Chapter 6: Assessing Applicability of Medical Test Studies in Systematic Reviews

Use of medical tests should be guided by research evidence about the accuracy and utility of those tests in clinical care settings. Systematic reviews of the literature about medical tests must address applicability to real-world decision-making. Challenges for reviews include: (1) lack of clarity in key questions about the intended applicability of the review, (2) numerous studies in many populations and settings, (3) publications that provide too little information to assess applicability, (4) secular trends in prevalence and the spectrum of the condition for which the test is done, and (5) changes in the technology of the test itself. We describe principles for crafting reviews that meet these challenges and capture the key elements from the literature necessary to understand applicability

TLR 2 and 4 responsiveness from isolated peripheral blood mononuclear cells from rats and humans as potential chronic pain biomarkers

Background: Chronic pain patients have increased peripheral blood mononuclear cell Interkeukin-1β production following TLR2 and TLR4 simulation. Here we have used a human-to-rat and rat-to-human approach to further investigate whether peripheral blood immune responses to TLR agonists might be suitable for development as possible systems biomarkers of chronic pain in humans. Methods and Results: Study 1: using a graded model of chronic constriction injury in rats, behavioral allodynia was assessed followed by in vitro quantification of TLR2 and TLR4 agonist-induced stimulation of IL-1β release by PBMCs and spinal cord tissues (n = 42; 6 rats per group). Statistical models were subsequently developed using the IL-1β responses, which distinguished the pain/no pain states and predicted the degree of allodynia. Study 2: the rat-derived statistical models were tested to assess their predictive utility in determining the pain status of a published human cohort that consists of a heterogeneous clinical pain population (n = 19) and a pain-free population (n = 11). The predictive ability of one of the rat models was able to distinguish pain patients from controls with a ROC AUC of 0.94. The rat model was used to predict the presence of pain in a new chronic pain cohort and was able to accurately predict the presence of pain in 28 out of the 34 chronic pain participants. Conclusions: These clinical findings confirm our previous discoveries of the involvement of the peripheral immune system in chronic pain. Given that these findings are reflected in the prospective graded rat data, it suggests that the TLR response from peripheral blood and spinal cord were related to pain and these clinical findings do indeed act as system biomarkers for the chronic pain state. Hence, they provide additional impetus to the neuroimmune interaction to be a drug target for chronic pain.Yuen H. Kwok, Jonathan Tuke, Lauren L. Nicotra, Peter M. Grace, Paul E. Rolan, Mark R. Hutchinso

Inboard and outboard radial electric field wells in the H- and I-mode pedestal of Alcator C-Mod and poloidal variations of impurity temperature

We present inboard (HFS) and outboard (LFS) radial electric field (E[subscript r]) and impurity temperature (T[subscript z]) measurements in the I-mode and H-mode pedestal of Alcator C-Mod. These measurements reveal strong Er wells at the HFS and the LFS midplane in both regimes and clear pedestals in T[subscript z], which are of similar shape and height for the HFS and LFS. While the H-mode E[subscript r] well has a radially symmetric structure, the E[subscript r] well in I-mode is asymmetric, with a stronger ExB shear layer at the outer edge of the E[subscript r] well, near the separatrix. Comparison of HFS and LFS profiles indicates that impurity temperature and plasma potential are not simultaneously flux functions. Uncertainties in radial alignment after mapping HFS measurements along flux surfaces to the LFS do not, however, allow direct determination as to which quantity varies poloidally and to what extent. Radially aligning HFS and LFS measurements based on the T[subscript z] profiles would result in substantial inboard-outboard variations of plasma potential and electron density. Aligning HFS and LFS E[subscript r] wells instead also approximately aligns the impurity poloidal flow profiles, while resulting in a LFS impurity temperature exceeding the HFS values in the region of steepest gradients by up to 70%. Considerations based on a simplified form of total parallel momentum balance and estimates of parallel and perpendicular heat transport time scales seem to favor an approximate alignment of the E[subscript r] wells and a substantial poloidal asymmetry in impurity temperature.United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512)Swiss National Science Foundatio

Vitamin D and subsequent all-age and premature mortality: a systematic review

<br>Background: All-cause mortality in the population < 65 years is 30% higher in Glasgow than in equally deprived Liverpool and Manchester. We investigated a hypothesis that low vitamin D in this population may be associated with premature mortality via a systematic review and meta-analysis.</br> <br>Methods: Medline, EMBASE, Web of Science, the Cochrane Library and grey literature sources were searched until February 2012 for relevant studies. Summary statistics were combined in an age-stratified meta-analysis.</br> <br>Results: Nine studies were included in the meta-analysis, representing 24,297 participants, 5,324 of whom died during follow-up. The pooled hazard ratio for low compared to high vitamin D demonstrated a significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D levels and all-cause mortality after adjustment for available confounders. In an age-stratified meta-analysis, the hazard ratio for older participants was 1.25 (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).</br> <br>Conclusions: Low vitamin D status is inversely associated with all-cause mortality but the risk is higher amongst older individuals and the relationship is prone to residual confounding. Further studies investigating the association between vitamin D deficiency and all-cause mortality in younger adults with adjustment for all important confounders (or using randomised trials of supplementation) are required to clarify this relationship.</br&gt

Protocol for a multicentre, parallel-arm, 12-month, randomised, controlled trial of arthroscopic surgery versus conservative care for femoroacetabular impingement syndrome (FASHIoN)

Introduction Femoroacetabular impingement (FAI) syndrome is a recognised cause of young adult hip pain. There has been a large increase in the number of patients undergoing arthroscopic surgery for FAI; however, a recent Cochrane review highlighted that there are no randomised controlled trials (RCTs) evaluating treatment effectiveness. We aim to compare the clinical and cost-effectiveness of arthroscopic surgery versus best conservative care for patients with FAI syndrome. Methods We will conduct a multicentre, pragmatic, assessor-blinded, two parallel arm, RCT comparing arthroscopic surgery to physiotherapy-led best conservative care. 24 hospitals treating NHS patients will recruit 344 patients over a 26-month recruitment period. Symptomatic adults with radiographic signs of FAI morphology who are considered suitable for arthroscopic surgery by their surgeon will be eligible. Patients will be excluded if they have radiographic evidence of osteoarthritis, previous significant hip pathology or previous shape changing surgery. Participants will be allocated in a ratio of 1:1 to receive arthroscopic surgery or conservative care. Recruitment will be monitored and supported by qualitative intervention to optimise informed consent and recruitment. The primary outcome will be pain and function assessed by the international hip outcome tool 33 (iHOT-33) measured 1-year following randomisation. Secondary outcomes include general health (short form 12), quality of life (EQ5D-5L) and patient satisfaction. The primary analysis will compare change in pain and function (iHOT-33) at 12 months between the treatment groups, on an intention-to-treat basis, presented as the mean difference between the trial groups with 95% CIs. The study is funded by the Health Technology Assessment Programme (13/103/02). Ethics and dissemination Ethical approval is granted by the Edgbaston Research Ethics committee (14/WM/0124). The results will be disseminated through open access peer-reviewed publications, including Health Technology Assessment, and presented at relevant conferences. Trial registration number ISRCTN64081839; Pre-results

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review

Background Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses. To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. Methods We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. Results Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. Conclusion There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect

Challenges to conducting research with older people living in nursing homes

<p>Abstract</p> <p>Background</p> <p>Although older people are increasingly cared for in nursing homes towards the end of life, there is a dearth of research exploring the views of residents. There are however, a number of challenges and methodological issues involved in doing this. The aim of this paper is to discuss some of these, along with residents' views on taking part in a study of the perceptions of dignity of older people in care homes and make recommendations for future research in these settings.</p> <p>Methods</p> <p>Qualitative interviews were used to obtain the views on maintaining dignity of 18 people aged 75 years and over, living in two private nursing homes in South East London. Detailed field notes on experiences of recruiting and interviewing participants were kept.</p> <p>Results</p> <p>Challenges included taking informed consent (completing reply slips and having a 'reasonable' understanding of their participation); finding opportunities to conduct interviews; involvement of care home staff and residents' families and trying to maintain privacy during the interviews. Most residents were positive about their participation in the study, however, five had concerns either before or during their interviews. Although 15 residents seemed to feel free to air their views, three seemed reluctant to express their opinions on their care in the home.</p> <p>Conclusion</p> <p>Although we experienced many challenges to conducting this study, they were not insurmountable, and once overcome, allowed this often unheard vulnerable group to express their views, with potential long-term benefits for future delivery of care.</p

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

Does the lateral intercondylar ridge disappear in ACL deficient patients?

The aim of this study was to determine whether there is a difference in the presence of the lateral intercondylar ridge and the lateral bifurcate ridge between patients with sub-acute and chronic ACL injuries. We hypothesized that the ridges would be present less often with chronic ACL deficiency. Twenty-five patients with a chronic ACL injury were matched for age and gender to 25 patients with a sub-acute ACL injury. The lateral intercondylar ridge and lateral bifurcate ridge were scored as either present, absent, or indeterminate due to insufficient visualization by three blinded observers. The kappa for the three observers was .61 for the lateral intercondylar ridge and .58 for the lateral bifurcate ridge. The lateral intercondylar ridge was present in 88% of the sub-acute patients and 88% of the chronic patients. The lateral bifurcate ridge was present in 48% of the sub-acute and 48% of the chronic patients. This matched-pairs case–control study was unable to show a difference in the presence of the femoral bony ridges between patients with acute and chronic ACL injuries. The authors would suggest looking for the ridges as a landmark of the native ACL insertion site during ACL reconstruction in both acute and chronic ACL injuries