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INTRODUCTION: Oral diseases are more prevalent in people with severe mental illness (SMI) compared to those without mental illnees. A greater focus on oral health is needed to reverse unacceptable but often neglected oral health inequality in people with SMI. This provided the impetus for developing 'The Right to Smile' consensus statement. We aimed to develop and disseminate a consensus statement to address oral health inequality, highlighting the main areas for concern and recommending an evidence-based 5-year action plan to improve oral health in people with SMI. METHODS: The Right to Smile consensus statement was developed by experts from several professional disciplines and practice settings (mental, dental and public health) and people with lived experience, including carers. Stakeholders participated in a series of online workshops to develop a rights-based consensus statement. Subsequent dissemination activities were conducted to maximise its reach and impact. RESULTS: The consensus statement was developed to focus on how oral health inequalities could be addressed through a set of 5-year improvement targets for practice, policy and training. The consensus was reached on three 5-year action plans: 'Any assessment of physical health in people experiencing SMI must include consideration of oral health', 'Access to dental services for people with SMI needs to improve' and 'The importance of oral health for people experiencing SMI should be recognised in healthcare training, systems, and structures'. CONCLUSION: This consensus statement urges researchers, services and policymakers to embrace a 5-year action plan to improve oral health for people with SMI. PATIENT OR PUBLIC CONTRIBUTION: The team included people with lived experience of SMI, their carers/family members and mental and dental health service providers. They were involved in every stage of developing the consensus statement, from conception to development and dissemination.
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Consensus , Mental Disorders , Oral Health , Humans , Mental Disorders/therapy , Health Services Accessibility , Health Status DisparitiesABSTRACT
PURPOSE: We report the chances of 14-year-old males becoming victims of firearm injury or death before age 25 in Philadelphia, Pennsylvania. METHODS: Using life table methods, we followed 4,501 Black males aged 14 years, and a comparison group of 1,751 White males, over 11 years. RESULTS: Among 14-year-old Black males, the risk of a nonfatal firearm injury before age 25 was 10.1% (95% confidence interval, 9.2%-11.0%), the risk of death from firearms was 2.5% (1.7%-3.2%), and the combined risk was 12.5% (11.0%-14.1%). Among White males, the risk of nonfatal firearm injury was 0.8% (0.3%-1.2%), the risk of death was 0.3% (0.02%-0.5%), and the combined risk was 1.0% (0.5%-1.5%). DISCUSSION: Risk estimates reveal the dire likelihood of firearm injury or death among Black adolescent males in Philadelphia. Immediate interventions are needed to de-escalate conflicts, provide supports, and address the upstream causes of violence like poverty and structural racism.
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This cross-sectional study provides a multistate description of utilization of Medicaid-covered peer support services in 2019 by enrollees with opioid use disorder (OUD).
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Medicaid , Opioid-Related Disorders , Peer Group , Humans , Opioid-Related Disorders/therapy , United States , Adult , Female , Male , Middle AgedABSTRACT
Purpose: Childhood exposure to domestic violence and abuse (DVA) can lead to major short- and long-term effects on the victim. Despite this, there is no accepted measure for children's experiences, with most existing measures being validated only in high income countries and not in low- and middle- income countries. As a result, international statistics are not comparable. This paper seeks to critically appraise existing measures and discuss whether any are fit-for-purpose on a global scale. Method: The COSMIN PROMs approach was followed to critically appraise and compare the appropriateness of measures. A comprehensive literature search was undertaken in seven journal databases for measures mentioned in formally peer-reviewed articles exploring childhood exposure to DVA. Results: A literature search resulted in the identification of 10 measures and, following criteria to only keep original measures and remove modifications, four measures which have been validated cross-culturally are discussed in detail in line with the COSMIN PROMs criterion: The Child Exposure to Domestic Violence Scale, Children's Perception of Interparental Conflict Scale, Juvenile Victimization Questionnaire and The Violence Exposure Scale for Children. Strengths and limitations of each are discussed, along with any validations undertaken not in the country of origin. Conclusion: Despite childhood exposure to DVA being an urgent research priority worldwide, the current measures to explore the extent of the issue are not validated cross-culturally, leading to concerns about comparisons across different population groups. The development and implementation of interventions to reduce the levels and effects of exposure relies heavily on cross-cultural comparisons, which may indicate different strategies are needed in different contexts. The lack of these validated comparisons is constraining advances, and the paper advocates for further efforts to be made in this regard.
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Domestic Violence , Humans , Domestic Violence/statistics & numerical data , Child , Surveys and Questionnaires , Exposure to Violence/psychology , Exposure to Violence/statistics & numerical data , Female , Global Health , Male , Child Abuse/statistics & numerical data , Crime Victims/statistics & numerical data , AdolescentABSTRACT
OBJECTIVE: Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis. DESIGN: We generated 312 intestinal epithelial organoids (IEOs) from mucosal biopsies of 168 patients with CD (n=72), UC (n=23) and healthy controls (n=73). We performed genome-wide molecular profiling including DNAm, bulk as well as single-cell RNA sequencing. Organoids were subjected to gene editing and the functional consequences of DNAm changes evaluated using an organoid-lymphocyte coculture and a nucleotide-binding oligomerisation domain, leucine-rich repeat and CARD domain containing 5 (NLRC5) dextran sulphate sodium (DSS) colitis knock-out mouse model. RESULTS: We identified highly stable, CD-associated loss of DNAm at major histocompatibility complex (MHC) class 1 loci including NLRC5 and cognate gene upregulation. Single-cell RNA sequencing of primary mucosal tissue and IEOs confirmed the role of NLRC5 as transcriptional transactivator in the intestinal epithelium. Increased mucosal MHC-I and NLRC5 expression in adult and paediatric patients with CD was validated in additional cohorts and the functional role of MHC-I highlighted by demonstrating a relative protection from DSS-mediated mucosal inflammation in NLRC5-deficient mice. MHC-I DNAm in IEOs showed a significant correlation with CD disease phenotype and outcomes. Application of machine learning approaches enabled the development of a disease prognostic epigenetic molecular signature. CONCLUSIONS: Our study has identified epigenetically regulated intestinal epithelial MHC-I as a novel mechanism in CD pathogenesis.
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Crohn Disease , DNA Methylation , Epigenesis, Genetic , Intestinal Mucosa , Organoids , Humans , Crohn Disease/genetics , Crohn Disease/pathology , Crohn Disease/metabolism , Organoids/metabolism , Organoids/pathology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Mice , Animals , Female , Male , Mice, Knockout , Biological Specimen Banks , Adult , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Disease Models, Animal , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolismABSTRACT
Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We show substantially increased levels of 5',8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find that the endoplasmic reticulum stress response is upregulated and reversal of the mutant genotype is associated with phenotypic rescue. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately. Although more work is required, this study presents insights with intervention potential.
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Induced Pluripotent Stem Cells , Xeroderma Pigmentosum , Xeroderma Pigmentosum/pathology , Xeroderma Pigmentosum/metabolism , Xeroderma Pigmentosum/genetics , Induced Pluripotent Stem Cells/metabolism , Humans , Neurons/metabolism , Neurons/pathology , Oxidative Stress , Endoplasmic Reticulum Stress , Proteasome Endopeptidase Complex/metabolism , Cell Differentiation , DNA Damage , Models, Biological , MultiomicsABSTRACT
OBJECTIVES: To summarize current evidence of high-dose influenza vaccine (HD-IV) vs standard-dose (SD-IV) regarding severe clinical outcomes. METHODS: A prespecified meta-analysis was conducted to assess relative vaccine effectiveness (rVE) of HD-IV vs SD-IV in reducing the rates of (1) pneumonia and influenza (P&I) hospitalization, (2) all hospitalizations, and (3) all-cause death in adults ≥ 65 years in randomized controlled trials. Pooled effect sizes were estimated using fixed-effects models with the inverse variance method. RESULTS: Five randomized trials were included encompassing 105,685 individuals. HD-IV vs SD-IV reduced P&I hospitalizations (rVE: 23.5 %, [95 %CI: 12.3 to 33.2]). HD-IV vs SD-IV also reduced rate of all-cause hospitalizations (rVE: 7.3 %, [95 %CI: 4.5 to 10.0]). No significant differences were observed in death rates (rVE = 1.6 % ([95 %CI: -2.0 to 5.0]) in HD-IV vs SD-IV. Sensitivity analyses omitting trials with participants sharing the same comorbidity, trials with ≥ 100 events, and random-effects models provided comparable estimates for all outcomes. CONCLUSIONS: HD-IV reduced the incidence of P&I and all-cause hospitalization vs SD-IV in adults ≥ 65 years in randomized trials, through no significant difference was observed in all-cause death rates. These findings, supported by evidence from several randomized studies, can benefit from replication in a fully powered, individually randomized trial.
Subject(s)
Hospitalization , Influenza Vaccines , Influenza, Human , Randomized Controlled Trials as Topic , Humans , Hospitalization/statistics & numerical data , Influenza Vaccines/administration & dosage , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Influenza, Human/mortality , Aged , Vaccine Efficacy , Pneumonia/prevention & control , Pneumonia/mortality , Male , Aged, 80 and over , FemaleABSTRACT
BACKGROUND: In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point. OBJECTIVE: To evaluate the effects of the successful nudging interventions on downstream clinical outcomes. DESIGN: Prespecified exploratory analysis of a nationwide randomized implementation trial. (ClinicalTrials.gov: NCT05542004). SETTING: The 2022 to 2023 influenza season. PARTICIPANTS: 964 870 Danish citizens aged 65 years or older. INTERVENTION: Usual care or 9 different electronically delivered behavioral nudging letters. MEASUREMENTS: Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023. RESULTS: The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care). LIMITATION: Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms. CONCLUSION: In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended. PRIMARY FUNDING SOURCE: Sanofi.
Subject(s)
Influenza Vaccines , Influenza, Human , Humans , Influenza, Human/prevention & control , Vaccination , Registries , HospitalizationABSTRACT
BACKGROUND: Urgent dental care may be the only place where many people, especially vulnerable groups, access care. This presents an opportunity for delivery of a behavioural intervention promoting planned dental visiting, which may help address one of the factors contributing to a socio-economic gradient in oral health. Although we know that cueing events such as having a cancer diagnosis may create a 'teachable moment' stimulating positive changes in health behaviour, we do not know whether delivering an opportunistic intervention in urgent dental care is feasible and acceptable to patients. METHODS: The feasibility study aimed to recruit 60 patients in a Dental Hospital and dental practices delivering urgent care within and outside working hours. Follow-up was by telephone, e mail and post over 4 months. RESULTS: Although the recruitment window was shortened because of COVID-19, of 47 patients assessed for eligibility, 28 were enrolled (70.1% of screened patients provided consent). A relatively high proportion were from disadvantaged backgrounds (46.4%, 13/28 receiving State benefits). Retention was 82.1% (23/28), which was also the rate of completion of the Oral Health Impact Profile co-primary outcome. The other primary outcome involved linking participant details at recruitment, with centrally-held data on services provided, with 84.6% (22/26) records partly or fully successfully matched. All intervention participants received at least some of the intervention, although we identified aspects of dental nurse training which would improve intervention fidelity. CONCLUSIONS: Despite recruitment being impacted by the pandemic, when the majority of clinical trials experienced reduced rates of recruitment, we found a high recruitment and consenting rate, even though patients were approached opportunistically to be enrolled in the trial and potentially receive an intervention. Retention rates were also high even though a relatively high proportion had a low socio-economic background. Therefore, even though patients may be in pain, and had not anticipated involvement before their urgent care visit, the study indicated that this was a feasible and acceptable setting in which to position an opportunistic intervention. This has the potential to harness the potential of the 'teachable moment' in people's lives, and provide support to help address health inequalities. TRIAL REGISTRATION: ISRCTN 10,853,330 07/10/2019.
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COVID-19 , Humans , Feasibility Studies , Surveys and Questionnaires , Ambulatory Care , Dental CareABSTRACT
OBJECTIVES: To evaluate the relative effectiveness of high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) against recurrent hospitalizations and its potential variation in relation to influenza circulation. METHODS: We did a post-hoc analysis of a pragmatic, open-label, randomized trial of QIV-HD versus QIV-SD performed during the 2021-2022 influenza season among adults aged 65-79 years. Participants were enrolled in October 2021-November, 2021 and followed for outcomes from 14 days postvaccination until 31 May, 2022. We investigated the following outcomes: Hospitalizations for pneumonia or influenza, respiratory hospitalizations, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations, and all-cause death. Outcomes were analysed as recurrent events. Cumulative numbers of events were assessed weekly. Cumulative relative effectiveness estimates were calculated and descriptively compared with influenza circulation. The trial is registered at Clinicaltrials.gov: NCT05048589. RESULTS: Among 12,477 randomly assigned participants, receiving QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza (10 vs. 33 events, incidence rate ratio [IRR] 0.30 [95% CI, 0.14-0.64]; p 0.002) and all-cause hospitalizations (647 vs. 742 events, IRR 0.87 [95% CI, 0.76-0.99]; p 0.032) compared with QIV-SD. Trends favouring QIV-HD were consistently observed over time including in the period before active influenza transmission; i.e. while the first week with a ≥10% influenza test positivity rate was calendar week 10, 2022, the first statistically significant reduction in hospitalizations for pneumonia or influenza was already observed by calendar week 3, 2022 (5 vs. 15 events, IRR 0.33 [95% CI, 0.11-0.94]; p 0.037). DISCUSSION: In a post-hoc analysis, QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza and all-cause hospitalizations compared with QIV-SD, with trends evident independent of influenza circulation levels. Our exploratory results correspond to a number needed to treat of 65 (95% CI 35-840) persons vaccinated with QIV-HD compared with QIV-SD to prevent one additional all-cause hospitalization per season. Further research is needed to confirm these hypothesis-generating findings.
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BACKGROUND: Studies to promote regular toothbrushing usually rely on self-reports of toothbrushing frequency (SRF). However, toothbrushing frequency measures may be open to responder bias since twice-daily toothbrushing is a commonly accepted social norm. The validity of SRF measures is unclear, meaning that their use as outcomes in interventional work may be flawed. The study's aim was to compare two different self-reported toothbrushing measures: SRF and the Self-Reported Behavioural Automaticity Index (SRBAI); with measurement of observed toothbrushing frequency tracked over 6 weeks. A secondary aim was to explore the interaction effect of various moderators (age, ethnicity, socioeconomic status (SES), sex, self-efficacy, participant personality and routine preference) upon the correlation between SRBAI and observed toothbrushing frequency. METHODS: One hundred and sixty-four adults were recruited via a number of different community groups and workplaces outside the dental setting. After consent, participants completed a questionnaire which collected demographic and participant characteristics measures (age, ethnicity, SES, sex, self-efficacy, participant personality and routine preference) and self-reported toothbrushing habits. Participants then attached a 'Brushlink' device to their toothbrush for 6 weeks to track their observed toothbrushing frequency. RESULTS: Using the Pearson correlation coefficient, a moderately strong positive linear association (r = 0.65) between SRBAI and observed toothbrushing frequency was found. By comparison, the correlation between SRF and observed toothbrushing frequency was weak (r = 0.39). There was a weak positive association between self-reported behaviour frequency and SRBAI score (r = 0.35). Using multivariable linear regression, no statistically significant interactional effect was demonstrated for any moderator variable upon the correlation coefficient of SRBAI and observed toothbrushing frequency. CONCLUSIONS: The SRBAI provided a stronger association with observed toothbrushing frequency than the SRF measure. A moderately strong relationship between SRBAI and observed toothbrushing frequency was found, compared to a weak positive relationship between self-reported behaviour frequency and SRBAI score. This suggests that the SRBAI score could be a suitable proxy to measure observed toothbrushing behaviour and preferable to SRF in interventional work.
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Histone modifications influence the recruitment of reader proteins to chromosomes to regulate events including transcription and cell division. The idea of a histone code, where combinations of modifications specify unique downstream functions, is widely accepted and can be demonstrated in vitro. For example, on synthetic peptides, phosphorylation of Histone H3 at threonine-3 (H3T3ph) prevents the binding of reader proteins that recognize trimethylation of the adjacent lysine-4 (H3K4me3), including the TAF3 component of TFIID. To study these combinatorial effects in cells, we analyzed the genome-wide distribution of H3T3ph and H3K4me2/3 during mitosis. We find that H3T3ph anti-correlates with adjacent H3K4me2/3 in cells, and that the PHD domain of TAF3 can bind H3K4me2/3 in isolated mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are still displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division.
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Histones , Transcription Factors , Histones/metabolism , Phosphorylation , Transcription Factors/metabolism , Reading , Chromosomes/genetics , Chromosomes/metabolism , Mitosis/geneticsABSTRACT
Background: India has the largest tuberculosis burden globally, but this burden varies nationwide. All-age tuberculosis prevalence in 2021 ranged from 747/100,000 in Delhi to 137/100,000 in Gujarat. Previous modelling has demonstrated the benefits and costs of introducing novel tuberculosis vaccines in India overall. However, no studies have compared the potential impact of tuberculosis vaccines in regions within India with differing tuberculosis disease and infection prevalence. We used mathematical modelling to investigate how the health and economic impact of two potential tuberculosis vaccines, M72/AS01E and BCG-revaccination, could differ in Delhi and Gujarat under varying delivery strategies. Methods: We applied a compartmental tuberculosis model separately for Delhi (higher disease and infection prevalence) and Gujarat (lower disease and infection prevalence), and projected epidemiological trends to 2050 assuming no new vaccine introduction. We simulated M72/AS01E and BCG-revaccination scenarios varying target ages and vaccine characteristics. We estimated cumulative cases, deaths, and disability-adjusted life years averted between 2025-2050 compared to the no-new-vaccine scenario and compared incremental cost-effectiveness ratios to three cost-effectiveness thresholds. Results: M72/AS01E averted a higher proportion of tuberculosis cases than BCG-revaccination in both regions (Delhi: 16.0% vs 8.3%, Gujarat: 8.5% vs 5.1%) and had higher vaccination costs (Delhi: USD$118 million vs USD$27 million, Gujarat: US$366 million vs US$97 million). M72/AS01E in Delhi could be cost-effective, or even cost-saving, for all modelled vaccine characteristics. M72/AS01E could be cost-effective in Gujarat, unless efficacy was assumed only for those with current infection at vaccination. BCG-revaccination could be cost-effective, or cost-saving, in both regions for all modelled vaccine scenarios. Discussion: M72/AS01E and BCG-revaccination could be impactful and cost-effective in Delhi and Gujarat. Differences in impact, costs, and cost-effectiveness between vaccines and regions, were determined partly by differences in disease and infection prevalence, and demography. Age-specific regional estimates of infection prevalence could help to inform delivery strategies for vaccines that may only be effective in people with a particular infection status. Evidence on the mechanism of effect of M72/AS01E and its effectiveness in uninfected individuals, which were important drivers of impact and cost-effectiveness, particularly in Gujarat, are also key to improve estimates of population-level impact.
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Lariat ethers are macrocyclic polyethers-crown ethers-to which sidearms are appended. 4,13-Diaza-18-crown-6 having twin alkyl chains at the nitrogens show biological activity. They exhibit antibiotic activity, but when co-administered at with an FDA-approved antibiotic, the latter's potency is often strongly enhanced. Potency enhancements and resistance reversals have been documented in vitro for a range of Gram-negative and Gram-positive bacteria with a variety of antimicrobials. Strains of E. coli and Staphylococcus aureus having resistance to a range of drugs have been studied and the potency enhancements (checkerboards) are reported here. Drugs included in the present study are ampicillin, cefepime, chlortetracycline, ciprofloxacin, doxycycline, kanamycin, minocycline, norfloxacin, oxycycline, penicillin G, and tetracycline. Enhancements of norfloxacin potency against S. aureus 1199B of up to 128-fold were observed. The properties of these lariat ethers have been studied to determine solubility, their membrane penetration, cytotoxicity and mammalian cell survival, and their effect on bacterial efflux pumps. It is shown that in some cases, the lariat ethers have complex antimicrobials with considerable selectivity. Based on these observations, including 1:1 complexation between lariat ethers and antimicrobials and the cytotoxicity of the MeI salts showing a separation index of 32-fold, they hold significant potential for further development.
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Background: The upper (URT) and lower (LRT) respiratory tract feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the URT and LRT and explore their relationship with development during childhood. Methods: We employed V4 16S rDNA sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 183 subjects between 20 weeks and 18 years of age. These samples were collected prior to elective procedures at the Children's Hospital of Philadelphia over the course of 20 weeks in 2020, from otherwise healthy subjects enrolled in a study investigating potential reservoirs of SARS-CoV-2. Findings: After extraction, sequencing, and quality control, we studied the remaining 124 nasopharyngeal swabs and 98 tracheal aspirates, including 85 subject-matched pairs of samples. V4 16S rDNA sequencing revealed that the nasopharynx is colonized by few, highly-abundant taxa, while the tracheal aspirates feature a diverse assembly of microbes. While no taxa co-occur in the URT and LRT of the same subject, clusters of microbiomes in the URT correlate with clusters of microbiomes in the LRT. The clusters identified in the URT correlate with subject age across childhood development. Interpretations: The correlation between clusters of taxa across sites may suggest a mutual influence from either a third site, such as the oropharynx, or host-extrinsic, environmental features. The identification of a pattern of upper respiratory microbiota development across the first 18 years of life suggests that the patterns observed in early childhood may extend beyond the early life window.
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In the genomic era, the availability of gene panel and whole genome/exome sequencing is rapidly increasing. Opportunities for providing former patients with new genetic information are also increasing over time and recontacting former patients with new information is likely to become more common. Breast cancer Refined Analysis of Sequence Tests-Risk And Penetrance (BRA-STRAP) is an Australian study of individuals who had previously undertaken BRCA1 and BRCA2 genetic testing, with no pathogenic variants detected. Using a waiver of consent, stored DNA samples were retested using a breast/ovarian cancer gene panel and clinically significant results returned to the patient (or next of kin, if deceased). This qualitative study aimed to explore patient experiences, opinions, and expectations of recontacting in the Australian hereditary cancer setting. Participants were familial cancer clinic patients (or next of kin) who were notified of a new pathogenic variant identified via BRA-STRAP. In-depth, semi-structured interviews were conducted approximately 6 weeks post-result. Interviews were transcribed verbatim and analyzed using an inductive thematic approach. Thirty participants (all female; average age = 57; range 36-84) were interviewed. Twenty-five were probands, and five were next of kin. Most women reported initial shock upon being recontacted with unexpected news, after having obtained a sense of closure related to their initial genetic testing experiences and cancer diagnosis. For most, this initial distress was short-lived, followed by a process of readjustment, meaning-making and adaptation that was facilitated by perceived clinical and personal utility of the information. Women were overall satisfied with the waiver of consent approach and recontacting process. Results are in line with previous studies suggesting that patients have positive attitudes about recontacting. Women in this study valued new genetic information gained from retesting and were satisfied with the BRA-STRAP recontact model. Practice implications to facilitate readjustment and promote psychosocial adaptation were identified.