The Future of Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: A Global Qualitative Consultation on Provider Perspectives on New Products and Differentiated Service Delivery.

Differentiated service delivery and new products, such as long-acting injectable cabotegravir (CAB-LA) and the dapivirine vaginal ring (DVR), could increase uptake and use of pre-exposure prophylaxis (PrEP) for HIV prevention. We explored PrEP provider perspectives on differentiated PrEP service delivery and new PrEP products to inform World Health Organization (WHO) guidelines and programme implementation. 150 PrEP providers who participated in a WHO survey were randomly selected and 67 were invited for interviews based on geographic representation, provider cadre, gender, experience with community-based PrEP service delivery, and familiarity with new PrEP products. Semi-structured interviews were conducted virtually. Key themes were inductively extracted relating to differentiated service delivery and benefits and concerns regarding new PrEP products. 30 PrEP providers from 24 countries were interviewed. Across regions, providers were supportive of differentiated service delivery to respond to clients' needs and preferences, maintain services during COVID-19, and ensure access for priority populations that may face access challenges. Providers welcomed prospects of offering CAB-LA to their clients but had concerns about HIV testing, costs, and the need for clinic-based services, including staff who can administer injections. Providers felt the DVR was potentially important for some cisgender women, especially young clients and female sex workers, and raised fewer concerns compared to injectable PrEP. Providers' views are critical for the development of guidelines and implementing programmes that will best serve PrEP users. Understanding areas where provider capacities and biases may create barriers can define opportunities for training and support to ensure that providers can deliver effective programmes.

Variation in human water turnover associated with environmental and lifestyle factors.

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking (2H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.

The cardio-respiratory effects of passive heating and the human thermoneutral zone.

The thermoneutral zone (TNZ) defines the range of ambient temperatures at which resting metabolic rate (MR) is at a minimum. While the TNZ lower limit has been characterized, it is still unclear whether there is an upper limit, that is, beyond which MR during rest increases, and if so, what physiological upregulations explain this. We take the first step to fill this knowledge gap by measuring MR and multiple physiological variables in participants exposed to ambient heat stress while resting. Thirteen participants were exposed for an hour to 28℃-50% relative humidity (RH) air, and both 40 and 50℃ each in 25% RH and humid (50% RH) conditions. Core and skin temperatures, blood pressure, sweat-, heart-, and breathing-rate, minute ventilation, and movement levels were recorded throughout each condition. MR increased 35% (p = .015) during exposure to 40℃-25% RH compared to baseline and a further 13% (p = .000) at in 50℃-50%RH. This was not explained by increased fidgeting (p = .26), suggesting physiological upregulation. However, while greater heat stress invoked increases in heart rate (64%, p = .000), minute ventilation (78%, p = .000), and sweat rate (74%. p = .000) when comparing 50℃-50% RH with baseline, the exact size of their relative energy cost is unclear and, therefore, so is their contribution to this increase in MR. Our study shows clear evidence that resting MR increases in humans at high temperature-there is a metabolic upper critical temperature, at least as low as 40℃. Further studies should pinpoint this value and fully explain this increased MR.

The Subjective Experience of Inner Speech in Aphasia Is a Meaningful Reflection of Lexical Retrieval.

Purpose Individuals with aphasia often report that they feel able to say words in their heads, regardless of speech output ability. Here, we examine whether these subjective reports of successful "inner speech" (IS) are meaningful and test the hypothesis that they reflect lexical retrieval. Method Participants were 53 individuals with chronic aphasia. During silent picture naming, participants reported whether or not they could say the name of each item inside their heads. Using the same items, they also completed 3 picture-based tasks that required phonological retrieval and 3 matched auditory tasks that did not. We compared participants' performance on these tasks for items they reported being able to say internally versus those they reported being unable to say internally. Then, we examined the relationship of psycholinguistic word features to self-reported IS and spoken naming accuracy. Results Twenty-six participants reported successful IS on nearly all items, so they could not be included in the item-level analyses. These individuals performed correspondingly better than the remaining participants on tasks requiring phonological retrieval, but not on most other language measures. In the remaining group ( n = 27), IS reports related item-wise to performance on tasks requiring phonological retrieval, but not to matched control tasks. Additionally, IS reports were related to 3 word characteristics associated with lexical retrieval, but not to articulatory complexity; spoken naming accuracy related to all 4 word characteristics. Six participants demonstrated evidence of unreliable IS reporting; compared with the group, they also detected fewer errors in their spoken responses and showed more severe language impairments overall. Conclusions Self-reported IS is meaningful in many individuals with aphasia and reflects lexical phonological retrieval. These findings have potential implications for treatment planning in aphasia and for our understanding of IS in the general population.

Self-reported inner speech relates to phonological retrieval ability in people with aphasia.

Many individuals with aphasia report the ability to say words in their heads despite spoken naming difficulty. Here, we examined individual differences in the experience of inner speech (IS) in participants with aphasia to test the hypotheses that self-reported IS reflects intact phonological retrieval and that articulatory output processing is not essential to IS. Participants (N = 53) reported their ability to name items correctly internally during a silent picture-naming task. We compared this measure of self-reported IS to spoken picture naming and a battery of tasks measuring the underlying processes required for naming (i.e., phonological retrieval and output processing). Results from three separate analyses of these measures indicate that self-reported IS relates to phonological retrieval and that speech output processes are not a necessary component of IS. We suggest that self-reported IS may be a clinically valuable measure that could assist in clinical decision-making regarding anomia diagnosis and treatment.

The BBaRTS Healthy Teeth Behaviour Change Programme for preventing dental caries in primary school children: study protocol for a cluster randomised controlled trial.

BACKGROUND: Oral health behaviours such as establishing twice-daily toothbrushing and sugar control intake need parental self-efficacy (PSE) to prevent the development of childhood dental caries. A previous study has shown that behaviour change techniques (BCTs) delivered via a storybook can improve parental self-efficacy to undertake twice-daily toothbrushing. OBJECTIVE: to determine whether an intervention (BBaRTS, Bedtime Brush and Read Together to Sleep), designed to increase PSE; delivered through storybooks with embedded BCTs, parenting skills and oral health messages, can improve child oral health compared to (1) an exactly similar intervention containing no behaviour change techniques, and (2) the BBaRTS intervention supplemented with home supply of fluoride toothpaste and supervised toothbrushing on schooldays. METHODS/DESIGN: A 2-year, three-arm, multicentre, cluster randomised controlled trial. PARTICIPANTS: children (estimated 2000-2600) aged 5-7 years and their families from 60 UK primary schools. INTERVENTION: Test group 1: a series of eight children's storybooks developed by a psychologist, public health dentist, science educator, children's author and illustrators, with guidance from the Department for Education (England). The books feature animal characters and contain embedded dental health messages, parenting skills and BCTs to promote good oral health routines focused on controlling sugar intake and toothbrushing, as well as reading at bedtime. Books are given out over 2 years. Test group 2: as Test group 1 plus home supplies of fluoride toothpaste (1000 ppmF), and daily supervised toothbrushing in school on schooldays. Active Control group: series of eight books with exactly the same stories, characters and illustrations, but without BCTs, dental health messages or parenting skills. Annual child dental examinations and parental questionnaires will be undertaken. A sub-set of participants will be invited to join an embedded study of the child's diet and salivary microbiota composition. PRIMARY OUTCOME MEASURE: dental caries experience in permanent teeth at age 7-8 years. DISCUSSION: A multi-disciplinary team was established to develop the BBaRTS Children's Healthy Teeth Programme. The books were developed in partnership with the Department for Education (England), informed by a series of focus groups with children, teachers and parents. TRIAL REGISTRATION: ISRCTN21461006 (date of registration 23 September 2015).

A new primary dental care service compared with standard care for child and family to reduce the re-occurrence of childhood dental caries (Dental RECUR): study protocol for a randomised controlled trial.

BACKGROUND: In England and Scotland, dental extraction is the single highest cause of planned admission to the hospital for children under 11 years. Traditional dental services have had limited success in reducing this disease burden. Interventions based on motivational interviewing have been shown to impact positively dental health behaviours and could facilitate the prevention of re-occurrence of dental caries in this high-risk population. The objective of the study is to evaluate whether a new, dental nurse-led service, delivered using a brief negotiated interview based on motivational interviewing, is a more cost-effective service than treatment as usual, in reducing the re-occurrence of dental decay in young children with previous dental extractions. METHODS/DESIGN: This 2-year, two-arm, multicentre, randomised controlled trial will include 224 child participants, initially aged 5 to 7 years, who are scheduled to have one or more primary teeth extracted for dental caries under general anaesthesia (GA), relative analgesia (RA: inhalation sedation) or local anaesthesia (LA). The trial will be conducted in University Dental Hospitals, Secondary Care Centres or other providers of dental extraction services across the United Kingdom. The intervention will include a brief negotiated interview (based on the principles of motivational interviewing) delivered between enrollment and 6 weeks post-extraction, followed by directed prevention in primary dental care. Participants will be followed up for 2 years. The main outcome measure will be the dental caries experienced by 2 years post-enrollment at the level of dentine involvement on any tooth in either dentition, which had been caries-free at the baseline assessment. DISCUSSION: The participants are a hard-to-reach group in which secondary prevention is a challenge. Lack of engagement with dental care makes the children and their families scheduled for extraction particularly difficult to recruit to an RCT. Variations in service delivery between sites have also added to the challenges in implementing the Dental RECUR protocol during the recruitment phase. TRIAL REGISTRATION: ISRCTN24958829 (date of registration: 27 September 2013), Current protocol version: 5.0.

Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to intermarriage. The parent-child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies.

Assessing Smart Phones for Generating Life-space Indicators.

Life-space is a promising method for estimating older adults' functional status. However, traditional life-space measures are costly and time consuming because they often rely on active subject participation. This study assesses the feasibility of using the global positioning system (GPS) function of smart phones to generate life-space indicators. We first evaluated the location accuracy of smart phone collected GPS points versus those acquired by a commercial GPS unit. We then assessed the specificity of the smart phone processed life-space information against the traditional diary method. Our results suggested comparable location accuracy between the smart phone and the standard GPS unit in most outdoor situations. In addition, the smart phone method revealed more comprehensive life-space information than the diary method, which leads to higher and more consistent life-space scores. We conclude that the smart phone method is more reliable than traditional methods for measuring life-space. Further improvements will be required to develop a robust application of this method that is suitable for health-related practices.

Next generation genome-wide association tool: design and coverage of a high-throughput European-optimized SNP array.

The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies.

Management of postoperative pain in children following extractions of primary teeth under general anaesthesia: a comparison of paracetamol, Voltarol and no analgesia.

OBJECTIVE: The aim of this study was to compare three different pain relief regimes and the respective levels of pain recorded by children undergoing extractions of primary teeth under general anaesthesia. METHODS: This was a tri-sited study carried out in three similar hospital settings, each with a different pain relief protocol. The subjects were 70 children from each site who were aged between 3 and 12 years, and were undergoing routine extractions of primary teeth. All children from the three centres used a self-report visual analogue scale to record pain preoperatively and postoperatively (15 min after recovery), and relevant pain-relief medication was noted. The efficacy of the three different pain relief regimes was then compared. RESULTS: Children reported significantly less pain when rectal Voltarol was provided prior to the extractions, as compared to paracetamol or no analgesia. The greatest amount of pain was reported by the group who had received no analgesia. CONCLUSIONS: Voltarol appears to be the better pre-emptive analgesic for dental extractions under general anaesthesia when compared with paracetamol and no analgesia.

Sensitivity and inter-observer variability for capsule endoscopy image analysis in a cohort of novice readers.

AIM: To determine the performance of novice readers (4th year medical students) for detecting capsule endoscopy findings. METHODS: Ten capsule endoscopy cases of small bowel lesions were administered to the readers. Gold standard findings were pre-defined by gastroenterologists. Ten gold standard "targets" were identified among the 10 cases. Readers were given a 30-min overview of Rapid Reader software and instructed to mark any potential areas of abnormalities. A software program was developed using SAS to analyze the thumbnailed findings. RESULTS: The overall sensitivity for detecting the gold standard findings was 80%. As a group, at least 5 out of 10 readers detected each gold standard finding per recording. All the gold standard targets were identified when the readers' results were combined. Incidental finding/false positive rate ranged between 8.2-59.8 per reader. CONCLUSION: A panel of medical students with minimal endoscopic experience can achieve high sensitivity in detecting lesions on capsule endoscopy. A group of novice readers can pre-screen recordings to thumbnail potential areas of small bowel lesions for further review. These thumbnails must be reviewed to determine the clinical relevance. Further studies are ongoing to assess other cohorts.

Do depressed older adults who attribute depression to "old age" believe it is important to seek care?

OBJECTIVE: To determine whether depressed older adults who attribute becoming depressed to "old age" rather than illness are more likely to believe it is not important to seek treatment for depression. DESIGN: Cross-sectional mailed survey. SETTING: Academically affiliated primary care physicians' network. PARTICIPANTS: Surveys were mailed to 588 patients age > or =65 years who were randomly identified from patient lists of 20 physicians. Surveys were returned by 429 patients (73%). Patients were eligible for this study if they scored > or =2 points on the 5-item Geriatric Depression Scale (n = 94) and were not missing key variables (final n = 90). MEASUREMENTS AND MAIN RESULTS: Of the 90 depressed patients, 48 (53%) believed that feeling depressed was very important to discuss with a doctor. In unadjusted analysis, older adults who did not believe it is very important to discuss feeling depressed with a doctor were more likely to attribute becoming depressed to aging (41% vs 17%; P =.012). In a logistic regression model adjusting for sociodemographic characteristics, number of impairments in basic and instrumental activities of daily living, medical comorbidity, and physical (PCS-12) and mental (MCS-12) component summary scores from the Medical Outcomes Study Short-Form-12, depressed older adults who attributed depression to aging had a 4.3 times greater odds than those who attributed depression to illness to not believe it is very important to discuss depression with a doctor (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.3 to 14.5). CONCLUSIONS: Among older persons with depression, attributing feeling depressed to old age may be an important barrier to care seeking.