Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review

This narrative review aims to provide an overview of the current literature on thepharmacology, safety, efficacy and tolerability of intranasal esketamine, the S-enantiomerof ketamine, for the treatment of treatment-resistant depression (TRD). A literature searchusing Medline, Embase, PsycINFO and Cochrane Central was conducted (January 2000 toJuly 2019). Product information and www.clinicaltrials.gov were also reviewed. The literaturesearch was limited to human studies published in English. PhaseI, II, and III studies ofintranasal esketamine for TRD were reviewed. About a third of patients with major depressivedisorder fail to achieve remission despite treatment with multiple antidepressants. Thisarticle examines the trials that led to the approval of esketamine in the United States, aswell as other recent studies of esketamine for TRD. The findings from limited phaseIII trialsillustrate that intranasal esketamine is effective and safe in reducing depressive symptomsand achieving clinical response in patients with TRD. The optimum duration and frequency ofuse are not fully understood. Although the nasal spray is a convenient dosage form, its use inpractice may be limited by cost and administrative regulation. While it may prove beneficialto many patients who suffer from TRD, further long-term data are required, along withcomparative trials with the R-isomer (arketamine). In the interim, care and monitoring shouldbe exercised in its use in clinical practice

Self-directed digital interventions for the improvement of emotion regulation-effectiveness for mental health and functioning in adolescents: protocol for a systematic review.

INTRODUCTION: Research suggests that problems with emotion regulation, that is, how a person manages and responds to an emotional experience, are related to a range of psychological disorders (eg, bipolar disorder, anxiety and depression). Interventions targeting emotion regulation have been shown to improve mental health in adults, but evidence on related interventions for adolescents is still emerging. Increasingly, self-directed digital interventions (eg, mobile apps) are being developed to target emotion regulation in this population, but questions remain about their effectiveness. This systematic review aimed to synthesise evidence on current self-directed digital interventions available to adolescents (aged 11-18 years) and their effectiveness in addressing emotion regulation, psychopathology and functioning (eg, academic achievement). METHODS AND ANALYSIS: Several electronic databases will be searched (eg, MEDLINE, PsycINFO, ACM Digital Library) to identify all studies published any time after January 2010 examining self-directed digital interventions for adolescents, which include an emotion regulation component. This search will be updated periodically to identify any new relevant research from the selected databases. Data on the study characteristics (eg, author(s)) and methodology, participant characteristics (eg, age) and the digital interventions used to address emotion (dys-)regulation (eg, name, focus) will be extracted. A narrative synthesis of all studies will be presented. If feasible, the effectiveness data will be synthesised using appropriate statistical techniques. The methodological quality of the included studies will be assessed with the Effective Public Health Practice Project quality assessment tool. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. Findings will be disseminated widely via peer-reviewed publications and presentations at conferences related to this field. REGISTRATION DETAILS: PROSPERO CRD42022385547

Perceptions of graduating students from eight medical schools in Vietnam on acquisition of key skills identified by teachers

<p>Abstract</p> <p>Background</p> <p>The eight main Vietnamese medical schools recently cooperated to produce a book listing the knowledge, attitudes and skills expected of a graduate, including specification of the required level for each skill. The teaching program should ensure that students can reach that level. The objective of this study was to determine the perception of graduating students on whether they had achieved the level set for a selection of clinical and public health skills as a guide for the schools to adjust either the levels or the teaching.</p> <p>Methods</p> <p>From all eight schools, 1136 of the 1528 final year students completed questionnaires just before completed all the requirements for graduation, a response rate of 87% overall (ranging from 74–99% per school). They rated their own competence on a scale of 0–5 for 129 skills selected from the 557 skills listed in the book, and reported where they thought they had learned them. The scores that the students gave themselves were then compared to the levels proposed by the teachers for each skill. The proportions of the self-assessed achievement to the levels expected by the teachers, means self-assessed scores and the coefficients of variation were calculated to make comparisons among disciplines, among schools and among learning sites.</p> <p>Results</p> <p>Most students felt they had learned most of the skills for key clinical departments to the required level; this varied little among the schools. Self-assessed skill acquisition in public health and minor clinical disciplines was lower and varied more. Sites outside the classroom were especially important for learning skills. The results revealed key similarities and differences between the teachers and the students in their perception about what could be learned and where</p> <p>Conclusion</p> <p>Revising a curriculum for medical schools demands inputs from all stakeholders. Graduating class students can provide valuable feedback on what they have learned in the existing system. Learning objectives should always be checked with students who have followed their study under existing teaching conditions. The information from the graduates helped to identify potential problem areas where either the objectives or the teaching need adjustment.</p

Language Conflict in Algeria: From Colonialism to Post-Independence

Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula. Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy—including foetal malformations, spontaneous abortion and stillbirths—in livestock, and associated with miscarriage in humans. No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy. To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins. ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use. Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats. In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep. Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.</p

The IBER study: a feasibility randomised controlled trial of imagery based emotion regulation for the treatment of anxiety in bipolar disorder

BACKGROUND: Intrusive mental imagery is associated with anxiety and mood instability within bipolar disorder and therefore represents a novel treatment target. Imagery Based Emotion Regulation (IBER) is a brief structured psychological intervention developed to enable people to use the skills required to regulate the emotional impact of these images. METHODS: Participants aged 18 and over with a diagnosis of bipolar disorder and at least a mild level of anxiety were randomly assigned (1:1) to receive IBER plus treatment as usual (IBER + TAU) or treatment as usual alone (TAU). IBER was delivered in up to 12 sessions overs 16 weeks. Clinical and health economic data were collected at baseline, end of treatment and 16-weeks follow-up. Objectives were to inform the recruitment process, timeline and sample size estimate for a definitive trial and to refine trial procedures. We also explored the impact on participant outcomes of anxiety, depression, mania, and mood stability at 16-weeks and 32-weeks follow-up. RESULTS: Fifty-seven (28: IBER + TAU, 27: TAU) participants from two sites were randomised, with 50 being recruited within the first 12 months. Forty-seven (82%) participants provided outcome data at 16 and 32-weeks follow-up. Thirty-five participants engaged in daily mood monitoring at the 32-week follow-up stage. Retention in IBER treatment was high with 27 (96%) attending ≥ 7 sessions. No study participants experienced a serious adverse event. DISCUSSION: The feasibility criteria of recruitment, outcome completion, and intervention retention were broadly achieved, indicating that imagery-focused interventions for bipolar disorder are worthy of further investigation

Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents

A UK population-based case–control study of Hodgkin's disease (HD) in young adults (16–24 years) included 118 cases and 237 controls matched on year of birth, gender and county of residence. The majority (103) of the cases were classified by Epstein–Barr virus (EBV) status (EBV present in Reed–Stenberg cells), with 19 being EBV-positive. Analyses using conditional logistic regression are presented of subject reports of prior infectious disease (infectious mononucleosis (IM), chicken pox, measles, mumps, pertussis and rubella). In these analyses HD cases are compared with matched controls, EBV-positive cases and EBV-negative cases are compared separately with their controls and formal tests of differences of association by EBV status are applied. A prior history of IM was positively associated with HD (odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.10–5.33) and with EBV-positive HD (OR = 9.16, 95% CI = 1.07–78.31) and the difference between EBV-positive and EBV-negative HD was statistically significant (P = 0.013). The remaining infectious illnesses (combined) were negatively associated with HD, EBV-positive HD and EBV-negative HD (in the total series, for ≥2 episodes compared with ≤1, OR = 0.45, 95% CI = 0.25–0.83). These results support previous evidence that early exposure to infection protects against HD and that IM increases subsequent risk; the comparisons of EBV-positive and EBV-negative HD are new and generate hypotheses for further study. © 2000 Cancer ResearchCampaig

The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

The use of biomedicine, complementary and alternative medicine, and ethnomedicine for the treatment of epilepsy among people of South Asian origin in the UK

Studies have shown that a significant proportion of people with epilepsy use complementary and alternative medicine (CAM). CAM use is known to vary between different ethnic groups and cultural contexts; however, little attention has been devoted to inter-ethnic differences within the UK population. We studied the use of biomedicine, complementary and alternative medicine, and ethnomedicine in a sample of people with epilepsy of South Asian origin living in the north of England. Interviews were conducted with 30 people of South Asian origin and 16 carers drawn from a sampling frame of patients over 18 years old with epilepsy, compiled from epilepsy registers and hospital databases. All interviews were tape-recorded, translated if required and transcribed. A framework approach was adopted to analyse the data. All those interviewed were taking conventional anti-epileptic drugs. Most had also sought help from traditional South Asian practitioners, but only two people had tried conventional CAM. Decisions to consult a traditional healer were taken by families rather than by individuals with epilepsy. Those who made the decision to consult a traditional healer were usually older family members and their motivations and perceptions of safety and efficacy often differed from those of the recipients of the treatment. No-one had discussed the use of traditional therapies with their doctor. The patterns observed in the UK mirrored those reported among people with epilepsy in India and Pakistan. The health care-seeking behaviour of study participants, although mainly confined within the ethnomedicine sector, shared much in common with that of people who use global CAM. The appeal of traditional therapies lay in their religious and moral legitimacy within the South Asian community, especially to the older generation who were disproportionately influential in the determination of treatment choices. As a second generation made up of people of Pakistani origin born in the UK reach the age when they are the influential decision makers in their families, resort to traditional therapies may decline. People had long experience of navigating plural systems of health care and avoided potential conflict by maintaining strict separation between different sectors. Health care practitioners need to approach these issues with sensitivity and to regard traditional healers as potential allies, rather than competitors or quacks