•Factors that are experienced as distressing are understudied within bipolar.•Themes surrounding loss, uncertainty and threat were highlighted.•Stigma and fearing relapse interlinked other areas of ...reported distress.•Interventions focus on symptom reduction, not what is described as most distressing.•Findings were not specific to bipolar, suggesting possible transdiagnostic factors.
Bipolar disorder (BD) is considered to have a significantly negative impact on functioning and prognosis is considered poor. Current treatments are modestly effective and predominantly focus on reducing extreme mood fluctuations and symptoms, yet less is known about what patients themselves describe as distressing. Therefore we aimed to assess this through a systematic review.
A comprehensive literature search was conducted in four major bibliographic databases in August 2017, updated in July 2018. Qualitative studies exploring BD were included if they contained themes related to distress. First person accounts from people with BD discussing what they experience as distressing were extracted and synthesised using thematic synthesis. Author interpretations were also extracted to support the synthesis.
Twenty-four studies were included. Five main analytical themes were developed: 1) diagnosis, 2) loss, 3) uncertainty, 4) threat and 5) relationships. Two further crosscutting themes were identified as 1) stigma and 2) fear of relapse. Implications for interventions to focus on these causes of distress also emerged.
The included studies did not adequately examine the authors’ potential own biases and influences within their interpretations of the data. One author predominantly undertook data extraction and coding for the current review, although research team discussions led to an agreed consensus on themes.
This was the first qualitative study to specifically explore distress in BD. The meta-synthesis highlights important areas that people with BD experience as distressing. Adaptations to current interventions, to focus on what people find distressing could seek to improve treatment outcomes.
The quality of parent-child relationships during adolescence has the potential to impact adolescents' mental health. This study explored how seven dyads (parent-child) might experience a ...two-component intervention (Method of Levels therapy-MOL and a parent-child activity) over four months. Following this, six dyads were interviewed and a thematic analysis was conducted. The most helpful aspect of the intervention for participants was the opportunity to talk. The intervention facilitated helpful conversations that increased participants' awareness and broadened their perspective on the topics discussed. This process helped participants find solutions to their problems. Young people and parents reported that the Shared Goals activity helped them improve their communication and relationships. Young people stated that MOL allowed them to figure things out for themselves.
Psychological difficulties among young people are common. Various initiatives are being proposed in schools, yet no evidence-based data is available on how to address family difficulties (the most ...prevalent issues in school-based counselling). The current study examined the use of a two-component intervention based on the principles of Perceptual Control Theory (PCT). One is Method of Levels therapy (MOL) and the other is a parent-child activity (Shared Goals). Young people were invited to choose how often to engage in both MOL and the Shared Goals activity as well as the topics discussed during sessions for four months. Seven dyads were recruited and six were retained. At the end of the intervention, five young people were considered recovered.
Bipolar disorder (BD) is considered a severe and lifelong mental health diagnosis. However, there is growing evidence of people defying the odds and recovering. Processes underlying recovery remain ...poorly understood. This study aimed to explore these recovery processes and extend on the length of recovery defined within previous research. Twelve people previously diagnosed with BD, who had not experienced an episode of depression and/or mania for four or more years, were interviewed. Standardised diagnostic interviews (Structured Clinical Interview for Diagnostic and Statistical Manual‐V, Research version) confirmed past diagnosis and recovery time. Qualitative methodology via grounded theory was used to analyse these personal accounts. The analysis revealed 10 overarching categories of what participants reported to be important in their recovery: support, recognition of the problem, believing that things can change and not giving up, instinctive curiosity, medication, psychological therapy, becoming the director of your own life, changing how I think, accepting who I am and how I feel, and looking after me. A model was developed to represent how categories were related. The study was limited by recruitment not leading to the inclusion of people who had distanced themselves from the label of BD. Potential transdiagnostic recovery processes also require further direct exploration. Critically, the study highlights that following a diagnosis of BD, people do experience long‐term recovery achieved through self‐determined pathways and that being able to live the life you want is therefore achievable. This challenges current diagnostic perspectives and societal messages of lifelong conditions.
Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound ...healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans.
Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care ...treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer.
KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636.
Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7–30·4). Median overall survival was 12·7 months (95% CI 11·5–13·6) in the pembrolizumab group versus 10·9 months (9·9–11·6) in the placebo group (hazard ratio 0·83 95% CI 0·72–0·95; one-sided p=0·0034 significance threshold, p=0·0200). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events.
Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer.
Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
Research that examines the intersections of Indigenous Peoples' health and wellbeing with climate change and biodiversity loss is abundant in the global scholarship. A synthesis of this evidence base ...is crucial in order to map current pathways of impact, as well as to identify responses across the global literature that advance Indigenous health and wellbeing, all while centering Indigenous voices and perspectives. This protocol details our proposed methodology to systematically conduct an umbrella review (or review of reviews) of the synthesized literature on climate change, biodiversity loss, and the health and wellbeing of Indigenous Peoples globally.
A multidisciplinary team of Indigenous and non-Indigenous scholars will conduct the review, guided by an engagement process with an Indigenous Experts group. A search hedge will be used to search PubMed®, Scopus®, Web of Science™, CINAHL (via EBSCOHost®), and Campbell Collaboration databases and adapted for use in grey literature sources. Two independent reviewers will conduct level one (title/abstract) and level two (full-text) eligibility screening using inclusion/exclusion criteria. Data will be extracted from included records and analyzed using quantitative (e.g., basic descriptive statistics) and qualitative methods (e.g., thematic analysis, using a constant comparative method).
This protocol outlines our approach to systematically and transparently review synthesized literature that examines the intersections of climate change, biodiversity loss, and Indigenous Peoples' health and wellbeing globally.
This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on April 24, 2023 (registration number: CRD42023417060).
This study investigated clinical and process factors involved in a client-led psychological intervention (Method of Levels therapy - MOL). MOL offered 16 adolescents choice and control over ...attendance (by using a self-booking system) and topics discussed in sessions. Process measures examining empowerment and ability to resolve psychological conflict were used to explore the impact MOL might have on these. Young people booked a wide-ranging number of sessions at differing intervals and set goals related to their emotional or mental wellbeing. On completion, the majority of adolescents displayed an increase in scores for empowerment and ability to resolve psychological conflict and overall distress levels decreased. Benefits were sustained two months after completion of the study.
Baclofen is a racemic GABA(B) receptor agonist that has a number of significant pharmacokinetic limitations, including a narrow window of absorption in the upper small intestine and rapid clearance ...from the blood. Arbaclofen placarbil is a novel transported prodrug of the pharmacologically active R-isomer of baclofen designed to be absorbed throughout the intestine by both passive and active mechanisms via the monocarboxylate type 1 transporter. Arbaclofen placarbil is rapidly converted to R-baclofen in human and animal tissues in vitro. This conversion seems to be primarily catalyzed in human tissues by human carboxylesterase-2, a major carboxylesterase expressed at high levels in various tissues including human intestinal cells. Arbaclofen placarbil was efficiently absorbed and rapidly converted to R-baclofen after oral dosing in rats, dogs, and monkeys. Exposure to R-baclofen was proportional to arbaclofen placarbil dose, whereas exposure to intact prodrug was low. Arbaclofen placarbil demonstrated enhanced colonic absorption, i.e., 5-fold higher R-baclofen exposure in rats and 12-fold higher in monkeys compared with intracolonic administration of R-baclofen. Sustained release formulations of arbaclofen placarbil demonstrated sustained R-baclofen exposure in dogs with bioavailability up to 68%. In clinical use, arbaclofen placarbil may improve the treatment of patients with gastroesophageal reflux disease, spasticity, and numerous other conditions by prolonging exposure and decreasing the fluctuations in plasma levels of R-baclofen.
Highlights • Spider-fearful participants attempted to control their distance from spider images. • High and low control groups were yoked for level of exposure in a computer task. • High control led ...to closer approach post-exposure and less avoidance after 17 days. • There were no group differences in distress and GSR during exposure. q
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