Examining patient demographics and major adverse cardiac events following noncardiac surgery: Applying a health equity lens.

BACKGROUND: Major adverse cardiac events (MACE) are a major contributor to postoperative complications. This study employed a health equity lens to examine rates of postoperative MACE by race and ethnicity. METHODS: This single-center, retrospective observational cohort study followed patients with and without pre-existing coronary artery stents from 2008 to 2018 who underwent non-cardiac surgery. MACE was the primary outcome (death, acute MI, repeated coronary revascularization, in-stent thrombosis) and self-reported race and ethnicity was the primary predictor. A propensity score model of a 1:1 cohort of non-Hispanic White (NHW) patients and all other racial and ethnic minority populations (Hispanic and Black) was used to compare the rate of perioperative MACE in this cohort. RESULTS: During the study period, 79,686 cases were included in the analytic sample; 950 patients (1.2 %) had pre-existing coronary artery stents. <1 % of patients experienced MACE within 30 days following non-cardiac surgery (0.8 %). After confounder adjustment and propensity score matching, there were no statistically significant differences in MACE among racial and ethnic minority patients compared to NHW patients (OR = 0.77; 95 % CI: 0.48, 1.25). In our sensitivity analyses, stratifying by sex, there were no differences in MACE by race and ethnicity. CONCLUSIONS: The study found no statistically significant differences in MACE by race and ethnicity among patients who underwent non-cardiac surgery. Access to a high-volume, high-quality hospital such as the one studied may reduce the presence of healthcare disparities and may explain why our findings are not consistent with previous studies.

Risk of Fractures and Falls in Men with Advanced or Metastatic Prostate Cancer Receiving Androgen Deprivation Therapy and Treated with Novel Androgen Receptor Signalling Inhibitors: A Systematic Review and Meta-analysis of Randomised Controlled Trials.

CONTEXT: The addition of androgen receptor signalling inhibitors (ARSIs) to standard androgen deprivation therapy (ADT) has improved survival outcomes in patients with advanced prostate cancer (PCa). Advanced PCa patients have a higher incidence of osteoporosis, compounded by rapid bone density loss upon commencement of ADT resulting in an increased fracture risk. The effect of treatment intensification with ARSIs on fall and fracture risk is unclear. OBJECTIVE: To assess the risk of falls and fractures in men with PCa treated with ARSIs. EVIDENCE ACQUISITION: A systematic review of EMBASE, MEDLINE, The Cochrane Library, and The Health Technology Assessment Database for randomised control trials between 1990 and June 2023 was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analyses guidance. Risk ratios were estimated for the incidence of fracture and fall events. Subgroup analyses by grade of event and disease state were conducted. EVIDENCE SYNTHESIS: Twenty-three studies were eligible for inclusion. Fracture outcomes were reported in 17 studies (N = 18 811) and fall outcomes in 16 studies (N = 16 537). A pooled analysis demonstrated that ARSIs increased the risk of fractures (relative risk [RR] 2.32, 95% confidence interval [CI] 2.00-2.71; p < 0.01) and falls (RR 2.22, 95% CI 1.81-2.72; p < 0.01) compared with control. A subgroup analysis demonstrated an increased risk of both fractures (RR 2.13, 95% CI 1.70-2.67; p < 0.01) and falls (RR 2.19, 95% CI 1.53-3.12; p < 0.0001) in metastatic hormone-sensitive PCa patients, and an increased risk of fractures in the nonmetastatic (RR 2.27, 95% CI 1.60-3.20; p < 0.00001) and metastatic castrate-resistant (RR 2.85, 95% CI 2.16-3.76; p < 0.00001) settings. The key limitations include an inability to distinguish fragility from pathological fractures and potential for a competing risk bias. CONCLUSIONS: Addition of an ARSI to standard ADT significantly increases the risk of fractures and falls in men with prostate cancer. PATIENT SUMMARY: We found a significantly increased risk of both fractures and falls with a combination of novel androgen signalling inhibitors and traditional forms of hormone therapy.

"Ten Days of Paid Incarceration and Mental Torture" Experiences of Quarantined Individuals Arriving in the UK from Red Listed Countries in Southern Africa Amid the COVID-19 Pandemic.

COVID-19 has affected many communities across the world prompting different strategies of containing it. The strategies to contain COVID-19 included restrictive environments such as self-isolation and quarantine. This research study was set to explore the experiences of quarantined individuals arriving in the United Kingdom (UK) from red listed countries in Southern Africa. This research study utilises an exploratory qualitative approach. Semi-structured interviews were used to collect data from twenty-five research participants. A thematic approach underpinning the four phases of data analysis in The Silence Framework (TSF) was used to analyse the data. The study found that the research participants reported confinement, dehumanisation, feeling swindled, depressed, anxious and stigmatised. Less restrictive and non-oppressive quarantine regimes should be considered to foster positive mental health outcomes on individuals undergoing quarantine during pandemics.

A tailored approach to horizon scanning for cancer medicines.

BACKGROUND: Horizon scanning (HS) is the systematic identification of emerging therapies to inform policy and decision-makers. We developed an agile and tailored HS methodology that combined multi-criteria decision analysis weighting and Delphi rounds. As secondary objectives, we aimed to identify new medicines in melanoma, non-small cell lung cancer and colorectal cancer most likely to impact the Australian government's pharmaceutical budget by 2025 and to compare clinician and consumer priorities in cancer medicine reimbursement. METHOD: Three cancer-specific clinician panels (total n = 27) and a consumer panel (n = 7) were formed. Six prioritisation criteria were developed with consumer input. Criteria weightings were elicited using the Analytic Hierarchy Process (AHP). Candidate medicines were identified and filtered from a primary database and validated against secondary and tertiary sources. Clinician panels participated in a three-round Delphi survey to identify and score the top five medicines in each cancer type. RESULTS: The AHP and Delphi process was completed in eight weeks. Prioritisation criteria focused on toxicity, quality of life (QoL), cost savings, strength of evidence, survival, and unmet need. In both curative and non-curative settings, consumers prioritised toxicity and QoL over survival gains, whereas clinicians prioritised survival. HS results project the ongoing prevalence of high-cost medicines. Since completion in October 2021, the HS has identified 70 % of relevant medicines submitted for Pharmaceutical Benefit Advisory Committee assessment and 60% of the medicines that received a positive recommendation. CONCLUSION: Tested in the Australian context, our method appears to be an efficient and flexible approach to HS that can be tailored to address specific disease types by using elicited weights to prioritise according to incremental value from both a consumer and clinical perspective. POLICY SUMMARY: Since HS is of global interest, our example provides a reproducible blueprint for adaptation to other healthcare settings that integrates consumer input and priorities.

Prioritising Cochrane reviews to be updated with health equity focus.

BACKGROUND: The prioritisation of updating published systematic reviews of interventions is vital to prevent research waste and ensure relevance to stakeholders. The consideration of health equity in reviews is also important to ensure interventions will not exacerbate the existing inequities of the disadvantaged if universally implemented. This study aimed to pilot a priority setting exercise based on systematic reviews of interventions published in the Cochrane Library, to identify and prioritise reviews to be updated with a focus on health equity. METHODS: We conducted a priority setting exercise with a group of 13 international stakeholders. We identified Cochrane reviews of interventions that showed a reduction in mortality, had at least one Summary of Findings table and that focused on one of 42 conditions with a high global burden of disease from the 2019 WHO Global Burden of Disease report. This included 21 conditions used as indicators of success of the United Nations Universal Health Coverage in attaining the Sustainable Development Goals. Stakeholders prioritised reviews that were relevant to disadvantaged populations, or to characteristics of potential disadvantage within the general population. RESULTS: After searching for Cochrane reviews of interventions within 42 conditions, we identified 359 reviews that assessed mortality and included at least one Summary of Findings table. These pertained to 29 of the 42 conditions; 13 priority conditions had no reviews with the outcome mortality. Reducing the list to only reviews showing a clinically important reduction in mortality left 33 reviews. Stakeholders ranked these reviews in order of priority to be updated with a focus on health equity. CONCLUSIONS: This project developed and implemented a methodology to set priorities for updating systematic reviews spanning multiple health topics with a health equity focus. It prioritised reviews that reduce overall mortality, are relevant to disadvantaged populations, and focus on conditions with a high global burden of disease. This approach to the prioritisation of systematic reviews of interventions that reduce mortality provides a template that can be extended to reducing morbidity, and the combination of mortality and morbidity as represented in Disability-Adjusted Life Years and Quality-Adjusted Life Years.

A low-cost automated titration system for colorimetric endpoint detection.

An auto titrator system was developed to accurately and precisely detect colorimetric endpoints for spectrochemical titrations. This system was constructed using inexpensive components such as a Raspberry Pi® single-board computer, 3D-printed components, and a commercially available spectral sensor. The auto titrator was evaluated by performing a standard method for determination of water hardness. Regardless of analyst experience, the auto titrator performed better than the traditional titration approach that involves manual dosing of titrant and visual detection of the endpoint. Inter-day, intra-day, inter-instrumental, and intra-instrumental validation studies were performed to establish the accuracy and precision of endpoint detection. The auto titrator eliminates the subjective bias in color perception and produces accurate and precise endpoint results.

COVID-19 IDD: Findings from a global survey exploring family members' and paid staff's perceptions of the impact of COVID-19 on individuals with intellectual and developmental disabilities (IDD) and their caregivers.

Background: A growing body of evidence attests to the disproportionate impact of COVID-19 on persons with intellectual and developmental disabilities (IDD) during the pandemic. This study asked caregivers about their perceptions of how COVID-19 impacted them and the people they support. Method: An online survey was conducted in 12 countries during August-September 2020 and sought information on demographics, support practices, information and training, experiences of COVID-19, social distancing, and wellbeing, as measured by the DASS12. This study reports on 3,754 family members, direct support professionals, and managers who participated in the survey. Results: Caregivers observed increases in depression/anxiety, stereotyped behaviours, aggression towards others and weight gain in the person(s) they supported. They also reported difficulties supporting the person(s) to access healthcare.  Families reported reducing or ceasing employment and absorbed additional costs when supporting their family member. Direct support professionals experienced changes in staff shifts, staff absences, increased workload and hiring of casual staff. Caregivers' wellbeing revealed high levels of stress, depression, and less so anxiety. The strongest predictor of wellbeing among families was observation of changes in mood in the person(s) they supported, while for direct support professionals, the strongest predictors of wellbeing were reorganisation of staff shifts and increases in new direct support staff.  Discussion: Findings support the contention of this population experiencing a disproportionate burden during the COVID-19 pandemic, reflecting historical inequities in access to healthcare and other human rights violations which are now protected under the United Nations Convention on the Rights of Persons with Disabilities.

Potential Risks for Healthcare Disparities Among Individuals With Voice and Upper Airway Disorders: A Systematic Review.

PURPOSE: To assess the potential epidemiological association between various possible risk factors and healthcare disparities specifically related to the access, use and/or quality of speech language pathology services for individuals with voice and upper airway disorders. METHOD: A systematic review was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis. Full text journal articles were identified through PubMed, PsycINFO and Web of Science. The reference sections of included articles were also manually screened and identified four additional studies for consideration of inclusion. Included articles specifically addressed healthcare disparities in voice and upper airway disorders related to speech pathology care. International literature was excluded. Eligible studies were reviewed and data extracted. Risk of bias of each eligible study was performed using the quality assessment tool from National Institute of Health for observational cohort and cross-sectional studies. Data from eligible studies were synthesized thematically. RESULTS: A total of 1,101 resources were retrieved from the search; of these, 133 were duplicates. Titles and abstracts of 968 articles were screened, with 14 selected for full-text review. Eleven articles were considered eligible for inclusion. Voice disorders were the condition most frequently examined followed by only one article addressing upper airways disorders. There was considerable heterogeneity in the methodology and statistical analyses among the eligible papers. There was a lack of standard methodology for collecting and accurately determining patient characteristics as well as variability in measuring confounding variables and providing statistical analyses for such adjustments that may have impacted the findings. The information extracted from these articles revealed healthcare disparities related to sex/gender, age, insurance status/coverage, race/ethnicity, among others including etiology and preferred language. CONCLUSIONS: This systematic review highlights the limited research on speech language pathology-specific healthcare disparities for individuals with voice and upper airway disorders. There was significant clinical and methodological heterogeneity between studies which may have contributed to varied results between studies. There is a need for greater methodological rigor and prospectively designed studies to better characterize the impact of disparities in the access to, use of, and quality of speech pathology care for this patient population.

Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

The views and experiences of LGBTQ+ people regarding midwifery care: A systematic review of the international evidence.

BACKGROUND: There has been growing attention to addressing the health inequalities and concerns of LGBTQ+ people, with research evidence highlighting areas requiring further attention and development. The distinct concerns of LGBTQ+ people when accessing midwifery care and support is an issue requiring a specific focus to ensure needs are met effectively. AIM: The aim of this systematic review was to critically appraise and synthesise the best available evidence regarding the views and experiences of LGBTQ+ people in relation to midwifery care and supports. METHOD: A systematic review was undertaken to identify all relevant studies meeting the inclusion criteria. A total of eleven papers were included in the review, utilising the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) method. Methodological quality was evaluated using the Mixed Methods Assessment Tool (MMAT). FINDINGS: Following data analysis, the themes that emerged were: (i) Contemplating pregnancy and ante-natal experiences, (ii) pregnancy and labour issues and concerns, and (iii) post-natal ongoing care and supports. CONCLUSION AND IMPLICATIONS FOR PRACTICE: It has become apparent from this systematic review that LGBTQ+ individuals have variable experiences when accessing midwifery care and support. Midwifery policies and practice guidelines should be reflective of the distinct needs of LGBTQ+ people and their families and friends. Future studies could focus more on the impact and outcomes of their care experiences within midwifery services.

Feasibility of a Web-Based Platform (Trial My App) to Efficiently Conduct Randomized Controlled Trials of mHealth Apps For Patients With Cardiovascular Risk Factors: Protocol For Evaluating an mHealth App for Hypertension.

BACKGROUND: Mobile health (mHealth) interventions can improve health by improving cardiovascular risk factors, but their adoption in care by physicians and patients is untapped. Few mHealth apps have been evaluated in clinical trials, and due to the fast pace of technological development, those previously evaluated are often outdated by the time trial results are available. Given the rapid pace of change in this field, it is not feasible to rigorously evaluate mHealth apps with current methodologies. OBJECTIVE: The overall aim of this pilot study was to test the feasibility of using a web research platform called Trial My App to conduct efficient and rigorous web-based randomized controlled trials (RCTs) of mHealth apps relevant to patients with cardiovascular risk factors by evaluating an app that targets hypertension. METHODS: For this study, 200 participants with suboptimally controlled hypertension will be recruited through advertisements in newsletters, media, and the internet, as well as through referrals from their health care providers. Screening, consent, randomization, and collection of patient-important health confidence and self-management ability outcomes will be conducted online through the Trial My App research platform. Participants will be randomized into 2 groups: 100 that will use an mHealth app for tracking hypertension and 100 that will be considered as an educational control. All participants will complete questionnaires at 0, 1, 3 and 6 months after enrolment. A substudy to validate the method of blood pressure readings and the consistency of data entered through Trial My App will be conducted with 40 participants. RESULTS: The development of the Trial My App web platform has been completed. The creation of survey instruments has been completed in collaboration with our patient partners and advisory board. Recruitment is expected to begin in the first quarter of 2021; data collection and analysis are expected to be completed approximately 1 year after study commencement. Results will be disseminated through conferences and publications. The primary outcomes of this study include the feasibility of conducting an RCT using the Trial My App platform by reporting recruitment, retention, and completion statistics. We will validate app-entered data with a standard 7-day home blood pressure measurement method. Lastly, the pilot, nonblinded RCT will assess the effectiveness of the mHealth app in improving the control of hypertension compared with the control of hypertension in the educational control group. CONCLUSIONS: This study will determine if it is feasible to use the Trial My App web-based platform to evaluate the effectiveness of mHealth apps for patients with cardiovascular risk factors. As more mHealth apps are evaluated in RCTs, patients will be able to select apps that meet their needs and physicians will be able to make evidence-based recommendations to their patients for apps aimed at improving cardiovascular health. TRIAL REGISTRATION: ClinicalTrials.gov NCT04528654; https://clinicaltrials.gov/ct2/show/NCT04528654. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/26155.

The views and experiences of bisexual people regarding their psychosocial support needs: a qualitative evidence synthesis.

WHAT IS KNOWN ON THE SUBJECT?: Bisexual people experience significantly poorer mental health and higher rates of self-harm and suicidality than their gay, lesbian or heterosexual counterparts. Although little is understood about why these disparities exist, bisexual people have been found to have unique life experiences that separate them from other sexual minority groups. Despite these health disparities and unique experiences, in research and in clinical settings, bisexual people are often incorporated under the LGBTQI+ umbrella and their needs are not seen as being different to those of other sub-groups. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This paper brings together the findings of the small but growing body of literature reporting on the psychosocial support needs of bisexual people. The findings reported on herein provide novel insights, collated and synthesized that will prove valuable to policy makers, service providers and researchers. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This paper clearly illustrates that bisexual people experience significant barriers to accessing the support services they need and that current competent service provision for this population is severely limited. The findings presented in this paper shed light on the unique psychosocial needs of bisexual people and highlight the need for practice change to reduce barriers to service access and ensure inclusive and culturally competent care for this community. ABSTRACT: Introduction Despite consistent evidence of poor mental health among what is a relatively large population group, research examining bisexual mental health remains sparse. Aim To identify the psychosocial needs of people who are bisexual and establish factors that may support or inhibit access to appropriate psychosocial interventions and supports. Method A qualitative evidence syntheses of the empirical evidence. Results A total of 15 papers were included in the review. The PRISMA process was used. Following data analysis, four main themes emerged that were (a) experiences of being bisexual, (b) mental health experiences and concerns, (c) service access and responses and (iv) communities and supports. Discussion Bisexual people have unique and specific psychosocial support needs that relate to, but are also different from, the needs of the broader LGBTIQ+ community. This study provides valuable insights into how future policy, practice, education and training and research can better address the needs of this highly vulnerable group. Implications for Practice This study highlights the psychosocial complexities associated with bisexuality and provides evidence for the need for improvement in current support services to ensure inclusivity and culturally competent care.

Tranexamic acid is associated with decreased transfusion, hospital length of stay, and hospital cost in simultaneous bilateral total knee arthroplasty.

Tranexamic acid (TXA) reduces blood loss and transfusion rates in unilateral total knee arthroplasty (TKA), but there is limited data regarding its efficacy in bilateral TKA. This study reports the impact TXA has on clinical outcomes and hospital cost of care in simultaneous, primary bilateral TKA. The 449 patients were retrospectively reviewed. Primary outcomes included the rates of allogeneic and autologous blood transfusion. Secondary outcomes included hospital length of stay (HLOS), post-hospital discharge disposition, 30-day thromboembolic events (TEE), and mean hospital cost of care. Total direct medical costs were obtained from an institutional research database and adjusted to nationally representative unit costs in 2013 inflation-adjusted dollars. Our study revealed that in patients undergoing simultaneous bilateral TKA, TXA use was associated with reduced allogeneic (OR 0.181, 95% CI 0.090-0.366, p < 0.001) and combined allogeneic and autologous transfusion rates (OR 0.451, 95% CI 0.235-0.865, p = 0.017). TXA was associated with a HLOS reduction of 0.9 days (ß-coefficient -0.582, 95% CI -1.008--0.156, p = 0.008), an increased likelihood of hospital discharge over skilled nursing facility (SNF) (OR 2.25, 95% CI 1.117-4.531, p = 0.023) and reduced total hospital cost of care by 6.45% (p < 0.001), room and board costs by 11.76% (p < 0.001), and transfusion costs by 81.65% (p < 0.001). In conclusion, TXA use in bilateral TKA is associated with lower blood transfusion rates, reduced hospital length of stay, reduced cost of hospital care and skilled nursing facility avoidance.

How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis.

OBJECTIVES: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics. DESIGN: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials. SETTING: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit. PARTICIPANTS: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included. MAIN OUTCOME MEASURES: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers. RESULTS: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials. CONCLUSIONS: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.

A preliminary assessment of oral monepantel's tolerability and pharmacokinetics in individuals with treatment-refractory solid tumors.

PURPOSE: Monepantel is an approved veterinary anthelmintic with a strong safety profile. Preclinical evidence suggests novel mTOR pathway-associated anticancer activity. An open-label Phase I trial assessed tolerability, pharmacokinetics, pharmacodynamics and PET-CT imaging following oral Zolvix® monepantel administration to adults with treatment refractory, progressing and unresectable solid tumors. METHODS: Subjects were scheduled to daily home-based monepantel administration for 28 days in a 3 + 3 dose escalation study (5.0, 25.0 and 62.5 mg/kg bw). RESULTS: Of 41 reported drug-related AEs, 68% were Grade 1 and 24% were Grade 2; 35 AEs related to gastrointestinal effects including very poor palatability. DLT and MTD could not be determined due to early termination. Myelosuppression was not observed at the lowest level tested. Three of four Cohort 1 subjects had reduced mTOR pathway marker p-RPS6KB1 levels in PBMCs and achieved RECISTv1.1 SD by CT; one had progressive bony metastases by FDG-PET. One subject recorded PD on day 28, correlating with no detectable plasma monepantel from day 7. Monepantel sulfone dominated monepantel in pharmacokinetics. Both Cohort 2 subjects withdrew early due to AEs and the trial was terminated. CONCLUSIONS: Short-term 5 mg/kg bw monepantel administration provides a combined steady-state trough plasma monepantel and monepantel sulfone concentration of 0.5 µM. Gastrointestinal AEs including very poor palatability are concerning and suggested to be resolved by future drug product reformulation. RECISTv1.1, p-RPS6KB1 and plasma tumor marker outcomes provide preliminary evidence of anticancer activity.

Effects of cost surface uncertainty on current density estimates from circuit theory.

BACKGROUND: Conservation practitioners are often interested in developing land use plans that increase landscape connectivity, which is defined as the degree to which the landscape facilitates or impedes movement among resource patches. Landscape connectivity is often estimated with a cost surface that indicates the varying costs experienced by an organism in moving across a landscape. True, or absolute costs are rarely known however, and therefore assigning costs to different landscape elements is often a challenge in creating cost surface maps. As such, we consider it important to understand the sensitivity of connectivity estimates to uncertainty in cost estimates. METHODS: We used simulated landscapes to test the sensitivity of current density estimates from circuit theory to varying relative cost values, fragmentation, and number of cost classes (i.e., thematic resolution). Current density is proportional to the probability of use during a random walk. Using Circuitscape software, we simulated electrical current between pairs of nodes to create current density maps. We then measured the correlation of the current density values across scenarios. RESULTS: In general, we found that cost values were highly correlated across scenarios with different cost weights (mean correlation ranged from 0.87 to 0.92). Changing the spatial configuration of landscape elements by varying the degree of fragmentation reduced correlation in current density across maps. We also found that correlations were more variable when the range of cost values in a map was high. DISCUSSION: The low sensitivity of current density estimates to relative cost weights suggests that the measure may be reliable for land use applications even when there is uncertainty about absolute cost values, provided that the user has the costs correctly ranked. This finding should facilitate the use of cost surfaces by conservation practitioners interested in estimating connectivity and planning linkages and corridors.

Parents' experiences of transition from hospital to home of a child with complex health needs: A systematic literature review.

AIMS AND OBJECTIVES: To critically appraise primary research on the views and experiences of parents of children with complex health needs during the transition from hospital to home. BACKGROUND: Children with complex health needs frequently transition across and within healthcare systems, due to their age, care needs and ongoing health conditions. Repeated and unplanned admissions are significantly higher for children with complex health needs. Yet parents, as the primary providers of care, report being unsupported and unprepared during the transition from hospital back to home due to poor communication, inadequate discharge planning and education, resulting in stress and anxiety within the home environment. DESIGN: Systematic review following PRISMA guidelines. METHODS: A systematic search was completed of the databases CINAHL, MEDLINE, PsycINFO, EMBASE and the Cochrane Library Review between January 2009 and September 2019. Data were extracted, categorised and analysed using a thematic analysis approach. An adapted CASP qualitative assessment tool was utilised for quality assessment. All included articles were marked for validity and relevance to current research with an overall score from 0-20. RESULTS: A total of 13 studies of mixed quality were identified. CASP quality scores ranged from 13-18. Four themes emerged highlighting parents' experiences of the emotional processes, communication, coordination and support and resources when transitioning from hospital to home. CONCLUSIONS: Hospital discharge and transition from hospital to home is a complicated and at times frustrating process for parents of children with complex health needs. Parents report being exhausted and stressed during this often-challenging period of adjustment which was perceived as a difficult and emotional process. There is a clear lack of support available for parents both from hospital and community services.

The needs of LGBTI+ people within student nurse education programmes: A new conceptualisation.

There is a growing body of international research evidence highlighting concerns around social exclusion and discrimination, significant health inequalities and health needs, and barriers to accessing effective healthcare for LGBTI + people. However, ways in which the healthcare needs of LGBTI + people can be addressed in student nurse education programmes have yet to be fully explored. The aim of this discussion paper is to present the evidence to support the inclusion of LGBTI + health throughout the nursing curriculum. A new conceptualisation of the full and effective integration of LGBTI + health content across and within the nursing curriculum is proposed. This can be achieved by further developing theory, skills simulation and practice learning opportunities. There is a need to ensure that nursing students are positioned and adequately prepared to effectively address concerns of social justice, reducing health inequalities, and providing responsive person-centred care for LGBTI + health service users.