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1.  New insight on the Xq28 association with systemic sclerosis 
Annals of the rheumatic diseases  2013;72(12):10.1136/annrheumdis-2012-202742.
Objective
To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2).
Methods
We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc.
Results
IRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (PFDR=4.12×10−3, OR=1.27, 95% CI 1.09 to 1.47, and PFDR=5.26×10−4, OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (PFDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF− (p=0.025, OR=1.26, 95% CI 1.03 to 1.55).
Conclusions
Our data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease.
doi:10.1136/annrheumdis-2012-202742
PMCID: PMC3818491  PMID: 23444193
2.  The Systemic Lupus Erythematosus IRF5 Risk Haplotype Is Associated with Systemic Sclerosis 
PLoS ONE  2013;8(1):e54419.
Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10−8, OR  = 1.22, CI 95%  = 1.14–1.30; rs2004640: P  = 4.60×10−7, OR  = 0.84, CI 95%  = 0.78–0.90; rs10488631: P  = 7.53×10−20, OR  = 1.63, CI 95%  = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10−22, OR  = 1.75, CI 95%  = 1.56–1.97) better explained the observed association (likelihood P-value  = 1.48×10−4), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.
doi:10.1371/journal.pone.0054419
PMCID: PMC3553151  PMID: 23372721
3.  Mortality as an indicator of patient safety in orthopaedics: lessons from qualitative analysis of a database of medical errors 
Background
Orthopaedic surgery is a high-risk specialty in which errors will undoubtedly occur. Patient safety incidents can yield valuable information to generate solutions and prevent future cases of avoidable harm. The aim of this study was to understand the causative factors leading to all unnecessary deaths in orthopaedics and trauma surgery reported to the National Patient Safety Agency (NPSA) over a four-year period (2005–2009), using a qualitative approach.
Methods
Reports made to the NPSA are categorised and stored in the database as free-text data. A search was undertaken to identify the cases of all-cause mortality in orthopaedic and trauma surgery, and the free-text elements were used for thematic analysis. Descriptive statistics were calculated based on the incidents reported. This included presenting the number of times categories of incidents had the same or similar response. Superordinate and subordinate categories were created.
Results
A total of 257 incident reports were analysed. Four main thematic categories emerged. These were: (1) stages of the surgical journey – 118/191 (62%) of deaths occurred in the post-operative phase; (2) causes of patient deaths – 32% were related to severe infections; (3) reported quality of medical interventions – 65% of patients experienced minimal or delayed treatment; (4) skills of healthcare professionals – 44% of deaths had a failure in non-technical skills.
Conclusions
Most complications in orthopaedic surgery can be dealt with adequately, provided they are anticipated and that risk-reduction strategies are instituted. Surgeons take pride in the precision of operative techniques; perhaps it is time to enshrine the multimodal tools available to ensure safer patient care.
doi:10.1186/1471-2474-13-93
PMCID: PMC3416713  PMID: 22682470
Patient safety; Errors; Orthopaedics; Trauma surgery; Quality improvement
4.  Correction: Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy 
Gorlova, Olga | Martin, Jose-Ezequiel | Rueda, Blanca | Koeleman, Bobby P. C. | Ying, Jun | Teruel, Maria | Diaz-Gallo, Lina-Marcela | Broen, Jasper C. | Vonk, Madelon C. | Simeon, Carmen P. | Alizadeh, Behrooz Z. | Coenen, Marieke J. H. | Voskuyl, Alexandre E. | Schuerwegh, Annemie J. | van Riel, Piet L. C. M. | Vanthuyne, Marie | van 't Slot, Ruben | Italiaander, Annet | Ophoff, Roel A. | Hunzelmann, Nicolas | Fonollosa, Vicente | Ortego-Centeno, Norberto | González-Gay, Miguel A. | García-Hernández, Francisco J. | González-Escribano, María F. | Airo, Paolo | van Laar, Jacob | Worthington, Jane | Hesselstrand, Roger | Smith, Vanessa | de Keyser, Filip | Houssiau, Fredric | Chee, Meng May | Madhok, Rajan | Shiels, Paul G. | Westhovens, Rene | Kreuter, Alexander | de Baere, Elfride | Witte, Torsten | Padyukov, Leonid | Nordin, Annika | Scorza, Raffaella | Lunardi, Claudio | Lie, Benedicte A. | Hoffmann-Vold, Anna-Maria | Palm, Øyvind | García de la Peña, Paloma | Carreira, Patricia | Varga, John | Hinchcliff, Monique | Lee, Annette T. | Gourh, Pravitt | Amos, Christopher I. | Wigley, Frederick M. | Hummers, Laura K. | Nelson, J. Lee | Riemekasten, Gabriella | Herrick, Ariane | Beretta, Lorenzo | Fonseca, Carmen | Denton, Christopher P. | Gregersen, Peter K. | Agarwal, Sandeep | Assassi, Shervin | Tan, Filemon K. | Arnett, Frank C. | Radstake, Timothy R. D. J. | Mayes, Maureen D. | Martin, Javier
PLoS Genetics  2011;7(8):10.1371/annotation/3aeebb2e-64e5-4548-8d65-1f2d5dfeb073.
doi:10.1371/annotation/3aeebb2e-64e5-4548-8d65-1f2d5dfeb073
PMCID: PMC3166261
5.  Correction: Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy 
Gorlova, Olga | Martin, Jose-Ezequiel | Rueda, Blanca | Koeleman, Bobby P. C. | Ying, Jun | Teruel, Maria | Diaz-Gallo, Lina-Marcela | Broen, Jasper C. | Vonk, Madelon C. | Simeon, Carmen P. | Alizadeh, Behrooz Z. | Coenen, Marieke J. H. | Voskuyl, Alexandre E. | Schuerwegh, Annemie J. | van Riel, Piet L. C. M. | Vanthuyne, Marie | van 't Slot, Ruben | Italiaander, Annet | Ophoff, Roel A. | Hunzelmann, Nicolas | Fonollosa, Vicente | Ortego-Centeno, Norberto | González-Gay, Miguel A. | García-Hernández, Francisco J. | González-Escribano, María F. | Airo, Paolo | van Laar, Jacob | Worthington, Jane | Hesselstrand, Roger | Smith, Vanessa | de Keyser, Filip | Houssiau, Fredric | Chee, Meng May | Madhok, Rajan | Shiels, Paul G. | Westhovens, Rene | Kreuter, Alexander | de Baere, Elfride | Witte, Torsten | Padyukov, Leonid | Nordin, Annika | Scorza, Raffaella | Lunardi, Claudio | Lie, Benedicte A. | Hoffmann-Vold, Anna-Maria | Palm, Øyvind | García de la Peña, Paloma | Carreira, Patricia | Varga, John | Hinchcliff, Monique | Lee, Annette T. | Gourh, Pravitt | Amos, Christopher I. | Wigley, Frederick M. | Hummers, Laura K. | Nelson, J. Lee | Riemekasten, Gabriella | Herrick, Ariane | Beretta, Lorenzo | Fonseca, Carmen | Denton, Christopher P. | Gregersen, Peter K. | Agarwal, Sandeep | Assassi, Shervin | Tan, Filemon K. | Arnett, Frank C. | Radstake, Timothy R. D. J. | Mayes, Maureen D. | Martin, Javier
PLoS Genetics  2011;7(8):10.1371/annotation/7a52649c-0942-4bd8-a5d3-3cdacca03cd8.
doi:10.1371/annotation/7a52649c-0942-4bd8-a5d3-3cdacca03cd8
PMCID: PMC3166262
6.  Systemic lupus erythematosus 
Clinical Evidence  2009;2009:1123.
Introduction
Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies widely worldwide, ranging from about 1 in 3500 women (regardless of race) in the UK, to 1 in 1000 women in China, to 1 in 250 African-American women in the USA.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments on joint symptoms (arthralgia/arthritis) and other non-organ-threatening symptoms (such as serositis and fatigue) in people with systemic lupus erythematosus? What are the effects of interventions for cutaneous involvement in people with systemic lupus erythematosus? What are the effects of treatments in people with proliferative lupus nephritis (WHO grades 3–5)? What are the effects of treatments for neuropsychiatric involvement in people with systemic lupus nephritis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 11 systematic reviews or RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acitretin; antipsychotic drugs; chloroquine; combination corticosteroids plus immunosuppressants; corticosteroids; hydroxychloroquine; intravenous immunoglobulin; methotrexate; non-steroidal anti-inflammatory drugs (NSAIDs); plasmapheresis; and sunblock.
Key Points
Systemic lupus erythematosus (SLE) is a chronic, multi-system, inflammatory connective tissue disorder of unknown cause that can involve joints, kidneys, serous surfaces, skin, and vessel walls. It occurs predominantly in young women, but also in children. The course of SLE is highly variable, involving non-organ-threatening symptoms (such as arthritis, arthralgia, and rashes), organ-threatening symptoms (such as lupus nephritis), and neuropsychiatric disorders (such as seizures and cognitive dysfunction).
The prevalence of SLE varies widely worldwide, ranging from about 1 in 3500 women (regardless of race) in the UK, to 1 in 1000 women in China, to 1 in 250 African-American women in the USA.
There is consensus that NSAIDs and corticosteroids are useful in relieving pain caused by arthralgia/arthritis, and pleuritis and pericarditis associated with SLE. We found no evidence that the well-documented adverse effects of NSAIDs differ in people with SLE. There is also consensus that corticosteroids and sunscreens are effective in reducing cutaneous manifestations of SLE.
Hydroxychloroquine or chloroquine are likely to be effective in reducing arthritis, pleuritis, and pericarditis. They may also improve cutaneous symptoms. Methotrexate may also be effective for both joint and cutaneous symptoms, but is associated with adverse effects.
Combining immunosuppressants plus corticosteroids may be more effective than corticosteroids alone in people with lupus nephritis, but with an increase in adverse effects. We don't know how corticosteroids alone compare with immunosuppressants alone in people with proliferative lupus nephritis.
We don't know whether corticosteroids, immunosuppressants, plasmapheresis, or intravenous immunoglobulin are effective in people with neuropsychiatric symptoms of lupus. Most people with neuropsychiatric lupus and psychotic symptoms will be offered antipsychotic drugs to control symptoms unless there are contraindications, despite the lack of RCTs assessing their effectiveness.
PMCID: PMC2907829  PMID: 21696649
7.  Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy 
Gorlova, Olga | Martin, Jose-Ezequiel | Rueda, Blanca | Koeleman, Bobby P. C. | Ying, Jun | Teruel, Maria | Diaz-Gallo, Lina-Marcela | Broen, Jasper C. | Vonk, Madelon C. | Simeon, Carmen P. | Alizadeh, Behrooz Z. | Coenen, Marieke J. H. | Voskuyl, Alexandre E. | Schuerwegh, Annemie J. | van Riel, Piet L. C. M. | Vanthuyne, Marie | van 't Slot, Ruben | Italiaander, Annet | Ophoff, Roel A. | Hunzelmann, Nicolas | Fonollosa, Vicente | Ortego-Centeno, Norberto | González-Gay, Miguel A. | García-Hernández, Francisco J. | González-Escribano, María F. | Airo, Paolo | van Laar, Jacob | Worthington, Jane | Hesselstrand, Roger | Smith, Vanessa | de Keyser, Filip | Houssiau, Fredric | Chee, Meng May | Madhok, Rajan | Shiels, Paul G. | Westhovens, Rene | Kreuter, Alexander | de Baere, Elfride | Witte, Torsten | Padyukov, Leonid | Nordin, Annika | Scorza, Raffaella | Lunardi, Claudio | Lie, Benedicte A. | Hoffmann-Vold, Anna-Maria | Palm, Øyvind | García de la Peña, Paloma | Carreira, Patricia | Varga, John | Hinchcliff, Monique | Lee, Annette T. | Gourh, Pravitt | Amos, Christopher I. | Wigley, Frederick M. | Hummers, Laura K. | Hummers, J. | Nelson, J. Lee | Riemekasten, Gabriella | Herrick, Ariane | Beretta, Lorenzo | Fonseca, Carmen | Denton, Christopher P. | Gregersen, Peter K. | Agarwal, Sandeep | Assassi, Shervin | Tan, Filemon K. | Arnett, Frank C. | Radstake, Timothy R. D. J. | Mayes, Maureen D. | Martin, Javier
PLoS Genetics  2011;7(7):e1002178.
The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10−12, OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 × 10−6, OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39×10−7, OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10−61, OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57×10−76, OR = 8.84), and in NOTCH4 with ACA P = 8.84×10−21, OR = 0.55) and ATA (P = 1.14×10−8, OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
Author Summary
Scleroderma or systemic sclerosis is a complex autoimmune disease affecting one individual of every 100,000 in Caucasian populations. Even though current genetic studies have led to better understanding of the pathogenesis of the disease, much remains unknown. Scleroderma is a heterogeneous disease, which can be subdivided according to different criteria, such as the involvement of organs and the presence of specific autoantibodies. Such subgroups present more homogeneous genetic groups, and some genetic associations with these manifestations have already been described. Through reanalysis of a genome-wide association study data, we identify three novel genes containing genetic variations which predispose to subphenotypes of the disease (IRF8, GRB10, and SOX5). Also, we better characterize the patterns of associated loci found in the HLA region. Together, our findings lead to a better understanding of the genetic component of scleroderma.
doi:10.1371/journal.pgen.1002178
PMCID: PMC3136437  PMID: 21779181
8.  Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double‐blind placebo‐controlled MASCOT study 
Annals of the Rheumatic Diseases  2006;66(2):235-241.
Background
Optimal use of disease‐modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies.
Aim
To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP.
Methods
A randomised controlled study of step‐up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) ⩾2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS.
Results
At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy.
Conclusions
In this “true‐to‐life” study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies.
doi:10.1136/ard.2006.057133
PMCID: PMC1798490  PMID: 16926184
9.  Protocol for the ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation) trial: a pragmatic multi-centre randomised controlled trial of surgical versus non-surgical treatment for proximal fracture of the humerus in adults 
Background
Proximal humeral fractures, which occur mainly in older adults, account for approximately 4 to 5% of all fractures. Approximately 40% of these fractures are displaced fractures involving the surgical neck. Management of this group of fractures is often challenging and the outcome is frequently unsatisfactory. In particular it is not clear whether surgery gives better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform this decision.
Methods/Design
We aim to undertake a pragmatic UK-based multi-centre randomised controlled trial evaluating the effectiveness and cost-effectiveness of surgical versus standard non-surgical treatment for adults with an acute closed displaced fracture of the proximal humerus with involvement of the surgical neck. The choice of surgical intervention is left to the surgeon, who must use techniques that they are fully experienced with. This will avoid 'learning curve' problems. We will promote good standards of non-surgical care, similarly insisting on care-provider competence, and emphasize the need for comparable provision of rehabilitation for both groups of patients.
We aim to recruit 250 patients from a minimum of 18 NHS trauma centres throughout the UK. These patients will be followed-up for 2 years. The primary outcome is the Oxford Shoulder Score, which will be collected via questionnaires completed by the trial participants at 6, 12 and 24 months. This is a 12-item condition-specific questionnaire providing a total score based on the person's subjective assessment of pain and activities of daily living impairment. We will also collect data for other outcomes, including general health measures and complications, and for an economic evaluation. Additionally, we plan a systematic collection of reasons for non-inclusion of eligible patients who were not recruited into the trial, and their baseline characteristics, treatment preferences and intended treatment.
Discussion
This article presents the protocol for a multi-centre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.
Trial Registration
Current Controlled Trials ISRCTN50850043
doi:10.1186/1471-2474-10-140
PMCID: PMC2780379  PMID: 19917097
10.  The Cochrane Collaboration: A leading role in producing reliable evidence to inform healthcare decisions in musculoskeletal trauma and disorders 
Indian Journal of Orthopaedics  2008;42(3):247-251.
Systematic reviews are a key component of evidence-based practice. A valuable and accessible source of good quality systematic reviews on topics in musculoskeletal trauma and disorders is the Cochrane Database of Systematic Reviews, published in The Cochrane Library. These reviews are produced by members of The Cochrane Collaboration, an international not-for-profit organization that aims to make up-to-date, accurate information about the effects of healthcare readily available worldwide. Contributions from orthopedic specialists in India and neighboring countries are required to make the Cochrane Database an even more useful and comprehensive resource of reliable evidence. Linked with this is the opportunity for orthopedic specialists to take a leading role in generating the evidence to inform their practice.
doi:10.4103/0019-5413.41849
PMCID: PMC2739468  PMID: 19753148
Evidence-based medicine; meta-analysis; orthopedics; randomized controlled trials
11.  Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis 
The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of acute myocardial infarction (AMI). The association between the risks of AMI with nonselective NSAIDs is less clear. We reviewed the published evidence and assessed the risk of AMI with nonselective NSAIDs. We performed a meta-analysis of all studies containing data from population databases that compared the risk of AMI in NSAID users with that in non-users or remote NSAID users. The primary outcome was objectively confirmed AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis. Nonselective NSAIDs as a class was associated with increased AMI risk (relative AMI risk 1.19, 95% confidence interval [CI] 1.08 to 1.31). Similar findings were found with diclofenac (relative AMI risk 1.38, 95% CI 1.22–1.57) and ibuprofen (relative AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not observed with naproxen (relative AMI risk 0.99, 95% CI 0.88–1.11). In conclusion, based on current evidence, there is a general direction of effect, which suggests that at least some nonselective NSAIDs increase AMI risk. Analysis based on the limited data available for individual NSAIDs, including diclofenac and ibuprofen, supported this finding; however, this was not the case for naproxen. Nonselective NSAIDs are frequently prescribed, and so further investigation into the risk of AMI is warranted because the potential for harm can be substantial.
doi:10.1186/ar2047
PMCID: PMC1779447  PMID: 16995929
12.  From evidence to best practice in the management of fractures of the distal radius in adults: working towards a research agenda 
Background
Fracture of the distal radius is a common clinical problem, particularly in older white women with osteoporosis. We report our work towards evidence-based and patient-centred care for adults with these injuries.
Methods
We developed a systematic programme of research that built on our systematic review of the evidence of effectiveness of treatment interventions for these fractures. We devised schemata showing 'typical' care pathways and identified over 100 patient management questions. These depicted the more important decisions taken when progressing along each care pathway. We compiled a comprehensive document summarising the evidence available for each decision point from our reviews of randomised trials of treatment interventions. Using these documents, we undertook a formal and structured consultation process involving key players, including a patient representative, to obtain their views on the available evidence and to establish a research agenda. The resulting feedback was then processed and interpreted, using systematic methods.
Results
Some evidence from 114 randomised trials was available for 31 of the 117 patient management questions. However, there was sufficient evidence to base some conclusions of effectiveness for particular interventions in only five of these.
Though only 60% of those approached responded, the responses received from the consultation group were often comprehensive and provided important insights into treatment practice and policy. There was a clear acceptance of the aims of the project and, aside from some suggestions for the more explicit inclusion of secondary prevention and management of complications, of the care pathways scheme. Though some respondents stressed that randomised trials were not always appropriate, there was no direct overall criticism of the evidence document and underlying processes. We were able to identify important core themes that underpin management decisions and research from the feedback of the consultation exercise.
Conclusions
Overall, this project is an important advance towards evidence-based and patient-centred management of adults with distal radial fractures. It exposes the serious deficiency in the available evidence but also provides a template for further action. As well as being a valuable basis for viewing and informing current practice, the insights gained from this project should inform a future research agenda.
doi:10.1186/1471-2474-4-27
PMCID: PMC317324  PMID: 14641927
13.  Randomised trials in surgery  
BMJ : British Medical Journal  2002;325(7365):658.
PMCID: PMC1124173  PMID: 12242186
14.  Crossing the quality chasm: lessons from health care quality improvement efforts in England 
The second report from the US Institute of Medicine Crossing the Quality Chasm, highlighted the deficiencies in health care quality in the USA, analyzed the contributory factors, and proposed 13 recommendations for improvements. Clearly, the challenges are enormous. Can anything be learned from the experiences of other countries? This article describes the author's experiences of health care quality improvement efforts in the National Health Service in England and their implications for the USA and for Baylor Health Care System.
PMCID: PMC1276338  PMID: 16333409
15.  Rheumatology 
BMJ : British Medical Journal  2000;321(7265):882-885.
PMCID: PMC1118683  PMID: 11021871
16.  Patient surveys identify needs 
BMJ : British Medical Journal  2000;320(7230):314.
PMCID: PMC1117500  PMID: 10650041
20.  Extracontractual referrals 
BMJ : British Medical Journal  1991;303(6805):788-789.
PMCID: PMC1671014

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