Diversity, Equity, and Inclusion in Patient and Family Advisory Councils: Advancing Best Practice in Children's Hospitals.

INTRODUCTION: This qualitative research study explored practices that support and advance diverse membership in Patient and Family Advisory Councils (PFACs) in children's hospitals and the involvement of PFACs in organization-level diversity, equity, and inclusion work. METHOD: This study consisted of a focused literature review and 17 key informant interviews. The study sought to identify important learnings about (1) recruiting and supporting patient and family advisors (PFAs) from historically marginalized populations and (2) ways to develop and sustain meaningful partnerships with PFAs and PFACs in diversity, equity, and inclusion work. RESULTS: The study findings highlighted a number of best practices for hospitals to adopt, including more actively reaching out to communities served, addressing barriers to participation through approaches and structures such as specialty PFACs and "tiered" options for participation by PFAs, and co-creation of inclusive environments. DISCUSSION: To move forward with this work, additional research, true commitment from health care organizations, and shared guidance and tools for the field are needed.

Screening and Treating Urinary Incontinence in Primary Care: A Missed Opportunity.

More than 60% of adult women in the United States have urinary incontinence (UI), with the prevalence increasing to over 80% in women over age 65. Despite its high prevalence, most patients do not seek care and few clinicians screen for UI. The Medicare Health Outcomes Survey queries patients about satisfaction with their provider's discussion and management of UI, but formal recommendations about screening, diagnosis, and treatment are lacking. This review presents a practical algorithm for primary care providers to incorporate management of UI into routine preventive care for women, and outlines UI prevalence, risk factors, screening, and non-surgical treatment options.

Treating common mental disorder including psychotic experiences in the primary care improving access to psychological therapies programme (the TYPPEX study): protocol for a stepped wedge cluster randomised controlled trial with nested economic and process evaluation of a training package for therapists.

INTRODUCTION: At least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap. METHODS AND ANALYSIS: This is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56-80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT service and have PE according to the Community Assessment of Psychic Experiences-Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery. ETHICS AND DISSEMINATION: The study received the following approvals: South Central-Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN93895792.

Updated Prevalence of Urinary Incontinence in Women: 2015-2018 National Population-Based Survey Data.

OBJECTIVES: This study aimed to update estimates of urinary incontinence (UI) prevalence and associated risk factors for adult women in the United States, using the National Health and Nutrition Examination Survey (NHANES). METHODS: We used descriptive analysis of 2015-2018 NHANES weighted data for women to estimate prevalence and characterize UI types and severity. Logistic regression modeling determined adjusted associations with UI. RESULTS: Complete data were available for 5,006 women. In weighted analyses, 61.8% had UI, corresponding to 78,297,094 adult U.S. women, with 32.4% of all women reporting symptoms at least monthly. Of those with UI, 37.5% had stress urinary incontinence, 22.0% had urgency urinary incontinence, 31.3% had mixed symptoms, and 9.2% had unspecified incontinence. The prevalence of moderate or more severe UI by Sandvik Severity Index was 22.1%, corresponding to 28,454,778 adult U.S. women. In multivariate models, increasing age, body mass index ≥25, prior vaginal birth, anxiety, depression, functional dependence, and non-Hispanic White ethnicity and race were associated with any and moderate UI. Urinary incontinence was not associated with diabetes, education level, prior hysterectomy, smoking status, physical activity level, or current pregnancy status. CONCLUSIONS: More than 60% of community-dwelling adult women in the United States experience any UI and an increase from prior estimates (38%-49%) using NHANES data from 1999 to 2004; more than 20% experience moderate or more severe UI. Increases in UI prevalence may be related to population aging and increasing obesity prevalence. Age greater than 70 years, body mass index >40, and vaginal birth had the strongest association with UI in multivariate modeling.

Determinants of patient-reported outcome trajectories and symptomatic recovery in Improving Access to Psychological Therapies (IAPT) services.

BACKGROUND: Despite evidence for the general effectiveness of psychological therapies, there exists substantial heterogeneity in patient outcomes. We aimed to identify factors associated with baseline severity of depression and anxiety symptoms, rate of symptomatic change over the course of therapy, and symptomatic recovery in a primary mental health care setting. METHODS: Using data from a service evaluation involving 35 527 patients in England's psychological and wellbeing [Improving Access to Psychological Therapies (IAPT)] services, we applied latent growth models to explore which routinely-collected sociodemographic, clinical, and therapeutic variables were associated with baseline symptom severity and rate of symptomatic change. We used a multilevel logit model to determine variables associated with symptomatic recovery. RESULTS: Being female, younger, more functionally impaired, and more socioeconomically disadvantaged was associated with higher baseline severity of both depression and anxiety symptoms. Being older, less functionally impaired, and having more severe baseline symptomatology was associated with more rapid improvement of both depression and anxiety symptoms (male gender and greater socioeconomic disadvantage were further associated with rate of change for depression only). Therapy intensity and appointment frequency seemed to have no correlation with rate of symptomatic improvement. Patients with lower baseline symptom severity, less functional impairment, and older age had a greater likelihood of achieving symptomatic recovery (as defined by IAPT criteria). CONCLUSIONS: We must continue to investigate how best to tailor psychotherapeutic interventions to fit patients' needs. Patients who begin therapy with more severe depression and/or anxiety symptoms and poorer functioning merit special attention, as these characteristics may negatively impact recovery.

Urinary Tract Injury During Gynecologic Surgery: Prevention, Recognition, and Management.

Lower urinary tract (LUT) injuries may occur during gynecologic surgery due to the close proximity of pelvic organs and vary by procedure, surgical indication, and route. Prevention of LUT injury should be a primary goal of gynecologic surgery. LUT injuries are more common in patients with aberrant anatomy, during difficult procedures, and with surgeons with less experience. Immediate recognition and management of LUT injuries is optimal, although delayed postoperative diagnoses may be unavoidable. Surgical management is based on the size and location of injury and should be performed by an experienced surgeon with thorough knowledge of pelvic anatomy, surgical technique, and postoperative management.

Enterocele manifesting as recurrent anterior rectal prolapse: A case report.

INTRODUCTION AND IMPORTANCE: An enterocele is a true herniation of small bowel through the rectovaginal septum, most commonly occurring transvaginally. Although the prevalence of enterocele is not as low as previously thought, enteroceles manifesting transrectally or with rectal prolapse are exceedingly rare and without established surgical guidance. CASE PRESENTATION: A medically complex, oxygen-dependent patient presented with full fecal incontinence and transrectal enterocele associated with recurrent anterior rectal prolapse. This was diagnosed via defecography and repaired under regional anesthesia through an open transabdominal approach of posterior cul-de-sac obliteration, uterosacral ligament vaginal vault suspension and simplified ventral suture rectopexy. Surgical planning was determined through a multidisciplinary care-conference, with preference for an approach with minimal respiratory compromise and repair durability. Short-term, this patient has complete resolution of bulge symptoms, and improved fecal continence. CLINICAL DISCUSSION: In addition to history and examination, dynamic imaging of the pelvic floor, specifically defecography, is particularly useful in identifying enteroceles that present as a component of pelvic organ or anorectal prolapse. As there are no established standard surgical treatment approaches for these rare conditions, surgeons must consider several points prior to proceeding: the repair of the defect, the symptoms the repair targets, and repair durability. CONCLUSIONS: Complete assessment and specialist consultation should be pursued prior to surgical repair for anorectal pathology. For this patient, an open transabdominal native tissue repair under regional anesthesia was successful, emphasizing that approaches to surgical correction of such rare presentations must be individualized.

Accuracy in Referrals to Gynecologic Oncologists Based on Clinical Presentation for Ovarian Mass.

Ovarian cancer is one of the most lethal gynecological cancers in women due to late diagnosis. Despite technological advancements, experienced physicians have high sensitivities and specificities in subjective assessments when combining ultrasound findings and clinical history in analyzing adnexal masses. This study aims to demonstrate general obstetricians and gynecologists' (OB/GYN) appropriateness in gynecologic oncologist referrals for malignant ovarian masses based on history and physical (H&P), imaging, and available tumor markers. Three board certified OB/GYNs were given 148 cases and determined whether or not they would refer them to a gynecologic oncologist. Results showed that OB/GYNs were 81-85% accurate in diagnosing patients with a benign or malignant disease. Among the malignant cases, reviewers had a high sensitivity ranging from 74-81% in appropriately referring a malignancy. In our study, OB/GYNs referred between 23-32% of ovarian masses to a gynecologic oncologist with only 9.5% of cases found to be malignant. Despite the high referral rates, generalists showed a high degree of sensitivity in accurately referring malignant diseases based solely on clinical experience and imaging studies, which could improve survival rates with early intervention by gynecologic oncologists.

Transcriptional changes before and after forgetting of a long-term sensitization memory in Aplysia californica.

Most long-term memories are forgotten, becoming progressively less likely to be recalled. Still, some memory fragments may persist, as savings memory (easier relearning) can be detected long after recall has become impossible. What happens to a memory trace during forgetting that makes it inaccessible for recall and yet still effective to spark easier re-learning? We are addressing this question by tracking the transcriptional changes that accompany learning and then forgetting of a long-term sensitization memory in the tail-elicited siphon withdrawal reflex of Aplysia californica. First, we tracked savings memory. We found that even though recall of sensitization fades completely within 1 week of training, savings memory is still detectable at 2 weeks post training. Next, we tracked the time-course of regulation of 11 transcripts we previously identified as potentially being regulated after recall has become impossible. Remarkably, 3 transcripts still show strong regulation 2 weeks after training and an additional 4 are regulated for at least 1 week. These long-lasting changes in gene expression always begin early in the memory process, within 1 day of training. We present a synthesis of our results tracking gene expression changes accompanying sensitization and provide a testable model of how sensitization memory is forgotten.

Feedback-informed treatment versus usual psychological treatment for depression and anxiety: a multisite, open-label, cluster randomised controlled trial.

BACKGROUND: Previous research suggests that the use of outcome feedback technology can enable psychological therapists to identify and resolve obstacles to clinical improvement. We aimed to assess the effectiveness of an outcome feedback quality assurance system applied in stepped care psychological services. METHODS: This multisite, open-label, cluster randomised controlled trial was done at eight National Health Service (NHS) Trusts in England, involving therapists who were qualified to deliver evidence-based low-intensity or high-intensity psychological interventions. Adult patients (18 years or older) who accessed individual therapy with participating therapists were eligible for inclusion, except patients who accessed group therapies and those who attended less than two individual therapy sessions. Therapists were randomly assigned (1:1) to an outcome feedback intervention group or a treatment-as-usual control group by use of a computer-generated randomisation algorithm. The allocation of patients to therapists was quasi-random, whereby patients on waiting lists were allocated sequentially on the basis of therapist availability. All patients received low-intensity (less than eight sessions) or high-intensity (up to 20 sessions) psychological therapies for the duration of the 1-year study period. An automated computer algorithm alerted therapists in the outcome feedback group to patients who were not on track, and primed them to review these patients in clinical supervision. The primary outcome was symptom severity on validated depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalised Anxiety Disorder-7 [GAD-7]) measures after treatment of varying durations, which were compared between groups with multilevel modelling, controlling for cluster (therapist) effects. We used an intention-to-treat approach. This trial was prospectively registered with ISRCTN, number ISRCTN12459454. FINDINGS: In total, 79 therapists were recruited to the study between Jan 8, 2016, and July 15, 2016, but two did not participate. Of these participants, 39 (51%) were randomly assigned to the outcome feedback group and 38 (49%) to the control group. Overall, 2233 patients were included in the trial (1176 [53%] were treated by therapists in the outcome feedback group, and 1057 [47%] by therapists in the control group). Patients classified as not on track had less severe symptoms after treatment if they were allocated to the outcome feedback group than those in the control group (PHQ-9 d=0·23, B=-1·03 [95% CI -1·84 to -0·23], p=0·012; GAD-7 d=0·19, B=-0·85 [-1·56 to -0·14], p=0·019). INTERPRETATION: Supplementing psychological therapy with low-cost feedback technology can reduce symptom severity in patients at risk of poor response to treatment. This evidence supports the implementation of outcome feedback in stepped care psychological services. FUNDING: English NHS and Department of Health Sciences, University of York, York, UK.

Savings memory is accompanied by transcriptional changes that persist beyond the decay of recall.

Most long-term memories are forgotten. What happens, then, to the changes in neuronal gene expression that were initially required to encode and maintain the memory? Here we show that the decay of recall for long-term sensitization memory in Aplysia is accompanied both by a form of savings memory (easier relearning) and by persistent transcriptional regulation. A behavioral experiment (N = 14) shows that sensitization training produces a robust long-term sensitization memory, but that recall fades completely within 1 wk. This apparent forgetting, though, is belied by persistent savings memory, as we found that a weak reminder protocol reinstates a long-term sensitization memory only on the previously trained side of the body. Using microarray (N = 8 biological replicates), we found that transcriptional regulation largely decays along with recall. Of the transcripts known to be regulated 1 d after training, 98% (1172/1198) are no longer significantly regulated 7 d after training. Still, there is a small set of transcripts which remain strongly regulated even when recall is absent. Using qPCR (N = 11 additional biological replicates) we confirmed that these include the peptide transmitter FMRFamide, a transcript encoding a putative homolog of spectrin beta chain (Genbank: EB255259) , a transcript encoding a protein with a predicted EF-hand calcium-binding domain (Genbank: EB257711), and eight uncharacterized transcripts. To our knowledge, this is the first work to show that transcriptional changes evoked by learning can outlast recall. The small set of transcriptional changes that persist could mediate the rapid relearning of the memory (savings), or the decay of recall, or both, or neither.

Transcriptional correlates of memory maintenance following long-term sensitization of Aplysia californica.

We characterized the transcriptional response accompanying maintenance of long-term sensitization (LTS) memory in the pleural ganglia of Aplysia californica using microarray (N = 8) and qPCR (N = 11 additional samples). We found that 24 h after memory induction there is strong regulation of 1198 transcripts (748 up and 450 down) in a pattern that is almost completely distinct from what is observed during memory encoding (1 h after training). There is widespread up-regulation of transcripts related to all levels of protein production, from transcription (e.g., subunits of transcription initiation factors) to translation (e.g., subunits of eIF1, eIF2, eIF3, eIF4, eIF5, and eIF2B) to activation of components of the unfolded protein response (e.g., CREB3/Luman, BiP, AATF). In addition, there are widespread changes in transcripts related to cytoskeleton function, synaptic targeting, synaptic function, neurotransmitter regulation, and neuronal signaling. Many of the transcripts identified have previously been linked to memory and plasticity (e.g., Egr, menin, TOB1, IGF2 mRNA binding protein 1/ZBP-1), though the majority are novel and/or uncharacterized. Interestingly, there is regulation that could contribute to metaplasticity potentially opposing or even eroding LTS memory (down-regulation of adenylate cyclase and a putative serotonin receptor, up-regulation of FMRFa and a FMRFa receptor). This study reveals that maintenance of a "simple" nonassociative memory is accompanied by an astonishingly complex transcriptional response.

The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer.

BACKGROUND: Ovarian cancer (OVC) is the deadliest of all gynecologic cancers, primarily as a consequence of asymptomatic progression. The complex nature of OVC creates challenges for early detection, and there is a lack of specific and sensitive biomarkers suitable for screening and detecting early stage OVC. METHODS: Potential OVC biomarkers were identified by bioinformatic analysis. Candidates were further screened for differential expression in a library of OVC cell lines. OVC-specific overexpression of a candidate gene, PRSS8, which encodes prostasin, was confirmed against 18 major human cancer types from 390 cancer samples by qRT-PCR. PRSS8 expression profiles stratified by OVC tumor stage-, grade- and subtype were generated using cDNA samples from 159 OVC samples. Cell-specific expression and localization of prostasin was determined by immunohistological tissue array analysis of more than 500 normal, benign, and cancerous ovarian tissues. The presence of prostasin in normal, benign, and OVC serum samples was also determined. RESULTS: Gene expression analysis indicated that PRSS8 was expressed in OVC at levels more than 100 fold greater than found in normal or benign ovarian lesions. This overexpression signature was found in early stages of OVC and was maintained in higher stages and grades of OVC. The PRSS8 overexpression signature was specific for OVC and urinary bladder cancer among 18 human cancer types. The majority of ovarian cell lines overexpressed PRSS8. In situ hybridization and histopathology studies of OVC tissues indicated that overexpression of prostasin was largely localized to tumor epithelium and was absent in neighboring stroma. Significantly higher levels of prostasin were found in early stage OVC serum samples compared to benign ovarian and normal donor samples. CONCLUSIONS: The abundant amounts of secreted prostasin found in sera of early stage OVC can potentially be used as a minimally invasive screening biomarker for early stage OVC. Overexpression of PRSS8 mRNA and high levels of prostasin in multiple subtypes of early stage ovarian tumors may provide clinical biomarkers for early detection of OVC, which can potentially be used with CA125 and HE4.

Prevalence; Characteristics and Management of Endometriosis Amongst Infertile Women: A One Year Retrospective Study.

BACKGROUND: Endometriosis appears to affect every aspect of a women's reproductive system resulting in infertility and spontaneous pregnancy loss. This study aims to find out the prevalence & clinical characteristics of endometriosis amongst infertile women. SETTINGS AND DESIGN: A Hospital based retrospective study over a period of one year. MATERIALS AND METHODS: It is a retrospective study conducted in the gynaecology department in Institute of Kidney Diseases & Research Centre; Ahmedabad from April 2012 to March 2013 amongst women with a primary complaint of infertility (Primary/Secondary).A total of 372 patients underwent diagnostic hysterolaparoscopy and of these 180 patients who had laparoscopic evidence of endometriosis was included in the study. All of these patients and their findings were analysed with respect to the clinical signs and symptoms. The outcome after appropriate management was analysed in subsequent follow up. STATISTICAL ANALYSIS: All collected data was entered into the SPSS version 20. Categorical data are expressed in frequency or percentage. Chi-Square test and Fisher-Exact test has been performed to carry out p-value for categorical data. P-value <0.05 shows statistically significant difference. RESULTS: The frequency of endometriosis among women with infertility subjected to diagnostic hysterolaparoscopy was found to be 48.38%. Statistical significant association with severity of disease was associated with symptoms like dysmenorrhea, chronic pelvic pain, restricted uterine mobility and adnexal tenderness. (p <0.01) Ultrasound finding of endometrioma with ground glas appearance also had statistical significant association with staging of disease (p <0.01). CONCLUSION: Endometriosis amongst infertile women is increasingly being detected due to greater use of laparoscopy in evaluation of infertility.Though most signs do not correlate with severity of disease however the presence of restricted uterine mobility, adnexal tenderness & chronic pelvic pain should always raise the suspicion of endometriosis. Laparoscopy remains the gold standard for diagnosing and staging endometriosis.

Generics: are all immunosuppression agents created equally?

BACKGROUND: The Affordable Care Act initiated innumerable cost-containment measures, including promoting generic conversion from brand medications and directing the Food and Drug Administration to decrease requirements for generic approvals. Despite this mandate, few data existed on generic conversion of immunosuppressant medications with narrow therapeutic troughs. METHODS: A retrospective analysis of our initial experience with generic tacrolimus (n = 39) was performed using a control cohort from our renal transplant database. A rejection and cost analysis was performed using a consecutive 2-year prior cohort (n = 159) as a control to determine the effect of generic conversion on tacrolimus a narrow therapeutic index immunosuppressant medication. RESULTS: During the first year after transplantation, the generic group had a greater drug variability (20% ± change in trough levels) that required more dosage adjustments (5.42 vs 3.59 drug dosage changes; P = .038) to obtain a stable dose, required increased number of intravenous magnesium infusions (4.95 vs 1.68 infusions; P = .001), and incurred a greater incidence of rejection (23.1% vs 10.2%; P = .024). A yearly institutional cost was evaluated against a negotiated $18,000/yearly central pharmacy cost savings compared with a $652,862 institutional cost to treat unanticipated rejections. CONCLUSION: Programmatic conversion from brand to generic tacrolimus resulted in increased drug variability, a greater incidence of magnesium wasting, and more episodes of rejection, leading to increases in institutional costs of care. This government-driven attempt at cost containment may be applicable to noncritical medications such as antibiotics and antihypertensives, but this policy should be reconsidered for narrow therapeutic index medications, such as tacrolimus and other immunosuppressant medications.

Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by vanadium pentoxide (V2O5).

Interstitial lung diseases (ILDs) are characterized by injury, inflammation, and scarring of alveoli, leading to impaired function. The etiology of idiopathic forms of ILD is not understood, making them particularly difficult to study due to the lack of appropriate animal models. Consequently, few effective therapies have emerged. We developed an inbred mouse model of ILD using vanadium pentoxide (V2O5), the most common form of a transition metal found in cigarette smoke, fuel ash, mineral ores, and steel alloys. Pulmonary responses to V2O5, including dose-dependent increases in lung permeability, inflammation, collagen content, and dysfunction, were significantly greater in DBA/2J mice compared to C57BL/6J mice. Inflammatory and fibrotic responses persisted for 4 mo in DBA/2J mice, while limited responses in C57BL/6J mice resolved. We investigated the genetic basis for differential responses through genetic mapping of V2O5-induced lung collagen content in BXD recombinant inbred (RI) strains and identified significant linkage on chromosome 4 with candidate genes that associate with V2O5-induced collagen content across the RI strains. Results suggest that V2O5 may induce pulmonary fibrosis through mechanisms distinct from those in other models of pulmonary fibrosis. These findings should further advance our understanding of mechanisms involved in ILD and thereby aid in identification of new therapeutic targets.

An unstable support surface does not increase scapulothoracic stabilizing muscle activity during push up and push up plus exercises.

BACKGROUND: The aim of the current study is to determine if performing push up exercise variations on an unstable surface (Swiss ball) influences EMG amplitude of the scapulothoracic muscles when compared with a stable surface (Bench). METHODS: Ten males were recruited from a convenience sample of college students. Surface electromyograms were recorded from the upper trapezius, lower trapezius, serratus anterior and biceps brachii while performing push up exercises with the feet or hands placed on a bench and separately on a Swiss ball. A push up plus exercise was also evaluated with hands on the different support surfaces. RESULTS: There was no statistically significant (p<0.05) difference in mean EMG amplitude on a Swiss ball when compared with the same exercise performed on a bench. Significant differences in muscle activity were seen in the upper trapezius and serratus anterior as a result of changes in foot position relative to hand position irrespective of surface stability. INTERPRETATION: The unstable surface used in this study is not a sufficient condition to generate an increase in muscle activity in select scapulothoracic and glenohumeral muscles during push up exercise variations. Elevating the feet above the hands appeared to have a greater influence on shoulder stabilizing musculature amplitude than the addition of a Swiss ball.