Pulmonary hypertension impairs vasomotor function in rat diaphragm arterioles.

Pulmonary hypertension (PH) is a chronic, progressive condition in which respiratory muscle dysfunction is a primary contributor to exercise intolerance and dyspnea in patients. Contractile function, blood flow distribution, and the hyperemic response are altered in the diaphragm with PH, and we sought to determine whether this may be attributed, in part, to impaired vasoreactivity of the resistance vasculature. We hypothesized that there would be blunted endothelium-dependent vasodilation and impaired myogenic responsiveness in arterioles from the diaphragm of PH rats. Female Sprague-Dawley rats were randomized into healthy control (HC, n = 9) and monocrotaline-induced PH rats (MCT, n = 9). Endothelium-dependent and -independent vasodilation and myogenic responses were assessed in first-order arterioles (1As) from the medial costal diaphragm in vitro. There was a significant reduction in endothelium-dependent (via acetylcholine; HC, 78 ± 15% vs. MCT, 47 ± 17%; P < 0.05) and -independent (via sodium nitroprusside; HC, 89 ± 10% vs. MCT, 66 ± 10%; P < 0.05) vasodilation in 1As from MCT rats. MCT-induced PH also diminished myogenic constriction (P < 0.05) but did not alter passive pressure responses. The diaphragmatic weakness, impaired hyperemia, and blood flow redistribution associated with PH may be due, in part, to diaphragm vascular dysfunction and thus compromised oxygen delivery which occurs through both endothelium-dependent and -independent mechanisms.

Evaluating remission of type 2 diabetes using a metabolic intervention including fixed-ratio insulin degludec and liraglutide: A randomized controlled trial.

AIM: To evaluate the effect on type 2 diabetes remission of short-term intensive metabolic intervention consisting of frequent dietary, exercise and diabetes management coaching, metformin and fixed-ratio insulin degludec/liraglutide. METHODS: In a multicentre open-label randomized controlled trial, insulin-naïve participants within 5 years of diabetes diagnosis were assigned to a 16-week remission intervention regimen or standard care, and followed for relapse of diabetes and sustained remission for an additional year after stopping glucose-lowering drugs. RESULTS: A total of 159 participants aged 57 ± 10 years, with diabetes duration 2.6 ± 1.5 years, body mass index 33.5 ± 6.5 kg/m2, and glycated haemoglobin (HbA1c) level 53 ± 7 mmol/mol were randomized and analysed (79 intervention, 80 control). At the end of the 16-week intervention period, compared to controls, intervention participants achieved lower HbA1c levels (40 ± 4 vs. 51 ± 7 mmol/mol; p < 0.0001), and lost more weight (3.3 ± 4.4% vs. 1.9 ± 3.0%; p = 0.02). There was a lower hazard of diabetes relapse overall in the intervention group compared to controls (hazard ratio 0.63, 95% confidence interval [CI] 0.45, 0.88; p = 0.007), although this was not sustained over time. Remission rates in the intervention group were not significantly higher than in the control group at 12 weeks (17.7% vs. 12.5%, relative risk [RR] 1.42, 95% CI 0.67, 3.00; p = 0.36) or at 52 weeks (6.3% vs. 3.8%, RR 1.69, 95% CI 0.42, 6.82) following the intervention period. CONCLUSIONS: An intensive remission-induction intervention including fixed-ratio insulin degludec/liraglutide reduced the risk of type 2 diabetes relapse within 1 year without sustained remission.

The impact of the affordable care act on perinatal mood and anxiety disorder diagnosis and treatment rates among Michigan Medicaid enrollees 2012-2018.

BACKGROUND: Perinatal Mood and Anxiety Disorders (PMADs) affect one in five birthing individuals and represent a leading cause of maternal mortality. While these disorders are associated with a variety of poor outcomes and generate significant societal burden, underdiagnosis and undertreatment remain significant barriers to improved outcomes. We aimed to quantify whether the Patient Protection Affordable Care Act (ACA) improved PMAD diagnosis and treatment rates among Michigan Medicaid enrollees. METHODS: We applied an interrupted time series framework to administrative Michigan Medicaid claims data to determine if PMAD monthly diagnosis or treatment rates changed after ACA implementation for births 2012 through 2018. We evaluated three treatment types, including psychotherapy, prescription medication, and either psychotherapy or prescription medication. Participants included the 170,690 Medicaid enrollees who had at least one live birth between 2012 and 2018, with continuous enrollment from 9 months before birth through 3 months postpartum. RESULTS: ACA implementation was associated with a statistically significant 0.76% point increase in PMAD diagnosis rates (95% CI: 0.01 to 1.52). However, there were no statistically significant changes in treatment rates among enrollees with a PMAD diagnosis. CONCLUSION: The ACA may have improved PMAD detection and documentation in clinical settings. While a higher rate of PMAD cases were identified after ACA Implementation, Post-ACA cases were treated at similar rates as Pre-ACA cases.

Anxiety in Alzheimer's disease rats is independent of memory and impacted by genotype, age, sex, and exercise.

INTRODUCTION: Alzheimer's disease (AD) is characterized by cognitive impairments; however, heightened anxiety often accompanies and, in some cases, exacerbates cognitive its. The present study aims to understand the influence of multiple variables on anxiety-like behavior in TgF344-AD rats and determine whether anxiety impacts memory performance. METHODS: An elevated plus maze was used to assess anxiety-like behavior in the established colony (n = 107). Influences of age, sex, genotype, and exercise on anxiety were evaluated via multiple linear regression. Correlation analysis evaluated the relationship between anxiety and memory performance. RESULTS: Age (P < 0.05) and AD genotype (P < 0.001) were associated with increasing anxiety, while exercise (P < 0.05) was associated with decreasing anxiety. Female AD animals displayed more anxiety-like behavior versus wild-type female (P < 0.001) and AD male (P < 0.05) littermates. DISCUSSION: Concluding that while factors such as age, sex, AD genotype, and training status can impact anxiety levels in the TgF344-AD model, anxiety level did not impact memory performance. HIGHLIGHTS: Increased anxiety-like behavior in TgF344-AD rats does not correlate with declines in memory performance. Predictors of higher anxiety-like behaviors in the TgF344-AD rat include age, Alzheimer's disease (AD) genotype, and sex with female AD animals experiencing greater anxiety compared to female wild-type or male AD. Exercise training leads to decreased anxiety-like behaviors in the TgF344-AD rat.

A scoping review and narrative synthesis of neonatal skin injury severity scales.

BACKGROUND: Mechanical force skin injuries are common for critical care patients, especially neonates. Currently, identification and severity assessments of injuries are dependent on clinical experience and/or utilization of severity tools. Compared with adults, neonates sustain skin injuries in different anatomical locations and have decreased layers of healthy tissue (from 0.9 to 1.2 mm) creating questions around direct application of adult injury severity scales reliant on visual assessment. AIM: The aim of this scoping review (ScR) was to investigate severity scales used to report hospital acquired skin injuries for neonates. METHODS: This study utilized the 2015 Joanna Briggs Institute methodology for scoping reviews and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews extension. PubMed, CINAHL, COCHRANE Central, Scopus, and the reference lists of included studies were searched for studies published between 2001 and 2023, that included severity scales use within neonatal population. Two authors independently identified studies for full review, data extraction, and quality assessment. RESULTS: A systematic database search returned 1163 records. After full test review of 109 studies, 35 studies were included. A majority of studies included were cohort or action research and conducted in the United States of America. Most studies (57%, n = 20) reported skin injuries acquired throughout the body, 14 (40%) of the studies reported the nasal area alone and one study reported no anatomical location. A total of nine severity scales or combination of scales were utilized within studies (n = 31) and four studies did not report a scale. Various versions of scales from the National Pressure Ulcer Advisory Panel (n = 16), European Pressure Ulcer Advisory Panel (n = 8) or Neonatal Skin Condition Score (n = 4) were reported, compared with locally developed classifications/scales (n = 4). Scales were predominantly of ordinal grouping (74%, n = 26) or categorical assessment (14%, n = 5). Only one scale from 2004 was validated for neonates. CONCLUSION: Neonatal skin injuries will continue to be reported subjectively until severity scales are consistently applied or other measurements are identified to support assessment. Additionally, without skin injury assessment uniformity, critical examination of effectiveness of skin care treatment practices will have subjective comparison. This review suggests there is a need for consistent skin assessment and severity scales that are valid for the neonatal population and their unique skin considerations. RELEVANCE TO CLINICAL PRACTICE: In the context of neonatal skin, with its unique characteristics and heightened risk for injury, clinicians must stage, categorise, and describe injury locations to provide objective information on injury severity. Given the risk for injuries across the entire body, including mucous membranes, describing the depth of the injury is essential regardless of the anatomical site. Although not originally designed for this population, a modified version of the National Pressure Injury Advisory Panel (NPIAP) classification system, which incorporates additional classifications (e.g., skin tears), remains the most applicable severity assessment system currently available. This should be supplemented by clinical images or detailed descriptive language (e.g., subtle redness) until rigorously validated severity and assessment scales, based on neonatal data, are developed-particularly for infants born at less than 27 weeks gestation. [Correction added on 25 October 2024, after first online publication: The Relevance to Clinical Practice subsection in Abstract has been added on this version.].

Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial.

AIM: Non-surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short-term intensive glucose-lowering therapy. METHODS: In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care. Participants with glycated haemoglobin (HbA1c) <7.3% (56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for an additional 52 weeks. The primary outcome was diabetes relapse defined as HbA1c ≥6.5% (48 mmol/mol) at 24 weeks or thereafter, capillary glucose ≥10 mmol/L on ≥50% of readings, or use of diabetes medications, analysed as time-to-event. Main secondary outcomes included complete or partial diabetes remission at 24, 36, 48 and 64 weeks defined as HbA1c <6.5% (48 mmol/mol) off diabetes medications since 12 weeks after randomisation. A hierarchical testing strategy was applied. RESULTS: The intervention significantly reduced the hazard of diabetes relapse by 43% (adjusted hazard ratio 0.57, 95% confidence interval 0.40-0.81; p = .002). Complete or partial diabetes remission was achieved in 30 (38.0%) intervention group participants versus 16 (19.8%) controls at 24 weeks and 25 (31.6%) versus 14 (17.3%) at 36 weeks [relative risk 1.92 (95% confidence interval 1.14-3.24) and 1.83 (1.03-3.26), respectively]. The relative risk of diabetes remission in the intervention versus control group was 1.88 (1.00-3.53) at 48 weeks and 2.05 (0.98-4.29) at 64 weeks. CONCLUSIONS: A 12-week intensive intervention comprising insulin glargine/lixisenatide, metformin and lifestyle approaches can induce remission of diabetes.

Use of comprehensive recruitment strategies in the glycemia reduction approaches in diabetes: A comparative effectiveness study (GRADE) multi-center clinical trial.

BACKGROUND/AIMS: We present and describe recruitment strategies implemented from 2013 to 2017 across 45 clinical sites in the United States, participating in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study, an unmasked, randomized controlled trial evaluating four glucose-lowering medications added to metformin in individuals with type 2 diabetes mellitus (duration of diabetes <10 years). We examined the yield of participants recruited through Electronic Health Records systems compared to traditional recruitment methods to leverage access to type 2 diabetes patients in primary care. METHODS: Site selection criteria included availability of the study population, geographic representation, the ability to recruit and retain a diverse pool of participants including traditionally underrepresented groups, and prior site research experience in diabetes clinical trials. Recruitment initiatives were employed to support and monitor recruitment, such as creation of a Recruitment and Retention Committee, development of criteria for Electronic Health Record systems queries, conduct of remote site visits, development of a public screening website, and other central and local initiatives. Notably, the study supported a dedicated recruitment coordinator at each site to manage local recruitment and facilitate screening of potential participants identified by Electronic Health Record systems. RESULTS: The study achieved the enrollment goal of 5000 participants, meeting its target with Black/African American (20%), Hispanic/Latino (18%), and age ≧60 years (42%) subgroups but not with women (36%). Recruitment required 1 year more than the 3 years originally planned. Sites included academic hospitals, integrated health systems, and Veterans Affairs Medical Centers. Participants were enrolled through Electronic Health Record queries (68%), physician referral (13%), traditional mail outreach (7%), TV, radio, flyers, and Internet (7%), and other strategies (5%). Early implementation of targeted Electronic Health Record queries yielded a greater number of eligible participants compared to other recruitment methods. Efforts over time increasingly emphasized engagement with primary care networks. CONCLUSION: Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness successfully recruited a diverse study population with relatively new onset of type 2 diabetes mellitus, relying to a large extent on the use of Electronic Health Record to screen potential participants. A comprehensive approach to recruitment with frequent monitoring was critical to meet the recruitment goal.

Leveraging Population Health Datasets to Advance Maternal Health Research.

BACKGROUND: Maternal mortality is a public health crisis in the U.S., with no improvement in decades and worsening disparities during COVID-19. Social determinants of health (SDoH) shape risk for morbidity and mortality but maternal structural and SDoH are under-researched using population health data. To expand knowledge of those at risk for or who have experienced maternal morbidity and inform clinical, policy, and legislative action, creative use of and leveraging existing population health datasets is logical and needed. METHODS: We review a sample of population health datasets and highlight recommended changes to the datasets or data collection to better inform existing gaps in maternal health research. RESULTS: Across each of the datasets we found insufficient representation of pregnant and postpartum individuals and provide recommendations to enhance these datasets to inform maternal health research. CONCLUSIONS: Pregnant and postpartum individuals should be oversampled in population health data to facilitate rapid policy and program evaluation. Postpartum individuals should no longer be hidden within population health datasets. Individuals with pregnancies resulting in outcomes other than livebirth (e.g., abortion, stillbirth, miscarriage) should be included, or asked about these experiences.

SIGNIFICANCE: We review population health datasets and provide recommendations that would enable maternal health researchers to unlock the full potential of these datasets by exploring the influence of structural factors and SDoH on maternal health among under-researched groups.

Capillary hemodynamics and contracting skeletal muscle oxygen pressures in male rats with heart failure: Impact of soluble guanylyl cyclase activator.

In heart failure with reduced ejection fraction (HFrEF), nitric oxide-soluble guanylyl cyclase (sGC) pathway dysfunction impairs skeletal muscle arteriolar vasodilation and thus capillary hemodynamics, contributing to impaired oxygen uptake (V̇O2) kinetics. Targeting this pathway with sGC activators offers a new treatment approach to HFrEF. We tested the hypotheses that sGC activator administration would increase the O2 delivery (Q̇O2)-to-V̇O2 ratio in the skeletal muscle interstitial space (PO2is) of HFrEF rats during twitch contractions due, in part, to increases in red blood cell (RBC) flux (fRBC), velocity (VRBC), and capillary hematocrit (Hctcap). HFrEF was induced in male Sprague-Dawley rats via myocardial infarction. After 3 weeks, rats were treated with 0.3 mg/kg of the sGC activator BAY 60-2770 (HFrEF + BAY; n = 11) or solvent (HFrEF; n = 9) via gavage b.i.d for 5 days prior to phosphorescence quenching (PO2is, in contracting muscle) and intravital microscopy (resting) measurements in the spinotrapezius muscle. Intravital microscopy revealed higher fRBC (70 ± 9 vs 25 ± 8 RBC/s), VRBC (490 ± 43 vs 226 ± 35 µm/s), Hctcap (16 ± 1 vs 10 ± 1%) and a greater number of capillaries supporting flow (91 ± 3 vs 82 ± 3%) in HFrEF + BAY vs HFrEF (all P < 0.05). Additionally, PO2is was especially higher during 12-34s of contractions in HFrEF + BAY vs HFrEF (P < 0.05). Our findings suggest that sGC activators improved resting Q̇O2 via increased fRBC, VRBC, and Hctcap allowing for better Q̇O2-to-V̇O2 matching during the rest-contraction transient, supporting sGC activators as a potential therapeutic to target skeletal muscle vasomotor dysfunction in HFrEF.

Oncology telepractice orientation program.

Telepractice in oncology is an evolving practice for nurses and cancer patients. Understanding the needs of our patients led the nursing leaders of a large academic teaching centre to undertake the challenge of creating a measurable and sustainable Telephone Readiness Assessment and Orientation Program. The experiences of patients and families regarding telephone interactions triggered the launch of Live Voice Answer, a centre-wide telepractice change. To support the transition from clinic practice to telepractice with the introduction of Live Voice Answer, an orientation program was created to lay the foundation for nurses to provide excellent standardized telepractice care. A Practice Training Process map was designed to depict three stages required to successfully complete the orientation: Telephone Readiness Assessment, Telephone Practice Training session, and Practical Application. The frameworks used to support the Practice Training Process includes COSTaRS, College of Nurses of Ontario Practice Guideline: Telepractice, Cancer Care Ontario: Oncology Nursing Telepractice Standard, Cancer Care Ontario - Symptom Management Guides as well as our organizational policies. Benner's Novice to Expert Theory is also embedded to guide the skill/competency development. The purpose of this manuscript is to describe the telephone practice orientation program and share lessons learned that have contributed to its current evolution.

Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.

BACKGROUND: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. METHODS: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001). INTERPRETATION: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. FUNDING: Eli Lilly and Company.

Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial.

BACKGROUND: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. METHODS: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p<0·0001), with HRs of 0·89 (0·78-1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39-1·44; p=0·39) for chronic renal replacement therapy. INTERPRETATION: Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes. FUNDING: Eli Lilly and Company.

Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail: a post hoc analysis.

BACKGROUND: The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants METHODS: We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models. RESULTS: Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82-0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80-0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87-0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82-0.99) p = 0.028]. CONCLUSIONS: These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gouv . Unique Identifier NCT01394952).

Perinatal mood and anxiety disorders, serious mental illness, and delivery-related health outcomes, United States, 2006-2015.

BACKGROUND: National estimates of perinatal mood and anxiety disorders (PMAD) and serious mental illness (SMI) among delivering women over time, as well as associated outcomes and costs, are lacking. The prevalence of perinatal mood and anxiety disorders and serious mental illness from 2006 to 2015 were estimated as well as associated risk of adverse obstetric outcomes, including severe maternal morbidity and mortality (SMMM), and delivery costs. METHODS: The study was a serial, cross-sectional analysis of National Inpatient Sample data. The prevalence of PMAD and SMI was estimated among delivering women as well as obstetric outcomes, healthcare utilization, and delivery costs using adjusted weighted logistic with predictive margins and generalized linear regression models, respectively. RESULTS: The study included an estimated 39,025,974 delivery hospitalizations from 2006 to 2015 in the U.S. PMAD increased from 18.4 (95% CI 16.4-20.0) to 40.4 (95% CI 39.3-41.6) per 1000 deliveries. SMI also increased among delivering women over time, from 4.2 (95% CI 3.9-4.6) to 8.1 (95% CI 7.9-8.4) per 1000 deliveries. Medicaid covered 72% (95% CI 71.2-72.9) of deliveries complicated by SMI compared to 44% (95% CI 43.1-45.0) and 43.5% (95% CI 42.5-44.5) among PMAD and all other deliveries, respectively. Women with PMAD and SMI experienced higher incidence of SMMM, and increased hospital transfers, lengths of stay, and delivery-related costs compared to other deliveries (P < .001 for all). CONCLUSION: Over the past decade, the prevalence of both PMAD and SMI among delivering women increased substantially across the United States, and affected women had more adverse obstetric outcomes and delivery-related costs compared to other deliveries.

Muscle wasting: A review of exercise, classical and non-classical RAS axes.

This review identifies how the classical/non-classical renin-angiotensin system (RAS) and exercise influence muscle wasting. The classical RAS axis enhances muscle loss through the interaction with NADPH oxidase (NOX), ubiquitin proteasome system (UPS), protein synthesis and fibrosis pathways. The mainstream hypothesis identifies reactive oxygen species (ROS) as the key pathway in muscle, this review recognizes alternative pathways that lead to an increase in muscle wasting through the classical RAS axis. In addition, pathways in which the non-classical RAS axis and exercise inhibit the classical RAS axis are also explored. The non-classical RAS axis and exercise have a significant negative impact on ROS production and protein synthesis. The non-classical RAS axis has been identified in this review to directly affect protein synthesis pathways not by altering the pre-existing intracellular ROS level, further supporting the idea that muscle wasting caused by the classical RAS system is not entirely due to ROS production. Exercise has been identified to modify the RAS axes making it a therapeutic option.

Effectiveness of tobacco cessation pharmacotherapy in the Veterans Health Administration.

INTRODUCTION: In 2003, the Veterans Health Administration (VHA) implemented a directive that cessation pharmacotherapy be made available to all who use tobacco and are interested in quitting. Despite the efficacy of cessation pharmacotherapy shown in clinical trials, the generalisability of the results in real-world settings has been challenged. Hence, the specific aim of this study was to determine the effectiveness of cessation pharmacotherapies in the VHA. METHODS: This retrospective cohort study used VHA's electronic medical record data to compare quit rates among those who use tobacco and who did vs. did not receive any type of cessation pharmacotherapy. Included were 589 862 Veterans identified as current tobacco users during fiscal year 2011 who had not received cessation pharmacotherapy in the prior 12 months. Following a 6-month period to assess treatment, quit rates among those who were treated versus untreated were compared during the 7-18 months (12 months) post-treatment follow-up period. The estimated treatment effect was calculated from a logistic regression model adjusting for inverse probability of treatment weights (IPTWs) and covariates. Marginal probabilities of quitting were also obtained among those treated versus untreated. RESULTS: Adjusting for IPTWs and covariates, the odds of quitting were 24% higher among those treated versus untreated (OR=1.24, 95% CI 1.23 to 1.25, p<0.001). The marginal probabilities of quitting were 16.7% for the untreated versus 19.8% for the treated based on the weighted model. CONCLUSION: The increased quit rates among Veterans treated support the effectiveness and continuation of the VHA tobacco cessation pharmacotherapy policy.

A Multicomponent, Multi-Trigger Intervention to Enhance Asthma Control in High-Risk African American Children.

INTRODUCTION: We evaluated the effectiveness and feasibility of implementation of a multicomponent, multi-trigger (MCMT) intervention through a public health department in a high risk population of African American children. METHODS: This was a pragmatic quasi-experimental pretest-posttest study. The population consisted of African American children enrolled in Medicaid and Children's Medical Services who had poorly controlled asthma. The MCMT intervention included 4 educational sessions and home asthma trigger reduction. Parents reported outcomes at baseline and at 1 to 3 months, 6 months, and 12 months after the MCMT intervention. Analysis used the McNemar χ2 test and Student t test for paired observations. Data were collected during 2014 through 2016 in Augusta, Georgia. RESULTS: The number of children with asthma that was assessed as well controlled increased from 4 to 17 out of 20 (P < .001). Compared with baseline, at 12 months parents reported fewer days of school missed (6.4 vs 4.2, P = .01), fewer emergency department visits (1.7 vs 0.6, P = .02) and fewer hospitalizations (0.59 vs 0.18, P = .05). The most common environmental interventions were dust mitigation, getting a mattress or pillow protector, and cockroach mitigation. CONCLUSION: An MCMT intervention in high risk African American children with poorly controlled asthma administered through the health department was associated with significant improvements in asthma control, days of school missed, and emergency department visits. Broader implementation of these strategies is warranted.

Trends and Patient Characteristics Associated with Tobacco Pharmacotherapy Dispensed in the Veterans Health Administration.

Introduction: There is evidence suggesting that certain subgroups of people who use tobacco do not receive tobacco pharmacology as consistently as others. Methods: This retrospective, cohort study examined the trend in the use of cessation pharmacotherapy from 2004 to 2013 using Veterans Health Administration (VHA) administrative data. Among Veterans who used tobacco in the fiscal year (FY) 2011 and had not received pharmacotherapy in the prior year, multivariable Cox regression was used to assess the independent associations between patient clinical and demographic characteristics and pharmacotherapy initiation in the 6-months follow-up period. Results: Smoking cessation pharmacotherapy in the VHA increased from 13.8% in 2004 to 25.6% in 2013. In 2011, Veterans (N = 838309) who were more likely to newly receive pharmacotherapy included those with psychiatric disorders (depression, bipolar disorder, non-alcohol substance use disorder, other anxiety, and post-traumatic stress disorder), chronic pulmonary disease, peripheral vascular disorders, and younger Veterans (adjusted rate ratios (ARRs) ranged from 1.03 to 1.92, all p < .001). Veterans less likely to receive pharmacotherapy were those with schizophrenia or other psychosis, males, Hispanics, and those with a medical condition (uncomplicated diabetes, uncomplicated hypertension, fluid and electrolyte disorders, cardiac arrhythmia, valvular disease, hypothyroidism, acquired immunodeficiency syndrome/human immunodeficiency virus, deficiency anemia, renal failure, paralysis, coagulopathy, metastatic cancer, and other neurological disorders) (ARRs ranged from 0.74 to 0.93, all p < .001). Conclusions: Although VHA cessation pharmacotherapy use nearly doubled from 13.8% in 2004 to 25.6% in 2013, reaching undertreated subgroups, especially those with medical comorbidities, may improve cessation outcomes. Implications: Despite evidence that demographics influence the use of pharmacotherapy in smoking cessation, there is limited and contradictory information regarding how psychiatric and chronic medical illnesses affect pharmacotherapy use. Administrative data were used to determine trends and patient characteristics of those receiving pharmacotherapy to aid in smoking cessation in the Veterans Health Administration. From 2004 to 2013, pharmacotherapy use increased from 13.8% to 25.6% of current smokers. Factors associated with increased pharmacotherapy initiation were psychiatric disorders, chronic pulmonary disease, peripheral vascular disorders, and younger age. Veterans with schizophrenia or other psychosis, males, Hispanics, and most medical conditions were less likely to receive pharmacotherapy.

Validation of the MENQOL for use with women who have been treated for gynecologic or breast cancer.

PURPOSE: To conduct a psychometric evaluation of the MENQOL, a condition-specific, self-report instrument to assess menopausal symptoms in women with gynecologic and breast cancers. METHODS: Identify face and content validity of the MENQOL with experts, and reliability and construct validity with a group of women diagnosed with cancer who are suffering from treatment-induced menopause. RESULTS: Eighty-two women with treatment-induced menopause completed the MENQOL, EORTC-C30, and the SVQ. The MENQOL was shown to have good face and content validity, and acceptable reliability (homogeneity and test-retest) and validity (concurrent and construct). Additionally, 85.5% of the women reported experiencing hot flashes. However, the most bothersome symptoms were weight gain and fatigue (feeling worn out). IMPLICATIONS: The MENQOL can be used to assess treatment-induced menopausal symptoms in women diagnosed with breast or gynecologic cancer.