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1.  Total Hip Replacement for the Treatment of End Stage Arthritis of the Hip: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(7):e99804.
Evolvements in the design, fixation methods, size, and bearing surface of implants for total hip replacement (THR) have led to a variety of options for healthcare professionals to consider. The need to determine the most optimal combinations of THR implant is warranted. This systematic review evaluated the clinical effectiveness of different types of THR used for the treatment of end stage arthritis of the hip.
A comprehensive literature search was undertaken in major health databases. Randomised controlled trials (RCTs) and systematic reviews published from 2008 onwards comparing different types of primary THR in patients with end stage arthritis of the hip were included.
Fourteen RCTs and five systematic reviews were included. Patients experienced significant post-THR improvements in Harris Hip scores, but this did not differ between impact types. There was a reduced risk of implant dislocation after receiving a larger femoral head size (36 mm vs. 28 mm; RR = 0.17, 95% CI: 0.04, 0.78) or cemented cup (vs. cementless cup; pooled odds ratio: 0.34, 95% CI: 0.13, 0.89). Recipients of cross-linked vs. conventional polyethylene cup liners experienced reduced femoral head penetration and revision. There was no impact of femoral stem fixation and cup shell design on implant survival rates. Evidence on mortality and complications (aseptic loosening, femoral fracture) was inconclusive.
The majority of evidence was inconclusive due to poor reporting, missing data, or uncertainty in treatment estimates. The findings warrant cautious interpretation given the risk of bias (blinding, attrition), methodological limitations (small sample size, low event counts, short follow-up), and poor reporting. Long-term pragmatic RCTs are needed to allow for more definitive conclusions. Authors are encouraged to specify the minimal clinically important difference and power calculation for their primary outcome(s) as well CONSORT, PRISMA and STROBE guidelines to ensure better reporting and more reliable production and assessment of evidence.
PMCID: PMC4086719  PMID: 25003202
2.  Clinical effectiveness of manual therapy for the management of musculoskeletal and non-musculoskeletal conditions: systematic review and update of UK evidence report 
This systematic review updated and extended the "UK evidence report" by Bronfort et al. (Chiropr Osteopath 18:3, 2010) with respect to conditions/interventions that received an 'inconclusive’ or 'negative’ evidence rating or were not covered in the report.
A literature search of more than 10 general medical and specialised databases was conducted in August 2011 and updated in March 2013. Systematic reviews, primary comparative studies and qualitative studies of patients with musculoskeletal or non-musculoskeletal conditions treated with manual therapy and reporting clinical outcomes were included. Study quality was assessed using standardised instruments, studies were summarised, and the results were compared against the evidence ratings of Bronfort. These were either confirmed, updated, or new categories not assessed by Bronfort were added.
25,539 records were found; 178 new and additional studies were identified, of which 72 were systematic reviews, 96 were randomised controlled trials, and 10 were non-randomised primary studies. Most 'inconclusive’ or 'moderate’ evidence ratings of the UK evidence report were confirmed. Evidence ratings changed in a positive direction from inconclusive to moderate evidence ratings in only three cases (manipulation/mobilisation [with exercise] for rotator cuff disorder; spinal mobilisation for cervicogenic headache; and mobilisation for miscellaneous headache). In addition, evidence was identified on a large number of non-musculoskeletal conditions not previously considered; most of this evidence was rated as inconclusive.
Overall, there was limited high quality evidence for the effectiveness of manual therapy. Most reviewed evidence was of low to moderate quality and inconsistent due to substantial methodological and clinical diversity. Areas requiring further research are highlighted.
PMCID: PMC3997823  PMID: 24679336
Clinical effectiveness; Manual therapy; Systematic review; Musculoskeletal; Bronfort
3.  Treatments for macular oedema following central retinal vein occlusion: systematic review 
BMJ Open  2014;4(2):e004120.
To review systematically the randomised controlled trial (RCT) evidence for treatment of macular oedema due to central retinal vein occlusion (CRVO).
Data sources
MEDLINE, EMBASE, CDSR, DARE, HTA, NHSEED, CENTRAL and meeting abstracts (January 2005 to March 2013).
Study eligibility criteria, participants and interventions
RCTs with at least 12 months of follow-up assessing pharmacological treatments for CRVO were included with no language restrictions.
Study appraisal and synthesis methods
2 authors screened titles and abstracts and conducted data extracted and Cochrane risk of bias assessment. Meta-analysis was not possible due to lack of comparable studies.
8 studies (35 articles, 1714 eyes) were included, assessing aflibercept (n=2), triamcinolone (n=2), bevacizumab (n=1), pegaptanib (n=1), dexamethasone (n=1) and ranibizumab (n=1). In general, bevacizumab, ranibizumab, aflibercept and triamcinolone resulted in clinically significant increases in the proportion of participants with an improvement in visual acuity of ≥15 letters, with 40–60% gaining ≥15 letters on active drugs, compared to 12–28% with sham. Results for pegaptanib and dexamethasone were mixed. Steroids were associated with cataract formation and increased intraocular pressure. No overall increase in adverse events was found with bevacizumab, ranibizumab, aflibercept or pegaptanib compared with control. Quality of life was poorly reported. All studies had a low or unclear risk of bias.
All studies evaluated a relatively short primary follow-up (1 year or less). Most had an unmasked extension phase. There was no head-to-head evidence. The majority of participants included had non-ischaemic CRVO.
Conclusions and implications of key findings
Bevacizumab, ranibizumab, aflibercept and triamcinolone appear to be effective in treating macular oedema secondary to CRVO. Long-term data on effectiveness and safety are needed. Head-to-head trials and research to identify ‘responders’ is needed to help clinicians make the right choices for their patients. Research aimed to improve sight in people with ischaemic CRVO is required.
PMCID: PMC3927713  PMID: 24513867
Systematic Review; Anti-VEGF; Central Retinal Vein Occlusion; Macular Oedema
4.  Belimumab: a technological advance for systemic lupus erythematosus patients? Report of a systematic review and meta-analysis 
BMJ Open  2013;3(7):e002852.
To undertake a systematic review and meta-analysis to investigate clinical effectiveness of belimumab for patients with systemic lupus erythematosus (SLE) and antinuclear and/or anti-double-stranded DNA (dsDNA) autoantibodies.
We searched eight electronic databases and reference lists for randomised controlled trials (RCTs) of belimumab against placebo or best supportive care. Quality assessment and random effects meta-analysis were undertaken.
A meta-analysis of RCTs.
2133 SLE patients.
Primary and secondary outcome measures
SLE Responder Index (SRI) at week 52.
Three double-blind placebo-controlled RCTs (L02, BLISS-52 BLISS-76) investigated 2133 SLE patients. BLISS-52 and BLISS-76 trials recruited patients with antinuclear and/or anti-dsDNA autoantibodies and demonstrated belimumab effectiveness for the SRI at week 52. Ethnicity and geographical location of participants varied considerably between BLISS trials. Although tests for statistical heterogeneity were negative, BLISS-52 results were systematically more favourable for all measured outcomes. Meta-analysis of pooled 52-week SRI BLISS results showed benefit for belimumab (OR 1.63, 95% CI 1.27 to 2.09). By week 76, the primary SRI outcome in BLISS-76 was not statistically significant (OR 1.31, 95% CI 0.919 to 1.855).
PMCID: PMC3717447  PMID: 23872289
Clinical Pharmacology; Epidemiology; Preventive Medicine; Public Health
5.  Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes 
BMJ Open  2012;2(5):e001007.
Despite the number of medications for type 2 diabetes, many people with the condition do not achieve good glycaemic control. Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia. Type 2 diabetes tends to be a progressive disease, and most patients require treatment with combinations of glucose-lowering agents. The sodium glucose co-transporter 2 (SGLT2) receptor inhibitors are a new class of glucose-lowering agents.
To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes.
Data sources
MEDLINE, Embase, Cochrane Library (all sections); Science Citation Index; trial registries; conference abstracts; drug regulatory authorities; bibliographies of retrieved papers.
Inclusion criteria
Randomised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy.
Systematic review. Quality assessment used the Cochrane risk of bias score.
Seven trials, published in full, assessed dapagliflozin and one assessed canagliflozin. Trial quality appeared good. Dapagliflozin 10 mg reduced HbA1c by −0.54% (weighted mean differences (WMD), 95% CI −0.67 to −0.40) compared to placebo, but there was no difference compared to glipizide. Canagliflozin reduced HbA1c slightly more than sitagliptin (up to −0.21% vs sitagliptin). Both dapagliflozin and canagliflozin led to weight loss (dapagliflozin WMD −1.81 kg (95% CI −2.04 to −1.57), canagliflozin up to −2.3 kg compared to placebo).
Long-term trial extensions suggested that effects were maintained over time. Data on canagliflozin are currently available from only one paper. Costs of the drugs are not known so cost-effectiveness cannot be assessed. More data on safety are needed, with the Food and Drug Administration having concerns about breast and bladder cancers.
Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes, although more safety data are needed.
PMCID: PMC3488745  PMID: 23087012
Diabetes & Endocrinology; Clinical Pharmacology

Results 1-5 (5)