The MAPP Room Memory Test: Examining Contextual Memory Using a Novel Computerized Test in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer's Disease.

Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer's disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify in which visual scene target items were previously presented. We hypothesized that cognitively-unimpaired carriers of an autosomal dominant AD mutation (Presenilin-1 E280A, n=15) would perform more poorly on this test than non-carrier family members (n=31). Compared to non-carriers, the carriers had significantly worse delayed room recognition. The results indicate that the MAPP Room Memory Test may be sensitive to subtle cognitive changes associated with risk of AD. Future studies with larger samples using the MAPP Room Memory Test and biomarkers are needed to examine whether this test may also be sensitive to the earliest pathological changes in preclinical AD.

Employing the theory of planned behaviour to design an e-cigarette education resource for use in secondary schools.

BACKGROUND: An extended version of the theory of planned behaviour (TPB) was used to inform the design of a framework for an educational resource around e-cigarette use in young people. METHODS: A sequential exploratory design was employed. In Phase 1, elicited behavioural, normative and control beliefs, via 7 focus groups with 51 participants, aged 11-16 years, identified salient beliefs around e-cigarette use. These were used to construct a questionnaire administered to 1511 young people aged 11-16 years, which determined predictors of e-cigarette use and ever use. In Phase 2, sociodemographic variables, e-cigarette knowledge, access, use, marketing and purchasing of e-cigarettes and smoking behaviour were also gathered. The composite findings from Phase 1 and 2 informed the design of a post primary educational resource in Phase 3 around e-cigarette use. RESULTS: Current e-cigarette use was 4%, with almost 23% reporting ever use, suggesting current use is stable but experimentation may be increasing in this cohort. Sociodemographic variables, knowledge of e-cigarettes, smoking behaviour and TPB variables (direct and indirect measures of attitudes, subjective norm, and perceived behavioural control) accounted for 17% of the variance in current e-cigarette use, with higher intentions to use e-cigarettes within the next month, having the strongest impact on use (p < 0.001), followed by self-efficacy (p = 0.016). Sociodemographic and TPB variables accounted for 65% of the variance in intentions to use e-cigarettes in the next month; current e-cigarette use (p < 0.001), more positive attitudes (p < 0.001), stronger social influence (p < 0.001), higher self-efficacy (p < 0.001), higher control beliefs (p < 0.001) and greater motivation to use e-cigarettes (p < 0.001) were the main predictors of intentions. Phases 1 and 2 informed the mapping of key predictors of intentions and use of e-cigarettes onto the Theoretical Domains Framework, which identified appropriate intervention functions and behaviour change techniques. CONCLUSIONS: This paper is the first to bridge the theoretical-practice gap in an area of significant public health importance through the development of a framework for a novel theory driven school-based educational resource aimed at reducing experimentation and uptake of e-cigarette use in young people.

Knowledge and behavioural interventions to reduce human health risk from private groundwater systems: A global review and pooled analysis based on development status.

Groundwater contamination constitutes a significant health risk for private well users residing in rural areas. As the responsibility to safeguard rural private domestic groundwater typically rests with non-expert homeowners, interventions promoting risk mitigation and awareness represent the most viable means of preventing supply contamination. However, no global review or pooled analyses of these interventions has been undertaken to date. The current study sought to identify and quantify the performance of private well interventions from 1990 to 2018 via a global systematised review and pooled analysis. The PICO (Population-Intervention-Comparison-Outcome) approach was employed for literature identification. Relevant studies were statistically analysed across two quantitative outcome (performance) types, namely knowledge and behaviour, controlling for intervention characteristics and country development status. Mean behavioural and knowledge attainment across interventions was 53% and 48%, respectively, with interventions in economically developed regions exhibiting higher behavioural outcomes (56% vs. 45%) than those in developing regions. Geographically, interventions were located in southern or southeast Asia (n = 23), North America (n = 15), Central America (n = 1) and Africa (n = 1), with none identified in Australia/Oceania, Europe, or South America. Behavioural outcomes were significantly associated with presence of educational/research coordinator (p = 0.023), with these interventions attaining higher levels of efficacy (+74%) than those implemented by other coordinator types. Findings indicate that instructor-led, practical interventions allied with both large- and local-scale awareness-raising campaigns represent an optimum approach for future private well risk interventions. Subsequent adoption of such interventions may lead to increased levels of private well maintenance and provide a point of reference for myriad water and health communication contexts.

Effect of ocular hypertension on the pattern of retinal ganglion cell subtype loss in a mouse model of early-onset glaucoma.

Glaucoma is a neurodegenerative disease with elevated intraocular pressure as one of the major risk factors. Glaucoma leads to irreversible loss of vision and its progression involves optic nerve head cupping, axonal degeneration, retinal ganglion cell (RGC) loss, and visual field defects. Despite its high global prevalence, glaucoma still remains a major neurodegenerative disease. Introduction of mouse models of experimental glaucoma has become integral to glaucoma research due to well-studied genetics as well as ease of manipulations. Many established inherent and inducible mouse models of glaucoma are used to study the molecular and physiological progression of the disease. One such model of spontaneous mutation is the nee model, which is caused by mutation of the Sh3pxd2b gene. In both humans and mice, mutations disrupting function of the SH3PXD2B adaptor protein cause a developmental syndrome including secondary congenital glaucoma. The purpose of this study was to characterize the early onset nee glaucoma phenotype on the C57BL/6J background and to evaluate the pattern of RGC loss and axonal degeneration in specific RGC subtypes. We found that the B6.Sh3pxd2bnee mutant animals exhibit glaucoma phenotypes of elevated intraocular pressure, RGC loss and axonal degeneration. Moreover, the non-image forming RGCs survived longer than the On-Off direction selective RGCs (DSGC), and the axonal death in these RGCs was independent of their respective RGC subtype. In conclusion, through this study we characterized an experimental model of early onset glaucoma on a C57BL/6J background exhibiting key glaucoma phenotypes. In addition, we describe that RGC death has subtype-specific sensitivities and follows a specific pattern of cell death under glaucomatous conditions.

Physical activity correlates among older adults with probable generalized anxiety disorder: Results from The Irish Longitudinal Study on Ageing.

OBJECTIVES: This study assessed physical activity (PA) correlates among 1237 (69.0% female; age ≥ 50 years) community-dwelling adults with probable-generalized anxiety disorder (GAD). METHODS: Wave 1 data from The Irish Longitudinal Study on Ageing were analysed. PA was measured using the short-form International PA Questionnaire. Probable-GAD caseness was indicated by a score of ≥23 on the abbreviated Penn State Worry Questionnaire. Potential correlates were analysed using binomial logistic regression. Hierarchical logistic regression consisting of three blocks (sociodemographic variables; quality of life (QoL) variables; physical health and performance variables) examined the proportion of the variance for PA that was explained at each step of the regression model. RESULTS: Five hundred thirty-five participants (43.2%) met PA guidelines. After adjustment for age and sex, younger age and being male were associated with increased likelihood of meeting PA guidelines. Significant correlates of PA were in employment, higher QoL (CASP-19), social connectedness, and grip-strength. Additionally, polypharmacy (i.e., taking ≥five medications), antidepressant use, at-risk waist circumference (i.e., Males: >94 cm; Females >80 cm), up-and-go time, and number of self-reported physical limitations were significantly negatively associated with meeting PA guidelines. Physical health and performance variables explained significant variation (8.4%) in meeting physical activity guidelines beyond that of sociodemographics, and QoL variables. CONCLUSIONS: This study identified a range of sociodemographic, physical, and psychological variables that were associated with meeting or not meeting PA guidelines among older adults with probable-GAD.

Associations of physical activity with anxiety symptoms and status: results from The Irish longitudinal study on ageing.

AIMS: Anxiety is debilitating and associated with numerous mental and physical comorbidities. There is a need to identify and investigate low-risk prevention and treatment strategies. Therefore, the purpose of this study was to investigate cross-sectional and longitudinal associations between different volumes of moderate-to-vigorous physical activity (PA) and anxiety symptoms and status among older adults in Ireland. METHODS: Participants (n = 4175; 56.8% female) aged ⩾50 years completed the International PA Questionnaire (IPAQ) at baseline, and the anxiety subscale of the Hospital Anxiety and Depression Scale at baseline and follow-up (2009-2013). Participants were classified according to meeting World Health Organisation PA guidelines, and divided into IPAQ categories. Respondents without anxiety at baseline (n = 3165) were included in prospective analyses. Data were analysed in 2017. RESULTS: Anxiety symptoms were significantly higher among females than males (p < 0.001). Models were adjusted for age, sex, waist circumference, social class, smoking status and pain. In cross-sectional analyses, meeting PA guidelines was associated with 9.3% (OR = 0.91, 95% confidence interval 0.78-1.06) lower odds of anxiety. Compared with the inactive group, the minimally- and very-active groups were associated with 8.4% (OR = 0.92, 0.76-1.10) and 18.8% (OR = 0.81, 0.67-0.98) lower odds of anxiety, respectively. In prospective analyses, meeting guidelines was associated with 6.3% (OR = 0.94, 0.63-1.40) reduced odds of anxiety. Compared with the inactive group, the minimally and very-active groups were associated with 43.5% (OR = 1.44, 0.89-2.32) increased, and 4.3% (OR = 0.96, 0.56-1.63) reduced odds of anxiety. The presence of pain, included in models as a covariate, was associated with a 108.7% (OR = 2.09, 1.80-2.42) increase in odds of prevalent anxiety, and a 109.7% (OR = 2.10, 1.41-3.11) increase in odds of incident anxiety. CONCLUSION: High volumes of PA are cross-sectionally associated with lower anxiety symptoms and status, with a potential dose-response apparent. However, significant associations were not observed in prospective analyses. The low absolute number of incident anxiety cases (n = 109) potentially influenced these findings. Further, as older adults may tend to experience and/or report more somatic anxiety symptoms, and the HADS focuses primarily on cognitive symptoms, it is plausible that the HADS was not an optimal measure of anxiety symptoms in the current population.

Associations of physical activity and depression: Results from the Irish Longitudinal Study on Ageing.

Physical activity (PA) can protect against depression, but few studies have assessed whether meeting PA guidelines is sufficient, or if benefits can be derived from greater volumes of PA. The present study examines cross-sectional and prospective associations between different volumes of moderate-to-vigorous PA (MVPA) and walking, and depressive symptoms and status. Participants (n = 4556; 56.7% female) aged ≥ 50 years completed the International PA Questionnaire (IPAQ) at baseline and the Center for Epidemiological Studies Depression Scale at baseline and two years later. Prevalence and incidence of depression were 9.0% (n = 410) and 5.0% (n = 207), respectively. After full adjustment, odds of prevalent depression were: 40% (OR = 0.60, 95%CI: 0.48-0.76) lower among those meeting PA guidelines; 23% (OR = 0.77, 0.49-1.21) and 43% (OR = 0.57, 0.45-0.73) lower among those in moderate and high categories, respectively; and, 22% (OR = 0.78, 0.61-1.01) and 44.0% (OR = 0.56, 0.42-0.74) lower among those in moderate and high walking tertiles, respectively. Odds of incident depression were: 23% (OR = 0.77, 0.58-1.04) lower among those meeting PA guidelines; 37% (OR = 0.63, 0.32-1.22) and 20.0% (OR = 0.80, 0.59-1.09) lower among those in moderate and high categories, respectively; and, 21% (OR = 0.79, 0.56-1.12) and 25% (OR = 0.75, 0.52-1.07) lower among those in moderate and high walking tertiles, respectively. Moderate and high volumes of MVPA were significantly associated with lower odds of concurrent depression, and significantly and non-significantly associated with reduced odds of incident depression, respectively. Meeting recommended levels of MVPA and walking were associated with significantly lower odds of concurrent depression, and non-significantly reduced odds of the development of depression over two years.

Subtype-specific response of retinal ganglion cells to optic nerve crush.

Glaucoma is a neurodegenerative disease with retinal ganglion cell (RGC) loss, optic nerve degeneration and subsequent vision loss. There are about 30 different subtypes of RGCs whose response to glaucomatous injury is not well characterized. The purpose of this study was to evaluate the response of 4 RGC subtypes in a mouse model of optic nerve crush (ONC). In this study, we also evaluated the pattern of axonal degeneration in RGC subtypes after nerve injury. We found that out of the 4 subtypes, transient-Off α RGCs are the most susceptible to injury followed by On-Off direction selective RGCs (DSGC). Non-image forming RGCs are more resilient with ipRGCs exhibiting the most resistance of them all. In contrast, axons degenerate irrespective of their retinal soma after ONC injury. In conclusion, we show that RGCs have subtype specific cell death response to ONC injury and that RGC axons disintegrate in an autonomous fashion undergoing Wallerian degeneration. These discoveries can further direct us towards effective diagnostic and therapeutic approaches to treat optic neuropathies, such as glaucoma.

pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO2R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO2R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

Simvastatin for patients with acute respiratory distress syndrome: long-term outcomes and cost-effectiveness from a randomised controlled trial.

BACKGROUND: Simvastatin therapy for patients with acute respiratory distress syndrome (ARDS) has been shown to be safe and associated with minimal adverse effects, but it does not improve clinical outcomes. The aim of this research was to report on mortality and cost-effectiveness of simvastatin in patients with ARDS at 12 months. METHODS: This was a cost-utility analysis alongside a multicentre, double-blind, randomised controlled trial carried out in the UK and Ireland. Five hundred and forty intubated and mechanically ventilated patients with ARDS were randomly assigned (1:1) to receive once-daily simvastatin (at a dose of 80 mg) or identical placebo tablets enterally for up to 28 days. RESULTS: Mortality was lower in the simvastatin group (31.8%, 95% confidence interval (CI) 26.1-37.5) compared to the placebo group (37.3%, 95% CI 31.6-43.0) at 12 months, although this was not significant. Simvastatin was associated with statistically significant quality-adjusted life year (QALY) gain (incremental QALYs 0.064, 95% CI 0.002-0.127) compared to placebo. Simvastatin was also less costly (incremental total costs -£3601, 95% CI -8061 to 859). At a willingness-to-pay threshold of £20,000 per QALY, the probability of simvastatin being cost-effective was 99%. Sensitivity analyses indicated that the results were robust to changes in methodological assumptions with the probability of cost-effectiveness never dropping below 90%. CONCLUSION: Simvastatin was found to be cost-effective for the treatment of ARDS, being associated with both a significant QALY gain and a cost saving. There was no significant reduction in mortality at 12 months, TRIAL REGISTRATION: ISRCTN, 88244364. Registered 26 November 2010.

Individual patient data analysis of tidal volumes used in three large randomized control trials involving patients with acute respiratory distress syndrome.

BACKGROUND.: The acute respiratory distress syndrome (ARDS) is a condition with a high mortality and morbidity. Mechanical ventilation prevents immediate mortality but may further damage patients' lungs. Low tidal volume lung-protective strategies have been shown to increase survival by reducing this iatrogenic damage. Current guidelines recommend tidal volumes of 6-8 ml kg -1 of predicted body weight. We used data from three large randomized controlled trials of treatments for ARDS to determine compliance with these recommendations. METHODS.: We used the tidal volume recorded at randomization for all patients in the OSCAR, HARP-2, and BALTI-2 studies. In addition, we used the ventilation data for control arm patients in OSCAR and all patients in HARP-2 at days 1 and 7 after randomization. RESULTS.: The three trials enrolled 1660 patients, with tidal volume data available at least at one time point in 1412 patients. Compliance with the 6-8 ml kg -1 recommendation for tidal volume ranged from 20 to 39% of patients across all time points in all three trials. CONCLUSION.: Poor compliance with the guidelines for tidal volume in patients with ARDS has been demonstrated before in case series, but not in clinical trials where the patient population is specifically selected against standard ARDS diagnostic criteria and the investigators were encouraged to use low tidal volumes. This study may indicate a need to improve implementation and compliance with protective lung ventilation.

Association between antidepressant prescribing and suicide rates in OECD countries: an ecological study.

INTRODUCTION: We have conducted an ecological study to assess the association between antidepressant prescribing and suicide rates using the Organisation for Economic Co-operation and Development (OECD) health data, making this the largest ecological study in recent times. METHOD: Data were derived for the years 1995-2008 from the OECD health data set. The residuals for all variables were adjusted for country and year within each country. These were then analysed to identify predictors of suicide rate. Pearson's rank correlation coefficient and linear regression model were employed to assess associations and identify significant predictors of suicide rate. RESULTS: Suicide rate has significant positive correlations with antidepressant rates (p=0.031) and unemployment (p=0.028). It also has a significant negative correlation with inpatient psychiatric beds (p=0.039). The actual coefficients are less than ±0.16, indicating weak relationships. After adjusting for other variables, the only variable that is a statistically significant predictor of suicide rate is antidepressant prescribing (p=0.005, r²=0.09). DISCUSSION: Our analysis using this large data set suggests a statistically significant, albeit weak positive, association between antidepressant prescribing and suicide rates.

Description and predictors of hospital costs of oesophageal cancer during the first year following diagnosis in Northern Ireland.

The cost-effectiveness of novel interventions in the treatment of cancer is well researched; however, relatively little attention is paid to the cost of many aspects of routine care. Oesophageal cancer is the ninth most common cancer in the UK and sixth most common cause of cancer death. It usually presents late and has a poor prognosis. The hospital costs incurred by oesophageal cancer patients diagnosed in Northern Ireland in 2005 (n = 198) were determined by review of medical records. The average cost of hospital care per patient in the 12 months from presentation was £7847. Variations in total hospital costs by age at diagnosis, gender, cancer stage, histological type, mortality at 1 year, co-morbidity count and socio-economic status were analysed using multiple regression analyses. Higher costs were associated with earlier stages of cancer and cancer stage remained a significant predictor of costs after controlling for cancer type, patient age and mortality at 1 year. Thus, although early detection of cancer usually improves survival, this would mean increased costs in the first year. Deprivation achieved borderline significance with those from more deprived areas having lower resource consumption relative to the more affluent.

Development and validation of a patient-reported disability measurement tool for patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease can impact on a patient's ability to maintain normal physical and mental function, and fulfil their social, family and work roles. Aspects of disability in IBD have received little attention. AIM: To develop, validate and apply a questionnaire directed towards evaluating these disease aspects. METHODS: A literature review on disability in IBD was undertaken, and opinion about aspects of disability to measure was sought from six IBD-specialised gastroenterologists. A questionnaire was developed, and IBD patients completed the new disability questionnaire, the SF-36 and the short-IBD (SIBDQ - 10 point). A subgroup of patients completed the questionnaire again 4 weeks later. Healthy volunteers were studied as a control group. RESULTS: A total of 116 IBD out-patients were approached, of whom 81 (52 Crohn's disease and 28 ulcerative colitis) participated. Nineteen patients were re-evaluated at 4 weeks. Twenty-five controls were studied. All subscales demonstrated good Cronbach's alpha reliability and reproducibility. There was a significant inverse correlation between the disability score and the SIBDQ and between the disability score and the SF36 and a positive correlation with the Crohn's Disease Activity Index (CDAI) (all P < 0.001). Disability differed between ulcerative colitis and controls, but not between active and inactive disease. CONCLUSIONS: The new disability questionnaire is sensitive for detecting disability, is reliable and reproducible, and correlates with disease activity in Crohn's disease, but not ulcerative colitis. Further prospective testing is now needed in the longer term, larger patient populations and in different countries and ethnicities.

Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study.

BACKGROUND: To determine the incidence of acute retinal necrosis (ARN) in the United Kingdom and to describe the demographics, management, and visual outcome in these patients. METHODS: This was a prospective study carried out by the British Ophthalmological Surveillance Unit (BOSU) between September 2007 and October 2008. Initial and 6-month questionnaires were sent to UK ophthalmologists who reported cases of ARN via the monthly BOSU report card system. RESULTS: In all, 45 confirmed cases (52 eyes) of ARN were reported in the 14-month study period, giving a minimum incidence of 0.63 cases per million population per year. There were 20 females and 25 males. Age ranged from 10 to 94 years. Eight patients had a history of herpetic CNS disease. Aqueous sampling was carried out in 13 patients, vitreous in 27, and cerebrospinal fluid (CSF) in 4. Varicella-zoster virus followed by herpes simplex were the most common causative agents. Treatment in 76% of the cases was with intravenous antivirals; however, 24% received only oral antivirals. In all, 47% of patients had intravitreal antiviral therapy. Visual outcome at 6 months was <6/60 in 48% of the affected eyes. CONCLUSION: The minimum incidence of ARN in the UK is 0.63 cases per million. Patients with a history of herpetic CNS disease should be warned to immediately report any visual symptoms. There is increased use of oral and intravitreal antivirals in initial treatment.

Clinical phenotype of cystic fibrosis patients with the G551D mutation.

BACKGROUND: Data on whether the phenotype of cystic fibrosis (CF) patients with compound heterozygocity for G551D (Gly551Asp) differs from patients with F508del (Phe508del) homozygous mutations is divergent. AIM: We hypothesized that CF patients with the G551D mutation would have less severe disease than F508del homozygotes. DESIGN: We compared the clinical phenotype of adult patients with a G551D mutation with adult patients homozygous for F508del and those with the missense mutation R117H (Arg117His). Compound heterozygotes for the G551D and R117H were analysed separately. METHODS: Data were collected for 101 adult CF patients. Group 1-4 represents in order F508del homozygote patients (n = 61), those with the G551D mutation and a more severe mutation (n = 13), those with R117H mutation and a more severe mutation (n = 23) and also those compound for both the R117H and G551D mutations (n = 4). RESULTS: Our findings have shown that adult patients with the G551D mutation and a second severe mutation have a milder clinical phenotype than F508del homozygous adult patients. Higher FEV(1) and body mass index and less impaired glucose tolerance was demonstrated in the patients with G551D and R117H compared to F508del homozygotes. There was a reduced yearly rate of decline of FEV(1) (P < 0.05), infection with Pseudomonas aeruginosa along with reduced burden of care. Compound heterozygosity for G551D and R117H mutations was associated with normal spirometry, body mass index, no chronic infection and no symptoms. CONCLUSION: Mutations on different chromosomes are not independent of each other for the overall impact on the amount of functional CFTR. This study suggests that patients with the G551D mutation and a second severe mutation have a milder clinical phenotype than F508del homozygous patients, but the phenotype is not as mild as patients with the R117H mutation.

The Cancer Research UK experience of pre-clinical toxicology studies to support early clinical trials with novel cancer therapies.

Pre-clinical toxicology studies in rodents and Phase I clinical trial data are summarised for 14 novel anticancer therapies. With only one exception, an antifolate antimetabolite, rodent toxicology predicted a safe Phase I trial starting dose and the majority of the dose limiting toxicities, in particular haematological toxicity. For targeted agents with well-defined pharmacodynamic markers, illustrated in the current study by 3 anti-endocrine drugs and one resistance modifier, the definition of a maximum tolerated dose can be avoided. Together with earlier data, the current study confirms that pre-clinical toxicology studies in a non-rodent species are not routinely needed for the safe conduct of early clinical trials with new cancer chemotherapies.

Utility of digital photographs of the hand for assessing the presence of hand osteoarthritis.

OBJECTIVES: Nodal osteoarthritis of the hand (hand OA) is a subset of OA with a strong heritable component. Multiple genetic analyses of this condition have been performed and are underway. Highest yield from any genetic study depends upon a clear clinical phenotype for case definition. Radiographs may provide the most detail about the nature of the lesion. Physical examination is an imperfect means of evaluating each patient, particularly when hundreds or thousands of patients are required for study. Our study evaluated the accuracy, relative to a radiograph, of a digital photograph of the hands for the presence of OA in a particular joint, as well as for the diagnosis of nodal hand OA. METHODS: Consecutive patients were evaluated as part of the I-NODAL study (Investigation of Nodal Osteoarthritis to Detect an Association with Loci encoding Interleukin-1 [IL-1]). Evaluation included a physical examination by a trained rheumatologist, a postero-anterior radiograph of the hands, and a digital photograph of each hand. Radiographs were read by one trained observer using the Kellgren-Lawrence scale. Photographs were taken by one individual and were analyzed by an experienced rheumatologist. Kappa statistics were determined for each modality and accuracy was assessed using radiographic readings as a gold standard. RESULTS: Intra-reader reliability for radiograph interpretation was good for the overall diagnosis of hand OA (kappa0.76 [0.45,1.07]), but varied widely for the presence or absence of K-L grades 2-4 in individual joints (median kappa0.70, range 0.49-0.87 for ACR index joints). Distal interphalangeal joint (DIP) nodes on physical examination were sensitive (median 96.27, 93.94-100), but not specific for radiographic hand OA in the corresponding joint (median 33.0, 17.24-42.86). Physical examination evidence of OA in the 1st carpo-metacarpal (CMC) and proximal interphalangeal (PIP) joints provided only moderate sensitivity and specificity. However, the negative predictive value of the examination of individual joints was good (median negative predictive value was 82.58 for IP joints with a range 68.29-100.00), particularly in the DIP joints. Specificity of a node visualized on hand photograph was variable (median for all IP joints and 1st CMC 83.77, range 53.37-96.97), with greatest specificity for radiographic OA in the corresponding joint found in the 1st CMC and the PIP joints. Clinical hand OA was sensitive, but not specific for the radiographic diagnosis of hand OA; while, photographic OA was moderately specific, but insensitive. CONCLUSION: The visualization of a node on a digital photograph of the hand provides fair to moderate specificity for radiographic hand OA in the corresponding joint, with generally poor sensitivity. A photograph has limited value as a screening tool for the diagnosis of radiographic hand OA.