Progesterone receptor mediates ovulatory transcription through RUNX transcription factor interactions and chromatin remodelling.

Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that culminates in follicle rupture. However, the molecular mechanisms for this specialized PGR function in ovulation is poorly understood. We have assembled a detailed genomic profile of PGR action through combined ATAC-seq, RNA-seq and ChIP-seq analysis in wildtype and isoform-specific PGR null mice. We demonstrate that stimulating ovulation rapidly reprograms chromatin accessibility in two-thirds of sites, correlating with altered gene expression. An ovary-specific PGR action involving interaction with RUNX transcription factors was observed with 70% of PGR-bound regions also bound by RUNX1. These transcriptional complexes direct PGR binding to proximal promoter regions. Additionally, direct PGR binding to the canonical NR3C motif enable chromatin accessibility. Together these PGR actions mediate induction of essential ovulatory genes. Our findings highlight a novel PGR transcriptional mechanism specific to ovulation, providing new targets for infertility treatments or new contraceptives that block ovulation.

Granulosa cell metabolism at ovulation correlates with oocyte competence and is disrupted by obesity and aging.

STUDY QUESTION: Is oocyte developmental competence associated with changes in granulosa cell (GC) metabolism? SUMMARY ANSWER: GC metabolism is regulated by the LH surge, altered by obesity and reproductive aging, and, in women, specific metabolic profiles are associated with failed fertilization versus increased blastocyst development. WHAT IS KNOWN ALREADY: The cellular environment in which an oocyte matures is critical to its future developmental competence. Metabolism is emerging as a potentially important factor; however, relative energy production profiles between GCs and cumulus cells and their use of differential substrates under normal in vivo ovulatory conditions are not well understood. STUDY DESIGN, SIZE, DURATION: This study identified metabolic and substrate utilization profiles within ovarian cells in response to the LH surge, using mouse models and GCs of women undergoing gonadotropin-induced oocyte aspiration followed by IVF/ICSI. PARTICIPANTS/MATERIALS, SETTING, METHODS: To comprehensively assess follicular energy metabolism, we used real-time metabolic analysis (Seahorse XFe96) to map energy metabolism dynamics (mitochondrial respiration, glycolysis, and fatty acid oxidation) in mouse GCs and cumulus-oocyte complexes (COCs) across a detailed time course in the lead up to ovulation. In parallel, the metabolic profile of GCs was measured in a cohort of 85 women undergoing IVF/ICSI (n = 21 with normal ovarian function; n = 64 with ovarian infertility) and correlated with clinical parameters and cycle outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Our study reveals dynamic changes in GC energy metabolism in response to ovulatory LH, with mitochondrial respiration and glycolysis differentially affected by obesity versus aging, in both mice and women. High respiration in GCs is associated with failed fertilization (P < 0.05) in a subset of women, while glycolytic reserve and mitochondrial ATP production are correlated with on-time development at Day 3 (P < 0.05) and blastocyst formation (P < 0.01) respectively. These data provide new insights into the cellular mechanisms of infertility, by uncovering significant associations between metabolism within the ovarian follicle and oocyte developmental competence. LIMITATIONS, REASONS FOR CAUTION: A larger prospective study is needed before the metabolic markers that were positively and negatively associated with oocyte quality can be used clinically to predict embryo outcomes. WIDER IMPLICATIONS OF THE FINDINGS: This study offers new insights into the importance of GC metabolism for subsequent embryonic development and highlights the potential for therapeutic strategies focused on optimizing mitochondrial metabolism to support embryonic development. STUDY FUNDING/COMPETING INTEREST(S): National Health and Medical Research Council (Australia). The authors have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The Success of Mifepristone and Misoprostol in the Management of Early Pregnancy Loss at a Community Hospital: A Prospective Study.

BACKGROUND: This prospective single-arm study was conducted to understand the expulsion rate of the gestational sac in the management of early pregnancy loss (EPL). METHODS: We recruited 441 participants; 188 met eligibility criteria. Participants were 18 years of age and older who experienced a confirmed early pregnancy loss (<12 weeks gestational age) defined by an intrauterine pregnancy with a non-viable embryonic or anembryonic gestational sac with no fetal heart activity. Participants were given 200 mg of mifepristone pretreatment orally followed by two doses of misoprostol 800 mcg vaginally after 24 and 48 hours. Participants were seen in follow-up on day 14 to confirm the absence of a gestational sac, classified as treatment success. For failed treatment (defined by retained gestational sac), we offered expectant management or a third dose of misoprostol and/or dilatation and curettage (D & C). We followed all participants for 30 days. We collected data on overtreatment for retained products of conception and hospital admissions for adverse events. RESULTS: 181 participants followed the protocol, and 169 (93.3%) participants had a complete expulsion of the gestational sac by the second visit (day 14). Twelve (6.6%) failed the treatment and one had an adverse event of heavy vaginal bleeding requiring D & C. Despite the expulsion of the gestational sac, 29 cases (17.1%) at subsequent follow-up were diagnosed as retained products of conception based on ultrasound assessment of thickened endometrium. CONCLUSION: Pretreatment with mifepristone followed by 2 doses of misoprostol with a 14-day follow-up resulted in a high expulsion rate and is a safe management option for EPL.

Correction: Internet Tool to Support Self-Assessment and Self-Swabbing of Sore Throat: Development and Feasibility Study.

[This corrects the article DOI: 10.2196/39791.].

Coping strategies as a causal mediator of the effect of loss-related memory characteristics and negative loss-related appraisals on symptoms of PGD, PTSD and depression.

BACKGROUND: Psychological models of posttraumatic stress disorder (PTSD) and prolonged grief disorder (PGD) make predictions about the role of unhelpful coping strategies in maintaining difficulties by blocking self-correction of negative appraisals and memory integration following stressful life events like bereavement. However, few studies have tested these predictions directly. METHOD: We used counterfactually based causal mediation to assess whether unhelpful coping strategies mediated the relationship between (1) loss-related memory characteristics and/or (2) negative grief-related appraisals and symptoms of PGD, PTSD and depression using a three-wave longitudinal sample (N = 275). Appraisals and memory characteristics were measured at time point 1, unhelpful coping strategies at T2, and symptom variables at T3. Additionally, multiple mediation analyses within a structural equation modelling (SEM) framework assessed which types of coping strategies differentially mediated symptoms of PGD, PTSD and depression. RESULTS: Coping strategies mediated the relationship between negative appraisals and memory characteristics and symptoms of PGD, PTSD and depression after adjusting for demographics and loss characteristics. Sensitivity analyses suggested that these results were most robust for PGD, followed by PTSD and then depression. Multiple mediation analyses suggested that all four subscales (avoidance, proximity seeking, loss rumination and injustice rumination) individually mediated the effect of memory characteristics and appraisals on PGD. CONCLUSIONS: These results suggest that core predictions of the cognitive model for PTSD and the cognitive behavioural model of PGD are useful in predicting symptoms of post-loss mental health problems in the first 12-18 months after loss. Targeting unhelpful coping strategies is likely to reduce symptoms of PGD, PTSD and depression.

'I accept his manhood is on life-support': A qualitative understanding of the impact of diabetes on sexual relationships among men and women living with type 2 diabetes and their partners in South Africa.

AIMS: To explore the impact of diabetes on sexual relationships among men and women living with type 2 diabetes People living with type 2 diabetes (PLWD) and their partners in Cape Town, South Africa. METHODS: As part of a larger study developing an intervention to improve type 2 diabetes mellitus (T2DM) self management, we conducted in-depth individual interviews with 10 PLWD and their partners without diabetes about experiences living with T2DM, between July 2020 and January 2021. We used inductive thematic analysis. RESULTS: Both PLWD and partners felt that their sexual relationships and desires changed post-diagnosis, in ways beyond biomedical issues. Although couples' reports on the quality of their sexual relationships were concordant, most participants had not communicated their sexual desires and concerns with each other, causing unhappiness and fears of disappointing or losing their partner. Participants felt uninformed about sexual dysfunction but had not discussed this with their healthcare provider, leading to increased anxiety. CONCLUSION: PLWD and their partners need more informational support to increase their understanding of diabetes-associated sexual dysfunction and to decrease fears and anxiety. Strengthening communication within couples on sexual issues may empower them to find solutions to problems experienced. This may improve couples' relationships and quality of life, and indirectly result in better self management of T2DM.

Internet Tool to Support Self-Assessment and Self-Swabbing of Sore Throat: Development and Feasibility Study.

BACKGROUND: Sore throat is a common problem and a common reason for the overuse of antibiotics. A web-based tool that helps people assess their sore throat, through the use of clinical prediction rules, taking throat swabs or saliva samples, and taking throat photographs, has the potential to improve self-management and help identify those who are the most and least likely to benefit from antibiotics. OBJECTIVE: We aimed to develop a web-based tool to help patients and parents or carers self-assess sore throat symptoms and take throat photographs, swabs, and saliva samples for diagnostic testing. We then explored the acceptability and feasibility of using the tool in adults and children with sore throats. METHODS: We used the Person-Based Approach to develop a web-based tool and then recruited adults and children with sore throats who participated in this study by attending general practices or through social media advertising. Participants self-assessed the presence of FeverPAIN and Centor score criteria and attempted to photograph their throat and take throat swabs and saliva tests. Study processes were observed via video call, and participants were interviewed about their views on using the web-based tool. Self-assessed throat inflammation and pus were compared to clinician evaluation of patients' throat photographs. RESULTS: A total of 45 participants (33 adults and 12 children) were recruited. Of these, 35 (78%) and 32 (71%) participants completed all scoring elements for FeverPAIN and Centor scores, respectively, and most (30/45, 67%) of them reported finding self-assessment relatively easy. No valid response was provided for swollen lymph nodes, throat inflammation, and pus on the throat by 11 (24%), 9 (20%), and 13 (29%) participants respectively. A total of 18 (40%) participants provided a throat photograph of adequate quality for clinical assessment. Patient assessment of inflammation had a sensitivity of 100% (3/3) and specificity of 47% (7/15) compared with the clinician-assessed photographs. For pus on the throat, the sensitivity was 100% (3/3) and the specificity was 71% (10/14). A total of 89% (40/45), 93% (42/45), 89% (40/45), and 80% (30/45) of participants provided analyzable bacterial swabs, viral swabs, saliva sponges, and saliva drool samples, respectively. Participants were generally happy and confident in providing samples, with saliva samples rated as slightly more acceptable than swab samples. CONCLUSIONS: Most adult and parent participants were able to use a web-based intervention to assess the clinical features of throat infections and generate scores using clinical prediction rules. However, some had difficulties assessing clinical signs, such as lymph nodes, throat pus, and inflammation, and scores were assessed as sensitive but not specific. Many participants had problems taking photographs of adequate quality, but most were able to take throat swabs and saliva samples.

Kava (Piper methysticum) in the United States: the quiet rise of a substance with often subtle effects.

Background: Piper methysticum, commonly called kava, has long been consumed in beverage form in the Pacific Islands. Kava use in the US has slowly increased since the 1990s, but is not assessed in major epidemiological surveys.Objectives: To analyze social-media posts about kava from current, past, and prospective users, for motivations, patterns of co-use, and effects.Methods: Text from Reddit posts, and accompanying metadata, were collected and thematically coded by two independent raters.Results: 423 posts were collected, spanning January 2006 through December 2021. Of the 1,211 thematic codes applied, 1,098 (90. 7%) were concordant. Motivations for use bifurcated into self-treatment (for psychiatric or physical health conditions) and recreation; these were not mutually exclusive. Kava was rarely considered strongly euphoriant, but was valued as an anxiolytic. Kava was frequently used with other substances, most commonly kratom. Kava was used at lower doses for self-treatment than for other purposes (pseudo-R2 = 0.11). Undesirable effects (gastrointestinal upset, fatigue) were mentioned, though less often than benefits. Hepatotoxicity, reported elsewhere as a rare, non-dose-related risk, was disputed on the basis of its not having been experienced by those posting.Conclusion: Kava appears to be conceptualized among Reddit posters as an anxiolytic with few risks or adverse effects. As it grows in popularity, especially among people who use other drugs that are more liable to misuse or addiction, it should be assessed in probability samples (i.e. in the major national drug surveys) and clinical practice for its risks, potential benefits, and possible drug-drug interactions.

How the bereaved behave: a cross-cultural study of emotional display behaviours and rules.

Cultural norms may dictate how grief is displayed. The present study explores the display behaviours and rules in the bereavement context from a cross-cultural perspective. 86 German-speaking Swiss and 99 Chinese bereaved people who lost their first-degree relative completed the adapted bereavement version of the Display Rules Assessment Inventory. Results indicated that the German-speaking Swiss bereaved displayed more emotions than the Chinese bereaved. The Chinese bereaved, but not the German-speaking Swiss bereaved, thought that bereaved people should display more emotions than they actually did when they were with their close others (but not when they were alone). Bereaved people endorsed more emotional expression "when alone" than "when with close others", demonstrating a social disconnection tendency, which was more evident in the Chinese sample. Bereaved people endorsed more expression of positive emotions (e.g. affection/love) and less expression of powerful negative emotions (e.g. blame/guilt, anger) across cultures. Compared to their Chinese counterparts, the German-speaking Swiss sample indicated more actual expressions for most emotion types (i.e. joy/happiness, affection/love, sadness, anger, and denial) but thought bereaved people should express more joy/happiness and less blame/guilt. The results suggest that bereaved people's display behaviours and rules are influenced by culture, situation, and type of emotion.

Factors Associated with High-Risk Substance Use in Persons Receiving Psychiatric Treatment for a Primary Trauma- and Stressor-Related Disorder Diagnosis.

OBJECTIVE: Although mental health disorders and high-risk substance use frequently co-occur, they are typically investigated independently. Clinical trials focused on treatment for individuals with trauma- and stressor-related disorders often exclude individuals with high-risk substance use. Little is also known about the role of gender in the relationship between trauma- and stressor-related disorders and high-risk substance use. We examined the relationship between trauma- and stressor-related disorders, high-risk substance use, and gender. METHODS: Using the Mental Health Client-Level Data dataset, we examined 15,772 adults receiving treatment in psychiatric hospitals in the United States from 2013 to 2019. RESULTS: A logistic regression model showed that for men, relative to women, having multiple mental health diagnoses and having a serious mental illness or serious emotional disturbance was associated with greater odds of high-risk substance use. CONCLUSIONS: This study underscores the value of comprehensive gender-centered treatment for people with trauma- and stressor-related disorders engaging in high-risk substance use.

Existential isolation and prolonged grief in bereaved people: The moderating role of culture.

OBJECTIVE: Existential isolation refers to an individual's awareness of the unbridgeable gulf between oneself, other people and the world. This kind of isolation has been found to be higher in individuals with nonnormative experiences, such as racial or sexual minorities. Bereaved individuals may experience a stronger sense of existential isolation and feel that no one shares their feelings or perceptions. However, research on bereaved people's experiences of existential isolation and its effects on post-loss adaptation is scarce. This study aims to validate the German and Chinese versions of the Existential Isolation Scale, investigate cultural and gender differences in existential isolation and explore the associations between existential isolation and prolonged grief symptoms in German-speaking and Chinese bereaved individuals. METHODS: A cross-sectional study with 267 Chinese and 158 German-speaking bereaved participants was conducted. The participants completed self-report questionnaires assessing existential isolation, prolonged grief symptoms, social networks, loneliness and social acknowledgement. RESULTS: The results indicated that the German and Chinese versions of the Existential Isolation Scale demonstrated adequate validity and reliability. No cultural or gender differences (or their interaction) were found for existential isolation. Higher existential isolation was associated with elevated prolonged grief symptoms, which was further moderated by the cultural group. The relationship between existential isolation and prolonged grief symptoms was significant for the German-speaking bereaved people but not significant for those from China. CONCLUSION: The findings highlight the role of existential isolation in the adaptation to bereavement and how different cultural backgrounds moderate the effect of existential isolation on post-loss reactions. Theoretical and practical implications are discussed.

Effects of a modern exhibit design on captive tiger welfare.

Offering captive animals larger, more complex spaces are thought to benefit their welfare. To this end, some zoos use trail systems linked to several enclosures. Since little is known about the effects of such designs on the welfare of captive carnivores specifically, we timed the behaviors exhibited by four tigers (Panthera tigris [Linnaeus]) given access to three exhibit configurations: one exhibit only (E, baseline); one exhibit and approximately 19 m2 of trail (ET); and two exhibits connected by approximately 46 m2 of trail (E2T). Behaviors were recorded during 1-h AM, Noon, and PM periods in Phase I (2017), and 2-h AM and PM periods in Phase II (2018). Percentages of behavior occurrence were analyzed using generalized linear mixed models (GLMM), with treatment and time of day as fixed effects. Tigers were least active at noon (Phase I), while active behaviors were prevalent during mornings and afternoons in both Phases. In Phase II (E2T vs. E), active and exploratory behaviors such as sniffing increased, while pacing and inactivity decreased (all p ≤ .001). We also examined nocturnal tiger movement using infrared motion-activated cameras. In parallel with diurnal observations, tiger activity in E2T greatly exceeded that in E. Nocturnal movement was most pronounced from 1800 to 2200 and least frequent from 0100 to 0400, closely matching patterns observed in the wild. Results indicate that offering tigers voluntary access to larger and more complex spaces stimulates natural behaviors and decreases stereotypical behaviors.

Kratom use as more than a "self-treatment".

Background: Mitragyna speciosa (kratom) is increasingly used in the United States for its pharmacological effects. Kratom's relative novelty makes for a dynamic situation, such that use motivations are not firmly established and may be changing. Investigators and clinicians require frequent updates on kratom trends.Objectives: To assess the current state of kratom-use initiation, sourcing, motivations, preference, conceptualizations, and perceived stigma, using survey responses from current and former users.Methods: Between April-May 2021 we recontacted 289 respondents who reported lifetime kratom use (on an unrelated survey) to answer kratom-specific questions.Results: The sample (N=129) was majority female (51.9%) and white (71.9%). Most (69.0%) reported first trying kratom after 2015. Mean age of use initiation (29.9 years) was older than for other substances, including opioids. Kratom ranked as a preferred substance by 48.5%. The strongest drug association with past-year kratom use was vaped nicotine (OR=3.31,95% CI 1.23-8.88). Use was less likely among those prescribed buprenorphine in the past year (OR=0.03, CI 0.01-0.28). Past-month cannabis use (OR=4.18,CI 1.80-9.72) had the strongest association with past-month kratom use. Over 40 use motivations were endorsed, many (but not all) supporting the "self-treatment" narrative of kratom use, including use as an opioid, alcohol, or stimulant substitute. Treatment shortfalls were associated with decisions to try kratom.Conclusions: Kratom use motivations are diversifying, with multiple factors driving use. As sales continue to increase, the public-health, clinical, and policy responses to kratom should be grounded in rigorous bench-to-bedside scientific research. Comprehensive study of kratom is currently lacking.

Exploring the self-reported motivations of kratom (Mitragyna speciosa Korth.) use: a cross-sectional investigation.

Background: Kratom (Mitragyna speciosa Korth.) use outside of Southeast Asia has increased over the past decade. Objectives: This investigation clarifies kratom's role in perceived well-being, overall health, and temporal correlation with drug use to understand kratom's role in the self-treatment of substance use disorders (SUDs). Methods: Between July 2019 and July 2020 an anonymous, cross-sectional, online survey was taken by 7,381 people who use kratom (PWUK) recruited through social media and other online resources. This included an assessment of (a) the relationship between self-reported overall health, concomitant use of drugs of misuse, and demographics; (b) the perceived effectiveness of kratom in self-treating diagnosed health conditions or symptoms; (c) the profile of PWUK primarily for drug dependence, pain, and mood or mental health conditions based on demographics. Results: A total of 5,152 valid responses (45.9% females/53.7% males) were collected. Kratom was primarily used for self-treating pain (73.0%) and improving emotional or mental health conditions (42.2%) without clinical supervision. Those with a SUD (synthetic opioids, methadone, benzodiazepines, or heroin) used kratom after discontinuing illicit or other drugs (94.8%). The primary substances taken before or concomitantly with kratom were cannabis, cannabidiol, benzodiazepines, or kava. PWUKs report a dose-dependent benefit for alleviating pain and relieving negative moods. Adverse effects were primarily gastrointestinal, typically at high (>5 g/dose) and frequent (>22 doses/week) dosing. Conclusions: Kratom was primarily used as a harm-reduction agent for SUDs and self-treatment of chronic conditions. Healthcare professionals need better information about kratom, its potential adverse effects, and clinically significant drug interactions.

How essential is kratom availability and use during COVID-19? Use pattern analysis based on survey and social media data.

Background: Kratom, a tree native to Southeast Asia, is increasingly used in Western countries for self-treatment of pain, psychiatric disorders, and mitigation of withdrawal symptoms from drugs of abuse. Because kratom is solely supplied from its native locations, supply shortages during the COVID-19 pandemic may impact the availability of preparations and hence force consumers to change their patterns of use. The aim of this study was to understand if and how COVID-19 was influencing kratom purchasing and use. Methods: Additional questions specific to kratom availability and changes in use during COVID-19 were added to an international online survey with responses collected between January and July 2020. During the same period, kratom-related social media posts to Twitter, Reddit, and Bluelight were analyzed for themes similar to the survey questions. Results: The survey results indicated no changes in kratom use patterns although the sample size was relatively small (n = 70) with younger consumers reporting a potential issue in obtaining their desired products from their usual sources. The survey respondents identified primarily as non-Hispanic whites (87.1%). Social media themes revolved primarily around quitting kratom during COVID-19, misinformation about the effects of kratom on COVID-19, and other non-COVID-related discussions. While some consumers may increase their kratom dose because of additional stress, a majority of discussions centered around reducing or rationing kratom due to COVID-19 or a perceived dependence. Access to quality kratom products was also a major discussion topic on social media. Conclusions: Kratom use patterns did not change due to COVID-19 but consumers were concerned about potential product shortages and resulting quality issues. Clinicians and public health officials need to be informed and educated about kratom use as a potential mitigation strategy for substance use disorders and for self-treatment of pain.

Need for clarity and context in case reports on kratom use, assessment, and intervention.

This Letter to the Editor is a response to Broyan and colleagues who recently published a Case Report presenting data on 28 patients in the United States who identified kratom as their primary substance of use and who were subsequently induced on buprenorphine/naloxone for a reported diagnosis of kratom use disorder. We applaud the authors for helping to advance the science on kratom and recognize the difficulties in conducting kratom-related clinical assessment and research. However, a number of inconsistences and generalizations were identified in this Case Report, which also lacked some critical context. Importantly, such inconsistencies and generalizations can be observed throughout kratom-specific case reports. We feel this is now an important opportunity to highlight these issues that are present in the Broyan and colleagues Case report but emphasize that they are not unique to it. We do this with the hope that by acknowledging these issues it can help inform editors, clinicians, and researchers who may not be familiar with kratom and, as a result of this unfamiliarity, may inadvertently present findings in a manner that could confuse readers and even misinform clinical researchers and practitioners.

Systematic Debriefing for Critical Events Facilitates Team Dynamics, Education, and Process Improvement.

BACKGROUND: Debriefing is used in clinical settings to support interprofessional staff, improve processes, and identify educational needs. Nurses who lead debriefing sessions are empowered to improve processes. PROBLEM: Nurse leaders identified the need for debriefing outside the critical care areas due to the rising acuity levels. APPROACH: Two nurse leaders developed a debriefing initiative in one urban teaching hospital following rapid responses, codes, and stressful situations. Nurses developed a Debriefing Facilitation Guide to collect qualitative aspects of clinical emergencies to improve processes, education, and team dynamics. OUTCOMES: Following each debriefing session, we deductively purposively coded the qualitative data into 3 a priori themes: the American Heart Association's team dynamics, process improvement, and educational opportunities. We identified opportunities for improvement for these themes during our first 54 debriefing sessions. CONCLUSIONS: Following each debriefing session, the debriefing nurse leader intervened on all educational and process improvement opportunities identified and facilitated positive team dynamics.

Support needs and barriers to accessing support: Baseline results of a mixed-methods national survey of people bereaved during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is a mass bereavement event which has profoundly disrupted grief experiences. Understanding support needs and access to support among people bereaved at this time is crucial to ensuring appropriate bereavement support infrastructure. AIM: To investigate grief experiences, support needs and use of formal and informal bereavement support among people bereaved during the pandemic. DESIGN: Baseline results from a longitudinal survey. Support needs and experiences of accessing support are reported using descriptive statistics and thematic analysis of free-text data. SETTING/PARTICIPANTS: 711 adults bereaved in the UK between March and December 2020, recruited via media, social media, national associations and community/charitable organisations. RESULTS: High-level needs for emotional support were identified. Most participants had not sought support from bereavement services (59%, n = 422) or their General-Practitioner (60%, n = 428). Of participants who had sought such support, over half experienced difficulties accessing bereavement services (56%, n = 149)/General-Practitioner support (52%, n = 135). About 51% reported high/severe vulnerability in grief; among these, 74% were not accessing bereavement or mental-health services. Barriers included limited availability, lack of appropriate support, discomfort asking for help and not knowing how to access services. About 39% (n = 279) experienced difficulties getting support from family/friends, including relational challenges, little face-to-face contact and disrupted collective mourning. The perceived uniqueness of pandemic bereavement and wider societal strains exacerbated their isolation. CONCLUSIONS: People bereaved during the pandemic have high levels of support needs alongside difficulties accessing support. We recommend increased provision and tailoring of bereavement services, improved information on support options and social/educational initiatives to bolster informal support and ameliorate isolation.

When an obscurity becomes trend: social-media descriptions of tianeptine use and associated atypical drug use.

Background: Originally believed to be an atypical antidepressant acting at serotonin transporters, tianeptine is now known to also be an atypical agonist at mu-opioid receptors. Its nonmedical use may be increasing amidst the broader context of novel drug and supplement use.Objectives: To analyze social-media text from current, former, and prospective tianeptine users for better understanding of their conceptualizations of tianeptine, motives for and patterns of use, and reported benefits and harms.Methods: Reddit posts were obtained and thematically coded; additional quantitative analyses were conducted.Results: A total of 210 posts mentioning tianeptine were made between 2012 and 2020. Eighteen thematic categories were identified, 10 of which were consistent with expected themes. Two independent raters coded all text, generating 1,382 unique codes, of which 1,090 were concordant (78.9% interrater agreement). Tianeptine use was frequently associated with use of other drugs, particularly kratom, phenibut, and racetams. People conceptualized and variously used tianeptine as an opioid, antidepressant, and "nootropic" (cognitive enhancer). Between 2014 and 2020, mentions of positive effects decreased, while mentions of adverse effects and withdrawal increased. Motivations for use included substitution or withdrawal mitigation for other drugs (especially opioids) and for kratom itself; self-treatment for psychiatric symptoms; and improvement of quality of life, mood, or performance. Descriptions of tolerance, withdrawal, and addiction were evident. Intravenous use was rare and strongly discouraged, with detrimental effects described.Conclusion: Tianeptine is recognized as an opioid (though not only an opioid) in online communities. Posts describe benefits, acute risks, and patterns of co-use that warrant greater clinical attention.

A Qualitative Exploration of Perceptions of a Digital Intervention to Promote Physical Activity in Older Adults.

PURPOSE: This study explored participant views of a web-based physical activity intervention for older adults and examined how they resonate with the key principles that guided intervention development. METHODS: Qualitative interviews were carried out with 52 older adults. A deductive qualitative analysis approach was taken, based around the intervention's key principles. RESULTS: Participants expressed mostly positive views of the intervention features, broadly confirming the appropriateness of the key principles, which were to: (a) encourage intrinsic motivation for physical activity, (b) minimize the risk of users receiving activity suggestions that are inappropriate or unsafe, (c) offer users choice regarding the activities they engage with and build confidence to undertake more activity, and (d) minimize the cognitive load and need to engage with the intervention website. The findings also identified ways in which content could be improved to further increase acceptability. CONCLUSION: This study illustrates how using the person-based approach has enabled the identification and implementation of features that older adults appreciate.