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Low Traffic Neighbourhoods in London reduce road traffic injuries: a controlled before-and-after analysis (2012-2024).
Get PDFBACKGROUND: Between 2015 and 2024, 113 Low Traffic Neighbourhoods (LTNs) were implemented across Greater London, with 27 subsequently removed. We investigated their impacts on road traffic injuries inside LTNs and on 'boundary roads' immediately surrounding the LTNs. METHODS: We matched police-recorded injuries from STATS19 data to Ordnance Survey road links that were spatially intersected with LTNs/boundary roads. Conditional fixed-effects Poisson regression models used the number of injuries per road link per quarter of each year (January 2012 to June 2024) to test whether LTN implementation was associated with changes in injury rates. RESULTS: LTN implementation was associated with a 35% (95% CI 29% to 40%; p<0.001) decrease in all injuries and a 37% (95% CI 24% to 48%; p<0.001) decrease in people Killed or Seriously Injured (KSI). Injuries decreased across a range of casualty and LTN characteristics. However, there was evidence of a smaller benefit in LTNs implemented in Outer London since 2020. Following the removal of an LTN, injury numbers increased back to pre-intervention levels. On boundary roads, there was no evidence of a change in total injury numbers (estimate -2%, 95% CI -5% to +2%) or KSI injury numbers (estimate 0%, 95% CI -7% to +8%). This reflected decreased numbers of injuries on boundary roads for cyclists and motorcyclists, and no change for pedestrians and other motor vehicle users. CONCLUSION: LTNs in London reduced road traffic injuries among all road users inside the LTN areas, with no evidence of overall impact (and for cyclists and motorcyclists a benefit) on boundary roads
“I can't show them on the phone so it's what I say and I'm not saying a lot.” – The loss of nonverbal and visual cues during telephone consultations, equity of access and the impact on marginalised patients: a qualitative study
Get PDFBackground: There has been an increase in the use of telephone consultations in General Practice in the UK during and since the COVID-19 pandemic. This results in a reliance on verbal communication alone due to the loss of non-verbal and visual cues. The consequences of this for inequities of healthcare in marginalised groups is underexplored. This paper examines accounts of patients from marginalised groups of the impact of a loss of non-verbal and visual cues during telephone GP consultations and effects on experiences of care. Design: and setting: Ethnography and interview study (n = 15) undertaken at three sites in London: a foodbank, a community development organisation, and a drop-in advice centre for migrants. Additionally, GPs (n = 5) working at practices in London, Digital Health Hub staff (n = 4) and staff at fieldwork sites (n = 3) were interviewed. Method: Ethnographic observation (n = 84hrs) and semi-structured interviews (n = 27). Interviews were conducted in-person and over the phone and data were analysed through reflexive thematic analysis. Results: Analysis identified challenges in effectively conveying information during telephone GP consultations as a result of language barriers, health literacy, and concerns around sensitive disclosure as a result of a loss of non-verbal and visual cues. Additionally, GPs reported mitigation techniques employed during telephone consultations including increased use of questioning, referrals for additional tests, and converting to face-to-face consultations in an effort to improve care
Melatonin as a Therapeutic Adjunct in Obstructive Sleep Apnea: A Review of Potential Benefits
Get PDFObstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by recurrent upper airway obstruction, leading to intermittent hypoxia, sleep fragmentation, and increased risk of cardiovascular, metabolic, and neurocognitive complications. Chronic intermittent hypoxia (CIH), a hallmark of OSA, contributes significantly to oxidative stress, systemic inflammation, endothelial dysfunction, and neuronal injury. These mechanisms underlie the development of comorbidities such as hypertension, diabetes mellitus, dyslipidemia, and cognitive impairment. While continuous positive airway pressure is the standard treatment, poor adherence highlights the need for adjunctive therapies. Melatonin, a neurohormone with potent antioxidant, anti-inflammatory, and neuroprotective properties, has emerged as a promising therapeutic agent for mitigating CIH-related complications. Preclinical studies demonstrate that melatonin reduces oxidative stress and inflammation, improves endothelial function, and ameliorates metabolic dysfunction, including insulin resistance and lipid dysregulation. Additionally, melatonin has shown potential in preventing CIH-induced cognitive decline by reducing hippocampal oxidative damage, preserving synaptic plasticity, and enhancing neurogenesis. These neuroprotective effects may counteract the cognitive impairments frequently observed in OSA patients. This narrative review examines the impact of melatonin administration on cardiovascular, metabolic, and neurocognitive sequelae of OSA, focusing on its molecular mechanisms of action and therapeutic potential. While preclinical studies provide compelling evidence for its efficacy, clinical trials are needed to establish optimal dosing, safety, and long-term benefits of melatonin therapy in OSA patients. Integrating melatonin as an adjunctive therapy may offer a novel approach to reducing the burden of OSA-related diseases
The effect of pertussis vaccination in pregnancy on the immunogenicity of acellular or whole-cell pertussis vaccination in Gambian infants (GaPS): a single-centre, randomised, controlled, double-blind, phase 4 trial.
Get PDFBACKGROUND: Vaccinating women against pertussis in pregnancy protects young infants from severe disease and death. Vaccination-induced maternally derived antibodies, however, might subsequently modulate (and specifically blunt) the infant's serological response to their primary series of pertussis vaccinations. We examined the effect of pertussis immunisation in pregnancy on the immunogenicity of primary acellular or whole-cell pertussis vaccines in a west African cohort. METHODS: GaPs was a randomised, controlled, double-blind, phase 4 trial conducted in The Gambia. We used a predefined block randomisation scheme to randomly assign healthy, HIV-negative, pregnant participants (1:1) to receive a pertussis-containing (tetanus-diphtheria-acellular pertussis-inactivated polio virus [Tdap-IPV]) or tetanus-toxoid only vaccine at 28-34 weeks' gestation. At the same time, their infants were randomly assigned (1:1) to receive diphtheria-tetanus-acellular pertussis (DTaP) or diphtheria-tetanus-whole-cell pertussis (DTwP) primary vaccine at 8, 12, and 16 weeks postnatally. Participants and trial staff were masked to the allocation of the maternal vaccine. The field team and participants became unmasked to the allocation of the infant vaccine at 16 weeks; laboratory staff and all other investigators remained masked to infant vaccine allocation until the end of the trial. The primary outcome was geometric mean concentration (GMC) of infant pertussis toxin-specific antibodies at 20 weeks and 9 months postnatally and was assessed in infants who received all three doses of the primary vaccine. Secondary outcomes included memory B-cell responses, and exploratory outcomes were total pertussis-specific antibody binding concentrations and functional antibody titres (pertussis toxin-specific neutralising activity [PTNA] and serum bactericidal activity [SBA]). Vaccine reactogenicity was assessed in mothers and infants for 3 days after each vaccine dose. Pregnant women had an extra safety visit 7 days after vaccination. The study is registered with ClinicalTrials.gov, NCT03606096. FINDINGS: Between Feb 13, 2019, and May 17, 2021, we enrolled 343 maternal-infant pairs. 239 (77%) infants were included in the per-protocol immunogenicity analysis. Among infants of mothers receiving Tdap-IPV in pregnancy, at 20 weeks postnatally, the GMCs of anti-pertussis toxin IgG were more than three-fold lower in infants vaccinated with three doses of DTwP (n=64) than in infants vaccinated with three doses of DTaP (n=53; adjusted geometric mean ratio 0·28, 98·75% CI 0·16-0·50). This difference persisted up to 9 months (0·31, 0·17-0·55). Conversely, among infants born to tetanus toxoid-immunised mothers, post-vaccination GMCs of anti-pertussis toxin IgG at 9 months were higher in those vaccinated with DTwP (n=58) than in those vaccinated with DTaP (n=64; 2·02, 1·15-3·55). Tdap-IPV immunisation in pregnancy blunted anti-pertussis toxin IgG following primary vaccination in all infants but particularly in those receiving DTwP, with GMCs of anti-pertussis toxin IgG more than eight-fold lower in DTwP-vaccinated infants born to Tdap-IPV-vaccinated mothers than in DTwP-vaccinated infants born to tetanus toxoid-immunised mothers (0·12, 98·75% CI 0·07-0·22 at 20 weeks; 0·07, 0·03-0·17 at 9 months). Similarly, DTwP-vaccinated infants born to Tdap-IPV-vaccinated mothers also showed significant blunting of PTNA, SBA, total pertussis-specific antibody binding, and memory B-cell responses after primary immunisation, whereas minimal blunting was observed among DTaP-vaccinated infants. However, the absolute levels of these responses generated by DTwP-vaccinated infants remained similar to or, in many cases, were higher than those generated by DTaP-vaccinated infants. There was no difference in reactogenicity between the two maternal vaccines, with most reactions graded 0 or 1. There were no serious adverse events related to vaccination or trial participation. INTERPRETATION: Vaccinating women with Tdap-IPV in pregnancy was safe and well tolerated in a sub-Saharan African setting and boosted the quantity and quality of pertussis-specific antibodies in infants in early life. Although Tdap-IPV was associated with relative blunting of the immune response to the DTwP primary vaccination series, pertussis-specific antibody quality and memory B-cell responses were nevertheless preserved, regardless of the vaccine given during pregnancy. FUNDING: GaPs was conducted as part of the Pertussis Correlates Of Protection Europe (PERISCOPE) consortium, which received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 115910. This Joint Undertaking receives support from the EU's Horizon 2020 research and innovation programme, the European Federation of Pharmaceutical Industries and Associations, and the Bill & Melinda Gates Foundation
Co-creating gender-transformative interventions for adolescent mental, sexual, and reproductive health and rights: Influence of context and actors on process and content in Niger, Ghana, and Burkina Faso.
Get PDFThis paper explores how context and actors influence processes and content efforts to co-create gender transformative primary health care systems for adolescents in West Africa and draws out lessons for co-creation of effective adolescent mental, sexual, and reproductive health and rights (AMSRHR) interventions in low and middle income countries. The study design was a multi country case study with the case defined as "processes, context, actors and content of co-creation of gender-transformative adolescent mental, sexual, and reproductive health interventions". Data are from mixed qualitative sources in two research phases: a situational/context analysis and co-creation/data validation workshops. Findings reveal that while national AMSRHR policies promote gender-sensitive approaches, actual programmes remain largely gender-neutral or gender-blind. Important considerations in co-creating AMSRHR interventions include how to effectively engage powerful stakeholders with diverse positions, pay attention to gendered power imbalances in co-creation processes, and raise critical consciousness of complex AMSRHR issues through non-threatening, participatory approaches
Vertical transmission of hepatitis B virus in the WHO African region: a systematic review and meta-analysis.
Get PDFBACKGROUND: More new infections with hepatitis B virus (HBV) occur annually in the WHO African region than in the rest of the world combined. We did a systematic review and meta-analysis to estimate the prevalence of hepatitis B surface antigen (HBsAg) in pregnant women and vertical transmission events in the region.
METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, Africa Index Medicus, and Africa Journals Online for publications between Jan 1, 1992, and Jan 7, 2024, with no language restrictions. HBsAg prevalence and vertical transmission (HBsAg positivity in children aged 6-12 months) were estimated with the use of binomial mixed models with logit links, stratified by infant vaccination status. We estimated HBsAg prevalence for subregions of Africa and for the WHO African region by weighting by estimated livebirths for each subregion. We estimated transmission events using WHO and UNICEF vaccine coverage data and UN population estimates.
FINDINGS: We included 113 studies reporting on HBsAg prevalence from 190 983 pregnant women and 11 studies reporting on vertical transmission. HBsAg prevalence in women receiving antenatal care in the WHO African region (based on 2014-23 data) was 6·2% (95% CI 5·3-7·2). No relationship between risk of bias and HBsAg prevalence was observed. In 2022, an estimated 172 000 vertical transmission events (95% CI 82 000-383 000) occurred (0·4% of livebirths), a fall from a peak of 339 000 (149 000-634 000; 1·2% of all livebirths) in 2001. Increasing birth dose vaccination coverage to the WHO target of 90% could reduce vertical transmission by 43·7% (95% CI 11·6-78·0) to 97 000 events per year (95% CI 58 000-160 000). Adding maternal antiviral prophylaxis with 90% coverage could reduce transmission by 86·3% (95% CI 78·4-94·6) to 24 000 events per year (95% CI 14 000-39 000; 0·06% of livebirths) and achieve WHO elimination targets.
INTERPRETATION: Vertical transmission is an important contributor to HBV transmission in the WHO African region. Scaling up of hepatitis B birth dose vaccination and antiviral prophylaxis is urgently needed, which could achieve elimination of vertical transmission.
FUNDING: Wellcome Trust
A Qualitative Analysis of Human-Animal Interactions with Respect to Zoonoses in Nepal.
Get PDFInfectious diseases of zoonotic origin are a serious threat to human health and livelihoods globally. Habitat encroachment and deforestation bring humans and animals into contact, increase potential for disease spread, and foster human-animal conflict. Our aim, using thematic analysis, was to qualitatively examine the zoonotic disease landscape in Nepal from public, policymaker, and healthcare practitioner perspectives, and to describe key human-animal interactions. Community participants at six sites were interviewed or took part in focus groups (n = 73); 20 healthcare practitioner and policymaker representatives were interviewed. Lack of data complicates understanding of the zoonotic disease landscape in Nepal and limits evidence-informed policymaking. Some participants were aware of the potential significance of Nipah virus in Nepal, but insufficient data precluded planning for potential outbreaks. Drivers of some zoonoses, such as leptospirosis, may be difficult to address as they are related to traditional practices, such as consumption of rodents or barefoot paddy planting. Community participants identified rodents as frequently responsible for human-animal conflict in both rural and urban areas. Most participant photographs included evidence of rodent damage or mitigation against rodents. Habitat encroachment and deforestation have increased wild animal sightings and may increase contact between these and domestic animals, and humans. Although community participants reported no longer killing and eating wild animals, some health/policy participants questioned whether communities adhere to relevant regulations. This underlines the importance of involving communities in culturally appropriate policy development and implementation. To strengthen policymaking around zoonotic disease prevention and human-animal conflict, with the aim of reducing spread of zoonoses, we recommend public engagement between affected communities, healthcare practitioners, and policymakers to agree priorities (e.g. rodent damage and potential mitigation); and further research on effects of anthropogenic environmental changes in conjunction with members of communities most likely to be affected by increased contact with wild animals
The utility of integrating nanopore sequencing into routine HIV-1 drug resistance surveillance.
Get PDFHIV continues to be a significant global public health concern. In 2022, an estimated 29.8 million people living with HIV received antiretroviral treatment (ART). From this, an estimated 10-15% of individuals living with HIV have drug-resistant strains of the virus. Testing for resistance to antiretroviral drugs is recommended before initiating ART. However, such services are often inaccessible due to costs and the need for complex laboratory infrastructure. The assessment of HIV drug resistance (HIVDR) relies on genotyping sequencing and algorithms to interpret genotypic resistance test results. Genotypic assays involve Sanger sequencing of the reverse transcriptase (RT), protease (PR) and integrase (IN) genes of circulating RNA in plasma to detect mutations that are known to confer drug resistance. While state-of-the-art sequencing technologies have swept the globe and enhanced our global pandemic response capabilities, they are still sparingly used for HIVDR surveillance. The scale-up of ART, especially in low- and middle-income countries, necessitates the establishment of cheap, expeditious and decentralized methods for HIVDR monitoring. Here, we outline how one low-capital next-generation sequencing platform, namely, nanopore sequencing, could augment efforts in expanding HIVDR surveillance efforts, especially in resource-limited settings. We discuss that because of its versatility, nanopore sequencing can accelerate HIVDR surveillance in conjunction with scaling up ART efforts and outline some of the challenges that need to be considered before its widespread and routine adaptation to detect drug resistance rapidly
Five-year trajectories of HbA1c by age, sex, ethnicity and deprivation in adults with newly diagnosed type 2 diabetes: Observational study in England.
Get PDFBACKGROUND: The burden of diabetes mellitus (DM) is increasing worldwide, putting significant pressure on healthcare systems. Diabetes is often managed in primary care and includes a significant proportion of adults needing treatment. HbA1c is considered the gold standard for monitoring overall glycaemic level control: while guidelines generally recommend maintaining HbA1c levels below 52 mmol/mol (7%) for most individuals with diabetes, personalized management strategies are advocated.1 However, the regular monitoring of HbA1c in real-world settings differs from that in controlled clinical trials.
This study investigates five-year HbA1c trajectories in newly diagnosed individuals with type 2 diabetes (T2DM) in routine primary care clinical practice in relation to age, sex, ethnicity and socioeconomic deprivation. We aim to identify disparities in HbA1c trajectories arising from these demographic factors, and to inform the development of more personalized and equitable approaches to diabetes care by identifying subgroups that may require targeted interventions or additional strategies for better diabetes glycaemic management
HIV-1 drug resistance among people living with HIV receiving dolutegravir-based anti-retroviral regimens in Uganda: a national laboratory-based survey using remnant viral load samples, 2022.
Get PDFBACKGROUND AND OBJECTIVES: Uganda adopted dolutegravir as its preferred HIV treatment regimen in the national guidelines for treatment of HIV and AIDS in 2018. We conducted a survey to estimate dolutegravir resistance 4 years post-dolutegravir introduction in routine clinical settings. This was a cross-sectional survey to estimate the prevalence of HIV drug resistance (HIVDR) to dolutegravir among children and adults with viral non-suppression (VNS; ≥1000 copies/mL) receiving dolutegravir-based antiretroviral therapy for at least 9 months. METHODS: We used remnant specimens from routine viral load monitoring stored at Central Public Health Laboratories during February-April 2022. Genotyping of the protease, reverse transcriptase and integrase regions of the HIV-1 pol gene was done using Thermo Fisher® kits and analysed using the Stanford HIVDR database. Weighted prevalences of HIVDR with 95% confidence intervals (CI) were estimated for adults (≥15 years) and children (0-14 years). RESULTS: We randomly selected 857 specimens including 457 from adults and 400 from children for HIVDR testing from 3578 eligible specimens collected during February-April 2022. Five hundred and eleven (59.6%) were successfully genotyped in the integrase region. Intermediate- to high-level dolutegravir HIVDR prevalence was 3.9% (CI: 0.7, 7.1) for adults and 6.6% (CI: 3.5, 9.6) for children. CONCLUSION: HIVDR to dolutegravir was uncommon but present among both children and adults with VNS after 9 months or more of exposure to dolutegravir. Additional longitudinal outcomes data are needed to determine if adherence counselling for patients with VNS on dolutegravir regimens might improve outcomes