Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis.

INTRODUCTION: The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA). AIM: The aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators. METHODS: Descriptive and pharmacovigilance disproportionality analyses was performed. RESULTS: A total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 'serious' cases related to selected ADRs were registered during 2005-2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide). DISCUSSION: Suicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations. CONCLUSIONS: With the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.

New/emerging psychoactive substances and associated psychopathological consequences.

BACKGROUND: The present paper provides an updated review of both the large number of new/novel/emerging psychoactive substances (NPS) and their associated psychopathological consequences. Focus was here given on identification of those NPS being commented in specialised online sources and the related short-/long-term psychopathological and medical ill-health effects. METHODS: NPS have been identified through an innovative crawling/navigating software, called the 'NPS.Finder®', created in order to facilitate the process of early recognition of NPS online. A range of information regarding NPS, including chemical and street names; chemical formula; three-dimensional image and anecdotally reported clinical/psychoactive effects, were here made available. RESULTS: Using the 'NPS.Finder®' approach, a few thousand NPS were here preliminarily identified, a number which is about 4-fold higher than those figures suggested by European and international drug agencies. NPS most commonly associated with the onset of psychopathological consequences included here synthetic cannabinoids/cannabimimetics; new synthetic opioids; ketamine-like dissociatives; novel stimulants; novel psychedelics and several prescription and over-the-counter medicines. CONCLUSIONS: The ever-increasing changes in terms of recreational psychotropics' availability represent a relatively new challenge for psychiatry, as the pharmacodynamics and pharmacokinetics of many NPS have not been thoroughly understood. Health/mental health professionals should be informed about the range of NPS; their intake modalities; their psychoactive sought-after effects; the idiosyncratic psychotropics' combinations and finally, their medical and psychopathological risks.

Factors impacting antiretroviral therapy adherence among human immunodeficiency virus-positive adolescents in Sub-Saharan Africa: a systematic review.

OBJECTIVES: Eighty-two percent of human immunodeficiency virus (HIV)-positive adolescents live in Sub-Saharan Africa (SSA). Despite the availability of antiretroviral therapy (ART), adherence levels are suboptimal, leading to poor outcomes. This systematic review investigated factors impacting ART adherence among adolescents in SSA, including religious beliefs and intimate relationships. METHODS: A systematic review was conducted between June and August 2016 using eight electronic databases, including Cochrane and PubMed. Published, ongoing and unpublished research, conducted in SSA from 2004 to 2016, was identified and thematic analysis was used to summarise findings. RESULTS: Eleven studies from eight SSA countries, published in English between 2011 and 2016, reported on factors impacting ART adherence among adolescents living with HIV (ALHIV). Forty-four barriers and 29 facilitators to adherence were identified, representing a complex web of factors. The main barriers were stigma, ART side-effects, lack of assistance and forgetfulness. Facilitators included caregiver support, peer support groups and knowledge of HIV status. CONCLUSIONS: Stigma reflects difficult relations between ALHIV and their HIV-negative peers and adults. Most interventions target only those with HIV, suggesting a policy shift towards the wider community could be beneficial. Recommendations include engaging religious leaders and schools to change negative societal attitudes. Limitations of the review include the urban settings and recruitment of predominantly vertically infected participants in most included studies. Therefore, the findings cannot be extrapolated to ALHIV residing in rural locations or horizontally infected ALHIV, highlighting the need for further research in those areas.

Death rates from ecstasy (MDMA, MDA) and polydrug use in England and Wales 1996-2002.

The present study reports on all deaths related to taking ecstasy (alone, or in a polydrug combination) occurring in England and Wales in the time frame August 1996-April 2002. Data presented here are based on all information recorded in the National Programme on Substance Abuse Deaths (np-SAD) database. The np-SAD regularly receives all information on drug related deaths in addicts and non addicts from coroners. A total of 202 ecstasy-related fatalities occurred in the chosen time-frame, showing a steady increase in the number of deaths each year. The ratio male:female was 4:1 and 3 of 4 victims were younger than 29. In 17% of cases ecstasy was the sole drug implicated in death and in the remaining cases a number of other drugs (mostly alcohol, cocaine, amphetamines and opiates) have been found. According to toxicology results, MDMA accounted for 86% of cases and MDA for 13% of cases; single deaths were associated with MDEA and PMA. This is the largest sample of ecstasy related deaths so far; possible explanations are given for the observed steady increase in ecstasy-related deaths and a tentative 'rationale' for this polypharmacy combination is then proposed.

Anterior resection for megarectosigmoid in congenital anorectal malformations.

PURPOSE: The aim of this study was to review the effectiveness of resecting dilated distal bowel in children suffering unmanageable constipation or soiling who have been operated on previously for anorectal malformations. METHODS: A retrospective review was performed of 9 children. Each child underwent excision of dilated bowel to leave normal caliber bowel anastomosed by hand to a rectal reservoir at the peritoneal reflection. The documented follow-up was reviewed. RESULTS: The 9 children had primary surgery for the following anomalies: high (n = 1), intermediate (n = 1), low (n = 3), rectal stenosis (n = 3), and anal stenosis (n = 3), Seven children had persistent fecalomas, and 7 had major problems with soiling. All were on large doses of laxatives, with 5 having regular rectal washouts and 4 having regular enemas. In all radiologic studies there was a prompt change from normal caliber bowel to dilated bowel at the upper limit of the dilatation. The mean age at operation for excision was 4 years, 11 months (range, 11 months to 9 years, 11 months). The mean period of follow-up was 4 years, 7 months (range, 2 years, 3 months to 10 years). Follow-up showed that all children improved. None had major complications. All were having between one and 3 bowel actions per day. Three continued to soil but improved. Of the remaining 6, only 2 required occasional laxatives and had regular spontaneous bowel actions without soiling. No child was having enemas or washouts. CONCLUSION: Anterior resection for the treatment of megarectosigmoid is a safe and effective procedure.

Cysts of the ejaculatory system--a treatable cause of recurrent epididymo-orchitis in children.

PURPOSE: The commonest causes of acutely painful scrotum are torsion (of appendix of the testis or the testis itself) and epididymo-orchitis. Exploration is the only way to prove the diagnosis and multiple such procedures are performed in patients with recurrent epididymo-orchitis. The purpose of our study was to investigate the cause of recurrent epididymo-orchitis in pre-pubertal children. Four children, aged three years or less, were investigated for recurrent left epididymo-orchitis. All four had cystic dilatation of the ejaculatory duct in the region of the prostatic utriculus, associated in two children with ectopic opening of the vas in the bladder. Initial ultrasound appeared to be normal in all four patients, a retrospective review of the sonographic films, however, revealed a retrovesical cyst in three of them. The diagnosis was established by a combination of urethroscopy with retrograde contrast study via the utriculus and open vasography. All four cases were treated operatively by a transtrigonal approach. The cyst was excised in each case. In one, a vasovasostomy was performed between the left and the normal right vas; in the other three the left vas was anastomosed to the blind end of the contralateral seminal vesicle. All four are symptom-free at one year follow-up. Cysts of the ejaculatory duct are a treatable cause of recurrent epididymo-orchitis. Pre-pubertal children with recurrent epididymo-orchitis and no obvious underlying cause should have a thorough sonographic examination of the retrovesical region for cystic lesions.

Postoperative pneumatosis intestinalis in infants does not automatically preclude enteral feeding.

BACKGROUND: A degree of feed intolerance after neonatal abdominal surgery is common but in an otherwise well baby enteral feeding usually is continued at the highest tolerated level. However, the presence of rectal bleeding, pneumatosis intestinalis, or portal vein gas seen on plain abdominal x-rays suggest the possibility of postoperative necrotising enterocolitis. When this happens feedings usually are stopped for 7 to 10 days, and intravenous antibiotics and total parental nutrition are commenced. METHODS: The authors report 12 episodes of rectal bleeding and 11 episodes of pneumatosis intestinalis in 3 infants who previously had undergone neonatal abdominal surgery for intestinal malformations. In 7 of these episodes, feedings were neither stopped nor were antibiotics given. At the time of these 7 episodes, the infants were more than 3 kg in weight, had no significant cardiac or respiratory pathology, were all clinically stable, had no evidence of peritonitis, had no thrombocytopenia, and were greater than 37 weeks postconception. RESULTS: The 3 infants were monitored closely. There were no early or late problems observed attributable to this management. CONCLUSION: Carefully selected clinically stable patients that have postoperative pneumatosis intestinalis or exhibit rectal bleeding may be successfully managed by reduced enteral feedings with no antibiotics. J Pediatr Surg 36:1820-1823.

Single-system ectopic ureter: a 15-year review.

Ectopic ureters present in childhood with symptoms related to an abnormal site or structure (refluxing, obstructed) of the ureteric orifice. The majority drain duplex kidneys. The diagnosis is relatively easy if the poles are functioning or hydronephrotic. Associated malformations are rarely seen and the results of surgery are gratifying. If an ectopic ureter drains a single kidney, it is called a single-system ectopic ureter (SSEU). We reviewed a 15-year experience (1980-1995) with 127 ectopic ureters from our hospital:11 SSEUs in ten consecutive children were managed during this period. Our data lead us to believe that SSEUs are a special subset of ectopic ureters. Diagnosis is often delayed because the ectopic ureter may be associated with a single small, dysplastic, poorly-functioning, non-visualised kidney and the child may be thought to have a contralateral normal "solitary kidney". Associated systemic malformations are common. Residual symptoms of wetting may persist in the early postoperative period. A high degree of suspicion must be maintained for this entity when a child presents with urinary symptoms of wetting or recurrent infection and a "solitary kidney". Early endoscopic examination of the genitourinary tract will clinch the diagnosis in the majority of cases. Residual symptoms of wetting in the postoperative period generally resolve with passage of time.

The primary management of testicular maldescent in gastroschisis.

Gastroschisis (GS) is the commonest abdominal-wall defect in the Western world. The conventional practice has been reduction of the viscera and closure of the abdominal wall as an emergency procedure. The testis is often a part of the prolapsed viscera along with the bowel loops, stomach, fallopian tube, etc. The primary management of prolapsed (PT) (3) and intra-abdominal (5) testes (IAT) in this condition was studied in 16 consecutive male babies with GS, each was managed by simple reposition of the testes and closure of the abdominal wall. The babies were followed up for spontaneous descent of the testes. At 18-month follow-up, all five IAT had descended into the scrotum spontaneously and were palpably normal. Of the three extra-abdominal PT, two had descended into the scrotum and were normal in size and on palpation. One was palpable in the superficial inguinal pouch. Simple reposition of the testes into the abdomen and closure of the abdominal defect is the correct approach for primary management of PT or IAT in a newborn with GS.

Central-venous access through the peripheral route in surgical neonates: an audit of 125 consecutive lines from a regional neonatal centre.

A long Percutaneous silastic IV line is frequently used in surgical neonates for infusion of hyperosmolar parenteral nutrition fluid into a central vein for several days without the need for operative insertion of a Broviac catheter or risks of direct puncture of a central vein. Our study was aimed at auditing the performance of 125 consecutive lines over a 2-year period. During this period, insertion was attempted in 125 babies; in 13 cases the line could not be inserted because of technical problems. The gestational ages varied between 25 and 41 weeks and weights between 630 g and 4.2 kg. Success did not appear to be related to the age or weight of the baby. The mean duration of complication-free performance was 22.4 days. There was a significant difference between the complication rate of lines inserted in the operating theatre versus those on the ward (P < 0.05). There was no significant increase in complications in lines used for over 4 weeks. The technique adopted by us for inserting these lines is likely to succeed in the majority of cases, including premature and small-for-dates babies. In our experience, lines inserted in the controlled theatre environment either before or after abdominal surgery performed better. The manufacturer's recommendation to electively change the line every 4 weeks needs further prospective evaluation.

Consensus scoring: A method for obtaining improved hit rates from docking databases of three-dimensional structures into proteins.

We present the results of an extensive computational study in which we show that combining scoring functions in an intersection-based consensus approach results in an enhancement in the ability to discriminate between active and inactive enzyme inhibitors. This is illustrated in the context of docking collections of three-dimensional structures into three different enzymes of pharmaceutical interest: p38 MAP kinase, inosine monophosphate dehydrogenase, and HIV protease. An analysis of two different docking methods and thirteen scoring functions provides insights into which functions perform well, both singly and in combination. Our data shows that consensus scoring further provides a dramatic reduction in the number of false positives identified by individual scoring functions, thus leading to a significant enhancement in hit-rates.

Drug abuse-related mortality: a study of teenage addicts over a 20-year period.

BACKGROUND: There is growing concern about increase in illicit drug use and associated fatalities in young people. METHOD: This longitudinal analysis of successive cohorts of addicts in England and Wales aged 15-19 years followed up over a 20-year period covering 1974 to 1993 (1) investigated trends in all-causes mortality; (2) examined teenage-specific mortality, i.e. deaths during ages 15-19 years; (3) determined excess teenage-specific mortality; and (4) identified the main underlying causes of teenage-specific death in this population. The main outcome measures were overall mortality rates, teenage-specific mortality and standardised mortality ratios calculated for four 5-year (period) successive cohorts. RESULTS: Overall mortality rate in the study population (N = 9491) was 4.7/1000 person-years. The median age at death was 23 years (semi interquartile range = 3), with the majority (91.3%) of deaths occurring between ages 15 and 29 years. Excess teenage-specific mortality in the population was 10.7 in males and 21.2 in females (general population = 1), and increase in excess mortality in both sexes was evident in the last 5-year period of study. The majority of deaths (64.3%) resulted from accidental poisoning. Methadone and heroine/morphine accounted for about two-thirds of accidental poisoning deaths, while suicide accounted for 11.4% of teenage-specific deaths. CONCLUSIONS: It is strongly recommended that treatment services should be more responsive to the need for careful prescribing, dispensing and administration of substitute medication to teenage addicts in their care. The development of needs-led, case-sensitive treatment services for young addicts is indicated.

Suicide among drug addicts in the UK.

BACKGROUND: The extent of suicide among addicts in the UK has not been sufficiently examined. AIMS: To examine suicide trends among registered addicts in the UK over a 25-year period. METHOD: We quantified suicide using International Classification of Diseases (ICD) external death codes E950-959, calculated annual age-standardised suicide rates, standardised mortality ratios (SMRs) and described trends in methods of suicide and drug overdose suicides in five successive cohorts of registered addicts. RESULTS: Male and female suicide rates are 69.0 and 44.8 per 100,000 person-years, respectively. There was a consistent decline in suicide rate throughout the 25-year period. Among males, the SMR for suicide declined from 17.2 in 1968-1972 to 4.4 in 1988-1992 (SMR ratio = 3.9, 95% CI = 2.5-6.1); among females it declined from 52.6 to 11.3 in the same period (SMR ratio = 4.7, 95% CI = 1.9-10.8). Drug overdose was the most common method of suicide, accounting for 45% of cases. Significant increase in antidepressant (percentage difference = 23.5%, 95% CI = 15.2-31.8) and methadone (percentage difference = 11.0%, 95% CI = 0.5, 21.5) overdose in 1988-1992 compared with 1968-1972 was reported. CONCLUSIONS: The findings confirm that addicts are still at higher risk of suicide than the general population and that prescribed drugs, notably antidepressants and methadone, influence this heightened risk.

Cisapride reduces neonatal postoperative ileus: randomised placebo controlled trial.

AIM: To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery. METHODS: A prospective, randomised, double blind trial comparing rectal cisapride (1.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates. RESULTS: Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup. CONCLUSION: Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.

Parenteral nutrition-related cholestasis in postsurgical neonates: multivariate analysis of risk factors.

The medical records of 74 neonates dependent on parenteral nutrition for at least 21 days after emergency abdominal surgery (performed between 1988 and 1992) were reviewed respectively. The role of enteral starvation, prematurity, composition and duration of parenteral nutrition, and sepsis in the evolution of parenteral nutrition-related cholestasis was evaluated by multiple regression analysis. The most important factors for cholestasis were low gestational age (median, 34 weeks), early exposure to parenteral nutrition, and sepsis. Episodes of sepsis were associated with a 30% increase in the bilirubin level. Enteral starvation and composition and the duration of parenteral nutrition solutions did not correlate significantly with the development of cholestasis. Prevention of sepsis should be the priority in minimising cholestasis in postsurgical neonates who are dependent on parenteral nutrition.

Duodenal atresia: a comparison of three modes of treatment.

To determine the most successful mode of treatment, 33 consecutive cases of duodenal atresia treated by duodenoduodenostomy and not associated with other gastro-intestinal anomalies were analysed retrospectively. These patients have been placed in a nonrandomised fashion into one of three groups: Group A: Duodenostomy (side to side) with gastrostomy and transanastomotic feeding tube (n = 12); Group B: Duodenoduodenostomy (diamond shape) with jejunostomy feeding tube (n = 12); Group C: Duodenoduodenostomy (diamond shape) only (n = 9). A nasogastric tube was used in all cases. There was no difference between the groups for gestational age, birthweight, and age at operation. The outcome measures used to compare these groups were the time taken to achieve full preanastomotic feeds and the duration of hospital stay. There was no difference in time taken to achieve full pre-anastomotic feeds between Group A and Group B. Patients in Group C took significantly less time to achieve full pre-anastomotic feeds than either of the other two groups (p < 0.05, Mann-Whitney U). The duration of hospital stay was also significantly shorter for patients in Group C (median = 12 days) than for patients in either Group A or B (median = 24, 20 days respectively) (p < 0.05, Mann-Whitney U).

Partial or near-total pancreatectomy for nesidioblastosis?

We report on 11 consecutive cases of nesidioblastosis successfully managed, in a 22-year period from 1972-1993 at The Children's Hospital, Birmingham, England. In the pre-operative period all patients were managed by constant glucose administration ( > 10 mg/kg/min) and hyperglycaemic agents such as diazoxide, glucagon, growth hormone and somatostatin either singly or in combination. Seven patients underwent partial pancreatectomy, 2 of whom needed a subsequent near-total resection; 4 others had a near-total pancreatectomy as the primary procedure. The 5 patients who have had partial pancreatectomies are healthy and on no regular medication. Of the 6 patients who had near-total pancreatectomy 3 require insulin for diabetes mellitus and 3 are on pancreatin for pancreatic exocrine deficiency. We recommend partial pancreatectomy as the first operation in the treatment of nesidioblastosis.