Space-time clustering analyses of childhood acute lymphoblastic leukaemia by immunophenotype

Space-time clustering analyses of acute lymphoblastic leukaemia in children, by immunophenotype, were carried out using a population-based registry. Significant evidence was found of space-time clustering for cases of the precursor B-cell sub-type, in the childhood peak, based on time and location at birth

An infectious aetiology for childhood brain tumours? Evidence from space–time clustering and seasonality analyses

To investigate whether infections or other environmental exposures may be involved in the aetiology of childhood central nervous system tumours, we have analysed for space–time clustering and seasonality using population-based data from the North West of England for the period 1954 to 1998. Knox tests for space–time interactions between cases were applied with fixed thresholds of close in space, <5 km, and close in time, <1 year apart. Addresses at birth and diagnosis were used. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. Tests for heterogeneity and Edwards' test for sinusoidal variation were applied to examine changes of incidence with month of birth or diagnosis. There was strong evidence of space–time clustering, particularly involving cases of astrocytoma and ependymoma. Analyses of seasonal variation showed excesses of cases born in the late Autumn or Winter. Results are consistent with a role for infections in a proportion of cases from these diagnostic groups. Further studies are needed to identify putative infectious agents

Image-guided versus blind corticosteroid injections in adults with shoulder pain: A systematic review

<p>Abstract</p> <p>Background</p> <p>Corticosteroid injections can be performed blind (landmark-guided) or with image guidance, and this may account for variable clinical outcomes. The objective of this study was to assess the effectiveness and safety of image-guided versus blind corticosteroid injections in improving pain and function among adults with shoulder pain.</p> <p>Methods</p> <p>MEDLINE, the Cochrane Controlled Trials Register and EMBASE were searched to May 2010. Additional studies were identified by searching bibliographies of shortlisted articles. Search items included blind, landmark, anatomical, clinical exam, image-guided, ultrasound, fluoroscopy, steroid injection, frozen shoulder, random allocation, randomized controlled trial (RCT) and clinical trial.</p> <p>Randomized controlled studies comparing image-guided versus blind (landmark-guided) corticosteroid shoulder injections that examined pain, function and/or adverse events were included. Independent extraction was done by two authors using a form with pre-specified data fields, including risk of bias appraisal. Conflicts were resolved by discussion. The decision to pool data was based on assessment of clinical design homogeneity. When warranted, studies were pooled under a random-effects model.</p> <p>Results</p> <p>Two RCTs for pain, function and adverse events (n = 101) met eligibility criteria. No serious threats to validity were found. Both trials compared ultrasound-guided versus landmark-guided injections and were judged similar in clinical design. Low to moderate heterogeneity was observed: shoulder pain I²= 60%, function I²= 22%. A meta-analysis demonstrated greater improvement with ultrasound-guided injections at 6 weeks after injection in both pain (mean difference = 2.23 [95% CI: 1.27, 3.18]), as assessed with a 0 to 10 visual analogue scale, and shoulder function (standardised mean difference = 1.09 [95% CI: 0.61, 1.57]) as assessed with shoulder function scores. Although more adverse events (all mild) were reported with landmark-guided injections, the difference was not statistically significant (risk ratio = 0.20 [95% CI: 0.04, 1.13]).</p> <p>This review was only based on two moderate-sized trials. Blinding of patients was not performed in both trials, causing some risk of bias in outcome assessment since primary endpoints were wholly or partially patient-reported.</p> <p>Conclusion</p> <p>There is a paucity of RCTs on image-guided versus landmark-guided corticosteroid shoulder injections examining pain, function and adverse events. In this review, patients who underwent image-guided (ultrasound) injections had statistically significant greater improvement in shoulder pain and function at 6 weeks after injection. Image-guided (ultrasound) corticosteroid injections potentially offer a significantly greater clinical improvement over blind (landmark-guided) injections in adults with shoulder pain. However, this apparent benefit requires confirmation from further studies (adequately-powered and well-executed RCTs).</p

Do quantitative and qualitative shear wave elastography have a role in evaluating musculoskeletal soft tissue masses?

Objectives: To determine if quantitative and qualitative shear wave elastography have roles in evaluating musculoskeletal masses. Methods: 105 consecutive patients, prospectively referred for biopsy within a specialist sarcoma centre, underwent B-mode, quantitative (m/s) and qualitative (colour map) shear wave elastography. Reference was histology from subsequent biopsy or excision where possible. Statistical modelling was performed to test elastography data and/or B-mode imaging in predicting malignancy. Results: Of 105 masses, 39 were malignant and 6 had no histology but benign characteristics at 12 months. Radiologist agreement for B-mode and elastography was moderate to excellent Kw 0.52-0.64; PABAKw 0.85-0.90). B-Mode imaging had 78.8% specificity, 76.9% sensitivity for malignancy. Quantitatively, adjusting for age, B-mode and lesion volume there was no statistically significant association between longitudinal velocity and malignancy (OR [95% CI] 0.40[0.10, 1.60], p=0.193), but some evidence that higher transverse velocity was associated with decreased odds of malignancy (0.28[0.06, 1.28], p=0.101). Qualitatively malignant masses tended to be towards the blue spectrum (lower velocities); 39.5% (17/43) of predominantly blue masses were malignant, compared to 14.3% (1/7) of red lesions. Conclusions: Quantitatively and qualitatively there is no statistically significant association between shear wave velocity and malignancy. There is no clear additional role to B-mode imaging currently. Key Points: • Correlation between shear wave velocity and soft tissue malignancy was statistically insignificant• B-mode ultrasound is 76.9 % sensitive and 78.8 % specific• Statistical models show elastography does not significantly add to lesion assessmen

Is tibial tuberosity-trochlear groove distance an appropriate measure for the identification of knees with patellar instability?

PURPOSE - Tibial tuberosity-trochlear groove distance (TT-TG) has been regarded as a useful tool for establishing therapeutic choices for patellar instability. Recently, it has been shown that TT-TG negatively correlated with the quadriceps angle, suggesting that if used individually, neither provide a valid measure of instability. This study aimed to compare TT-TG distance between both knees in patients with unilateral instability to assess whether this measurement is a decisive element in the management decisions for patellar instability. METHODS - Sixty-two patients (18 male and 44 female), reporting to a specialist patella clinic for recurrent unilateral patellar instability, were included in the study. Patients underwent bilateral long leg computed tomography scan to determine TT-TG distance in both knees. Tibial TT-TG in symptomatic and asymptomatic knees in the same individual was compared statistically. RESULTS - Mean TT-TG distance in the symptomatic knee was 16.9 (±4.9) mm, compared to 15.6 (±5.6) mm in the asymptomatic knee. Tibial TT-TG was not significantly different between stable and unstable knees (n.s.). CONCLUSIONS - The lack of difference in TT-TG distance between stable and unstable knees suggests that TT-TG distance alone may not be a decisive element in establishing therapeutic choices for patellar instability. It should, therefore, be interpreted with caution during clinical evaluations. LEVEL OF EVIDENCE: II

Is tibial tuberosity-trochlear groove distance an appropriate measure for the identification of knees with patellar instability?

PURPOSE - Tibial tuberosity-trochlear groove distance (TT-TG) has been regarded as a useful tool for establishing therapeutic choices for patellar instability. Recently, it has been shown that TT-TG negatively correlated with the quadriceps angle, suggesting that if used individually, neither provide a valid measure of instability. This study aimed to compare TT-TG distance between both knees in patients with unilateral instability to assess whether this measurement is a decisive element in the management decisions for patellar instability. METHODS - Sixty-two patients (18 male and 44 female), reporting to a specialist patella clinic for recurrent unilateral patellar instability, were included in the study. Patients underwent bilateral long leg computed tomography scan to determine TT-TG distance in both knees. Tibial TT-TG in symptomatic and asymptomatic knees in the same individual was compared statistically. RESULTS - Mean TT-TG distance in the symptomatic knee was 16.9 (±4.9) mm, compared to 15.6 (±5.6) mm in the asymptomatic knee. Tibial TT-TG was not significantly different between stable and unstable knees (n.s.). CONCLUSIONS - The lack of difference in TT-TG distance between stable and unstable knees suggests that TT-TG distance alone may not be a decisive element in establishing therapeutic choices for patellar instability. It should, therefore, be interpreted with caution during clinical evaluations. LEVEL OF EVIDENCE: II

Activation of Estrogen Receptor-α by E2 or EGF Induces Temporally Distinct Patterns of Large-Scale Chromatin Modification and mRNA Transcription

Estrogen receptor-α (ER) transcription function is regulated in a ligand-dependent (e.g., estradiol, E2) or ligand-independent (e.g., growth factors) manner. Our laboratory seeks to understand these two modes of action. Using a cell line that contains a visible prolactin enhancer/promoter array (PRL-HeLa) regulated by ER, we analyzed ER response to E2 and EGF by quantifying image-based results. Data show differential recruitment of GFP-ER to the array, with the AF1 domain playing a vital role in EGF-mediated responsiveness. Temporal analyses of large-scale chromatin dynamics, and accumulation of array-localized reporter mRNA over 24 hours showed that the EGF response consists of a single pulse of reporter mRNA accumulation concomitant with transient increase in array decondensation. Estradiol induced a novel cyclical pattern of mRNA accumulation with a sustained increase in array decondensation. Collectively, our work shows that there is a stimuli-specific pattern of large-scale chromatin modification and transcript levels by ER

A prospective study of shoulder pain in primary care: Prevalence of imaged pathology and response to guided diagnostic blocks

<p>Abstract</p> <p>Background</p> <p>The prevalence of imaged pathology in primary care has received little attention and the relevance of identified pathology to symptoms remains unclear. This paper reports the prevalence of imaged pathology and the association between pathology and response to diagnostic blocks into the subacromial bursa (SAB), acromioclavicular joint (ACJ) and glenohumeral joint (GHJ).</p> <p>Methods</p> <p>Consecutive patients with shoulder pain recruited from primary care underwent standardised x-ray, diagnostic ultrasound scan and diagnostic injections of local anaesthetic into the SAB and ACJ. Subjects who reported less than 80% reduction in pain following either of these injections were referred for a magnetic resonance arthrogram (MRA) and GHJ diagnostic block. Differences in proportions of positive and negative imaging findings in the anaesthetic response groups were assessed using Fishers test and odds ratios were calculated a for positive anaesthetic response (PAR) to diagnostic blocks.</p> <p>Results</p> <p>In the 208 subjects recruited, the rotator cuff and SAB displayed the highest prevalence of pathology on both ultrasound (50% and 31% respectively) and MRA (65% and 76% respectively). The prevalence of PAR following SAB injection was 34% and ACJ injection 14%. Of the 59% reporting a negative anaesthetic response (NAR) for both of these injections, 16% demonstrated a PAR to GHJ injection. A full thickness tear of supraspinatus on ultrasound was associated with PAR to SAB injection (OR 5.02; <it>p </it>< 0.05). Ultrasound evidence of a biceps tendon sheath effusion (OR 8.0; <it>p </it>< 0.01) and an intact rotator cuff (OR 1.3; <it>p </it>< 0.05) were associated with PAR to GHJ injection. No imaging findings were strongly associated with PAR to ACJ injection (<it>p </it>≤ 0.05).</p> <p>Conclusions</p> <p>Rotator cuff and SAB pathology were the most common findings on ultrasound and MRA. Evidence of a full thickness supraspinatus tear was associated with symptoms arising from the subacromial region, and a biceps tendon sheath effusion and an intact rotator cuff were associated with an intra-articular GHJ pain source. When combined with clinical information, these results may help guide diagnostic decision making in primary care.</p