Detection of Rater Errors on Cognitive Instruments in a Clinical Trial Setting.

OBJECTIVES: This study examines errors committed by raters in a clinical trial of a memory enhancement compound. BACKGROUND: Findings of clinical trials are directly dependent on the quality of the data obtained but there is little literature on rates or nature of rater errors on cognitive instruments in a multi-site setting. DESIGN: Double-blind placebo-controlled study. SETTING: 21 clinical sites in North America. PARTICIPANTS: Two hundred seventy-five participants. MEASUREMENTS: MMSE, WMS-R Logical Memory I and II, WMS-R Verbal Paired Associates I, WASi Vocabulary, WASi Matrix Reasoning, GDS and MAC-Q. RESULTS: The WMS-R Logical Memory I and II and WASi Vocabulary tests were found to have the greatest number of scoring errors. Few substantive errors were detected on source document review of the MMSE, GDS, MAC-Q and WMS-R Verbal Paired Associates I. Some additional administration and scoring issues were identified during feedback sessions with the raters. CONCLUSIONS: Cognitive measures used in clinical trials are prone to errors which can be detected with proper monitoring. Some instruments are particularly prone to inter-rater variably and should therefore be targets for focused training and ongoing monitoring. Areas in need of further investigation to help inform and optimize quality of clinical trial data are discussed.

Telephone-based CBT and the therapeutic relationship: The views and experiences of IAPT practitioners in a low-intensity service.

WHAT IS KNOWN ON THE SUBJECT: There is a move towards the use of new ways of delivering mental health care, particularly via an increased use of telephone therapies. Although some studies have noted the advantages of telephone-delivered therapies (e.g., removing access barriers) and reported on equivalent therapeutic effects when compared to face-to-face, there are concerns about how telephone-based therapy adversely affects the therapeutic relationship. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: It contributes new knowledge regarding psychological practitioners' experience and views about using telephone-based therapies and how this affects the therapeutic relationship. WHAT ARE THE IMPLICATIONS FOR PRACTICE: This paper provides data about the new practitioner workforce (IAPT Psychological Wellbeing Practitioners) and adds to a growing area of research regarding their clinical role. It has relevance for mental health nursing, because health services internationally and across the professions are exploring how telehealth can improve health care. This paper suggests that mental health services need to focus on what type of therapeutic relationship their practice facilitates and on offering transparency to service users. It concludes that telephone work in IAPT can accommodate a working alliance, but not other types of therapeutic relationship, which practitioners and service users hoped for. Services need to focus on what facilitates and inhibits deeper therapeutic closeness and connection. ABSTRACT: Introduction Over-the-telephone (OTT)-delivered psychological therapies as an alternative method to face-to-face (F2F) are becoming more prevalent in mental health care. Research suggests a range of benefits of OTT use in therapy, but there are growing concerns about its consequences for the therapeutic relationship. This paper presents new knowledge regarding psychological practitioners' experience and views of OTT work and its potential effects on the therapeutic relationship in the context of the UK's Increasing Access to Psychological Therapy (IAPT) programme. Aim This paper presents IAPT practitioners' experiences and views of OTT work and its potential effects on the therapeutic relationship. Methods Completed questionnaires (exploring OTT versus F2F work) which were distributed to IAPT practitioners revealed a concern about the therapeutic relationship in OTT. To explore this further, nine in-depth semi-structured interviews with PWPs were conducted and the findings from this qualitative study are reported here. Results Practitioners noted OTT use facilitated access and flexibility for service users; however, they expressed some concern over the adverse effect of OTT on the therapeutic relationship. Discussion Although a working alliance was possible OTT, this research suggests the type of therapeutic relationship formed OTT in a "low contact-high volume" service such as IAPT needs to be better defined. By addressing this, dissonance which might arise between practitioner aims and the aims of IAPT can be reduced. This research also contributes to wider debates regarding mental health care and its provision in the UK. Implications for practice This paper concludes that mental health services need to focus on what type of therapeutic relationship their practice facilitates and to offer transparency to service users. The findings suggest that telephone work in IAPT can accommodate a working alliance, but not other types of therapeutic relationship, which practitioners and service users hoped for. Services need to offer a more nuanced understanding of the concept of a therapeutic relationship and focus on what facilitates and inhibits deeper therapeutic closeness and connection.

Human immunology studies using organ donors: Impact of clinical variations on immune parameters in tissues and circulation.

Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here a coordinate analysis of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (2 months-93 years; n = 291) across eight clinical parameters. Overall, the blood of donors exhibited similar monocyte and lymphocyte content and low serum levels of pro-inflammatory cytokines as healthy controls; however, donor blood had increased neutrophils and serum levels of IL-8, IL-6, and MCP-1 which varied with cause of death. In tissues, the frequency and composition of monocytes, neutrophils, B lymphocytes and T cell subsets in lymphoid or mucosal sites did not vary with clinical state, and was similar in donors independent of the extent of clinical complications. Our results reveal that organ donors maintain tissue homeostasis, and are a valuable resource for fundamental studies in human immunology.

The role of C4d deposition in the diagnosis of antibody-mediated rejection after lung transplantation.

Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody-depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR.

Assessment of wetland/upland vegetation communities and evaluation of soil-plant contamination by polycyclic aromatic hydrocarbons and trace metals in regions near oil sands mining in Alberta.

Oil sands mining in Alberta, Canada, has been steadily increasing over the last 50years. The extent to which the surrounding vegetation has been altered/contaminated by pollutants released during bitumen extraction has not been a focus of oil sands environmental monitoring efforts. The objectives of this study were to assess plant species richness and composition in wetlands and uplands in the vicinity of oil sands mining areas and to measure levels of contamination of trace metals and polycyclic aromatic hydrocarbons (PAHs) in soils and plants. Twenty-two sites were selected in three locations: near to (OS, n=7), West (n=7), and East (n=8) of oil sands mining operations. Aboveground plant species were inventoried and soil was collected for a seedbank study. Soils and plants were collected for analyses of 28 metals and 40 parent and alkylated PAHs. Plant species richness and composition differed significantly among locations. More species were found in the OS sites, many of them being non-native, than in East and West sites, which contained almost exclusively native perennials. PAH levels were significantly higher in OS sites, and were mostly comprised of alkylated PAHs. Patterns of PAH distribution indicated contamination from bitumen/petroleum in four sites; other combustion types may have affected five additional sites at different levels. Metals were also elevated in OS sites. Metal levels were significantly correlated with distance to upgrader facilities. Ratios of some metals in soil vs. above- and belowground plant parts were significantly higher in West and East than in OS sites, likely due in part to pH as soil was acidic at the East and West locations but alkaline at OS sites. This study showed that sites located near oil sands mining operations were contaminated with PAHs and metals, and that the vegetation composition at these sites greatly differed from less disturbed areas.

Combined Percutaneous Transrenal and Transfemoral Endovascular Recanalization and Angioplastic Reconstruction of a Disrupted Transplant Renal Artery Stent: A Novel Salvage Technique.

Renal artery stenosis is the most common vascular complication following renal transplantation. Percutaneous endovascular transluminal angioplasty with stenting is the treatment of choice for clinically significant renal artery stenosis. The authors present a case describing a novel combined transrenal parenchyma and transfemoral approach to repairing a disrupted transplant renal artery stent. The patient's allograft renal artery stenosis was initially managed via the standard percutaneous approach, but during follow-up the stent became disrupted and crushed, causing partial occlusion of the renal artery. This was manifested by persistently elevated serum creatinine values, lower extremity edema, and four-medication hypertension. After a failed traditional percutaneous transfemoral attempt, the authors were able to successfully access the renal arterial system via a combined transrenal and transfemoral approach, using an upper-pole artery through the renal parenchyma. This transrenal approach used a 3 Fr system, allowing the authors to get a wire across the stent, which they were previously unable to do. With wire access, they performed a balloon angioplastic reconstruction to restore the stent's patency, resulting in a reduction in serum creatinine, lower extremity edema, and blood pressure. This technique avoided a potentially difficult reoperative repair without immediate complication and provides a method for vascular access to the renal arterial system in select patients.

Evaluating trivalent chromium toxicity on wild terrestrial and wetland plants.

Elevated chromium levels in soil from mining can impact the environment, including plants. Mining of chromium is concentrated in South Africa, several Asian countries, and potentially in Northern Ontario, Canada, raising concerns since chromium toxicity to wild plants is poorly understood. In the first experiment, concentration-response tests were conducted to evaluate effects of chromium on terrestrial and wetland plants. Following established guidelines using artificial soil, seeds of 32 species were exposed to chromium (Cr(3+)) at concentrations simulating contamination (0-1000 mg kg(-1)). This study found that low levels of chromium (250 mg kg(-1)) adversely affected the germination of 22% of species (33% of all families), while higher levels (500 and 1000 mg kg(-1)) affected 69% and 94% of species, respectively, from 89% of the families. Secondly, effects on seedbanks were studied using soil collected in Northern Ontario and exposed to Cr(3+) at equivalent concentrations (0-1000 mg kg(-1)). Effects were less severe in the seedbank study with significant differences only observed at 1000 mg kg(-1). Seeds exposed to Cr(3+) during stratification were greatly affected. Seed size was a contributing factor as was possibly the seed coat barrier. This study represents an initial step in understanding Cr(3+) toxicity on wild plants and could form the basis for future risk assessments.

Upper and lower conjunctival fornix depth in healthy white caucasian eyes: a method of objective assessment.

PurposeEvaluating anti-scarring therapies require objective assessment of scarring, and knowledge of normal fornix anatomy. Measurement of conjunctival scarring has focused on inferior fornix shortening, although the superior fornix is often overlooked. There are data on normal fornix depth (FD) in South Asians, but there are no studies investigating normal conjunctival FD in white Caucasians. We designed a fornix depth measurer (FDM) for objective measurement of upper and lower conjunctival FD. The purpose of this study was to evaluate intra- and inter-observer variability, and to establish a reference for normal conjunctival FD in an ethnically white Caucasian population.Patients and methodsProspective cross-sectional study evaluating conjunctival FD in 252 clinically normal white Caucasian participants aged 20-80. Paired observers evaluated inter- and intra-observer variability. Data was analyzed using Bland-Altman plots and analysis of variance.ResultsFor white Caucasian subjects, mean upper and lower conjunctival fornix depths were 15.6 mm (95% confidence interval (CI), 12.5-18.8) and 10.9 mm (95% CI, 8.0-13.7), respectively. Females have smaller FDs (upper FD 15.3 mm±1.6 females, 16.2 mm±1.4 males, P<0.001; lower FD 10.6 mm±1.3 females, 11.3 mm±1.4 males, P<0.001). There was a progressive decline in FD with age (upper fornix depth 16.3 mm±1.2 at age 20-29, and 15.0 mm±1.8 at age 80+ (P=0.04)). There was 94-100% intra-observer and inter-observer agreement for upper and lower fornix measurements.ConclusionsUsing a slightly different custom-designed FDM, central conjunctival fornix depth in white Caucasian eyes appears to be similar to data previously reported in South Asian eyes. Fornix depth measurements were repeatable and reproducible.

Applying the resources and supports in self-management framework to examine ophthalmologist-patient communication and glaucoma medication adherence.

Little is known about how ophthalmologist-patient communication over time is associated with glaucoma patient long-term adherence. The purpose of our study was to examine the association between provider use of components of the resources and supports in self-management model when communicating with patients and adherence to glaucoma medications measured electronically over an 8-month period. In this longitudinal prospective cohort study, the main variables studied were ophthalmologist communication-individualized assessment, collaborative goal setting and skills enhancement. Patients with glaucoma who were newly prescribed or on glaucoma medications were recruited from six ophthalmology clinics. Patients' baseline and next follow-up visits were videotape-recorded. Patients were interviewed after their visits. Patients used medication event monitoring systems (MEMS) for 8 months after enrollment into the study, and adherence was measured electronically using MEMS for 240 days after their visits. Two hundred and seventy-nine patients participated. Patient race and regimen complexity were negatively associated with glaucoma medication adherence over an 8-month period. Provider communication behaviors, including providing education and positive reinforcement, can improve patient adherence to glaucoma medications over an 8-month period.

Antimicrobial susceptibility patterns of clinical Escherichia coli isolates from dogs and cats in the United States: January 2008 through January 2013.

Escherichia coli is among the most common bacterial pathogens in dogs and cats. The lack of a national monitoring program limits evidence-based empirical antimicrobial choices in the United States. This study describes antimicrobial susceptibility patterns for presumed clinical E. coli isolates from dogs (n=2392) or cats (n=780) collected from six geographic regions in the United States between May 2008 and January 2013. Minimum inhibitory concentrations (MIC) were determined for 17 drugs representing 6 drug classes. Urinary tract isolates were most common (71%). Population MIC distributions were generally bimodal with the second mode above the resistant breakpoint for all drugs except gentamicin, amikacin, and meropenem. The MIC90 exceeded the susceptible breakpoint for ampicillin, amoxicillin-clavulanic acid, cephalothin (surrogate drug for cephalexin), and doxycycline but was below the susceptible breakpoint for all others. None of isolates was susceptible or resistant to all drug tested; 46% were resistant to 1 or 2 antimicrobial categories, and 52% to more than three categories. The resistance percentages were as follows: doxycycline (100%), cephalothin (98%)>ampicillin (48%)>amoxicillin-clavulanic acid (40%)>ticarcillin-clavulanic acid (18%)>cefpodoxime (13%), cefotaxime (12%), cefoxitin (11%), cefazolin (11%), enrofloxacin (10%), chloramphenicol (9.6%)>ciprofloxacin (9.2%), ceftazidime (8.7%), trimethoprim-sulfamethoxazole (7.9%), gentamicin (7.9%)>meropenem (1.5%), amikacin (0.7%) (P<0.05). Resistance to ampicillin and amoxicillin-clavulanic acid was greatest in the South-Central region (P<0.05). E. coli resistance may preclude empirical treatment with doxycycline, cephalexin, ampicillin, or amoxicillin-clavulanic acid. Based on susceptibility patterns, trimethoprim-sulfonamides may be the preferred empirical oral treatment.

Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures.

UNLABELLED: While type 2 diabetes (T2D) is associated with higher skeletal fragility, specific risk stratification remains incompletely understood. We found volumetric bone mineral density, geometry, and serum sclerostin differences between low-fracture risk and high-fracture risk T2D women. These features might help identify T2D individuals at high fracture risk in the future. INTRODUCTION: Diabetic bone disease, an increasingly recognized complication of type 2 diabetes mellitus (T2D), is associated with high skeletal fragility. Exactly which T2D individuals are at higher risk for fracture, however, remains incompletely understood. Here, we analyzed volumetric bone mineral density (vBMD), geometry, and serum sclerostin levels in two specific T2D subsets with different fracture risk profiles. We examined a T2D group with prior history of fragility fractures (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low-risk group) and compared their results to nondiabetic controls with (Fx) and without fragility fractures (Co). METHODS: Eighty postmenopausal women (n = 20 per group) underwent quantitative computed tomography (QCT) to compute vBMD and bone geometry of the proximal femur. Additionally, serum sclerostin, vitamin D, parathyroid hormone (PTH), HbA1c, and glomerular filtration rate (GFR) levels were measured. Statistical analyses employed linear regression models. RESULTS: DMFx subjects exhibited up to 33 % lower femoral neck vBMD than DM subjects across all femoral sites (-19 % ≤ ΔvBMD ≤ -33 %, 0.008 ≤ p ≤0.021). Additionally, DMFx subjects showed significantly thinner cortices (-6 %, p = 0.046) and a trend toward larger bone volume (+10 %, p = 0.055) relative to DM women and higher serum sclerostin levels when compared to DM (+31.4 %, p = 0.013), Fx (+25.2 %, p = 0.033), and control (+22.4 %, p = 0.028) subjects. CONCLUSION: Our data suggest that volumetric bone parameters by QCT and serum sclerostin levels can identify T2D individuals at high risk of fracture and might therefore show promise as clinical tools for fracture risk assessment in T2D. However, future research is needed to establish diabetes-specific QCT- and sclerostin-reference databases.

Herbicide impact on non-target plant reproduction: what are the toxicological and ecological implications?

Declining plant diversity and abundance have been widely reported in agro-ecosystems of North America and Europe. Intensive use of herbicides within cropfields and the associated drift in adjacent habitats are partly responsible for this change. The objectives of this work were to quantify the phenological stages of non-target plants in in-situ field situations during herbicide spray and to compare plant susceptibility at different phenological stages. Results demonstrated that a large number of non-target plants had reached reproductive stages during herbicide spray events in woodlots and hedgerows, both in Canada and Denmark where vegetation varies considerably. In addition, delays in flowering and reduced seed production occurred widely on plants sprayed at the seedling stage or at later reproductive periods, with plants sprayed at reproductive stages often exhibiting more sensitivity than those sprayed as seedlings. Ecological risk assessments need to include reproductive endpoints.

Increased T cell glucose uptake reflects acute rejection in lung grafts.

Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [(18)F]fluorodeoxyglucose ([(18)F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the grafts of syngeneic and allogeneic recipients with or without immunosuppression treatment. Pulmonary microPET scans demonstrated significantly higher [(18)F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [(18)F]FDG uptake was also markedly attenuated following T cell depletion therapy in lung recipients with ongoing acute rejection. Flow cytometric analysis using the fluorescent deoxyglucose analog 2-NBDG revealed that T cells, and in particular CD8(+) T cells, were the largest glucose utilizers in acutely rejecting lung grafts followed by neutrophils and antigen-presenting cells. These data indicate that imaging modalities tailored toward assessing T cell metabolism may be useful in identifying acute rejection in lung recipients.