"You can feel the fresh air " Rural Alaska Native household perceptions of home air purifiers and health.

Alaska Native and American Indian children experience frequent respiratory illness. Indoor air quality is associated with the severity and frequency of respiratory infections in children. High efficiency particulate air (HEPA) purifiers effectively improve indoor air quality and may protect respiratory health. In 2019, the Yukon-Kuskokwim Health Corporation implemented a pilot programme that provided education and HEPA purifiers to households of children with chronic lung conditions. The team evaluated HEPA purifier acceptability and use by interviewing representatives from 11 households that participated in the pilot programme. All interviewees reported improvement in their child's health, and some believed that the health of other household members was also improved because of the HEPA purifier. Interviewees reported that the HEPA purifiers were easy to use, quiet, and not expensive to run. Five of 11 households were still using the HEPA purifier at the time of the interview, which was about three years after receipt of the unit. The most common reasons for discontinuing use were equipment failure and lack of replacement filter, suggesting that programme support could increase sustainability. Our evaluation suggests that HEPA purifiers are acceptable and feasible for use in rural Alaska Native households.

Effectiveness of COVID-19 mRNA Vaccines in Preventing COVID-19-Associated Outpatient Visits and Hospitalizations Among American Indian and Alaska Native Persons, January-November 2021: A Test-Negative Case-Control Analysis Using Surveillance Data.

Background: Despite the disproportionate morbidity and mortality experienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. Methods: We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. Results: The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0-97.6) than outpatient participants (86.5%; 95% CI, 63.0-95.0), but confidence intervals overlapped. Conclusions: Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population.

Simulation-Based Teaching of Telemedicine for Future Users of Teleconsultation and Tele-Expertise: Feasibility Study.

BACKGROUND: Health care professionals worldwide are increasingly using telemedicine in their daily clinical practice. However, there is still a lack of dedicated education and training even though it is needed to improve the quality of the diverse range of telemedicine activities. Simulation-based training may be a useful tool in telemedicine education and training delivery. OBJECTIVE: This study aims to assess the feasibility and acceptability of simulation-based telemedicine training. METHODS: We assessed five telemedicine training sessions conducted in a simulation laboratory. The training was focused on video teleconsultations between a patient and a health care professional. The assessment included the participants' satisfaction and attitudes toward the training. RESULTS: We included 29 participants in total. Participant satisfaction was high (mean score 4.9 of 5), and those that took part stated the high applicability of the simulation-based training to their telemedicine practices (mean score 4.6 of 5). They also stated that they intended to use telemedicine in the future (mean score 4.5 of 5). CONCLUSIONS: Simulation-based training of telemedicine dedicated to video teleconsultation was feasible and showed high satisfaction from participants. However, it remains difficult to scale for a high number of health care professionals.

Community water service and incidence of respiratory, skin, and gastrointestinal infections in rural Alaska, 2013-2015.

BACKGROUND: Communities in rural Alaska have access to multiple types of water service (piped, vehicle-hauled, and self-hauled) and experience varying levels of water service coverage. We assessed the incidence rate of inpatient and outpatient infectious disease visits among communities with different water service types and coverage levels. METHODS: We classified ICD-9 codes for inpatient and outpatient visits to the Yukon-Kuskokwim Health Corporation facilities between 2013 and 2015 into six infectious disease categories. Using Poisson models, we compared the incidence of visits in each category across communities with differing water service coverage levels as defined by water service billing data for the same years. Using census data, we adjusted for community median household income, median age, crowding, and health aide staffing. RESULTS: We included 48 communities in this analysis. After adjusting for possible confounders, each 10% increase in piped water coverage was associated with a 4% lower incidence of pneumonia/influenza visits (adjusted incidence rate ratio [IRR] 0.96, 95% CI 0.93-0.98), a 2% lower incidence of other respiratory infection visits (adjusted IRR 0.98, 95% CI 0.97-0.99), an 8% lower incidence of methicillin-resistant Staphylococcus visits (adjusted IRR 0.92, 95% CI 0.87-0.97), and a 4% lower incidence of other skin infections visits (adjusted IRR 0.96, 95% CI 0.95-0.98). Each 10% increase in vehicle-hauled water coverage was associated with a 2% lower incidence of respiratory infection visits (adjusted IRR 0.98, 95% CI 0.97-0.996) and a 3% lower incidence of skin infection visits (adjusted IRR 0.97, 95% CI 0.95-0.99), also after adjustment. CONCLUSIONS: Higher levels of water service coverage were associated with lower incidence rates of visits for several infectious disease categories. These associations were more pronounced for communities with piped water service compared to vehicle-hauled water service.

Heparan Sulfate Structure Affects Autophagy, Lifespan, Responses to Oxidative Stress, and Cell Degeneration in Drosophila parkin Mutants.

Autophagy is a catabolic process that provides cells with energy and molecular building blocks during nutritional stress. Autophagy also removes misfolded proteins and damaged organelles, a critical mechanism for cellular repair. Earlier work demonstrated that heparan sulfate proteoglycans, an abundant class of carbohydrate-modified proteins found on cell surfaces and in the extracellular matrix, suppress basal levels of autophagy in several cell types during development in Drosophila melanogaster In studies reported here, we examined the capacity of heparan sulfate synthesis to influence events affected by autophagy, including lifespan, resistance to reactive oxygen species (ROS) stress, and accumulation of ubiquitin-modified proteins in the brain. Compromising heparan sulfate synthesis increased autophagy-dependent processes, evident by extended lifespan, increased resistance to ROS, and reduced accumulation of ubiquitin-modified proteins in the brains of ROS exposed adults. The capacity of altering heparan sulfate biosynthesis to protect cells from injury was also evaluated in two different models of neurodegeneration, overexpression of Presenilin and parkin mutants. Presenilin overexpression in the retina produces cell loss, and compromising heparan sulfate biosynthesis rescued retinal patterning and size abnormalities in these animals. parkin is the fly homolog of human PARK2, one of the genes responsible for juvenile onset Parkinson's Disease. Parkin is involved in mitochondrial surveillance and compromising parkin function results in degeneration of both flight muscle and dopaminergic neurons in Drosophila Altering heparan sulfate biosynthesis suppressed flight muscle degeneration and mitochondrial dysmorphology, indicating that activation of autophagy-mediated removal of mitochondria (mitophagy) is potentiated in these animals. These findings provide in vivo evidence that altering the levels of heparan sulfate synthesis activates autophagy and can provide protection from a variety of cellular stressors.

Impact of home remediation and household education on indoor air quality, respiratory visits and symptoms in Alaska Native children.

Alaska Native children experience high rates of lower respiratory tract infections (LRTIs) and lung conditions, which are associated with substandard indoor air quality (IAQ). We conducted an intervention of home remediation and education to assess the impact on IAQ, respiratory symptoms and LRTI visits. We enrolled households of children 1-12 years of age with lung conditions. Home remediation included improving ventilation and replacing leaky woodstoves. We provided education about IAQ and respiratory health. We monitored indoor airborne particles (PM2.5), CO2, relative humidity and volatile organic compounds (VOCs), and interviewed caregivers about children's symptoms before, and for 1 year after intervention. We evaluated the association between children's respiratory visits, symptoms and IAQ indicators using multiple logistic regression. A total of 60 of 63 homes completed the study. VOCs decreased (coefficient = -0.20; p < 0.001); however, PM2.5 (coeff. = -0.010; p = 0.89) did not decrease. Burning wood for heat, VOCs and PM2.5 were associated with respiratory symptoms. After remediation, parents reported decreases in runny nose, cough between colds, wet cough, wheezing with colds, wheezing between colds and school absences. Children had an age-adjusted decrease in LRTI visits (coefficient = -0.33; p = 0.028). Home remediation and education reduced respiratory symptoms, LRTI visits and school absenteeism in children with lung conditions.

Children's perspectives on the benefits and burdens of research participation.

BACKGROUND: Participation in research is associated with benefits and burdens for individual research participants. Children living with a chronic illness are considered particularly vulnerable as they are already burdened with symptoms of their illness. In particular contexts, such as learning health care systems (LHS), where research and clinical care are integrated, children with chronic illnesses may be asked to participate in research related to their illness. A growing body of literature has focused on children's perspectives as research subjects; however, a relatively understudied aspect concerns children's experiences of research in clinics where they are also patients. METHODS: We interviewed 25 Canadian children and adolescents living with inflammatory bowel disease (IBD) about their experiences of research participation. RESULTS: Our participants described aspects of the research process and particular experiences as benefits and others as burdens. Benefits included helping others, receiving incentives, receiving the results of previous studies, and participating in fun activities. Burdens included the time required for particular types of research, physical and psychological discomfort, and feelings of obligation. CONCLUSIONS: Our study describes the experiences of children participating in research at a site that integrates research and clinical care. Our participants described experiences that often go unreported (such as feelings of obligation); we mention these as important considerations to be mindful of when interacting with children as (potential) research participants in an LHS and when thinking about research ethics protocols or the assent/consent process.

Heuristic decision-making about research participation in children with cystic fibrosis.

RATIONALE: Traditional perspectives on informed consent assume that when faced with decisions about whether to participate in research, individuals behave according to principles of classical rationality, taking into account all available information to weigh risks and benefits to come to a decision that is optimal for them. However, theoretical and empirical research in psychology suggests that people may not make decisions in this way. Less is known about decision-making processes as they pertain to participating in biomedical research, particularly when the participants are children. OBJECTIVE: We sought to better understand research decision processes especially in children who tend to participate extensively in research due to chronic illness. METHODS: To learn more about children's decision-making in this context, we interviewed 19 young patients with cystic fibrosis (male n = 7; female n = 12) aged 8-18 years (M = 13 years) at a children's hospital in Canada between April and August 2013. RESULTS: We found that participants generally had a default approach to participation decisions, which they attributed to their parents' attitudes to research, experiences of having grown up participating in research, trusting the researchers, and wanting to help. Most of our participants made the decision to participate in research based on a heuristic with a baseline to say "yes", subject to change based on aspects of the research or particular preferences. In particular, concerns with the procedure, unwillingness to talk about cystic fibrosis, logistical challenges, and perceptions of risk all influenced the decision, as did the perceived importance or personal relevance of the research. CONCLUSION: Our study illustrates that rather than conducting risk/benefit analyses, participants tended to adopt a heuristic-like approach, consistent with decision theories that view heuristic decision-making as ecologically rational.

Surveillance for Eurasian-origin and intercontinental reassortant highly pathogenic influenza A viruses in Alaska, spring and 2015.

BACKGROUND: Eurasian-origin and intercontinental reassortant highly pathogenic (HP) influenza A viruses (IAVs) were first detected in North America in wild, captive, and domestic birds during November-December 2014. Detections of HP viruses in wild birds in the contiguous United States and southern Canadian provinces continued into winter and spring of 2015 raising concerns that migratory birds could potentially disperse viruses to more northerly breeding areas where they could be maintained to eventually seed future poultry outbreaks. RESULTS: We sampled 1,129 wild birds on the Yukon-Kuskokwim Delta, Alaska, one of the largest breeding areas for waterfowl in North America, during spring and summer of 2015 to test for Eurasian lineage and intercontinental reassortant HP H5 IAVs and potential progeny viruses. We did not detect HP IAVs in our sample collection from western Alaska; however, we isolated five low pathogenic (LP) viruses. Four isolates were of the H6N1 (n = 2), H6N2, and H9N2 combined subtypes whereas the fifth isolate was a mixed infection that included H3 and N7 gene segments. Genetic characterization of these five LP IAVs isolated from cackling (Branta hutchinsii; n = 2) and greater white-fronted geese (Anser albifrons; n = 3), revealed three viral gene segments sharing high nucleotide identity with HP H5 viruses recently detected in North America. Additionally, one of the five isolates was comprised of multiple Eurasian lineage gene segments. CONCLUSIONS: Our results did not provide direct evidence for circulation of HP IAVs in the Yukon-Kuskokwim Delta region of Alaska during spring and summer of 2015. Prevalence and genetic characteristics of LP IAVs during the sampling period are concordant with previous findings of relatively low viral prevalence in geese during spring, non-detection of IAVs in geese during summer, and evidence for intercontinental exchange of viruses in western Alaska.

Consuming untreated water in four southwestern Alaska Native communities: reasons revealed and recommendations for change.

In this article, the authors provide the first in-depth account of why some Alaska Native people drink untreated water when treated water is available. Their qualitative research was conducted in four Alaska Native village communities that have treated water available from a centralized distribution point. Most respondents (n = 172; 82%) reported that some of their household's drinking water came from an untreated source. Motives for drinking untreated water emerged from analysis of open-ended questions about drinking water practice and could be categorized into six themes: chemicals, taste, health, access, tradition, and cost. Importantly, some residents reported consuming untreated water because they both liked untreated water and disliked treated water. As such, interventions to increase safe water consumption should address this dichotomy by providing education about the benefits of treated water alongside the risks involved with drinking untreated water. Based on the findings, the authors provide specific recommendations for developing behavior change interventions that address influences at multiple social-ecological levels.

Exertional heat-related illnesses at the Grand Canyon National Park, 2004-2009.

BACKGROUND: The Grand Canyon National Park has approximately 4 million visitors between April and September each year. During this period, outdoor activity such as hiking is potentially hazardous owing to extreme heat, limited shade, and steep, long ascents. Given the high visitation and the public health interest in the effects of extreme heat, this study calculated morbidity rates and described heat-related illness (HRI) among visitors. METHODS: We conducted a retrospective cross-sectional study from April 1 through September 30, during 2004-2009. From a review of Ranger Emergency Medical Services (EMS) incident report files, we extracted information on those that met the case definition of greater than 1 hour of outdoor heat exposure with an HRI assessment or diagnosis, HRI self-report, or signs or symptoms of HRI without another etiology noted. Visitor and temperature data were obtained from respective official sources. RESULTS: Grand Canyon EMS responded to 474 nonfatal and 6 fatal HRI cases, with the majority (84%) being US residents, 29% from Western states. Of the nonfatal cases, 51% were women, the median age was 43 years (range, 11-83 years), and 18% reported a cardiovascular condition. Clinical HRI assessments included dehydration (25%), heat exhaustion (23%), and suspected hyponatremia (19%). Almost all (90%) were hiking; 40% required helicopter evacuation. The highest HRI rates were seen in May. CONCLUSIONS: HRI remains a public health concern at the Grand Canyon. High-risk evacuations and life-threatening conditions were found. Majority were hikers, middle-aged adults, and US residents. These findings support the park's hiker HRI prevention efforts and use of park EMS data to measure HRI.

Acute Surgical Unit: a new model of care.

The traditional on-call system for the management of acute general surgical admissions is inefficient and outdated. A new model, Acute Surgical Unit (ASU), was developed at Nepean Hospital in 2006. The ASU is a consultant-driven, independent unit that manages all acute general surgical admissions. The team has the same make up 7 days a week and functions the same every day, including weekends and public holidays. The consultant does a 24-h period of on-call, from 7 pm to 7 pm. They are on remote call from 7 pm to 7 am and are in the hospital from 7 am to 7 pm with their sole responsibility being to the ASU. The ASU has a day team with two registrars, two residents and a nurse practitioner. All patients are admitted and stay in the ASU until discharge or transfer to other units. Handover of the patients at the end of each day is facilitated by a comprehensive ASU database. The implementation of the ASU at Nepean Hospital has improved the timing of assessment by the surgical unit. There has been significant improvement in the timing of operative management, with an increased number and proportion of cases being done during daylight hours, with an associated reduction in the proportion of cases performed afterhours. There is greater trainee supervision with regard to patient assessment, management and operative procedures. There has been an improvement in the consultants' work conditions. The ASU provides an excellent training opportunity for surgical trainees, residents and interns in the assessment and management of acute surgical conditions.

The landscape of somatic copy-number alteration across human cancers.

A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.

Vaccinia-expressed human papillomavirus 16 and 18 e6 and e7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia.

PURPOSE: Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia. EXPERIMENTAL DESIGN: Twelve women, aged 42-54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18. RESULTS: The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of women showed some improvement with an average decrease in lesion size of 40%. All cases showed an increased IgG titer and T-cell response to the vaccinia virus. An IFN-gamma enzyme-linked immunospot assay using pooled 22-mer peptides spanning HPV-16 E6 and E7 showed an increased specific T-cell response after vaccination in 6 of the 10 cases available for testing. There was no increase in specific cytotoxic response to selected individual HLA class I-restricted HPV-16 E6/7 peptides. CONCLUSIONS: The results suggest that the vaccine may have an effect on HPV-positive vulval intraepithelial neoplasia/vaginal intraepithelial neoplasia and that additional studies are warranted to develop an effective therapeutic vaccine.

Immunological and clinical responses in women with vulval intraepithelial neoplasia vaccinated with a vaccinia virus encoding human papillomavirus 16/18 oncoproteins.

This study assessed the immunological and clinical responses of women with human papillomavirus (HPV) 16-associated high-grade vulval intraepithelial neoplasia (VIN) vaccinated with TA-HPV, a recombinant vaccinia virus encoding modified HPV 16 and 18 E6 and E7. Eighteen women with HPV 16-positive high-grade VIN were vaccinated with TA-HPV. The extent of their baseline disease was compared after 24 weeks by lesion measurements and histological analysis. Viral load was assessed pre- and postvaccination by real time PCR. Cell-mediated immunity to HPV 16 E6 and/or E7 peptides (HLA-A2 epitopes) or vaccinia-infected cell lysates was determined by IFN-gamma enzyme-linked immunospot (ELISPOT) and T cell proliferation using an HPV 16 L2E6E7 fusion protein. Antibodies were measured by ELISA using vaccinia-infected cell lysates or HPV 16 and 18 E6 and E7 glutathione S-transferase-fusion proteins. Lesion-infiltrating CD4(+), CD8(+), CD1a(+), and CD68(+) immune cells were assessed by immunohistochemistry. The single vaccination with TA-HPV was well tolerated, and all patients showed an increased ELISPOT and/or antibody response to vaccinia. There were significant differences in HPV-16 E7-specific ELISPOT and L2E6E7 proliferative responses in the patients at one or more time points postvaccination as compared with the prevaccination status; two patients showed transient increased antibody responses. Overall, 13 women showed an increased HPV 16-specific immune response by one or more methodologies after immunization. Eight patients demonstrated a reduction in lesion diameter of at least 50% and a further four patients showed significant symptom relief. Viral load was reduced or cleared in six of eight lesion responders but also in six of ten nonresponders. Before vaccination, clinical responders had significantly higher levels of lesion-associated CD4(+), CD8(+), and CD1a(+)-immune cells than nonresponders. There were no differences in CD68 (macrophages) between responders and nonresponders before or after vaccination. Nonresponders did show a significant increase in CD4(+)- and CD8(+)- but not CD1a(+)-immune cells postvaccination but at lower levels overall than responder patients. Local immune infiltration may be a critical factor in potential responsiveness to vaccine therapy in HPV-associated neoplasia and should be carefully monitored in future placebo-controlled trials of immunotherapy for VIN.

Development of vaccines to help treat drug dependence.

The social and economic consequences of drug addiction are immense. Although many methods are adopted to treat addiction, including therapeutic intervention and counseling, the long-term success rate has been limited and there continues to be a need for more effective treatments. A novel approach that has sparked a significant degree of interest recently is the use of vaccines designed to raise specific antibodies against drugs of abuse. Antibodies that prevent addictive substances crossing the blood-brain barrier may prove to be an effective mechanism that will help prevent relapse during efforts to abstain from the drug. Proof-of-principle for this approach has been established in numerous animal models. Currently a cocaine vaccine is in phase II clinical trials and, more recently, two vaccines to nicotine have entered phase I trials. Key efficacy trials are required to establish the true potential of these therapeutic vaccines.