Effect of evolocumab on carotid plaque composition in asymptomatic carotid artery stenosis (EVOCAR-1) using magnetic resonance imaging.

BACKGROUND AND AIMS: To determine the effect of evolocumab treatment in patients with asymptomatic carotid artery stenosis ≥50 % on carotid plaque morphology and composition, as determined by magnetic resonance imaging. METHODS: We conducted a double-blind randomized controlled trial in patients with asymptomatic carotid artery plaque with ≥50 % stenosis and low-density lipoprotein-associated cholesterol (LDL-C) ≥1.8 mmol/L, despite standard lipid-lowering therapy, with 12 months of evolocumab or placebo injection every two weeks. The primary endpoint was the between group difference in the absolute change from baseline in carotid plaque lipid-rich necrotic core (LRNC), assessed by carotid magnetic resonance. RESULTS: Due to interrupted recruitment during the COVID-19 pandemic, 33 patients (36 % female) were randomised, which was less than the target of 52. Mean age was 68.7 years (SD, 8.5) and baseline LDL-C 2.4 mmol/L(SD, 0.7). LDL-C was reduced with evolocumab to 0.8 mmol/L (SD, 0.5) vs 2.2 mmol/L (SD, 0.7) with placebo at 3 months (between group absolute difference -1.3 mmol/L [95 % CI, -1.7 to -0.9], p < 0.001). Evolocumab treatment was associated with a favourable change in LRNC at 12 months of -16 mm3 (SD, 54) whereas the placebo group showed -4 mm3 (SD, 44). Between group differences did not show statistically significance with a placebo-adjusted LRNC change of -17 mm3 ([95 % CI, -45 to 12], p = 0.25). Percentage carotid plaque LRNC also numerically reduced at 12 months, however this did not reach statistical significance (-2.4 % vessel wall volume [95 % CI, -5.7 to 0.9], p = 0.16). CONCLUSION: Intensive LDL-C lowering with the addition of evolocumab to maximally tolerated lipid-lowering therapy did not lead to a statistically significant change in vulnerable plaque phenotype characteristics in patients with asymptomatic carotid artery stenosis, but the study was underpowered due to under-recruitment in the context of the COVID-19 pandemic.

Systematic Review and Meta-analysis: The Three-year Post-colonoscopy Colorectal Cancer Rate as per the World Endoscopy Organization Methodology.

BACKGROUND & AIMS: In 2018, the World Endoscopy Organization (WEO) introduced standardized methods for calculating post-colonoscopy colorectal cancer-3yr rates (PCCRC-3yr). This systematic review aimed to calculate the global PCCRC-3yr according to the WEO methodology, its change over time, and to measure the association between risk factors and PCCRC occurrences. METHODS: We searched 5 databases from inception until January 2024 for PCCRC-3yr studies that strictly adhered to the WEO methodology. The overall pooled PCCRC-3yr was calculated. For risk factors and time-trend analyses, the pooled PCCRC-3yr and odds ratios (ORs) of subgroups were compared. RESULTS: Several studies failed to adhere to the WEO methodology. Eight studies from 4 Western European and 2 Northern American countries were included, totalling 220,106 detected-colorectal cancers (CRCs) and 18,148 PCCRCs between 2002 and 2017. The pooled Western World PCCRC-3yr was 7.5% (95% confidence interval [CI], 6.4%-8.7%). The PCCRC-3yr significantly (P < .05) decreased from 7.9% (95% CI, 6.6%-9.4%) in 2006 to 6.7% (95% CI, 6.1%-7.3%) in 2012 (OR, 0.79; 95% CI, 0.72-0.87). There were significantly higher rates for people with inflammatory bowel disease (PCCRC-3yr, 29.3%; OR, 6.17; 95% CI, 4.73-8.06), prior CRC (PCCRC-3yr, 29.8%; OR, 3.03; 95% CI, 1.34-4.72), proximal CRC (PCCRC-3yr, 8.6%; OR, 1.51; 95% CI, 1.41-1.61), diverticular disease (PCCRC 3-yr, 11.6%; OR, 1.74; 95% CI, 1.37-2.10), and female sex (PCCRC-3yr, 7.9%; OR, 1.15; 95% CI, 1.11-1.20). CONCLUSION: According to the WEO methodology, the Western World PCCRC-3yr was 7.5%. Reassuringly, this has decreased over time, but further work is required to identify the reasons for PCCRCs, especially in higher-risk groups. We devised a WEO methodology checklist to increase its adoption and standardise the categorization of patients in future PCCRC-3yr studies.

Add-on Sodium Benzoate and N-Acetylcysteine in Patients With Early Schizophrenia Spectrum Disorder: A Multicenter, Double-Blind, Randomized Placebo-Controlled Feasibility Trial.

Background and Hypothesis: Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. N-acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia. Study Design: A multicenter, 12 weeks, 2 × 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed. Study Results: We recruited our desired sample (n = 68) and retained 78% (n = 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes. Conclusions: We demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge. Trial Registration: ClinicalTrials.gov: NCT03510741.

Sequential levetiracetam and phenytoin in electroencephalographic neonatal seizures unresponsive to phenobarbital: a multicenter prospective observational study in India.

Background: Although levetiracetam and phenytoin are widely used antiseizure medications (ASM) in neonates, their efficacy on seizure freedom is unclear. We evaluated electroencephalographic (EEG) seizure freedom following sequential levetiracetam and phenytoin in neonatal seizures unresponsive to phenobarbital. Methods: We recruited neonates born ≥35 weeks and aged <72 h who had continued electrographic seizures despite phenobarbital, from three Indian hospitals, between 20 June 2020 and 31 July 2022. The neonates were treated with intravenous levetiracetam (20 mg/kg x 2 doses, second line) followed by phenytoin (20 mg/kg x 2 doses, third line) if seizures persisted. The primary outcome was complete seizure freedom, defined as an absence of seizures on EEG for at least 60 min within 40 min from the start of infusion. Findings: Of the 206 neonates with continued seizures despite phenobarbital, 152 received levetiracetam with EEG. Of these one EEG was missing, 47 (31.1%) were in status epilepticus, and primary outcome data were available in 145. Seizure freedom occurred in 20 (13.8%; 95% CI 8.6%-20.5%) after levetiracetam; 16 (80.0%) responded to the first dose and 4 (20.0%) to the second dose. Of the 125 neonates with persisting seizures after levetiracetam, 114 received phenytoin under EEG monitoring. Of these, the primary outcome data were available in 104. Seizure freedom occurred in 59 (56.7%; 95% CI 46.7%-66.4%) neonates; 54 (91.5%) responded to the first dose and 5 (8.5%) to the second dose. Interpretation: With the conventional doses, levetiracetam was associated with immediate EEG seizure cessation in only 14% of phenobarbital unresponsive neonatal seizures. Additional treatment with phenytoin along with levetiracetam attained seizure freedom in further 57%. Safety and efficacy of higher doses of levetiracetam should be evaluated in well-designed randomised controlled trials. Funding: National Institute for Health and Care Research (NIHR) Research and Innovation for Global Health Transformation (NIHR200144).

The effectiveness of bone anchored maxillary protraction (BAMP) in the management of class III skeletal malocclusion in children aged 11-14 years compared with an untreated control group: A multicentre two-arm parallel randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of bone anchored maxillary protraction (BAMP) in the management of class III skeletal malocclusion in children aged 11-14 years compared with an untreated control group in terms of perceived need for orthognathic surgery, skeletal and dental change, and psychological impact. DESIGN: A multicentre two-armed parallel randomised controlled trial. SETTING: Six UK hospital orthodontic units. METHODS: A total of 57 patients were randomly allocated into either the BAMP group (BAMPG) (n = 28) or a no treatment control group (CG) (n = 29). OUTCOMES: Data collection occurred at registration (DC1),18 months (DC2) and 3 years (DC3), where skeletal and dental changes were measured from lateral cephalograms and study models. Oral Aesthetic Subjective Impact Score (OASIS) and Oral Quality of Life (OHQOL) questionnaires were used to assess the psychological impact of treatment. RESULTS: The mean age was 12.9 ± 0.7 years and 12.6 ± 0.9 years in the BAMPG and CG, respectively. At DC2, the BAMPG achieved a class III ANB improvement of +0.6° compared with -0.7° in the CG (P = 0.004). The overjet improvement was +1.4 mm for the BAMPG and -0.2 mm for the CG (P = 0.002). There was no evidence of any other group differences for the other skeletal or dental cephalometric outcomes (P > 0.05) or the questionnaire data (OASIS P = 0.10, OHQOL P = 0.75). At DC2, the 18-month follow-up, 22% of the BAMPG achieved a positive overjet. At the 3-year follow-up (DC3), fewer participants in the BAMPG were perceived to need orthognathic surgery (48%) compared with 75% of participants in the CG (P = 0.04), with an odds ratio of 0.31 (95% confidence interval = 0.10-0.95). CONCLUSION: The BAMP technique did not show any social or psychological benefits; however, the skeletal class III improvement in ANB and the overjet change were sufficient to reduce the perceived need for orthognathic surgery by 27% compared with the CG.

Epilepsy professionals' views on sudden unexpected death in epilepsy counselling: A tale of two countries.

BACKGROUND AND PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of epilepsy mortality. All international guidance strongly advocates for clinicians working with people with epilepsy (PWE) to discuss SUDEP. Clinician views working with PWE in the UK and Norway on SUDEP counselling are compared. METHODS: A cross-sectional online mixed methodology survey of 17 Likert and free-text response questions using validated themes was circulated via International League against Epilepsy/Epilepsy Specialist Nurses Association in the UK and International League against Epilepsy/Epilepsinet in Norway using a non-discriminatory exponential snowballing technique leading to non-probability sampling. Quantitative data were analysed using descriptive statistics and Mann-Whitney, Kruskal-Wallis, chi-squared and Fisher's exact tests. Significance was accepted at p < 0.05. Thematic analysis was conducted on free-text responses. RESULTS: Of 309 (UK 197, Norway 112) responses, UK clinicians were more likely to have experienced an SUDEP (p < 0.001), put greater importance on SUDEP communication (p < 0.001), discuss SUDEP with all PWE particularly new patients (p < 0.001), have access and refer to bereavement support (p < 0.001) and were less likely to never discuss SUDEP (p < 0.001). Significant differences existed between both countries' neurologists and nurses in SUDEP counselling with UK clinicians generally being more supportive. UK responders were more likely to be able to identify bereavement support (p < 0.001). Thematic analysis highlighted four shared themes and two specific to Norwegians. DISCUSSION: Despite all international guidelines stating the need/importance to discuss SUDEP with all PWE there remain hesitation, avoidance and subjectivity in clinicians having SUDEP-related conversations, more so in Norway than the UK. Training and education are required to improve communication, engagement and decision making.

Autologous bone marrow derived mesenchymal stem cells are safe for the treatment of Achilles tendinopathy.

Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 106, range 5-19 × 106 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial.

Women and men with distressing low sexual desire exhibit sexually dimorphic brain processing.

Distressing low sexual desire, termed Hypoactive Sexual Desire Disorder (HSDD), affects approximately 10% of women and 8% of men. In women, the 'top-down' theory of HSDD describes hyperactivity in higher-level cognitive brain regions, suppressing lower-level emotional/sexual brain areas. However, it is unknown how this neurofunctional disturbance compares to HSDD in men. To investigate this, we employed task-based functional MRI in 32 women and 32 men with HSDD to measure sexual-brain processing during sexual versus non-sexual videos, as well as psychometric questionnaires to assess sexual desire/arousal. We demonstrate that women had greater activation in higher-level and lower-level brain regions, compared to men. Indeed, women who had greater hypothalamic activation in response to sexual videos, reported higher psychometric scores in the evaluative (r = 0.55, P = 0.001), motivational (r = 0.56, P = 0.003), and physiological (r = 0.57, P = 0.0006) domains of sexual desire and arousal after watching the sexual videos in the scanner. By contrast, no similar correlations were observed in men. Taken together, this is the first direct comparison of the neural correlates of distressing low sexual desire between women and men. The data supports the 'top-down' theory of HSDD in women, whereas in men HSDD appears to be associated with different neurofunctional processes.

Identifying co-morbidities and risk in people with epilepsy: The Maltese experience.

BACKGROUND: People with epilepsy are at increased risk of multiple co-morbidities that may influence risk of adverse outcomes including impact on quality of life and premature mortality. These risk factors include potentially modifiable clinical characteristics associated with sudden unexpected death in epilepsy (SUDEP). For services to tackle risk, the clinical complexity of the target epilepsy population needs to be defined. While this has been comprehensively studied in large, economically developed countries little knowledge of these issues exist in small economically developed countries, like Malta (population: 500,000). METHODS: This was a single centre study focused exclusively on patients attending Gozo General Hospital (GGH) Malta. STROBE guidance for reporting cross sectional studies was used to design and report the study. This was a retrospective review of standard care and SUDEP and seizure risks provided to all adults (over 18 years) with epilepsy attending GGH (2018-2021). RESULTS: The review identified 68 people and 92% were compliant with their anti-seizure medication. A fifth (21%) had an intellectual disability. Despite only one patient having a psychotic illness, 19% were on antipsychotic medication. Only 18% of patients had a specific epilepsy care plan, 6% nocturnal surveillance and none had received advice on SUDEP. DISCUSSION: Patient outcomes may be improved with increasing rates of personalized epilepsy care plans, appropriate nocturnal surveillance and reducing the prescription of antipsychotic medication as it is associated with greater risk of mortality. Issues such as stigma and shame appear to play a significant role in small communities and their access to care.

Randomized Trial of Remote Assessment of Patients After an Acute Coronary Syndrome.

BACKGROUND: Telemedicine programs can provide remote diagnostic information to aid clinical decisions that could optimize care and reduce unplanned readmissions post-acute coronary syndrome (ACS). OBJECTIVES: TELE-ACS (Remote Acute Assessment of Patients With High Cardiovascular Risk Post-Acute Coronary Syndrome) is a randomized controlled trial that aims to compare a telemedicine-based approach vs standard care in patients following ACS. METHODS: Patients were suitable for inclusion with at least 1 cardiovascular risk factor and presenting with ACS and were randomized (1:1) before discharge. The primary outcome was time to first readmission at 6 months. Secondary outcomes included emergency department (ED) visits, major adverse cardiovascular events, and patient-reported symptoms. The primary analysis was performed according to intention to treat. RESULTS: A total of 337 patients were randomized from January 2022 to April 2023, with a 3.6% drop-out rate. The mean age was 58.1 years. There was a reduced rate of readmission over 6 months (HR: 0.24; 95% CI: 0.13-0.44; P < 0.001) and ED attendance (HR: 0.59; 95% CI: 0.40-0.89) in the telemedicine arm, and fewer unplanned coronary revascularizations (3% in telemedicine arm vs 9% in standard therapy arm). The occurrence of chest pain (9% vs 24%), breathlessness (21% vs 39%), and dizziness (6% vs 18%) at 6 months was lower in the telemedicine group. CONCLUSIONS: The TELE-ACS study has shown that a telemedicine-based approach for the management of patients following ACS was associated with a reduction in hospital readmission, ED visits, unplanned coronary revascularization, and patient-reported symptoms. (Telemedicine in High-Risk Cardiovascular Patients Post-ACS [TELE-ACS]; NCT05015634).

The relationship between clinical presentation and the nature of care in adults with intellectual disability and epilepsy - national comparative cohort study.

BACKGROUND: A quarter of People with Intellectual Disabilities (PwID) have epilepsy compared with 1% of the general population. Epilepsy in PwID is a bellwether for premature mortality, multimorbidity and polypharmacy. This group depends on their care provider to give relevant information for management, especially epilepsy. There is no research on care status relationship and clinical characteristics of PwID and epilepsy. AIM: Explore and compare the clinical characteristics of PwID with epilepsy across different care settings. METHOD: A retrospective multicentre cohort study across England and Wales collected information on seizure characteristics, intellectual disability severity, neurodevelopmental/biological/psychiatric comorbidities, medication including psychotropics/anti-seizure medication, and care status. Clinical characteristics were compared across different care settings, and those aged over and younger than 40 years. RESULTS: Of 618 adult PwID across six centres (male:female = 61%:39%), 338 (55%) received professional care whereas 258 (42%) lived with family. Significant differences between the care groups existed in intellectual disability severity (P = 0.01), autism presence (P < 0.001), challenging behaviour (P < 0.001) and comorbid physical conditions (P = 0.008). The two groups did not vary in intellectual disability severity/genetic conditions/seizure type and frequency/psychiatric disorders. The professional care cohort experienced increased polypharmacy (P < 0.001) and antipsychotic/psychotropic use (P < 0.001/P = 0.008).The over-40s cohort had lower autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) comorbidity (P < 0.001/P = 0.007), increased psychiatric comorbidity and challenging behaviour (P < 0.05), physical multimorbidity (P < 0.001), polypharmacy (P < 0.001) and antipsychotic use (P < 0.001) but reduced numbers of seizures (P = 0.007). CONCLUSION: PwID and epilepsy over 40 years in professional care have more complex clinical characteristics, increased polypharmacy and antipsychotic prescribing but fewer seizures.

Chronic constipation in people with intellectual disabilities in the community: cross-sectional study.

BACKGROUND: One-third to half of people with intellectual disabilities suffer from chronic constipation (defined as two or fewer bowel movements weekly or taking regular laxatives three or more times weekly), a cause of significant morbidity and premature mortality. Research on risk factors associated with constipation is limited. AIMS: To enumerate risk factors associated with constipation in this population. METHOD: A questionnaire was developed on possible risk factors for constipation. The questionnaire was sent to carers of people with intellectual disabilities on the case-loads of four specialist intellectual disability services in England. Data analysis focused on descriptively summarising responses and comparing those reported with and without constipation. RESULTS: Of the 181 people with intellectual disabilities whose carers returned the questionnaire, 42% reported chronic constipation. Constipation was significantly associated with more severe intellectual disability, dysphagia, cerebral palsy, poor mobility, polypharmacy including antipsychotics and antiseizure medication, and the need for greater toileting support. There were no associations with age or gender. CONCLUSIONS: People with intellectual disabilities may be more vulnerable to chronic constipation if they are more severely intellectually disabled. The associations of constipation with dysphagia, cerebral palsy, poor mobility and the need for greater toileting support suggests people with intellectual disabilities with significant physical disabilities are more at risk. People with the above disabilities need closer monitoring of their bowel health. Reducing medication to the minimum necessary may reduce the risk of constipation and is a modifiable risk factor that it is important to monitor. By screening patients using the constipation questionnaire, individualised bowel care plans could be implemented.

People with Intellectual Disabilities, Dysphagia and Post-Covid Syndrome.

People with Intellectual Disability (ID) were more likely to contract COVID-19 infection and more likely to die from the consequences. However, there is no evidence on the long-term impact of COVID-19 infection in people with ID. Post-Covid Syndrome (PCS) is an established diagnosis that requires specialist clinical support. To date there is no data on how common PCS is in people with ID, or how symptoms present. Dysphagia is identified as a clinical marker because of the known association with PCS, and the clear objective diagnostic criteria applicable through specialist assessment. This investigation presents a cohort of people with ID, who developed dysphagia/worsening of dysphagia post diagnosis with COVID-19. Cases were identified through support from the Royal College of Speech and Language Therapists. Data was collected by electronic survey, including application of the COVID-19 Yorkshire Rehabilitation Scale-modified (C19-YRSm). The C19-YRSm is a validated assessment tool for PCS and it's impact upon functional disability. This case series identifies that symptoms consistent with PCS are present in people with ID, post-COVID-19 infection. The risk of diagnostic overshadowing or misdiagnosis is high due to the subjective nature and the quality of PCS symptoms. People with ID who develop PCS may not be readily identified by clinical services and therefore not be accessing the specialist medical support required. Furthermore, changes in behaviour secondary to PCS may lead to unnecessary increased prescribing of psychotropic medication which in itself risks worsening dysphagia. Dysphagia could be an important bellwether to identify PCS in people with ID.

Bacteriuria in patients with stented ureters: predictors of infection in patients presenting to the hospital and when not to treat.

PURPOSE: Patients with ureteric stents have symptoms that overlap with infection symptoms. Thus, clinicians unnecessarily give antibiotics to stented patients with bacteriuria despite guidelines. In stented patients, little is known about risk factors for developing bacteriuria or urosepsis. The objectives were to identify the frequency and risk factors for developing bacteriuria and urosepsis in patients with stents. METHODS: In this retrospective cohort study, we reviewed patients with ureteric stents placed or exchanged over 1 year. We examined associations between bacteriuria or urosepsis and host risk factors. Univariable and multivariable logistic analyses were performed. RESULTS: Of 286 patients (mean age: 57.2 years), 167 (58.4%) were male. The main stent indications were stone, stricture, cancer and extrinsic compression. The median stented period was 61 days. The frequency of bacteriuria was 59/286 (21%). ASA status 3 and 4 had 5 times the odds of having bacteriuria relative to ASA status 1. Stent duration > 2 months had 5.5 times the odds relative to ≤ 2 months. Urosepsis was infrequent, 13/286 (4.5%). Five patients had bacteraemia. A stent duration over 2 months had nearly 6 times the odds of urosepsis. CONCLUSION: ASA status higher than 2 and stent time greater than 2 months raise the odds of developing bacteriuria. A stent duration longer than 2 months was the only predictor of urosepsis. Though 21% of patients had bacteriuria, 4.5% had urosepsis. Hence, bacteriuria without sepsis should not be treated with antibiotics, thus aiding antimicrobial stewardship.

Perspectives on Self-Harm and Suicidal Ideation in Nigeria: A Mixed-Methods Study of Patients, Family Caregivers, Clinicians, and the Public.

BACKGROUND: Suicide and self-harm are global disease burden that contributes significantly to years of lost life and mortality. Despite the increasing rates of suicide and self-harm in Nigeria, this topic is understudied. METHODS: A mixed-methods design was adopted. Study 1 interviewed n = 18 participants (n = 11 clinicians; n = 5 patients with a history of self-harm and suicide ideation; and n = 2 caregivers). All interviews were audio-recorded, transcribed verbatim, and analyzed using IPA. Study 2 surveyed n = 562 non-clinical sample about their tolerance toward self-harm and the data was analyzed using One-way ANOVA in SPSS. RESULTS: Study 1 qualitative findings showed substance use, perceived rejection and social isolation were considered predisposing factors for suicide and self-harm. Cultural and religious beliefs shaped help-seeking behaviours. Although Study 2 found no significant differences in demographic characteristics concerning public tolerance toward persons with a history of self-harm, 64% believed that individuals who died by suicide would face punishment after death; 51% believed that victims of attempted suicide are a source of shame to their families; and 33.8% agreed that dying by suicide is the correct behaviour. CONCLUSIONS: Patients with a history of self-harm and suicidal ideation consider family members and close friends as valuable sources of support. Due to the potential clinical implication of cultural and religious beliefs, as shown in the present study's findings, the authors recommend a co-development of culturally appropriate psychological intervention for persons with a history of self-harm and suicidal ideation to be tested in randomized control trials.

Severe COVID anxiety among adults in the United Kingdom: cohort study and nested feasibility trial.

BACKGROUND: People with severe COVID anxiety have poor mental health and impaired functioning, but the course of severe COVID anxiety is unknown and the quality of evidence on the acceptability and impact of psychological interventions is low. METHODS: A quantitative cohort study with a nested feasibility trial. Potential participants aged 18 and over, living in the UK with severe COVID anxiety, were recruited online and from primary care services. We examined levels of COVID anxiety in the six months after recruitment, and factors that influenced this, using linear regression. Those scoring above 20 on the short Health Anxiety Inventory were invited to participate in a feasibility trial of remotely delivered Cognitive Behavioural Therapy for Health Anxiety (CBT-HA). Exclusion criteria were recent COVID-19, current self-isolation, or current receipt of psychological treatment. Key outcomes for the feasibility trial were the level of uptake of CBT-HA and the rate of follow-up. RESULTS: 204 (70.2%) of 285 people who took part in the cohort study completed the six month follow-up, for whom levels of COVID anxiety fell from 12.4 at baseline to 6.8 at six months (difference = -5.5, 95% CI = -6.0 to -4.9). Reductions in COVID anxiety were lower among older people, those living with a vulnerable person, those with lower baseline COVID anxiety, and those with higher levels of generalised anxiety and health anxiety at baseline. 36 (90%) of 40 participants enrolled in the nested feasibility trial were followed up at six months. 17 (80.9%) of 21 people in the active arm of the trial received four or more sessions of CBT-HA. We found improved mental health and social functioning among those in the active, but not the control arm of the trial (Mean difference in total score on the Work and Social Adjustment Scale between baseline and follow up, was 9.7 (95% CI = 5.8-13.6) among those in the active, and 1.0 (95% C.I. = -4.6 to 6.6) among those in the control arm of the trial. CONCLUSIONS: While the mental health of people with severe COVID anxiety appears to improve over time, many continue to experience high levels of anxiety and poor social functioning. Health anxiety is highly prevalent among people with severe COVID anxiety and may provide a target for psychological treatment. TRIAL REGISTRATION: Retrospectively registered at ISRCTN14973494 on 09/09/2021.

Duration of birth depression and neurodevelopmental outcomes after whole-body hypothermia for hypoxic ischemic encephalopathy in India, Sri Lanka and Bangladesh - an exploratory analysis of the HELIX trial.

Background: Effect of duration of birth depression on neurodevelopmental outcomes in low- and middle-income countries (LMICs) is not known. We examined the association of birth depression with brain injury, neurodevelopmental outcomes, and hypothermia after hypoxic ischemic encephalopathy (HIE) in south Asia. Methods: We compared cerebral magnetic resonance (MR) at 2 weeks, and adverse outcomes (death or moderate or severe disability) at 18 months in 408 babies with moderate or severe HIE who had long birth depression (positive pressure ventilation (PPV) >10 min or Apgar score<6 at 10 min or cord pH < 7.0) and short birth depression (PPV for 5-10 min or Apgar score<6 at 5 min, but ≥6 at 10 min). Findings: Long depression group (n = 201) had more severe HIE (32.8% versus 6.8%), mortality (47.5% versus 26.4%), death or disability at 18 months (62.2% versus 35.4%) (all p < 0.001), MR injury (Odds ratio; 95% CI) to basal ganglia (2.4 (1.3, 4.1); p = 0.003), posterior limb of internal capsule (2.3 (1.3, 4.3); p < 0.001) and white matter (1.7 (1.1, 2.7); p = 0.021), and lower thalamic N-acetylaspartate levels (7.69 ± 1.84 versus 8.29 ± 1.60); p = 0.031) than short depression group (n = 207). Three babies had no heartbeat at 5 min, of which 1 died and 2 survived with severe disability. No significant interaction between the duration of birth depression and whole-body hypothermia was seen for any of the MR biomarker or clinical outcomes. Interpretation: Long birth depression was associated with more brain injury and adverse outcomes than short depression. Effect of hypothermia was not modified by duration of birth depression. Funding: National Institute for Health Research.

Exploring methods of improving patient understanding and communication in a complex anal fistula clinic: results from a randomized controlled feasibility study.

AIM: Patient understanding of disease can guide decision-making in the management of anal fistula. This prospective feasibility study aimed to assess the acceptability and methods of assessing the impact of viewing realistic models on patients with anal fistula. METHODS: New referrals to a tertiary clinic participated in this single-centre, parallel-group randomized controlled study. Baseline characteristics, Decisional Conflict Scale and understanding of disease were assessed pre-consultation. Participants were randomized to a standard consultation, where disease and treatment options were explained using magnetic resonance images and drawn diagrams, or a similar consultation supplemented with an appropriate generic three-dimensional (3D) printed model. Understanding of disease and proposed surgery, Decisional Conflict Scale and ratings of visual aids were assessed post-consultation, along with 3D model feedback. RESULTS: All 52 patients who were approached agreed to be randomized (25 standard, 27 3D consultation). Understanding of disease increased post-consultation in both groups. Post-consultation decisional conflict (0, no; 100, high decisional conflict) was low (median 27 post-standard vs. 24 post-3D consultation). Patients scored highly on measures assessing understanding of proposed surgery. 3D models were rated highly, with 96% of patients wanting to see them again in future consultations. CONCLUSIONS: Three-dimensional printed fistula models are a welcome addition to outpatient consultations with results suggesting that understanding of surgery is improved. A future trial should be powered to detect whether 3D models result in a significant improvement in understanding beyond traditional methods of explanation and explore the conditions in which models have their maximal utility. GOV REGISTRATION ID: This study was registered on ClinicalTrials.gov (ID: NCT04069728). Registered on 23 August 2019.