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1.  Clinical effectiveness of manual therapy for the management of musculoskeletal and non-musculoskeletal conditions: systematic review and update of UK evidence report 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/2045-709X-22-12
PMCID: PMC3997823  PMID: 24679336
Clinical effectiveness; Manual therapy; Systematic review; Musculoskeletal; Bronfort
2.  Treatments for macular oedema following central retinal vein occlusion: systematic review 
BMJ Open  2014;4(2):e004120.
Objectives
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.
Results
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.
Limitations
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.
doi:10.1136/bmjopen-2013-004120
PMCID: PMC3927713  PMID: 24513867
Systematic Review; Anti-VEGF; Central Retinal Vein Occlusion; Macular Oedema
3.  Belimumab: a technological advance for systemic lupus erythematosus patients? Report of a systematic review and meta-analysis 
BMJ Open  2013;3(7):e002852.
Objectives
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.
Methods
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.
Design
A meta-analysis of RCTs.
Participants
2133 SLE patients.
Primary and secondary outcome measures
SLE Responder Index (SRI) at week 52.
Results
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).
doi:10.1136/bmjopen-2013-002852
PMCID: PMC3717447  PMID: 23872289
Clinical Pharmacology; Epidemiology; Preventive Medicine; Public Health
4.  Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes 
BMJ Open  2012;2(5):e001007.
Background
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.
Objective
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.
Methods
Systematic review. Quality assessment used the Cochrane risk of bias score.
Results
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).
Limitations
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.
Conclusions
Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes, although more safety data are needed.
doi:10.1136/bmjopen-2012-001007
PMCID: PMC3488745  PMID: 23087012
Diabetes & Endocrinology; Clinical Pharmacology

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