1c levels from baseline to 12 months using an intention-to-treat difference-in-differences analysis comparing EC-HR with UC-HR groups. We conducted follow-up semistructured interviews to understand EC-HR participant experiences with the intervention. RESULTS: HbA1c decreased by 0.41% (4.5 mmol/mol; P=.04) more from baseline to 12 months among participants in the EC-HR group than among those in UC-HR; however, only 61 (32.9%) of 185 EC-HR participants engaged in the program. Among the EC-HR participants who wore continuous glucose monitors (61/185, 32.9%), HbA1c was 1.1% lower at 12 months compared with baseline (P<.001). Interviews revealed themes related to EC-HR participants' program engagement and continuous glucose monitor use. CONCLUSIONS: Among patients with suboptimally controlled T2DM, a combined approach that includes continuous glucose monitoring and low-carbohydrate nutrition counseling can improve glycemic control compared with the standard of care.

Technology-Facilitated Depression Self-Management Linked with Lay Supporters and Primary Care Clinics: Randomized Controlled Trial in a Low-Income Sample.

Purpose: To test whether technology-facilitated self-management support improves depression in primary care settings. Methods: We randomized 204 low-income primary care patients who had at least moderate depressive symptoms to intervention or control. Intervention participants received 12 months of weekly automated interactive voice response telephone calls that assessed their symptom severity and provided self-management strategies. Their patient-nominated supporter (CarePartner) received corresponding guidance on self-management support, and their primary care team received urgent notifications. Those randomized to enhanced usual care received printed generic self-management instructions. Results: One-year attrition rate was 14%. By month 6, symptom severity on the Patient Health Questionnaire-9 (PHQ-9) decreased 2.5 points more in the intervention arm than in the control arm (95% CI -4.2 to -0.8, p = 0.003). This benefit was similar at month 12 (p = 0.004). Intervention was also over twice as likely to lead to ≥50% reduction in symptom severity by month 6 (OR = 2.2 (1.1, 4.7)) and a decrease of ≥5 PHQ-9 points by month 12 (OR = 2.3 (1.2, 4.4)). Conclusions: Technology-facilitated self-management guidance with lay support and clinician notifications improves depression for primary care patients. Subsequent research should examine implementation and generalization to other chronic conditions. clinicaltrials.gov, identifier NCT01834534.

Physician Suicide in the United States:Updated Estimates from the National Violent Death Reporting System.

Physician suicide and well-being are critical issues but studies use varying methodologies and suicide is frequently underreported. This study sought to update data on physician suicides in the United States. The National Violent Death Reporting System (NVDRS) at the Centers for Disease Control collects details about violent deaths. The study used 2010-2015 data from 27 NVDRS states to identify suicide deaths among physicians or non-physicians and calculate annual standardized mortality rates (SMR). Of 63,780 victims total, there were 357 physicians identified over 6 years, (307 men and 50 women). If results are extrapolated to all 50 states, there would be approximately 119 physician suicides annually. The SMR for physicians overall was not statistically different from that of non-physicians. This is the first study in 16 years to update estimated physician suicide rates in the United States. The research used strict criteria to identify physicians so results likely represent the lower boundary of physician suicides. Findings show that physician suicide is not significantly lower than that of non-physicians and emphasizes the importance of focusing on structural changes to reduce stigma around mental health in the medical community.

Changes in Serum, Red Blood Cell, and Colonic Fatty Acids in a Personalized Omega-3 Fatty Acid Supplementation Trial.

This study evaluated changes in fatty acids from sera, red blood cells, and colonic biopsies from a phase Ib clinical trial of personalized ω-3 fatty acid dosing in 47 healthy volunteers. The trial aimed to reduce colonic prostaglandin E2 (PGE2), a pro-inflammatory product of arachidonic acid (AA) oxidation. The personalized doses ranged 2-10 grams/day (54% eicosapentaenoic acid, EPA, 24% other ω-3 fatty acids). In colon, increases in ω-3 highly unsaturated fatty acids (HUFA) and EPA:AA ratios each were correlated with decreases in PGE2. Changes in either colonic EPA:AA ratios or ω-3 HUFA were significantly correlated with changes in the same fatty acid measures in red blood cells or serum. The only blood-based measure significantly correlated with changes in colonic PGE2 was change in red blood cell ω-3 HUFA (ρ = -0.39), and the increase in red blood cell ω-3 HUFA was significantly greater in participants who had at least a median reduction in colonic PGE2 vs. those who did not. In summary, fatty acid changes in blood did reflect fatty acid changes in the colon, but additional factors will be needed for optimizing dosing models that seek to predict the anti-inflammatory effects of ω-3 fatty acids on the colon.

Patient-Centered Home Cancer Screening Attitudes During COVID-19 Pandemic.

The COVID-19 pandemic disrupted health care delivery of cancer screenings. The primary aim of our work was to evaluate the degree to which populations were accepting of home-based screenings for colorectal cancer (CRC) and cervical cancer (ie, primary human papillomavirus [HPV] testing). Three groups of adults having distinct health burdens that may affect acceptance of home-based cancer screening were identified through outpatient electronic medical records: those having survived a COVID-19 hospitalization; those having been positive for a non-COVID-19 respiratory illness; or those having type 2 diabetes. A total of 132 respondents (58% female) completed an online survey with hypothetical cases about their acceptance of home-based CRC or cervical cancer screening. Among women respondents, urine and vaginal screening for primary HPV testing was acceptable to 64% and 59%, respectively. Among both men and women, at-home CRC screening with fecal immunochemical test or Cologuard® was acceptable to 60% of the respondents. When adjusting for education, women with a positive attitude toward home-based urine and vaginal screening were 49 times and 23 times more likely, respectively, to have a positive attitude toward CRC screening. These findings indicate that home-based cancer screens for CRC and primary HPV testing are acceptable to men and women and may allow for greater compliance with screening in the future.