Randomized Evaluation of a Remote Management Program to Improve Guideline-Directed Medical Therapy: The DRIVE Trial.

BACKGROUND: Several SGLT2i (sodium-glucose transport protein 2 inhibitors) and GLP1-RA (glucagon-like peptide-1 receptor agonists) reduce cardiovascular events and improve kidney outcomes in patients with type 2 diabetes; however, utilization remains low despite guideline recommendations. METHODS: A randomized, remote implementation trial in the Mass General Brigham network enrolled patients with type 2 diabetes with increased cardiovascular or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP1-RA were randomly assigned to simultaneous virtual patient education with concurrent prescription of SGLT2i or GLP1-RA (ie, Simultaneous) or 2 months of virtual education followed by medication prescription (ie, Education-First) delivered by a multidisciplinary team driven by nonlicensed navigators and clinical pharmacists who prescribed SGLT2i or GLP1-RA using a standardized treatment algorithm. The primary outcome was the proportion of patients with prescriptions for either SGLT2i or GLP1-RA by 6 months. RESULTS: Between March 2021 and December 2022, 200 patients were randomized. The mean age was 66.5 years; 36.5% were female, and 22.0% were non-White. Overall, 30.0% had cardiovascular disease, 5.0% had cerebrovascular disease, and 1.5% had both. Mean estimated glomerular filtration rate was 77.9 mL/(min‧1.73 m2), and mean urine/albumin creatinine ratio was 88.6 mg/g. After 2 months, 69 of 200 (34.5%) patients received a new prescription for either SGLT2i or GLP1-RA: 53.4% of patients in the Simultaneous arm and 8.3% of patients in the Education-First arm (P<0.001). After 6 months, 128 of 200 (64.0%) received a new prescription: 69.8% of patients in the Simultaneous arm and 56.0% of patients in Education-First (P<0.001). Patient self-report of taking SGLT2i or GLP1-RA within 6 months of trial entry was similarly greater in the Simultaneous versus Education-First arm (69 of 116 [59.5%] versus 37 of 84 [44.0%]; P<0.001) Median time to first prescription was 24 (interquartile range [IQR], 13-50) versus 85 days (IQR, 65-106), respectively (P<0.001). CONCLUSIONS: In this randomized trial, a remote, team-based program identifies patients with type 2 diabetes and high cardiovascular or kidney risk, provides virtual education, prescribes SGLT2i or GLP1-RA, and improves guideline-directed medical therapy. These findings support greater utilization of virtual team-based approaches to optimize chronic disease management. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06046560.

Dynamic interactions between SPX proteins, the ubiquitination machinery, and signalling molecules for stress adaptation at a whole-plant level.

The plant macronutrient phosphorus is a scarce resource and plant-available phosphate is limiting in most soil types. Generally, a gene regulatory module called the phosphate starvation response (PSR) enables efficient phosphate acquisition by roots and translocation to other organs. Plants growing on moderate to nutrient-rich soils need to co-ordinate availability of different nutrients and repress the highly efficient PSR to adjust phosphate acquisition to the availability of other macro- and micronutrients, and in particular nitrogen. PSR repression is mediated by a small family of single SYG1/Pho81/XPR1 (SPX) domain proteins. The SPX domain binds higher order inositol pyrophosphates that signal cellular phosphorus status and modulate SPX protein interaction with PHOSPHATE STARVATION RESPONSE1 (PHR1), the central transcriptional regulator of PSR. Sequestration by SPX repressors restricts PHR1 access to PSR gene promoters. Here we focus on SPX4 that primarily acts in shoots and sequesters many transcription factors other than PHR1 in the cytosol to control processes beyond the classical PSR, such as nitrate, auxin, and jasmonic acid signalling. Unlike SPX1 and SPX2, SPX4 is subject to proteasomal degradation not only by singular E3 ligases, but also by SCF-CRL complexes. Emerging models for these different layers of control and their consequences for plant acclimation to the environment will be discussed.

Role of the HOXA cluster in HSC emergence and blood cancer.

Hematopoiesis, the process of blood formation, is controlled by a complex developmental program that involves intrinsic and extrinsic regulators. Blood formation is critical to normal embryonic development and during embryogenesis distinct waves of hematopoiesis have been defined that represent the emergence of hematopoietic stem or progenitor cells. The Class I family of homeobox (HOX) genes are also critical for normal embryonic development, whereby mutations are associated with malformations and deformity. Recently, members of the HOXA cluster (comprising 11 genes and non-coding RNA elements) have been associated with the emergence and maintenance of long-term repopulating HSCs. Previous studies identified a gradient of HOXA expression from high in HSCs to low in circulating peripheral cells, indicating their importance in maintaining blood cell numbers and differentiation state. Indeed, dysregulation of HOXA genes either directly or by genetic lesions of upstream regulators correlates with a malignant phenotype. This review discusses the role of the HOXA cluster in both HSC emergence and blood cancer formation highlighting the need for further research to identify specific roles of these master regulators in normal and malignant hematopoiesis.

Mapping the global endemicity and clinical burden of Plasmodium vivax, 2000-17: a spatial and temporal modelling study.

BACKGROUND: Plasmodium vivax exacts a significant toll on health worldwide, yet few efforts to date have quantified the extent and temporal trends of its global distribution. Given the challenges associated with the proper diagnosis and treatment of P vivax, national malaria programmes-particularly those pursuing malaria elimination strategies-require up to date assessments of P vivax endemicity and disease impact. This study presents the first global maps of P vivax clinical burden from 2000 to 2017. METHODS: In this spatial and temporal modelling study, we adjusted routine malariometric surveillance data for known biases and used socioeconomic indicators to generate time series of the clinical burden of P vivax. These data informed Bayesian geospatial models, which produced fine-scale predictions of P vivax clinical incidence and infection prevalence over time. Within sub-Saharan Africa, where routine surveillance for P vivax is not standard practice, we combined predicted surfaces of Plasmodium falciparum with country-specific ratios of P vivax to P falciparum. These results were combined with surveillance-based outputs outside of Africa to generate global maps. FINDINGS: We present the first high-resolution maps of P vivax burden. These results are combined with those for P falciparum (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The burden of P vivax malaria decreased by 41·6%, from 24·5 million cases (95% uncertainty interval 22·5-27·0) in 2000 to 14·3 million cases (13·7-15·0) in 2017. The Americas had a reduction of 56·8% (47·6-67·0) in total cases since 2000, while South-East Asia recorded declines of 50·5% (50·3-50·6) and the Western Pacific regions recorded declines of 51·3% (48·0-55·4). Europe achieved zero P vivax cases during the study period. Nonetheless, rates of decline have stalled in the past five years for many countries, with particular increases noted in regions affected by political and economic instability. INTERPRETATION: Our study highlights important spatial and temporal patterns in the clinical burden and prevalence of P vivax. Amid substantial progress worldwide, plateauing gains and areas of increased burden signal the potential for challenges that are greater than expected on the road to malaria elimination. These results support global monitoring systems and can inform the optimisation of diagnosis and treatment where P vivax has most impact. FUNDING: Bill & Melinda Gates Foundation and the Wellcome Trust.

Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum, 2000-17: a spatial and temporal modelling study.

BACKGROUND: Since 2000, the scale-up of malaria control interventions has substantially reduced morbidity and mortality caused by the disease globally, fuelling bold aims for disease elimination. In tandem with increased availability of geospatially resolved data, malaria control programmes increasingly use high-resolution maps to characterise spatially heterogeneous patterns of disease risk and thus efficiently target areas of high burden. METHODS: We updated and refined the Plasmodium falciparum parasite rate and clinical incidence models for sub-Saharan Africa, which rely on cross-sectional survey data for parasite rate and intervention coverage. For malaria endemic countries outside of sub-Saharan Africa, we produced estimates of parasite rate and incidence by applying an ecological downscaling approach to malaria incidence data acquired via routine surveillance. Mortality estimates were derived by linking incidence to systematically derived vital registration and verbal autopsy data. Informed by high-resolution covariate surfaces, we estimated P falciparum parasite rate, clinical incidence, and mortality at national, subnational, and 5 × 5 km pixel scales with corresponding uncertainty metrics. FINDINGS: We present the first global, high-resolution map of P falciparum malaria mortality and the first global prevalence and incidence maps since 2010. These results are combined with those for Plasmodium vivax (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The P falciparum estimates span the period 2000-17, and illustrate the rapid decline in burden between 2005 and 2017, with incidence declining by 27·9% and mortality declining by 42·5%. Despite a growing population in endemic regions, P falciparum cases declined between 2005 and 2017, from 232·3 million (95% uncertainty interval 198·8-277·7) to 193·9 million (156·6-240·2) and deaths declined from 925 800 (596 900-1 341 100) to 618 700 (368 600-952 200). Despite the declines in burden, 90·1% of people within sub-Saharan Africa continue to reside in endemic areas, and this region accounted for 79·4% of cases and 87·6% of deaths in 2017. INTERPRETATION: High-resolution maps of P falciparum provide a contemporary resource for informing global policy and malaria control planning, programme implementation, and monitoring initiatives. Amid progress in reducing global malaria burden, areas where incidence trends have plateaued or increased in the past 5 years underscore the fragility of hard-won gains against malaria. Efforts towards elimination should be strengthened in such areas, and those where burden remained high throughout the study period. FUNDING: Bill & Melinda Gates Foundation.

Mapping malaria seasonality in Madagascar using health facility data.

BACKGROUND: Many malaria-endemic areas experience seasonal fluctuations in case incidence as Anopheles mosquito and Plasmodium parasite life cycles respond to changing environmental conditions. Identifying location-specific seasonality characteristics is useful for planning interventions. While most existing maps of malaria seasonality use fixed thresholds of rainfall, temperature, and/or vegetation indices to identify suitable transmission months, we construct a statistical modelling framework for characterising the seasonal patterns derived directly from monthly health facility data. METHODS: With data from 2669 of the 3247 health facilities in Madagascar, a spatiotemporal regression model was used to estimate seasonal patterns across the island. In the absence of catchment population estimates or the ability to aggregate to the district level, this focused on the monthly proportions of total annual cases by health facility level. The model was informed by dynamic environmental covariates known to directly influence seasonal malaria trends. To identify operationally relevant characteristics such as the transmission start months and associated uncertainty measures, an algorithm was developed and applied to model realisations. A seasonality index was used to incorporate burden information from household prevalence surveys and summarise 'how seasonal' locations are relative to their surroundings. RESULTS: Positive associations were detected between monthly case proportions and temporally lagged covariates of rainfall and temperature suitability. Consistent with the existing literature, model estimates indicate that while most parts of Madagascar experience peaks in malaria transmission near March-April, the eastern coast experiences an earlier peak around February. Transmission was estimated to start in southeast districts before southwest districts, suggesting that indoor residual spraying should be completed in the same order. In regions where the data suggested conflicting seasonal signals or two transmission seasons, estimates of seasonal features had larger deviations and therefore less certainty. CONCLUSIONS: Monthly health facility data can be used to establish seasonal patterns in malaria burden and augment the information provided by household prevalence surveys. The proposed modelling framework allows for evidence-based and cohesive inferences on location-specific seasonal characteristics. As health surveillance systems continue to improve, it is hoped that more of such data will be available to improve our understanding and planning of intervention strategies.

Global estimation of anti-malarial drug effectiveness for the treatment of uncomplicated Plasmodium falciparum malaria 1991-2019.

BACKGROUND: Anti-malarial drugs play a critical role in reducing malaria morbidity and mortality, but their role is mediated by their effectiveness. Effectiveness is defined as the probability that an anti-malarial drug will successfully treat an individual infected with malaria parasites under routine health care delivery system. Anti-malarial drug effectiveness (AmE) is influenced by drug resistance, drug quality, health system quality, and patient adherence to drug use; its influence on malaria burden varies through space and time. METHODS: This study uses data from 232 efficacy trials comprised of 86,776 infected individuals to estimate the artemisinin-based and non-artemisinin-based AmE for treating falciparum malaria between 1991 and 2019. Bayesian spatiotemporal models were fitted and used to predict effectiveness at the pixel-level (5 km × 5 km). The median and interquartile ranges (IQR) of AmE are presented for all malaria-endemic countries. RESULTS: The global effectiveness of artemisinin-based drugs was 67.4% (IQR: 33.3-75.8), 70.1% (43.6-76.0) and 71.8% (46.9-76.4) for the 1991-2000, 2006-2010, and 2016-2019 periods, respectively. Countries in central Africa, a few in South America, and in the Asian region faced the challenge of lower effectiveness of artemisinin-based anti-malarials. However, improvements were seen after 2016, leaving only a few hotspots in Southeast Asia where resistance to artemisinin and partner drugs is currently problematic and in the central Africa where socio-demographic challenges limit effectiveness. The use of artemisinin-based combination therapy (ACT) with a competent partner drug and having multiple ACT as first-line treatment choice sustained high levels of effectiveness. High levels of access to healthcare, human resource capacity, education, and proximity to cities were associated with increased effectiveness. Effectiveness of non-artemisinin-based drugs was much lower than that of artemisinin-based with no improvement over time: 52.3% (17.9-74.9) for 1991-2000 and 55.5% (27.1-73.4) for 2011-2015. Overall, AmE for artemisinin-based and non-artemisinin-based drugs were, respectively, 29.6 and 36% below clinical efficacy as measured in anti-malarial drug trials. CONCLUSIONS: This study provides evidence that health system performance, drug quality and patient adherence influence the effectiveness of anti-malarials used in treating uncomplicated falciparum malaria. These results provide guidance to countries' treatment practises and are critical inputs for malaria prevalence and incidence models used to estimate national level malaria burden.

Measuring exposure to bullying and harassment in health professional students in a clinical workplace environment: Evaluating the psychometric properties of the clinical workplace learning NAQ-R scale.

Background: Instruments that measure exposure to bullying and harassment of students learning in a clinical workplace environment (CWE) that contain validity evidence are scarce. The aim of this study was to develop such a measure and provide some validity evidence for its use.Method: We took an instrument for detecting bullying of employees in the workplace, called the Negative Acts Questionnaire - Revised (NAQ-R). Items on the NAQ-R were adapted to align with our context of health professional students learning in a CWE and added two new factors of sexual and ethnic harassment. This new instrument, named the Clinical Workplace Learning NAQ-R, was distributed to 540 medical and nursing undergraduate students and we undertook a Confirmatory Factor Analysis (CFA) to investigate its construct validity and factorial structure.Results: The results provided support for the construct validity and factorial structure of the new scale comprising five factors: workplace learning-related bullying (WLRB), person-related bullying (PRB), physically intimidating bullying (PIB), sexual harassment (SH), and ethnic harassment (EH). The reliability estimates for all factors ranged from 0.79 to 0.94.Conclusion: This study provides a tool to measure the exposure to bullying and harassment in health professional students learning in a CWE.

"They cared about us students:" learning from exemplar clinical teaching environments.

PURPOSE: In order to foster positive student experiences in the clinical learning environment, we wanted to better understand which teaching practices they regard highly. METHODS: In 2016, the authors undertook a paper 'exemplar' survey (ES) of all fifth year medical students at one tertiary teaching site. Students had experienced all assigned clinical rotations over a two year period. Following a 66% response rate, we identified two clear exemplar clinical areas (ECAs). Over 2016-7, six focus groups with multidisciplinary staff members from these clinical areas were held, with the aim to identify, discuss and understand their specific teaching practices in more detail. RESULTS: The authors present descriptions of positive student experiences and related staff practices, in five themes. Themes emerged around foundational logistic and personal factors: central to student and staff data is that 'welcome' on a daily, and ongoing basis, can be foundational to learning. Central to ECA staff data are universal practices by which all staff purposefully work to develop a functional staff-student relationship and play a part in organising/teaching students. Students and ECA staff groups both understood teacher values to be central to student learning and that cultivating a student's values is one of their major educational tasks. CONCLUSIONS: The framework formed by this thematic analysis is useful, clear and transferrable to other clinical teaching contexts. It also aligns with current thinking about best supporting student learning and cultivating student values as part of developing professionalism. Instigating such practices might help to optimise clinical teaching. We also tentatively suggest that such practices might help where resources are scarce, and perhaps also help ameliorate student bullying.

It's 'probably the teacher!' A strategic framework for clinical staff engagement in clinical student bullying intervention.

BACKGROUND: Student bullying in clinical practice persists, and poor outcomes continue: for learning, academic achievement and career goals, for their mental and physical health and potentially affecting all staff and patients in a clinical workplace. We describe an emergent framework for the strategic design of a bullying intervention, presented as a staff development opportunity. METHODS: CAPLE (Creating A Positive Learning Environment) was a bullying intervention designed around current best evidence about ameliorating student bullying in the clinical environment. CAPLE was also an action research project delivered in two eight- week cycles, one in 2016 & another in 2017. CAPLE's primary practical foci were to offer clinical staff in two separate hospital wards an opportunity to develop their clinical teaching skills and to guide them in reflection and cultivation of values around students and learning. Research foci were: 1. to gain insight into staff experiences of CAPLE as a development process and 2. to evaluate how CAPLE might best help staff reflect on, discuss and develop values around student learning, to include bullying. Staff undertook five active learning workshops combined with supportive contact with one researcher over the research period. Data include individual interviews, staff and researchers' reflective journals and a paper survey about staff experiences of the 2017 intervention. RESULTS: We confirm the effectiveness of best evidence from the literature and also that a strategic four-part framework of approach, process, content and person can further enhance a bullying intervention by increasing the likelihood of participant engagement, learning and values change. CONCLUSIONS: This research aggregates and adds weight to the current literature about student bullying and adds important pragmatic detail about best practice for bullying intervention design and delivery. Ultimately, this emergent framework offers insight to help move past some persistent barriers encountered by those wishing to improve workplace behaviour.

Interventions addressing student bullying in the clinical workplace: a narrative review.

BACKGROUND: Student bullying in the clinical environment continues to have a substantial impact, despite numerous attempts to rectify the situation. However, there are significant gaps in the literature about interventions to help students, particularly a lack of specific guidance around which to formulate an intervention program likely to be effective. With this narrative review about student bullying interventions in the clinical learning environment, we examine and draw together the available, but patchy, information about 'what works' to inform better practice and further research. METHODS: We initially followed a PICO approach to obtain and analyse data from 38 articles from seven databases. We then used a general inductive approach to form themes about effective student bullying intervention practice, and potential unintended consequences of some of these, which we further developed into six final themes. RESULTS: The diverse literature presents difficulties in comparison of intervention efficacy and substantive guidance is sparse and inconsistently reported. The final analytical approach we employed was challenging but useful because it enabled us to reveal the more effective elements of bullying interventions, as well as information about what to avoid: an interventionist and institution need to, together, 1. understand bullying catalysts, 2. address staff needs, 3. have, but not rely on policy or reporting process about behaviour, 4. avoid targeting specific staff groups, but aim for saturation, 5. frame the intervention to encourage good behaviour, not target poor behaviour, and 6. possess specific knowledge and specialised teaching and facilitation skills. We present the themed evidence pragmatically to help practitioners and institutions design an effective program and avoid instigating practices which have now been found to be ineffective or deleterious. CONCLUSIONS: Despite challenges with the complexity of the literature and in determining a useful approach for analysis and reporting, results are important and ideas about practice useful. These inform a way forward for further, more effective student bullying intervention and research: an active learning approach addressing staff needs, which is non-targeted and positively and skilfully administered. (331w).

Trajectories of Depressive Symptomatology and Loneliness in Older Adult Sexual Minorities and Heterosexual Groups.

OBJECTIVES: This article examines whether sexual minority men and women experience greater increases in depressive symptoms and loneliness with age compared to heterosexual men and women. METHODS: Using three waves of data from sexual minority (nMen = 87 and nWomen = 62) and heterosexual (nMen = 1,297 and nWomen = 1,362) older adults in the National Social Life, Health, and Aging Project, we used latent growth curve modeling to test whether change in depressive symptoms and loneliness varies across sexual orientation and whether annual household income and family support accounted for this change. RESULTS: Although differences in the growth trajectories of depressive symptoms and loneliness across sexual orientation were not observed, gender differences were. Annual household income and family support more strongly influenced initial depressive symptoms and loneliness in sexual minority men and women than in heterosexual men and women. CONCLUSIONS: Trajectories of depressive symptoms and loneliness in older adulthood do not vary by sexual orientation. Economic and family resources may allow sexual minorities to cope effectively with depressive symptoms and loneliness. CLINICAL IMPLICATIONS: Clinicians should be cautious about assuming that older sexual minority group members are more susceptible to depressive symptoms and loneliness than heterosexual groups by virtue of their sexual preference.

Variation in the use of definitive treatment options in the management of Graves' disease: a UK clinician survey.

BACKGROUND: Graves' disease can be treated with antithyroid drugs (ATDs), radioiodine or surgery. Use of definitive treatments (radioiodine or surgery) varies widely across centres. Specific clinical circumstances, local facilities, patient and clinician preferences and perceptions will affect the choice of treatment. Detailed understanding of UK clinicians' views and their rationale for different treatments is lacking. AIMS: To study the preferences and perceptions of UK clinicians on the role of surgery and radioiodine in the management of Graves' disease. METHODS: 'British Thyroid Association' (BTA), 'Society for Endocrinology' (SFE) and 'British Association of Endocrine and Thyroid Surgeons' (BAETS) members were invited to complete an online survey examining their management decisions in Graves' disease and factors that influenced their decisions. RESULTS: 158 responses from UK consultants were included. The ratio of physicians to surgeons was 11:5 and males to females was 12:4. Most clinicians would commence ATDs in uncomplicated first presentation of Graves' disease. A wide range of risk estimates on the effectiveness and risks of treatment was given by clinicians. Radioiodine was used most frequently in relapsed Graves' disease. However, severe eye disease and pregnancy strongly influenced choice in favour of surgery. Surgeons underestimated the success of radioiodine (p<0.01) and were more likely to recommend thyroidectomy than physicians. CONCLUSIONS: This survey demonstrates significant variation in clinicians' perceptions of risks of treatment and their choice of management options for relapsed Graves' disease. The variation appeared to be dependent on patient and disease-specific factors as well as physician experience, gender and specialty.

Outcomes in non-surgical management for bowel dysfunction.

This retrospective review considers clinical outcomes of patients following non-surgical management of bowel dysfunction (faecal incontinence and constipation), within a tertiary centre's pelvic floor unit. Between November 2010 and January 2013, 443 patients were entered into a database and the results of their treatment were recorded. To capture the treatment modalities that patients received they were grouped into three categories: defaecatory techniques and/or pelvic floor exercises; dietary advice and/or medication recommendations; rectal irrigation or the use of anal plugs. Patients received a median number of three sessions with a specialist nurse or physiotherapist. After completing a programme of therapy, 81% of patients had an improved St Mark's incontinence score and 75% of patients had an improved Thompson's functional constipation score. Subjective symptom improvement was reported in 78% of patients. The majority of these patients were discharged in 2011 and 2012 and have not required follow-up, suggesting that non-surgical management is effective on a medium-term basis.

'It was horrible to watch, horrible to be a part of': Midwives' perspectives of obstetric violence.

BACKGROUND: Obstetric violence, including unconsented interventions, coercion and disrespect, violates human rights; impacting the physical and psychosocial health of women. The perspective and experience of midwives related to obstetric violence have been explored in low and middle-income countries, with limited research into the experience of midwives in high income nations. AIM: To explore Australian midwives' perspectives of obstetric violence. METHODS: Thematic analysis of qualitative in-depth interviews with 15 midwives experienced in supporting women during birth. Critical feminist theory underpinned each stage of the research. FINDINGS: Interviews with 15 Australian midwives from diverse care settings were analysed thematically. Four key themes were developed from the data: 'the operationalisation of obstetric violence', 'the impact of obstetric violence' 'the historical and situational context' and 'hope for the future'. Midwives considered entrenched patriarchal structures and gender inequity as fundamental to the occurrence of obstetric violence. This societal scaffold is intensified within health care systems where power imbalances facilitate maternal mistreatment through coercion and grooming women for compliance in the antenatal period. Fragmented care models expose women to mistreatment with continuity models being protective only to a point. Midwives experience their own trauma, as a result of what they have witnessed, and due to the lack of support they receive when advocating for women. CONCLUSIONS: Obstetric violence occurs in Australian maternity systems with unconsented interventions, overmedicalisation, coercion, and disrespect observed by midwives. Care-related trauma impacts on the mental health of midwives, raising workforce concerns for policy makers, consumer advocates and professional bodies.

Uncovering the genetic diversity in Aedes aegypti insecticide resistance genes through global comparative genomics.

Aedes aegypti is vector of many arboviruses including Zika, dengue, yellow fever, West Nile, and Chikungunya. Its control efforts are hampered by widespread insecticide resistance reported in the Americas and Asia, while data from Africa is more limited. Here we use publicly available 729 Ae. aegypti whole-genome sequencing samples from 15 countries, including nine in Africa, to investigate the genetic diversity in four insecticide resistance linked genes: ace-1, GSTe2, rdl and vgsc. Apart from vgsc, the other genes have been less investigated in Ae. aegypti, and almost no genetic diversity information is available. Among the four genes, we identified 1,829 genetic variants including 474 non-synonymous substitutions, some of which have been previously documented, as well as putative copy number variations in GSTe2 and vgsc. Global insecticide resistance phenotypic data demonstrated variable resistance in geographic areas with resistant genotypes. Overall, our work provides the first global catalogue and geographic distribution of known and new amino-acid mutations and duplications that can be used to guide the identification of resistance drivers in Ae. aegypti and thereby support monitoring efforts and strategies for vector control.

Telehealth use in maternity care during a pandemic: A lot of bad, some good and possibility.

BACKGROUND: To reduce transmission risk during the COVID-19 pandemic, 'telehealth' (health care delivered via telephone/video-conferencing) was implemented into Australian maternity services. Whilst some reports on telehealth implementation ensued, there was scant evidence on women and midwives' perspectives regarding telehealth use. METHODS: A qualitative study was conducted in Australia during 2020-2021 using two data sources from the Birth in the Time of COVID-19 (BITTOC) study: i) interviews and ii) surveys (open-text responses). Content analysis was utilised to analyse the data and explore telehealth from the perspective of midwives and women accessing maternity care services. In-depth interviews were conducted with 20 women and 16 midwives. Survey responses were provided from 687 midwives and 2525 women who were pregnant or gave birth in 2021, generating 212 and 812 comments respectively. FINDINGS: Telehealth delivery was variable nationally and undertaken primarily by telephone/videoconferencing. Perceived benefits included: reduced COVID-19 transmission risk, increased flexibility, convenience and cost efficiency. However, women described inadequate assessment, and negative impacts on communication and rapport development. Midwives had similar concerns and also reported technological challenges. CONCLUSION: During the COVID-19 pandemic, telehealth offered flexibility, convenience and cost efficiency whilst reducing COVID-19 transmission, yet benefits came at a cost. Telehealth may particularly suit women in rural and remote areas, however, it also has the potential to further reduce equitable, and appropriate care delivery for those at greatest risk of poor outcomes. Telehealth may play an adjunct role in post-pandemic maternity services, but is not a suitable replacement to traditional face-to-face maternity care.

Midwives' experiences with PPE during the COVID-19 pandemic: The Birth in the Time of COVID (BITTOC) study.

BACKGROUND: The COVID-19 pandemic resulted in rapid changes aimed at reducing disease transmission in maternity services in Australia. An increase in personal protective equipment (PPE) in the clinical and community setting was a key strategy. There was variation in the type of PPE and when it was to be worn in clincial practice. AIM: This paper reports on Australian midwives' experiences of PPE during the pandemic. METHODS: This sequential mixed methods study was part of the Birth in the Time of COVID-19 (BITTOC 2020) study. Data were obtained from in-depth semi-structured interviews with midwives in 2020 followed by a national survey undertaken at two time points (2020 and 2021). Qualitative open-text survey responses and interview data were analysed using content analysis. FINDINGS: 16 midwives were interviewed and 687 midwives provided survey responses (2020 n = 477, 2021 n = 210). Whilst midwives largley understood the need for increased PPE, and were mainly happy with this, as it was protective, they reported a number of concerns. These included: inconsistency with PPE type, use, availability, quality, fit and policy; the impact of PPE on the physical and psychological comfort of midwives; and the barriers PPE use placed on communication and woman centred care. This at times resulted in midwives working outside of policy. CONCLUSION: These findings highlight the need for future comprehensive pandemic preparedness that ensures policy and procedure recommendations are consistent and PPE is available, of approriate quality, and individually fitted in order to ensure that Australian maternity services are well placed to manage future pandemics.

Genomic surveillance of Anopheles mosquitoes on the Bijagós Archipelago using custom targeted amplicon sequencing identifies mutations associated with insecticide resistance.

BACKGROUND: Insecticide resistance is reducing the efficacy of vector control interventions, consequently threatening efforts to control vector-borne diseases, including malaria. Investigating the prevalence of molecular markers of resistance is a useful tool for monitoring the spread of insecticide resistance in disease vectors. The Bijagós Archipelago (Bijagós) in Guinea-Bissau is a region of stable malaria transmission where insecticide-treated nets are the mainstay for malaria control. However, the prevalence of molecular markers of insecticide resistance in malaria vectors is not well understood. METHODS: A total of 214 Anopheles mosquitoes were analysed from 13 islands across the Bijagós. These mosquitoes were collected using CDC light traps in November 2019, during the peak malaria transmission season. High-throughput multiplex amplicon sequencing was used to investigate the prevalence of 17 different molecular markers associated with insecticide resistance in four genes: vgsc, rdl, ace1 and gste2. RESULTS: Of the 17 screened mutations, four were identified in mosquitoes from the Bijagós: vgsc L995F (12.2%), N1570Y (6.2%) and A1746S (0.7%) and rdl A269G (1.1%). This study is the first to report the L995F knock-down resistance (kdr)-west allele in Anopheles melas on the Archipelago. An additional eight non-synonymous single-nucleotide polymorphisms were identified across the four genes which have not been described previously. The prevalences of the vgsc L995F and N1570Y mutations were higher on Bubaque Island than on the other islands in this study; Bubaque is the most populous island in the archipelago, with the greatest population mobility and connection to continental Guinea-Bissau. CONCLUSIONS: This study provides the first surveillance data for genetic markers present in malaria vectors from islands across the Bijagós Archipelago. Overall prevalence of insecticide resistance mutations was found to be low. However, the identification of the vgsc L995F and N1570Y mutations associated with pyrethroid resistance warrants further monitoring. This is particularly important as the mainstay of malaria control on the islands is the use of pyrethroid insecticide-treated nets.