Adaptation and Formative Evaluation of Online Decision Support to Implement Evidence-Based Strategies to Increase HPV Vaccination Rates in Pediatric Clinics

Human papilloma virus (HPV) vaccination rates remain below national goals in the United States despite the availability of evidence-based strategies to increase rates. The Adolescent Vaccination Program (AVP) is a multi-component intervention demonstrated to increase HPV vaccination rates in pediatric clinics through the implementation of six evidence-based strategies. The purpose of this study, conducted in Houston, Texas, from 2019-2021, was to adapt the AVP into an online decision support implementation tool for standalone use and to evaluate its feasibility for use in community clinics. Phase 1 (Adaptation) comprised clinic interviews

Symptom management in people dying with COVID-19: multinational observational study

Objectives To describe multinational prescribing practices by palliative care services for symptom management in patients dying with COVID-19 and the perceived effectiveness of medicines.Methods We surveyed specialist palliative care services, contacted via relevant organisations between April and July 2020. Descriptive statistics for categorical variables were expressed as counts and percentages. Content analysis explored free text responses about symptom management in COVID-19. Medicines were classified using British National Formulary categories. Perceptions on effectiveness of medicines were grouped into five categories; effective, some, limited or unclear effectiveness, no effect.Results 458 services responded; 277 UK, 85 rest of Europe, 95 rest of the world, 1 missing country. 358 services had managed patients with confirmed or suspected COVID-19. 289 services had protocols for symptom management in COVID-19. Services tended to prescribe medicines for symptom control comparable to medicines used in people without COVID-19; mainly opioids and benzodiazepines for breathlessness, benzodiazepines and antipsychotics for agitation, opioids and cough linctus for cough, paracetamol and non-steroidal anti-inflammatory drugs for fever, and opioids and paracetamol for pain. Medicines were considered to be mostly effective but varied by patient’s condition, route of administration and dose.Conclusions Services were largely consistent in prescribing for symptom management in people dying with COVID-19. Medicines used prior to COVID-19 were mostly considered effective in controlling common symptoms

Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPSs to interact with the host as well as those with potential probiotic properties

Estimating excess visual loss from neovascular age-related macular degeneration in the UK during the COVID-19 pandemic: a retrospective clinical audit and simulation model

OBJECTIVES: To report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at 1 year. DESIGN: Retrospective clinical audit and simulation model. SETTING: Multiple UK National Health Service (NHS) ophthalmology centres. PARTICIPANTS: Data on the reduction in new nAMD referrals were obtained from four NHS Trusts comparing April 2020 with April 2019. To estimate the potential impact on 1-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20 825 nAMD eyes from 27 NHS Trusts. MAIN OUTCOME MEASURES: Simulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at 1 year under four hypothetical scenarios: 0-month, 3-month, 6-month and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at 1 year nationally. RESULTS: The number of nAMD referrals dropped on average by 72% (range 65%-87%). Simulated 1-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2%-17.9%) to 23.3% (20.7%-25.9%), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1%-38.1%) to 26.4% (23.8%-29.2%). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level for 1 month nationally, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at 1 year. CONCLUSIONS: We report a large decrease in nAMD referrals during the COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at 1 year

What should we report? Lessons learnt from the development and implementation of serious adverse event reporting procedures in non-pharmacological trials in palliative care

Background/aims: Serious adverse event reporting guidelines have largely been developed for pharmaceutical trials. There is evidence that serious adverse events, such as psychological distress, can also occur in non-pharmaceutical trials. Managing serious adverse event reporting and monitoring in palliative care non-pharmaceutical trials can be particularly challenging. This is because patients living with advanced malignant or non-malignant disease have a high risk of hospitalisation and/or death as a result of progression of their disease rather than due to the trial intervention or procedures. This paper presents a number of recommendations for managing serious adverse event reporting that are drawn from two palliative care non-pharmacological trials. Methods: The recommendations were iteratively developed across a number of exemplar trials. This included examining national and international safety reporting guidance, reviewing serious adverse event reporting procedures from other pharmacological and non-pharmacological trials, a review of the literature and collaboration between the ACTION study team and Data Safety Monitoring Committee. These two groups included expertise in oncology, palliative care, statistics and medical ethics and this collaboration led to the development of serious adverse event reporting procedures. Results: The recommendations included; allowing adequate time at the study planning stage to develop serious adverse event reporting procedures, especially in multi-national studies or research naïve settings; reviewing the level of trial oversight required; defining what a serious adverse event is in your trial based on your study population; development and implementation of standard operating procedures and training; refining the reporting procedures during the trial if necessary and publishing serious adverse events in findings papers. Conclusions: There is a need for researchers to share their experiences of managing this challenging aspect of trial conduct. This will ensure that the processes for managing serious adverse event reporting are continually refined and improved so optimising patient safety. Trial registration: ACTION trial registration number: ISRCTN63110516 (date of registration 03/10/2014). Namaste trial registra

What should we report? Lessons learnt from the development and implementation of serious adverse event reporting procedures in non-pharmacological trials in palliative care

Background/aims: Serious adverse event reporting guidelines have largely been developed for pharmaceutical trials. There is evidence that serious adverse events, such as psychological distress, can also occur in non-pharmaceutical trials. Managing serious adverse event reporting and monitoring in palliative care non-pharmaceutical trials can be particularly challenging. This is because patients living with advanced malignant or non-malignant disease have a high risk of hospitalisation and/or death as a result of progression of their disease rather than due to the trial intervention or procedures. This paper presents a number of recommendations for managing serious adverse event reporting that are drawn from two palliative care non-pharmacological trials. Methods: The recommendations were iteratively developed across a number of exemplar trials. This included examining national and international safety reporting guidance, reviewing serious adverse event reporting procedures from other pharmacological and non-pharmacological trials, a review of the literature and collaboration between the ACTION study team and Data Safety Monitoring Committee. These two groups included expertise in oncology, palliative care, statistics and medical ethics and this collaboration led to the development of serious adverse event reporting procedures. Results: The recommendations included; allowing adequate time at the study planning stage to develop serious adverse event reporting procedures, especially in multi-national studies or research naïve settings; reviewing the level of trial oversight required; defining what a serious adverse event is in your trial based on your study population; development and implementation of standard operating procedures and training; refining the reporting procedures during the trial if necessary and publishing serious adverse events in findings papers. Conclusions: There is a need for researchers to share their experiences of managing this challenging aspect of trial conduct. This will ensure that the processes for managing serious adverse event reporting are continually refined and improved so optimising patient safety. Trial registration: ACTION trial registration number: ISRCTN63110516 (date of registration 03/10/2014). Namaste trial registration number: ISRCTN14948133 (date of registration 04/10/2017)

Eight Americas: Investigating Mortality Disparities across Races, Counties, and Race-Counties in the United States

BACKGROUND: The gap between the highest and lowest life expectancies for race-county combinations in the United States is over 35 y. We divided the race-county combinations of the US population into eight distinct groups, referred to as the “eight Americas,” to explore the causes of the disparities that can inform specific public health intervention policies and programs. METHODS AND FINDINGS: The eight Americas were defined based on race, location of the county of residence, population density, race-specific county-level per capita income, and cumulative homicide rate. Data sources for population and mortality figures were the Bureau of the Census and the National Center for Health Statistics. We estimated life expectancy, the risk of mortality from specific diseases, health insurance, and health-care utilization for the eight Americas. The life expectancy gap between the 3.4 million high-risk urban black males and the 5.6 million Asian females was 20.7 y in 2001. Within the sexes, the life expectancy gap between the best-off and the worst-off groups was 15.4 y for males (Asians versus high-risk urban blacks) and 12.8 y for females (Asians versus low-income southern rural blacks). Mortality disparities among the eight Americas were largest for young (15–44 y) and middle-aged (45–59 y) adults, especially for men. The disparities were caused primarily by a number of chronic diseases and injuries with well-established risk factors. Between 1982 and 2001, the ordering of life expectancy among the eight Americas and the absolute difference between the advantaged and disadvantaged groups remained largely unchanged. Self-reported health plan coverage was lowest for western Native Americans and low-income southern rural blacks. Crude self-reported health-care utilization, however, was slightly higher for the more disadvantaged populations. CONCLUSIONS: Disparities in mortality across the eight Americas, each consisting of millions or tens of millions of Americans, are enormous by all international standards. The observed disparities in life expectancy cannot be explained by race, income, or basic health-care access and utilization alone. Because policies aimed at reducing fundamental socioeconomic inequalities are currently practically absent in the US, health disparities will have to be at least partly addressed through public health strategies that reduce risk factors for chronic diseases and injuries

Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPSs to interact with the host as well as those with potential probiotic properties

Development of a candidate reference material for adventitious virus detection in vaccine and biologicals manufacturing by deep sequencing.

Unbiased deep sequencing offers the potential for improved adventitious virus screening in vaccines and biotherapeutics. Successful implementation of such assays will require appropriate control materials to confirm assay performance and sensitivity. A common reference material containing 25 target viruses was produced and 16 laboratories were invited to process it using their preferred adventitious virus detection assay. Fifteen laboratories returned results, obtained using a wide range of wet-lab and informatics methods. Six of 25 target viruses were detected by all laboratories, with the remaining viruses detected by 4-14 laboratories. Six non-target viruses were detected by three or more laboratories. The study demonstrated that a wide range of methods are currently used for adventitious virus detection screening in biological products by deep sequencing and that they can yield significantly different results. This underscores the need for common reference materials to ensure satisfactory assay performance and enable comparisons between laboratories

Genetic and Non-Genetic Influences during Pregnancy on Infant Global and Site Specific DNA Methylation: Role for Folate Gene Variants and Vitamin B12

Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA) and gene specific (IGF2, ZNT5, IGFBP3) DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT) involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032) and inversely with ZNT5 methylation (rho = −0.13, p = 0.017). Methylation of the IGFBP3 locus correlated inversely with infant vitamin B12 concentration (rho = −0.16, p = 0.007), whilst global DNA methylation correlated inversely with maternal vitamin B12 concentrations (rho = 0.18, p = 0.044). Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ2 = 8.82, p = 0.003) and maternal MTHFR 677C>T genotype with IGF2 methylation (χ2 = 2.77, p = 0.006). These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for DNA methylation. In addition, gestational length appears to be an important determinant of infant DNA methylation patterns