Search

OBJECTIVES Maximizing quality of life (QoL) is the ultimate goal of long-term dementia care. However, routine QoL measurement is rare in nursing home (NH) and assisted living (AL) facilities. Routine QoL measurement might lead to improvements in resident QoL. Our objective was to assess the feasibility of using DEMQOL-CH, completed by long-term care staff in video calls with researchers, to assess health-related quality of life (HrQoL) of NH and AL residents with dementia or other cognitive impairment. DESIGN Cross-sectional study. SETTING AND PARTICIPANTS We included a convenience sample of 5 NHs and 5 AL facilities in the Canadian province of Alberta. Forty-two care staff who had worked in the facility for ≥3 months completed DEMQOL-CH assessments of 183 residents who had lived in the facility for 3 months or more and were aged ≥65 years. Sixteen residents were assessed independently by 2 care staff to assess inter-rater reliability. METHODS We assessed HrQoL in people with dementia or other cognitive impairment using DEMQOL-CH, and assessed time to complete, inter-rater reliability, internal consistency reliability, and care staff ratings of feasibility of completing the DEMQOL-CH. RESULTS Average time to complete DEMQOL-CH was

Quality of life is an important outcome in older-adult care. Measuring resident quality of life may offer ways to improve it and to improve quality of care. However, in the UK quality of life is rarely measured as a part of routine care. Our study aimed to understand the views of care home staff about using a quality of life instrument as a part of routine care in order to support its implementation into routine practice. In a qualitative study, we conducted 35 interviews with care home staff and two focus groups with four care home managers from three care homes in East Sussex, England. Data were collected between September 2015 and February 2016. Care staff and managers were aged on average 40 (SD = 12.2) and 43.7 (SD = 14.4) years and had worked in the care sector an average of 11.4 (SD = 10.2) and 23.7 (SD = 14.1) years, respectively. Participants were predominantly female and white British. Interviews and focus groups were analysed using thematic analysis. Findings identified two overarching themes of 'Perceived gains' and 'Implementation'. Overall, there was a lot of positivity towards using a quality of life instrument in routine practice. This positivity was an important feature in how the instrument was perceived as fitting into practice. Participants identified several barriers and discussed how to overcome them. Results from the study demonstrate that routine measurement of quality of life is positively received by care staff. They believed that measuring quality of life as a part of care practice could lead to improvements in resident quality of life, staff knowledge and understanding and care practices. The findings suggest that routinely measuring quality of life as a part of normal care could also have more far-reaching effects on the provision of person-centred care provided by care staff.

Recent research suggests the positive effect of physical activity on health-related quality of life in people with dementia may be mediated through improved activities of daily living and reduced depressive symptoms. One hundred and twenty-four people with dementia and their informal carers were recruited from the South East of England for this observational study. A subset of participants wore an accelerometer for 30 days. A series of bivariate analyses were completed, alongside mediation analyses. In people with mild to moderate severity dementia, weak positive associations were widely reported between physical activity indices and health-related quality of life, though only a single association reached statistical significance (rs = .25, p = .03). Mediation analysis revealed no significant indirect effects across the models after controlling for cognition. Future research needs to explore such relationships with a greater emphasis on the modality and psychosocial components of physical activity rather than just frequency, duration, and intensity.

Historic observations suggest that survivors of smallpox maintained lifelong immunity and protection to subsequent infection compared to vaccinated individuals. Although protective immunity by vaccination using a related virus (vaccinia virus (VACV) strains) was the key for smallpox eradication, it does not uniformly provide long term, or lifelong protective immunity (Heiner et al., 1971). To determine differences in humoral immune responses, mice were inoculated with VACV either systemically, using intranasal inoculation (IN), or locally by an intradermal (ID) route. We hypothesized that sub-lethal IN infections may mimic systemic or naturally occurring infection and lead to an immunodominance reaction, in contrast to localized ID immunization. The results demonstrated systemic immunization through an IN route led to enhanced adaptive immunity to VACV-expressed protein targets both in magnitude and in diversity when compared to an ID route using a VACV protein microarray. In addition, cytokine responses, assessed using a Luminex® mouse cytokine multiplex kit, following IN infection was greater than that stemming from ID infection. Overall, the results suggest that the route of immunization (or infection) influences antibody responses. The greater magnitude and diversity of response in systemic infection provides indirect evidence for anecdotal observations made during the smallpox era that survivors maintain lifelong protection. These findings also suggest that systemic or disseminated host immune induction may result in a superior response, that may influence the magnitude of, as well as duration of protective responses.

COVID-19 vaccination reduces SARS-CoV-2 infection and transmission. However, evidence is emerging on the degree of protection across variants and in high-transmission settings. To better understand the protection afforded by vaccination specifically in a high-transmission setting, we examined household transmission of SARS-CoV-2 during a period of high community incidence with predominant SARS-CoV-2 B.1.1.7 (Alpha) variant, among vaccinated and unvaccinated contacts.We conducted a household transmission investigation in San Diego County, California, and Denver, Colorado, during January-April 2021. Households were enrolled if they had at least one person with documented SARS-CoV-2 infection. We collected nasopharyngeal swabs, blood, demographic information, and vaccination history from all consenting household members. We compared infection risks (IRs), RT-PCR cycle threshold values, SARS-CoV-2 culture results, and antibody statuses among vaccinated and unvaccinated household contacts.We enrolled 493 individuals from 138 households. The SARS-CoV-2 variant was identified from 121/138 households (88%). The most common variants were Alpha (75/121, 62%) and Epsilon (19/121, 16%). There were no households with discordant lineages among household members. One fully vaccinated secondary case was symptomatic (13%); the other 5 were asymptomatic (87%). Among unvaccinated secondary cases, 105/108 (97%) were symptomatic. Among 127 households with a single primary case, the IR for household contacts was 45% (146/322; 95% Confidence Interval [CI] 40-51%). The observed IR was higher in unvaccinated (130/257, 49%, 95% CI 45-57%) than fully vaccinated contacts (6/26, 23%, 95% CI 11-42%). A lower proportion of households with a fully vaccinated primary case had secondary cases (1/5, 20%) than households with an unvaccinated primary case (66/108, 62%).Although SARS-CoV-2 infections in vaccinated household contacts were reported in this high transmission setting, full vaccination protected against SARS-CoV-2 infection. These findings further support the protective effect of COVID-19 vaccination and highlight the need for ongoing vaccination among eligible persons.

To assess the household secondary infection risk (SIR) of B.1.1.7 (Alpha) and non-Alpha lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children.During January to April 2021, we prospectively followed households with a SARS-CoV-2 infection. We collected questionnaires, serial nasopharyngeal swabs for reverse transcription polymerase chain reaction testing and whole genome sequencing, and serial blood samples for serology testing. We calculated SIRs by primary case age (pediatric vs adult), household contact age, and viral lineage. We evaluated risk factors associated with transmission and described symptom profiles among children.Among 36 households with pediatric primary cases, 21 (58%) had secondary infections. Among 91 households with adult primary cases, 51 (56%) had secondary infections. SIRs among pediatric and adult primary cases were 45% and 54%, respectively (OR, 0.79; 95% CI, 0.41-1.54). SIRs among pediatric primary cases with Alpha and non-Alpha lineage were 55% and 46%, respectively (OR, 1.52; 95% CI, 0.51-4.53). SIRs among pediatric and adult household contacts were 55% and 49%, respectively (OR, 1.01; 95% CI, 0.68-1.50). Among pediatric contacts, no significant differences in the odds of acquiring infection by demographic or household characteristics were observed.Household transmission of SARS-CoV-2 from children and adult primary cases to household members was frequent. The risk of secondary infection was similar among child and adult household contacts. Among children, household transmission of SARS-CoV-2 and the risk of secondary infection was not influenced by lineage. Continued mitigation strategies (eg, masking, physical distancing, vaccination) are needed to protect at-risk groups regardless of virus lineage circulating in communities.

IntroductionDementia is a public health issue and a major risk factor for poor quality of life among older adults. In the absence of a cure, enhancing health-related quality of life (HRQoL) of people with dementia is the primary goal of care. Robust measurement of HRQoL is a prerequisite to effective improvement. The DEMQOL suite of instruments is considered among the best available to measure HRQoL in people with dementia; however, no review has systematically and comprehensively examined the use of the DEMQOL in research and summarised evidence to determine its feasibility, acceptability and appropriateness for use in research and practice.Methods and analysisWe will systematically search 12 electronic databases and reference lists of all included studies. We will include systematically conducted reviews, as well as, quantitative and qualitative research studies that report on the development, validation or use in research studies of any of the DEMQOL instruments. Two reviewers will independently screen all studies for eligibility, and assess the quality of each included study using one of four validated checklists appropriate for different study designs. Discrepancies at all stages of the review will be resolved by consensus. We will use descriptive statistics (frequencies, proportions, ranges), content analysis of narrative data and vote counting (for the measures of association) to summarise the data elements. Using narrative synthesis, we will summarise what is known about the development, validation, feasibility, acceptability, appropriateness and use of the DEMQOL. Our review methods will follow the reporting and conduct guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.Ethics and disseminationEthical approval is not required as this project does not involve primary data collection. We will disseminate our findings through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42020157851.

Objectives\ud ‘Dementia Friends’ is a programme used to raise awareness of dementia, developed by the Alzheimer's Society, which has been delivered across the UK to diverse populations, including adolescents. However, there is little evidence available with regards to adolescents' perceptions of the programme and its impact. This study aims to explore this in a group of adolescents from the south of England.\ud \ud Study design\ud Focus group discussions.\ud \ud Methods\ud Thirty adolescents aged between 11 and 16 years were recruited from two schools in East Sussex, England. All had participated in a Dementia Friends session in the past month. Focus group discussions were transcribed, coded and themes were created using inductive thematic analysis.\ud \ud Results\ud Four themes were identified: (1) perceptions and experiences of dementia, (2) outcomes and learning from Dementia Friends session, (3) reactions to the Dementia Friends session and (4) identified future learning needs.\ud \ud Conclusions\ud Adolescents had generally positive opinions about Dementia Friends, particularly the interactive nature of the session. Whilst they felt participating in Dementia Friends improved their attitudes and knowledge, they were often left wanting to learn more. Future research needs to empirically evaluate the extent to which Dementia Friends may improve attitudes and knowledge of dementia.

Background The nature and commonality of late-life risk factors for mild cognitive impairment (MCI), dementia, and mortality remain unclear. Our aim was to investigate potential risk factors, simultaneously in a single cohort including many individuals initially with normal cognition and followed for 6 years. Methods We classified 873 community-dwelling individuals (70–90 years old and without dementia at baseline) from the Sydney Memory and Ageing Study as cognitively normal (CN), having MCI or dementia, or deceased 6 years after baseline. Associations with baseline demographic, lifestyle, health, and medical factors were investigated, including apolipoprotein (APOE) genotype, MCI at baseline, and reversion from MCI to CN within 2 years of baseline. Results Eighty-three (9.5%) participants developed dementia and 114 (13%) died within 6 years; nearly 33% had MCI at baseline, of whom 28% reverted to CN within 2 years. A core set of baseline factors was associated with MCI and dementia at 6 years, including older age (per year: odds ratios and 95% confidence intervals = 1.08, 1.01–1.14 for MCI; 1.19, 1.09–1.31 for dementia), MCI at baseline (5.75, 3.49–9.49; 8.23, 3.93–17.22), poorer smelling ability (per extra test point: 0.89, 0.79–1.02; 0.80, 0.68–0.94), slower walking speed (per second: 1.12, 1.00–1.25; 1.21, 1.05–1.39), and being an APOE e4 carrier (1.84, 1.07–3.14; 3.63, 1.68–7.82). All except APOE genotype were also associated with mortality (age: 1.11, 1.03–1.20; MCI: 3.87, 1.97–7.59; smelling ability: 0.83, 0.70–0.97; walking speed: 1.18, 1.03–1.34). Compared with stable CN participants, individuals reverting from MCI to CN after 2 years were at greater risk of future MCI (3.06, 1.63–5.72). Those who reverted exhibited some different associations between baseline risk factors and 6-year outcomes than individuals with stable MCI. Conclusion A core group of late-life risk factors indicative of physical and mental frailty are associated with each of dementia, MCI, and mortality after 6 years. Tests for slower walking speed and poorer smelling ability may help screen for cognitive decline. Individuals with normal cognition are at greater risk of future cognitive impairment if they have a history of MCI.

Introduction: Physical activity may have a number of physical and mental health benefits for people with dementia and their carers. However, there is limited evidence about factors that influence physical activity participation in these groups. This study therefore looks at the barriers, facilitators and motivators of physical activity in people with dementia, from both the perspective of the person with dementia and their carer. \ud \ud Method: Thirty participants (15 sets of community-dwelling people with dementia and their family carers) were recruited from the South East of England. The participants took part in semi-structured dyadic interviews about their views of physical activity. Interviews were analysed using inductive thematic analysis at an individual level and comparisons were made between the groups. \ud \ud Results: Common motivator themes across persons with dementia and family carers were emotional and physical wellbeing, and social connectedness. Physical health was seen as a common barrier in both groups. Physical activity in the person with dementia was encouraged and supported by the family carer. For the carer, their caring role, and limited time acted as barriers to their participation. \ud \ud Conclusion: Themes such as social connectedness, positive emotion and health were seen as key motivators to physical activity, which indicate that people with dementia and carers use physical activity as a means to maintain and improve their quality of life. Supporting family members to better facilitate such activities could encourage physical activity in people with dementia.

Objectives: There is a lack of understanding about how adolescents perceive dementia, and what their dementia related experiences are. Without such information, it is hard to make a case for the need to raise awareness of dementia in adolescents, and the best strategies to achieve this.\ud \ud Methods: In a cohort of 901 adolescents (aged 13–18) from the South East of England, we explored what the experiences and perceptions of dementia were using a series of questionnaires. Descriptive data of individual items were reported, comparing differences between genders.\ud \ud Results: The adolescents within this study tended to have positive or neutral attitudes towards dementia, though there was evidence that a proportion of adolescents had misconceptions or held negative attitudes (e.g. 28.5% of adolescents disagreed with the statement ‘In general, I have positive attitudes about people with dementia’). We also identified that the adolescents had a range of experiences of dementia including providing some form of care for someone with dementia (23.2%), though most had indirect contact with dementia through TV and movies (77.3%), or adverts (80.2%). Females nearly always had better attitudes towards dementia and had significantly more contact with dementia.\ud \ud Conclusions: Considering that adolescents are already forming negative attitudes and misconceptions of dementia, it is important that we raise awareness about dementia in this age group.

Zika virus (ZIKV) infection remains a public health concern necessitating demand for long-term virus production for diagnostic assays and RD activities. Inactivated virus constitutes an important component of the Trioplex rRT-PCR assay and serological IgM assay (MAC-ELISA). The aim of our study is to establish standard methods of ZIKV inactivation while maintaining antigenicity and RNA integrity. We tested viral supernatants by four different inactivation methods: 1. Heat inactivation at 56 °C and 60 °C; 2. Gamma-Irradiation; 3. Chemical inactivation by Beta-propiolactone (BPL) and 4. Fast-acting commercial disinfecting agents. Effectivity was measured by cytopathic effect (CPE) and plaque assay. RNA stability and antigenicity were measured by RT-PCR and MAC-ELISA, respectively. Results: Heat inactivation: Low titer samples, incubated at 56 °C for 2 h, showed neither CPE or plaques compared to high titer supernatants that required 2.5 h. Inactivation occurred at 60 °C for 60 min with all virus titers. Gamma irradiation: Samples irradiated at ≥3 Mrad for low virus concentrations and ≥5Mrad for high virus titer completely inactivated virus. Chemical Inactivation: Neither CPE nor plaques were observed with ≥0.045 % BPL inactivation of ZIKV. Disinfectant: Treatment of viral supernatants with Micro-Chem Plus™, inactivated virus in 2 min, whereas, Ethanol (70 %) and STERIS Coverage® Spray TB inactivated the virus in 5 min.

Background:Over 400,000 people live in care home settings in the UK. One way of understanding and improving the quality of care provided is by measuring and understanding the quality of life (QoL) of those living in care homes. This review aimed to identify and examine the psychometric properties including feasibility of use of dementia-specific QoL measures developed or validated for use in care settings.Design:Systematic review.Methods:Instruments were identified using four electronic databases (PubMed, PsycINFO, Web of Science, and CINAHL) and lateral search techniques. Searches were conducted in January 2017. Studies which reported on the development and/or validation of dementia specific QoL instruments for use in care settings written in English were eligible for inclusion. The methodological quality of the studies was assessed using the COSMIN checklist. Feasibility was assessed using a checklist developed specifically for the review.Results:Six hundred and sixteen articles were identified in the initial search. After de-duplication, screening and further lateral searches were performed, 25 studies reporting on 9 dementia-specific QoL instruments for use in care home settings were included in the review. Limited evidence was available on the psychometric properties of many instruments identified. Higher-quality instruments were not easily accessible or had low feasibility of use.Conclusions:Few high-quality instruments of QoL validated for use in care home settings are readily or freely available. This review highlights the need to develop a well-validated measure of QoL for use within care homes that is also feasible and accessible.

Objectives: Interoception is a general sensitivity to bodily sensations that informs motivational processes and behaviours. Interoceptive abilities seem to be impaired in several clinical conditions, and the development of new pragmatic instruments to assess subjective components of interoception are crucially needed. An easy to use paper and pencil questionnaire measuring sensitivity to bodily sensations was validated in an Italian sample (Self‐Awareness Questionnaire; SAQ). Methods: In the present study, we created and evaluated an electronic version of the SAQ in Italian and English language. Results: Psychometric properties of both electronic versions of the SAQ were validated in an Italian (n= 206) and an English (n= 275) sample, using factorial analyses. Differences in factorial structures observed between the two samples were discussed in terms of cultural impact on emotional regulation and bodily sensations processing. Conclusions: The electronic version of SAQ in English and Italian provides a pragmatic and validated tool to evaluate bodily signal sensitivity in clinical settings,informing the development of a new therapy targeting interoceptive processes, in a wide range of psychopathological conditions.

The development of dementia friendly communities is a current global and national priority for the UK. As a response to policy, there have been a number of dementia awareness initiatives disseminated with the aim of reducing the stigma associated with a diagnosis of dementia. The inclusion of adolescents in such initiatives is imperative in order to sustain dementia friendly communities. With this in mind, the aim of this study was to establish the dementia education needs of adolescents and effective dissemination strategies to convey key messages. A total of 42 adolescents aged 12 to 18 years participated in eight focus group discussions. Key themes to emerge from discussions included: the importance of dementia awareness, topics of interest within dementia, preferred methods of learning, the inclusion of the person living with dementia and the use of social media. The findings of the study will enable the development of appropriate dementia awareness initiatives for adolescents and thus facilitate the sustainability of dementia friendly communities.

Physical activity questionnaires are an important means to assess habitual physical activity. It remains unclear what questionnaires are used and whether they are appropriate for people with dementia who have impaired information recall but are also often largely sedentary. This scoping review aimed to identify and quantify the use of physical activity questionnaires within a dementia population. Eighteen studies met the inclusion criteria for this review. The majority of studies used questionnaires that were validated for use within an older adult population (e.g., Modified Baecke Questionnaire for the Elderly), though none had specifically been validated for use in people with dementia. Interestingly, just over half of studies (N= 10, 55.6%) adapted the questionnaires from the original validated version by allowing a proxy to provide input into the responses. Future research needs to robustly validate the use of proxy-report measures of physical activity in people with dementia.

Vitamin D has previously been quantified in some plants and algae, particularly in leaves of the Solanaceae family. We measured the vitamin D content of Australian native food plants and Australian-grown edible seaweed. Using liquid chromatography with triple quadrupole mass spectrometry, 13 samples (including leaf, fruit, and seed) were analyzed in duplicate for vitamin D2, vitamin D3, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3. Five samples contained vitamin D2: raw wattleseed (Acacia victoriae) (0.03 &micro, g/100 g dry weight (DW)), fresh and dried lemon myrtle (Backhousia citriodora) leaves (0.03 and 0.24 &micro, g/100 g DW, respectively), and dried leaves and berries of Tasmanian mountain pepper (Tasmannia lanceolata) (0.67 and 0.05 &micro, g/100 g DW, respectively). Fresh kombu (Lessonia corrugata) contained vitamin D3 (0.01 &micro, g/100 g DW). Detected amounts were low, however, it is possible that exposure to ultraviolet radiation may increase the vitamin D content of plants and algae if vitamin D precursors are present.

Importance Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. Objective To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer–specific mortality. Design, Setting, and Participants The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. Intervention An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Main Outcomes and Measures Primary outcome: prostate cancer–specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Results Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, −0.013 per 1000 person-years [95% CI, −0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P

The eradication of smallpox and the cessation of global vaccination led to the increased prevalence of human infections in Central Africa. Serologic and protein-based diagnostic assay for MPXV detection is difficult due to cross-reactive antibodies that do not differentiate between diverse orthopoxvirus (OPXV) species. A previously characterized monoclonal antibody (mAb 69-126-3-7) against MPXV [1] was retested for cross-reactivity with various OPXVs. The 14.5 kDa band protein that reacted with mAb 69-126-3 was identified to be MPXV A29 protein (homolog of vaccinia virus Copenhagen A27). Amino acid sequence analysis of the MPXV A29 with other OPXV homologs identified four amino acid changes. Peptides corresponding to these regions were designed and evaluated for binding to mAb 69-126-3 by ELISA and BioLayer Interferometry (BLI). Further refinement and truncations mapped the specificity of this antibody to a single amino acid difference in a 30-mer peptide compared to other OPXV homologs. This particular residue is proposed to be essential for heparin binding by VACV A27 protein. Despite this substitution, MPXV A29 bound to heparin with similar affinity to that of VACV A27 protein, suggesting flexibility of this motif for heparin binding. Although binding of mAb 69-126-3-7 to MPXV A29 prevented interaction with heparin, it did not have any effect on the infectivity of MPXV. Characterization of 69-126-3-7 mAb antibody allows for the possibility of the generation of a serological based species-specific detection of OPXVs despite high proteomic homology.

Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.

OBJECTIVE • To estimate rates of prostate-specific antigen (PSA) testing in UK general practices by age, deprivation index and geographical location. SUBJECTS AND METHODS • Practice-based, retrospective data on PSA testing patterns in 2007 were collected from a random sample of 87 general practices using EMIS LV computer systems within the passively observed non-intervention arm of a cluster-randomized controlled trial. • Information for a total of 126 716 men aged 45-89 years with no recorded diagnosis of prostate cancer prior to 1 January 2007 was collected. RESULTS • In all, 7902 (6.2%) of 126 716 men aged 45-89 without a prior diagnosis of prostate cancer underwent at least one PSA test from their general practitioner during 2007 [95% confidence interval (CI) 5.6-7.0%; practice-based inter-quartile range 3.6-8.4%]. • PSA testing rates were 1.4% (95% CI 1.1-1.6%) in men aged 45-49, rising to 11.3% (95% CI 10.0-12.9%) at age 75-79 years (P for trend

Background In cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. To minimise bias, the UCD should be independently verified by expert reviewers, blinded to death certificate data and trial arm. We investigated whether standardising the information submitted for UCD assignment in a population-based randomised controlled trial of prostate-specific antigen (PSA) testing for prostate cancer reduced the reviewers’ ability to correctly guess the trial arm. Methods Over 550 General Practitioner (GP) practices (>415,000 men aged 50–69 years) were cluster-randomised to PSA testing (intervention arm) or the National Health Service (NHS) prostate cancer risk management programme (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews of researcher-written clinical vignettes that masked trial arm and death certificate information. A period of time after the process began (the initial phase), we analysed whether the reviewers could correctly identify trial arm from the vignettes, and the reasons for their choice. This feedback led to further standardisation of information (second phase), after which we re-assessed the extent of correct identification of trial arm. Results 1099 assessments of 509 vignettes were completed by January 2014. In the initial phase (n = 510 assessments), reviewers were unsure of trial arm in 33% of intervention and 30% of control arm assessments and were influenced by symptoms at diagnosis, PSA test result and study-specific criteria. In the second phase (n = 589), the respective proportions of uncertainty were 45% and 48%. The percentage of cases whereby reviewers were unable to determine the trial arm was greater following the standardisation of information provided in the vignettes. The chances of a correct guess and an incorrect guess were equalised in each arm, following further standardisation. Conclusions It is possible to mask trial arm from cause of death reviewers, by using their feedback to standardise the information submitted to them. Trial registration ISRCTN92187251 Electronic supplementary material The online version of this article (doi:10.1186/1471-2288-15-6) contains supplementary material, which is available to authorized users.

OBJECTIVE • To estimate rates of prostate-specific antigen (PSA) testing in UK general practices by age, deprivation index and geographical location. SUBJECTS AND METHODS • Practice-based, retrospective data on PSA testing patterns in 2007 were collected from a random sample of 87 general practices using EMIS LV computer systems within the passively observed non-intervention arm of a cluster-randomized controlled trial. • Information for a total of 126 716 men aged 45-89 years with no recorded diagnosis of prostate cancer prior to 1 January 2007 was collected. RESULTS • In all, 7902 (6.2%) of 126 716 men aged 45-89 without a prior diagnosis of prostate cancer underwent at least one PSA test from their general practitioner during 2007 [95% confidence interval (CI) 5.6-7.0%; practice-based inter-quartile range 3.6-8.4%]. • PSA testing rates were 1.4% (95% CI 1.1-1.6%) in men aged 45-49, rising to 11.3% (95% CI 10.0-12.9%) at age 75-79 years (P for trend0.001). • Testing rates were lowest in the three northern centres (3.5-5.7%) vs the three more southern centres (7.1-8.9%; P0.001). • For every 20 points increase in the index of multiple deprivation score, the proportion of men tested fell by 1.7% (95% CI -2.5 to -0.8%; P0.001). • Lower proportions of men were subsequently diagnosed with prostate cancer in practices testing more men (odds ratio for a one unit increase in the natural log of testing 0.76; 95% CI 0.60-0.97; P= 0.025). CONCLUSION • Overall levels of PSA testing in UK general practice remain low, but for those tested there are important variations by age, deprivation and geographical location that do not appear to reflect clinical need or the intention of current policy. • PSA testing in general practice is currently skewed towards older men, and current policy enabling all men to make an informed choice about PSA testing is not being effectively implemented as uptake clearly varies by socioeconomic status. • This reinforces the need for robust evidence regarding the costs and benefits of using the PSA test for the detection of localized prostate cancer in the UK, a full assessment of the health economic implications and a revision of the current policy.