Early-life pulmonary viral infection leads to long-term functional and lower airway structural changes in the lungs.

Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in TSLPR-/- mice that have previously been shown to have reduced immune cell accumulation associated with a persistent Th2 environment. Importantly, long-term effects were demonstrated using a secondary RSV infection 3 mo following the initial early-life RSV infection and led to significant additional defects in lung function, with severe mucus deposition within the airways, and consolidation of the alveolar spaces. These studies suggest that early-life respiratory viral infection leads to alterations in lung structure/repair that predispose to diminished lung function later in life.NEW & NOTEWORTHY These studies outline a novel finding that early-life respiratory virus infection can alter lung structure and function long-term. Importantly, the data also indicate that there are critical links between inflammatory responses and subsequent events that produce a more severe pathogenic response later in life. The findings provide additional data to support that early-life infections during lung development can alter the trajectory of airway function.

Prevalence and nature of workplace bullying and harassment and associations with mental health conditions in England: a cross-sectional probability sample survey.

BACKGROUND: Evidence on workplace bullying and harassment (WBH) in the UK has not used probability-sample surveys with robust mental health assessments. This study aimed to profile the prevalence and nature of WBH in England, identify inequalities in WBH exposure, and quantify adjusted associations with mental health. METHODS: Data were from the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional probability-sample survey of the household population in England, interviewed with verbal informed consent. Criteria for inclusion in the secondary analysis were being aged 16-70 years and in paid work in the past month (n=3838). Common mental disorders were assessed using the Clinical Interview Schedule-Revised and mental wellbeing using the Warwick-Edinburgh Mental Wellbeing Scale. Analyses were weighted. We examined associations between past-year WBH and current common mental disorders using multivariable regression modelling, adjusting for demographic and socioeconomic factors. Interaction terms tested for gender differences in associations. The study received ethics approval (ETH21220-299). FINDINGS: One in ten employees (10·6% (weighted), n=444/3838) reported past-year experience of WBH, with rates higher in women (12·2%, n=284/2189); those of mixed, multiple, and other ethnicity (21·0%, n=15/92); and people in debt (15·2%, n=50/281) or living in cold homes (14·6%, n=42/234). Most commonly identified perpetrators of WBH were line managers (53·6%, n=244/444) or colleagues (42·8%, n=194/444). Excessive criticism (49·3%, n=212/444), verbal abuse (42·6%, n=187/444), and humiliation (31·4%, n=142/444) were the most common types. WBH was associated with all adverse mental health indicators, including common mental disorders (adjusted odds ratio [aOR] 2·65, 95% CI 2·02-3·49), and 11 of 14 mental wellbeing indicators, including lower levels of confidence (aOR 0·57, 0·46-0·72) and of closeness to others (aOR 0·57, 0·46-0·72). Patterns of association between WBH and mental health were similar in men and women. INTERPRETATION: These findings reinforce a need for more cohesive UK legislation at the national level; guidance on recognition of bullying behaviours for employees, managers, and human resources at the organisational level, focusing on prevention and early intervention, and increased awareness of the impact of WBH on mental health among health-service practitioners. Study limitations include reliance on cross-sectional data collected before pandemic-related and other major changes in workplace practices. Longitudinal data are needed to improve evidence on causality and the longevity of mental health impacts. FUNDING: UK Prevention Research Partnership.

Prevalence and nature of workplace bullying and harassment and associations with mental health conditions in England: a cross-sectional probability sample survey.

BACKGROUND: Evidence on workplace bullying and harassment (WBH) in the UK has not used probability-sample surveys with robust mental health assessments. This study aimed to profile the prevalence and nature of WBH in England, identify inequalities in exposure, and quantify adjusted associations with mental health. METHODS: Data were from the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional probability-sample survey of the household population in England. Criteria for inclusion in the secondary analysis were being aged 16-70 years and in paid work in the past month (n = 3838). Common mental disorders (CMDs) were assessed using the Clinical Interview Schedule-Revised and mental wellbeing using the Warwick-Edinburgh Mental Wellbeing Scale. Analyses were weighted. We examined associations between past-year WBH and current CMD using multivariable regression modelling, adjusting for sociodemographic factors. Interaction terms tested for gender differences in associations. The study received ethical approval (ETH21220-299). RESULTS: One in ten employees (10.6%, n = 444/3838) reported past-year experience of WBH, with rates higher in women (12.2%, n = 284/2189), those of mixed, multiple, and other ethnicity (21.0%, n = 15/92), and people in debt (15.2%, n = 50/281) or living in cold homes (14.6%, n = 42/234). Most commonly identified perpetrators of WBH were line managers (53.6%, n = 244/444) or colleagues (42.8%, n = 194/444). Excessive criticism (49.3%, n = 212/444), verbal abuse (42.6%, n = 187/444), and humiliation (31.4%, n = 142/444) were the most common types. WBH was associated with all indicators of poor mental health, including CMD (adjusted odds ratio [aOR] 2.65, 95% CI 2.02-3.49), and 11 of 14 mental wellbeing indicators, including lower levels of confidence (aOR 0.57, 0.46-0.72) and closeness to others (aOR 0.57, 0.46-0.72). Patterns of association between WBH and mental health were similar in men and women. CONCLUSIONS: These findings reinforce a need for more cohesive UK legislation against WBH; guidance on recognition of bullying behaviours for employees, managers, and human resources, focusing on prevention and early intervention, and increased awareness of the impact of WBH on mental health among health service practitioners. Limitations include reliance on cross-sectional data collected before pandemic-related and other changes in workplace practices. Longitudinal data are needed to improve evidence on causality and the longevity of mental health impacts.

The experiences of familial mental illness stigma among individuals living with mental illnesses.

Persons with mental illnesses may experience stigma from their immediate family members in addition to other forms of stigma. Using semi-structured interviews, we investigated experiences of familial mental illness stigma among 15 people diagnosed with mental illnesses in a mid-sized city in Canada. We identified five themes that speak to participants' experiences of familial mental illness stigma and ways to reduce it. The themes include the following: diagnosis as a 'double-edged sword,' potential familial isolation, familial stigma as societal stigma localized, stories of acceptance, and confronting potential familial mental illness stigma. Participants' narratives indicate that familial mental illness stigma is rooted in the broader social or public stigma, which sees its way into familial relations as well. This stigma takes various forms, including relationship bias or unfair treatment, breakdown in romantic relationships, loss of status, verbal and emotional abuse, exclusion from decision-making, and alienation within their immediate and extended families. Familial mental illness stigma experiences negatively impact participant's psychological well-being and personal empowerment. However, participants also shared ways that family members create supportive environments or actively confront or prevent stigma. Overall, this study has contributed to knowledge on mental illness stigma, particularly familial mental illness stigma from the perspective of participants living with a mental illness in a high-income country. Suggestions for future research include a focus on strategies to prevent ongoing familial mental illness stigma and large-scale studies to explore familial mental illness stigma to understand why families might perpetrate stigma.

Dose Range-Finding Toxicity Study in Rats With Recombinant Human Lactoferrin Produced in Komagataella phaffii.

The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000 mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to help select dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 57 × Helaina's intended commercial use in adults, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies.

TSLP-Driven Chromatin Remodeling and Trained Systemic Immunity after Neonatal Respiratory Viral Infection.

Our studies have previously shown a role for persistent TSLP production in the lungs of mice after early-life respiratory syncytial virus (RSV) infection that leads to an altered immune phenotype, including accumulation of "inflammatory" dendritic cells (DC). This study investigates the role of TSLP driving systemic trained immunity in DC in early-life RSV-infected mice. Bone marrow-derived DCs (BMDC) from early-life RSV-infected mice at 4 wk postinfection showed enhanced expression of costimulatory molecules and cytokines, including Tslp, that regulate immune cell function. The adoptive transfer of BMDC grown from early-life RSV-infected mice was sufficient to exacerbate allergic disease development. The addition of recombinant TSLP during differentiation of BMDC from naive mice induced a similar altered phenotype as BMDC grown from early-life RSV-infected mice, suggesting a role for TSLP in the phenotypic changes. To assess the role of TSLP in these changes, global transcriptomic characterization of TSLPR-/- BMDC infected with RSV was performed and showed a higher upregulation of type 1 IFN genes and concomitant downregulation of inflammatory genes. Assay for transposase-accessible chromatin using sequencing analysis demonstrated that TSLPR-/- BMDC had a parallel gain in physical chromatin accessibility near type 1 genes and loss in accessibility near genes related to RSV pathology, with IFN regulatory factor 4 (IRF4) and STAT3 predicted as top transcription factors binding within differentially accessible regions in wild-type. Importantly, these studies show that in the absence of TSLP signaling, BMDC are able to mount an appropriate type 1 IFN-associated antiviral response to RSV. In summary, RSV-induced TSLP alters chromatin structure in DC to drive trained innate immunity and activates pathogenic gene programs in mice.

The impact of urinary incontinence on multiple health outcomes: an umbrella review of meta-analysis of observational studies.

BACKGROUND AND AIM: We aimed to capture the breadth of health outcomes that have been associated with the presence of Urinary Incontinence (UI) and systematically assess the quality, strength, and credibility of these associations through an umbrella review and integrated meta-analyses. METHODS: We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p-values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). RESULTS AND DISCUSSION: From 3172 articles returned in search of the literature, 9 systematic reviews were included with a total of 41 outcomes. Overall, 37 out of the 41 outcomes reported nominally significant summary results (p < 0.05), with 22 associations surviving the application of a more stringent p-value (p < 10-6). UI was associated with worse scores than controls in female sexual function (Class II), while it was also associated with a higher prevalence of depression (odds ratio [OR] = 1.815; 95% confidence interval [CI]: 1.551-2.124), and anxiety (OR = 1.498; 95% CI: 1.273-1.762) (Class IV). UI was associated with poorer quality of life (QoL), higher rate of mortality (hazard ratio = 2.392; 95% CI: 2.053-2.787) an increase in falls, frailty, pressure ulcers, diabetes, arthritis, and fecal incontinence (Class IV). CONCLUSIONS: UI is associated with female sexual dysfunction, with highly suggestive evidence. However, the evidence of other adverse outcomes including depression, anxiety, poorer QoL, higher mortality, falls, pressure ulcers, diabetes, arthritis, fecal incontinence, and frailty is only weak. A multidimensional approach should be taken in managing UI in the clinical setting.

How Resources Combining Expertise and Social Support Help Breastfeeding Women Address Self-Doubt and Increase Breastfeeding Self-Efficacy: A Mixed-Methods Study.

Existing research on parental information literacy focuses on parents' ability to evaluate information. This approach does not account for conflicting or unwanted information and obscures the emotional impact of unsought information. We aimed to (1) document the sources women use most frequently for accessing breastfeeding information, (2) explore the reasons women choose some sources over others, (3) test the relationship between source characteristics and breastfeeding self-efficacy, and (4) determine the extent to which four source characteristics - competence, trustworthiness, goodwill, and social support - predict breastfeeding self-efficacy. This study was conducted in two phases. The first phase consisted of interviews and focus groups, which we analyzed inductively using a grounded theory approach. In phase two, we conducted a cross-sectional survey of women who were currently breastfeeding, collecting data on the source credibility and social support associated with the source they use most frequently and the participants' breastfeeding self-efficacy. We used multiple regression to analyze our survey data. The frequency with which our participants encountered conflicting and unsought prompted them to view sources that combine expertise and social support as ideal. However, these sources are often difficult to access, leading to a reliance on online sources. This compromise has implications for breastfeeding tenure, as both competence and social support predicted breastfeeding self-efficacy. This study demonstrates how emotional aspects of information seeking shape women's preferred sources, how accessibility limits the use of preferred sources, and how source competence and social support influence breastfeeding self-efficacy.

Managing high-risk behaviours and challenges to prevent housing loss in permanent supportive housing: a rapid review.

Permanent supportive housing is an effective intervention for stably housing most people experiencing homelessness and mental illness who have complex support needs. However, high-risk behaviours and challenges are prevalent among this population and have the potential to seriously harm health and threaten housing tenures. Yet, the research on the relationship between high-risk issues and housing stability in permanent supportive housing has not been previously synthesized. This rapid review aimed to identify the housing-related outcomes of high-risk behaviours and challenges in permanent supportive housing settings, as well as the approaches used by agencies and residents to address them. A range of high-risk behaviours and challenges were examined, including risks to self (overdose, suicide/suicide attempts, non-suicidal self-injury, falls/fall-related injuries), and risks to multiple parties and/or building (fire-setting/arson, hoarding, apartment takeovers, physical/sexual violence, property damage, drug selling, sex trafficking). The search strategy included four components to identify relevant academic and grey literature: (1) searches of MEDLINE, APA PsycINFO, and CINAHL Plus; (2) hand searches of three journals with aims specific to housing and homelessness; (3) website browsing/searching of seven homelessness, supportive housing, and mental health agencies and networks; and (4) Advanced Google searches. A total of 32 articles were eligible and included in the review. Six studies examined the impacts of high-risk behaviours and challenges on housing tenancies, with overdose being identified as a notable cause of death. Twenty-six studies examined approaches and barriers to managing high-risk behaviours and challenges in PSH programs. These were categorized into eight types of approaches: (1) clinical, (2) relational/educational, (3) surveillant, (4) restrictive, (5) strategic, (6) design-based, (7) legal, and (8) self-defence. Consistent across all approaches was a lack of rigorous examination of their effectiveness. Further, some approaches that are legal, restrictive, surveillant, or strategic in nature may be used to promote safety, but may conflict with other program objectives, including housing stability, or resident empowerment and choice. Research priorities were identified to address the key evidence gaps and move toward best practices for preventing and managing high-risk behaviours and challenges in permanent supportive housing.

Characterization of Human Immunodeficiency Virus (HIV) Infections in Women Who Received Injectable Cabotegravir or Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Prevention: HPTN 084.

BACKGROUND: HIV Prevention Trials Network 084 demonstrated that long-acting injectable cabotegravir (CAB) was superior to daily oral tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) for preventing human immunodeficiency virus (HIV) infection in sub-Saharan African women. This report describes HIV infections that occurred in the trial before unblinding. METHODS: Testing was performed using HIV diagnostic assays, viral load testing, a single-copy RNA assay, and HIV genotyping. Plasma CAB, plasma TFV, and intraerythrocytic TFV-diphosphate concentrations were determined by liquid chromatography-tandem mass spectrometry. RESULTS: Forty HIV infections were identified (CAB arm, 1 baseline infection, 3 incident infections; TDF/FTC arm, 36 incident infections). The incident infections in the CAB arm included 2 with no recent drug exposure and no CAB injections and 1 with delayed injections; in 35 of 36 cases in the TDF/FTC arm, drug concentrations indicated low or no adherence. None of the cases had CAB resistance. Nine women in the TDF/FTC arm had nonnucleoside reverse-transcriptase inhibitor resistance; 1 had the nucleoside reverse-transcriptase inhibitor resistance mutation, M184V. CONCLUSIONS: Almost all incident HIV infections occurred in the setting of unquantifiable or low drug concentrations. CAB resistance was not detected. Transmitted nonnucleoside reverse-transcriptase inhibitor resistance was common; 1 woman may have acquired nucleoside reverse-transcriptase inhibitor resistance from study drug exposure.

Upregulation of H3K27 Demethylase KDM6 During Respiratory Syncytial Virus Infection Enhances Proinflammatory Responses and Immunopathology.

Severe disease following respiratory syncytial virus (RSV) infection has been linked to enhanced proinflammatory cytokine production that promotes a Th2-type immune environment. Epigenetic regulation in immune cells following viral infection plays a role in the inflammatory response and may result from upregulation of key epigenetic modifiers. In this study, we show that RSV-infected bone marrow-derived dendritic cells (BMDC) as well as pulmonary dendritic cells (DC) from RSV-infected mice upregulated the expression of Kdm6b/Jmjd3 and Kdm6a/Utx, H3K27 demethylases. KDM6-specific chemical inhibition (GSK J4) in BMDC led to decreased production of chemokines and cytokines associated with the inflammatory response during RSV infection (i.e., CCL-2, CCL-3, CCL-5, IL-6) as well as decreased MHC class II and costimulatory marker (CD80/86) expression. RSV-infected BMDC treated with GSK J4 altered coactivation of T cell cytokine production to RSV as well as a primary OVA response. Airway sensitization of naive mice with RSV-infected BMDCs exacerbate a live challenge with RSV infection but was inhibited when BMDCs were treated with GSK J4 prior to sensitization. Finally, in vivo treatment with the KDM6 inhibitor, GSK J4, during RSV infection reduced inflammatory DC in the lungs along with IL-13 levels and overall inflammation. These results suggest that KDM6 expression in DC enhances proinflammatory innate cytokine production to promote an altered Th2 immune response following RSV infection that leads to more severe immunopathology.

Social Contact: Next Steps in an Effective Strategy to Mitigate the Stigma of Mental Illness.

People living with mental illnesses and their families may conceal their conditions to avoid prejudice and discrimination. Stigma often prevents people from receiving adequate health care and other social support services which could exacerbate social and health consequences such as unemployment, homelessness, substance use, and compulsory hospitalization. In this paper, we discuss social contact as a promising anti-stigma strategy for enhancing social interactions among people with mental illnesses, their families, and those without mental illnesses. In particularly, we consider next steps for an approach that works to reduce the stigma-related burden of mental illness. For social contact to be effective in reducing mental illness stigma, it requires broad social buy-in as well as implementation within care systems. Engagement with this approach can be driven through diverse contact-based education using collaborative efforts of society, academic institutions, policy-makers, health professionals, media, and governments. Ultimately, this work aims to consider the next steps in enacting social contact as an anti-stigma strategy through direct interventions and contact-based education. The success of this approach requires pragmatic public policies to support its implementation.

Physical multimorbidity and incident urinary incontinence among community-dwelling adults aged ≥50 years: findings from a prospective analysis of the Irish Longitudinal Study on Ageing.

BACKGROUND: There are no prospective studies on the association between multimorbidity and urinary incontinence (UI), while mediators in this association are unknown. Thus, we aimed to (i) investigate the longitudinal association between multimorbidity and UI in a large sample of Irish adults aged ≥50 years and (ii) investigate to what extent physical activity, polypharmacy, cognitive function, sleep problems, handgrip strength and disability mediate the association. METHODS: Data on 5,946 adults aged ≥50 years old from the Irish Longitudinal Study on Aging were analysed. The baseline survey was conducted between 2009 and 2011 and follow-up after 2 years was conducted. Information on self-reported occurrence of UI in the past 12 months and lifetime diagnosis of 14 chronic conditions were obtained. Multivariable logistic regression and mediation analysis were conducted. RESULTS: After adjustment for potential confounders, compared to having no chronic conditions at baseline, having three (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.30-2.48) and four or more (OR = 1.86; 95% CI = 1.32-2.60), chronic conditions were significantly associated with incident UI. Mediation analysis showed that polypharmacy, sleep problems and disability explained 22.7, 17.8 and 14.7% of the association between multimorbidity (i.e. two or more chronic conditions) and incident UI, respectively. CONCLUSION: A greater number of chronic conditions at baseline were associated with a higher risk for incident UI at 2-year follow-up among adults aged ≥50 years in Ireland. Considering the effects of different medications on UI and improving sleep quality and disability among people aged ≥50 years with multimorbidity may reduce the incidence of UI.

Contributions of the EURO 2020 football championship events to a third wave of SARS-CoV-2 in Scotland, 11 June to 7 July 2021.

Public Health Scotland used Scottish national contact tracing data to estimate the European football championship (EURO 2020) contributions to a third wave of SARS-CoV-2 infections. From 11 June to 7 July 2021, 2,632 (4%) of 63,874 SARS-CoV-2 cases self-reported attending a EURO 2020 event; 90% were male, of whom 73% were 20-39-year-olds. Most cases attended unofficial gatherings and averaged more contacts than the general population. Targeted guidance on celebrating safely in closed spaces is key.

Policies and Interventions to Reduce Familial Mental Illness Stigma: A Scoping Review of Empirical Literature.

Although research to date has shown that there can be no health or sustainable development without good mental health, mental illness continues to significantly impact societies. A major challenge confronting people with mental illnesses and their families is the stigma that they endure. In this study, empirical literature was reviewed to assess policies and interventions that seek to reduce familial mental illness stigma across four countries. We used Arksey and O'Malley methodological framework, and a qualitative content analysis was employed to augment the descriptive data extracted. Seven studies published between 2000 and 2020 were analyzed. We propose herein three themes that align with interventions to reduce familial mental illness stigma: transformative education, sharing and disclosure, and social networking and support. The findings indicate that persuasive and purposeful education directed at the public to correct misconceptions surrounding mental illness, with attention to language, may help in reducing familial mental illness stigma. Disclosure of mental illness is encouraged among persons with mental illnesses and their families as a strategy to enhance mutual understanding. Social sharing also affords persons with mental illnesses opportunities to engage with their peers at different levels within the public sphere. Apart from these recommendations, we have noted a paucity of broad governmental-level policies and interventions to comprehensively address the negative attitudes of families toward their relatives. Future work must address this gap to identify effective interventions to create healthier and supportive environments that address familial mental illness stigma.

Inhibition of uric acid or IL-1ß ameliorates respiratory syncytial virus immunopathology and development of asthma.

BACKGROUND: Respiratory syncytial virus (RSV) affects most infants early in life and is associated with increased asthma risk. The specific mechanism remains unknown. OBJECTIVE: To investigate the role of uric acid (UA) and IL-1ß in RSV immunopathology and asthma predisposition. METHODS: Tracheal aspirates from human infants with and without RSV were collected and analyzed for pro-IL-1ß mRNA and protein to establish a correlation in human disease. Neonatal mouse models of RSV were employed, wherein mice infected at 6-7 days of life were analyzed at 8 days postinfection, 5 weeks postinfection, or after a chronic cockroach allergen asthma model. A xanthine oxidase inhibitor or IL-1 receptor antagonist was administered during RSV infection. RESULTS: Human tracheal aspirates from RSV-infected infants showed elevated pro-IL-1ß mRNA and protein. Inhibition of UA or IL-1ß during neonatal murine RSV infection decreased mucus production, reduced cellular infiltrates to the lung (especially ILC2s), and decreased type 2 immune responses. Inhibition of either UA or IL-1ß during RSV infection led to chronic reductions in pulmonary immune cell composition and reduced type 2 immune responses and reduced similar responses after challenge with cockroach antigen. CONCLUSIONS: Inhibiting UA and IL-1ß during RSV infection ameliorates RSV immunopathology, reduces the consequences of allergen-induced asthma, and presents new therapeutic targets to reduce early-life viral-induced asthma development.

Patient and carer experience of nutrition care throughout treatment for head and neck cancer: a systematic qualitative review and thematic synthesis.

Nutrition care plays a critical role in the provision of best practice care to head and neck cancer (HNC) patients, with carers playing an important role in supporting patients to maintain nutrition intake. This qualitative systematic review investigated patient and carer experience of nutrition care throughout and beyond HNC treatment. Five databases were systematically searched for qualitative studies reporting on patient and carer experience of nutrition care throughout HNC. Twenty-five studies including 435 patients and 46 carers were identified, revealing three themes: information and support in the healthcare setting, enteral feeding challenges and management, and life outside hospital. Findings highlight the importance of providing individualised person-centred nutrition care to patients with HNC and their carers. Further qualitative research is needed to inform healthcare professionals about the needs of patients and carers to provide appropriate support throughout the treatment trajectory across and between different treatment modalities.

Analysis of the effects of mEHT on the treatment-related toxicity and quality of life of HIV-positive cervical cancer patients.

Introduction: HIV infection is associated with increased treatment-related toxicity and worse outcomes in locally advanced cervical cancer patients (LACC), especially in resource-constrained settings. Local control (LC) in a phase III randomized, controlled trial investigating modulated electro-hyperthermia (mEHT) on LACC patients in South Africa (ethics registration: M120477/M190295), was significantly higher in participants randomized to receive chemoradiotherapy (CRT) with mEHT compared to CRT alone (stratum: HIV status, accounting for age and stage). This analysis investigates whether mEHT adds to the toxicity profile of CRT in HIV-positive LACC participants.Methods: Inclusion criteria: signed informed consent; International Federation of Gynecology and Obstetrics stages IIB to IIIB squamous cell carcinoma of the cervix; HIV-positive patients: CD4 count >200 cell/µL/on antiretroviral treatment for >6 months; eligible for CRT with radical intent. Recruitment: January 2014 to November 2017 (ClinicalTrials.gov: NCT03332069). Acute toxicity (evaluated using CTCAE v4 criteria) and quality of life (according to EORTC forms) in 206 participants randomized for treatment were evaluated alongside the LC results to determine safety and efficacy in HIV-positive participants.Results: Compliance to mEHT treatment was high (97% completed ≥8 treatments) with no significant differences in CRT-related toxicity between treatment groups or between HIV-positive and -negative participants. Adverse events attributed to mEHT were minor, even in obese patients, and did not affect CRT compliance. Participants treated with mEHT reported improved fatigue, pain, emotional and cognitive functioning.Conclusion: mEHT did not cause unexpected CRT-related toxicities and is a safe treatment modality for HIV-positive patients, with minor limitations regarding body weight, even in a low-resource setting.

Adequate tumour cellularity is essential for accurate PD-L1 immunohistochemistry assessment on cytology cell-block specimens.

OBJECTIVES: PD-L1 immunohistochemistry (IHC) is an essential predictive biomarker for patients with non-small cell lung cancer (NSCLC), required to inform treatment decisions regarding anti-PD-1 immune checkpoint inhibitor therapy. This study aims to investigate the concordance between PD-L1 IHC assessed on NSCLC cytology and histology specimens and to determine the impactce of tumour cellularity. METHODS: Matched cytology and histology NSCLC specimens were retrieved from the archives of the Royal Melbourne Hospital and the Royal Prince Alfred Hospital. PD-L1 IHC was performed concurrently on both specimens at the Peter MacCallum Cancer Centre using the SP263 assay kit on the Ventana Benchmark Ultra staining platform and scored by two experienced pathologists. RESULTS: Overall agreement between matched cytology and histology specimens was good (intraclass correlation coefficient = 0.653, n = 58); however, markedly increased when the analysis was limited to cell-blocks with >100 tumour cells (intraclass correlation coefficient = 0.957, n = 29). Specificity at both 1% and 50% cut-offs was high regardless of cellularity; however, sensitivity decreased in samples with <100 tumour cells. CONCLUSIONS: PD-L1 IHC on cytology cell-block specimens in NSCLC is an acceptable alternative to histological specimens, provided adequate tumour cells are present. Clinicians and pathologists should be mindful of the risk of false negative PD-L1 IHC in samples with low tumour cellularity, to avoid excluding patients from potentially beneficial treatment.

Interventions to address burden among family caregivers of persons aging with TBI: A scoping review.

PURPOSE: To capture the scope of literature exploring interventions for caregivers of aging persons with TBI. METHODS: A scoping review of peer reviewed literature was conducted in two phases. Phase I: Searching seven databases, two independent raters screened articles using a set of predetermined criteria. Included articles were reviewed, and categorized according to common themes. Phase II: Five stakeholders were engaged in a consultation. A content analysis was performed by extracting statements from each interview using an inductive strategy, and organizing each into themes. FINDINGS: A total of 11 articles were included in the final analysis. Inter-rater reliability was assessed at both the title and abstract search [98.8% agreement; k = 0.3425 (95% CI, .246 to .439), p < .05]; and the full-text review [83% agreement; k = 0.542 (95% CI, 0.340 to 0.745), p < .05] phases. Seven articles identified potential interventions, and four identified and evaluated an intervention. Interventions targeted subjective burden (n = 4) and objective burden (n = 4), with caregiver knowledge and skill development (n = 3) classified as a sub-category of objective burden. Stakeholders overwhelmingly emphasized the need for interventions to reduce objective burden. IMPLICATIONS: Included articles were primarily composed of levels six and seven evidence, suggesting that this literature is in an early stage of development. Future research should emphasize the development and evaluation of interventions to reduce objective burden.