IMPLEMENTING BACK PAIN TREATMENT PATHWAYS IN CLINICAL PRACTICE: QUALITATATIVE ANALYSIS OF STAKEHOLDER PERCEPTIONS

Background
Evidence-based practice advocates utilising best current research evidence, while reflecting patient preference and clinical expertise in decision making. Successfully incorporating this evidence into practice is a complex process. Based on recommendations of existing guidelines and systematic evidence reviews conducted using the GRADE approach, treatment pathways for common spinal pain disorders were developed.

Aims
The aim of this study was to identify important potential facilitators to the integration of these pathways into routine clinical practice.

Methods
A 22 person stakeholder group consisting of patient representatives, clinicians, researchers and members of relevant clinical interest groups took part in a series of moderated focus groups, followed up with individual, semi-structured interviews. Data were analysed using content analysis.

Results
Participants identified a number of issues which were categorized into broad themes. Common facilitators to implementation included continual education and synthesis of research evidence which is reflective of everyday practice; as well as the use of clear, unambiguous messages in recommendations. Meeting additional training needs in new or extended areas of practice was also recognized as an important factor. Different stakeholders identified specific areas which could be associated with successful uptake. Patients frequently defined early involvement in a shared decision making process as important. Clinicians identified case based examples and information on important prognostic indicators as useful tools to aiding decisions.

Conclusion
A number of potential implementation strategies were identified. Further work will examine the impact of these and other important factors on the integration of evidence-based treatment recommendations into clinical practice.

A comparison of Diamond Forrester and coronary calcium scores as gatekeepers for investigations of stable chest pain

To determine if calcium scores (CS) could act as a more effective gatekeeper than Diamond Forrester (DF) in the assessment of patients with suspected coronary artery disease (CAD). A sub-study of the Cardiac CT for the Assessment of Chest Pain and Plaque (CAPP) study, a randomised control trial evaluating the cost-effectiveness of cardiac CT in symptomatic patients with stable chest pain. Stable pain was defined as troponin negative pain without symptoms of unstable angina. 250 patients undergoing cardiac CT had both DF scores and CS calculated, with the accuracy of both evaluated against CT coronary angiogram. Criteria given in UK national guidelines were compared. Of the 250 patients, 4 withdrew. 140 (57 %) patients were male. The mean DF was 47.8 and mean CS 172.5. Of the 144 patients with non-anginal pain 19.4 % had significant disease (>50 % stenosis). In general the DF over estimated the presence of CAD whereas the CS reclassified patients to lower risk groups, with 91 in the high risk DF category compared to 26 in the CS. Both receiver operating curve and McNemar Bowker test analysis suggested the DF was less accurate in the prediction of CAD compared to CS [Formula: see text] Projected downstream investigations were also calculated, with the cost per number of significant stenoses identified cheaper with the CS criteria. Patients with suspected stable CAD are more accurately risk stratified by CS compared to the traditional DF. CS was more successful in the prediction of significant stenosis and appears to be more effective at targeting clinical resources to those patients that are in need of them.

Improved detection of acute myocardial infarction in patients with chest pain and significant left main stem coronary stenosis.

Background: Non-invasive diagnosis of acute myocardial infarction (AMI) associated with significant left main stem (LMS) stenosis remains challenging.

Methods: Consecutive patients presenting with acute ischaemic-type chest pain from 2000 to 2010 were analysed. Entry criteria: 12-lead ECG and Body Surface Potential Map (BSPM) at presentation, cardiac troponin T (cTnT) =12?h and coronary angiography during admission. cTnT =0.03?µg/l defined AMI. ECG abnormalities assessed: STEMI by Minnesota criteria; ST elevation (STE) aVR =0.5?mm; ST depression (STD) =0.5?mm in =2 contiguous leads (CL); T-wave inversion (TWI) =1?mm in =2 CL. BSPM STE was =2?mm in anterior, =1?mm in lateral, inferior, right ventricular or high right anterior and =0.5?mm in posterior territories. Significant LMS stenosis was =70%.

Results: Enrolled were 2810 patients (aged 60?±?12 years; 71% male). Of these, 116 (4.1%) had significant LMS stenosis with AMI occurring in 92 (79%). STEMI by Minnesota criteria occurred in 13 (11%) (sensitivity 12%, specificity 92%), STE in lead aVR in 23 (20%) (sensitivity 23%, specificity 92%), TWI in 38 (33%) (sensitivity 34%, specificity 71%) and STD in 51 (44%) (sensitivity 49%, specificity 75%). BSPM STE occurred in 85 (73%): sensitivity 88%, specificity 83%, positive predictive value 95% and negative predictive value 65%. Of those with AMI, 74% had STE in either the high right anterior or right ventricular territories not identified by the 12-lead ECG. C-Statistic for AMI diagnosis using BSPM STE was 0.800 (P?<?0.001).

Conclusion: In patients with significant LMS stenosis presenting with chest pain, BSPM STE has improved sensitivity (88%), with specificity 83%, over 12-lead ECG in the diagnosis of AMI.

Evidence-Based Clinical Pathways To Manage Urinary Tract Infections in Long-Term Care Facilities:A Qualitative Case Study Describing Administrator and Nursing Staff Views

Objectives: This article examines the views of nursing staff and administrators in long-term care facilities (LTCFs) regarding a clinical pathway for managing urinary tract infections (UTIs) in LTCF residents. Design: A qualitative (case study) design was used. Setting: Data were collected from 8 LTCFs in southern Ontario and 2 in Iowa enrolled in a larger randomized controlled trial of clinical pathway for managing UTIs in LTCF residents, conducted between September 2001 and March 2003. The clinical pathway, designed to more effectively identify, diagnose, and treat UTIs, and reduce inappropriate antibiotics use for asymptomatic UTIs, introduced 2 decision tools to determine when to order a urine culture and initiate antibiotic treatment for suspected UTIs. Participants: We conducted 19 individual interviews with administrators and 10 focus groups with 52 nurses. Findings: Nurses generally thought that the pathways were well developed and easy to use, and administrators believed they were an important educational resource. Barriers to their use varied by group-initial lack of buy-in from nurses (medical directors), additional work (directors of nursing), and the need to change the protocol to exclude certain residents based on prior health conditions and/or pressure from physicians or families (nurses). Conclusions: Both administrators and staff, once familiar with a new clinical protocol to improve UTI management in LTCFs, generally supported its use. © 2007 American Medical Directors Association.

Are there clinical features of a sensitized cough reflex?

Cough reflex hypersensitization is a key feature in patients with troublesome cough. The clinical consequence of this hypersensitive state is typified by bouts of coughing often triggered by low threshold stimuli encountered by the patient during normal daily activities including exposure to aerosols, scents and odours, a change in air temperature and when talking or laughing. These features are often perceived by cough patients to be the most disruptive aspect of their condition and undoubtedly contribute to impaired quality of life. Patients with troublesome cough may describe a range of additional symptoms and sensations including an 'urge to cough' or the feeling of an 'itch' at the back of the throat, or a choking sensation and occasionally chest pain or breathlessness. It is uncertain if these features arise due to the processes responsible for cough reflex sensitization or as a direct consequence of the underlying cough aetiology. In an attempt to understand the clinical features of a sensitized cough reflex, the spectrum of symptoms typically described by cough patients will be reviewed and possible underlying mechanisms considered. Since an intact cough reflex is crucial to airway protection, anti-tussive treatment that attenuates the hypersensitive cough state rather than abolishing the cough reflex completely would be preferable. Identifying such agents remains a clinical, scientific and pharmacological challenge. (c) 2008 Elsevier Ltd. All rights reserved.

Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T

Aims: To evaluate the role of novel biomarkers in early detection of acute myocardial infarction (MI) in patients admitted with acute chest pain.
Methods and results: A prospective study of 664 patients presenting to two coronary care units with chest pain was conducted over 3 years from 2003. Patients were assessed on admission: clinical characteristics, ECG (electrocardiogram), renal function, cardiac troponin T (cTnT), heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, NT-pro-brain natriuretic peptide, D-dimer, hsCRP (high sensitivity C-reactive protein), myeloperoxidase, matrix metalloproteinase-9, pregnancy associated plasma protein-A, soluble CD40 ligand. A =12 h cTnT sample was also obtained. MI was defined as cTnT = 0.03 µg/L. In patients presenting <4 h of symptom onset, sensitivity of H-FABP for MI was significantly higher than admission cTnT (73 vs. 55%; P = 0.043). Specificity of H-FABP was 71%. None of the other biomarkers challenged cTnT. Combined use of H-FABP and cTnT (either one elevated initially) significantly improved the sensitivities of H-FABP or cTnT (85%; P = 0.004). This combined approach also improved the negative predictive value, negative likelihood ratio, and the risk ratio.
Conclusion: Assessment of H-FABP within the first 4 h of symptoms is superior to cTnT for detection of MI, and is a useful additional biomarker for patients with acute chest pain.

Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease-A Meta-Analysis

BACKGROUND: Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source.

METHODS AND FINDINGS: Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive) were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92) for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9). Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US $ -13,371.94) per correctly treated patient.

CONCLUSIONS: Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost-effective; it was also a superior biomarker in infants. Further research is recommended for point-of-care procalcitonin testing and Markov modelling to incorporate cost per QALY with a life-time model.

Intermedin and calcitonin gene-related peptide fail to shine in acute coronary syndrome

Aims: To measure levels of intermedin and calcitonin gene-related peptide (CGRP) in acute coronary syndrome (ACS) and to determine if they are elevated. 
Methods and results: 81 patients admitted with suspected ACS were enrolled into the study. 50 were confirmed ACS by ACC (2000) guidelines and 31 were in a control group as non-cardiac chest pain. Intermedin was nonsignificantly elevated 6.14 pg/ml vs 4.84 pg/ml b8 h in the ACS group; sensitivity 68%, specificity 63% on presenting sample. Intermedinwas significantly elevated in those patientswho had an initially negative troponin T (b0.03 ng/ml) on presentation, 6.67 pg/ml vs 4.84 pg/ml, p = 0.03. CGRP was significantly elevated in ACS patients, 8–b16 h after pain onset, 8.67 pg/ml vs 7.08 pg/ml, p= 0.036. However, it didn't aid diagnosis in initially negative troponin patients; sensitivity 61%, specificity 60% on presenting sample. Both intermedin and CGRP were elevated in STEMI patients on a first sample, but only intermedin was significantly elevated; 7.03 pg/ml vs 4.84 pg/ml, p =0.02 and 8.87 pg/ml vs 7.03 pg/ml p = 0.093, respectively. High sensitivity troponin T was significant elevated in the ACS group at b8 h (414.9 vs 17.22, p= 0.006) and at 8–b16 h (3325.27 vs 21.54, p = 0.02). 
Conclusions: Both intermedin and CGRP are detectable in human patients. Levels showa trend to elevation in ACS, with CGRP being significantly raised N8 h after pain onset. The degree of elevation will have limited clinical applicability.

Serum- and HDL3-serum amyloid A and HDL3-LCAT activity are influenced by increased CVD-burden

BACKGROUND: High density lipoproteins (HDL) protect against cardiovascular disease (CVD). However, increased serum amyloid-A (SAA) related inflammation may negate this property. This study investigated if SAA was related to CVD-burden.

METHODS: Subjects referred to the rapid chest pain clinic (n = 240) had atherosclerotic burden assessed by cardiac computerised tomography angiography. Subjects were classified as: no-CVD (n = 106), non-obstructive-CVD, stenosis<50% (n = 58) or moderate/significant-CVD, stenosis ≥50% (n = 76). HDL was subfractionated into HDL2 and HDL3 by rapid-ultracentrifugation. SAA-concentration was measured by ELISA and lecithin cholesterol acyltransferase (LCAT) activity measured by a fluorimetric assay.

RESULTS: We illustrated that serum-SAA and HDL3-SAA-concentration were higher and HDL3-LCAT-activity lower in the moderate/significant-CVD-group, compared to the no-CVD and non-obstructive-CVD-groups (percent differences: serum-SAA, +33% & +30%: HDL3-SAA, +65% and +39%: HDL3-LCAT, -6% & -3%; p < 0.05 for all comparisons). We also identified a positive correlation between serum-SAA and HDL3-SAA (r = 0.698; p < 0.001) and a negative correlation between HDL3-SAA and HDL3-LCAT-activity (r = -0.295; p = 0.003), while CVD-burden positively correlated with serum-SAA (r = 0.150; p < 0.05) and HDL3-SAA (r = 0.252; p < 0.001) and negatively correlated with HDL3-LCAT-activity (r = -0.182; p = 0.006). Additionally, multivariate regression analysis adjusted for age, gender, CRP and serum-SAA illustrated that HDL3-SAA was significantly associated with modifying CVD-risk of moderate/significant CVD-risk (p < 0.05).

CONCLUSION: This study has demonstrated increased SAA-related inflammation in subjects with moderate/significant CVD-burden, which appeared to impact on the antiatherogenic potential of HDL. We suggest that SAA may be a useful biomarker to illustrate increased CVD-burden, although this requires further investigation.

A descriptive study of the usage of spinal manipulative therapy techniques within a randomised clinical trial in acute low back pain

The majority of randomized clinical trials (RCTs) of spinal manipulative therapy have not adequately de?ned the terms ‘mobilization’ and ‘manipulation’, nor distinguished between these terms in reporting the trial interventions. The purpose of this study was to describe the spinal manipulative therapy techniques utilized within a RCT of manipulative therapy (MT; n=80), interferential therapy (IFT; n=80), and a combination of both (CT; n=80) for people with acute low back pain (LBP). Spinal manipulative therapy was de?ned as any ‘mobilization’ (low velocity manual force without a thrust) or ‘manipulation’ (high velocity
thrust) techniques of the spine described by Maitland and Cyriax.
The 16 physiotherapists, all members of the Society of Orthopaedic Medicine, utilized three spinal manipulative therapy patterns in the RCT: Maitland Mobilization (40.4%, n=59), Maitland Mobilization/Cyriax Manipulation (40.4%, n=59) and Cyriax Manipulation (19.1%, n=28). There was a signi?cant difference between the MT and CT groups in their usage of spinal manipulative therapy techniques (w2=9.178; df=2;P=0.01); subjects randomized to the CT group received three times more Cyriax Manipulation (29.2%, n=21/72) than those randomized to the MT group (9.5%, n=7/74; df=1; P=0.003).
The use of mobilization techniques within the trial was comparable with their usage by the general population of physiotherapists in Britain and Ireland for LBP management. However, the usage of manipulation techniques was considerably higher than reported in physiotherapy surveys and may re?ect the postgraduate training of trial therapists.

Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid

Background: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated. Methods: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes. Results: Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings. Conclusion: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.