Through the eyes of community health workers: what was needed to increase COVID-19 vaccine uptake in the Missouri Southeast region.

Public health emergencies, such as the COVID-19 pandemic, elucidate the strengths, weaknesses, and significant gaps in infrastructure, compatibility and consistency in communication systems, as well as the quality of collaborative relationships, and provider and workforce capacity. They also expose longstanding patterns of mistrust in the government and healthcare systems, and inadequacy in socio-economic infrastructures. These issues resulted in higher COVID-19 infection and mortality rates, and lower vaccination rates in many rural counties across the nation, including Missouri. In response to these challenges, the COVID-19 Response Network was formed in the Southeast corner of the state. The Network was a community-academic partnership that brought together community and faith-based leaders, academicians, healthcare providers and administrators, public health practitioners, and pharmacists to facilitate collaboration on education and outreach efforts aimed at reducing vaccine inequity in the 16-county project area. Importantly, the Network also included Community Health Workers (CHWs) who worked with these different agencies and organizations and were at the heart of implementing Network activities. The intent of this study was to assess their perspectives on the factors that influenced community engagement and communication strategies, and increased vaccine uptake in rural Missouri. Qualitative methods, including in-depth interviews, were used to explore the professional and personal experiences of CHWs working at the grassroots level during an ongoing pandemic. Narrative analysis revealed effective communication and engagement strategies for increasing vaccine uptake in rural communities. For instance, fear-based messaging was perceived as coercive and met with resistance. In contrast, messages that shared personal experiences and catered to the human need to protect their loved ones were more effective. Trust in the source of information was critical. This study highlights the significance of exploring and leveraging the capacities of trusted community members like CHWs to increase the effectiveness of public health interventions in rural communities.

Natural History of Oral HPV Infection among Indigenous South Australians.

This study aims to describe the natural history of and identify the risk factors associated with oral human papillomavirus (HPV) infections in an Australian Indigenous cohort. A longitudinal cohort study design, with baseline (2018), 12-month, and 24-month data obtained from Indigenous Australians aged 18+ years in South Australia, was performed. Face-to-face interviews were conducted, and saliva samples for HPV testing were collected at each time point. Basic descriptive analyses were conducted to calculate prevalence, incidence, persistence, clearance, and incidence proportions of any HPV infection. Multivariable logistic regression analyses with adjusted prevalence ratios (PRs) were conducted to identify risk factors associated with oral HPV infection. Among 993 participants with valid saliva samples, 44 HPV types were identified. The prevalence of infection with any oral HPV infection was 51.3%, high-risk HPV was 11%, and types implicated in Heck's disease (HPV 13 or 32) was 37.4%. The incidence, persistence, and clearance of any and high-risk HPV infections were 30.7%, 11.8% and 33.3% vs. 9.3%, 2.8%, and 9%, respectively. Our findings indicate that the prevalence, incidence, and persistence of oral HPV infection in a large sample of Indigenous Australians were high, and clearance was low. Oral sex behaviours and recreational drug use were risk factors associated with incident high-risk HPV infection.

Advanced statistics identification of participant and treatment predictors associated with severe adverse effects induced by fluoropyrimidine-based chemotherapy.

PURPOSE: Adverse effects following fluoropyrimidine-based chemotherapy regimens are common. However, there are no current accepted diagnostic markers for prediction prior to treatment, and the underlying mechanisms remain unclear. This study aimed to determine genetic and non-genetic predictors of adverse effects. METHODS: Genomic DNA was analyzed for 25 single nucleotide polymorphisms (SNPs). Demographics, comorbidities, cancer and fluoropyrimidine-based chemotherapy regimen types, and adverse effect data were obtained from clinical records for 155 Australian White participants. Associations were determined by bivariate analysis, logistic regression modeling and Bayesian network analysis. RESULTS: Twelve different adverse effects were observed in the participants, the most common severe adverse effect was diarrhea (12.9%). Bivariate analysis revealed associations between all adverse effects except neutropenia, between genetic and non-genetic predictors, and between 8 genetic and 12 non-genetic predictors with more than 1 adverse effect. Logistic regression modeling of adverse effects revealed a greater/sole role for six genetic predictors in overall gastrointestinal toxicity, nausea and/or vomiting, constipation, and neutropenia, and for nine non-genetic predictors in diarrhea, mucositis, neuropathy, generalized pain, hand-foot syndrome, skin toxicity, cardiotoxicity and fatigue. The Bayesian network analysis revealed less directly associated predictors (one genetic and six non-genetic) with adverse effects and confirmed associations between six adverse effects, eight genetic predictors and nine non-genetic predictors. CONCLUSION: This study is the first to link both genetic and non-genetic predictors with adverse effects following fluoropyrimidine-based chemotherapy. Collectively, we report a wealth of information that warrants further investigation to elucidate the clinical significance, especially associations with genetic predictors and adverse effects.

The Indigenous Australian Human Papillomavirus (HPV) Cohort Study 2, Continuation for 5 to 10 Years: Protocol for a Longitudinal Study.

BACKGROUND: Human papillomavirus (HPV) infection, a common sexually transmitted disease, is associated with cancers of the cervix, vulva, vagina, penis, anus, and head and neck. Oropharyngeal squamous cell carcinoma (OPSCC; throat cancer) is a type of cancer involving the head and neck area that is rapidly increasing across the globe. There are higher rates of OPSCC among Indigenous populations relative to non-Indigenous Australian populations, although the HPV-attributable fraction remains unknown. For the first time at a global level, we plan to extend an Indigenous Australian adult cohort to monitor, screen, and ultimately prevent HPV-associated OPSCC and to undertake extensive cost-effectiveness modelling around HPV vaccination. OBJECTIVE: This study aims to (1) extend follow-up to a minimum of 7 years post recruitment to describe the prevalence, incidence, clearance, and persistence of oral HPV infection; and (2) conduct clinical examinations of the head and neck, oral cavity, and oropharynx and collect saliva samples for early-stage OPSCC testing. METHODS: We will continue to implement a longitudinal design for the next study phase, where we will ascertain the prevalence, incidence, clearance, and persistence of oral HPV infection at 48, 60, and 72 months; undertake clinical examinations/saliva assessments to detect early-stage OPSCC; and refer for treatment. The primary outcome measures are changes in oral HPV infection status, biomarker measures of early HPV-related cancer, and clinical evidence of early-stage OPSCC. RESULTS: Participant 48-month follow-up will commence in January 2023. The first results are expected to be submitted for publication 1 year after 48-month follow-up begins. CONCLUSIONS: Our findings have potential to change the way in which OPSCC among Australian Indigenous adults is managed, with desired impacts including cost-savings on expensive cancer treatments; improved nutritional, social, and emotional outcomes; and improved quality of life for both Indigenous adults and the Indigenous community more broadly. Continuing a large, representative Indigenous adult cohort to track oral HPV infection and monitor early OPSCC is essential to yield critical information to include in the management armamentarium of health and well-being recommendations for Australia's First Nations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44593.

Mitochondrial brain proteome acetylation levels and behavioural responsiveness to amphetamine are altered in mice lacking Sirt3.

Post-translational modification of mitochondrial proteins represents one mechanism by which the functional activity of mitochondria can be regulated. In the brain, these modifications can influence the functional properties of different neural circuitries. Given that the sirtuin family member Sirt3 represents the primary protein deacetylase enzyme in mitochondria, we tested whether brain mitochondrial proteome acetylation would increase in male or female mice lacking Sirt3. Our results confirm that whole brain mitochondrial proteome acetylation levels are indeed elevated in both sexes of Sirt3-KO mice relative to controls. Consistently, we found the mitochondria of mouse embryonic fibroblast (MEF) cells derived from Sirt3-KO mice were smaller in size, and fewer in number than in wild-type MEFs, and that mitochondrial free calcium levels were elevated within the mitochondria of these cells. As protein acetylation can influence mitochondrial function, and changes in mitochondrial function have been linked to alterations in neural circuit function regulating motor activity and anxiety-like behavior, we tested whether Sirt3-deficient mice would display sensitized responsiveness to the stimulant amphetamine. Both male and female Sirt3-KO mice displayed hyper-locomotion and attenuated anxiety-like behavior in response to a dose of amphetamine that was insufficient to promote any behavioural responses in wild-type mice. Collectively, these results confirm that Sirt3 regulates mitochondrial proteome acetylation levels in brain tissue, and that the absence of Sirt3 increases the sensitivity of neural systems to amphetamine-induced behavioural responses.

Implementation and evaluation of social determinants of health practice models within community pharmacy.

BACKGROUND: While community pharmacies are an ideal setting for social needs screening and referral programs, information on social risk assessment within pharmacy practice is limited. OBJECTIVES: Our primary objective was to describe 2 social determinant of health (SDOH) practice models implemented within community pharmacies. The secondary objective was to evaluate implementation practices utilizing the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. PRACTICE DESCRIPTION: Two pharmacy groups participated in a 3-month study, one in New York (9 pharmacies) and another in Missouri (1 pharmacy). The New York pharmacies implemented an SDOH specialist practice model, in which pharmacy staff members facilitate the program. The Missouri pharmacy implemented a community health worker (CHW) model by cross training their technicians. Each pharmacy developed their program using the Community Pharmacy Enhanced Services Network Care Model. PRACTICE INNOVATION: Both programs expanded the technician role to take on additional responsibilities. The SDOH specialist model partnered with a local independent practice association to create a social needs referral program using a technology platform for closed-loop communication. All workflow steps of the self-contained CHW program were completed within the pharmacy, placing additional responsibility on the CHW and pharmacy staff. EVALUATION METHODS: RE-AIM framework dimensions of Reach, Effectiveness, and Adoption. RESULTS: Social challenges were identified in 49 of 76 (65%) generated SDOH screenings. The most prevalent social needs reported were affordability of daily needs (33%) and health care system navigation (15%). While most pharmacy staff indicated that workflow steps were clearly defined, assessments and referral tools were identified as potential gaps. While approximately 50% of pharmacy staff were comfortable with their assigned roles and in addressing SDOH challenges, physical and mental health concerns required additional education for intervention. CONCLUSION: The successful implementation of community pharmacy SDOH programs connected patients with local resources. Community pharmacies are ideally positioned to expand their public health footprint through SDOH interactions that consequently improve patient care.

Factors Associated With Oral Mucositis Severity in Children Who Have Received Chemotherapy.

Oral mucositis (OM) is a major complication for pediatric oncology patients undergoing cancer therapy. This paper aimed to report on the relationship between OM severity and various patient factors as well as to compare 2 scales used to assess OM severity. The severity of 68 separate episodes of OM in 47 pediatric oncology patients who had received chemotherapy was regularly assessed using the Children's International Mucositis Evaluation Scale (ChIMES) and World Health Organization (WHO) scale. The mean time from the start of the patients' chemotherapy block to the onset of OM was 8.4 days (±4.0), the median duration of OM was 7.0 days (4.0, 10.5) and median admission duration was 7.0 days (4.5, 13.5). There was a significant relationship between the severity of OM and the duration of symptoms ( P <0.001), patient's admission length ( P <0.001) and low neutrophil count. With decreasing neutrophil count, the severity of OM and number of pain medications used increased. Neutrophil count recovery coincided with resolution of OM. No significant relationship was found between OM severity and the child's cancer diagnosis. The 2 scales used to measure OM severity showed substantial agreement.

An update on Heck's disease-a systematic review.

BACKGROUND: Previous research has suggested an ethnic association of Heck's disease with a prominent genetic and familial inheritance pattern, but no systematic review has been reported, which has collected all the evidence in one paper. The aim was estimation of the updated age estimates and gender predilection of this disease and also questioning its proposed link to ethnic and geographical factors. METHODS: Heck's disease from 1966 until present are tabulated, including various descriptive characteristics. After removal of duplicates and adhering to all the inclusion criteria, we shortlisted 95 case reports. The quality assessment of all included studies has been done following STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guidelines. RESULTS: We found an age range of 3-92 years (mean: 23.1 years) with a male to female ratio of 3:4. Geographical distribution revealed one of the main findings of this study, which was an increased incidence of Heck's disease in the European region. CONCLUSIONS: As already observed and established, there is a much greater prevalence of this disease in the indigenous populations of the world and more research should be encouraged to understand the correct transmission and pattern of spread of this disease.

Diagnostic Accuracy of Confocal Laser Endomicroscopy for the Diagnosis of Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Advances in treatment approaches for patients with oral squamous cell carcinoma (OSCC) have been unsuccessful in preventing frequent recurrences and distant metastases, leading to a poor prognosis. Early detection and prevention enable an improved 5-year survival and better prognosis. Confocal Laser Endomicroscopy (CLE) is a non-invasive imaging instrument that could enable an earlier diagnosis and possibly help in reducing unnecessary invasive surgical procedures. OBJECTIVE: To present an up to date systematic review and meta-analysis assessing the diagnostic accuracy of CLE in diagnosing OSCC. MATERIALS AND METHODS: PubMed, Scopus, and Web of Science databases were explored up to 30 June 2021, to collect articles concerning the diagnosis of OSCC through CLE. Screening: data extraction and appraisal was done by two reviewers. The quality of the methodology followed by the studies included in this review was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A random effects model was used for the meta-analysis. RESULTS: Six studies were included, leading to a total number of 361 lesions in 213 patients. The pooled sensitivity and specificity were 95% (95% CI, 92-97%; I2 = 77.5%) and 93% (95% CI, 90-95%; I2 = 68.6%); the pooled positive likelihood ratios and negative likelihood ratios were 10.85 (95% CI, 5.4-21.7; I2 = 55.9%) and 0.08 (95% CI, 0.03-0.2; I2 = 83.5%); and the pooled diagnostic odds ratio was 174.45 (95% CI, 34.51-881.69; I2 = 73.6%). Although risk of bias and heterogeneity is observed, this study validates that CLE may have a noteworthy clinical influence on the diagnosis of OSCC, through its high sensitivity and specificity. CONCLUSIONS: This review indicates an exceptionally high sensitivity and specificity of CLE for diagnosing OSCC. Whilst it is a promising diagnostic instrument, the limited number of existing studies and potential risk of bias of included studies does not allow us to draw firm conclusions. A conclusive inference can be drawn when more studies, possibly with homogeneous methodological approach, are performed.

Differences in SMA-like polymer architecture dictate the conformational changes exhibited by the membrane protein rhodopsin encapsulated in lipid nano-particles.

Membrane proteins are of fundamental importance to cellular processes and nano-encapsulation strategies that preserve their native lipid bilayer environment are particularly attractive for studying and exploiting these proteins. Poly(styrene-co-maleic acid) (SMA) and related polymers poly(styrene-co-(N-(3-N',N'-dimethylaminopropyl)maleimide)) (SMI) and poly(diisobutylene-alt-maleic acid) (DIBMA) have revolutionised the study of membrane proteins by spontaneously solubilising membrane proteins direct from cell membranes within nanoscale discs of native bilayer called SMA lipid particles (SMALPs), SMILPs and DIBMALPs respectively. This systematic study shows for the first time, that conformational changes of the encapsulated protein are dictated by the solubilising polymer. The photoactivation pathway of rhodopsin (Rho), a G-protein-coupled receptor (GPCR), comprises structurally-defined intermediates with characteristic absorbance spectra that revealed conformational restrictions with styrene-containing SMA and SMI, so that photoactivation proceeded only as far as metarhodopsin-I, absorbing at 478 nm, in a SMALP or SMILP. In contrast, full attainment of metarhodopsin-II, absorbing at 382 nm, was observed in a DIBMALP. Consequently, different intermediate states of Rho could be generated readily by simply employing different SMA-like polymers. Dynamic light-scattering and analytical ultracentrifugation revealed differences in size and thermostability between SMALP, SMILP and DIBMALP. Moreover, encapsulated Rho exhibited different stability in a SMALP, SMILP or DIBMALP. Overall, we establish that SMA, SMI and DIBMA constitute a 'toolkit' of solubilising polymers, so that selection of the appropriate solubilising polymer provides a spectrum of useful attributes for studying membrane proteins.

Cohort profile: indigenous human papillomavirus and oropharyngeal squamous cell carcinoma study - a prospective longitudinal cohort.

PURPOSE: Our aims are to: (1) estimate prevalence, incidence, clearance and persistence of oral human papillomavirus (HPV) infection among Indigenous Australians; (2) identify risk factors associated with oropharyngeal squamous cell carcinoma (OPSCC)-related HPV types (HPV 16 or 18); (3) develop HPV-related health state valuations and; (4) determine the impact on OPSCC and cervical cancers, and the cost-effectiveness of extending publicly-funded HPV vaccination among Indigenous Australians. PARTICIPANTS: Participants were recruited from February 2018 to January 2019. Twelve-month follow-up occurred from March 2019 to March 2020. Participants provided socio-demographic characteristics, health-related behaviours including tobacco and alcohol use and sexual history. Health state preferences in regard to HPV vaccination, knowledge regarding HPV infection, OPSCC and cervical cancer were collected using a two-stage standard gamble approach. Participants provided saliva samples and DNA for microbial genotyping was extracted. FINDINGS TO DATE: Of the 910 participants who were positive for ß-globin at baseline, 35% had any oral HPV infection. The most prevalent HPV types were 13 or 32 (Heck's disease; 23%). The second most prevalent types were associated with OPSCC (HPV 16 or 18; 3.3%). Of the 645 participants who were positive for ß-globin at 12-month follow-up, 43% had any HPV infection. Of these, 33% were HPV types 13 or 32 and 2.5% were HPV 16 or 18. Some 588 participants had ß-globin positive oral samples at baseline and 12-month follow-up. The prevalence of any oral HPV infection increased from 34% at baseline to 44% at 12-month follow-up; due to increases in HPV types 13 or 32 (20% at baseline and 34% at 12-month follow-up). FUTURE PLANS: Further funding will be sought to continue follow-up of this cohort, and to include (after a full medical history) a thorough clinical examination of the external head and neck; a complete oral examination and examination of the oropharynx. Blood tests for early stage OPSCC will also be undertaken.

A systematic review and meta-analysis of the prevalence of human papillomavirus infection in Indigenous populations - A Global Picture.

BACKGROUND AND AIM: Recent trends have shown a decline in the rates of human papillomavirus (HPV)-associated cervical cancer in the vaccinated population but there has been a spike in the HPV-associated oropharyngeal, anal and penile cancers in the majority of the unvaccinated population which are young and middle-aged males. Indigenous populations at an international level carry a disproportionate burden of most diseases. The aim of this meta-analysis was to ascertain the worldwide prevalence of HPV infection in Indigenous populations stratified by sex and site and to document the most commonly reported HPV types. METHODS: Published articles on HPV infection in Indigenous populations from PubMed, Scopus, EMBASE and Web of Science were systematically searched from inception until 23 December 2019. RESULTS: A total of 41 studies were included in the final analysis. The pooled worldwide prevalence of HPV infection (for both oral and genital sites, both males and females) in Indigenous populations was 34.2% (95% CI: 28.9%-39.8%). Subgroup analysis (geographical) showed that the pooled prevalence for African Indigenous, American Indigenous and Asian-Oceanic Indigenous populations were 33.0% (95% CI: 12.8%-57.1%), 33.0% (95% CI: 27.4%-38.9%) and 33.3% (95% CI: 0.17.5%-51.3%), respectively. CONCLUSION: There are not enough data on the burden of the infection carried by males especially with respect to highly suspicious sites like oropharynx. Also, we conclude an overall high prevalence of HPV infection in the Indigenous populations and increasing their susceptibility to benign and malignant manifestations of HPV.

Addressing social determinants of health in community pharmacy: Innovative opportunities and practice models.

Social determinants of health (SDoH) account for up to 90% of health outcomes, whereas medical care accounts for only 10%-15%; despite this disparity, only 24% of hospitals and 16% of physician practices screen for the 5 social needs. Community-embedded and highly accessible, pharmacies are uniquely positioned to connect individuals to local community and social resources and thereby address SDoH. In this article, we explore novel community pharmacy practice models that address SDoH, provide real-world examples of these models, and discuss pathways for reimbursement and sustainability. A number of innovative community pharmacy practice models that focus on social issues are currently being explored. These include integrating community health workers (CHWs) or SDoH specialists, wherein CHWs are frontline public health workers who can effectively bridge the health care system and their community, whereas SDoH specialists are pharmacy team members trained with substantial SDoH knowledge and how to use it to connect pharmacy patients to community resources. Three community pharmacy networks have implemented pilot programs using either a CHW or SDoH specialist model. An essential component for program success in all cases has been partnership development and increased interdependence between the pharmacies, local community organizations, and the public health sector. New payment models and financial incentives will be necessary to expand and sustain these programs. A potential Approach may be the use of Z codes, a subset of ICD-10-CM codes specific to assessing SDoH. Although opportunities are developing for community pharmacies to play a major role in sustainably addressing SDoH, additional work is needed before there is a widespread acceptance of pharmacies becoming service referral destinations for patients with social needs. Evaluation of these models on a wider scale will be necessary to fully evaluate their effectiveness, costs, and implementation within different community pharmacy settings.

Choice of faecal immunochemical test matters: comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer.

OBJECTIVES: Currently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 µg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed. METHODS: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons. RESULTS: A total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 µg Hb/g faeces for both tests found an agreement of 88.1%, at 10 µg Hb/g faeces 91.7% and at 150 µg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001. CONCLUSIONS: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb.

High-Risk Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma Among Non-Indigenous and Indigenous Populations: A Systematic Review.

OBJECTIVE: To estimate the prevalence of oral high-risk human papillomavirus (hr-HPV) infection and the proportion of hr-HPV-related oropharyngeal squamous cell carcinoma (OPSCC) among Indigenous and non-Indigenous populations. DATA SOURCE: Electronic database searches of PubMed, PubMed Central, Embase, MEDLINE, Scope, and Google Scholar were conducted for articles published from January 2000 until November 2019. REVIEW METHODS: Studies were included with a minimum of 100 cases assessing hr-HPV infection in either population samples or oropharyngeal cancer tumor series. The objective was to conduct meta-analyses to calculate the pooled prevalence of oral hr-HPV infection by adjusting for age group or sex in primary studies, the incidence of OPSCC, and the proportion of hr-HPV-related OPSCC in Indigenous people and non-Indigenous/general populations. RESULTS: We identified 47 eligible studies from 157 articles for meta-analyses. The pooled prevalence of oral hr-HPV infection was 7.494% (95% CI, 5.699%-9.289%) in a general population, with a higher prevalence among men (10.651%) than women (5.176%). The pooled incidence rate was 13.395 (95% CI, 9.315-17.475) and 7.206 (95% CI, 4.961-9.450) per 100,000 person-years in Indigenous and non-Indigenous populations, respectively. The overall pooled proportion of hr-HPV-related OPSCC was 50.812% (95 CI, 41.656%-59.969%). The highest proportion was in North America (60.221%), while the lowest proportion was in the Asia-Pacific (34.246%). CONCLUSION: Our findings suggest that in the general population, the prevalence of oral hr-HPV infection is lower among females and those in younger age groups. The incidence of OPSCC was higher among Indigenous than non-Indigenous populations, with the proportion being highest in North America.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.

BACKGROUND: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis. METHODS: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions. CONCLUSIONS: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer.

Prevalence of Oral Human Papillomavirus Infection Among Australian Indigenous Adults.

Importance: Human papillomavirus (HPV) infection is associated with oropharyngeal squamous cell carcinoma. International estimates suggest overall oral HPV prevalence is 7.5%, with prevalence of oral HPV types 16 and 18 being 1.6%; prior Australian estimates suggest oral HPV prevalence is 2.3%, with HPV-16 and HPV-18 being 1.3%. Objectives: To estimate the prevalence of oral HPV infection among Indigenous Australians and to report the prevalence of factors associated with high-risk HPV types (ie, HPV-16 and HPV-18) and HPV types linked with Heck disease (ie, HPV-13 and HPV-32). Design, Setting, and Participants: This cross-sectional study analyzed HPV screening results from saliva samples collected from 1011 Indigenous Australians between February 2018 and January 2019. Data were analyzed from May 2018 to May 2019. Recruitment occurred through Aboriginal Community Controlled Health Organisations in South Australia. Eligibility included identifying as Indigenous, residing in South Australia, and being aged 18 years or older. Main Outcomes and Measures: Saliva samples were collected, with microbial DNA for genotyping extracted. Sociodemographic parameters, health-related behaviors, and sexual history data were collected. Analyses were stratified by sex as well as by HPV types 13 and 32 (Heck disease) and 16 and 18 (high risk of oropharyngeal squamous cell carcinoma). Multivariable analyses were conducted to obtain adjusted odds ratios (ORs). Results: Data were obtained for 910 participants (median [interquartile range] age, 37 [27-51] years); 595 participants (65%) were female and 572 (63%) resided in nonmetropolitan locations. In all, 321 saliva samples (35.3%; 95% CI, 32.2%-38.4%) were positive for oral HPV (106 [33.7%] men; 215 [36.1%] women). The highest prevalence was found for HPV types 13 and 32 (207 [22.7%] total; 60 [19.0%] men; 147 [24.7%] women) followed by HPV types 16 and 18 (30 [3.3%] total; 9 [2.9%] men; 21 [3.5%] women). After multivariable analysis, risk factors associated with HPV types 13 and 32 included nonmetropolitan residential status (OR, 2.06; 95% CI, 1.10-3.88) and not having had a tonsillectomy (OR, 2.74; 95% CI, 1.05-7.16). Among women, having obtained a high school education or less was associated with lower odds of HPV-16 and HPV-18 infection (OR, 0.16; 95% CI, 0.03-0.97). Conclusions and Relevance: Prevalence of oral HPV infection in a large sample of Indigenous Australians was high, with one-third testing positive. The most prevalent HPV types were those associated with Heck disease. The prevalence of HPV types associated with oropharyngeal squamous cell carcinoma exceeded both Australian and international population-level estimates.

Systematic review of growth factors and cytokines for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To update the clinical practice guidelines for the use of growth factors and cytokines for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: recommendation, suggestion, and no guideline possible. RESULTS: A total of 15 new papers were identified within the scope of this section and were merged with 51 papers that were reviewed in the previous guidelines update. Of these, 14, 5, 13, 2, and 1 were randomized controlled trials about KGF-1, G-CSF, GM-CSF, EGF, and erythropoietin, respectively. For the remaining agents there were no new RCTs. The previous recommendation for intravenous KGF-1 in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) conditioned with high-dose chemotherapy and TBI-based regimens is confirmed. The previous suggestion against the use of topical GM-CSF for the prevention of OM in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation remains unchanged. CONCLUSIONS: Of the growth factors and cytokines studied for the management of OM, the evidence supports a recommendation in favor of KGF-1 and a suggestion against GM-CSF in certain clinical settings.

Combining bacteriophage engineering and linear dichroism spectroscopy to produce a DNA hybridisation assay.

Nucleic acid detection is an important part of our bio-detection arsenal, with the COVID-19 pandemic clearly demonstrating the importance to healthcare of rapid and efficient detection of specific pathogenic sequences. As part of the drive to establish new DNA detection methodologies and signal read-outs, here we show how linear dichroism (LD) spectroscopy can be used to produce a rapid and modular detection system for detecting quantities of DNA from both bacterial and viral pathogens. The LD sensing method exploits changes in fluid alignment of bionanoparticles (bacteriophage M13) engineered with DNA stands covalently attached to their surfaces, with the read-out signal induced by the formation of complementary duplexes between DNA targets and two M13 bionanoparticles. This new sandwich assay can detect pathogenic material down to picomolar levels in under 1 minute without amplification, as demonstrated by the successful sensing of DNA sequences from a plant virus (Potato virus Y) and an ampicillin resistance gene, ampR.

The Management of Pediatric Oncology Inpatients With Oral Mucositis.

The purpose of the study was to investigate the management of chemotherapy-induced oral mucositis (OM) in pediatric patients. A total of 68 separate episodes of OM were assessed in 47 children who had received chemotherapy. The severity of the child's OM was assessed using 2 scales, and relevant clinical information was collected. The mean onset time of OM was 8.4 days (±4.0), with a median duration of 7.0 days (4.0, 10.5), with median admission of 7.0 days (4.5, 13.5). The overall adherence to an oral health protocol was 59%, which decreased with more severe OM. A third of patients used chlorhexidine mouthwash only, which was used in preference in cases of severe OM. Almost all patients had some systemic analgesia administered, with a significant increase in patient-controlled analgesia/nurse-controlled analgesia and intravenous ketamine in severe cases. Various types of prophylaxis/treatment of secondary infections and supportive care were associated with the severity of OM. The management of OM in children is important to limit its burden. An oral care protocol was recommended. Chlorhexidine mouthwash can maintain some form of oral care when brushing becomes too uncomfortable in severe OM. Pain management is important for the management of OM, and its intensity increases with increasing severity of OM.