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1.
Cell ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39163861

ABSTRACT

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

2.
Cell ; 185(26): 4921-4936.e15, 2022 12 22.
Article in English | MEDLINE | ID: mdl-36563663

ABSTRACT

The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 year of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes associated with diet-related adaptations. Infant gut metabolomes were less diverse than maternal but featured hundreds of unique metabolites and microbe-metabolite associations not detected in mothers. Metabolomes and serum cytokine signatures of infants who received regular-but not extensively hydrolyzed-formula were distinct from those of exclusively breastfed infants. Taken together, our integrative analysis expands the concept of vertical transmission of the gut microbiome and provides original insights into the development of maternal and infant microbiomes and metabolomes during late pregnancy and early life.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Female , Humans , Infant , Pregnancy , Gastrointestinal Microbiome/genetics , Microbiota/genetics , Mothers , Breast Feeding , Feces , Interspersed Repetitive Sequences
3.
Immunity ; 46(1): 29-37, 2017 01 17.
Article in English | MEDLINE | ID: mdl-28087240

ABSTRACT

Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4+ T cells compared to those with Lactobacillus crispatus-dominant communities. We identified specific bacterial taxa linked with reduced (L. crispatus) or elevated (Prevotella, Sneathia, and other anaerobes) inflammation and HIV infection and found that high-risk bacteria increased numbers of activated genital CD4+ T cells in a murine model. Our results suggest that highly prevalent genital bacteria increase HIV risk by inducing mucosal HIV target cells. These findings might be leveraged to reduce HIV acquisition in women living in sub-Saharan Africa.


Subject(s)
Cervix Uteri/microbiology , HIV Infections/microbiology , Vagina/microbiology , Animals , Bacteria, Anaerobic , CD4-Positive T-Lymphocytes/immunology , Cohort Studies , Female , Flow Cytometry , Humans , Lactobacillus , Mice , Microbiota/immunology , Prevotella , South Africa
4.
Mol Ecol ; : e17422, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842022

ABSTRACT

During hybrid speciation, homoeologues combine in a single genome. Homoeologue expression bias (HEB) occurs when one homoeologue has higher gene expression than another. HEB has been well characterized in plants but rarely investigated in animals, especially invertebrates. Consequently, we have little idea as to the role that HEB plays in allopolyploid invertebrate genomes. If HEB is constrained by features of the parental genomes, then we predict repeated evolution of similar HEB patterns among hybrid genomes formed from the same parental lineages. To address this, we reconstructed the history of hybridization between the New Zealand stick insect genera Acanthoxyla and Clitarchus using a high-quality genome assembly from Clitarchus hookeri to call variants and phase alleles. These analyses revealed the formation of three independent diploid and triploid hybrid lineages between these genera. RNA sequencing revealed a similar magnitude and direction of HEB among these hybrid lineages, and we observed that many enriched functions and pathways were also shared among lineages, consistent with repeated evolution due to parental genome constraints. In most hybrid lineages, a slight majority of the genes involved in mitochondrial function showed HEB towards the maternal homoeologues, consistent with only weak effects of mitonuclear incompatibility. We also observed a proteasome functional enrichment in most lineages and hypothesize this may result from the need to maintain proteostasis in hybrid genomes. Reference bias was a pervasive problem, and we caution against relying on HEB estimates from a single parental reference genome.

5.
BMC Public Health ; 24(1): 1059, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627716

ABSTRACT

BACKGROUND: Prevalence of self-harm In England is rising, however contact with statutory services remains relatively low. There is growing recognition of the potential role voluntary, community and social enterprise sector (VCSE) organisations have in the provision of self-harm support. We aimed to explore individuals' experiences of using these services and the barriers and facilitators to accessing support. METHODS: Qualitative, online interviews with 23 adults (18+) who have accessed support from VCSE organisations for self-harm in the Yorkshire and the Humber region were undertaken. Interviews were audio recorded and transcribed verbatim. Thematic analysis was undertaken using NVivo software. RESULTS: Participants described how a lack of service flexibility and the perception that their individual needs were not being heard often made them less likely to engage with both statutory and VCSE organisations. The complexity of care pathways made it difficult for them to access appropriate support when required, as did a lack of awareness of the types of support available. Participants described how engagement was improved by services that fostered a sense of community. The delivery of peer support played a key role in creating this sense of belonging. Education and workplace settings were also viewed as key sources of support for individuals, with a lack of mental health literacy acting as a barrier to access in these environments. CONCLUSIONS: VCSE organisations can play a crucial role in the provision of support for self-harm, however, pathways into these services remain complex and links between statutory and non-statutory services need to be strengthened. The provision of peer support is viewed as a crucial component of effective support in VCSE organisations. Further supervision and training should be offered to those providing peer support to ensure that their own mental health is protected.


Subject(s)
Mental Health , Self-Injurious Behavior , Adult , Humans , Feedback , Qualitative Research , England/epidemiology , Self-Injurious Behavior/epidemiology , Self-Injurious Behavior/prevention & control , Self-Injurious Behavior/psychology
6.
Clin Obstet Gynecol ; 67(1): 79-88, 2024 03 01.
Article in English | MEDLINE | ID: mdl-38032828

ABSTRACT

This review summarizes our current understanding of associations of the postmenopausal vaginal microbiome with genitourinary syndrome of menopause. We review the normal postmenopausal microbiota, examine the association of the microbiome with vulvovaginal symptoms, describe microbial communities associated with physical and laboratory findings, and report the impact of different treatments for genitourinary syndrome of menopause on microbiota and symptom improvement. Postmenopausal vaginal symptoms have an underlying pathophysiology that has not been fully elucidated. Estrogen treatment may not be sufficient to relieve symptoms of vaginal discomfort in all postmenopausal individuals. In addition, other interventions targeted at changing the microbiota or pH do not consistently improve symptom severity.


Subject(s)
Microbiota , Postmenopause , Female , Humans , Menopause , Vagina/pathology , Estrogens , Atrophy
7.
Thorax ; 78(1): 50-60, 2023 01.
Article in English | MEDLINE | ID: mdl-35074900

ABSTRACT

BACKGROUND: Many patients in sub-Saharan Africa whom a diagnosis of tuberculosis is considered are subsequently not diagnosed with tuberculosis. The proportion of patients this represents, and their alternative diagnoses, have not previously been systematically reviewed. METHODS: We searched four databases from inception to 27 April 2020, without language restrictions. We included all adult pulmonary tuberculosis diagnostic studies from sub-Saharan Africa, excluding case series and inpatient studies. We extracted the proportion of patients with presumed tuberculosis subsequently not diagnosed with tuberculosis and any alternative diagnoses received. We conducted a random effects meta-analysis to obtain pooled estimates stratified by passive and active case finding. RESULTS: Our search identified 1799 studies, of which 18 studies (2002-2019) with 14 527 participants from 10 African countries were included. The proportion of patients with presumed tuberculosis subsequently not diagnosed with tuberculosis was 48.5% (95% CI 39.0 to 58.0) in passive and 92.8% (95% CI 85.0 to 96.7) in active case-finding studies. This proportion increased with declining numbers of clinically diagnosed tuberculosis cases. A history of tuberculosis was documented in 55% of studies, with just five out of 18 reporting any alternative diagnoses. DISCUSSION: Nearly half of all patients with presumed tuberculosis in sub-Saharan Africa do not have a final diagnosis of active tuberculosis. This proportion may be higher when active case-finding strategies are used. Little is known about the healthcare needs of these patients. Research is required to better characterise these patient populations and plan health system solutions that meet their needs. PROSPERO REGISTRATION NUMBER: CRD42018100004.


Subject(s)
Tuberculosis, Pulmonary , Tuberculosis , Adult , Humans , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Africa South of the Sahara/epidemiology , Inpatients , Prevalence
8.
Rheumatology (Oxford) ; 62(2): 758-765, 2023 02 01.
Article in English | MEDLINE | ID: mdl-35639659

ABSTRACT

OBJECTIVES: PMR causes pain, stiffness and disability in older adults. Measuring the impact of the condition from the patient's perspective is vital to high-quality research and patient-centred care, yet there are no validated patient-reported outcome measures (PROMs) for PMR. We set out to develop and psychometrically evaluate a PMR-specific PROM. METHODS: Two cross-sectional postal surveys of people with a confirmed diagnosis of PMR were used to provide data for field testing and psychometric evaluation. A total of 256 participants completed the draft PROM. Distribution of item responses was examined, and exploratory factor analysis and Rasch analysis were used to inform item reduction, formation of dimension structure and scoring system development. Some 179 participants completed the PROM at two time points, along with comparator questionnaires and anchor questions. Test-retest reliability, construct validity and responsiveness were evaluated. RESULTS: Results from the field-testing study led to the formation of the PMR-Impact Scale (PMR-IS), comprising four domains (symptoms, function, psychological and emotional well-being, and steroid side effects). Construct validity and test-retest reliability met accepted quality criteria for each domain. There was insufficient evidence from this study to determine its ability to detect flares/deterioration, but the PMR-IS was responsive to improvements in the condition. CONCLUSION: The PMR-IS offers researchers a new way to assess patient-reported outcomes in clinical studies of PMR. It has been developed robustly, with patient input at every stage. It has good construct validity and test-retest reliability. Further work is needed to fully establish its responsiveness and interpretability parameters, and to assess its real-world clinical utility.


Subject(s)
Giant Cell Arteritis , Polymyalgia Rheumatica , Humans , Aged , Polymyalgia Rheumatica/diagnosis , Polymyalgia Rheumatica/drug therapy , Psychometrics , Reproducibility of Results , Cross-Sectional Studies , Patient Reported Outcome Measures , Surveys and Questionnaires
9.
Article in English | MEDLINE | ID: mdl-38097211

ABSTRACT

ISSUE ADDRESSED: The Deadly RED redesign and implementation research aimed to improve take own leave (TOL) rates within a Queensland emergency department by providing a culturally competent care pathway. METHODOLOGY: A mixed methods pre/post evaluation of the feasibility, acceptability and usability of the Deadly RED pathway for First Nations patients presenting to ED was performed. This pathway combined early welcome and information sharing, introduction of screening and follow up for patients who TOL and enhanced access to alternative community healthcare. Yarning circles facilitated co-design of research protocols and tools while a purposefully designed research Yarn enhanced understanding of the 'story' of the people. Qualitative analysis of Yarns allowed deductive themes to be extracted. A Participatory Action Research (PAR) approach and Indigenous research methodology involving First Nations people in design, knowledge sharing and joint ownership of results was used. RESULTS: Common themes from the 85 yarns included the negative impact of long waiting times and positive impact from wholistic care. Unique themes identified included interpretation of waiting room placement and paracetamol prescription as a dismissal. Knowledge dissemination from yarning drove improvements in communications and processes to promote treatment completion resulting in elimination of these themes in post implementation yarns. Eighteen patients who had TOL were included in the post implementation yarns, however only eight of these believed that their treatment was incomplete. CONCLUSION: The use of yarning for consumer engagement has allowed deeper understanding of the reasons for TOL in First Nations emergency patients. The reciprocal knowledge sharing has guided targeted improvements in wholistic emergency care and communication resulting in First Nations patients feeling their care is complete even when the 'number' reports otherwise. SO WHAT?: Indigenous Research methodology including yarning with First Nations patients suggests alternative engagement methods to guide enhanced quality of care monitoring for ED presentations.

10.
Clin Infect Dis ; 74(Suppl_2): S144-S151, 2022 04 13.
Article in English | MEDLINE | ID: mdl-35416968

ABSTRACT

In preparation for the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections (STIs) treatment guidelines, the CDC convened an advisory group in 2019 to examine recent literature addressing updates in the epidemiology, diagnosis, and management of STIs. This article summarizes recent data in each of these key topic areas as they pertain to bacterial vaginosis (BV), the most common cause of vaginal discharge. The evidence reviewed primarily focused on updates in the global epidemiology of BV, risk factors for BV, data supportive of sexual transmission of BV-associated bacteria, BV molecular diagnostic tests, and novel treatment regimens. Additionally, recent literature on alcohol abstinence in the setting of 5-nitroimidazole use was reviewed.


Subject(s)
Sexually Transmitted Diseases , Vaginosis, Bacterial , Centers for Disease Control and Prevention, U.S. , Female , Humans , Molecular Diagnostic Techniques , Risk Factors , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/drug therapy , Sexually Transmitted Diseases/prevention & control , United States/epidemiology , Vagina/microbiology , Vaginosis, Bacterial/diagnosis , Vaginosis, Bacterial/drug therapy , Vaginosis, Bacterial/epidemiology
11.
Pediatr Res ; 91(3): 672-680, 2022 02.
Article in English | MEDLINE | ID: mdl-33824455

ABSTRACT

BACKGROUND: We assessed differences in plasma levels of metabolic health and inflammation biomarkers during mid-childhood and early adolescence between children born by cesarean section vs. vaginal delivery. METHODS: Mother-child pairs (N = 942) enrolled during pregnancy in obstetric practices and child follow-up started at birth. Risk biomarkers were assessed in blood samples collected at the mild-childhood (median = 7 years) and early adolescence (median = 13 years) in-person visits. RESULTS: Two hundred and six children (22%) were born by cesarean section. There were no significant differences in biomarker levels between children born by cesarean and children born vaginally in mid-childhood. However, adolescents born by cesarean section had significantly lower adiponectin [% difference (95% confidence interval (CI)) = -11.3 (-18.1, -4.0) µg/mL] compared to vaginal delivery. We also found some suggestion of higher insulin resistance [insulin levels % difference (95% CI) = 11.5 (-0.40, 25.0) µU/mL and HOMA-IR (homeostatic model assessment of insulin resistance) % difference (95% CI) = 9.1 (-2.30, 21.8) U] in adolescents born by cesarean section compared to those born vaginally. CONCLUSIONS: We found suggestive evidence that adolescents born by cesarean section show differences in certain metabolic health biomarkers relative to adolescents born by vaginal delivery. Further studies are needed to reevaluate these associations since the clinical significance of these differences is unclear. IMPACT: Multiple studies show that children born by cesarean section are at higher risk of obesity compared to those born vaginally. It is unclear yet to what extent this elevated risk may extend to a more adverse profile of biomarkers of metabolic health and inflammation. Adolescents born by cesarean section show small differences in adiponectin and insulin relative to adolescents born by vaginal delivery. Adolescents born by cesarean section may be at higher risk to a more adverse profile of biomarkers of metabolic health and inflammation, but the clinical significance of these differences is uncertain.


Subject(s)
Cesarean Section , Insulin Resistance , Adiponectin , Adolescent , Biomarkers , Cesarean Section/adverse effects , Child , Delivery, Obstetric/adverse effects , Female , Humans , Infant, Newborn , Inflammation/etiology , Insulin , Pregnancy , Prospective Studies
12.
BJOG ; 129(7): 1211-1228, 2022 06.
Article in English | MEDLINE | ID: mdl-35139580

ABSTRACT

Within this document we use the terms pregnant woman and women's health. However, it is important to acknowledge that it is not only people who identify as women for whom it is necessary to access care. Obstetric and gynaecology services and delivery of care must therefore be appropriate, inclusive and sensitive to the needs of those individuals whose gender identity does not align with the sex they were assigned at birth.


Subject(s)
Maternal Health Services , Maternal Mortality , Female , Gender Identity , Humans , Infant, Newborn , Male , Pregnancy , Social Determinants of Health , Women's Health
13.
Med Educ ; 56(5): 489-503, 2022 05.
Article in English | MEDLINE | ID: mdl-34842290

ABSTRACT

CONTEXT: Person-centeredness is a stated aim for medical education; however, studies suggest this is not being achieved. There is a gap in our understanding of how, why and in what circumstances medical education interventions that aim to develop person-centredness are successful. METHODS: A realist review was conducted with a search of Medline, Embase, HMIC and ERIC databases and the grey literature using the terms 'medical education' and 'person-centred' and related synonyms. Studies that involved a planned educational intervention in medical education with data on outcomes related to person-centredness were included. The analysis focused on how and why different educational strategies interact with biomedical learner perspectives to trigger mechanisms that may or may not lead to a change in perspective towards person-centredness. RESULTS: Sixty-one papers representing fifty-three interventions were included in the final synthesis. Nine context-intervention-mechanism-outcome configuration (CIMOc) statements generated from the data synthesis make up our refined programme theory. Where educational interventions focused on communication skills learning or experiences without person-centred theory, learners experienced dissonance with their biomedical perspective which they resolved by minimising the importance of the learning, resulting in perspective endurance. Where educational interventions applied person-centred theory to meaningful experiences and included support for sense making, learners understood the relevance of person-centeredness and felt able to process their responses to learning, resulting in perspective transformation towards person-centredness. CONCLUSION: Our findings offer explanations as to why communication skills-based interventions may be insufficient to develop learners' person-centredness. Integrating experiential person-centred learning with theory on why person-centredness matters to clinical practice and enabling learners to make sense of their responses to learning, may support perspective transformation towards person-centredness. Our findings offer programme and policymakers testable theory to inform the development of medical education strategies that aim to support person-centredness.


Subject(s)
Education, Medical , Humans , Learning , Patient-Centered Care , Problem-Based Learning
14.
Health Expect ; 25(3): 1131-1139, 2022 06.
Article in English | MEDLINE | ID: mdl-35297137

ABSTRACT

BACKGROUND: As the UK population ages, the prevalence of both dementia and cancer will increase. Family carers of people with dementia who are subsequently diagnosed with cancer are often involved in treatment decisions about cancer. These decisions are uniquely challenging. OBJECTIVES: To explore the experience of carers involved in cancer treatment decisions for people with dementia. DESIGN: A cross-sectional qualitative interview study with inductive thematic analysis. SETTING AND PARTICIPANTS: Sixteen carers of people with dementia were identified via Primary Care Research Networks and the Join Dementia Research database. RESULTS: Three main themes were derived: 'already at breaking point', which describes the extreme strain that carers were already under when the cancer diagnosis was made; 'maintaining the status quo', which describes how despite the gravity of a cancer diagnosis, avoiding further dementia-related deterioration was of prime importance; and 'LPA', which explores the benefits and frustrations of the use of lasting powers of attorney. DISCUSSION: Current services are ill-equipped to deal with people who have a combination of dementia and cancer. Proxy decisions about cancer care are made in the context of carer stress and exhaustion, which is exacerbated by shortcomings in service provision. CONCLUSIONS: As the prevalence of comorbid cancer and dementia rises, there is an urgent need to improve services that support carers with proxy health care decision-making. PATIENT OR PUBLIC CONTRIBUTION: The study design was codeveloped with a local dementia-specific patient and public involvement (PPI) group. A project-specific PPI group was formed with support from the Alzheimer's Society Research Partnership scheme to provide further bespoke input.


Subject(s)
Dementia , Neoplasms , Caregivers , Comorbidity , Cross-Sectional Studies , Dementia/epidemiology , Dementia/therapy , Humans , Neoplasms/epidemiology , Neoplasms/therapy , Qualitative Research
15.
J Infect Dis ; 224(12 Suppl 2): S29-S35, 2021 08 16.
Article in English | MEDLINE | ID: mdl-34396407

ABSTRACT

Pelvic inflammatory disease (PID) is a clinical syndrome that has been associated with a wide range of potential causal pathogens. Three broad groups of organisms have been isolated from the genital tract of people with PID: sexually transmitted organisms such as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis; bacterial vaginosis (BV)-associated species and genera such as Atopobium vaginae, Sneathia, and Megasphaera; and genera and species usually associated with the gastrointestinal or respiratory tracts such as Bacteroides, Escherichia coli, Streptococcus, or Haemophilus influenza. Although PID is often considered to be synonymous with gonorrhea or chlamydia, these pathogens are found in only one quarter to one third of people with PID, suggesting that broader screening and diagnostic and treatment strategies need to be considered to reduce the burden of PID and its associated sequelae.


Subject(s)
Pelvic Inflammatory Disease , Sexually Transmitted Diseases/microbiology , Vagina/microbiology , Chlamydia Infections/diagnosis , Chlamydia Infections/epidemiology , Chlamydia trachomatis , Female , Gonorrhea/diagnosis , Gonorrhea/epidemiology , Humans , Mycoplasma Infections/epidemiology , Mycoplasma genitalium , Neisseria gonorrhoeae , Pelvic Inflammatory Disease/diagnosis , Pelvic Inflammatory Disease/etiology
16.
J Infect Dis ; 223(12): 2048-2052, 2021 06 15.
Article in English | MEDLINE | ID: mdl-33107562

ABSTRACT

The Nugent score is the reference standard for bacterial vaginosis (BV) diagnosis but has not been validated in postmenopausal women. We compared relative abundances from 16S ribosomal RNA gene sequencing of vaginal microbiota with Nugent score in cohorts of premenopausal (n = 220) and postmenopausal (n = 144) women. In premenopausal women, 33 taxa were significantly correlated with Nugent score, including the classic BV-associated taxa Gardnerella, Atopobium, Sneathia, Megasphaera, and Prevotella. In postmenopausal women, 11 taxa were significantly associated with Nugent score, including Prevotella but no other BV-associated genera. High Nugent scores should not be used to infer BV in postmenopausal women.


Subject(s)
Microbiota , Vagina , Vaginosis, Bacterial , Bacteria/classification , Female , Humans , Postmenopause , Premenopause , RNA, Ribosomal, 16S/genetics , Vagina/microbiology , Vaginosis, Bacterial/diagnosis
17.
J Infect Dis ; 224(11): 1945-1949, 2021 12 01.
Article in English | MEDLINE | ID: mdl-33367735

ABSTRACT

BACKGROUND: We compared vaginal microbial communities in postmenopausal black and white women. METHODS: Shotgun sequencing of vaginal swabs from postmenopausal women self-identified as black or white was compared using MiRKAT. RESULTS: Vaginal community dominance by Lactobacillus crispatus or Lactobacillusgasseri was more common in 44 postmenopausal black women (n = 12, 27%) than among 44 matched white women (n = 2, 5%; P = .01). No individual taxa were significantly more abundant in either group. CONCLUSIONS: We identified small overall differences in vaginal microbial communities of black and white postmenopausal women. L. crispatus dominance was more common in black women. CLINICAL TRIALS REGISTRATION: NCT02516202 (MsFLASH05) and NCT01418209 (MsFLASH03).


Subject(s)
Microbiota , Postmenopause , Vagina/microbiology , Aged , Black People/statistics & numerical data , Female , Humans , Lactobacillus crispatus , Middle Aged , Minnesota , RNA, Ribosomal, 16S/genetics , White People/statistics & numerical data
18.
Br J Cancer ; 125(8): 1100-1110, 2021 10.
Article in English | MEDLINE | ID: mdl-34453114

ABSTRACT

BACKGROUND: Cancer outcomes are poor in socioeconomically deprived communities, with low symptom awareness contributing to prolonged help-seeking and advanced disease. Targeted cancer awareness interventions require evaluation. METHODS: This is a randomised controlled trial involving adults aged 40+ years recruited in community and healthcare settings in deprived areas of South Yorkshire and South-East Wales. INTERVENTION: personalised behavioural advice facilitated by a trained lay advisor. CONTROL: usual care. Follow-up at two weeks and six months post-randomisation. PRIMARY OUTCOME: total cancer symptom recognition score two weeks post-randomisation. RESULTS: Two hundred and thirty-four participants were randomised. The difference in total symptom recognition at two weeks [adjusted mean difference (AMD) 0.6, 95% CI: -0.03, 1.17, p = 0.06] was not statistically significant. Intervention participants reported increased symptom recognition (AMD 0.8, 95% CI: 0.18, 1.37, p = 0.01) and earlier intended presentation (AMD -2.0, 95% CI: -3.02, -0.91, p < 0.001) at six months. "Lesser known" symptom recognition was higher in the intervention arm (2 weeks AMD 0.5, 95% CI: 0.03, 0.97 and six months AMD 0.7, 95% CI: 0.16, 1.17). Implementation cost per participant was £91.34, with no significant between-group differences in healthcare resource use post-intervention. CONCLUSIONS: Improved symptom recognition and earlier anticipated presentation occurred at longer-term follow-up. The ABACus Health Check is a viable low-cost intervention to increase cancer awareness in socioeconomically deprived communities. CLINICAL TRIAL REGISTRATION: ISRCTN16872545.


Subject(s)
Health Knowledge, Attitudes, Practice , Health Promotion/economics , Health Promotion/methods , Neoplasms , Adult , Cost-Benefit Analysis , Female , Healthcare Disparities , Humans , Male , Medically Underserved Area , Middle Aged , Poverty Areas , Surveys and Questionnaires , United Kingdom
19.
Am J Obstet Gynecol ; 225(2): 159.e1-159.e15, 2021 08.
Article in English | MEDLINE | ID: mdl-33675793

ABSTRACT

BACKGROUND: Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. OBJECTIVE: To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve. STUDY DESIGN: This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm. RESULTS: Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm. CONCLUSION: Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.


Subject(s)
Cytokines/metabolism , Estradiol/administration & dosage , Estrogens/administration & dosage , Female Urogenital Diseases/drug therapy , Inflammation/metabolism , Microbiota/genetics , Postmenopause , Vagina/microbiology , Administration, Intravaginal , Aged , Cytokines/immunology , Female , Female Urogenital Diseases/immunology , Female Urogenital Diseases/metabolism , Female Urogenital Diseases/microbiology , Humans , Hydrogen-Ion Concentration , Inflammation/immunology , Lactobacillus , Metabolome , Metabolomics , Middle Aged , RNA, Ribosomal, 16S/genetics , Severity of Illness Index , Treatment Outcome , Vagina/immunology , Vagina/metabolism , Vaginal Creams, Foams, and Jellies
20.
J Am Acad Dermatol ; 85(2): 523-528, 2021 Aug.
Article in English | MEDLINE | ID: mdl-31437544

ABSTRACT

The prevalence of acute vulvovaginal involvement in toxic epidermal necrolysis can be as high as 70%; up to 28% of female patients will also develop chronic vulvovaginal sequelae. There is little consensus regarding prevention and treatment of the gynecologic sequelae of both Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). We review acute and chronic sequelae, including erosions, scar formation, chronic skin changes, urethral complications, adenosis, malignant transformation, vulvodynia, and dyspareunia. We provide comprehensive recommendations for acute and long-term vulvovaginal care in adult and pediatric SJS/TEN patients. Treatment should include an ultrapotent topical steroid, followed by a nonirritating barrier cream applied to vulvar and perineal lesions. A steroid should be used intravaginally along with vaginal dilation in all adults (but should be avoided in prepubertal adolescents) with vaginal involvement. Menstrual suppression should be considered in all reproductive age patients until vulvovaginal lesions have healed. Last, referrals for pelvic floor physical therapy and to surgical subspecialties should be offered on a case-by-case basis. This guide summarizes the current available literature combined with expert opinion of both dermatologists and gynecologists who treat a high volume of SJS/TEN patients.


Subject(s)
Stevens-Johnson Syndrome/complications , Vaginal Diseases/etiology , Vaginal Diseases/therapy , Vulvar Diseases/etiology , Vulvar Diseases/therapy , Female , Humans , Practice Guidelines as Topic , Stevens-Johnson Syndrome/diagnosis , Vaginal Diseases/prevention & control , Vulvar Diseases/prevention & control
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