Burden of Disease and Treatment Patterns Amongst Patients With Vitiligo: Findings From a National, Longitudinal Retrospective Study in the United Kingdom.

This retrospective study, using UK Clinical Practice Research Datalink and Hospital Episode Statistics databases, analysed 17,239 incident patients with vitiligo. Mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years (range: 0.10 [2010-COVID] to 0.19 [2013/2018]); prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%), and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time were most commonly depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%), and sleep disturbance (12.7%); recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5%, and 3.9%, respectively. Mental health comorbidities were more common among White patients (eg, depression and/or anxiety, 29.0%) than Black (18.8%), Asian (16.1%), and other ethnicities (21.4%). In adolescents, depression and/or anxiety was most commonly diagnosed after vitiligo diagnosis (7.4% vs before, 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 person-years) and general practitioner consultations (97.9/100 person-years). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatments (ie, topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids, phototherapy), increasing to 82.0% the next year; median (95% CI) time from diagnosis to first treatment was 34.0 (31.6-36.4) months. Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments; 16.6% had a record of antidepressant and/or anxiolytic treatments. Most patients were not on vitiligo-related treatments within a year of diagnosis, with time to first treatment >2 years, suggesting that vitiligo may be dismissed as unimportant and not treated early, in part due to limited effectiveness of available treatments. New effective treatments, early initiation, and psychological intervention and support are needed to reduce vitiligo burden on patients.

The working mechanisms of imagery rescripting and eye movement desensitization and reprocessing: Findings from a randomised controlled trial.

We studied the mechanisms of eye movement desensitization and reprocessing (EMDR) and imagery rescripting (ImRs). We hypothesized that EMDR works via changes in memory vividness, that ImRs works via changes in encapsulated beliefs (EB), and that both treatments work via changes in memory distress. Patients (N = 155) with childhood-related posttraumatic stress disorder (Ch-PTSD) received 12 sessions of EMDR or ImRs. The vividness, distress, and EB related to the index trauma were measured with the Imagery Interview. PTSD severity was assessed with the Impact of Events Scale-Revised and the Clinician-Administered PTSD Scale for DSM-5. We conducted mixed regressions and Granger causality analyses. EMDR led to initially stronger changes in all predictors, but only for distress this was retained until the last assessment. No evidence for vividness as a predictive variable was found. However, changes in distress and EB predicted changes in PTSD severity during ImRs. These findings partially support the hypothesized mechanisms of ImRs, while no support was found for the hypothesized mechanisms of EMDR. Differences in the timing of addressing the index trauma during treatment and the timing of assessments could have influenced the findings. This study provides insight into the relative effectiveness and working mechanisms of these treatments.

EMDR v. other psychological therapies for PTSD: a systematic review and individual participant data meta-analysis.

BACKGROUND: This systematic review and individual participant data meta-analysis (IPDMA) examined the overall effectiveness of eye movement desensitization and reprocessing (EMDR) in reducing posttraumatic stress disorder (PTSD) symptoms, achieving response and remission, and reducing treatment dropout among adults with PTSD compared to other psychological treatments. Additionally, we examined available participant-level moderators of the efficacy of EMDR. METHODS: This study included randomized controlled trials. Eligible studies were identified by a systematic search in PubMed, Embase, PsyclNFO, PTSDpubs, and CENTRAL. The target population was adults with above-threshold baseline PTSD symptoms. Trials were eligible if at least 70% of study participants had been diagnosed with PTSD using a structured clinical interview. Primary outcomes included PTSD symptom severity, treatment response, and PTSD remission. Treatment dropout was a secondary outcome. The systematic search retrieved 15 eligible randomized controlled trials (RCTs); 8 of these 15 were able to be included in this IPDMA (346 patients). Comparator treatments included relaxation therapy, emotional freedom technique, trauma-focused cognitive behavioral psychotherapies, and REM-desensitization. RESULTS: One-stage IPDMA found no significant difference between EMDR and other psychological treatments in reducing PTSD symptom severity (ß = -0.24), achieving response (ß = 0.86), attaining remission (ß = 1.05), or reducing treatment dropout rates (ß = -0.25). Moderator analyses found unemployed participants receiving EMDR had higher PTSD symptom severity at the post-test, and males were more likely to drop out of EMDR treatment than females. CONCLUSION: The current study found no significant difference between EMDR and other psychological treatments. We found some indication of the moderating effects of gender and employment status.

Intraindividual variability and emotional change as predictors of sudden gains in imagery rescripting and EMDR for PTSD in adult survivors of childhood abuse.

Sudden gains, defined as large and stable improvements in symptom severity during psychological treatment, have consistently been found to be associated with better outcomes across treatments and diagnoses. Yet, insights on coherent predictors of sudden gains and on emotional changes around sudden gains in post-traumatic stress disorder (PTSD) are lacking. We aimed at replicating a measure of intraindividual variability as a predictor for sudden gains and testing its independence from change during treatment. Furthermore, we expected changes in emotions of guilt, shame and disgust prior to sudden gains to predict sudden gains. Data from a pre-registered randomized controlled trial (RCT) of eye-movement desensitization and reprocessing (emdr) and Imagery Rescripting (ImRs) for PTSD in 155 adult survivors of childhood abuse were used. Intraindividual variability of PTSD symptoms in both treatments did not predict sudden gains status and was not independent of change during treatment. In the EMDR condition, levels of shame during treatment predicted sudden gains and shame decreased shortly before a sudden gain in both treatments. Reductions in all emotions during sudden gains were significantly higher for participants with sudden gains than for comparable intervals in non-sudden gainers. Our findings do not support the predictive validity of intraindividual variability for sudden gains. The decrease of guilt, shame and disgust during sudden gains warrants further research on their role as a mechanism of treatment change for PTSD.

A Comprehensive Update of Prolotherapy in the Management of Osteoarthritis of the Knee.

This is a comprehensive review of the literature focusing on the use of prolotherapy in the treatment of osteoarthritis of the knee. It covers the background, efficacy, and advantages of prolotherapy in the management of osteoarthritis symptoms and then covers the existing evidence of the use of prolotherapy for this purpose. Current treatments for osteoarthritis of the knee are numerous, yet patients continue to endorse chronic pain and poor quality of life. Prolotherapy is a treatment that has been inadequately studied with poor sample sizes and lack of standardization between trials. However, in recent years the literature on prolotherapy in the treatment of knee osteoarthritis has grown. Although there is still a lack of homogeneity, trials have shown that dextrose prolotherapy, autologous conditioned serum, hyaluronic injections, and normal saline administered either intra- or peri-articularly are comparable in reducing pain scores to other primary treatment options. The mechanism of action for prolotherapy is still unclear, but researchers have found that prolotherapy plays some role in cartilage growth or chondrogenesis and has been shown to have improved radiographic outcomes. Prolotherapy appears to be a safe treatment alternative that has been shown to improve stiffness, pain, function, and quality of life in osteoarthritis of the knee. Knee osteoarthritis is remarkably prevalent in the United States and is one of the most common causes of disability in the elderly population. Although there are many treatment options, patients continue to live with chronic pain which can incur high costs for patients. A safe, long-term, and effective solution has not yet been identified. Prolotherapy has been shown to be a safe option for improving pain, function, and quality of life as effectively as other treatment options.

An Update on Posterior Tarsal Tunnel Syndrome.

Posterior tarsal tunnel syndrome (PTTS) is an entrapment neuropathy due to compression of the tibial nerve or one of its terminal branches within the tarsal tunnel in the medial ankle. The tarsal tunnel is formed by the flexor retinaculum, while the floor is composed of the distal tibia, talus, and calcaneal bones. The tarsal tunnel contains a number of significant structures, including the tendons of 3 muscles as well as the posterior tibial artery, vein, and nerve. Focal compressive neuropathy of PTTS can originate from anything that physically restricts the volume of the tarsal tunnel. The variety of etiologies includes distinct movements of the foot, trauma, vascular disorders, soft tissue inflammation, diabetes mellitus, compression lesions, bony lesions, masses, lower extremity edema, and postoperative injury. Generally, compression of the posterior tibial nerve results in clinical findings consisting of numbness, burning, and painful paresthesia in the heel, medial ankle, and plantar surface of the foot. Diagnosis of PTTS can be made with the presence of a positive Tinel sign in combination with the physical symptoms of pain and numbness along the plantar and medial surfaces of the foot. Initially, patients are treated conservatively unless there are signs of muscle atrophy or motor nerve involvement. Conservative treatment includes activity modification, heat, cryotherapy, non-steroidal anti-inflammatory drugs, corticosteroid injections, opioids, GABA analog medications, tricyclic antidepressants, vitamin B-complex supplements, physical therapy, and custom orthotics. If PTTS is recalcitrant to conservative treatment, standard open surgical decompression of the flexor retinaculum is indicated. In recent years, a number of alternative minimally invasive treatment options have been investigated, but these studies have small sample sizes or were conducted on cadaveric models.

Efficacy of acupuncture in the treatment of fibromyalgia.

PURPOSE OF REVIEW: Fibromyalgia is a highly prevalent chronic pain syndrome that affects up to 4% of the population and causes significant morbidity and disability, with an increasing associated cost. Though many approaches for treatment have been tested, therapy regimens are still elusive, and efficacy is limited. This review summarizes the background of fibromyalgia and acupuncture and reviews the latest and seminal literature discussing the application of acupuncture in fibromyalgia. RECENT FINDINGS: Fibromyalgia is hard to treat, owing both to its chronicity and poorly understood pathophysiology and etiology. Current treatments target symptoms primarily, and few attempt to address the source. Efficacious treatment requires long-term treatment by a multidisciplinary team. Though several treatments exist, they still fall short with a substantial number of patients. Acupuncture, a form of integrative medicine, has been a part of traditional Chinese medication for generations. Evidence shows that it effectively treats different kinds of pain conditions, including migraines and chronic musculoskeletal pain. Recent studies showed evidence to support its use in fibromyalgia. Clinical trials studying acupuncture in fibromyalgia have shown improvement in pain, quality of sleep, and quality of life, though the quality of evidence is mainly low to medium. Several studies were not able to provide evidence to support real over sham acupuncture. Weighing the overall evidence paints a picture of mixed results between equivocal results to positive. In analyzing these results, one must also consider publication bias supporting the dissemination of positive results. SUMMARY: An increasing number of studies support the utilization of acupuncture for the treatment of fibromyalgia. Though no head-to-head comparison was able to show the superiority of acupuncture to other therapies, mounting evidence supports its use as part of multimodal approaches to treatment with additive efficacy to traditional therapy. Further research will likely provide data on effective regimens and combination therapies.

The effect of twice-weekly versus once-weekly sessions of either imagery rescripting or eye movement desensitization and reprocessing for adults with PTSD from childhood trauma (IREM-Freq): a study protocol for an international randomized clinical trial.

BACKGROUND: Trauma-focused treatments for posttraumatic stress disorder (PTSD) are commonly delivered either once or twice a week. Initial evidence suggests that session frequency affects treatment response, but very few trials have investigated the effect of session frequency. The present study's aim is to compare treatment outcomes of twice-weekly versus once-weekly sessions of two treatments for PTSD related to childhood trauma, imagery rescripting (ImRs) and eye movement desensitization and reprocessing (EMDR). We hypothesize that both treatments will be more effective when delivered twice than once a week. How session frequency impacts treatment response, whether treatment type moderates the frequency effect, and which treatment type and frequency works best for whom will also be investigated. METHODS: The IREM-Freq trial is an international multicenter randomized clinical trial conducted in mental healthcare centers across Australia, Germany, and the Netherlands. We aim to recruit 220 participants, who will be randomized to one of four conditions: (1) EMDR once a week, (2) EMDR twice a week, (3) ImRs once a week, or (4) ImRs twice a week. Treatment consists of 12 sessions. Data are collected at baseline until one-year follow-up. The primary outcome measure is clinician-rated PTSD symptom severity. Secondary outcome measures include self-reported PTSD symptom severity, complex PTSD symptoms, trauma-related cognitions and emotions, depressive symptoms, dissociation, quality of life, and functioning. Process measures include memory, learning, therapeutic alliance, motivation, reluctance, and avoidance. Additional investigations will focus on predictors of treatment outcome and PTSD severity, change mechanisms of EMDR and ImRs, the role of emotions, cognitions, and memory, the optimization of treatment selection, learned helplessness, perspectives of patients and therapists, the network structure of PTSD symptoms, and sudden treatment gains. DISCUSSION: This study will extend our knowledge on trauma-focused treatments for PTSD related to childhood trauma and, more specifically, the importance of session frequency. More insight into the optimal session frequency could lead to improved treatment outcomes and less dropout, and in turn, to a reduction of healthcare costs. Moreover, the additional investigations will broaden our understanding of how the treatments work and variables that affect treatment outcome. TRIAL REGISTRATION: Netherlands Trial Register NL6965, registered 25/04/2018.

Differential Effects of Comorbid Psychiatric Disorders on Treatment Outcome in Posttraumatic Stress Disorder from Childhood Trauma.

Patients with posttraumatic stress disorder (PTSD) frequently have comorbid diagnoses such as major depressive disorder (MDD) and anxiety disorders (AD). Studies into the impact of these comorbidities on the outcome of PTSD treatment have yielded mixed results. The different treatments investigated in these studies might explain the varied outcome. The purpose of this study was to examine the impact of these comorbidities on the outcome of two specific PTSD treatments. MDD and AD were analyzed as predictors and moderators in a trial comparing 12 sessions of either eye movement desensitization and reprocessing (EMDR) or imagery rescripting (IR) in 155 adult patients with PTSD from childhood trauma. The primary outcome was reduction of PTSD symptoms (clinician-administered PTSD Scale for DSM-5, CAPS-5) assessed at eight-week follow-up and a secondary outcome was self-report PTSD symptoms (Impact of Event Scale, IES-R). MDD was not a predictor of treatment outcome but did have a significant moderator effect. Patients with MDD showed a better outcome if they were treated with IR, whereas patients without MDD improved more in the EMDR condition. No impact of AD emerged. It seems essential to consider comorbid MDD when planning PTSD treatment to improve treatment outcomes. More research is needed to replicate our findings and focus on different kinds of PTSD treatments and other comorbidities.

Trauma-focused treatments for depression. A systematic review and meta-analysis.

BACKGROUND: Trauma-focused treatments (TFTs) have demonstrated efficacy at decreasing depressive symptoms in individuals with PTSD. This systematic review and meta-analysis evaluated the effectiveness of TFTs for individuals with depression as their primary concern. METHODS: A systematic search was conducted for RCTs published before October 2019 in Cochrane CENTRAL, Pubmed, EMBASE, PsycInfo, and additional sources. Trials examining the impact of TFTs on participants with depression were included. Trials focusing on individuals with PTSD or another mental health condition were excluded. The primary outcome was the effect size for depression diagnosis or depressive symptoms. Heterogeneity, study quality, and publication bias were also explored. RESULTS: Eleven RCTs were included (n = 567) with ten of these using EMDR as the TFT and one using imagery rescripting. Analysis suggested these TFTs were effective in reducing depressive symptoms post-treatment with a large effect size [d = 1.17 (95% CI: 0.58~ 1.75)]. Removal of an outlier saw the effect size remain large [d = 0.83 (95% CI: 0.48~ 1.17)], while the heterogeneity decreased (I2 = 66%). Analysis of the 10 studies that used EMDR also showed a large effect [d = 1.30 (95% CI: 0.67~1.91)]. EMDR was superior to non trauma-focused CBT [d = 0.66 (95% CI: 0.31~1.02)] and analysis of EMDR and imagery rescripting studies suggest superiority over inactive control conditions [d = 1.19 (95% CI: 0.53~ 1.86)]. Analysis of follow-up data also supported the use of EMDR with this population [d = 0.71 (95% CI: 1.04~0.38)]. No publication bias was identified. CONCLUSIONS: Current evidence suggests that EMDR can be an effective treatment for depression. There were insufficient RCTs on other trauma-focused interventions to conclude whether TFTs in general were effective for treating depression. Larger studies with robust methodology using EMDR and other trauma-focused interventions are needed to build on these findings.

Ingestion of food grade hydrogen peroxide with resultant gastrointestinal and neurologic symptoms treated with hyperbaric oxygen therapy: case report and review with emphasis on the therapeutic value of HBO2 in vascular gas embolism.

A 52-year-old male accidentally ingested approximately 100 mL of 35% hydrogen peroxide (H2O2), resulting in the sudden onset of gastrointestinal and neurologic symptoms. Non-contrast abdominal CT revealed extensive portal venous gas and gastric pneumatosis. The patient was treated with hyperbaric oxygen therapy which resulted in complete resolution of symptoms. The case highlights the therapeutic value of hyperbaric oxygen therapy in the treatment of vascular gas embolism and mitigation of concentrated H2O2 ingestion toxicity.

A randomized controlled trial examining the impact of individual trauma-focused therapy for individuals receiving group treatment for depression.

OBJECTIVES: Adverse life events are associated with increased likelihood of depression and poorer prognosis. Trauma-focused treatments (TFT) appear to be effective in decreasing comorbid depressive symptoms. Accordingly, the aim of this study was to evaluate the effectiveness of a TFT on the memories of aversive events for individuals with a primary diagnosis of depression. METHODS: A randomized controlled trial was conducted with 49 participants recruited from a 10-day outpatient group programme. All participants showed symptoms of depression with a subgroup (80%) meeting the DSM-5 criteria for a major depressive episode. Participants received treatment as usual (TAU); three additional individual trauma-focused sessions; or three additional individual assertiveness training sessions. Participants were assessed with regards to depression diagnosis and related symptoms. RESULTS: For participants with a major depressive episode, the addition of trauma-focused sessions significantly increased the likelihood of remission when compared to TAU, or additional assertiveness training. While no significant treatment difference was noted in depressive symptom change post-treatment, six weeks after treatment those who received an adjunct treatment were more likely to maintain treatment gains than those who received TAU. Furthermore, at 12-week follow-up, participants who received a TFT reported significantly fewer depressive symptoms than those who received assertiveness training. CONCLUSIONS: While differences in outcomes were minimal immediately post-treatment, differences among treatment groups increased over time. Thus, as few as three additional TFT sessions may impact positively on symptom change for people completing a group programme for the treatment of depression. PRACTITIONER POINTS: Depression is the greatest cause of disability worldwide. Adverse experiences are linked with an increased likelihood of depression, more severe symptoms and poor treatment outcomes following evidence-based interventions. As few as three trauma-focused sessions can improve treatment outcomes in terms of depression diagnosis and related symptoms for individuals receiving group cognitive behavioural therapy.

Mindfulness in persons with anorexia nervosa and the relationships between eating disorder symptomology, anxiety and pain.

Mindfulness is useful for some psychiatric illnesses, but limited research exists among persons with anorexia nervosa (AN). This study aimed to determine the relationship between mindfulness, eating disorder symptomology and indicators of health in women with AN (n = 59) entering residential treatment. Participants completed a self-administered survey, including the Cognitive Affective Mindfulness Scale and other measures. Additional data from medical records were collected. Greater mindfulness was associated with less eating disorder symptoms (p = .049). This relationship was most profound in individuals with AN, including restrictive and binge-purge subtypes compared to individuals with atypical AN (interaction p-value = 0.044). Greater mindfulness was significantly associated with less shape (p = .023) and weight concern (p = .047). Expectedly, anxiety was inversely associated with eating disorder symptoms (p = .001). Greater pain was associated with less eating disorder symptoms (p = .024). Overall, mindfulness may be a protective factor against some eating disorder symptomology.

Exploring Factors Associated With Long-Term Opioid Therapy in Cancer Survivors: An Integrative Review.

CONTEXT: The prevalence of chronic pain in cancer survivors is double that of the general U.S. POPULATION: Opioids have been the foundation of cancer pain management for decades; however, there is a paucity of literature on long-term opioid therapy (LTOT) in cancer survivors. An understanding of factors related to LTOT use in cancer survivors is needed to address chronic pain and balance opioid harms in the expanding population of cancer survivors. OBJECTIVES: To analyze the research of LTOT utilization and factors associated with persistent opioid use in cancer survivors. METHODS: A five-stage integrative review process was adapted from Whittemore and Knafl. Data sources searched included Web of Science, PubMed, Embase, Cochrane, and Google Scholar. Quantitative research studies from 2010 to present related to cancer survivors managed on LTOT were included. Editorials, reviews, or abstracts were excluded. RESULTS: After reviewing 315 articles, 21 articles were included. We found that there were several definitions of LTOT in the reviewed studies, but the duration of opioid use (i.e., more than three months after completion of curative treatment) was the most common. The reviewed literature describes a relationship between LTOT and important biopsychosocial factors (cancer type, socioeconomic factors, and comorbidities). CONCLUSION: The studies in this review shed light on the factors associated with LTOT in cancer survivors. LTOT was common in certain populations of cancer survivors and those with a collection of patient-specific characteristics. This review suggests that there is a critical need for specialized research on chronic cancer pain and opioid safety in cancer survivors.

Use of cannabidiol (CBD) for the treatment of chronic pain.

Chronic pain can be recurrent or constant pain that lasts for longer than 3 months and can result in disability, suffering, and a physical disturbance. Related to the complex nature of chronic pain, treatments have a pharmacological and non-pharmacological approach. Due to the opioid epidemic, alternative therapies have been introduced, and components of the plant Cannabis Sativa, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have gained recent interest as a choice of treatment. The exact mechanism for CBD is currently unknown, but unlike the CBD's psychoactive counterpart, THC, the side effects of CBD itself have been shown to be overall much more benign. The current pharmaceutical products for the treatment of chronic pain are known as nabiximols, and they contain a ratio of THC combined with CBD, which has been promising. This review focuses on the treatment efficacy of CBD, THC: CBD-based treatments for chronic pain and adverse events with each.

Imagery rescripting and eye movement desensitisation and reprocessing as treatment for adults with post-traumatic stress disorder from childhood trauma: randomised clinical trial.

BACKGROUND: Investigation of treatments that effectively treat adults with post-traumatic stress disorder from childhood experiences (Ch-PTSD) and are well tolerated by patients is needed to improve outcomes for this population. AIMS: The purpose of this study was to compare the effectiveness of two trauma-focused treatments, imagery rescripting (ImRs) and eye movement desensitisation and reprocessing (EMDR), for treating Ch-PTSD. METHOD: We conducted an international, multicentre, randomised clinical trial, recruiting adults with Ch-PTSD from childhood trauma before 16 years of age. Participants were randomised to treatment condition and assessed by blind raters at multiple time points. Participants received up to 12 90-min sessions of either ImRs or EMDR, biweekly. RESULTS: A total of 155 participants were included in the final intent-to-treat analysis. Drop-out rates were low, at 7.7%. A generalised linear mixed model of repeated measures showed that observer-rated post-traumatic stress disorder (PTSD) symptoms significantly decreased for both ImRs (d = 1.72) and EMDR (d = 1.73) at the 8-week post-treatment assessment. Similar results were seen with secondary outcome measures and self-reported PTSD symptoms. There were no significant differences between the two treatments on any standardised measure at post-treatment and follow-up. CONCLUSIONS: ImRs and EMDR treatments were found to be effective in treating PTSD symptoms arising from childhood trauma, and in reducing other symptoms such as depression, dissociation and trauma-related cognitions. The low drop-out rates suggest that the treatments were well tolerated by participants. The results from this study provide evidence for the use of trauma-focused treatments for Ch-PTSD.

The association between longer durations of the latent phase of labor and subsequent perinatal processes and outcomes among midwifery patients.

BACKGROUND/OBJECTIVE: To evaluate the association between the duration of the latent phase of labor and subsequent processes and outcomes. METHODS: Secondary analysis of prospectively collected data among 1,189 women with low-risk pregnancies and spontaneous labor. RESULTS: Longer latent phase duration was associated with labor dystocia (eg, nulliparous ≥ mean [compared with < mean] aOR 3.95 [2.70-5.79]; multiparous ≥ mean [compared with < mean] aOR 5.45 [3.43-8.65]), interventions to ameliorate dystocia, and epidurals to cope or rest (eg, oxytocin augmentation: nulliparous > 80th% [compared with < 80th%] aOR 6.39 [4.04-10.12]; multiparous ≥ 80th% [compared with < 80th%] aOR 6.35 [3.79-10.64]). Longer latent phase duration was also associated with longer active phase and second stage. There were no associations between latent phase duration and risk for cesarean delivery or postpartum hemorrhage in a practice setting with relatively low rates of primary cesarean. Newborns born to multiparous women with latent phase of labor durations at and beyond the 80th% were more frequently admitted to the NICU (≥80th% [compared with < 80th%] aOR 2.7 [1.22-5.84]); however, two-thirds of these NICU admissions were likely for observation only. CONCLUSIONS: Longer duration of the spontaneous latent phase of labor among women with low-risk pregnancies may signal longer total labor processes, leading to an increase in diagnosis of dystocia, interventions to manage dystocia, and epidural use. Apart from multiparous neonatal NICU admission, no other maternal or child morbidity outcomes were elevated with longer duration of the latent phase of labor.

Role of Spirituality on the Association Between Depression and Quality of Life in Stroke Survivor-Care Partner Dyads.

BACKGROUND: Little is known about the protective effect of spirituality on the association between known risk factors such as depression and quality of life (QOL) in stroke survivor-care partner dyads. Therefore, the aim of this study was to evaluate the moderating role of spirituality on the association between depressive symptomatology and QOL in stroke survivor-care partner dyads. METHODS AND RESULTS: Longitudinal design with 223 stroke survivor-care partner dyads enrolled at survivor discharge from rehabilitation hospitals. Data collection was performed over 12 months. We measured survivors' and care partners' depression, quality of life, and spirituality. Examining the moderating role of spirituality on the association between depressive symptoms and QOL within survivor-care partner dyads, we used a traditional Actor-Partner-Interdependence Model and a basic Actor-Partner-Interdependence Model moderation model for a mixed variable. Survivors (51% male) and care partners (66% female) were 70.7 and 52.3 years old, respectively. The survivor's spirituality significantly moderated the association between care partner depressive symptomatology and survivor psychological QOL (B=0.03, P<0.05) and moderated the association between care partner depressive symptoms and care partner physical (B=0.05, P<0.001) and psychological (B=0.04, P<0.001) QOL. The care partner's own level of spirituality was significantly positively associated with their physical QOL (B=0.28, P<0.001). CONCLUSIONS: The findings from this study have broad implications for the role of spirituality in relation to QOL in medical-health contexts and the importance of examining such concepts within a dyadic framework. Greater awareness of the importance of spirituality among clinicians and nurses may improve cultural competence in healthcare services.

Identification and local delivery of vasodilators for the reduction of ureteral contractions.

Kidney stones and ureteral stents can cause ureteral colic and pain. By decreasing contractions in the ureter, clinically prescribed oral vasodilators may improve spontaneous stone passage rates and reduce the pain caused by ureteral stenting. We hypothesized that ureteral relaxation can be improved via the local administration of vasodilators and other smooth muscle relaxants. Here, by examining 18 candidate small molecules in an automated screening assay to determine the extent of ureteral relaxation, we show that the calcium channel blocker nifedipine and the Rho-kinase inhibitor ROCKi significantly relax human ureteral smooth muscle cells. We also show, by using ex vivo porcine ureter segments and sedated pigs that, with respect to the administration of a placebo, the local delivery of a clinically deployable formulation of the two drugs reduced ureteral contraction amplitude and frequency by 90% and 50%, respectively. Finally, we show that standard oral vasodilator therapy reduced contraction amplitude by only 50% and had a minimal effect on contraction frequency. Locally delivered ureteral relaxants therefore may improve ureter-related conditions.

Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN; ClinicalTrials.gov identifier: NCT03689712) has begun.