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High Ankle Sprains in Professional Ice Hockey Players: Prognosis and Correlation Between Magnetic Resonance Imaging Patterns of Injury and Return to Play.
No full textBackground
Hockey players sustain a greater incidence of ankle syndesmosis injuries than other athletes. These injuries have a higher morbidity and more unpredictable recovery than lateral ankle sprains. Magnetic resonance imaging (MRI) has been used to establish the diagnosis but has not been evaluated for its ability to predict return to play.
Hypothesis
We hypothesized that patterns of injury defined on MRI could be used to predict return to play in a cohort of professional hockey players with syndesmosis sprains.
Study Design
Cohort study; Level of evidence, 3.
Methods
A prospectively collected National Hockey League (NHL) database was analyzed from the 2006-2007 to 2011-2012 seasons to assess return to play after an injury. A separate retrospective review of ankle MRI scans from professional hockey players with a documented high ankle sprain sustained between 2007 and 2012 was performed. Injuries were classified on MRI as complete or partial tears of the anterior-inferior tibiofibular ligament (AITFL), posterior-inferior tibiofibular ligament (PITFL), anterior talofibular ligament (ATFL), posterior talofibular ligament (PTFL), calcaneofibular ligament (CFL), and deltoid ligament. Fractures, bone contusions, and osteochondral lesions were also recorded.
Results
A total of 105 NHL athletes sustained high ankle sprains over the 5 seasons studied. Of these athletes, 85 were unable to play and missed a median of 8 games (range, 0-65 games). A retrospective MRI evaluation of 21 scans identified complete AITFL tears in 13 (62%) and high-grade partial tears in 5 (24%) cases. In contrast, the PITFL was partially torn in 9 (43%) and normal in 12 (57%) cases. Bone contusions were seen in 71% of cases and lacked a consistent pattern. The most commonly associated ligamentous injury was of the ATFL, which was injured in 52% of cases (11/21; 3 complete and 8 partial). There was no difference in the mean number of days lost when players were stratified by patterns of injury (incomplete/complete AITFL tear ± additional ligamentous injury, bone contusion, syndesmosis width).
Conclusion
A high ankle sprain resulted in significant variations in time of recovery among professional hockey players. A torn AITFL and bone bruising were the most common patterns of injury. Although MRI can be used to confirm the diagnosis of a syndesmosis injury, it did not predict return to play in this population
Phosphatidylinositol 3-kinase delta pathway: a novel therapeutic target for Sjögren's syndrome.
No full textBACKGROUND
The phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration and has been successfully targeted in B-cell malignancies. Primary Sjögren's syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration and B-cell hyperactivation which results in systemic manifestations, autoantibody production and loss of glandular function. Given the central role of B cells in pSS pathogenesis, we investigated PI3Kδ pathway activation in pSS and the functional consequences of blocking PI3Kδ in a murine model of focal sialoadenitis that mimics some features of pSS.
METHODS AND RESULTS
Target validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands. In vivo blockade of PI3Kδ activity with seletalisib, a PI3Kδ-selective inhibitor, in a murine model of focal sialoadenitis decreased accumulation of lymphocytes and plasma cells within the glands of treated mice in the prophylactic and therapeutic regimes. Additionally, production of lymphoid chemokines and cytokines associated with ectopic lymphoneogenesis and, remarkably, saliva flow and autoantibody production, were significantly affected by treatment with seletalisib.
CONCLUSION
These data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition
Clinical and laboratory features of seventy-eight UK patients with Good's syndrome (thymoma and hypogammaglobulinaemia).
No full textGood's syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were female, were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and nine (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were significantly lower in these patients with malignant thymoma. Seventy-four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren's syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good's syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinaemia
Home parenteral nutrition in patients receiving palliative care: a curriculum-based review.
No full textDifficulty with maintaining nutritional intake is common in patients with cancer. European guidance suggests that wherever possible nutritional support should first be provided by the oral or enteral route. Where this is not possible, for example, in malignant small bowel obstruction, parenteral nutrition (PN) may be considered. In palliative care, it is generally accepted that the significant risks and burdens of PN outweigh the potential benefits in patients with an expected survival <2 months. Determining prognosis is crucial when helping patients to make decisions regarding appropriate care pathways; however, this remains challenging. An overview of clinical issues and prognostic indicators related to selecting patients appropriately for palliative PN is given to cover the relevant advanced competencies of the 2010 Gastroenterology Curriculum. The organisation of Home Parenteral Nutrition (HPN) services in England is described including the associated risks and burdens of HPN in the palliative patient
Interobserver variability in comfort scores for screening colonoscopy.
No full textObjective
To investigate the agreement in comfort scores between patients, endoscopist and specialist screening practitioner (SSP) for colonoscopy, and which factors influence comfort.
Design
Prospective observational study.
Setting
Single-centre UK Bowel Cancer Screening Program colonoscopy service from April 2017 to March 2018.
Patients
498 patients undergoing bowel cancer screening colonoscopy, with median age of 68 (IQR 64-71). 320 (64.3%) were men.
Intervention
All patients underwent screening colonoscopy.
Main outcome measure
Comfort scores on a validated 1 (best) to 5 (worst) ordinal scale were assigned for each colonoscopy by the patient, endoscopist and SSP. Inter-rater agreement of discomfort scores between endoscopist, patient and SSP was investigated using Cohen's Kappa statistic. Multivariate ordinal logistic regression was used to investigate the effects of patient and colonoscopy factors on comfort scores.
Results
SSPs had superior comfort score agreement with patients (0.638; 'moderate agreement') than endoscopists had with the same patients (0.526; 'weak agreement'). Male patients reported lower scores than female patients (OR 0.483, OR 0.499 [95% CI 0.344 to 0.723]; p<0.001). Endoscopists reported lower scores when there was better bowel prep (OR 0.512 [95% CI 0.279 to 0.938]; p=0.030). Agreement was worse at higher levels of discomfort.
Conclusion
There is variability in perceived comfort levels between healthcare providers and patients during screening colonoscopy, which is greater at worse levels of discomfort. Endoscopists who undertake screening colonoscopies may wish to consider both patient and healthcare provider comfort scores in order to improve patient experience while ensuring optimal quality assurance
A Practical Guide to Assess the Reproducibility of Echocardiographic Measurements.
No full textEchocardiography plays an essential role in the diagnosis and assessment of cardiovascular disease. Measurements derived from echocardiography are also used to determine the severity of disease, its progression over time, and to aid in the choice of optimal therapy. It is therefore clinically important that echocardiographic measurements be reproducible, repeatable, and reliable. There are a variety of statistical tests available to assess these parameters, and in this article the authors summarize those available for use by echocardiographers to improve their clinical practice. Correlation coefficients, linear regression, Bland-Altman plots, and the coefficient of variation are explored, along with their limitations. The authors also provide an online tool for the easy calculation of these statistics in the clinical environment (www.birmingham.ac.uk/echo). Quantifying and enhancing the reproducibility of echocardiography has important potential to improve the value of echocardiography as the basis for good clinical decision-making
Development of the FAST-M maternal sepsis care bundle for use in low resource settings: a modified Delphi process.
No full textOBJECTIVE
To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings.
DESIGN
Modified Delphi process.
SETTING
Participants from 34 countries.
POPULATION
Healthcare practitioners working in low resource settings (n=143; 34 countries), members of an expert panel (n=11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group.
METHODS
We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in-person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering its use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts.
MAIN OUTCOME MEASURE
Consensus on bundle items.
RESULTS
Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: i) Fluids, ii) Antibiotics, iii) Source identification and control, iv) Transfer (to appropriate higher-level care) and v) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym "FAST-M".
CONCLUSION
A clinically relevant maternal sepsis care bundle for low resource settings has been developed by international consensus
Ethnic differences in inflammatory bowel disease: Results from the United Kingdom inception cohort epidemiology study.
No full textBACKGROUND
The current epidemiology of inflammatory bowel disease (IBD) in the multi-ethnic United Kingdom is unknown. The last incidence study in the United Kingdom was carried out over 20 years ago.
AIM
To describe the incidence and phenotype of IBD and distribution within ethnic groups.
METHODS
Adult patients (> 16 years) with newly diagnosed IBD (fulfilling Copenhagen diagnostic criteria) were prospectively recruited over one year in 5 urban catchment areas with high South Asian population. Patient demographics, ethnic codes, disease phenotype (Montreal classification), disease activity and treatment within 3 months of diagnosis were recorded onto the Epicom database.
RESULTS
Across a population of 2271406 adults, 339 adult patients were diagnosed with IBD over one year: 218 with ulcerative colitis (UC, 64.3%), 115 with Crohn's disease (CD, 33.9%) and 6 with IBD unclassified (1.8%). The crude incidence of IBD, UC and CD was 17.0/100000, 11.3/100000 and 5.3/100000 respectively. The age adjusted incidence of IBD and UC were significantly higher in the Indian group (25.2/100000 and 20.5/100000) compared to White European (14.9/100000, = 0.009 and 8.2/100000, < 0.001) and Pakistani groups (14.9/100000, = 0.001 and 11.2/100000, = 0.007). The Indian group were significantly more likely to have extensive disease than White Europeans (52.7% 41.7%, = 0.031). There was no significant difference in time to diagnosis, disease activity and treatment.
CONCLUSION
This is the only prospective study to report the incidence of IBD in an ethnically diverse United Kingdom population. The Indian ethnic group showed the highest age-adjusted incidence of UC (20.5/100000). Further studies on dietary, microbial and metabolic factors that might explain these findings in UC are underway
Clinical significance of 2-alkyl-4-quinolone quorum-sensing signal molecules for long-term outcomes in adults with cystic fibrosis.
No full textis an important respiratory pathogen in cystic fibrosis (CF), which is associated with an accelerated decline in lung function, frequent pulmonary exacerbations and increased mortality. produces intercellular signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence-factor production and biofilm formation in the CF airways. Studies have shown that AQs are detectable in the sputum and plasma of adults with CF and chronic pulmonary . We tested the hypothesis that the presence of six AQs in plasma or sputum obtained from adults with CF was associated with long-term adverse clinical outcomes. We analysed clinical data over an 8 year follow period for 90 people with CF who had previously provided samples for AQ analysis at clinical stability. The primary outcome was all cause mortality or lung transplantation. Secondary outcomes were the rate of lung-function decline and the number of intravenous (IV) antibiotic days for pulmonary exacerbations. There was no statistical association between the presence of any of the six measured AQs and the primary outcomes or the secondary outcome of decline in lung function. One of the six AQs was associated with IV antibiotic usage. The presence of 2-nonyl-3-hydroxy-4(1 h)-quinolone (C9-PQS) in sputum was associated with an increase in the number of IV antibiotic days in the follow-up period (Mann-Whitney; =0.011). Further investigation to confirm the hypothesis that C9-PQS may be associated with increased antibiotic usage for pulmonary exacerbations is warranted as AQ-dependent signalling is a potential future target for anti-virulence therapies
Fluocinolone Acetonide Intravitreal Implant for Treating Recurrent Non-infectious Uveitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.
No full textThe National Institute for Health and Care Excellence (NICE) invited Alimera Sciences, the company manufacturing fluocinolone acetonide intravitreal implant (FAc) 0.19 mg (tradename ILUVIEN), to submit evidence on the clinical and cost-effectiveness of FAc for treating recurrent non-infectious uveitis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre + , was commissioned to act as the independent Evidence Review Group (ERG). This paper contains a summary of the clinical and cost-effectiveness evidence submitted by the company, the ERG's critique on the submitted evidence, and the guidance issued by the NICE Appraisal Committee (AC). The company submission (CS) was mainly informed by the PSV-FAI-001 trial in which FAc was compared with (limited) current practice [(L)CP], which was not considered to be representative of UK clinical practice by the ERG. There was no comparison of FAc to any treatment listed in the final scope, and especially to the dexamethasone intravitreal implant (dexamethasone), which was considered to be a relevant comparator by the AC. The primary outcome of the PSV-FAI-001 was recurrence of uveitis in the treated eye. Most of the events for the primary outcome were imputed during the PSV-FAI-001 trial, which probably led to an overestimation of the number of recurrences of disease, and a biased estimate of the relative effectiveness of FAc versus (L)CP. Finally, the place of FAc in the treatment pathway was not clearly defined by the company. Substantial uncertainty surrounded the cost-effectiveness results due to the shortcomings of the clinical evidence. Additionally, the quality of life of patients was not measured during the PSV-FAI-001 trial and long-term effectiveness data of FAc were lacking. The ERG adjusted several issues identified in the CS and added dexamethasone as a comparator in the decision analytic model. The ERG presented multiple analyses as base-cases because several elements of the assessment remained uncertain. The fully incremental ERG results ranged from dexamethasone (extendedly) dominating FAc (when assuming a hazard ratio of 1 or 0.7 for dexamethasone versus FAc) to an incremental cost-effectiveness ratio (ICER) of £30,153 per quality-adjusted life-year (QALY) gained for FAc versus (L)CP [when assuming a hazard ratio of 0.456 for dexamethasone versus (L)CP]. The ICER of FAc versus (L)CP ranged from £12,325 to £30,153 per QALY gained. After a second AC meeting where alternative company scenarios comparing FAc with dexamethasone were considered by the AC, the AC concluded that "the results of the company's analyses ranged from the fluocinolone acetonide implant being dominant (that is, it was more effective and costs less), to an ICER of £29,461 per QALY gained, and most of the ICERs were below £20,000 per QALY gained". Therefore, the AC recommended FAc as a cost-effective use of National Health Service (NHS) resources for treating recurrent non-infectious uveitis affecting the posterior segment of the eye in the final TA590 guidance (published July 2019)