Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls.

BACKGROUND & AIMS: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA-treated external controls. METHODS: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. RESULTS: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10-0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12-0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03-1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09-1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21-0.85) including hepatic decompensation. CONCLUSIONS: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.

Reproducibility of 19 F-MR ventilation imaging in healthy volunteers.

PURPOSE: To assess the reproducibility of percentage ventilated lung volume (%VV) measurements in healthy volunteers acquired by fluorine (19 F)-MRI of inhaled perfluoropropane, implemented at two research sites. METHODS: In this prospective, ethically approved study, 40 healthy participants were recruited (May 2018-June 2019) to one of two research sites. Participants underwent a single MRI scan session on a 3T scanner, involving periodic inhalation of a 79% perfluoropropane/21% oxygen gas mixture. Each gas inhalation session lasted about 30 seconds, consisting of three deep breaths of gas followed by a breath-hold. Four 19 F-MR ventilation images were acquired per participant, each separated by approximately 6 minutes. The value of %VV was determined by registering separately acquired 1 H images to ventilation images before semi-automated image segmentation, performed independently by two observers. Reproducibility of %VV measurements was assessed by components of variance, intraclass correlation coefficients, coefficients of variation (CoV), and the Dice similarity coefficient. RESULTS: The MRI scans were well tolerated throughout, with no adverse events. There was a high degree of consistency in %VV measurements for each participant (CoVobserver1 = 0.43%; CoVobserver2 = 0.63%), with overall precision of %VV measurements determined to be within ± 1.7% (95% confidence interval). Interobserver agreement in %VV measurements revealed a high mean Dice similarity coefficient (SD) of 0.97 (0.02), with only minor discrepancies between observers. CONCLUSION: We demonstrate good reproducibility of %VV measurements in a group of healthy participants using 19 F-MRI of inhaled perfluoropropane. Our methods have been successfully implemented across two different study sites, supporting the feasibility of performing larger multicenter clinical studies.

CDC's Community-Based Organization Behavioral Outcomes Project: Perspectives for Researchers, Implementers and Funders.

Behavioral interventions have been a crucial tool for the prevention of HIV transmission since early in the epidemic. The Centers for Disease Control and Prevention (CDC) has provided funding for evidence-based behavioral interventions (EBIs) at health departments and community-based organizations (CBOs) since 2004. From 2006 to 2015, CDC funded 25 CBOs to evaluate one or more of seven EBIs designed to prevent HIV through the Community-based Organization Behavioral Outcomes Project (CBOP) as implemented outside of a research setting. For each EBI, CBOP showed that most HIV risk behaviors improved after the intervention, and improvements were similar to those observed in research studies. Our findings show that behavioral interventions can be successfully implemented in real-world settings. Although the focus of HIV prevention has largely shifted toward biomedical interventions in recent years, successful implementation often depends on behavioral components. Lessons from CBOP can inform future efforts to develop and implement behavioral interventions for HIV and other areas of public health.

Pruritus Is Common and Undertreated in Patients With Primary Biliary Cholangitis in the United Kingdom.

BACKGROUND AND AIMS: Little is known about the prevalence or treatment of pruritus associated with primary biliary cholangitis (PBC). We analyzed data from patients with PBC recruited from all clinical centers in the United Kingdom (UK) to characterize the prevalence, severity, progression, and treatment of pruritus. METHODS: We performed cross-sectional and longitudinal studies of patients in the UK-PBC cohort to assess trajectories of pruritus. Data on pruritus frequency, severity, and therapy were collected via paper questionnaires completed by 2194 patients at their initial assessment in 2011 and then again in 2014 and 2017. Self-reported treatment data were validated against the prescription record of PBC cohort in the Clinical Practice Research Datalink, a primary care database. We defined persistent pruritus as itch that occurs frequently or all the time and severe pruritus as PBC-40 pruritus domain scores of 12 or more, throughout their disease course. Latent class mixed models were used to study pruritus trajectories and identify factors associated with high pruritus. RESULTS: At initial assessment, 1613 (73.5%) patients had experienced pruritus at some point since their development of PBC-persistent pruritus was reported by 34.5% of the patients and severe pruritus by 11.7%. Only 37.4% of patients with persistent pruritus and 50% with severe pruritus reported ever receiving cholestyramine. Frequencies of rifampicin use were 11% in patients with persistent pruritus and 23% in patients with severe pruritus. Comparison of 2011 and 2014 surveys (comprising 1423 patients) showed consistent self-reported data on pruritus. Proportions of patients in the UK-PBC cohort treated with cholestyramine or naltrexone (37.4% and 4.4%) did not differ significantly from proportions treated in the Clinical Practice Research Datalink cohort (30.4% and 4.4%) (P = .07 for cholestyramine and P = .32 for naltrexone). Latent class mixed models (n = 1753) identified 3 different groups of pruritus. Multivariable analysis identified younger age at diagnosis and higher level of alkaline phosphatase at 12 months after diagnosis as factors significantly associated with persistent high pruritus. CONCLUSIONS: In a large national cohort study of patients with PBC, we found a high prevalence of pruritus and inadequate guideline-recommended therapy. Patient-reported data used to determine pruritus prevalence and treatment are reliable. Younger age and levels of higher alkaline phosphatase were associated with persistent pruritus. We need to increase awareness and management of pruritus in PBC in the UK.

The Impact of Autoimmune Hepatitis and Its Treatment on Health Utility.

Patient reporting suggests that the physical and psychological effects of autoimmune hepatitis (AIH) can be substantial. However, health-related quality of life (HRQOL) in patients with AIH remains incompletely characterized, and health utility remains to be explored. Treatment for AIH often includes the use of corticosteroids, which are agents that can be associated with significant adverse effects. Here we explore the impact of AIH and its treatments on patient-reported HRQOL and health utility in a large cohort of prevalent cases from the United Kingdom Autoimmune Hepatitis (UK-AIH) national study. Data were collected from 990 adult participants with a clinical diagnosis of AIH using validated HRQOL tools including the European Quality-of-Life 5-Dimension 5-Level (EQ-5D-5L) and clinical data forms. The EQ-5D-5L dimension scores were compared with UK population norms and with a disease control cohort with primary biliary cholangitis (PBC). Within the AIH cohort, regression analysis was used to explore associations between HRQOL and demographic and clinical variables with a particular focus on the impact of AIH therapies including corticosteroid use. HRQOL, measured by the EQ-5D-5L utility index, is shown to be significantly impaired in our cohort of AIH patients compared with population norms. Within the AIH cohort, corticosteroid use was found to be significantly associated with impaired HRQOL, even when controlling for biochemical disease activity status. CONCLUSION: Our data show evidence of HRQOL impairment in a large cohort of AIH patients compared with the general population. Furthermore, corticosteroid use is strongly associated with decreased HRQOL, independent of remission status. This highlights the need for better corticosteroid-free therapy approaches and it emphasizes the need for future novel therapeutic trials in AIH. (Hepatology 2018; 00:000-000).

A case-control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE).

Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p-value = 6.24 × 10-8 ), rs74477937 (p-value = 8.56 × 10-8 ) and rs78707086 (p-value = 8.55 × 10-8 ) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta-analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.

Improving Linkage, Retention, and Reengagement in HIV Care in 12 Metropolitan Areas.

The Centers for Disease Control and Prevention developed the Enhanced Comprehensive HIV Prevention Planning (ECHPP) project to support 12 health departments' improvement of their HIV prevention and care portfolios in response to new national guidelines. We systematically analyzed 3 years of progress reports to learn how grantees put into practice local intervention strategies intended to link people to, and keep them in, HIV care. All grantees initiated seven activities to support these strategies: (1) improve surveillance data systems, (2) revise staffing duties and infrastructures, (3) update policies and procedures, (4) establish or strengthen partnerships, (5) identify persons not in care, (6) train personnel, and (7) create ways to overcome obstacles to receiving care. Factors supporting ECHPP grantee successes were thorough planning, attention to detail, and strong collaboration among health department units, and between the health department and external stakeholders. Other jurisdictions may consider adopting similar strategies when planning and enhancing HIV linkage, retention, and reengagement efforts in their areas. ECHPP experiences, lessons learned, and best practices may be relevant when applying new public health policies that affect community and health care practices jurisdiction-wide.

The Changing Landscape of HIV Prevention in the United States: Health Department Experiences and Local Adaptations in Response to the National HIV/AIDS Strategy and High-Impact Prevention Approach.

OBJECTIVE: HIV prevention has changed substantially in recent years due to changes in national priorities, biomedical advances, and health care reform. Starting in 2010, motivated by the National HIV/AIDS Strategy (NHAS) and the Centers for Disease Control and Prevention's (CDC's) High-Impact Prevention (HIP), health departments realigned resources so that cost-effective, evidence-based interventions were targeted to groups at risk in areas most affected by HIV. This analysis describes how health departments in diverse settings were affected by NHAS and HIP. METHODS: We conducted interviews and a consultation with health departments from 16 jurisdictions and interviewed CDC project officers who monitored programs in 5 of the jurisdictions. Participants were asked to describe changes since NHAS and HIP and how they adapted. We used inductive qualitative analysis to identify themes of change. RESULTS: Health departments improved their HIV prevention practices in different ways. They aligned jurisdictional plans with NHAS and HIP goals, increased local data use to monitor program performance, streamlined services, and strengthened partnerships to increase service delivery to persons at highest risk for infection/transmission. They shifted efforts to focus more on the needs of people with diagnosed HIV infection, increased HIV testing and routine HIV screening in clinical settings, raised provider and community awareness about preexposure prophylaxis, and used nontraditional strategies to successfully engage out-of-care people with diagnosed HIV infection. However, staff-, provider-, and data-related barriers that could slow scale-up of priority programs were consistently reported by participants, potentially impeding the ability to meet national goals. CONCLUSION: Findings suggest progress toward NHAS and HIP goals has been made in some jurisdictions but highlight the need to monitor prevention programs in different contexts to identify areas for improvement and increase the likelihood of national success. Health departments and federal funders alike can benefit from the routine sharing of successes and challenges associated with local policy implementation, considering effects on the overall portfolio of programs.

Network analysis among HIV-infected young black men who have sex with men demonstrates high connectedness around few venues.

BACKGROUND: Network analysis is useful for understanding sexual transmission of HIV and other sexually transmitted infections. We conducted egocentric and affiliation network analysis among HIV-infected young black men who have sex with men (MSM) in the Jackson, Mississippi, area to understand networks and connectedness of this population. METHODS: We interviewed 22 black MSM aged 17 to 25 years diagnosed as having HIV in 2006 to 2008. Participants provided demographic and geographic information about each sex partner during the 12 months before diagnosis and identified venues where they met these partners. We created affiliation network diagrams to understand connectedness of this population and identify venues that linked participants. RESULTS: The median number of partners reported was 4 (range, 1-16); a total of 97 partners (88 of whom were male) were reported. All but 1 participant were connected through a network of venues where they had met partners during the 12 months before diagnosis. Three venues were named as places for meeting partners by 13 of 22 participants. Participants reported having partners from all regions of Mississippi and 5 other states. CONCLUSIONS: HIV-infected young black MSM in this analysis were linked by a small number of venues. These venues should be targeted for testing and prevention interventions. The pattern of meeting sex partners in a small number of venues suggests densely connected networks that propagate infection. This pattern, in combination with sexual partnerships with persons from outside Jackson, may contribute to spread of HIV and other sexually transmitted infections into or out the Jackson area.

Using the AR-V7 biomarker to determine treatment in metastatic castrate resistant prostate cancer, a feasibility randomised control trial, conclusions from the VARIANT trial [version 2; peer review: 2 approved].

Background: Prostate cancer is the most commonly diagnosed malignancy in the UK. Castrate resistant prostate cancer (CRPC) can be difficult to manage with response to next generation hormonal treatment variable. AR-V7 is a protein biomarker that can be used to predict response to treatment and potentially better inform management in these patients. Our aim was to establish the feasibility of conducting a definitive randomised controlled trial comparing the clinical utility of AR-V7 biomarker assay in personalising treatments for patients with metastatic CRPC within the United Kingdom (UK) National Health Service (NHS).  Due to a number of issues the trial was not completed successfully, we aim to discuss and share lessons learned herein. Methods: We conducted a randomised, open, feasibility trial, which aimed to recruit 70 adult men with metastatic CRPC within three secondary care NHS trusts in the UK to be run over an 18-month period. Participants were randomised to personalised treatment based on AR-V7 status (intervention) or standard care (control). The primary outcome was feasibility, which included: recruitment rate, retention and compliance. Additionally, a baseline prevalence of AR-V7 expression was to be estimated. Results: Fourteen participants were screened and 12 randomised with six into each arm over a nine-month period. Reliability issues with the AR-V7 assay meant prevalence was not estimated. Due to limited recruitment the study did not complete to target. Conclusions: Whilst the trial did not complete to target, we have ascertained that men with advanced cancer are willing to take part in trials utilising biomarker guided treatment. A number of issues were identified that serve as important learning points in future clinical trials.

'Persistent throat symptoms' versus 'laryngopharyngeal reflux': a cross-sectional study refining the clinical condition.

OBJECTIVE: Many patients are assessed for chronic symptoms including: dysphonia, 'globus', throat clearing, postnasal secretions and cough; commonly grouped together and attributed to 'laryngopharyngeal reflux'. This study aimed to explore a clinical trial's baseline dataset for patterns of presenting symptoms, which might provide a more rational basis for treatment. DESIGN: Baseline data were analysed for participants entering the Trial Of Proton-Pump Inhibitors in Throat Symptoms: age, body mass index, Reflux Symptom Index, Comprehensive Reflux Symptom Score, Laryngopharyngeal Reflux-Health-related Quality of Life questionnaire and Reflux Finding Score (RFS-endoscopic examination). The relationships between the questionnaires and demographic factors were assessed. Exploratory factor analysis (EFA) was conducted on individual symptom items in the combined questionnaires. The EFA factors were applied to a Cluster Analysis of participants, to explore the presence of identifiable patient. RESULTS: Throat clearing and globus were the highest ranked scores in the 344 participants. Increasing age was inversely associated with symptom severity (p<0.01). There was no relationship between the RFS and any of the three questionnaires. EFA resulted in a seven-factor model with clinically meaningful labels: voice, cough, gastrointestinal symptoms, airway symptoms and dysphagia, throat clearing, lump in throat, and life events. Cluster analysis failed to demonstrate any clinically meaningful clusters of patients. CONCLUSION: This study offers a framework for future research and demonstrates that individual symptoms cannot be used to group patients. The analysis supports the use of a broad 'umbrella' term such as persistent throat symptoms. TRIAL REGISTRATION NUMBER: ISRCTN38578686.

Student and School Characteristics Associated With COVID-19-Related Learning Decline Among Middle and High School Students in K-12 Schools.

BACKGROUND: COVID-19-disrupted schools, including shifts to virtual learning which may have impacted academic progress. This study assessed characteristics associated with changes in academic grades (before and during the pandemic) for different learning modalities for US students ages 13-19. METHODS: Students (N = 2152) completed a web survey on school-related experiences during the 2020-2021 school year. County social vulnerability and SARS-CoV-2 transmission data were merged with survey data. Multivariable logistic regression analysis for grade change was conducted with student and school characteristics for each learning modality, controlling for community characteristics. RESULTS: Greater proportions of remote/virtual (34.4%) and hybrid (30.1%) learning students reported grade decline compared to in-person students (19.9%). Among in-person students, odds of reporting same/improved grades were 65% lower among non-Hispanic black students and 66% lower among non-Hispanic students from other races, compared to non-Hispanic white students. Among hybrid students, odds of reporting same/improved grades for students reporting anxiety were 47% lower than students without anxiety, and odds of reporting same/improved grades among students reporting substance use were 40% lower than students not reporting substance use. Among remote/virtual students, odds of reporting same/improved grades among students with depression were 62% lower than odds of students not reporting depression symptoms. Remote/virtual students who received school-provided educational services also had 1.55 times the odds of reporting same/improved grades, compared to remote/virtual students not receiving these services. CONCLUSIONS: Academic grades were negatively impacted during COVID-19 and learning mode may have contributed. Understanding these impacts is critical to student health and academic achievement.

Conceptual Framework for Understanding Incident Management Systems During Public Health Emergencies.

OBJECTIVE: Effective incident management is essential for coordinating efforts of multiple disciplines and stakeholders when responding to emergencies, including public health disasters such as the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: Existing research frameworks tend to focus on formal structures and doctrine (eg, ICS-NIMS); however, organizational processes that underlie incident management have not been systematically assessed and synthesized into a coherent conceptual framework. RESULTS: The lack of a framework has hindered the development of measures of performance that could be used to further develop the evidence base and facilitate process improvement. To address this gap, we present a conceptual framework of incident management drawn from expert feedback and a review of literature on incident management and related fields. The framework features 23 measurement constructs grouped into 5 domains: (1) situational awareness and information sharing, (2) incident action and implementation planning, (3) resource management and mobilization, (4) coordination and collaboration, and (5) feedback and continuous quality improvement. CONCLUSIONS: As such, the article provides a first step toward the development of robust measures for assessing the performance and effectiveness of incident management systems.

Multidrug-resistant Uro-associated Escherichia coli Populations and Recurrent Urinary Tract Infections in Patients Performing Clean Intermittent Self-catheterisation.

BACKGROUND: The AnTIC trial linked continuous low-dose antibiotic prophylaxis treatments to a lower incidence of symptomatic urinary tract infections (UTIs) among individuals performing clean intermittent self-catheterisation (CISC). OBJECTIVE: To explore potential mechanisms underlying the protective effects of low-dose antibiotic prophylaxis treatments, blood and urine samples and uro-associated Escherichia coli isolates from AnTIC participants were analysed. DESIGN SETTING AND PARTICIPANTS: Blood samples (n = 204) were analysed for TLR gene polymorphisms associated with UTI susceptibility and multiple urine samples (n = 558) were analysed for host urogenital responses. E.coli sequence data for 45 temporal isolates recovered from the urine samples of 16 trial participants in the prophylaxis (n = 9) and no-prophylaxis (n = 7) study arms, and characterised by multidrug resistance (MDR), were used to classify individual strains. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: TLR polymorphism data were analysed using Poisson regression. Concentrations of urine host defence markers were analysed using linear mixed-effects models, which accounted for repeated urine samples. RESULTS AND LIMITATIONS: Urine samples from CISC users, irrespective of antibiotic treatment regimens, were associated with robust urothelial innate responses. No links were identified between TLR genotype and CISC user susceptibility to recurrent UTIs. Microbiological study data were limited to the predominant MDR E. coli population; participants prescribed low-dose prophylactic antibiotics were predominantly colonised by a single uro-associated E. coli strain, while participants given acute antibiotic treatments were each colonised by more than one E. coli strain. CONCLUSIONS: Antibiotic treatments did not impact urogenital responses to infection in CISC users. Host genetics in terms of TLR polymorphisms played no role in determining CISC user susceptibility to or protection from recurrent UTIs. Prophylactic antibiotic treatments associated with MDR E. coli were associated with colonisation by stable uro-associated E. coli genotypes. PATIENT SUMMARY: Our findings show that the natural urogenital defences of clean intermittent self-catheterisation (CISC) users were not impacted by antibiotic treatments. For some CISC users, prophylaxis with low-dose antibiotics selected for a stable, predominantly, Esherichia coli rich uromicrobiota.

Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT.

BACKGROUND: Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care. DESIGN: Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded. SETTING: Nine NHS head and neck cancer sites in England and Wales. PARTICIPANTS: A total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy. INTERVENTION: Random allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm2, irradiance 50 mW/cm2, exposure time 60 seconds and fluence 3 J/cm2. There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner. MAIN OUTCOME MEASURE: The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome. RESULTS: A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n = 44; sham arm, n = 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm. LIMITATIONS: The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth. CONCLUSIONS: This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services. FUTURE WORK: Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research. TRIAL REGISTRATION: This trial is registered as ISRCTN14224600. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.

Around 9 out of 10 head and neck cancer patients undergoing treatment experience pain, swelling and sores in their mouth (oral mucositis). This can lead to weight loss, painful ulcers, difficulty talking, eating and drinking, and even hospitalisation. Current care includes helping patients to keep their mouth and teeth clean, encouraging them to have a healthy diet and prescribing mouthwashes, painkillers and mouth-coating gels. However, these treatments give limited help in preventing or treating this condition. The LiTEFORM trial looked at whether or not low-level laser therapy could be used to prevent and treat oral mucositis. Patients were allocated to one of two arms at random: active laser or fake (sham) laser. Neither the patients nor the hospital staff knew which laser was being used. Eighty-seven people joined the study during the time allowed (44 received low-level laser therapy and 43 received sham treatment); however, this was a smaller number than the planned target of 380 people. As a result, no meaningful conclusion can be drawn from the results about whether the therapy is beneficial or cost-effective. People receiving the low-level laser therapy reported slightly more soreness in their mouth than those receiving the sham laser, but this could be down to chance. The number of participants is too small to draw conclusions about whether or not the low-level laser is helpful. Some patients found the laser treatment sessions to be difficult. Setting up a new service delivering laser therapy at the same time as cancer treatments was more complicated than originally anticipated. Problems included the scheduling of appointments, finding suitable rooms and having enough trained staff with time to deliver laser therapy. However, this study has provided us with knowledge on how best to set up a laser therapy service in the NHS as part of the cancer treatment pathway and the costs involved. These findings could help future studies looking into low-level laser therapy for those with head and neck cancer.

Evaluation of an HIV prevention intervention for African Americans and Hispanics: findings from the VOICES/VOCES Community-based Organization Behavioral Outcomes Project.

There is limited knowledge about whether the delivery of evidence-based, HIV prevention interventions in 'real world' settings will produce outcomes similar to efficacy trial outcomes. In this study, we describe longitudinal changes in sexual risk outcomes among African American and Hispanic participants in the Video Opportunities for Innovative Condom Education and Safer Sex (VOICES/VOCES) program at four CDC-funded agencies. VOICES/VOCES was delivered to 922 high-risk individuals in a variety of community settings such as substance abuse treatment centers, housing complex centers, private residences, shelters, clinics, and colleges. Significant risk reductions were consistently observed at 30- and 120-days post-intervention for all outcome measures (e.g., unprotected sex, self-reported STD infection). Risk reductions were strongest for African American participants, although Hispanic participants also reported reducing their risky behaviors. These results suggest that, over a decade after the first diffusion of VOICES/VOCES across the U.S. by CDC, this intervention remains an effective tool for reducing HIV risk behaviors among high-risk African American and Hispanic individuals.

Taxonomy for strengthening the identification of core elements for evidence-based behavioral interventions for HIV/AIDS prevention.

The concept of core elements was developed to denote characteristics of an intervention, such as activities or delivery methods, presumed to be responsible for the efficacy of evidence-based behavioral interventions (EBIs) for HIV/AIDS prevention. This paper describes the development of a taxonomy of core elements based on a literature review of theoretical approaches and characteristics of EBIs. Sixty-one categories of core elements were identified from the literature and grouped into three distinct domains: implementation, content and pedagogy. The taxonomy was tested by categorizing core elements from 20 HIV prevention EBIs disseminated by Centers for Disease Control and Prevention. Results indicated that core elements represented all three domains but several were difficult to operationalize due to vague language or the inclusion of numerous activities or constructs. A process is proposed to describe core elements in a method that overcomes some of these challenges. The taxonomy of core elements can be used to identify core elements of EBIs, strengthen the translation of EBIs from research to practice and guide future research seeking to identify essential core elements in prevention interventions.

Motivators of Continued Participation in Public Health Emergency Response Among Federal Public Health Workers: A Qualitative Study.

The purpose of this study was to identify factors that motivate public health workers to deploy to the field during an emergency event. We conducted 25 semistructured interviews with employees at the US Centers for Disease Control and Prevention, all of whom had deployed to the field for the 2014-2016 Ebola, 2016-2017 Zika, and 2017 hurricane responses. We used a grounded theory approach in our analysis of the data. Themes that emerged from the interviews related to responder autonomy, competence, and relatedness, which are consistent with self-determination theory. Motivating factors included having clarity about the response role, desire to be challenged, ability to apply existing skills in the field (or apply new skills learned during deployment to their home office), desire to be helpful, and feeling rewarded by working with affected populations, communities, and other response staff. These preliminary findings suggest that introjected and identified motivating factors may form the foundation of willingness among public health workers to assist during an emergency event. Understanding what motivates staff at public health agencies to participate in emergency deployment can inform the development of recruitment strategies, strengthen effectiveness of response activities, and improve overall agency preparedness.

Online resources for persons recently diagnosed with HIV/AIDS: an analysis of HIV-related webpages.

The Internet is a major source of HIV-related information and resources for persons recently diagnosed with HIV/AIDS (PRDHA). This study examined the types of HIV-related websites that appear as a result of HIV-related keyword searches and the extent to which website information targets PRDHA. The first page of HIV-related webpages from 18 keyword searches was coded. Among 137 webpages meeting inclusion criteria, 63% represented HIV-informational websites, 31% targeted HIV-positive individuals, and over half contained or provided access to HIV prevention, treatment, and transmission information. Thirty-three percent of webpages contained or provided access to PRDHA-targeted information, with a greater percentage of those webpages having mobile, non-English, and "Ask the Expert" features compared with non-PRDHA targeted webpages. Implications for PRDHA include the following: (1) they should explore HIV-related websites to gain insight into the credibility of the information contained on those sites; (2) PRDHA must be aware that HIV-related websites have the potential to elicit dated, emotionally distressing, or irrelevant information; and (3) to obtain information that relates to their demographic and situational profile, they may wish to use specific key terms (e.g., "HIV women") rather than attempting to navigate webpages that arise from general search terms (e.g., "HIV"). Recommendations for future development of online resources for PRDHA include providing HIV-relevant information in a stepwise fashion, providing demographically targeted HIV information, and greater utilization of mobile technology.

Applying the Ready, Willing, and Able Framework to Assess Agency Public Health Emergency Preparedness: The CDC Perspective.

Public health emergencies in the United States have been complex, frequent, and increasingly costly in the past decade, at times overwhelming government agencies that are primarily resourced for routine, nonemergency health functions. Emergencies are not always predictable, and adequate resources are not always available to prepare staff in advance for emergency response roles and to mobilize them quickly when a new threat emerges. Additionally, real-world data that connect preparedness levels to response outcomes may be difficult to obtain, further limiting continuous quality improvement efforts by public health officials. In this article, we apply the Ready, Willing, and Able (RWA) framework to identify areas for improvement related to organizational and staff readiness, willingness, and ability to respond during a public health emergency. We share emergency response deployment, training, and personnel data collected as part of emergency response activations (2008 to 2018) at the Centers for Disease Control and Prevention to illustrate how the framework may be applied at government agencies to improve response processes and effectiveness. Additionally, we propose potential metrics aligned with the framework constructs that may help emergency managers consistently assess agency preparedness and, over time, be incorporated into broader standardized measurement methods. We conclude that the RWA framework is a practical tool that can complement other preparedness approaches currently in use at government public health agencies.