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Background: Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival).Methods: Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters.Results: YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample size Cox regression models failed to demonstrate significance for nuclear YB-1 detection as independent prognostic marker.Conclusion: Monoclonal YB-1 antibody F-E2G5 should be of great value for prospective studies to validate YB-1 as a novel biomarker suitable to optimize breast cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The delivery of high-quality services in chronically underfunded social or long-term care systems is a major challenge internationally. National guidelines, developed by the National Institute for Health and Care Excellence, set out how local authorities in England and Wales should fund and provide care based on best available evidence. Theoretical and participatory approaches can usefully inform the design and evaluation of implementation strategies for guidelines. The aim of the study is to develop a Theory-of-Change for how the implementation of these guidelines is expected to lead to impacts from a local authority perspective., Methods: As part of a comparative case study (The 'Valuing Care Guidelines' study; February 2022 to April 2024) with three local authority sites in England and Wales, we involved altogether 17 participants in two Theory-of-Change online workshops per site, each of 2 hours. Additional data gathered from the same participants as part of the overall study were used to conceptualise and enrich information from the workshops., Results: Participants described the Theory-of-Change map as follows: A wide range of activities (categorised in stages of 'pre-implementation', 'implementation', 'sustainment and scaling') and skills were required to implement guidelines, and achieve long-term organisational sustainability and service delivery outcomes, leading to final impacts for service users and carers. Participants described a co-creation implementation model, led by 'Implementation Support Practitioners', who utilised relational skills to achieve motivation, trust, and confidence at different organisational levels, addressing contextual barriers such as inadequate staffing, lack of resources and of organisational support systems. Consistent use of guidelines by frontline staff could only be achieved if the value of guideline implementation was promoted widely, and if consideration was given to the roles of stakeholders, such as the inspection body, local health care providers, users and carers., Conclusions: Our study is the first to investigate the implementation of national social care guidelines by local authorities in England and Wales. It generates insights that can guide implementation practice as well as inform the evaluation of future implementation strategies., (© 2024. The Author(s).)

Multimodal therapy for peritoneal metastasis (PM) including cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provides long-term survival in highly selected colorectal cancer patients. Mechanisms behind HIPEC are unknown and may include induction of adaptive immunity. We therefore analyzed human PM samples and explored the impact of HIPEC in experimental models. Human samples from colorectal primary tumors (n = 19) and PM lesions (n = 37) were examined for the presence of CD8 + T-cells and their association with disease free (DFS) and overall survival (OS). CD8 + T cell response after HIPEC was assessed using an in-vivo PM mouse model, tumor cell lines and patient-derived tumor organoids. Patients with high intraepithelial CD8 + T cell counts showed longer DFS and OS. In the mouse model, HIPEC controlled growth of PM and increased numbers of functional granzyme positive CD8 + T cells within tumors. Cell lines and human organoids that were treated with heated chemotherapies showed immunogenic changes, reflected by significantly higher levels of MHC-class I molecules and expression of Cancer Testis Antigens Cyclin A1 and SSX-4. Using in-vitro co-culture assays, we noticed that cancer cells treated with heated chemotherapy primed dendritic cells, which subsequently enhanced effector functions of CD8 + T cells. The presence of CD8 + T-cells within PM lesions is associated with prolonged survival of patients with PM. Data from PM mouse model and in-vitro assay show that heated chemotherapies induce immunogenic changes on cancer cells leading to induction of CD8 + T-cells mediated immunity, which seems to control growth of PM lesions in mice after HIPEC., (© 2024. The Author(s).)

Hyperparathyroidism (HPT) with hypercalcemia, often deemed irreversible and detrimental to graft survival post-kidney transplantation (KT), prompts pre-transplant parathyroidectomy in hypercalcemic patients. In this retrospective analysis of 1212 kidney transplant recipients (KTRs) between 2006 and 2019, the incidence and effect of persistent HPT and hypercalcemia on graft and patient survival, and risk factors for persistence were analyzed until 60 months of follow up (FU). At KT, 5.7% (n = 69) had no HPT, 32.7% (n = 396) had HPT without hypercalcemia and 37.0% (n = 448) had HPT with hypercalcemia. At 2 years FU, 26.4% (n = 320) of patients had no HPT and 6% (n = 73) had HPT with hypercalcemia. Dialysis and dialysis duration were linked to HPT development, while dialysis, KT waiting time and donor type correlated with persisting hypercalcemia after KT. KTRs with normalized PTH and recovered hypercalcemia had improved death-censored graft survival ( p < 0.001) and overall patient survival ( p < 0.001). HPT with hypercalcemia is frequent at time of KT with normalization of PTH and calcium in a substantial proportion of patients after a KT. These findings question the routine pre-KT parathyroidectomy for suspected parathyroid autonomy. Persisting HPT, especially with hypercalcemia, adversely affects graft and patient survival, suggesting the need for more aggressive treatment of HPT, especially in cases of persisting hypercalcemia.

Background: Despite the high burden of perinatal depression in Nepal, the detection rate is low. Community-based strategies such as sensitization programmes and the Community Informant Detection Tool (CIDT) have been found to be effective in raising awareness and thus promoting the identification of mental health problems. This study aims to adapt these community strategies for perinatal depression in the Nepalese context., Methods: We followed a four-step process to adapt the existing community sensitization program manual and CIDT. Step 1 included in-depth interviews with women identified with perinatal depression (n=36), and focus group discussions were conducted with health workers trained in community mental health (n=13), female community health volunteers (FCHVs), cadre of Nepal government for the prevention and promotion of community maternal and child health (n=16), and psychosocial counsellors (n=5). We explored idioms and understanding of depression, perceived causes, and possible intervention. Step 2 included draft preparation based on the qualitative study. Step 3 included a one-day workshop with the psychosocial counsellors (n=2) and health workers (n=12) to assess the understandability and comprehensiveness of the draft and to refine the content. A review of the CIDT and community sensitization program manual by a psychiatrist was performed in Step 4., Results: The first step led to the content development for the CIDT and community sensitization manual. Multiple stakeholders and experts reviewed and refined the content from the second to fourth steps. Idioms of depression and commonly cited risk factors were incorporated in the CIDT. Additionally, myths of perinatal depression and the importance of the role of family were added to the community sensitization manual., Conclusion: Both the CIDT and community sensitization manual are grounded in the local context and are simple, clear, and easy to understand., (© 2024. The Author(s).)

Background: Stigma exacerbates power imbalances and societal disparities, significantly impacting diverse identities and health conditions, particularly for low and middle-income countries (LMICs). Though crucial for dismantling harmful stereotypes, and enhancing healthcare utilisation, existing research on anti-stigma interventions is limited with its condition-focused approach. We aimed to thoroughly evaluate peer-reviewed and non-peer-reviewed literature for a comprehensive review of anti-stigma interventions for diverse identities and all health conditions in LMICs., Methods: This review systematically explored peer-reviewed and non-peer-reviewed literature, in ten electronic databases up to January 30, 2024, covering all anti-stigma interventions across various stigmatised identities and health conditions in LMICs. Quality assessment for this systematic review was conducted as per Cochrane Collaboration's suggested inclusions. The review was registered with PROSPERO (Registration: 2017 CRD42017064283)., Findings: Systematic synthesis of the 192 included studies highlights regional imbalances, while providing valuable insights on robustness and reliability of anti-stigma research. Most studies used quasi-experimental design, and most centred on HIV/AIDS or mental health related stigma, with very little work on other issues. Certain high-population LMICs had no/little representation., Interpretation: The interventions targeted diverse segments of populations and consequently yielded a multitude of stigma-related outcomes. However, despite the heterogeneity of studies, most reported positive outcomes underscoring the effectiveness of existing interventions to reduce stigma., Funding: This study is supported by the UK Medical Research Council Indigo Partnership (MR/R023697/1) award., Competing Interests: None to declare., (© 2024 Published by Elsevier Ltd.)

In Kenya, approximately one in five girls aged 15-19 years old are pregnant or already a mother. Adolescent girls and young women experience significant mental health vulnerabilities during the pregnancy and postpartum periods, leading to poor antenatal and postnatal care attendance and inferior infant and maternal health outcomes. Pregnant adolescents often experience stigma and disenfranchisement due to their pregnancy status and at the same time lack access to mental health support within health settings, schools, religious institutions, and communities. This paper presents the results of qualitative interviews embedded within the human-centered design (HCD) process used to adapt the Helping Adolescents Thrive (HAT) program for Kenyan peripartum adolescents including young fathers. This qualitative study used two phases. First, a HAT advisory group participated in a series of four workshops to help identify and articulate mental health promotion needs and deepened the team's understanding of youth-centered thinking. Second, qualitative interviews were conducted with 39 pregnant and parenting adolescents to understand their perspectives on mental health prevention and promotion. Pregnant and parenting adolescents articulated different needs including poor support, stigma, and psychological disturbances. Parenting adolescents reported disturbed relationships, managing motherhood, poor health, and social empowerment. Participants highlighted sources of stress including economic challenges, fear of delivery, strained relationships, rejection, and stigma. Participants described psychological disturbances such as feeling stressed, worthless, withdrawn, and suicidal. Coping mechanisms reported by participants included engaging in domestic activities, hobbies, and social networking. Peers, family and spirituality were identified as important sources of support, as well as school integration, livelihoods, support groups and mentorships. Findings from this study can be used to strengthen and adapt HAT program, policy and practice for mental health prevention and promotion for pregnant and parenting adolescents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kathono et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To report on a concept of liver assessment during ex situ hypothermic oxygenated perfusion (HOPE) and its significant impact on liver utilization., Methods: An analysis of prospectively collected data on donation after circulatory death (DCD) livers, treated by HOPE at our institution, during a 11-year period between January 2012 and December 2022., Findings: Four hundred and fifteen DCD Maastricht III livers were offered during the study period in Switzerland, resulting in 249 liver transplants. Of those, we performed 158 DCD III liver transplants at our institution, with 1-year patient survival and death censored graft survival (death with functioning graft) of 87 and 89%, respectively, thus comparable to benchmark graft survivals of ideal DBD and DCD liver transplants (89% and 86%). Correspondingly, graft loss for primary non-function or cholangiopathy was overall low, i.e., 7/158 (4.4%) and 11/158 (6.9%), despite more than 82% of DCD liver grafts ranked high (6-10 points) or futile risk (>10 points) according to the UK-DCD score. Consistently, death censored graft survival was not different between low-, high-risk or futile DCD III livers. The key behind these achievements was the careful development and implementation of a routine perfusate assessment of mitochondrial biomarkers for injury and function, i.e., release of flavin mononucleotide from complex I, perfusate NADH, and mitochondrial CO 2 production during HOPE, allowing a more objective interpretation of liver quality on a subcellular level, compared to donor derived data., Interpretation: HOPE after cold storage is a highly suitable and easy to perform perfusion approach, which allows reliable liver graft assessment, enabling surgeons to make a fact based decision on whether or not to implant the organ. HOPE-treatment should be combined with viability assessment particularly when used for high-risk organs, including DCD livers or organs with relevant steatosis., Funding: This study was supported by the Swiss National Foundation (SNF) grant 320030&#95;189055/1 to PD., Competing Interests: Declaration of interests A.S. received consultant fees for presentations from Bridge to life LTD, all other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Malawi has a population of around 20 million people and is one of the world's most economically deprived nations. Severe mental illness (largely comprising psychoses and severe mood disorders) is managed by a very small number of staff in four tertiary facilities, aided by clinical officers and nurses in general hospitals and clinics. Given these constraints, psychosis is largely undetected and untreated, with a median duration of untreated psychosis (DUP) of around six years. Our aim is to work with people with lived experience (PWLE), caregivers, local communities and health leaders to develop acceptable and sustainable psychosis detection and management systems to increase psychosis awareness, reduce DUP, and to improve the health and lives of people with psychosis in Malawi. We will use the UK Medical Research Council guidance for developing and evaluating complex interventions, including qualitative work to explore diverse perspectives around psychosis detection, management, and outcomes, augmented by co-design with PWLE, and underpinned by a Theory of Change. Planned deliverables include a readily usable management blueprint encompassing education and community supports, with an integrated care pathway that includes Primary Health Centre clinics and District Mental Health Teams. PWLE and caregivers will be closely involved throughout to ensure that the interventions are shaped by the communities concerned. The effect of the interventions will be assessed with a quasi-experimental sequential implementation in three regions, in terms of DUP reduction, symptom remission, functional recovery and PWLE / caregiver impact, with quality of life as the primary outcome. As the study team is focused on long-term impact, we recognise the importance of having embedded, robust evaluation of the programme as a whole. We will therefore evaluate implementation processes and outcomes, and cost-effectiveness, to demonstrate the value of this approach to the Ministry of Health, and to encourage longer-term adoption across Malawi., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lawrie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mental health service delivery needs radical reimagination in the United States where unmet needs for care remain large and most metrics on the burden of mental health problems have worsened, despite significant numbers of mental health professionals, spending on service provision and research. The COVID-19 pandemic has exacerbated the need for mental health care. One path to a radical reimagination is "Community Initiated Care (CIC)" which equips and empowers communities to address by providing brief psychosocial interventions by people in community settings. We co-developed a theory of change (ToC) for CIC with 24 stakeholders including representatives from community-based, advocacy, philanthropic and faith-based organizations to understand how CIC could be developed and adapted for specific contexts. We present a ToC which describes ways in which the CIC initiative can promote and strengthen mental health in communities in the United States with respect to community organization and leadership; community care and inclusion and normalizing mental health. We propose 10 strategies as part of CIC and propose a way forward for implementation and evaluation. This CIC model is a local, tailored approach which can expand the role of community members to strengthen our response to mental health needs in the United States., Competing Interests: The authors do not have any conflicts of interest., (© The Author(s) 2023.)

Introduction: There is a lack of standard nomenclature and a limited understanding of programmes and services delivered to people in prisons as they transition into the community to support their integration and reduce reoffending related risk factors. The aim of this paper is to outline the protocol for a modified Delphi study designed to develop expert consensus on the nomenclature and best-practice principles of programmes and services for people transitioning from prison into the community., Methods and Analysis: An online, two-phase modified Delphi process will be conducted to develop an expert consensus on nomenclature and the best-practice principles for these programmes. In the preparatory phase , a questionnaire was developed comprising a list of potential best-practice statements identified from a systematic literature search. Subsequently, a heterogeneous sample of experts including service providers, Community and Justice Services, Not for Profits, First Nations stakeholders, those with lived experience, researchers and healthcare providers will participate in the consensus building phase (online survey rounds and online meeting) to achieve consensus on nomenclature and best-practice principles. Participants will indicate, via Likert scale, to what extent they agree with nomenclature and best-practice statements. If at least 80% of the experts agree to a term or statement (indicated via Likert scale), it will be included in a final list of nomenclature and best-practice statements. Statements will be excluded if 80% experts disagree. Nomenclature and statements not meeting positive or negative consensus will be explored in a facilitated online meeting. Approval from experts will be sought on the final list of nomenclature and best-practice statements., Ethics and Dissemination: Ethical approval has been received from the Justice Health and Forensic Mental Health Network Human Research Ethics Committee, the Aboriginal Health and Medical Research Council Human Research Ethics Committee, the Corrective Services New South Wales Ethics Committee and the University of Newcastle Human Research Ethics Committee. The results will be disseminated via peer-reviewed publication., Competing Interests: Competing interests: SH is the Executive Medical Director at Justice Health and Forensic Mental Health Network, LG is the Deputy Commissioner at Corrective Services NSW Department of Communities and Justice, RZ is a Senior Research Officer at Justice Health and Forensic Mental Health Network, and ES is the Custodial Health Research lead at Justice Health and Forensic Mental Health Network., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Surgical liver failure (SLF) develops when a marginal amount of hepatic mass is left after surgery, such as following excessive resection. SLF is the commonest cause of death due to liver surgery; however, its etiology remains obscure. Using mouse models of standard hepatectomy (sHx) (68%, resulting in full regeneration) or extended hepatectomy (eHx) (86%/91%, causing SLF), we explored the causes of early SLF related to portal hyperafflux. Assessing the levels of HIF2A with or without oxygenating agent inositol trispyrophosphate (ITPP) indicated hypoxia early after eHx. Subsequently, lipid oxidation (PPARA/PGC1α) was downregulated and associated with persisting steatosis. Mild oxidation with low-dose ITPP reduced the levels of HIF2A, restored downstream PPARA/PGC1α expression along with lipid oxidation activities (LOAs), and normalized steatosis and other metabolic or regenerative SLF deficiencies. Promotion of LOA with L-carnitine likewise normalized the SLF phenotype, and both ITPP and L-carnitine markedly raised survival in lethal SLF. In patients who underwent hepatectomy, pronounced increases in serum carnitine levels (reflecting LOA) were associated with better recovery. Lipid oxidation thus provides a link between the hyperafflux of O 2 -poor portal blood, the metabolic/regenerative deficits, and the increased mortality typifying SLF. Stimulation of lipid oxidation-the prime regenerative energy source-particularly through L-carnitine may offer a safe and feasible way to reduce SLF risks in the clinic., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: In one third of all patients with epilepsy, seizure freedom is not achieved through anti-seizure medication (ASM). These patients have an increased risk of earlier death, poorer cognitive development, and reduced quality of life. Cenobamate (CNB) has recently been approved as a promising novel ASM drug for the treatment of adults with focal-onset epilepsy. However, there is little experience for its application in pediatric patients., Methods: In a multicenter study we evaluated retrospectively the outcome of 16 pediatric patients treated "off label" with CNB., Results: In 16 patients with a mean age of 15.38 years, CNB was started at an age of 15.05 years due to DRE. Prior to initiation of therapy, an average of 10.56 (range 3-20) ASM were prescribed. At initiation, patients were taking 2.63 (range 1-4) ASM. CNB was increased by 0.47 ± 0.27mg/kg/d every 2 weeks with a mean maximum dosage of 3.1 mg/kg/d (range 0.89-7) and total daily dose of 182.81 mg (range 50-400 mg). Seizure freedom was achieved in 31.3% and a significant seizure reduction of >50% in 37.5%. Adverse events occurred in 10 patients with fatigue/somnolence as the most common. CNB is taken with high adherence in all but three patients with a median follow-up of 168.5 days., Conclusion: Cenobamate is an effective ASM for pediatric patients suffering from drug-resistant epilepsy. In addition to excellent seizure reduction or freedom, it is well-tolerated. Cenobamate should be considered as a novel treatment for DRE in pediatric patients., Competing Interests: TK-P and TM were employed by Epilepsiezentrum Kleinwachau gemeinnützige GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Makridis, Bast, Prager, Kovacevic-Preradovic, Bittigau, Mayer, Breuer and Kaindl.)

Infertility affects millions of people globally. Although an estimated 1 in 6 couples in Australia are unable to conceive without medical intervention, little is known about the mental health impacts of infertility. This study investigated how infertility impacts the mental health of women. The study used nationally representative Australian Longitudinal Study on Women's Health (ALSWH) data. We analysed data from survey periods 2-8 conducted every three years between 2000 and 2018 for 6582 women born in 1973-78. We used a Generalised Equation Modelling (GEE) method to investigate the association of primary, secondary and resolved fertility status and psychological distress over time. Multiple measures were used to measure psychological distress: the (1) the mental health index subscale of the 36-item short form survey (SF-36), (2) the Center for Epidemiological Studies Depression Scale (CESD-10), (3) the Goldberg Anxiety and Depression Scale (GADanx) anxiety subscale; and a (4) composite psychological distress variable. About a third (30%) of women reported infertility at any of the survey rounds; a steady increase over 18 years from 1.7% at round 2 to 19.3% at round 8. Half of the women reporting primary or secondary infertility reported psychological distress, with the odds of having psychological distress was higher in women reporting primary (odds ratio (OR) 1.24, 95% confidence interval (CI) 1.06-1.45), secondary (OR 1.27, 95% CI 1.10-1.46) or resolved infertility (OR 1.15, 95% CI 1.05-1.26) compared to women reporting normal fertility status. Women with partners, underweight or higher BMI, smoking, and high-risk alcohol use had higher odds of psychological distress, whereas women in paid work had significantly lower odds of psychological distress (p < 0.001). Diabetes, high blood pressure, asthma, and other chronic physical illness were independently associated with higher odds of psychological distress. Infertility has a significant impact on mental health even after it is resolved. Frequent mental health assessment and a holistic approach to address the lifestyle factors should be undertaken during the treatment of infertility., (© 2022. The Author(s).)

Background: Donation after circulatory death (DCD) represents up to 40% of used kidney grafts. While studies have shown similar outcomes compared with donation after brain death (DBD) in the short term and mid-term, no data on long-term outcomes exist., Methods: We retrospectively analysed patients transplanted at our institution between January 1985 and March 2000. All DCD recipients were matched one-to-one with patients transplanted with DBD grafts during this period according to sex, age and year of transplantation and followed up until December 2020. During this period, 1133 kidney transplantations were performed, of which 122 were with a DCD graft., Results: The median graft survival after 35 years of follow-up was 23 years [277 months {95% confidence interval (CI) 182-372}] in DBD recipients and 24.5 years [289 months (95% CI 245-333)] in DCD recipients (P = 0.65; hazard ratio 0.91). Delayed graft function occurred in 47 patients in the DCD group compared with 23 in the DBD group (P < 0.001), albeit without a significant long-term outcome difference in graft or patient survival. We could not show any difference in graft function in terms of creatinine levels (133 versus 119 µmol/L), proteinuria (370 versus 240 mg/24 h) and glomerular filtration rate slope (-0.6 versus -0.3 mL/min/year) between the two groups for graft survival >20 years., Conclusions: This is the first study to show similar graft survival and function in DCD kidneys compared with DBD kidneys after 35 years of follow-up. DCD grafts are a valuable resource and can be utilized in the same way as DBD grafts., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Peritoneal metastasis (PM) originating from gastrointestinal cancer was considered a terminal disease until recently. The advent of better systemic treatment, a better understanding of prognostic factors, and finally, the advent of novel loco-regional therapies, has opened the door for the multimodal treatment of PM. These strategies, including radical surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) showed surprisingly good results, leading to the prolonged survival of patients with peritoneal metastasis. This has triggered a significant body of research, leading to the molecular characterization of PM, which may further help in the development of novel treatments. This review summarizes current evidence on peritoneal metastasis and explores potential novel mechanisms and therapeutic approaches to treat patients with peritoneal metastasis.

Background: Women in prison are a vulnerable group, often with a history of abuse, out-of-home care, mental health problems and unemployment. Many are mothers when they become involved in the criminal justice system and their gender and parenting related needs are often not considered. The aim of this rapid review was to thematically synthesize the existing research on the needs and experiences of mothers while in, and following release from, prison in Australia., Methods: We conducted a rapid systematic search of electronic databases, search engines, the websites of key agencies, and contacted key agencies and researchers., Results: Twenty-two publications from 12 studies met the inclusion criteria and were thematically synthesized in relation to the mothers, their children, family and community, and systems and services which mothers had contact with. We found that mothers in prison have a history of disadvantage which is perpetuated by the trauma of imprisonment. Release from prison is a particularly challenging time for mothers. In relation to their children, the included studies showed that the imprisonment of mothers impacts their maternal identity and role and disrupts the mother-child relationship. Specific strategies are needed to maintain the mother-child relationship, and to ensure the needs and rights of the child are met. In relation to family and community, we found that although family and social support is an important need of women in prison, such support may not be available. Moreover, the stigma associated with having been in prison is a significant barrier to transitions into the community, including finding employment and housing. In relation to systems and services, although limited services exist to support women in prison and on release, these often do not consider the parenting role. Evaluations of parenting programs in prison found them to be acceptable and beneficial to participants but barriers to access limit the number of women who can participate., Conclusion: Mothers have gender- and parenting-specific needs which should be considered in planning for corrective services in Australia. Any service redesign must place the woman and her children at the centre of the service., (© 2021. The Author(s).)

Background: Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and little data are available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer., Methods: Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005 and 2017 at 4 centers were analyzed retrospectively., Results: A total of 505 patients undergoing CRS/HIPEC were analyzed. Of the patients, 82.1% received preoperative chemotherapy. Median peritoneal cancer index was 6 (interquartile range = 3-11). Median disease-free and overall survival was 12 (95% confidence interval [CI] = 11 to 14) months and 51 (95% CI = 43 to 62) months, respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 (95% CI = 18 to 31) months for isolated peritoneal and 22 (95% CI = 16 to 30) months for mixed recurrence, compared with 43 (95% CI = 31 to >121) months for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53; P = .001; and HR = 2.44, 95% CI = 1.61 to 3.79; P < .001). On multiple logistic regression analysis, RAS mutational status (odds ratio [OR] = 2.42, 95% CI = 1.11 to 5.47; P = .03) and positive nodal stage of the primary (OR = 3.88, 95% CI = 1.40 to 11.86; P = .01) were identified as predictive factors for peritoneal recurrence., Conclusions: This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Integrating mental health services into primary healthcare platforms is an established health systems strategy in low-to-middle-income countries. In South Africa, this was pursued through the Programme for Improving Mental Health Care (PRIME), a multi-country initiative that relied on task-sharing as a principle implementation strategy. Towards better describing the implementation processes, qualitative comparative analysis was adopted to explore causal pathways in the intervention., Objective: This study aimed to explore factors that could have influenced key outcomes of an integrated mental healthcare intervention in South Africa., Methods: Drawing from an embedded multiple case study design, the analysis used qualitative comparative analysis. Focusing on nine PHC clinics in the Dr Kenneth Kaunda District as cases, with depression reduction scores set as outcome measures, trial data variables were modelled in a hypothetical causal process. A fuzzy-set qualitative comparative analysis was performed by 1) developing the research questions, 2) developing the fuzzy set, 3) testing necessity and 4) testing sufficiency. These steps were undertaken collaboratively among the research team., Results: The data were calibrated during several meetings among team members to gain a degree of consensus. Necessity analyses suggested that none of the causal conditions exceeded the threshold of necessity and triviality, and confirmed the inclusion of relevant variables in line with the proposed models. Sufficiency analyses produced two configurations, which were subjected to standard and specific analyses. Ultimately, the results suggested that none of the causal conditions were necessary for a reduction in depression scores to occur, while programme fidelity was identified as a sufficient condition for a reduction in scores to occur., Conclusions: The study highlights the importance of understanding implementation pathways to enable better integration of mental health services within primary healthcare in low-to-middle-income settings. It underlines the importance of programme fidelity in achieving the goals of implementation.

Background: The PRogramme for Improving Mental Health carE (PRIME) evaluated the process and outcomes of the implementation of a mental healthcare plan (MHCP) in Chitwan, Nepal., Aims: To describe the process of implementation, the barriers and facilitating factors, and to evaluate the process indicators of the MHCP., Method: A case study design that combined qualitative and quantitative methods based on a programme theory of change (ToC) was used and included: (a) district-, community- and health-facility profiles; (b) monthly implementation logs; (c) pre- and post-training evaluation; (d) out-patient clinical data and (e) qualitative interviews with patients and caregivers., Results: The MHCP was able to achieve most of the indicators outlined by the ToC. Of the total 32 indicators, 21 (66%) were fully achieved, 10 (31%) partially achieved and 1 (3%) were not achieved at all. The proportion of primary care patients that received mental health services increased by 1200% over the 3-year implementation period. Major barriers included frequent transfer of trained health workers, lack of confidential space for consultation, no mental health supervision in the existing system, and stigma. Involvement of Ministry of Health, procurement of new psychotropic medicines through PRIME, motivation of health workers and the development of a new supervision system were key facilitating factors., Conclusions: Effective implementation of mental health services in primary care settings require interventions to increase demand for services and to ensure there is clinical supervision for health workers, private rooms for consultations, a separate cadre of psychosocial workers and a regular supply of psychotropic medicines.