Dengue Virus Immunity Increases Zika Virus-Induced Damage during Pregnancy.

Zika virus (ZIKV) has recently been associated with birth defects and pregnancy loss after maternal infection. Because dengue virus (DENV) and ZIKV co-circulate, understanding the role of antibody-dependent enhancement in the context of pregnancy is critical. Here, we showed that the presence of DENV-specific antibodies in ZIKV-infected pregnant mice significantly increased placental damage, fetal growth restriction, and fetal resorption. This was associated with enhanced viral replication in the placenta that coincided with an increased frequency of infected trophoblasts. ZIKV-infected human placental tissues also showed increased replication in the presence of DENV antibodies, which was reversed by FcγR blocking antibodies. Furthermore, ZIKV-mediated fetal pathogenesis was enhanced in mice in the presence of a DENV-reactive monoclonal antibody, but not in the presence of the LALA variant, indicating a dependence on FcγR engagement. Our data suggest a possible mechanism for the recent increase in severe pregnancy outcomes after ZIKV infection in DENV-endemic areas.

Brief Peer-Supported Web-Based Skills Training in Affective and Interpersonal Regulation (BPS webSTAIR) for Trauma-Exposed Veterans in the Community: Randomized Controlled Trial.

BACKGROUND: Peer-supported mobile health (mHealth) programs hold the promise of providing a low-burden approach to increasing access to care and improving mental health. While peer support has been shown to improve engagement in care, there is limited investigation into the impact of peers on symptom outcomes. Trauma-exposed populations frequently endure co-occurring posttraumatic stress and depressive symptoms as well as difficulties in day-to-day functioning. This study evaluated the potential benefits of a peer-supported, transdiagnostic mHealth program on symptom outcomes and functioning. OBJECTIVE: This randomized controlled trial tested the effectiveness of Brief Peer-Supported (BPS) web-based Skills Training in Affective and Interpersonal Regulation (webSTAIR), a 6-module transdiagnostic digital program derived from Skills Training in Affective and Interpersonal Regulation and compared to waitlist control in a community sample of veterans who screened positive for either posttraumatic stress disorder (PTSD) or depression. METHODS: A total of 178 veterans were enrolled in this study using a 2:1 randomization scheme with 117 assigned to BPS webSTAIR and 61 assigned to waitlist control. PTSD and depressive symptoms as well as emotion regulation and psychosocial functioning were assessed at pretreatment, posttreatment, and 8-week follow-up time points. Mixed-effects models were used to assess change in outcome measures across time points. Exploratory analyses were conducted to determine whether the type and number of peer interactions influenced outcomes. RESULTS: Significant interaction effects were observed for all outcomes such that participants randomized to BPS webSTAIR reported significantly greater improvement at the posttreatment time point compared to waitlist control with moderate effect sizes for PTSD (d=0.48), depression (d=0.64), emotion regulation (d=0.61), and functional impairment (d=0.61); gains were maintained at 8-week follow-up. An initial cohort of participants who were required to engage with a peer coach to progress through the modules interacted more frequently with peers but completed fewer modules compared to a later cohort for whom peer engagement was optional. Overall, those who completed more modules reported greater improvement in all outcomes. CONCLUSIONS: BPS webSTAIR was effective in improving PTSD and depression symptoms, emotion regulation, and psychosocial functioning in community veterans. Peer-supported, transdiagnostic mHealth programs may be a particularly efficient, effective, and low-burden approach to improving mental health among trauma-exposed populations. Investigation of peer-supported programs among other populations is necessary to evaluate the generalizability of the findings. Analyses comparing peer support that was required versus optional indicated that some veterans may not need or want peer support. Future research should evaluate how best to deliver peer support and for whom it is most beneficial. If successful, peer-supported tech programs may increase the Veteran Affairs workforce as well as improve veteran mental health services and outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04286165; https://clinicaltrials.gov/study/NCT04286165.

Celecoxib-tramadol co-crystal in patients with moderate-to-severe pain following bunionectomy with osteotomy: Secondary analyses by baseline pain intensity and use of rescue medication of a phase 3, randomized, double-blind, factorial, active- and placebo-controlled trial.

BACKGROUND: In the randomized, phase 3, SUSA-301 trial, celecoxib-tramadol co-crystal (CTC) provided significantly greater analgesia compared with celecoxib, tramadol, or placebo in adults with acute, moderate-to-severe, postoperative pain. This post hoc, secondary analysis further evaluated the use of rescue medication and the incidence of treatment-emergent adverse events (TEAEs). METHODS: Patients (N = 637) were randomized 2:2:2:1 to receive oral CTC 200 mg twice daily (BID; n = 184), tramadol 50 mg four times daily (QID; n = 183), celecoxib 100 mg BID (n = 181), or placebo QID (n = 89). Post hoc analyses were conducted on the use of rescue medications up to 4 and 48 h post-study drug dose, stratified by baseline pain intensity (moderate/severe), and on the incidence of TEAEs, stratified by rescue medication use. RESULTS: A significantly lower proportion of patients received any rescue medication within 4 h post-study dose with CTC (49.5%) versus tramadol (61.7%, p = 0.0178), celecoxib (65.2%, p = 0.0024), and placebo (75.3%, p = 0.0001); this was also seen for oxycodone use. Fewer patients in the CTC group received ≥3 doses of rescue medication compared with the other groups, irrespective of baseline pain intensity. In patients who did not receive opioid rescue medication, CTC was associated with a lower incidence of nausea and vomiting TEAEs versus tramadol alone. In patients who received rescue oxycodone, the incidence of nausea was similar in the CTC and tramadol groups, and higher versus celecoxib and placebo. CONCLUSION: Celecoxib-tramadol co-crystal was associated with reduced rescue medication use and an acceptable tolerability profile compared with tramadol or celecoxib alone in adults with acute, moderate-to-severe, postoperative pain.

Celecoxib-tramadol co-crystal in patients with moderate-to-severe pain following bunionectomy with osteotomy: A phase 3, randomized, double-blind, factorial, active- and placebo-controlled trial.

BACKGROUND: Celecoxib-tramadol co-crystal (CTC) is a first-in-class analgesic co-crystal of celecoxib and racemic tramadol with an improved pharmacologic profile, conferred by the co-crystal structure, compared with its active constituents administered alone/concomitantly. AIM: We evaluated CTC in moderate-to-severe acute postoperative pain. MATERIALS AND METHODS: This randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial (NCT03108482) was conducted at 6 US clinical research centers. Adults with moderate-to-severe acute pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [112 mg celecoxib/88 mg rac-tramadol hydrochloride] every 12 h), tramadol (50 mg every 6 h), celecoxib (100 mg every 12 h), or placebo for 48 h. Patients, investigators, and personnel were blinded to assignment. The primary endpoint was the 0-48 h sum of pain intensity differences (SPID0-48) in all randomized patients. Pain intensity was assessed on a 0-10 numerical rating scale (NRS). Safety was analyzed in patients who received study medication. Funded by ESTEVE Pharmaceuticals. RESULTS: In 2017 (March to November), 1323 patients were screened and 637 randomized to CTC (n = 184), tramadol (n = 183), celecoxib (n = 181), or placebo (n = 89). Mean baseline NRS was 6.7 in all active groups. CTC had a significantly greater effect on SPID0-48 (least-squares mean: -139.1 [95% confidence interval: -151.8, -126.5]) than tramadol (-109.1 [-121.7, -96.4]; p < 0.001), celecoxib (-103.7 [-116.4, -91.0]; p < 0.001), or placebo (-74.6 [-92.5, -56.6]; p < 0.001). Total treatment-emergent adverse events (TEAEs) were 358 for CTC and 394 for tramadol. Drug-related TEAEs occurred in 37.7% patients in the CTC group, compared with 48.6% in the tramadol group. There were no serious TEAEs/deaths. CONCLUSION: CTC provided greater analgesia than comparable daily doses of tramadol and celecoxib, with similar tolerability to tramadol. CTC is approved in the United States.

Ultrasound-Guided Injection Treatments Versus Surgical Neurectomy for Morton Neuroma: A Cost-Effectiveness Analysis.

BACKGROUND. Morton neuroma is a common, painful disorder of the foot with multiple treatment options of varying cost and effectiveness. OBJECTIVE. The aim of this study was to determine the most cost-effective treatment pathway for symptomatic Morton neuromas when conservative management has failed. METHODS. An incremental cost-utility analysis was performed comparing a direct to surgical neurectomy strategy with three selective injection strategies in which one or more ultrasound-guided injection therapies was tried first before surgery for patients who did not respond to treatment. The three selective injection strategies were selective steroid injection, selective alcohol injection, and selective steroid/alcohol injection in which both steroid injections and alcohol sclerosing injections were trialed successively before surgical neurectomy. The direct-to-surgery approach was compared with the three different selective injection strategies and with a no-treatment strategy in a decision-analytic model for a hypothetical group of patients with symptomatic Morton neuroma in whom conservative management had failed. Model parameters, including treatment costs, effectiveness, complication rates, and health utility states, were estimated from the literature, reimbursement databases, and expert opinion. The outcome was cost per quality-adjusted life year (QALY) with a time horizon of 3 years. A societal cost perspective was adopted with a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses for key model parameters were performed. RESULTS. For the base input values, the steroid/alcohol selective injection strategy was dominant and yielded an incremental cost-effectiveness ratio of $4401.61/QALY compared with no treatment. The probabilistic sensitivity analysis supported this strategy in 74% of 10,000 simulated trials. Results were robust with low sensitivity to most input parameters. However, when the probability of successful alcohol injection treatment dropped below 40%, the steroid selective injection strategy became most cost-effective. CONCLUSION. A trial of ultrasound-guided injection therapies for Morton neuroma is a cost-effective strategy compared with proceeding directly to surgical neurectomy. CLINICAL IMPACT. Ultrasound-guided injection therapies are indicated as first-line treatment of patients with symptomatic Morton neuromas when conservative management fails.

Likelihood of hip infection with image-guided hip aspiration dry tap: a 10-year retrospective study.

OBJECTIVE: To determine the rate of infection in patients with suspected hip septic arthritis who underwent image-guided aspiration (IHA) resulting in dry-tap, diagnostic value of subsequent lavage and re-aspiration, and if pre-aspiration MRI can help prevent a dry tap. MATERIALS AND METHODS: Retrospective review between 2010 to 2020 identified native hip (NH) and total hip arthroplasty (THA) patients who had a dry-tap following aspiration for suspected infection or periprosthetic joint infection (PJI). Serology tests, lavage/re-aspiration volumes, and aspirate cell-count/culture were assessed. On pre-aspiration MRI, presence/grade of joint effusion (JE), pseudocapsule dehiscence (PD), extraarticular fluid and sinus-tract were recorded. RESULTS: Out of 215 included dry-taps, 185 (86.0%) were non-infected and 30 (13.9%) infected. In subgroup analysis, 64/71(90.1%) NH and 121/144(84.0%) THA dry-taps were non-infected. Pre-aspiration MRI of THA group with dry-tap showed significant findings; PD with extraarticular fluid (8/12, 66.7%) and sinus tract (7/12, 58.3%) were higher in the infected compared to non-infected group (5/42, 11.9% and 0/42, 0.0%) (both p < 0.001). Among THA group, polymorphonuclear-leukocytes > 80% was present in 8/9 (88.9%) of infected versus 4/28 (14.3%) non-infected group (p < 0.001). Multivariable regression showed PD (p = 0.005) and JE (p = 0.042) being significant independent predictors of PJI, similarly the elevated CRP (p = 0.044) and JE (p = 0.017). CONCLUSION: Majority of patients suspected of hip joint infection with dry-tap were non-infected. Synovial PMN% following lavage maintains high sensitivity for detection of PJI. In patients with THA, PD and subsequent extraarticular collection can be associated with dry-tap therefore, pre-aspiration MRI can help determine their presence and plan the aspiration.

A Three-Year Analysis of the Impact of a Student-Run Gynecology Clinic on Access to Reproductive Health Care for Uninsured Women in East Harlem.

The East Harlem Health Outreach Partnership (EHHOP) is a medical student-run and attending-supervised clinic that provides primary care to predominantly Spanish-speaking, uninsured patients living in East Harlem, New York. In 2010, the clinic launched a Women's Health Clinic (WHC), to offer comprehensive gynecologic and reproductive healthcare under the guidance of faculty gynecologists. In this cross-sectional study, we analyzed WHC data from January 2018 to March 2021. Over this period, 59 individual patients were seen over 39 clinical sessions through a total of 164 clinical encounters staffed by 43 medical students and 19 faculty preceptors from the Department of Obstetrics and Gynecology at Mount Sinai. The most common reasons for referral to the EHHOP WHC were abnormal uterine bleeding, contraception counseling, and management of abnormal Pap smears; the most common procedures performed were Pap smears, long-acting reversible contraception placements and removals, and colposcopies. We discuss the critical role that student-run, physician-supervised reproductive health clinics play in reducing disparities in gynecologic care for uninsured women.

Imaging-based patient-reported outcomes (PROs) database: How we do it.

Patient-reported outcomes (PROs) provide an essential understanding of the impact a condition or treatment has on a patient, while complementing other, more traditional outcomes information like survival and time to symptom resolution. PROs have become increasingly important in medicine with the push toward patient-centered care. The creation of a PROs database within an institution or practice provides a way to collect, understand, and use this kind of patient feedback to inform quality improvement and develop the evidence base for medical decision-making and on a larger scale could potentially help determine national standards of care and treatment guidelines. This paper provides a first-hand account of our experience setting up an imaging-based PROs database at our institution and is organized into steps the reader can follow for creating a PROs database of their own. Given the limited use of PROs within both diagnostic and interventional radiology, we hope our paper stimulates a new interest among radiologists who may have never considered outcomes work in the past.

Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides.

Arthropod-borne viruses represent a significant public health threat worldwide, yet there are few antiviral therapies or prophylaxes targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy-acceptable antiviral compounds is to repurpose well-known and widely used FDA-approved drugs. In this study, we addressed the antiviral role of atovaquone, an FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides, indicating that atovaquone functions through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner, providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women and children.IMPORTANCE The ability to protect vulnerable populations such as pregnant women and children from Zika virus and other arbovirus infections is essential to preventing the devastating complications induced by these viruses. One class of antiviral therapies may lie in known pregnancy-acceptable drugs that have the potential to mitigate arbovirus infections and disease, yet this has not been explored in detail. In this study, we show that the common antiparasitic drug atovaquone inhibits arbovirus replication through intracellular nucleotide depletion and can impair ZIKV infection in an ex vivo human placental explant model. Our study provides a novel function for atovaquone and highlights that the rediscovery of pregnancy-acceptable drugs with potential antiviral effects can be the key to better addressing the immediate need for treating viral infections and preventing potential birth complications and future disease.

Symbol Digit Modalities Test: A valid clinical trial endpoint for measuring cognition in multiple sclerosis.

BACKGROUND: The need for more robust outcomes in multiple sclerosis (MS) clinical trials has been a main priority of the field for decades. Dissatisfaction with existing measures has led to several consensus meetings and initiatives over the past few decades in hopes of defining and gaining acceptance of measures that are valid, reliable, sensitive to change and progression, and most importantly, relevant to those living with MS. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed for this purpose. OBJECTIVE: The objective of this paper is to describe the results of the MSOAC plan to obtain qualification for a cognitive performance measure that meets these requirements. METHODS: Using data from 14 MS disease-modifying registration trials, we completed a comprehensive examination of the psychometric qualities of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) with the goal of compiling evidence to support the utilization of one of these measures in future clinical trials. RESULTS AND CONCLUSION: Consistent with the published literature, the SDMT proved superior to the PASAT. The SDMT should be considered the measure of choice for MS trials in assessing cognitive processing speed.

Trisomy 18: A survey of opinions, attitudes, and practices of neonatologists.

We conducted a survey-based study of the opinions, attitudes, and management practices of neonatologists across the United States regarding prenatally diagnosed Trisomy 18. The survey was designed based on previously validated surveys of severe fetal anomalies and collected demographic information on participants, as well as their attitudes, and management choices given a series of vignettes beginning in the prenatal period. The survey was sent to 3,143 American Academy of Pediatrics Section on Neonatal-Perinatal Medicine members of which 409 (13%) completed the survey. While the response rate was rather low, our respondent pool was representative of the national neonatologist population. Respondents were predominately white (81%), married (88%), Christian (54%), had children (86%), and were pro-choice in terms of abortion (68%). Eighty-three percent (83%) of respondents thought that trisomy 18 is a lethal condition and 60% thought that treatment is futile. Seventy-five percent (75%) expected that the best neurodevelopmental outcome in the case of infant survival would be profound intellectual disability. Regarding neonatal care, 95% stated that they would recommend palliative care only. Ninety-five percent (95%) would never recommend or recommend only if asked full code resuscitation for a neonate with full trisomy 18, yet, 44% would comply partially or in full with a full code request for resuscitation measures. The demographic features that correlated most significantly with these responses were clinician race and years in practice. The attitudes toward and management of infants affected with trisomy 18 seem to be largely driven by parental attitudes and wishes. © 2016 Wiley Periodicals, Inc.

Trisomy 18: A single-center evaluation of management trends and experience with aggressive obstetric or neonatal intervention.

We conducted a retrospective cohort study including all prenatal and postnatal diagnoses of trisomy 18 (T18) from 2004 to 2014 at a single tertiary referral center in the southern United States to evaluate the natural history and perinatal outcomes associated with T18 over the past decade. We analyzed pregnancy outcome, mode of delivery, and for live-births, the number and types of neonatal interventions, and characterized interventions as aggressive or non-aggressive. Survival analyses were conducted based on mode of delivery and aggressive compared to non-aggressive interventions. A total of 167 cases of T18 were identified, 150 with available records. There were 141 (94.0%) with full T18; the remainder had mosaicism (1.3%), a translocation (0.7%), or an isochromosome 18 (4.0%). Most diagnoses were prenatal (73.3%, n = 110). Of the 150 patients, there were 54 live births: 21 (38.9%) delivered vaginally, 32 (59.3%) delivered by cesarean, and mode of delivery could not be ascertained for one. Median duration of survival was 12 days (interquartile range 3-90 days). Over time, there were no changes toward increased intervention (obstetric or neonatal). For the 49 neonates who received some intervention, there was no significant difference in survival time between neonates receiving aggressive (n = 36, median survival 24 days, interquartile range 6-247) and non-aggressive (n = 13, median survival 30 days, interquartile range 8-148) intervention (P = 0.90). There was similarly no difference in neonatal survival based on mode of delivery (P = 0.79). Survival of infants with T18 is not improved with aggressive obstetric or neonatal care.

Time to finger point or fix? An invitation to join ongoing efforts to promote ethical authorship and other good publication practices.

In this commentary, we present evidence that unethical authorship (eg, guest and ghost authoring) and other publication practices are not restricted to the pharmaceutical industry; they also occur in academia. Such practices are not an industry problem--they are a research problem. To enhance trust in industry-sponsored research, companies have made rapid and far-reaching changes to their publication guidelines, policies, and procedures. Professional medical writers have adopted, and continue to implement, these changes. Although evidence indicates that industry practices are improving, there is certainly more to do, both in industry and academia. We invite readers to join ongoing efforts to promote ethical publication practices.

Current State of Platelet-rich Plasma in the Treatment of Rheumatic Disease: A Retrospective Review of the Literature.

INTRODUCTION: Rheumatic diseases are a spectrum of autoimmune or inflammatory diseases that cause damage to the musculoskeletal system as well as vital organs, such as the heart, lungs, kidneys, and central nervous system. METHODS: The study of rheumatic disease has made great progress in the understanding and management of these conditions in the last few decades using disease-modifying antirheumatic drugs and synthesized biological immunomodulating therapies. However, one potential treatment that has not been well investigated in rheumatic disease is platelet-rich plasma (PRP). PRP is proposed to facilitate the healing of injured tendons and ligaments through a variety of mechanisms, including mitogenesis, angiogenesis and macrophage activation via cytokine release, although its exact mechanism is unclear. RESULT: There has been a great deal of work in determining the exact preparation method and composition of PRP for regenerative purposes in orthopedic surgery, sports medicine, dentistry, cardiac surgery, pediatric surgery, gynecology, urology, plastic surgery, ophthalmology, and dermatology. Despite this, there is a paucity of research on the impact of PRP on rheumatic disease. CONCLUSION: This study aims to summarize and evaluate the current research concerning the use of PRP in rheumatic disease.

How frequently are contraindicated or warned against combinations of drugs prescribed to patients receiving long-term opioid therapy for chronic pain?

PURPOSE: To analyse the proportion of patients treated with an opioid for chronic pain who were prescribed concomitant medications that are warned against or contraindicated in the German summary of product characteristics to determine if warnings on drug-drug interactions (DDIs) are observed. METHODS: This retrospective analysis used longitudinal aggregated patient data from the Intercontinental Marketing Services Disease Analyzer in Germany. Patients with two or more prescriptions of morphine, hydromorphone, oxycodone or tramadol from 1 January 2006 to 31 December 2008 were included; drugs prescribed within 30 days of an opioid prescription were identified as concomitant medications. The frequency of concomitant treatment with drugs warned against or contraindicated in the German opioid summary of product characteristics was determined. Concomitant treatment with drugs metabolised by CYP3A4 inhibitors and inducers and CYP2D6 inhibitors was also considered. RESULTS: The Intercontinental Marketing Services database contained 13,405 eligible patients; 72% had concomitant diseases which may increase the risk for DDIs (hypertension, diabetes mellitus, renal failure, renal glomerular disease or renal tubulointerstitial disease). Very few patients received concomitant prescriptions of an opioid with a contraindicated drug. Many patients were prescribed opioids concomitantly with drugs with potential for harmful safety-related DDIs or DDIs that alter the effectiveness of one or more of the opioids. A large proportion of all concomitant prescriptions with potential for DDIs were given to at-risk patients aged 65 years and older. CONCLUSIONS: Many patients that received an opioid for chronic pain were prescribed concomitant medications with the potential for safety-related DDIs or interactions that would alter the effectiveness of the opioid.

Ruling out and ruling in neural codes.

The subject of neural coding has generated much debate. A key issue is whether the nervous system uses coarse or fine coding. Each has different strengths and weaknesses and, therefore, different implications for how the brain computes. For example, the strength of coarse coding is that it is robust to fluctuations in spike arrival times; downstream neurons do not have to keep track of the details of the spike train. The weakness, though, is that individual cells cannot carry much information, so downstream neurons have to pool signals across cells and/or time to obtain enough information to represent the sensory world and guide behavior. In contrast, with fine coding, individual cells can carry much more information, but downstream neurons have to resolve spike train structure to obtain it. Here, we set up a strategy to determine which codes are viable, and we apply it to the retina as a model system. We recorded from all the retinal output cells an animal uses to solve a task, evaluated the cells' spike trains for as long as the animal evaluates them, and used optimal, i.e., Bayesian, decoding. This approach makes it possible to obtain an upper bound on the performance of codes and thus eliminate those that are insufficient, that is, those that cannot account for behavioral performance. Our results show that standard coarse coding (spike count coding) is insufficient; finer, more information-rich codes are necessary.

Comparing the Ratio of Therapist Support to Internet Sessions in a Blended Therapy Delivered to Trauma-Exposed Veterans: Quasi-experimental Comparison Study.

BACKGROUND: Blended models of therapy, which incorporate elements of both internet and face-to-face methods, have been shown to be effective, but therapists and patients have expressed concerns that fewer face-to-face therapy sessions than self-guided internet sessions may be associated with lower therapeutic alliance, lower program completion rates, and poorer outcomes. OBJECTIVE: A multisite quasi-experimental comparison study with a noninferiority design implemented in routine clinical care was used to assess webSTAIR, a 10-module blended therapy derived from STAIR (skills training in affective and interpersonal regulation) for trauma-exposed individuals delivered with 10 weekly therapist sessions (termed Coach10) compared to 5 biweekly sessions (Coach5). It was hypothesized that Coach5 would be as good as Coach10 in a range of outcomes. METHODS: A total of 202 veterans were enrolled in the study with 101 assigned to Coach5 and 101 to Coach10. Posttraumatic stress disorder (PTSD) symptoms, depression, emotion regulation, interpersonal problems, and social functioning measures were collected pre-, mid-, and posttreatment, and at a 3-month follow-up. Noninferiority analyses were conducted on symptom outcome measures. Comparisons were made of continuous and categorical measures regarding participant and therapist activities. RESULTS: Participants reported moderate to severe levels of baseline PTSD, depression, or both. Significant reductions were obtained in all symptom measures posttreatment and at the 3-month follow up. Coach5 was not inferior to Coach10 in any outcome. Therapeutic alliance was at an equivalently high level across the 2 treatment conditions; completion rates and web usage were similar. Total session time was substantially less for the Coach5 therapists than the Coach10 therapists. Both programs were associated with a low, but equal number of therapist activities related to scheduling and crisis or motivational sessions. CONCLUSIONS: A blended model delivered with 5 sessions of therapist support was noninferior to 10 sessions in individuals with moderate to severe symptoms. Future studies identifying patient characteristics as moderators of outcomes with high versus low doses of therapist support will help create flexible, technology-based intervention programming.

Increasing access to care for trauma-exposed rural veterans: A mixed methods outcome evaluation of a web-based skills training program with telehealth-delivered coaching.

PURPOSE: While rural veterans with trauma exposure report high rates of posttraumatic stress disorder (PTSD), depression, and functional impairment, utilization of health services is low. This pilot study used mixed qualitative and quantitative methods to evaluate the potential benefits of a transdiagnostic web-based skills training program paired with telehealth-delivered coaching to address a range of symptoms and functional difficulties. The study directed substantial outreach efforts to women veterans who had experienced military sexual trauma given their growing representation in the Veterans Healthcare Administration (VHA) and identified need for services. METHODS: Participants were 32 trauma-exposed veterans enrolled in rural-serving VHA facilities who screened positive for either PTSD or depression. Symptoms of PTSD, depression, emotion regulation, and interpersonal problems were assessed at baseline, midpoint, posttreatment, and 3-month follow-up. Veterans completed exit interviews to identify benefits and limitations of the program. RESULTS: Intent-to-treat analyses revealed significant symptom reduction for all outcomes, with large to moderate effect sizes at 3-month follow-up. Outcomes did not differ by gender or military sexual trauma status. Veterans' rating of the therapeutic alliance was high and interview responses indicated that the presence of the coach was critical to success in the program. CONCLUSION: This remotely delivered transdiagnostic intervention provided significant benefits across a range of symptoms and functional outcomes and was viewed positively by veterans. The results indicate that further research (ie, a randomized controlled trial) is warranted. Attention to the role of the coach as a means by which to increase engagement and retention in technology-delivered interventions is warranted.

PPARdelta activation induces metabolic and contractile maturation of human pluripotent stem cell-derived cardiomyocytes.

Pluripotent stem-cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease, but they are functionally and structurally immature. Here, we induce efficient human PSC-CM (hPSC-CM) maturation through metabolic-pathway modulations. Specifically, we find that peroxisome-proliferator-associated receptor (PPAR) signaling regulates glycolysis and fatty acid oxidation (FAO) in an isoform-specific manner. While PPARalpha (PPARa) is the most active isoform in hPSC-CMs, PPARdelta (PPARd) activation efficiently upregulates the gene regulatory networks underlying FAO, increases mitochondrial and peroxisome content, enhances mitochondrial cristae formation, and augments FAO flux. PPARd activation further increases binucleation, enhances myofibril organization, and improves contractility. Transient lactate exposure, which is frequently used for hPSC-CM purification, induces an independent cardiac maturation program but, when combined with PPARd activation, still enhances oxidative metabolism. In summary, we investigate multiple metabolic modifications in hPSC-CMs and identify a role for PPARd signaling in inducing the metabolic switch from glycolysis to FAO in hPSC-CMs.

Effect of the presence of amniotic fluid for optical transabdominal fetal monitoring using Monte Carlo simulations.

About a third of babies are delivered by Cesarean section. There has been an increase in maternal deaths during labor due to complications with subsequent births after a C-section. Therefore, there is a clinical motivation to reduce the C-section rate. Current techniques are, however, inefficient at determining fetal distress leading to a high false positive rate for complications and ultimately a C-section. For the current study, Monte Carlo simulations were used to calculate the amount of signal received on a model of a pregnant mother, as well as, the percent of the signal that comes from the fetal layer. Models with and without a 1 mm amniotic fluid were compared and showed differing trends.