Indigenous access to clinical services along the lung cancer treatment pathway: a review of current evidence.

BACKGROUND: Lung cancer is a deadly cancer. Early diagnosis and access to timely treatment are essential to maximizing the likelihood of survival. Indigenous peoples experience enduring disparities in lung cancer survival, and disparities in access to and through lung cancer services is one of the important drivers of these disparities. In this manuscript, we aimed to examine the current evidence on disparities in Indigenous access to services along the lung cancer treatment pathway. METHODS: A narrative literature review was conducted for all manuscripts and reports published up until July 20, 2022, using Medline, Scopus, Embase, and Web of Science. Following the identification of eligible literature, full-text versions were scanned for relevance for inclusion in this review, and relevant information was extracted. After scanning 1,459 documents for inclusion, our final review included 36 manuscripts and reports that included information on lung cancer service access for Indigenous peoples relative to non-Indigenous peoples. These documents included data from Aotearoa New Zealand, Australia, Canada, and the USA (including Hawai'i). RESULTS: Our review found evidence of disparities in access to, and the journey through, lung cancer care for Indigenous peoples. Disparities were most obvious in access to early detection and surgery, with inconsistent evidence regarding other components of the pathway. CONCLUSION: These observations are made amid relatively scant data in a global sense, highlighting the need for improved data collection and monitoring of cancer care and outcomes for Indigenous peoples worldwide. Access to early detection and guideline-concordant treatment are essential to addressing enduring disparities in cancer survival experienced by Indigenous peoples globally.

Codesign and refinement of an optimised antenatal education session to better inform women and prepare them for labour and birth.

OBJECTIVE: Our objective was to codesign, implement, evaluate acceptability and refine an optimised antenatal education session to improve birth preparedness. DESIGN: There were four distinct phases: codesign (focus groups and codesign workshops with parents and staff); implementation of intervention; evaluation (interviews, questionnaires, structured feedback forms) and systematic refinement. SETTING: The study was set in a single maternity unit with approximately 5500 births annually. PARTICIPANTS: Postnatal and antenatal women/birthing people and birth partners were invited to participate in the intervention, and midwives were invited to deliver it. Both groups participated in feedback. OUTCOME MEASURES: We report on whether the optimised session is deliverable, acceptable, meets the needs of women/birthing people and partners, and explain how the intervention was refined with input from parents, clinicians and researchers. RESULTS: The codesign was undertaken by 35 women, partners and clinicians. Five midwives were trained and delivered 19 antenatal education (ACE) sessions to 142 women and 94 partners. 121 women and 33 birth partners completed the feedback questionnaire. Women/birthing people (79%) and birth partners (82%) felt more prepared after the class with most participants finding the content very helpful or helpful. Women/birthing people perceived classes were more useful and engaging than their partners. Interviews with 21 parents, a midwife focus group and a structured feedback form resulted in 38 recommended changes: 22 by parents, 5 by midwives and 11 by both. Suggested changes have been incorporated in the training resources to achieve an optimised intervention. CONCLUSIONS: Engaging stakeholders (women and staff) in codesigning an evidence-informed curriculum resulted in an antenatal class designed to improve preparedness for birth, including assisted birth, that is acceptable to women and their birthing partners, and has been refined to address feedback and is deliverable within National Health Service resource constraints. A nationally mandated antenatal education curriculum is needed to ensure parents receive high-quality antenatal education that targets birth preparedness.

Protocol for cost-effectiveness analysis of a randomised trial of mHealth coaching (Bump2Baby and Me) compared with usual care for healthy gestational weight gain and postnatal outcomes in at-risk women and their offspring in the UK, Australia, Ireland and Spain.

INTRODUCTION: Gestational diabetes mellitus and overweight are associated with an increased likelihood of complications during birth and for the newborn baby. These complications lead to increased immediate and long-term healthcare costs as well as reduced health and well-being in women and infants. This protocol presents the health economic evaluation to investigate the cost-effectiveness of Bump2Baby and Me (B2B&Me), which is a health coaching intervention delivered via smartphone to women at risk of gestational diabetes. METHODS AND ANALYSIS: Using data from the B2B&Me randomised controlled trial, this economic evaluation compares costs and health effects between the intervention and control group as an incremental cost-effectiveness ratio. Direct healthcare costs, costs of pharmaceuticals and intervention costs will be included in the analysis, body weight and quality-adjusted life-years for the mother will serve as the effect outcomes. To investigate the long-term cost-effectiveness of the trial, a Markov model will be employed. Deterministic and probabilistic sensitivity analysis will be employed. ETHICS AND DISSEMINATION: The National Maternity Hospital Human Research and Ethics Committee was the primary approval site (EC18.2020) with approvals from University College Dublin HREC-Sciences (LS-E-20-150-OReilly), Junta de Andalucia CEIM/CEI Provincial de Granada (2087-M1-22), Monash Health HREC (RES-20-0000-892A) and National Health Service Health Research Authority and Health and Care Research Wales (HCRW) (21/WA/0022). The results from the analysis will be disseminated in scientific papers, through conference presentations and through different channels for communication within the project. TRIAL REGISTRATION NUMBER: ACTRN12620001240932.

Cross Sectional Survey of Antenatal Educators' Views About Current Antenatal Education Provision.

OBJECTIVES: Antenatal education (ANE) is part of National Health Service (NHS) care and is recommended by The National Institute for Health and Care Excellence (NICE) to increase birth preparedness and help pregnant women/birthing people develop coping strategies for labour and birth. We aimed to understand antenatal educator views about how current ANE supports preparedness for childbirth, including coping strategy development with the aim of identifying targets for improvement. METHODS: A United Kingdom wide, cross-sectional online survey was conducted between October 2019 and May 2020. Antenatal educators including NHS midwives and private providers were purposively sampled. Counts and percentages were calculated for closed responses and thematic analysis used for open text responses. RESULTS: Ninety-nine participants responded, 62% of these did not believe that ANE prepared women for labour and birth. They identified practical barriers to accessing ANE, particularly for marginalised groups, including financial and language barriers. Educators believe class content is medically focused, and teaching is of variable quality with some midwives being ill-prepared to deliver antenatal education. 55% of antenatal educators believe the opportunity to develop coping strategies varies between location and educators and only those women who can pay for non-NHS classes are able to access all the coping strategies that can support them with labour and birth. CONCLUSIONS FOR PRACTICE: Antenatal educators believe current NHS ANE does not adequately prepare women for labour and birth, leading to disparities in birth preparedness for those who cannot access non-NHS classes. To reduce this healthcare inequality, NHS classes need to be standardised, with training for midwives in delivering ANE enhanced.

Maternity healthcare professionals' experiences of supporting women in decision-making for labour and birth: a qualitative study.

OBJECTIVES: To explore and characterise maternity healthcare professionals' (MHCPs) experience and practice of shared decision-making (SDM), to inform policy, research and practice development. DESIGN: Qualitative focus group study. SETTING: Large Maternity Unit in the Southwest of England. PARTICIPANTS: MHCPs who give information relating to clinical procedures and pregnancy care relating to labour and birth and are directly involved in decision-making conversations were purposively sampled to ensure representation across MHCP groups. DATA COLLECTION: A semistructured topic guide was used. DATA ANALYSIS: Reflexive thematic analysis was undertaken. RESULTS: Seven focus groups were conducted, comprising a total of 24 participants (3-5 per group). Two themes were developed: contextualising decision-making and controversies in current decision-making. Contextual factors that influenced decision-making practices included lack of time and challenges faced in intrapartum care. MHCPs reported variation in how they approach decision-making conversations and asked for more training on how to consistently achieve SDM. There were communication challenges with women who did not speak English. Three controversies were explored: the role of prior clinical experience, the validity of informed consent when women were in pain and during life-threatening emergencies and instances where women declined medical advice. CONCLUSIONS: We found that MHCPs are committed to SDM but need better support to deliver it. Structured processes including Core Information Sets, communication skills training and decision support aids may help to consistently deliver SDM in maternity care.

Equity of travel to access surgery and radiation therapy for lung cancer in New Zealand.

PURPOSE: Centralisation of lung cancer treatment can improve outcomes, but may result in differential access to care for those who do not reside within treatment centres. METHODS: We used national-level cancer registration and health care access data and used Geographic Information Systems (GIS) methods to determine the distance and time to access first relevant surgery and first radiation therapy among all New Zealanders diagnosed with lung cancer (2007-2019; N = 27,869), and compared these outcomes between ethnic groups. We also explored the likelihood of being treated at a high-, medium-, or low-volume hospital. Analysis involved both descriptive and adjusted logistic regression modelling. RESULTS: We found that Maori tend to need to travel further (with longer travel times) to access both surgery (median travel distance: Maori 57 km, European 34 km) and radiation therapy (Maori 75 km, European 35 km) than Europeans. Maori have greater odds of living more than 200 km away from both surgery (adjusted odds ratio [aOR] 1.83, 95% CI 1.49-2.25) and radiation therapy (aOR 1.41, 95% CI 1.25-1.60). CONCLUSIONS: Centralisation of care may often improve treatment outcomes, but it also makes accessing treatment even more difficult for populations who are more likely to live rurally and in deprivation, such as Maori.

Access to and Timeliness of Lung Cancer Surgery, Radiation Therapy, and Systemic Therapy in New Zealand: A Universal Health Care Context.

PURPOSE: Lung cancer is the biggest cancer killer of indigenous peoples worldwide, including Maori people in New Zealand. There is some evidence of disparities in access to lung cancer treatment between Maori and non-Maori patients, but an examination of the depth and breadth of these disparities is needed. Here, we use national-level data to examine disparities in access to surgery, radiation therapy and systemic therapy between Maori and European patients, as well as timing of treatment relative to diagnosis. METHODS: We included all lung cancer registrations across New Zealand from 2007 to 2019 (N = 27,869) and compared access with treatment and the timing of treatment using national-level inpatient, outpatient, and pharmaceutical records. RESULTS: Maori patients with lung cancer appeared less likely to access surgery than European patients (Maori, 14%; European, 20%; adjusted odds ratio [adj OR], 0.82 [95% CI, 0.73 to 0.92]), including curative surgery (Maori, 10%; European, 16%; adj OR, 0.72 [95% CI, 0.62 to 0.84]). These differences were only partially explained by stage and comorbidity. There were no differences in access to radiation therapy or systemic therapy once adjusted for confounding by age. Although it appeared that there was a longer time from diagnosis to radiation therapy for Maori patients compared with European patients, this difference was small and requires further investigation. CONCLUSION: Our observation of differences in surgery rates between Maori and European patients with lung cancer who were not explained by stage of disease, tumor type, or comorbidity suggests that Maori patients who may be good candidates for surgery are missing out on this treatment to a greater extent than their European counterparts.

Exposure to microplastics and human reproductive outcomes: A systematic review.

BACKGROUND: Microplastics, produced through degradation of environmental plastic pollution, have been detected in human tissues including placenta and fetal meconium. Cell culture and animal studies have demonstrated potential reproductive toxicity of these particles; however, their association with adverse fertility or pregnancy outcomes in humans is not known. OBJECTIVES: To synthesise evidence for the presence of microplastics in human reproductive tissue and their associations with environmental exposures and reproductive outcomes. SEARCH STRATEGY: MEDLINE, Embase, Emcare, CINAHL, ClinicalTrials.gov and ICTRP were searched from inception to 03/02/2023. SELECTION CRITERIA: Studies of human participants, assessing presence of microplastics in reproductive tissues, environmental exposures to microplastics, and fertility- or pregnancy-related outcomes. DATA COLLECTION AND ANALYSIS: Two independent reviewers selected studies and extracted data on study characteristics, microplastics detected, environmental exposures and reproductive outcomes. Narrative synthesis was performed due to methodological heterogeneity. MAIN RESULTS: Of 1094 citations, seven studies were included, covering 96 participants. Microplastics composed of 16 different polymer types were detected in both placental and meconium samples. Two studies reported associations between lifestyle factors (daily water intake, use of scrub cleanser or toothpaste, bottled water and takeaway food) and placental microplastics. One study reported associations between meconium microplastics and reduced microbiota diversity. One reported placental microplastic levels correlated with reduced birthweights and 1-minute Apgar scores. CONCLUSIONS: There is a need for high-quality observational studies to assess the effects of microplastics on human reproductive health.

Working Towards Holistic Scar Assessment and Improved Shared Decision Making in Global Burn Care.

Cutaneous burn scars impact various aspects of life. Scar treatment is mainly evaluated on scar characteristics. Consensus is needed on which other outcomes to capture, ensuring they are relevant to patients, clinicians, and researchers. The aim of this study was to identify, discuss and analyze outcomes related to cutaneous burn scarring, incorporating the voice of patients and views of healthcare professionals. For this, a Delphi process consisting of two survey rounds and a consensus meeting was initiated. Burn scar-related outcomes were identified from an existing comprehensive list of 100 outcomes by an international panel of patients, healthcare professionals and researchers. Fifty-nine outcomes were identified from the Delphi process as related to scarring (≥60% votes). Outcomes less impactful in relation to scar outcomes included psychosocial issues, sense of normality, understanding of treatment, costs and systemic issues. To represent a holistic assessment of outcomes related to cutaneous burn scarring, this Delphi process established a battery of outcomes currently included in scar quality assessment tools, and an expanded set of less frequently considered outcomes. Future work in this area must include the patient voice from developing countries. This is essential to identify globally applicable outcomes related to scarring.

The estimated health impact of alcohol interventions in New Zealand: A modelling study.

AIMS: To estimate the health impacts of key modelled alcohol interventions among Maori (indigenous peoples) and non-Maori in New Zealand (NZ). DESIGN: Multi-stage life-table intervention modelling study. We modelled two scenarios: (1) business-as-usual (BAU); and (2) an intervention package scenario that included a 50% alcohol tax increase, outlet density reduction from 63 to five outlets per 100 000 people, outlet hours reduction from 112 to 50 per week and a complete ban on all forms of alcohol marketing. SETTING AND PARTICIPANTS: The model's population replicates the 2018 NZ population by ethnicity (Maori/non-Maori), age and sex. MEASUREMENTS: Alcohol consumption was estimated using nationally representative survey data combined with sales data and corrected for tourist and unrecorded consumption. Disease incidence, prevalence and mortality were calculated using Ministry of Health data. We used dose-response relationships between alcohol and illness from the 2016 Global Burden of Disease study and calculated disability rates for each illness. Changes in consumption were based on the following effect sizes: total intervention package [-30.3%, standard deviation (SD) = 0.02); tax (-7.60%, SD = 0.01); outlet density (-8.64%, SD = 0.01); outlet hours (-9.24%, SD = 0.01); and marketing (-8.98%, SD = 0.02). We measured health gain using health-adjusted life years (HALYs) and life expectancy. FINDINGS: Compared with the BAU scenario, the total alcohol intervention package resulted in 726 000 [95% uncertainty interval (UI) = 492 000-913 000] HALYs gained during the life-time of the modelled population. Maori experienced greater HALY gains compared with non-Maori (0.21, 95% UI = 0.14-0.26 and 0.16, 95% UI = 0.11-0.20, respectively). When modelled individually, each alcohol intervention within the intervention package produced similar health gains (~200 000 HALYs per intervention) owing to the similar effect sizes. CONCLUSIONS: Modelled interventions for increased alcohol tax, reduced availability of alcohol and a ban on alcohol marketing among Maori and non-Maori in New Zealand (NZ) suggest substantial population-wide health gains and reduced health inequities between Maori and non-Maori.

Implementing weight management during and after pregnancy to reduce diabetes and CVD risk in maternal and child populations.

Maintaining a healthy weight during pregnancy is critical for both women's and children's health. Excessive gestational weight gain (GWG) can lead to complications such as gestational diabetes, hypertension and caesarean delivery. Insufficient GWG can cause fetal growth restriction and increase infant mortality risk. Additionally, postpartum weight retention raises risk of obesity, type 2 diabetes and other chronic diseases for both mother and child. This review seeks to identify current obstacles in weight management research during and after pregnancy and explore evidence-based strategies to overcome them. Pregnancy offers a window of opportunity for health behaviour changes as women are more receptive to education and have regular contact with health services. Staying within Institute of Medicine's recommended GWG ranges is associated with better maternal and fetal outcomes. Systematic review evidence supports structured diet and physical activity pregnancy interventions, leading to reduced GWG and fewer complications. Health economic evaluation indicates significant returns from implementation, surpassing investment costs due to decreased perinatal morbidity and adverse events. However, the most effective way to implement interventions within routine antenatal care remains unclear. Challenges increase in the postpartum period due to competing demands on women physically, mentally and socially, hindering intervention reach and retention. Flexible, technology-supported interventions are needed, requiring frameworks such as penetration-implementation-participation-effectiveness and template-for-intervention-description-and-replication for successful implementation. Greater research efforts are necessary to inform practice and investigate fidelity aspects through pragmatic implementation trials during the pregnancy and postpartum periods. Understanding the best ways to deliver interventions will empower women to maintain a healthy weight during their reproductive years.

Expanding the Anti-Phl p 7 Antibody Toolkit: An Anti-Idiotype Nanobody Inhibitor.

We have previously produced a toolkit of antibodies, comprising recombinant human antibodies of all but one of the human isotypes, directed against the polcalcin family antigen Phl p 7. In this work, we complete the toolkit of human antibody isotypes with the IgD version of the anti-Phl p 7 monoclonal antibody. We also raised a set of nanobodies against the IgD anti-Phl p 7 antibody and identify and characterize one paratope-specific nanobody. This nanobody also binds to the IgE isotype of this antibody, which shares the same idiotype, and orthosterically inhibits the interaction with Phl p 7. The 2.1 Å resolution X-ray crystal structure of the nanobody in complex with the IgD Fab is described.

A Complex mHealth Coaching Intervention to Prevent Overweight, Obesity, and Diabetes in High-Risk Women in Antenatal Care: Protocol for a Hybrid Type 2 Effectiveness-Implementation Study.

BACKGROUND: Women with overweight and obesity are at higher risk of developing complications in pregnancy such as gestational diabetes and longer-term chronic conditions. Research concerning health behavior change interventions during pregnancy and postpartum shows promising effects, but implementation into routine services is sparsely investigated. Most interventions focus on the antenatal or postpartum life stages, failing to meet the needs of women. IMPACT DIABETES Bump2Baby is a multicenter project across 4 high-income countries developed to test the implementation of an antenatal and postpartum evidence-based mobile health (mHealth) coaching intervention called Bump2Baby and Me (B2B&Me) designed to sit alongside usual care in the perinatal period. OBJECTIVE: We aim to explore the feasibility and implementation of the B2B&Me intervention and investigate the effectiveness of this intervention in women at risk of gestational diabetes. METHODS: IMPACT DIABETES Bump2Baby is a hybrid type 2 effectiveness-implementation study, which integrates an evidence-based mHealth coaching app that includes personalized health behavior change coaching provided by health care professionals alongside antenatal care from the first antenatal visit to 12 months postpartum. The mHealth app offers the possibility of synchronous calls, asynchronous contact (including coach-participant text and video messaging exchanges tailored to the participant's needs), and ongoing access to an extensive library of bespoke intervention materials. Participants will interact asynchronously with their health coach throughout the intervention via the app. This randomized controlled trial across 4 clinical sites within Ireland, the United Kingdom, Spain, and Australia will recruit 800 women in early pregnancy to evaluate the effectiveness on postpartum weight. The Exploration, Preparation, Implementation, and Sustainment implementation framework is the theoretical underpinning of the study. The implementation evaluation will be assessed at the individual, hospital staff, and broader community levels using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. Data sources for the RE-AIM evaluation will include app and platform analytics, screening and training records, participant medical records, key informant interviews, participant and partner exit interviews, cost data, study questionnaires, staff surveys, and blood sample analyses. RESULTS: The study was approved and registered with the Australian New Zealand Clinical Trials Registry on November 19, 2020. Recruitment commenced on February 9, 2021, and data collection is ongoing. Publication of the results is expected in 2024. CONCLUSIONS: This is the first hybrid effectiveness-implementation study of an 18-month mHealth coaching intervention in at-risk women that we are aware of. As research aims to move toward real-world implementable solutions, it is critical that hybrid studies are conducted. The data from this large multicenter study will be useful in planning the potential implementation and scale-up of evidence-based perinatal health behavior change interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620001240932; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380020&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51431.

Vaginal birth core information set: study protocol for a Delphi study to achieve a consensus on a 'core information set' for vaginal birth.

INTRODUCTION: Studies have shown that women are often underinformed about potential benefits and risks of vaginal birth. This is in contrast to other modes of birth, such as caesarean birth, for which the risks/benefits are often conveyed prior to undergoing the procedure. A core information set (CIS) is an agreed set of information points that should be discussed with all patients prior to undergoing a procedure or intervention. This CIS could improve the quality of information given regarding mode of birth options, as women will be given information prioritised by patients and stakeholders regarding vaginal birth, empowering them to make informed decisions about their birth. We aim to describe the protocol for the development of this vaginal birth CIS. METHODS AND ANALYSIS: We will develop the CIS by: (1) Compiling a 'long-list' of information points about vaginal birth by: undertaking a scoping review of studies and patient information leaflets; interviews with antenatal/postnatal women, an online survey of stakeholders. (2) Collating the 'long-list' of information points and developing the Delphi survey. Think-aloud interviews will refine the survey. (3) Conducting a two-round Delphi survey. 200 stakeholder participants will be recruited. Items rated critically important by ≥80% of participants in one stakeholder group, or with no consensus, will be carried through to a stakeholder consensus meeting to decide the final CIS. Planned start date is 1 June 2022. Planned end date is 31 August 2023. ETHICS AND DISSEMINATION: This project has been given a favourable ethics opinion by the University of Bristol Research Ethics Committee (Ref: 10530). Approval from the ethics committee will be sought for any protocol amendments, and the principal investigator will be responsible for these changes. Findings will be presented at relevant conferences and published in a high-impact journal. We will disseminate the CIS, via Policy Bristol, to clinical policy and guideline developers.

Protocol for a multi-site randomised controlled feasibility study investigating intermittently scanned blood continuous glucose monitoring use for gestational diabetes: the RECOGNISE study.

BACKGROUND: Incidence of gestational diabetes mellitus (GDM) is increasing and is associated with adverse perinatal outcomes including macrosomia, pre-eclampsia, and pre-term delivery. Optimum glycaemic control can reduce these adverse perinatal outcomes. Continuous glucose monitoring (CGM) informs users about interstitial glucose levels allowing early detection of glycaemic excursions and pharmacological or behavioural intervention. Few adequately powered RCTs to evaluate the impact of using CGM in women with GDM on perinatal outcomes have been undertaken. We aim to establish the feasibility of a multi-site RCT to evaluate the clinical- and cost-effectiveness of an intermittently scanned continuous glucose monitor (isCGM) compared with self-monitored blood glucose (SMBG) in women with GDM for reducing fetal macrosomia and improving maternal and fetal outcomes. We will evaluate recruitment and retention rates, adherence to device requirements, adequacy of data capture and acceptability of trial design and isCGM devices. METHODS: Open-label multicentre randomised controlled feasibility trial. INCLUSION CRITERIA: pregnant women, singleton pregnancy, recent diagnosis of GDM (within 14 days of commencing medication, up to 34 weeks gestation) prescribed metformin and/or insulin. Women will be consecutively recruited and randomised to isCGM (FreestyleLibre2) or SMBG. At every antenatal visit, glucose measurements will be evaluated. The SMBG group will use blinded isCGM for 14 days at baseline (~ 12-32 weeks) and ~ 34-36 weeks. The primary outcome is the recruitment rate and absolute number of women participating. Clinical assessments of maternal and fetal/infant health will be undertaken at baseline, birth, up to ~ 13 weeks post-natal. Psychological, behavioural and health economic measures will be assessed at baseline and ~ 34-36 weeks gestation. Qualitative interviews will be undertaken with study decliners, participants, and professionals to explore trial acceptability, of using isCGM and SMBG. DISCUSSION: GDM can be associated with adverse pregnancy outcomes. isCGM could offer a timely, easy-to-engage-with intervention, to improve glycaemic control, potentially reducing adverse pregnancy, birth and long-term health outcomes for mother and child. This study will determine the feasibility of conducting a large-scale multisite RCT of isCGM in women with GDM. TRIAL REGISTRATION: This study has been registered with the ISRCTN (reference: ISRCTN42125256 , Date registered: 07/11/2022).

Crystal structures of the human IgD Fab reveal insights into CH1 domain diversity.

Antibodies of the IgD isotype remain the least well characterized of the mammalian immunoglobulin isotypes. Here we report three-dimensional structures for the Fab region of IgD, based on four different crystal structures, at resolutions of 1.45-2.75 Å. These IgD Fab crystals provide the first high-resolution views of the unique Cδ1 domain. Structural comparisons identify regions of conformational diversity within the Cδ1 domain, as well as among the homologous domains of Cα1, Cγ1 and Cµ1. The IgD Fab structure also possesses a unique conformation of the upper hinge region, which may contribute to the overall disposition of the very long linker sequence between the Fab and Fc regions found in human IgD. Structural similarities observed between IgD and IgG, and differences with IgA and IgM, are consistent with predicted evolutionary relationships for the mammalian antibody isotypes.

Interventions to enhance medication adherence in pregnancy- a systematic review.

BACKGROUND: Sub-optimal medication adherence in pregnant women with chronic disease and pregnancy-related indications has the potential to adversely affect maternal and perinatal outcomes. Adherence to appropriate medications is advocated during and when planning pregnancy to reduce risk of adverse perinatal outcomes relating to chronic disease and pregnancy-related indications. We aimed to systematically identify effective interventions to promote medication adherence in women who are pregnant or planning to conceive and impact on perinatal, maternal disease-related and adherence outcomes. METHODS: Six bibliographic databases and two trial registries were searched from inception to 28th April 2022. We included quantitative studies evaluating medication adherence interventions in pregnant women and women planning pregnancy. Two reviewers selected studies and extracted data on study characteristics, outcomes, effectiveness, intervention description (TIDieR) and risk of bias (EPOC). Narrative synthesis was performed due to study population, intervention and outcome heterogeneity. RESULTS: Of 5614 citations, 13 were included. Five were RCTs, and eight non-randomised comparative studies. Participants had asthma (n = 2), HIV (n = 6), inflammatory bowel disease (IBD; n = 2), diabetes (n = 2) and risk of pre-eclampsia (n = 1). Interventions included education +/- counselling, financial incentives, text messaging, action plans, structured discussion and psychosocial support. One RCT found an effect  of the tested intervention on self-reported antiretroviral adherence but not objective adherence. Clinical outcomes were not evaluated. Seven non-randomised comparative studies found an association between the tested intervention and at least one outcome of interest: four found an association between receiving the intervention and both improved clinical or perinatal outcomes and adherence in women with IBD, gestational diabetes mellitus (GDM), and asthma. One study in women with IBD reported an association between receiving the intervention and maternal outcomes but not for self-reported adherence. Two studies measured only adherence outcomes and reported an association between receiving the intervention and self-reported and/or objective adherence in women with HIV and risk of pre-eclampsia. All studies had high or unclear risk of bias. Intervention reporting was adequate for replication in two studies according to the TIDieR checklist. CONCLUSIONS: There is a need for high-quality RCTs reporting replicable interventions to evaluate medication adherence interventions in pregnant women and those planning pregnancy. These should assess both clinical and adherence outcomes.

Emergency presentation prior to lung cancer diagnosis: A national-level examination of disparities and survival outcomes.

OBJECTIVES: A recent multinational investigation of emergency presentation within 30 days of cancer diagnosis, conducted within the International Cancer Benchmarking Programme (ICBP), observed that New Zealand had the highest rate of emergency presentation prior to lung cancer diagnosis compared to other similar countries. Here we use national-level health data to further investigate these trends, focussing on ethnic disparities in emergency presentation prior to lung cancer diagnosis. We have also compared survival outcomes between those who had an emergency presentation in the preceding 30 days to those who did not. MATERIALS AND METHODS: Our study included all lung cancer registrations between 2007 and 2019 on the New Zealand Cancer Registry (N = 27,869), linked to national hospitalisation and primary healthcare data. We used descriptive (crude and age-standardised proportions) and logistic regression (crude and adjusted odds ratios) analyses to examine primary care access prior to cancer diagnosis, emergency hospitalisation up to and including 30 days prior to diagnosis, and one-year mortality post-diagnosis, both for the total population and between ethnicities. Regression models adjusted for age, sex, deprivation, rurality, comorbidity, tumour type and stage. RESULTS: We found stark disparities by ethnic group, with 62% of Pacific peoples and 54% of Maori having an emergency presentation within 30 days prior to diagnosis, compared to 47% of Europeans. These disparities remained after adjusting for multiple covariates including comorbidity and deprivation (adj. OR: Maori 1.21, 95% CI 1.13-1.30; Pacific 1.50, 95% CI 1.31-1.71). Emergency presentation was associated with substantially poorer survival outcomes across ethnic groups (e.g. 1-year mortality for Maori: no emergency presentation 50%, emergency presentation 79%; adj. OR 2.40, 95% CI 2.10-2.74). CONCLUSIONS: These observations reinforce the need for improvements in the early detection of lung cancer, particularly for Maori and Pacific populations, with a view to preventing diagnosis of these cancers in an emergency setting.