Benzathine penicillin G stockouts and other barriers to documented syphilis treatment in pregnancy in Zambia.

OBJECTIVE: The prevalence of syphilis in Zambia remains high and is a critical public health concern. The Zambian Ministry of Health recommends universal screening and same-day treatment for syphilis in pregnancy, yet the syphilis screening rate is low, and treatment is poorly documented. The goal of this study was to document syphilis treatment rates and associated factors among pregnant women in care in Zambia. METHODS: This retrospective cohort study included pregnant women diagnosed with syphilis according to rapid plasma reagin (RPR) screening during routine antenatal care (ANC) in Lusaka, Zambia in 2018-2019. The main outcome of interest was lack of documented BPG treatment during pregnancy. Additional information about pregnancy and neonatal outcomes, partner referral for therapy, and facility level stockout data were included. Patient characteristics were compared by treatment status using Pearson Chi-Square Test and logistic regression models were created to estimate the association between individual level-factors, facility type, and lack of BPG treatment. A Cochran-Mantel-Haenszel test was used to evaluate facility-level data with significance set at p<0.05. RESULTS: Among 1,231 pregnant women who screened positive for syphilis at clinic, 643 (52%) lacked documented antibiotic treatment at the facility. BPG was the only antibiotic used to treat syphilis in the cohort and 8% of sex partners had evidence of referral for therapy. Preterm delivery rates were higher in women without documented BPG (43% vs 32%; p = 0.003). In adjusted models, only calendar year and hospital facility type were associated with lack of treatment. At the facility level, annual syphilis screening rates ranged from 37-65% and most (7/10) clinics reported at least one stockout of BPG. CONCLUSION: Treatment rates for syphilis in pregnancy in Zambia were low and BPG medication stockouts at the facility level were common. A consistent supply of BPG at all ANC facilities is needed to facilitate timely treatment and improve birth outcomes.

Identifying barriers to outpatient appointment attendance in patient groups at risk of inequity: a mixed methods study in a London NHS trust.

BACKGROUND: There is significant health inequity in the United Kingdom (U.K.), with different populations facing challenges accessing health services, which can impact health outcomes. At one London National Health Service (NHS) Trust, data showed that patients from deprived areas and minority ethnic groups had a higher likelihood of missing their first outpatient appointment. This study's objectives were to understand barriers to specific patient populations attending first outpatient appointments, explore systemic factors and assess appointment awareness. METHODS: Five high-volume specialties identified as having inequitable access based on ethnicity and deprivation were selected as the study setting. Mixed methods were employed to understand barriers to outpatient attendance, including qualitative semi-structured interviews with patients and staff, observations of staff workflows and interrogation of quantitative data on appointment communication. To identify barriers, semi-structured interviews were conducted with patients who missed their appointment and were from a minority ethnic group or deprived area. Staff interviews and observations were carried out to further understand attendance barriers. Patient interview data were analysed using inductive thematic analysis to create a thematic framework and triangulated with staff data. Subthemes were mapped onto a behavioural science framework highlighting behaviours that could be targeted. Quantitative data from patient interviews were analysed to assess appointment awareness and communication. RESULTS: Twenty-six patients and 11 staff were interviewed, with four staff observed. Seven themes were identified as barriers - communication factors, communication methods, healthcare system, system errors, transport, appointment, and personal factors. Knowledge about appointments was an important identified behaviour, supported by eight out of 26 patients answering that they were unaware of their missed appointment. Environmental context and resources were other strongly represented behavioural factors, highlighting systemic barriers that prevent attendance. CONCLUSION: This study showed the barriers preventing patients from minority ethnic groups or living in deprived areas from attending their outpatient appointment. These barriers included communication factors, communication methods, healthcare the system, system errors, transport, appointment, and personal factors. Healthcare services should acknowledge this and work with public members from these communities to co-design solutions supporting attendance. Our work provides a basis for future intervention design, informed by behavioural science and community involvement.

A pilot study evaluating online training for therapist delivery of interpersonal psychotherapy for eating disorders.

OBJECTIVE: Individuals with eating disorders (EDs) often do not receive evidence-based care, such as interpersonal psychotherapy (IPT), partly due to lack of accessible training in these treatments. The standard method of training (i.e., in-person workshops) is expensive and time consuming, prompting a need for more scalable training tools. The primary aim of this pilot and open trial was to examine the effects of an IPT online training platform on training outcomes (i.e., IPT fidelity, knowledge, and acceptance) and, secondarily, whether online training was different from in-person training (using a comparative sample from a separate study) in terms of training outcomes and patient symptoms. METHOD: Participants were therapists (N = 60) and student patients (N = 42) at 38 college counseling centers. Therapists completed baseline questionnaires and collected data from a student patient with ED symptoms. Therapists then participated in an IPT online training program and completed post-training assessments. RESULTS: Following online training, acceptance of evidence-based treatments, therapist knowledge of IPT, therapist acceptance of IPT, and treatment fidelity increased; acceptance of online training was high at baseline and remained stable after training. Using the 90% confidence interval on outcome effect sizes, results suggested IPT online training was not different from in-person training on most outcomes. Results are based on 60% of therapists who originally enrolled due to high dropout rate of therapist participants. CONCLUSIONS: Findings from this preliminary pilot study support the use of IPT online training, which could increase access to evidence-based ED treatment and improve patient care. PUBLIC SIGNIFICANCE: Lack of accessible therapist training has contributed to many therapists not delivering, and therefore many patients not receiving, evidence-based treatment. This study evaluated a highly disseminable online training and compared outcomes to traditional in-person training and found that training and patient outcomes were not different. Online training has the potential to enhance access to evidence-base care, which could in turn optimize patient outcomes.

Association of Daily Activities With Maternal-Child Bonding, Parenting Self-Efficacy, Social Support, and Parenting Behaviors Among Survivors Living in an Intimate Partner Violence Shelter: A Daily Diary Study.

Following a traumatic event such as intimate partner violence (IPV), survivors often experience stress related to the violence. These high levels of stress related to IPV can be associated with the daily activities of survivors and their relationships with their children, such as maternal-child bonding. The purpose of the current study is to explore the relationship between daily activities, daily stress levels, parenting self-efficacy and behaviors, and maternal-child bonding among survivors living in an IPV shelter using an ecological momentary assessment (EMA) methodology. Twenty-five mothers living in an IPV shelter in two states in the Southern United States completed a baseline survey and completed electronic daily diaries for 14 days. Higher daily stress was associated with the number of times the mothers met with the case manager. Higher daily stress was also related to lower parenting self-efficacy. The number of case management appointments and legal appointments were positively correlated with a higher bonding score. More social support was associated with more positive parenting. IPV and post-traumatic stress disorder symptoms were not significantly associated with maternal-child bonding, parenting behaviors, or parenting self-efficacy. Findings suggest that screening for maternal support may be particularly important for positive bonding and positive parenting. Findings also lend preliminary insight into practical places where service providers could act to protect the bonding process or mitigate risks to impede it. Future research should include objective data about the mother's emotions and her interactive behavior with her child. There is also a need to consider how federal programs fund and incentivize service providers to focus on mother-child dyads and how they can tailor services that promote bonding.

Starting a career in research nursing during a global pandemic.

In the spring of 2020, two nurses (KR and AJ) commenced their research nurse careers amid the SARS-Cov-2 (COVID-19) global pandemic. This reflective article discusses their experiences of beginning a clinical research nursing career, presented as a case study of their learning journey, rather than detailing the randomised controlled trial they delivered via GP practices. The main study compared standard care to nurse-led management of irritable bowel syndrome, the details of which will be published separately. The article identifies three overarching concepts: 'Green as grass, keen as mustard', 'Spires and steeples', and 'Down the rabbit hole'. The article offers insight from the two nurses for other professionals contemplating a career in research.

Multi-modal hallucinations across diagnoses: What relationships do they have with voice-related distress?

BACKGROUND: Research into hallucinatory experiences has focused primarily upon hallucinations within the auditory modality, to the relative neglect of other modalities. Furthermore, the exploration of auditory hallucinations (or 'voices') has focused primarily upon the experiences of people with a diagnosis of psychosis. The presence of multi-modal hallucinations may have implications across diagnoses for levels of distress, formulation and the targeting of psychological interventions. METHODS: This study presents a cross-sectional analysis of observational data from the PREFER survey (N = 335). Linear regression was used to explore the relationships between voice-related distress and the presence, number, type and timing of multi-modal hallucinations. RESULTS: Simple relationships were not found between distress and the presence of hallucinations in visual, tactile, olfactory or gustatory modalities, or in the number of modalities experienced. When considering the degree to which another modality hallucination was experienced simultaneously with voices, there was some evidence that the degree of co-occurrence with visual hallucinations was predictive of distress. CONCLUSIONS: The co-occurrence of voices with visual hallucinations may be associated with relatively greater distress, but not consistently, and the association between multimodal hallucinations and clinical impact appear complex and potentially variable from individual to individual. Further study of associated variables such as perceived voice power may further illuminate these relationships.

Excellent hepatitis C virus cure rates despite increasing complexity of people who use drugs: Integrated-Test-stage Treat study final outcomes.

Achieving hepatitic C virus (HCV) elimination requires linking people who use drugs (PWUD) into care. We report final direct-acting antivirals (DAAs)-based outcomes from the Integrated-Test-stage -Treat (ITTREAT) study. Project ITTREAT (2013-2021), based at an addiction centre, was a 'one-stop' service with innovative linkage to care strategies. Primary outcome was sustained virological response (SVR12) (intention to treat ITT) including whether individuals were recruited in first (period 1) versus last four (period 2 included the COVID-19 pandemic) years of the study. Number recruited were n = 765, mean age 40.9 ± 10.1 years, 78% males, history of current/past injecting drug use (IDU) and alcohol use being 77% and 90%, respectively. Prevalence of a positive HCV PCR was 84% with 19% having cirrhosis. Comparing those recruited in period 2 versus period 1, there was increasing prevalence of IDU, 90% versus 72% (p < .001); homelessness, 67% versus 50% (p < .001); psychiatric diagnosis, 84% versus 50% (p < .001); overdose history 71% versus 31% (p < .001), receiving opioid agonist treatment (OAT) 75% versus 52% (p < .001) and comorbidity 44% versus 25% (p < .001). Of those treated with DAAs (n = 272), ITT SVR rates were 86% (95% CI: 81%-90%), being similar in period 2 versus period 1. Predictors of non-SVR were receiving OAT (OR 0.33, 95% CI: 0.12-0.87, p = .025) and ≥80% adherence (OR 0.01, 95% CI: 0.003-0.041, p < .001). Reinfection rates period 2 versus period 1 (per 100 person-years) were 1.84 versus 1.70, respectively. In the treated cohort, mortality was 15%, being mostly drug-related. Despite increasing complexity of PWUD, high SVR12 rates are achievable with use of OAT and good adherence.

A co-produced service evaluation of ethnic minority community service user experiences of a specialist mental health service during the COVID-19 pandemic.

BACKGROUND: For ethnic minority communities in the UK, the COVID-19 pandemic amplified existing health inequalities and created other consequential disadvantages like increased vulnerability to COVID-19, higher rates of hospital admissions, increased mortality and poorer mental health outcomes. While longer-term impacts of COVID-19 are considered, it is crucial for NHS mental health services to understand the specific barriers and needs of ethnic minority communities to provide consistent and equitable access to mental health services. These aspects were the focus of a service evaluation of a Sussex-wide mental health service conducted in co-production with experts-by-experience, public members, health professionals and researchers from ethnic minority communities. METHODS: Co-designed creative workshops (n = 13) and semi-structured qualitative interviews (n = 13) were used to explore experiences of accessing specialist mental health services during the COVID-19 pandemic. Participants were: Sussex Partnership NHS Foundation Trust (SPFT) service users recruited between October 2021 and January 2022; aged 16+; from ethnic minority community backgrounds. Data was analysed using Thematic Analysis. RESULTS: The analysis yielded five overarching themes contextualising service users' experiences: (1) limited awareness of SPFT mental health services; (2) effects of COVID-19 in gaining access to SPFT; (3) SPFT reaching out to ethnic minorities; (4) being supported, 4a) hiding my mental health status from friends and families, 4b) lack of ethnic diversity in services, and 4c) better provision of information and support services, (5) relationship between childhood experiences and current mental health. These findings led to seven key recommendations for future service developments within SPFT. CONCLUSIONS: Although this evaluation was set in the context of COVID-19, findings have highlighted specific mental health service needs for ethnic minorities that are applicable beyond the confines of the pandemic. Many benefited from online sessions seen as more inclusive. Mental health advocates, outreach and joint working with communities could help further reduce stigmatising attitudes and improve engagement with mental health services. Improved service awareness of the impact of childhood or historical traumas experienced by ethnic minority communities on current mental health, the role of cultural awareness training and availability of culturally adapted therapies is also needed. Many service improvement recommendations provided could impact all service users.

Relating Therapy for Distressing Voices in the Context of Anorexia Nervosa: A Case Series.

ABSTRACT: Voice hearing experiences are commonly reported by patients with anorexia nervosa (AN) and are associated with negative outcomes. The "eating disorder voice" (EDV) can be understood within relational frameworks. Relating therapy (RT) has offered encouraging outcomes when targeted at voice hearing experiences transdiagnostically but has not been evaluated in the context of AN. This study aimed to offer a preliminary and mixed methods exploration of RT for the EDV. RT was delivered to three participants with a diagnosis of AN who were distressed by an EDV. Weight, negative impact of voices, and eating disorder cognitions were assessed at baseline, posttherapy and at brief follow-up. Participant experiences were explored through exit interviews. Therapy was completed by all participants. Weight gain was reported by two participants and maintained at brief follow-up. Positive changes were not reported on other measures. Qualitative data were suggestive of positive experiences that facilitated assertive responding.

"I feel like it gives me what I need to know": A qualitative study on adolescent perceptions of two contraceptive decision aids.

OBJECTIVES: We sought to understand how adolescents perceive two commonly used contraceptive decision aids and which elements adolescents identified as most important to them. STUDY DESIGN: We conducted a cross-sectional qualitative study of adolescents' perceptions of two decision aids, Your Birth Control Choices designed by the Reproductive Health Access Project and Birth Control: What's Important to You? designed by Power to Decide for Bedsider.org. We conducted semistructured interviews with 20 adolescents (aged 15-19 years) who were assigned female sex at birth and attended a single clinic in North Carolina. Interview questions addressed the decision aids' aesthetic design, informational content, inclusivity, and comprehensibility. We transcribed and analyzed interviews using Dedoose software. We developed a codebook using a combination of a priori and inductive codes followed by content analysis to identify themes. RESULTS: All participants agreed that both decision aids could be helpful with contraceptive decision-making and with patient-provider discussions. However, some phrasing and descriptions of contraceptive methods were confusing. Participants preferred realistic imagery, clear explanations of side effects, and details on method use. Participants expressed a preference for the information contained in the detailed Reproductive Health Access Project decision aid, while most favored the aesthetic design and layout of the Bedsider decision aid. CONCLUSIONS: Although adolescents expressed sentiments of increased knowledge and empowerment after reviewing the decision aids, this study suggests neither decision aid completely meets adolescent needs and preferences. Additional adaptations are necessary to create adolescent-centered contraceptive decision aids. IMPLICATIONS: Adolescents in this study found two contraceptive decision aids as useful adjuncts to conversations with providers. The decision aids improved contraceptive knowledge and may facilitate decision-making. However, neither of the studied decision aids fully met the perceived needs of adolescents. Future adaptations or designs should include additional adolescent-centered content.

Increasing access to CBT for psychosis patients: study protocol for a randomised controlled trial evaluating brief, targeted CBT for distressing voices delivered by assistant psychologists (GiVE3).

BACKGROUND: The National Institute for Health and Care Excellence (NICE) recommends that cognitive behaviour therapy (CBT) is offered to all patients with a psychosis diagnosis. However, only a minority of psychosis patients in England and Wales are offered CBT. This is attributable, in part, to the resource-intensive nature of CBT. One response to this problem has been the development of CBT in brief formats that are targeted at a single symptom and are deliverable by briefly trained therapists. We have developed Guided self-help CBT (the GiVE intervention) as a brief form of CBT for distressing voices and reported evidence for the feasibility of a randomised controlled trial (RCT) when the intervention was delivered by briefly trained therapists (assistant psychologists). This study will investigate the clinical and cost-effectiveness of the GiVE intervention when delivered by assistant psychologists following a brief training. METHODS: This study is a pragmatic, two-arm, parallel group, superiority RCT comparing the GiVE intervention (delivered by assistant psychologists) and treatment as usual to treatment as usual alone, recruiting across three sites, using 1:1 allocation and blind post-treatment and follow-up assessments. A nested qualitative study will develop a model for implementation. DISCUSSION: If the GiVE intervention is found to be effective when delivered by assistant psychologists, this intervention could significantly contribute to increasing access to evidence-based psychological interventions for psychosis patients. Furthermore, implementation across secondary care services within the UK's National Health Service may pave the way for other symptom-specific and less resource-intensive CBT-informed interventions for psychosis patients to be developed and evaluated. TRIAL REGISTRATION: Current Controlled Trials ISRCTN registration number: 12748453. Registered on 28 September 2022.

Trialling an optimised social groups intervention in services to enhance social connectedness and mental health in vulnerable young people (TOGETHER): Study protocol for a feasibility randomised controlled trial.

BACKGROUND: Calls have been made to rethink the mental health support currently available for young people. This study aims to help re-focus and reduce the inaccessibility of mental health services by offering an adapted version of a theoretically-driven, evidence-based, guided psychosocial intervention known as 'Groups 4 Health' (G4H). To date, the G4H intervention has mainly been trialled in Australia, with promising positive effects on social connection, mental health and well-being. The present study examines the feasibility of running a randomised controlled trial when delivering the G4H intervention for young people in the UK. METHODS: The TOGETHER study is a feasibility randomised controlled trial of an adapted version of the G4H intervention. Participants are aged 16-25, currently experiencing mental health difficulties and recruited from mental health services. The target sample size is 30, with 15 in each trial arm. Participants are randomly allocated to either G4H plus treatment as usual, or treatment as usual alone. The primary outcomes of interest are the feasibility of recruitment, randomisation, data collection and retention to the study at 10 and 14 week follow up, as well as the acceptability, and accessibility of the study protocol and G4H intervention. DISCUSSION: The results of this study will indicate if further optimisation is required to improve the feasibility, acceptability and accessibility of the intervention and study protocol procedures as perceived by end users and practitioners. This offers a significant opportunity to support the local and national demand for accessible, innovative, and effective psychosocial youth mental health support. TRIAL REGISTRATION: ISRCTN registry (ISRCTN12505807). Registration date: 11/04/2022.

Exploring the interagency collaboration between a pediatric oncology health care setting and community schools.

Globally, approximately 400,000 youth are diagnosed with pediatric cancer each year. Treatment-related side effects, psychosocial challenges, and frequent school absences may adversely impact learning and the education experience among these youth. Efforts to enhance interagency collaboration between health care settings and community schools are imperative to facilitate school reintegration. The Standards for the Psychosocial Care of Children with Cancer and Their Families outline specific guidelines related to the continuity of education for students impacted by pediatric cancer. In particular, the Academic Continuity and School Reentry Support and Monitoring and Assessment of Neuropsychological Outcomes standards of care highlighted within this article align with extant programmatic efforts for transitioning hospitalized school-aged children back into community schools. This article aims to describe systematic programmatic efforts within hospital-based psychosocial programs that are consistent with the Standards for the Psychosocial Care of Children with Cancer and Their Families, as well as interagency collaboration with community schools to support student-centered education for youth impacted by pediatric cancer. Resources for school psychologists, teachers, hospital-based programs, and others involved in student-centered education for pediatric cancer patients and survivors are presented. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

OUTdoor Swimming as a nature-based Intervention for DEpression (OUTSIDE): study protocol for a feasibility randomised control trial comparing an outdoor swimming intervention to usual care for adults experiencing mild to moderate symptoms of depression.

BACKGROUND: Depression is common and the prevalence increasing worldwide; at least 1 in 10 people will experience depression in their lifetime. It is associated with economic costs at the individual, healthcare and societal level. Recommended treatments include medication and psychological therapies. However, given the long waiting times, and sometimes poor concordance and engagement with these treatments, a greater range of approaches are needed. Evidence for the potential of outdoor swimming as an intervention to support recovery from depression is emerging, but randomised controlled trials (RCTs) evaluating clinical and cost-effectiveness are lacking. This study seeks to investigate the feasibility of conducting a definitive superiority RCT, comparing an 8-session outdoor swimming course offered in addition to usual care compared to usual care only, in adults who are experiencing mild to moderate symptoms of depression. Feasibility questions will examine recruitment and retention rates, acceptability of randomisation and measures, and identify the primary outcome measure that will inform the sample size calculation for a definitive full-scale RCT. This study will also explore potential facilitators and barriers of participation through evaluation questionnaires, focus-group discussions and interviews. METHODS/DESIGN: To address these aims and objectives, a feasibility superiority RCT with 1:1 allocation will be undertaken. We will recruit 88 participants with mild to moderate symptoms of depression through social prescribing organisations and social media in three sites in England. Participants will be randomised to either (1) intervention (8-session outdoor swimming course) plus usual care or (2) usual care only. Both groups will be followed up for a further 8 weeks. DISCUSSION: If findings from this feasibility RCT are favourable, a fully powered RCT will be conducted to investigate the clinical- and cost-effectiveness of the intervention. Findings from the definitive trial will provide evidence about outdoor swimming for depression for policymakers and has the potential to lead to greater choice of interventions for adults experiencing symptoms of depression. TRIAL REGISTRATION: Current controlled trial registration number is ISRCTN 90851983 registered on 19 May 2022.

The past, present, and future of immunotherapy for endometrial adenocarcinoma.

Incidences of endometrial adenocarcinoma are increasing in the USA with poor prognosis for patients with advanced disease. The current treatment standard is surgery including total hysterectomy and bilateral oophorectomy with surgical staging and adjunct treatment, such as chemotherapy or radiation. However, these methods do not present as an effective treatment option for poorly differentiated advanced cancers. Advancements in immunotherapy now offer a new approach for various types of cancer and specifically show promise in the treatment of endometrial adenocarcinoma. This review summarizes immunotherapeutic treatment options relevant to endometrial adenocarcinoma, such as immune checkpoint blockades, bispecific T-cell engager antibodies, vaccinations, and adoptive cell transfer. This study could be helpful for clinicians to identify treatment options more suitable for women with late-stage endometrial adenocarcinoma.

Developmental care pathway for hospitalised infants with CHD: on behalf of the Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative.

Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, "Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease," includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.

A new class of monoclonal Aß antibodies selectively targets and triggers deposition of Aß protofibrils.

Aggregation and accumulation of amyloid-ß peptide (Aß) are a critical trigger for the onset of Alzheimer's disease (AD). While the plaques are the most outstanding Aß pathological feature, much of the recent research emphasis has been on soluble Aß species because of their diffusible, proinflammatory, and toxic properties. The focus on soluble aggregated Aß species has also increased the interest in antibodies that are selective for different Aß conformations. In the current study, we developed and characterized a new class of monoclonal antibodies (referred to as mAbSL) that are selective for Aß protofibrils. Cloning and sequencing of the heavy and light chain variable regions for multiple antibodies identified sequence characteristics that may impart the conformational selectivity by the antibodies. Transfection of FreeStyle 293F cells with the plasmids permitted in-house expression and purification of mAbSL antibodies along with non-conformation-selective Aß monoclonal antibodies (Aß mAbs). Several of the purified mAbSL antibodies demonstrated significant affinity and selectivity for Aß42 protofibrils compared with Aß42 monomers and Aß42 fibrils. Competition ELISA assays assessing the best overall antibody, mAbSL 113, yielded affinity constants of 7 nM for the antibody-Aß42 protofibril interaction, while the affinity for either Aß42 monomers or Aß42 fibrils was roughly 80 times higher. mAbSL 113 significantly inhibited Aß42 monomer aggregation by a unique mechanism compared with the inhibition displayed by Aß mAb 513. Aß42 protofibril dynamics were also markedly altered in the presence of mAbSL 113, whereby insoluble complex formation and protofibril deposition were stimulated by the antibody at low substoichiometric molar ratios. As the field contemplates the therapeutic effectiveness of Aß conformation-selective antibodies, the findings presented here demonstrate new information on a monoclonal antibody that selectively targets Aß protofibrils and impacts Aß dynamics.

Combatting climate change using education and training in pharmacology and therapeutics.

The climate crisis has implications for the physical and mental health of people worldwide, while, paradoxically, healthcare itself contributes significant greenhouse gas emissions. Healthcare professionals need to be prepared to both mitigate the impacts of climate change and also manage the health effects of the climate crisis. Widespread adoption of sustainable healthcare models is required, with sustainability-driven improvements in clinical pharmacology intrinsically linked to this. Recognizing that education and training are essential steps to equip medical professionals with the knowledge to face the unprecedented challenges that the climate crisis presents, here, with reference to pharmacology and therapeutics, we discuss how the theme of Education for Sustainable Healthcare (ESH) can be integrated into undergraduate and postgraduate teaching programmes and how barriers to successful implementation can be tackled. We support the use of the Principles of Sustainable Clinical Practice as a framework to guide educational interventions and draw upon examples of our own practice at Brighton and Sussex Medical School where ESH has become a core component of medical education in our undergraduate curriculum.

A relatively high proportion of dogs with small apocrine gland anal sac adenocarcinoma (AGASACA) primary tumours present with locoregional lymph node metastasis.

Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly relevant disease in dogs, with a high rate of lymph node (LN) metastasis during the course of disease. A recent study showed that risk for death and disease progression was significantly associated with primary tumour size less than 2 and 1.3 cm, respectively. The objective of this study was to report the proportion of dogs that have primary tumours less than 2 cm in diameter, that are diagnosed with LN metastasis at presentation. This was a single site retrospective study of dogs that underwent treatment for AGASACA. Dogs were included if physical examination primary tumour measurements were available, abdominal staging was performed, and confirmation of abnormal lymph nodes by cytology or histology was done. Over a 5-year period, 116 dogs were included for review with 53 (46%) having metastatic LN at presentation. The metastatic rate for dogs with primary tumours <2 cm was 20% (9 of 46 dogs) compared to 63% (44 of 70 dogs) in dogs with primary tumours ≥2 cm. The association between tumour size group (<2 vs. ≥2 cm) and the presence of metastasis at presentation was significant (P < .0001) with an OR of 7.0 (95% CI: 2.9-15.7). Primary tumour size was significantly associated with LN metastasis at presentation but the proportion of dogs that presented with LN metastasis in the <2 cm group was relatively high. This data suggests that dogs with small tumours may still have aggressive tumour biology.