Exploring men's and women's experiences of depression and engagement with health professionals: more similarities than differences? A qualitative interview study

<p>Abstract</p> <p>Background</p> <p>It is argued that the ways in which women express emotional distress mean that they are more likely to be diagnosed with depression, while men's relative lack of articulacy means their depression is hidden. This may have consequences for communicating with health professionals. The purpose of this analysis was to explore how men and women with depression articulate their emotional distress, and examine whether there are gender differences or similarities in the strategies that respondents found useful when engaging with health professionals.</p> <p>Methods</p> <p>In-depth qualitative interviews with 22 women and 16 men in the UK who identified themselves as having had depression, recruited through general practitioners, psychiatrists and support groups.</p> <p>Results</p> <p>We found gender similarities and gender differences in our sample. Both men and women found it difficult to recognise and articulate mental health problems and this had consequences for their ability to communicate with health professionals. Key gender differences noted were that men tended to value skills which helped them to talk while women valued listening skills in health professionals, and that men emphasised the importance of getting practical results from talking therapies in their narratives, as opposed to other forms of therapy which they conceptualised as 'just talking'. We also found diversity among women and among men; some respondents valued a close personal relationship with health professionals, while others felt that this personal relationship was a barrier to communication and preferred 'talking to a stranger'.</p> <p>Conclusion</p> <p>Our findings suggest that there is not a straightforward relationship between gender and engagement with health professionals for people with depression. Health professionals need to be sensitive to patients who have difficulties in expressing emotional distress and critical of gender stereotypes which suggest that women invariably find it easy to express emotional distress and men invariably find it difficult. In addition it is important to recognise that, for a minority of patients, a personal relationship with health professionals can act as a barrier to the disclosure of emotional distress.</p

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein

Background: Although the founding members of the INhibitor of Growth (ING) family of histone mark readers, ING1 and ING2, were defined as tumour suppressors in animal models, the role of other ING proteins in cellular proliferation and cancer progression is unclear. Methods: We transduced ex vivo benign prostate hyperplasia tissues with inducible lentiviral particles to express ING proteins. Proliferation was assessed by H3S10phos immunohistochemistry (IHC). The expression of ING3 was assessed by IHC on a human prostate cancer tissue microarray (TMA). Gene expression was measured by DNA microarray and validated by real-time qPCR. Results: We found that ING3 stimulates cellular proliferation in ex vivo tissues, suggesting that ING3 could be oncogenic. Indeed, ING3 overexpression transformed normal human dermal fibroblasts. We observed elevated levels of ING3 in prostate cancer samples, which correlated with poorer patient survival. Consistent with an oncogenic role, gene-silencing experiments revealed that ING3 is required for the proliferation of breast, ovarian, and prostate cancer cells. Finally, ING3 controls the expression of an intricate network of cell cycle genes by associating with chromatin modifiers and the H3K4me3 mark at transcriptional start sites. Conclusions: Our investigations create a shift in the prevailing view that ING proteins are tumour suppressors and redefine ING3 as an oncoprotein

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Surgical management of an obstructive Müllerian Anomaly in a patient with anorectal malformation

Müllerian duct anomalies are rare in the general population, occurring in less than 3% of women, but much more prevalent in female patients with anorectal malformation, occurring in up to 30% of these patients. Unicornuate uterus with a rudimentary non-communicating horn is a congenital anomaly of Müllerian development which can be seen in isolation or in conjunction with other anomalies, with several case reports described in patients with VACTERL association. These anomalies may be asymptomatic until the patient develops dysmenorrhea or devastating obstetrical complications. We describe the successful surgical management of an obstructive Müllerian anomaly in a post-pubertal female patient with anorectal malformation

Acquired Urethrovaginal Fistula and Urethral Atresia in a Patient with a Sacrococcygeal Teratoma

© 2018 Elsevier Inc. Acquired urethrovaginal fistulae and urethral atresia are rare findings in pediatric patients, but have been described in adult patients related to trauma or iatrogenic injury. Little exists in the published literature to guide management of such conditions in children, but lessons learned from congenital causes can help. Herein we discuss the preoperative evaluation and management of a child with an acquired urethrovaginal fistula and urethral atresia likely related to in utero compression from an intrapelvic sacrococcygeal teratoma and provide several images detailing the complex anatomy

Gynecologic anatomic abnormalities following anorectal malformations repair

© 2017 Elsevier Inc. Background/aim: Patients may present with gynecologic concerns after previous posterior sagittal anorectoplasty (PSARP) for repair of an anorectal malformation (ARM). Common findings include an inadequate or shortened perineal body, as well as introital stenosis, retained vaginal septum, and remnant rectovestibular fistula. An inadequate or shortened perineal body may impact fecal continence, sexual function and recommendations regarding obstetrical mode of delivery. We describe our experience with female patients referred to our center for evaluation of their previously repaired ARM, with a specific focus on perineal body anatomy and concomitant gynecologic abnormalities. We outline our collaborative evaluation process and findings as well as subsequent repair and outcomes. Material/methods: A single site retrospective chart review from May 2014 to May 2016 was performed. Female patients with a history of prior ARM repair who required subsequent reoperative surgical repair with perineoplasty were included. The decision for reoperation was made collaboratively after a multidisciplinary evaluation by colorectal surgery, urology, and gynecology which included examination under anesthesia (EUA) with cystoscopy, vaginoscopy, rectal examination, and electrical stimulation of anal sphincters. The type of original malformation, indication for reoperative perineoplasty, findings leading to additional procedures performed at time of perineoplasty, postoperative complications, and the length of follow up were recorded. Results: During the study period 28 patients were referred for evaluation after primary ARM repair elsewhere and 15 patients (60%) met inclusion criteria. Thirteen patients (86.6%) originally had a rectovestibular fistula with prior PSARP and 2 patients (13.4%) originally had a cloacal malformation with prior posterior sagittal anorectovaginourethroplasty. The mean age at the time of the subsequent perineoplasty was 4.6 years (0.5–12). Patients had an inadequate perineal body requiring reoperative perineoplasty due to: anterior mislocation of the anus (n = 11, 73.3%), prior perineal wound dehiscence with perineal body breakdown (n = 2, 13.4%), acquired rectovaginal fistula (n = 1, 6.6%), and posterior mislocated introitus with invasion of the perineal body (n = 1, 6.6%). During the preoperative evaluation, additional gynecologic abnormalities were identified that required concomitant surgical intervention including: introital stenosis (n = 4, 26.6%), retained vaginal septum (n = 3, 20%) and remnant recto vestibular fistula (n = 2, 13.3%). Conclusions: Patients with a previously repaired ARM may present with gynecologic concerns that require subsequent surgical intervention. The most common finding was an inadequate perineal body, but other findings included introital stenosis, retained vaginal septum and remnant recto vestibular fistula. Multidisciplinary evaluation to assess and identify abnormalities and coordinate timing and surgical approach is crucial to assure optimal patient outcomes. Type of study: Case series with no comparison group. Level of evidence: IV

Gynecologic outflow tract obstruction - Pre-operative evaluation and surgical management

© 2020 Background: Approximately 7% of adolescent girls have reproductive tract anomalies. Anomalies associated with complete outflow track obstruction present with primary amenorrhea and cyclic abdominal pain. Some outflow tract obstructions may be associated with renal, anorectal, vertebral, cardiac, tracheoesophageal, and limb anomalies. Outflow tract obstructions may occur at varying anatomic locations – vaginal, cervical, or uterine, each requiring different surgical management. Methods: We present the preoperative evaluation and surgical management of three different gynecologic outflow tract obstructions. Results: Physical exam, ultrasound, and MRI were obtained for each patient. The first obstruction was a transverse vaginal septum, which was treated with transperineal resection to allow menstrual egress. The second obstruction was identified as distal vaginal atresia and managed with operative pull-through of her native vagina. The third obstruction was found to be cervico-vaginal atresia and required hysterectomy and salpingectomy with preservation of the ovaries. Conclusions: Preoperative examination of the perineum and imaging with accurate interpretation is crucial to identify subtle but important distinctions in diagnosis, which can result in markedly different interventions ranging from transperineal resection of a transverse vaginal septum, vaginal pull-through procedure, to hysterectomy. The location of the gynecologic outflow obstruction dictates the proper surgical treatment of these patients