The clinical utility of the Cornell Scale for Depression in Dementia as a routine assessment in nursing homes

Objective To examine the clinical utility of the Cornell Scale for Depression in Dementia (CSDD) in nursing homes. Setting 14 nursing homes in Sydney and Brisbane, Australia. Participants 92 residents with a mean age of 85 years. Measurements Consenting residents were assessed by care staff for depression using the CSDD as part of their routine assessment. Specialist clinicians conducted assessment of depression using the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders for residents without dementia or the Provisional Diagnostic Criteria for Depression in Alzheimer Disease for residents with dementia to establish expert clinical diagnoses of depression. The diagnostic performance of the staff completed CSDD was analyzed against expert diagnosis using receiver operating characteristic (ROC) curves. Results The CSDD showed low diagnostic accuracy, with areas under the ROC curve being 0.69, 0.68 and 0.70 for the total sample, residents with dementia and residents without dementia, respectively. At the standard CSDD cutoff score, the sensitivity and specificity were 71% and 59% for the total sample, 69% and 57% for residents with dementia, and 75% and 61% for residents without dementia. The Youden index (for optimizing cut-points) suggested different depression cutoff scores for residents with and without dementia. Conclusion When administered by nursing home staff the clinical utility of the CSDD is highly questionable in identifying depression. The complexity of the scale, the time required for collecting relevant information, and staff skills and knowledge of assessing depression in older people must be considered when using the CSDD in nursing homes.

Performance of R-N(R′)-R″ functionalised poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) monolithic sorbent for plasmid DNA adsorption

High-throughput plasmid DNA (pDNA) manufacture is obstructed predominantly by the performance of conventional stationary phases. For this reason, the search for new materials for fast chromatographic separation of pDNA is ongoing. A poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (GMA-EGDMA) monolithic material was synthesised via a thermal-free radical reaction, functionalised with different amino groups from urea, 2-chloro-N,N-diethylethylamine hydrochloride (DEAE-Cl) and ammonia in order to investigate their plasmid adsorption capacities. Physical characterisation of the monolithic polymer showed a macroporous polymer having a unimodal pore size distribution pivoted at 600 nm. Chromatographic characterisation of the functionalised polymers using pUC19 plasmid isolated from E. coli DH5α-pUC19 showed a maximum plasmid adsorption capacity of 18.73 mg pDNA/mL with a dissociation constant (KD) of 0.11 mg/mL for GMA-EGDMA/DEAE-Cl polymer. Studies on ligand leaching and degradation demonstrated the stability of GMA-EGDMA/DEAE-Cl after the functionalised polymers were contacted with 1.0 M NaOH, which is a model reagent for most 'cleaning in place' (CIP) systems. However, it is the economic advantage of an adsorbent material that makes it so attractive for commercial purification purposes. Economic evaluation of the performance of the functionalised polymers on the grounds of polymer cost (PC)/mg pDNA retained endorsed the suitability of GMA-EGDMA/DEAE-Cl polymer.

Utility of assessing nerve morphology in central cornea versus whorl area for diagnosing diabetic peripheral neuropathy

Purpose To compare small nerve fiber damage in the central cornea and whorl area in participants with diabetic peripheral neuropathy (DPN) and to examine the accuracy of evaluating these 2 anatomical sites for the diagnosis of DPN. Methods A cohort of 187 participants (107 with type 1 diabetes and 80 controls) was enrolled. The neuropathy disability score (NDS) was used for the identification of DPN. The corneal nerve fiber length at the central cornea (CNFLcenter) and whorl (CNFLwhorl) was quantified using corneal confocal microscopy and a fully automated morphometric technique and compared according to the DPN status. Receiver operating characteristic analyses were used to compare the accuracy of the 2 corneal locations for the diagnosis of DPN. Results CNFLcenter and CNFLwhorl were able to differentiate all 3 groups (diabetic participants with and without DPN and controls) (P < 0.001). There was a weak but significant linear relationship for CNFLcenter and CNFLwhorl versus NDS (P < 0.001); however, the corneal location x NDS interaction was not statistically significant (P = 0.17). The area under the receiver operating characteristic curve was similar for CNFLcenter and CNFLwhorl (0.76 and 0.77, respectively, P = 0.98). The sensitivity and specificity of the cutoff points were 0.9 and 0.5 for CNFLcenter and 0.8 and 0.6 for CNFLwhorl. Conclusions Small nerve fiber pathology is comparable at the central and whorl anatomical sites of the cornea. Quantification of CNFL from the corneal center is as accurate as CNFL quantification of the whorl area for the diagnosis of DPN.

The future for genetic studies in reproduction

Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies(GWAS) have revolutionized gene discovery forcommontraits and diseases. Results of GWAS are documented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publications for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at menopause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases.GWAS 'hits' provide novel insights into biological pathways and the translational value of these studies lies in discovery of novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility.

Axial spondyloarthritis: A new disease entity, not necessarily early ankylosing spondylitis

New classification criteria for axial spondyloarthritis have been developed with the goal of increasing sensitivity of criteria for early inflammatory spondyloarthritis. However these criteria substantially increase heterogeneity of the resulting disease group, reducing their value in both research and clinical settings. Further research to establish criteria based on better knowledge of the natural history of non-radiographic axial spondyloarthritis, its aetiopathogenesis and response to treatment is required. In the meantime the modified New York criteria for ankylosing spondylitis remain a very useful classification criteria set, defining a relatively homogenous group of cases for clinical use and research studies.

Spinal inflammation in the absence of sacroiliac joint inflammation on magnetic resonance imaging in patients with active nonradiographic axial spondyloarthritis

Objective: To evaluate the presence of spinal inflammation with and without sacroiliac (SI) joint inflammation on magnetic resonance imaging (MRI) in patients with active nonradiographic axial spondyloarthritis (SpA), and to compare the disease characteristics of these subgroups. Methods: ABILITY-1 is a multicenter, randomized, controlled trial of adalimumab versus placebo in patients with nonradiographic axial SpA classified using the Assessment of SpondyloArthritis international Society axial SpA criteria. Baseline MRIs were centrally scored independently by 2 readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method for the SI joints and the SPARCC 6-discovertebral unit method for the spine. Positive evidence of inflammation on MRI was defined as a SPARCC score of >2 for either the SI joints or the spine. Results: Among patients with baseline SPARCC scores, 40% had an SI joint score of >2 and 52% had a spine score of >2. Forty-nine percent of patients with baseline SI joint scores of <2, and 58% of those with baseline SI joint scores of >2, had a spine score of >2. Comparison of baseline disease characteristics by baseline SI joint and spine scores showed that a greater proportion of patients in the subgroup with a baseline SPARCC score of >2 for both SI joints and spine were male, and patients with spine and SI joint scores of <2 were younger and had shorter symptom duration. SPARCC spine scores correlated with baseline symptom duration, and SI joint scores correlated negatively with the baseline Bath Ankylosing Spondylitis Disease Activity Index, but neither correlated with the baseline Ankylosing Spondylitis Disease Activity Score, total back pain, the patient's global assessment of disease activity, the Bath Ankylosing Spondylitis Functional Index, morning stiffness, nocturnal pain, or C-reactive protein level. Conclusion: Assessment by experienced readers showed that spinal inflammation on MRI might be observed in half of patients with nonradiographic axial SpA without SI joint inflammation.

An immunodiagnostic assay for quantitation of specific ige to the major pollen allergen component, pas n 1, of the subtropical bahia grass

Background Pollens of the Panicoideae subfamily of grasses including Bahia (Paspalum notatum) are important allergen sources in subtropical regions of the world. An assay for specific IgE to the major molecular allergenic component, Pas n 1, of Bahia grass pollen (BaGP) would have immunodiagnostic utility for patients with pollen allergy in these regions. Methods Biotinylated Pas n 1 purified from BaGP was coated onto streptavidin ImmunoCAPs. Subjects were assessed by clinical history of allergic rhinitis and skin prick test (SPT) to aeroallergens. Serum total, BaGP-specific and Pas n 1-specific IgE were measured. Results: Pas n 1 IgE concentrations were highly correlated with BaGP SPT (r = 0.795, p < 0.0001) and BaGP IgE (r = 0.915, p < 0.0001). At 0.23 kU/l Pas n 1 IgE, the diagnostic sensitivity (92.4%) and specificity (93.1%) for the detection of BaGP allergy was high (area under receiver operator curve 0.960, p < 0.0001). The median concentrations of Pas n 1 IgE in non-Atopic subjects (0.01 kU/l, n = 67) and those with other allergies (0.02 kU/l, n = 59) showed no inter-group difference, whilst grass pollen-Allergic patients with allergic rhinitis showed elevated Pas n 1 IgE (6.71 kU/l, n = 182, p < 0.0001). The inter-Assay coefficient of variation for the BaGP-Allergic serum pool was 6.92%. Conclusions Pas n 1 IgE appears to account for most of the BaGP-specific IgE. This molecular component immunoassay for Pas n 1 IgE has potential utility to improve the sensitivity and accuracy of diagnosis of BaGP allergy for patients in subtropical regions.

Validity of currently used cutoff values of body mass index as a measure of obesity in Sri Lankan children

The aim of the study was to determine the reliability of body mass index based (BMI) cutoff values in diagnosing obesity among Sri Lankan children. Height, weight, waist circumference (WC) and hip circumference (HC) in 282 children were measured. Total body water was determined by deuterium dilution and fat mass (FM) derived using age and gender specific constants. A percentage FM of 30% for girls and 25% for boys were considered as cutoff levels for obesity. Two hundred and eighty two children (M/F: 158/124) were studied and 99 (80%) girls and 72 (45.5%) boys were obese based on % body fat. Eight (6.4%) girls and nine (5.7%) boys were obese based on International Obesity Task Force (IOTF) cutoff values. Percentage FM and WC centile charts were able to diagnose a significant proportion of children as true obese children. The FM and BMI were closely associated in both girls (r = 0.82, p < 0.001) and boys (r = 0.87, p < 0.001). Percentage FM and BMI had a very low but significant association; girls (r = 0.32, p < 0.001) and boys (r = 0.68, p < 0.001). FM had a significant association with WC and HC. BMI based cutoff values had a specificity of 100% but a very low sensitivity, varying between 8% and 23.6%. BMI is a poor indicator of the percentage fat and the commonly used cutoff values were not sensitive to detect cases of childhood obesity in Sri Lankan children.

Assessment of body composition in Sri Lankan children: Validation of a bioelectrical impedance prediction equation

Objective: To develop bioelectrical impedance analysis (BIA) equations to predict total body water (TBW) and fat-free mass (FFM) of Sri Lankan children. Subjects/Methods: Data were collected from 5- to 15-year-old healthy children. They were randomly assigned to validation (M/F: 105/83) and cross-validation (M/F: 53/41) groups. Height, weight and BIA were measured. TBW was assessed using isotope dilution method (D2 O). Multiple regression analysis was used to develop preliminary equations and cross-validated on an independent group. Final prediction equation was constructed combining the two groups and validated by PRESS (prediction of sum of squares) statistics. Impedance index (height2/impedance; cm2/Ω), weight and sex code (male = 1; female = 0) were used as variables. Results: Independent variables of the final prediction equation for TBW were able to predict 86.3% of variance with root means-squared error (RMSE) of 2.1l. PRESS statistics was 2.1l with press residuals of 1.2l. Independent variables were able to predict 86.9% of variance of FFM with RMSE of 2.7 kg. PRESS statistics was 2.8 kg with press residuals of 1.4 kg. Bland Altman technique showed that the majority of the residuals were within mean bias±1.96 s.d. Conclusions: Results of this study provide BIA equation for the prediction of TBW and FFM in Sri Lankan children. To the best of our knowledge there are no published BIA prediction equations validated on South Asian populations. Results of this study need to be affirmed by more studies on other closely related populations by using multi-component body composition assessment.

Evidence-based recommendations for the diagnosis of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

• As part of the 3E program, we conducted a systematic literature review and gathered consensus from 23 practising Australian rheumatologists to develop guidelines for early identification of ankylosing spondylitis and specialist referral. • In three rounds of break-out sessions followed by discussion and voting, the specialist panel addressed three questions related to diagnosis of ankylosing spondylitis: In individuals with back pain, what are the early clinical features that suggest ankylosing spondylitis? How useful is imaging in identifying early ankylosing spondylitis? Based on which clinical features should a general practitioner refer a patient to a rheumatologist for further evaluation? • The panel agreed on six recommendations related to the three questions: 1a. Early clinical features to suggest ankylosing spondylitis include inflammatory back pain and age at symptom onset < 45 years. 1b. The absence of symptomatic response to an appropriate course of non-steroidal anti-inflammatory drugs makes the diagnosis of ankylosing spondylitis less likely. 1c. Raised inflammatory markers are supportive, but their absence does not rule out the diagnosis of ankylosing spondylitis. 2a. Despite low sensitivity to detect changes of early ankylosing spondylitis, plain radiographs of the pelvis and spine are appropriate initial imaging techniques. 2b. Magnetic resonance imaging is a useful imaging modality for detecting early changes of ankylosing spondylitis. 3. Individuals with inflammatory back pain should be referred to a rheumatologist for further evaluation. • Effective dissemination and implementation of these recommendations are important to standardise the approach to early diagnosis of ankylosing spondylitis.

HLA-DR/DQ haplotype in rheumatoid arthritis: Novel allelic associations in UK Caucasians

Objective. To elucidate the relative importance of the HLA-DR and HLA-DQ loci in conferring genetic predisposition to rheumatoid arthritis (RA). Methods. HLA-DRB1 and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence-specific polymerase chain reaction. Allele and phenotype frequencies were compared with those in 2 large sets of historical, ethnically matched healthy controls, using the relative predispositional effect method. Results. Positive association was confirmed with the shared epitope positive HLA-DRB1 alleles associated with RA in Caucasians. A significant susceptibility effect was observed with HLA-DRB1*09, described in other ethnically diverse populations but not in Caucasians. A significant underrepresentation of the HLA-DRB1*0103 variant was noted among the RA cases, supporting the proposed protective role of the DERAA motif at residues 70-74 of the DRβ molecule. No HLA-DRB1 independent association of the HLA-DQB1 alleles, implicated in predisposing to RA, was evident. Conclusion. These data corroborate the shared epitope hypothesis of susceptibility to RA and provide strong evidence for the DRB1 locus as the primary RA susceptibility factor in the HLA region.

Circulating tumor cell detection in high-risk non-metastatic prostate cancer

Purpose The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method. Method Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method. Results The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age. Conclusion This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.

A study of the use of the Edinburgh postnatal depression scale with parent groups outside the postpartum period

The Edinburgh Postnatal Depression Scale (EPDS) was sent by post to 206 mothers and 201 fathers of toddlers (aged between 19 and 22 months). At the same time these parents also completed subscales of the Crown—Crisp Experiential Index (CCEI). The responses were used to assess the feasibility of postal completion of the EPDS and its acceptability to parents outside the postpartum year, particularly fathers for whom there have been no previous reports of its use. On a small sub-group, the sensitivity, specificity and predictive values of the measures were assessed using the Present. State Examination. Answers to the depression subscale of the CCEI to the EPDS and to the Present State Examination were compared to assess validity. Completion of the postally-administered EPDS was satisfactory, though some difficulties were experienced in a second postal administration to a subsample. The scale was completed without obvious error or omission and this, combined with positive comments from parents, suggests the acceptability of the scale to both mothers and fathers. The mean scores were higher for mothers than for fathers, but the pattern of distribution was similar with a marked positive skew and a distinct decline in scores above 10. Because the subsample of parents interviewed was small the calculation of sensitivity and specificity has to be treated with caution. However, the results for mothers suggest that the EPDS has satisfactory validity for this group and one superior to the depression subscale of the CCEI. Among the fathers interviewed there were insufficient cases to enable calculation of sensitivity and specificity. Other results were encouraging, however, and suggest the merit of further studies of the application and validity of the EPDS with fathers.

Diagnostic values for skin temperature assessment to detect diabetes-related foot complications

Background Skin temperature assessment is a promising modality for early detection of diabetic foot problems, but its diagnostic value has not been studied. Our aims were to investigate the diagnostic value of different cutoff skin temperature values for detecting diabetes-related foot complications such as ulceration, infection, and Charcot foot and to determine urgency of treatment in case of diagnosed infection or a red-hot swollen foot. Materials and Methods The plantar foot surfaces of 54 patients with diabetes visiting the outpatient foot clinic were imaged with an infrared camera. Nine patients had complications requiring immediate treatment, 25 patients had complications requiring non-immediate treatment, and 20 patients had no complications requiring treatment. Average pixel temperature was calculated for six predefined spots and for the whole foot. We calculated the area under the receiver operating characteristic curve for different cutoff skin temperature values using clinical assessment as reference and defined the sensitivity and specificity for the most optimal cutoff temperature value. Mean temperature difference between feet was analyzed using the Kruskal–Wallis tests. Results The most optimal cutoff skin temperature value for detection of diabetes-related foot complications was a 2.2°C difference between contralateral spots (sensitivity, 76%; specificity, 40%). The most optimal cutoff skin temperature value for determining urgency of treatment was a 1.35°C difference between the mean temperature of the left and right foot (sensitivity, 89%; specificity, 78%). Conclusions Detection of diabetes-related foot complications based on local skin temperature assessment is hindered by low diagnostic values. Mean temperature difference between two feet may be an adequate marker for determining urgency of treatment.

Evaluation of a 7-gene genetic profile for athletic endurance phenotype in Ironman championship triathletes

Polygenic profiling has been proposed for elite endurance performance, using an additive model determining the proportion of optimal alleles in endurance athletes. To investigate this model’s utility for elite triathletes, we genotyped seven polymorphisms previously associated with an endurance polygenic profile (ACE Ins/Del, ACTN3 Arg577Ter, AMPD1 Gln12Ter, CKMM 1170bp/985+185bp, HFE His63Asp, GDF8 Lys153Arg and PPARGC1A Gly482Ser) in a cohort of 196 elite athletes who participated in the 2008 Kona Ironman championship triathlon. Mean performance time (PT) was not significantly different in individual marker analysis. Age, sex, and continent of origin had a significant influence on PT and were adjusted for. Only the AMPD1 endurance-optimal Gln allele was found to be significantly associated with an improvement in PT (model p=5.79 x 10-17, AMPD1 genotype p=0.01). Individual genotypes were combined into a total genotype score (TGS); TGS distribution ranged from 28.6 to 92.9, concordant with prior studies in endurance athletes (mean±SD: 60.75±12.95). TGS distribution was shifted toward higher TGS in the top 10% of athletes, though the mean TGS was not significantly different (p=0.164) and not significantly associated with PT even when adjusted for age, sex, and origin. Receiver operating characteristic curve analysis determined that TGS alone could not significantly predict athlete finishing time with discriminating sensitivity and specificity for three outcomes (less than median PT, less than mean PT, or in the top 10%), though models with the age, sex, continent of origin, and either TGS or AMPD1 genotype could. These results suggest three things: that more sophisticated genetic models may be necessary to accurately predict athlete finishing time in endurance events; that non-genetic factors such as training are hugely influential and should be included in genetic analyses to prevent confounding; and that large collaborations may be necessary to obtain sufficient sample sizes for powerful and complex analyses of endurance performance.