Demographic and clinical correlates of suicidal ideation in individuals with at-risk mental state (ARMS): A study from Pakistan.

BACKGROUND: Suicide is a major public health concern and one of the leading causes of mortality worldwide. People with an at-risk-mental-state (ARMS) for psychosis are more vulnerable to psychiatric co-morbidity and suicide, however, there are limited data from low-middle-income countries. The present study aimed to identify the prevalence of depressive symptoms and suicidal ideation along with sociodemographic and clinical correlates of suicidal ideation in individuals with ARMS from Pakistan. METHOD: Participants between the age of 16 and 35 years who met the criteria for ARMS based on the Comprehensive Assessment of At-Risk Mental State (CAARMS), were recruited from the community, general practitioner clinics and psychiatric units across Pakistan (n = 326). Montgomery and Asberg Depression Rating Scale (MADRS) and Social-Occupational-Functional-Assessment-Scale (SOFAS) were administered to participants. RESULTS: The prevalence of depressive symptoms and suicidal thoughts in the sample at baseline were 91.1% (n = 297) and 61.0% (n = 199), respectively. There were significant mean differences between groups (mean difference [95% CI]; p-value) without suicidal ideation and with suicidal ideation on measures of MADRS (-5.47 [-7.14, -3.81]; p < .001), CAARMS non-bizarre ideas (-0.29 [-0.47, -0.11]; p = .002) and perceptual abnormalities (-0.23 [-0.41, -0.04]; p = .015). CONCLUSION: These findings indicate that suicidal ideation and depressive symptoms are highly prevalent in individuals with ARMS in Pakistan. Given the pivotal developmental stages that ARMS presents, and the poor outcomes associated with co-morbid depression, there is an urgent need to prioritize the development of low-cost and scalable evidence-based interventions to address psychiatric comorbidity and suicidality in the ARMS population in Pakistan.

Four-dimensional ultrasound guided embryo transfers improve live birth rates when compared to the clinical touch technique: a randomised controlled trial.

Most aspects of in-vitro fertilisation (IVF) have changed dramatically since introduction, but embryo transfer (ET) technique remains largely unaltered. We aimed to determine whether four-dimensional ultrasound guided embryo transfers (4D UGET) could improve pregnancy rates when compared with clinical touch technique (CTT). This was a single centre open labelled randomised controlled trial in a tertiary fertility centre in the UK. 320 women were randomised on the day of single ET. The primary outcome was clinical pregnancy rate (CPR), secondary outcomes included live birth rate (LBR), biochemical pregnancy rate (BPR), miscarriage, pregnancy of unknown location (PUL) and ectopic pregnancy. 4D-UGET resulted in significantly higher CPR [50% vs 36% p = 0.02, OR 1.78 (1.12-2.84)] and LBR [41% vs 28%, p = 0.02, OR 1.77 (1.09-2.87)] when compared to CTT technique. Miscarriage (p = 0.49), PUL (p = 0.14) and ectopic pregnancy (p = 0.96) were similar between the two groups. LBR, from this trial, are significantly higher than the current UK average (41% vs 24%). 4D UGET allows for superior imaging of the uterine cavity, whilst tailoring the embryo deposition point specifically to the patient. Further RCTs are required to determine if these results can be replicated in other units and whether 4D UGET is superior to 2D UGET.

Renal replacement and extracorporeal therapies in critical care: current and future directions.

There are a wide number of indications for extracorporeal therapies in the critical care environment. A common indication seen by the acute physician is continuous renal replacement therapy (CRRT) in a proportion of patients with acute kidney injury. It is therefore important that acute physicians have a sound understanding of the principles of CRRT in the acutely unwell patient. This review will outline the indications for its use, commonly used methods and anticoagulation considerations. It will discuss when to start and stop CRRT as well as describing potential treatment complications. This review will also discuss the role of therapeutic plasma exchange in critical care and novel extracorporeal therapies including blood purification in sepsis and carbon dioxide removal in acute respiratory distress syndrome and acute exacerbations of obstructive lung disease. Extracorporeal membrane oxygenation is outside of the scope of this article.

The diversity of hypospadias management in North America: a survey of pediatric urologists.

PURPOSE: To determine trends in hypospadias management, including surgical techniques and perioperative care, by pediatric urologists in North America. METHODS: An anonymous online survey was devised to assess approaches to hypospadias repair and management, including anesthetic considerations, catheter placement, choice of dressing, and postoperative antibiotic treatment. The survey was sent to all practicing members of the Societies for Pediatric Urology. RESULTS: The survey was completed by 133 (34.5%) respondents. Hypospadias repair was overwhelmingly recommended between ages 6-12 months (89.5%). A local or regional anesthetic block (caudal, penile, pudendal, spinal) is performed nearly universally (96.2%). The majority of surgeons perform distal repairs outpatient (70.7%), while fewer perform outpatient staged repairs (47.4%) or redo surgery (33.8%). Nearly all respondents preferred either VicrylTM/DexonTM (50.4%) or MaxonTM/PDSTM (48.1%) for urethroplasty. All but one respondent leaves a stent for midshaft to proximal repairs whereas stenting for glanular repairs was split with 53.4% leaving a stent. Most surgeons (60.9-70.9%) prescribe postoperative antibiotics regardless of severity and the majority (72.9%) prescribe narcotics for analgesia. CONCLUSIONS: Approaches to hypospadias repair are extremely varied such that there is a lack of consensus among pediatric urologists regarding most aspects of hypospadias management. Investigations comparing hypospadias practice patterns are necessary to develop a standard of care for this complex pediatric urologic entity.

Perceived social support attenuates increased hostile reactions to traumatic threat.

OBJECTIVE: Extant literature has seldom examined the naturalistic role of reaction to threat on downstream emotional distress while also considering buffers, such as perceived social support, to acute negative mental health outcomes. The present study examined how trauma symptoms, in reaction to a global stressor, predicted increased psychological distress via elevated emotional hostility and whether perceived social support modified such effects. We predicted a priori that increased exposure to trauma would be associated with increased hostility and global psychological distress, but that this path would be attenuated by greater levels of perceived social support, as individuals who report greater support exhibit greater emotional coping. METHODS: We recruited 408 adults from a large university in the Midwestern United States to participate in a survey assessing past-week trauma, hostility, distress, and perceived social support following the initial COVID-19 lockdown. The survey was conducted in March 2020, directly after strict shelter-in-place orders were locally mandated. To test our hypotheses, we employed a moderated mediation analysis approach. RESULTS: Results demonstrate that higher trauma predicted increased hostility, which in turn predicted increased distress, and trauma predicted distress via hostility (an indirect effect). As hypothesized, higher perceived social support attenuated the association between trauma and hostility. CONCLUSION: Results support a hostile emotional pathway that may increase distress in the context of increased traumatic impact; however, social support likely buffers these effects, particularly in the face of new or novel threats and stressors. Findings suggest broad application for understanding the relation between the introduction of stressors, psychological distress, and social support.

Cross-sectional quantitative validation of the paediatric Localized Scleroderma Quality of Life Instrument (LoSQI): A disease-specific patient-reported outcome measure.

BACKGROUND: The Localized Scleroderma Quality of Life Instrument (LoSQI) is a disease-specific patient-reported outcome (PRO) measure designed for children and adolescents with localized scleroderma (LS; morphea). This tool was developed using rigorous PRO methods and previously cognitively tested in a sample of paediatric patients with LS. OBJECTIVE: The purpose of this study was to evaluate the psychometric properties of the LoSQI in a clinical setting. METHODS: Cross-sectional data from four specialized clinics in the US and Canada were included in the analysis. Evaluation included reliability of scores, internal structure of the survey, evidence of convergent and divergent validity, and test-retest reliability. RESULTS: One hundred and ten patients with LS (age: 8-20 years) completed the LoSQI. Both exploratory and confirmatory factor analysis supported the use of two sub-scores: Pain and Physical Functioning, and Body Image and Social Support. Correlations with other PRO measures were consistent with pre-specified hypotheses. LIMITATIONS: This study did not evaluate longitudinal validity or responsiveness of scores. CONCLUSION: Results from a representative sample of children and adolescents with LS continue to support the validity of the LoSQI when used in a clinical setting. Future work to evaluate the responsiveness is ongoing.

Relationship of Age And Mobility Levels During Physical Rehabilitation With Clinical Outcomes in Critical Illness.

Objective: To determine whether age, mobility level, and change in mobility level across the first 3 physical rehabilitation sessions associate with clinical outcomes of patients who are critically ill. Design: Retrospective, observational cohort study. Setting: Medical Intensive Care Unit (MICU). Participants: Hospitalized adults (n = 132) who received 3 or more, consecutive rehabilitation sessions in the MICU. Interventions: Not applicable. Measurements and Main Results: Sample included 132 patients with 60 (45%) classified as younger (18-59 years) and 72 (55%) as older (60+ years). The most common diagnosis was sepsis/septicemia (32.6%). Older relative to younger patients had a significantly slower rate of improvement in ICU Mobility Scale (IMS) scores across rehabilitation sessions (mean slope coefficient 0.3 vs 0.6 points, P<.001), were less likely to be discharged to home (30.6% vs 55.0%, P=.005), and were more likely to die within 12 months (41.7% vs 25.0%, P=.046). Covariate-adjusted models indicated greater early improvement in IMS scores were associated with discharge home (P=.005). Longer time to first rehabilitation session, lower initial IMS scores, and slower improvement in IMS scores were associated with increased ICU days (all P<.03). Conclusion: Older age and not achieving the mobility milestone of sitting at edge of bed or limited progression of mobility across sessions is associated with poor patient outcomes. Our findings suggest that age and mobility level contribute to outcome prognostication, and can aide in clinical phenotyping and rehabilitative service allocation.

Proficiency and Retention of Five Clinical Veterinary Skills Using Multipurpose Reusable Canine Manikins vs. Live Animals: Model Development and Validation.

Simulation in veterinary education provides a safe and ethical alternative to using live animals, but most simulators are single purpose and unvalidated. In this study, canine training manikins were created using readily available materials to teach fine needle aspiration (FNA) of peripheral lymph nodes, jugular venipuncture, cephalic venipuncture, intravenous catheterization, and cystocentesis. Undergraduate subjects were prospectively enrolled and stratified by veterinary experience prior to randomization into two groups. Students were taught a new skill each week through a written description of the technique, video training, and hands-on practice (live animal vs. manikin). The following week, participants were scored on the performance of the previous week's skill on a live animal using a standardized rubric by reviewers blinded to the training group. Six weeks later, the assessment was repeated for all skills. Scores were compared between groups and time points using repeated-measures ANOVA after logarithmic transformation. p < .05 was significant. There were no significant differences in scores for any of the skills between the groups immediately following or 6 weeks after training. Initial proficiency and short-term retention of clinical skills do not differ for students trained using a manikin vs. a live dog.

Ataxia and mobility in children following surgical resection of posterior fossa tumour: A longitudinal cohort study.

PURPOSE: To report the course of ataxia in children up to 2 years post-operatively, following surgical resection of a posterior fossa tumour (PFT). METHODS: Thirty-five children, (median age 9 years, range 4-15) having resection of PFT, were assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Brief Ataxia Rating Scale (BARS) and the mobility domain of the Paediatric Evaluation of Disability Index (PEDI-m) at initial post-operative period (baseline), 3 months, 1 year and 2 years post-operatively. RESULTS: Baseline median scores of the SARA and BARS were 8.5 (range 0-35.5), and 7 (0-25) respectively. Ataxia improved at 3 months (median SARA and BARS reduction 3.5 and 4, respectively). Additional gradual improvements in SARA were recorded at 1 (median reduction 2) and 2 years post-operatively (median reduction 0.5). Median baseline PEDI-m was 54.75 (range 15.2-100) with improvement at 3 months (median increase 36.95) and small improvement at 1 year (median increase 2.5) and 2 years (median increase 5.8). Children with medulloblastoma and midline tumours (median baseline SARA 10 and 11, respectively) demonstrated more severe ataxia than children with low-grade gliomas and unilateral tumours (median baseline SARA 7.5 and 6.5, respectively). CONCLUSION: The largest improvement in ataxia scores and functional mobility scores is demonstrated within the first 3 months post-operatively, but ongoing gradual improvement is observed at 2 years. Children with medulloblastoma and midline tumour demonstrated higher ataxia scores long term.

Improved preservation of ovarian tissue morphology that is compatible with antigen detection using a fixative mixture of formalin and acetic acid.

STUDY QUESTION: Can ovarian tissue morphology be better preserved whilst enabling histological molecular analyses following fixation with a novel fixative, neutral buffered formalin (NBF) with 5% acetic acid (referred to hereafter as Form-Acetic)? SUMMARY ANSWER: Fixation with Form-Acetic improved ovarian tissue histology compared to NBF in multiple species while still enabling histological molecular analyses. WHAT IS KNOWN ALREADY: NBF fixation results in tissue shrinkage in various tissue types including the ovary. Components of ovarian tissue, notably follicles, are particularly susceptible to NBF-induced morphological alterations and can lead to data misrepresentation. Bouin's solution (which contains 5% acetic acid) better preserves tissue architecture compared to NBF but is limited for immunohistochemical analyses. STUDY DESIGN, SIZE, DURATION: A comparison of routinely used fixatives, NBF and Bouin's, and a new fixative, Form-Acetic was carried out. Ovarian tissue was used from three different species: human (n = 5 patients), sheep (n = 3; 6 ovaries; 3 animals per condition) and mouse (n = 14 mice; 3 ovaries from 3 different animals per condition). PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian tissue from humans (aged 13 weeks to 32 years), sheep (reproductively young i.e. 3-6 months) and mice (10 weeks old) were obtained and fixed in 2 ml NBF, Bouin's or Form-Acetic for 4, 8, and 24 h at room temperature. Tissues were embedded and sectioned. Five-micron sections were stained with haemotoxylin and eosin (H&E) and the percentage of artefact (clear space as a result of shrinkage) between ovarian structures was calculated. Additional histological staining using Periodic acid-Schiff and Masson's trichrome were performed on 8 and 24 h NBF, Bouin's and Form-Acetic fixed samples to assess the compatibility of the new fixative with stains. On ovarian tissue fixed for both 8 and 24 h in NBF and Form-Acetic, immunohistochemistry (IHC) studies to detect FOXO3a, FoxL2, collagen IV, laminin and anti-Müllerian hormone (AMH) proteins were performed in addition to the terminal deoxynucleotidyl transferase nick end labelling (TUNEL) assay to determine the compatibility of Form-Acetic fixation with types of histological molecular analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fixation in Form-Acetic improved ovarian tissue morphology compared to NBF from all three species and either slightly improved or was comparable to Bouin's for human, mouse and sheep tissues. Form-Acetic was compatible with H&E, Periodic acid-Schiff and Masson's trichrome staining and all proteins (FOXO3a, FoxL2, collagen IV and laminin and AMH) could be detected via IHC. Furthermore, Form-Acetic, unlike NBF, enabled antigen recognition for most of the proteins tested without the need for antigen retrieval. Form-Acetic also enabled the detection of damaged DNA via the TUNEL assay using fluorescence. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, IHC analysis was performed on a select number of protein types in ovarian tissue thus encouraging further studies to confirm the use of Form-Acetic in enabling the detection of a wider range of protein forms in addition to other tissue types. WIDER IMPLICATIONS OF THE FINDINGS: The simplicity in preparation of Form-Acetic and its superior preservative properties whilst enabling forms of histological molecular analyses make it a highly valuable tool for studying ovarian tissue. We, therefore, recommend that Form-Acetic replaces currently used fixatives and encourage others to introduce it into their research workflow. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Oxford Medical Research Council Doctoral Training Programme (Oxford MRC-DTP) grant awarded to B.D.B. (Grant no. MR/N013468/1), the Fondation Hoffmann supporting R.A. and the Petroleum Technology Development Fund (PTDF) awarded to B.V.A.

Pilot of the Patient Concerns Inventory - Ward Discharge in Patients following major reconstructive surgery for head and neck cancer.

Planning discharge from hospital following microvascular free-tissue surgery can be complex and challenging. Planning involves the patient, carers, and multiple health professionals. Poor communication and expectations can delay discharge or give a suboptimal discharge process. It was hypothesised that prompt-list modelled along the principals of the Patient Concerns Inventory (PCI) could be help in discharge planning. The aim of this study was to define the items and format of a PCI-Ward Discharge (PCI-WD) and undertake a small pilot. Items appropriate for the PCI-WD were formulated through discussion with patients, carers, ward staff, Head and Neck Clinical Nurse Specialists, and clinicians. The pilot took place over three months from December 2019 through to February 2020. Audit approval was given by the hospital Audit Department. The PCI-WD comprises 43 items. Items from existing PCIs for use at diagnosis and follow-up consultations were reduced in number and 38 new or modified items added; six treatment related, five social care and social well-being, four psychological, emotional, and spiritual well-being, seven physical and functional well-being, and 16 discharge related. The pilot involved 14 free-tissue transfer patients, seven male, seven female, with an age range of 57 to 87 and a mean age of 72. Eight PCI-WD were returned. PCI-WD items identified most frequently were 'surgery site other than head/neck', 'when do I come back to hospital', 'dental check-up/oral health care' and 'diet/eating'. Early findings suggest that PCI-WD could be a useful tool in aiding the discharge process. Further evaluation is required.

The use of Alloderm® for correction of severe chordee in children: An initial experience.

INTRODUCTION: Correction of chordee remains a prerequisite prior to urethroplasty in children with severe hypospadias. The use of an interposition graft is indicated when significant chordee (>300) persists after division of the urethral plate. The use of free dermis or tunica vaginalis are most often used, but the use of a pre-packaged graft material is attractive with regards to efficiency. The success with small intestine submucosa (SIS) has been variable and experience with Alloderm® has not been published. OBJECTIVE: To determine if Alloderm®, an acellular dermal matrix with regenerative properties, can effectively, safely, and efficiently be used for corporal grafting in cases of severe chordee in children associated with hypospadias or intersex STUDY DESIGN: All boys underwent planned staged repair of severe hypospadias (penoscrotal or more proximal). If artificial erection (AE) demonstrated chordee >450 after penile degloving and removal of fibrotic tissue, and again after urethral plate division, the ventral tunica albuginea was incised 1800 transversely and the oval defect measured in both axes. Alloderm® was trimmed to size and sewn into the defect. AE confirmed chordee correction. At the second stage repair (>6 months later), AE was performed to confirm continued absence of chordee. CONCLUSION: Alloderm®is safe, effective and simple to use graft material for correcting severe chordee. The benefits include performance efficiency without need for separate harvesting and donor site closure, and redundancy of material, if needed. Additional series and longer follow up must confirm these results and better assess durability.

Fertility preservation in boys: recent developments and new insights †.

BACKGROUND: Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility. OBJECTIVE AND RATIONALE: With this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss. SEARCH METHODS: Based on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity. OUTCOMES: Since the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic.Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation. LIMITATIONS REASONS FOR CAUTION: The review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention. WIDER IMPLICATIONS: The revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss. STUDY FUNDING/COMPETING INTERESTS: The work was funded by ESHRE. None of the authors has a conflict of interest.

Examination of preliminary behavioral and effective connectivity findings from treatment response to citalopram in cocaine use disorder: A dynamic causal modeling study.

We sought effective (directional) connectivity parameters associated with response to citalopram in cocaine use disorder (CUD) by conducting a functional magnetic resonance imaging (fMRI) experiment with participants diagnosed with CUD (n = 13) and matched healthy controls (HC; n = 17). CUD participants showed a positive correlation between bilateral DLPFC-to-putamen effective connectivity and treatment effectiveness score. These preliminary results support further investigation of prefrontal-striatal interactions in response to treatment in CUD.

STRAWB2 (Stress and Wellbeing After Childbirth): a randomised controlled trial of targeted self-help materials to prevent post-traumatic stress disorder following childbirth.

OBJECTIVES: To test whether providing psychological self-help materials would significantly lower the incidence of post-traumatic stress disorder (PTSD) at 6-12 weeks postnatally. DESIGN: Open-label randomised controlled trial, with blinded outcome assessment. SETTING: Community midwifery services in two National Health Service (NHS) trusts in the North West. SAMPLE: A cohort of 2419 women receiving normal NHS postnatal care. METHODS: Midwives screened women for traumatic birth experience; 678 women who screened positively (28.1%) were randomly allocated to self-help with usual care (n = 336) or to usual care alone (n = 342). The self-help materials were a leaflet and online film designed to prevent the development of PTSD after trauma exposure through explaining how to manage early psychological responses. MAIN OUTCOME MEASURE: The primary outcome was a composite of diagnostic and subdiagnostic PTSD at 6-12 weeks postnatally using the gold-standard Clinician-Administered PTSD Scale (CAPS-5) interview. RESULTS: Of the 678 women correctly randomised plus the nine women randomised in error, 478 (70.5%) were followed up. Diagnostic or subdiagnostic PTSD rates at follow-up did not differ between groups who received self-help (26.7%, 65/243) or usual care alone (26.2%, 64/244) (intention-to-treat analysis: RR 1.02, 95% CI 0.68-1.53). Findings remained consistent in the per-protocol analysis (RR 1.04, 95% CI 0.85-1.27). Women viewed the materials very positively. There were no adverse effects. Health economic micro-costing indicated implementation would be very low cost. CONCLUSIONS: Many women experience a traumatic birth and risk developing PTSD, but self-help strategies without professional support are insufficient and should not be routinely introduced. TWEETABLE ABSTRACT: Self-help information alone does not reduce the number of women developing PTSD after a traumatic childbirth.

Correction to: Development of a new reproductive tissue cryopreservation clinical service for children: the Oxford programme.

In the published version, the Acknowledgements section was missing a funding note of co-author Dr C Verrill. The corrected version should read as follows.