Minoritised ethnic women's experiences of inequities and discrimination in maternity services in North-West England: a mixed-methods study.

BACKGROUND: Minoritised ethnic perinatal women can experience judgemental and stigmatising care due to systemic racism. Discriminatory care contributes to increased risks of poor maternal and infant outcomes, including higher rates of mental ill-health. This study aimed to explore minoritised ethnic women's experiences of maternity services, including maternity care and mental health support, within a North-West England locality. Here we use an equity lens to report the findings that describe if and how women's personal, cultural, and spiritual needs were met, their experiences of discriminatory and prejudicial care, and to identify recommendations for service provision. METHODS: A mixed-methods study was undertaken comprising an online survey, interviews, and community consultations. Questions explored access to and experiences of antenatal care and education; information, communication, and choice; experiences of (dis)respect and judgement; mental health needs and support; cultural/religious needs and support; and overall experiences of maternity care. Eligibility criteria were: women, 18+ years, from self-reported minoritised ethnic backgrounds, who had given birth in the previous 2 years and received maternity care in the locality. Surveys were available in seven languages and distributed via social media, mother-baby groups, and community locations. English-speaking survey participants were invited to take part in a follow-up interview. Community staff were approached to collect data on behalf of the study team. Quantitative data were analysed descriptively (n, %) and merged with qualitative data into descriptive themes. RESULTS: Overall, 104 women provided data; most self-identified as Asian (65.0%) or Black (10.7%) and were aged between 30-34 (32.0%) or 25-29 years (23.3%). Four descriptive themes are reported: 'accessing care' details variations and barriers in accessing maternity care; 'communication needs, and resources' describes views on adaptions and resources for specific communication needs; 'meeting religious and cultural needs' outlines how various religious and cultural needs were met by maternity providers; 'discriminatory or stigmatising care' reports on experiences of pejorative and inequitable care. CONCLUSIONS: An equity lens helped identify areas of discriminatory and inequitable care. Key recommendations include cultural safety training for staff; service-user engagement and co-production of research and resources, and appropriate facilities and recording systems to facilitate individualised, needs-based maternity care.

Results from a Phase 1/2 trial of BB2603, a terbinafine-based topical nano-formulation, in onychomycosis and tinea pedis.

BB2603 is a nano-formulation of the antifungal drug terbinafine with the polymer polyhexamethylene biguanide (PHMB) as an excipient to enhance solubility and drug delivery to skin and nails. BB2603 is delivered topically using a low-velocity spray. It is being developed in different strength formulations for the treatment of fungal infections of the nail and skin, including onychomycosis and tinea pedis, with BB2603-1 (0.01% terbinafine) tested in the present trial. The aim of this study was to assess systemic exposure, safety and tolerability of BB2603-1 compared with Lamisil® AT 1% spray and BB2603-1 vehicle control in onychomycosis and tinea pedis. Preliminary mycological and clinical activity were also investigated. This was a single-centre Phase 1/2, randomised, partially blinded, active- and vehicle-controlled, parallel-group trial in 46 subjects with onychomycosis associated with tinea pedis. Part 1 investigated BB2603-1 versus Lamisil AT 1% spray and BB2603-1 vehicle (4 weeks treatment). Part 2 investigated BB2603-1 versus BB2603-1 vehicle (additional 48 weeks treatment). No measurable systemic exposure of terbinafine was shown over 52 weeks of treatment with BB2603-1. BB2603-1 had an excellent safety and tolerability profile with no drug-related safety findings and no evidence of skin sensitisation. BB2603-1 showed preliminary evidence of anti-dermatophyte activity, demonstrated by a reduction in dermatophyte positive cultures and a reduction in microscopic evidence of dermatophytes. The pharmacokinetic, safety and efficacy data from this trial support further development of the topical terbinafine-based nano-formulation BB2603 in fungal infections of the skin and nail, including onychomycosis and tinea pedis.

Resilience and post-traumatic growth in the transition to motherhood during the COVID-19 pandemic: A qualitative exploratory study.

Most perinatal research relating to COVID-19 focuses on its negative impact on maternal and parental mental health. Currently, there are limited data on how to optimise positive health during the pandemic. We aimed to bridge this knowledge gap by exploring how women have adapted to becoming a new parent during the pandemic and to identify elements of resilience and growth within their narratives. Mothers of infants under the age of 4 months were recruited as part of a wider UK mixed-methods study. Semi-structured interviews with 20 mothers elicited data about how COVID-19 had influenced their transition to parent a new infant, and if and how they adapted during the pandemic, what strategies they used, and if and how these had been effective. Directed qualitative content analysis was undertaken, and pre-existing theoretical frameworks of resilience and post-traumatic growth (PTG) were used to analyse and interpret the data set. The findings show evidence of a range of resilience and PTG concepts experienced during the pandemic in this cohort. Salient resilience themes included personal (active coping, reflective functioning, and meaning-making), relational (social support, partner relationships, and family relationships), and contextual (health and social connectedness) factors. There was also evidence of PTG in terms of the potential for new work-related and leisure opportunities, and women developing wider and more meaningful connections with others. Although further research is needed, and with individuals from diverse socioeconomic backgrounds, these findings emphasise the significance of social support and connectivity as vital to positive mental health. Opportunities to increase digital innovations to connect and support new parents should be maximised to buffer the negative impacts of further social distancing and crisis situations.

Could health information systems enhance the quality of Aboriginal health promotion? A retrospective audit of Aboriginal health programs in the Northern Territory of Australia.

BACKGROUND: In Australia, health services are seeking innovative ways to utilize data stored in health information systems to report on, and improve, health care quality and health system performance for Aboriginal Australians. However, there is little research about the use of health information systems in the context of Aboriginal health promotion. In 2008, the Northern Territory's publicly funded healthcare system introduced the quality improvement program planning system (QIPPS) as the centralized online system for recording information about health promotion programs. The purpose of this study was to explore the potential for utilizing data stored in QIPPS to report on quality of Aboriginal health promotion, using chronic disease prevention programs as exemplars. We identify the potential benefits and limitations of health information systems for enhancing Aboriginal health promotion. METHODS: A retrospective audit was undertaken on a sample of health promotion projects delivered between 2013 and 2016. A validated, paper-based audit tool was used to extract information stored in the QIPPS online system and report on Aboriginal health promotion quality. Simple frequency counts were calculated for dichotomous and categorical items. Text was extracted and thematically analyzed to describe community participation processes and strategies used in Aboriginal health promotion. RESULTS: 39 Aboriginal health promotion projects were included in the analysis. 34/39 projects recorded information pertaining to the health promotion planning phases, such as statements of project goals, 'needs assessment' findings, and processes for consulting Aboriginal people in the community. Evaluation findings were reported in approximately one third of projects and mostly limited to a recording of numbers of participants. For almost half of the projects analyzed, community participation strategies were not recorded. CONCLUSION: This is the first Australian study to shed light on the feasibility of utilizing data stored in a purposefully designed health promotion information system. Data availability and quality were limiting factors for reporting on Aboriginal health promotion quality. Based on our learnings of QIPPS, strategies to improve the quality and accuracy of data entry together with the use of quality improvement approaches are needed to reap the potential benefits of future health promotion information systems.

Initial experience of an investigational 3T MR scanner designed for use on neonatal wards.

OBJECTIVES: MR imaging of neonates is difficult for many reasons and a major factor is safe transport to the MR facilities. In this article we describe the use of a small, investigational 3-T MR customised for brain imaging and sited on a neonatal unit of a tertiary centre in the UK, which is in contrast to a 300-m journey to the whole-body MR scanner used at present for clinical cases. METHODS: We describe our methods for preparing babies for safe transport and scanning on an investigational 3-T MR scanner on a neonatal unit and the development of appropriate MR sequences. The MR scanner does not have CE marking at present so this early development work was undertaken on normal neonates whose parents consented to a research examination. RESULTS: Fifty-two babies were scanned and there were no serious adverse events. The MR examinations were considered to be diagnostically evaluable in all 52 cases and in 90% the imaging was considered to be at least as good as the quality obtained on the 1.5-T scanner currently used for clinical cases. CONCLUSION: We have shown that this investigational 3-T MR scanner can be used safely on a neonatal unit and we have refined the MR sequences to a point that they are clinically usable. KEY POINTS: • Access to neonatal MR imaging is limited. • We describe an investigational 3-T MR scanner site on a neonatal unit. • The scanner produces images suitable for clinical practice.

Alcohol in urban streetscapes: a comparison of the use of Google Street View and on-street observation.

BACKGROUND: Alcohol-related harm is a major global health issue, and controls on alcohol marketing are one intervention utilized by governments. This study investigated the use of Google Street View (GSV) as a novel research method for collecting alcohol-related data in the urban environment. METHODS: The efficacy of GSV and on-street observation by observer teams was compared by surveying 400 m stretches of 12 streets in Wellington, the capital city of New Zealand. Data on alcohol sale, alcohol-related advertising, health promotion materials, regulatory information and visible alcohol consumption were collected. RESULTS: A total of 403 retailers with evidence of alcohol sales and 1161 items of alcohol-related communication were identified in on-street observation. Of the latter, 1028 items (89 %) were for alcohol marketing and 133 (11 %) were for alcohol-related health promotion and alcohol regulation. GSV was found to be a less sensitive tool than on-street observation with only 50 % of the alcohol venues identified and 52 % of the venue-associated brand marketing identified. A high degree of inter-observer reliability was generally found between pairs of observers e.g., for the detection of alcohol retail venues the intra-class correlation coefficient (ICC) was 0.93 (95 % CI: 0.78 to 0.98) for on-street observation and 0.85 (95 % CI: 0.49 to 0.96) for using GSV. CONCLUSIONS: GSV does not seem suitable for the comprehensive study of the influences on alcohol consumption in the urban streetscape. However, it may still have value for large, static objects in the environment and be more time efficient than traditional on-street observation measures, especially when used to collect data across a wide geographical area. Furthermore, GSV might become a more useful research tool in settings with better image quality (such as more 'footpath views') and with more regularly updated GSV imagery.

Effect of a lower target oxygen saturation range on the risk of hypoxaemia and elevated NEWS2 scores at a university hospital: a retrospective study.

BACKGROUND: The optimal target oxygen saturation (SpO2) range for hospital inpatients not at risk of hypercapnia is unknown. The objective of this study was to assess the impact on oxygen usage and National Early Warning Score 2 (NEWS2) of changing the standard SpO2 target range from 94-98% to 92-96%. METHODS: In a metropolitan UK hospital, a database of electronic bedside SpO2 measurements, oxygen prescriptions and NEWS2 records was reviewed. Logistic regression was used to compare the proportion of hypoxaemic SpO2 values (<90%) and NEWS2 records ≥5 in 2019, when the target SpO2 range was 94-98%; with 2022, when the target range was 92-96%. RESULTS: In 2019, 218 of 224 936 (0.10%) observations on room air and 162 of 11 328 (1.43%) on oxygen recorded an SpO2 <90%, and in 2022, 251 of 225 970 (0.11%) and 233 of 12 845 (1.81%), respectively (risk difference 0.04%, 95% CI 0.02% to 0.07%). NEWS2 ≥5 was observed in 3009 of 236 264 (1.27%) observations in 2019 and 4061 of 238 815 (1.70%) in 2022 (risk difference 0.43%, 0.36% to 0.50%; p<0.001). The proportion of patients using supplemental oxygen with hyperoxaemia (SpO2 100%) was 5.4% in 2019 and 3.9% in 2022 (OR 0.71, 0.63 to 0.81; p<0.001). DISCUSSION: The proportion of observations with SpO2 <90% or NEWS2 ≥5 was greater with the 92-96% range; however, absolute differences were very small and of doubtful clinical relevance, in contrast to hyperoxaemia for which the proportion was markedly less in 2022. These findings support proposals that the British Thoracic Society oxygen guidelines could recommend a lower target SpO2 range.

Effect of automated titration of oxygen on time spent in a prescribed oxygen saturation range in adults in the ICU after cardiac surgery.

Objective: The objective of this study was to determine whether automated titration of the fraction of inspired oxygen (FiO2) increases the time spent with oxygen saturation (SpO2) within a predetermined target SpO2 range compared with manually adjusted high-flow oxygen therapy in postoperative cardiac surgical patients managed in the intensive care unit (ICU). Design: Single-centre, open-label, randomised clinical trial. Setting: Tertiary centre ICU. Participants: Recently extubated adults following elective cardiac surgery who required supplemental oxygen. Interventions: Automatically adjusted FiO2 (using an automated oxygen control system) compared with manual FiO2 titration, until cessation of oxygen therapy, ICU discharge, or 24 h (whichever was sooner). Main outcome measures: The primary outcome was the proportion of time receiving oxygen therapy with the SpO2 in a SpO2 target range of 92-96 %. Results: Among 65 participants, the percentage of time per patient spent in the target SpO2 range was a median of 97.7 % (interquartile range: 87.9-99.2 %) and 91.3 % (interquartile range: 77.1-96.1 %) in the automated (n = 28) and manual (n = 28) titration groups, respectively. The estimated effect of automated FiO2, compared to manual FiO2 titration, was to increase the percentage of time spent in the target range by a median of 4.8 percentage points (95 % confidence interval: 1.6 to 10.3 percentage points, p = 0.01). Conclusion: In patients recently extubated after cardiac surgery, automated FiO2 titration significantly increased time spent in a target SpO2 range of 92-96 % compared to manual FiO2 titration.

A pilot exploration of staff and service-user perceptions of a novel digital health technology (Virtual Engagement Rehabilitation Assistant) in complex inpatient rehabilitation.

PURPOSE: Digital health technologies have the potential to advance rehabilitation. The Virtual Engagement Rehabilitation Assistant (VERA) is a digital technology, co-designed to increase service-user engagement and promote self-management. This qualitative study explored staff and service-user perceptions of implementing VERA on a UK complex inpatient rehabilitation ward. METHODS: Purposively sampled service-users were allocated to VERA for up to six weeks. The Non-adoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework underpinned service-user post-intervention interviews and staff focus groups, and structured analysis of the data. Seven service-users were interviewed. Nine staff contributed to focus groups. RESULTS: A framework analysis identified themes (and subthemes) structured by the NASSS framework domains: 1. Nature of Clinical Condition, 2. Technology (Ease of Use, Holding Information/Resources in a single Digital Location, Appointments), 3. Value Proposition (Structuring Time, Feedback, Unexpected Benefits) 4. Adopters (Confidence in using Technology, Usefulness), 5. Wider Organisation. Ease of use and storage of key information in a single location were beneficial. Reliability, and provision of accurate and timely feedback to staff and service-users, were identified as essential. CONCLUSIONS: A blended approach is required to meet staff and service-user needs. The potential for VERA in a community setting was identified and requires further investigation. Learning from VERA will support development of other digital technologies and their implementation.

Digital health technologies have the potential to positively impact rehabilitation but may not be suitable for all service-users.Digital health technologies for rehabilitation must be easy to use and reliable.Relevant and informative feedback from the digital health technology was considered essential by both staff and service-users.Utilising a theoretical framework that focuses on key components of implementation was instrumental for development and evaluation of Virtual Engagement Rehabilitation Assistant (VERA).

Rapamycin delays disease onset and prevents PrP plaque deposition in a mouse model of Gerstmann-Sträussler-Scheinker disease.

Autophagy is a cell survival response to nutrient deprivation that delivers cellular components to lysosomes for digestion. In recent years, autophagy has also been shown to assist in the degradation of misfolded proteins linked to neurodegenerative disease (Ross and Poirier, 2004). In support of this, rapamycin, an autophagy inducer, improves the phenotype of several animal models of neurodegenerative disease. Our Tg(PrP-A116V) mice model Gerstmann-Sträussler-Scheinker disease (GSS), a genetic prion disease characterized by prominent ataxia and extracellular PrP amyloid plaque deposits in brain (Yang et al., 2009). To determine whether autophagy induction can mitigate the development of GSS, Tg(PrP-A116V) mice were chronically treated with 10 or 20 mg/kg rapamycin intraperitoneally thrice weekly, beginning at 6 weeks of age. We observed a dose-related delay in disease onset, a reduction in symptom severity, and an extension of survival in rapamycin-treated Tg(PrP-A116V) mice. Coincident with this response was an increase in the autophagy-specific marker LC3II, a reduction in insoluble PrP-A116V, and a near-complete absence of PrP amyloid plaques in the brain. An increase in glial cell apoptosis of unclear significance was also detected. These findings suggest autophagy induction enhances elimination of misfolded PrP before its accumulation in plaques. Because ataxia persisted in these mice despite the absence of plaque deposits, our findings also suggest that PrP plaque pathology, a histopathological marker for the diagnosis of GSS, is not essential for the GSS phenotype.

Pandemic politics: Exploring the intersection of state political affiliation and public universities' COVID-19 policies and messaging.

As coronavirus disease 2019 (COVID-19) spread within the United States, the challenge of responding to a large-scale health crisis was compounded as the federal government struggled to deliver a unified response. Decision-making powers for pandemic protocols were passed to individual states, whose responses were heavily influenced by their administrations' partisan political leanings. This study explores differences in the transparency of COVID-19 information on university websites and the restrictiveness of the measures they implemented by examining university messaging in all-Republican and all-Democrat controlled states. This study employs a quantitative content analysis of a census of websites (N = 265) from public universities located in states with government trifectas. The data reveal that masking, vaccination, and testing measures were significantly more restrictive among universities located in Democratic trifectas than in Republican trifectas. Additionally, universities in Democratic trifectas communicated more transparently, such that they were more likely to have a direct link to COVID-19 information on their homepages. The results indicate that universities in states where a single political party holds power implemented COVID-19 protocols that reflected the political -viewpoints on the health and economic responses to the pandemic. This finding offers important evidence that both governments and public universities based their public health decisions on political factors.

A decision-making framework for the optimal design of renewable energy systems under energy-water-land nexus considerations.

The optimal allocation of land for energy generation is of emergent concern due to an increasing demand for renewable power capacity, land scarcity, and the diminishing supply of water. Therefore, economically, socially and environmentally optimal design of new energy infrastructure systems require the holistic consideration of water, food and land resources. Despite huge efforts on the modeling and optimization of renewable energy systems, studies navigating the multi-faceted and interconnected food-energy-water-land nexus space, identifying opportunities for beneficial improvement, and systematically exploring interactions and trade-offs are still limited. In this work we present the foundations of a systems engineering decision-making framework for the trade-off analysis and optimization of water and land stressed renewable energy systems. The developed framework combines mathematical modeling, optimization, and data analytics to capture the interdependencies of the nexus elements and therefore facilitate informed decision making. The proposed framework has been adopted for a water-stressed region in south-central Texas. The optimal solutions of this case study highlight the significance of geographic factors and resource availability on the transition towards renewable energy generation.

A New Transgenic Mouse Model of Gerstmann-Straussler-Scheinker Syndrome Caused by the A117V Mutation of PRNP.

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a genetic prion disease typified clinically by the development of progressive ataxia and dementia, and histopathologically by the presence of prion protein (PrP) amyloid plaques in the CNS, especially within the cerebellum. Several mutations of the PrP gene (PRNP) are associated with GSS, but only the P102L mutation has been convincingly modeled in transgenic (Tg) mice. To determine whether other mutations carry specific GSS phenotypic information, we constructed Tg mice that express PrP carrying the mouse homolog of the GSS-associated A117V mutation. Tg(A116V) mice express approximately six times the endogenous levels of PrP, develop progressive ataxia by approximately 140 d, and die by approximately 170 d. Compared with a mouse model of transmissible Creutzfeldt-Jakob disease (CJD), the ataxia of Tg(A116V) mice is more prominent, and the course of disease is more protracted, paralleling that observed in human disease. Neuropathology includes mild scattered vacuolation and prominent, mainly cerebellar localized, thioflavin S-positive PrP plaques comprised of full-length PrP(A116V). In some mice, more prominent vacuolation or a noncerebellar distribution of PrP plaques was evident, suggesting some variability in phenotype. The biophysical properties of PrP from Tg(A116V) mice and human GSS(A117V) revealed a similarly low fraction of insoluble PrP and a weakly protease-resistant approximately 13 kDa midspan PrP fragment, not observed in CJD. Overall, Tg(A116V) mice recapitulate many clinicopathologic features of GSS(A117V) that are distinct from CJD, supporting PrP(A116V) to carry specific phenotypic information. The occasional variation in histopathology they exhibit may shed light on a similar observation in human GSS(A117V).

Sp1 and Sp3 regulate transcription of the cyclin-dependent kinase 5 regulatory subunit 2 (p39) promoter in neuronal cells.

Cyclin-dependent kinase 5 (cdk5) activity is critical for development and function of the nervous system. Cdk5 activity is dependent on association with the regulators p35 and p39 whose expression is highly regulated in the developing nervous system.We have identified a small 200 bp fragment of the p39 promoter that is sufficient for cell type-specific expression in neuronal cells. Mutational analysis revealed that a cluster of predicted binding sites for Sp1, AP-1/CREB/ATF and E box-binding transcription factors is essential for full activity of the p39 promoter. Electrophoretic mobility shift assays revealed that Sp1 and Sp3 bound to sequences required for p39 promoter function and chromatin immunoprecipitation assays confirmed binding of these proteins to the endogenous p39 promoter. Furthermore, depletion of either Sp1 or Sp3 by siRNA reduced expression from the p39 promoter. Our data suggest that the ubiquitously expressed transcription factors Sp1 and Sp3 regulate transcription of the cdk5 regulator p39 in neuronal cells, possibly in cooperation with tissue-specific transcription factors.

Predicting corticosteroid response in chronic obstructive pulmonary disease using exhaled nitric oxide.

RATIONALE: Predicting corticosteroid response in COPD is important but difficult. Response is more likely to occur in association with eosinophilic airway inflammation, for which the fraction of exhaled nitric oxide (Fe(NO)) is a good surrogate marker. OBJECTIVES: We aimed to establish whether Fe(NO) levels would predict the clinical response to oral corticosteroid in COPD. METHODS: We performed a double-blind, crossover trial of steroid in patients with COPD. After a 4-week washout of inhaled steroids, patients received prednisone 30 mg/d or matching placebo, in random order, with an intervening 4-week washout. The predictive values of Fe(NO) for clinically significant changes in 6-minute-walk distance (6MWD), spirometry (FEV(1)), and St. George's Respiratory Questionnaire (SGRQ) were calculated. MEASUREMENTS AND MAIN RESULTS: A total of 65 patients (mean FEV(1) = 57% predicted) were randomized. With prednisone, there was a net increase of 13 m in 6MWD (P = 0.02) and 0.06 L in postbronchodilator FEV(1) (P = 0.02) compared with placebo. The change in SGRQ was not significant. Using receiver operator characteristic analysis, the area under the curve for an increase of 0.2 L in FEV(1) was 0.69 (P = 0.04) with an optimum Fe(NO) cut-point of 50 ppb. The positive and negative predictive values were 67 and 82%, respectively. FE(NO) was not a significant predictor for changes in 6MWD or SGRQ. CONCLUSIONS: Fe(NO) is a weak predictor of short-term response to oral corticosteroid in COPD, its usefulness being limited to predicting increase in FEV(1). Clinical trial registered with www.anzctr.org.au (ACTRN12605000683639).

Clinical academic research internships for nurses, midwives and allied health professionals: a qualitative evaluation.

BACKGROUND: Nurses, midwives and allied health professionals are integral to research, yet rarely engage simultaneously in research and clinical practice. Clinical academic internships offer a route for accessing academic research training. AIM: To determine facilitators and barriers to nurses' participation and engagement in research internships, and to suggest improvements for future programmes. DISCUSSION: The experiences of ten health professional research interns were explored, using a method based on a synthesis between grounded theory and content analysis. Four categories emerged: integrating clinical and research aspirations; support - or lack of it; the hidden curriculum; and the legacy effect. Respondents identified facilitators and barriers to engagement in these categories, including unforeseen challenges. CONCLUSION: Formal support is necessary but is insufficient for fostering engagement and maximising benefits. Participation must be supported by colleagues and enabled by institutional structures. The potential effects of internships on engagement with research is considerable but requires collaboration between all stakeholders. IMPLICATIONS FOR PRACTICE: Deeper institutional engagement is needed so that internship opportunities are fully supported by all colleagues and practically enabled by institutional structures. Future schemes should attempt to promote opportunities to collaborate through group projects to reduce researchers' isolation.

Assessment of the nail penetration of antifungal agents, with different physico-chemical properties.

Onychomycosis, or fungal nail infection, is a common fungal infection largely caused by dermatophyte fungi, such as Trichophyton rubrum or Trichophyton mentagrophytes, which affects a significant number of people. Treatment is either through oral antifungal medicines, which are efficacious but have significant safety concerns, or with topical antifungal treatments that require long treatment regimens and have only limited efficacy. Thus, an efficacious topical therapy remains an unmet medical need. Among the barriers to topical delivery through the nail are the physico-chemical properties of the antifungal drugs. Here, we explore the ability of a range of antifungal compounds with different hydrophilicities to penetrate the nail. Human nail discs were clamped within static diffusion (Franz) cells and dosed with equimolar concentrations of antifungal drugs. Using LC-MS/MS we quantified the amount of drug that passed through the nail disc and that which remained associated with the nail. Our data identified increased drug flux through the nail for the more hydrophilic compounds (caffeine as a hydrophilic control and fluconazole, with LogP -0.07 and 0.5, respectively), while less hydrophilic efinaconazole, amorolfine and terbinafine (LogP 2.7, 5.6 and 5.9 respectively) had much lower flux through the nail. On the other hand, hydrophilicity alone did not account for the amount of drug associated with/bound to the nail itself. While there are other factors that are likely to combine to dictate nail penetration, this work supports earlier studies that implicate compound hydrophilicity as a critical factor for nail penetration.

Qualitative exploration of women's experiences of intramuscular pethidine or remifentanil patient-controlled analgesia for labour pain.

OBJECTIVES: To explore women's experiences of remifentanil or pethidine for labour pain and infant feeding behaviours at 6weeks post partum. DESIGN: Qualitative postnatal sub-study to the randomised controlled trial of remifentanil intravenous patient controlled analgesia (PCA) versus intramuscular pethidine for pain relief in labour (RESPITE). Semistructured telephone interviews were conducted at 6 weeks post partum, and thematic analysis was undertaken. SETTING: Women recruited to the RESPITE trial from seven UK hospitals. PARTICIPANTS: Eighty women consented and 49 (30 remifentanil group and 19 pethidine group) completed the interview. RESULTS: Eight themes emerged which encompassed women's antenatal plans for pain management (Birth Expectations) through to their future preferences for pain relief (Reflections for Future Choices). Many women who used remifentanil felt it provided effective pain relief (Effectiveness of Pain Relief), whereas women in the pethidine group expressed more mixed views. Both groups described side effects, with women using pethidine frequently reporting nausea (Negative Physiological Responses) and women using remifentanil describing more cognitive effects (Cognitive Effects). Some women who used remifentanil reported restricted movements due to technical aspects of drug administration and fear of analgesia running out (Issues with Drug Administration). Women described how remifentanil enabled them to maintain their ability to stay focused during the birth (Enabling a Sense of Control). There was little difference in reported breastfeeding initiation and continuation between pethidine and remifentanil groups (Impact on Infant Behaviour and Breastfeeding). CONCLUSIONS: Qualitative insights from a follow-up study to a trial which explored experiences of intravenous remifentanil PCA with intramuscular pethidine injection found that remifentanil appeared to provide effective pain relief while allowing women to remain alert and focused during labour, although as with pethidine, some side effects were noted. Overall, there was little difference in reported breastfeeding initiation and duration between the two groups. TRIAL REGISTRATION NUMBER: ISRCTN29654603.

The effect of ambient air pollution on respiratory health of school children: a panel study.

BACKGROUND: Adverse respiratory effects of particulate air pollution have been identified by epidemiological studies. We aimed to examine the health effects of ambient particulate air pollution from wood burning on school-age students in Christchurch, New Zealand, and to explore the utility of urine and exhaled breath condensate biomarkers of exposure in this population. METHODS: A panel study of 93 male students (26 with asthma) living in the boarding house of a metropolitan school was undertaken in the winter of 2004. Indoor and outdoor pollution data was continuously monitored. Longitudinal assessment of lung function (FEV1 and peak flow) and symptoms were undertaken, with event studies of high pollution on biomarkers of exposure (urinary 1-hydroxypyrene) and effect (exhaled breath condensate (EBC) pH and hydrogen peroxide concentration). RESULTS: Peak levels of air pollution were associated with small but statistically significant effects on lung function in the asthmatic students, but not healthy students. No significant effect of pollution could be seen either on airway inflammation and oxidative stress either in healthy students or students with asthma. Minor increases in respiratory symptoms were associated with high pollution exposure. Urinary 1-hydroxypyrene levels were raised in association with pollution events by comparison with low pollution control days. CONCLUSION: There is no significant effect of ambient wood-smoke particulate air pollution on lung function of healthy school-aged students, but a small effect on respiratory symptoms. Asthmatic students show small effects of peak pollution levels on lung function. Urinary 1-hydroxypyrene shows potential as a biomarker of exposure to wood smoke in this population; however measurement of EBC pH and hydrogen peroxide appears not to be useful for assessment of population health effects of air pollution.Some of the data presented in this paper has previously been published in Kingham and co-workers Atmospheric Environment, 2006 Jan; 40: 338-347 (details of pollution exposure), and Cavanagh and co-workers Sci Total Environ. 2007 Mar 1;374(1):51-9 (urine hydroxypyrene data).