Objective To indirectly compare aflibercept, bevacizumab, dexamethasone, ranibizumab and triamcinolone for treatment of macular oedema secondary to central retinal vein occlusion using a network ...meta-analysis (NMA). Design NMA. Data sources The following databases were searched from January 2005 to March 2013: MEDLINE, MEDLINE In-process, EMBASE; CDSR, DARE, HTA, NHSEED, CENTRAL; Science Citation Index and Conference Proceedings Citation Index-Science. Eligibility criteria for selecting studies Only randomised controlled trials assessing patients with macular oedema secondary to central retinal vein occlusion were included. Studies had to report either proportions of patients gaining ≥3 lines, losing ≥3 lines, or the mean change in best corrected visual acuity. Two authors screened titles and abstracts, extracted data and undertook risk of bias assessment. Bayesian NMA was used to compare the different interventions. Results Seven studies, assessing five drugs, were judged to be sufficiently comparable for inclusion in the NMA. For the proportions of patients gaining ≥3 lines, triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of being more effective than sham and dexamethasone. A smaller proportion of patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg or aflibercept 2 mg lost ≥3 lines of vision compared to those treated with sham. Patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of improvement in the mean best corrected visual acuity compared to those treated with sham injections. Conclusions We found no evidence of differences between ranibizumab, aflibercept, bevacizumab and triamcinolone for improving vision. The antivascular endothelial growth factors (VEGFs) are likely to be favoured because they are not associated with steroid-induced cataract formation. Aflibercept may be preferred by clinicians because it might require fewer injections. Systematic review registration Not registered.
A brief introduction to health economics Waugh, Norman; Mistry, Hema
Knee surgery, sports traumatology, arthroscopy,
06/2019, Letnik:
27, Številka:
6
Journal Article
Recenzirano
Odprti dostop
To convince policy-makers or funders of health care of the value of orthopaedic interventions, we need to consider value for money (cost-effectiveness), as well as clinical effectiveness. This ...article provides an introduction to health economics to set the scene for papers on the use of allografts in the knee.
It is generally believed that exhaustive searches of bibliographic databases are needed for systematic reviews of health care interventions. The CENTRAL database of controlled trials (RCTs) has been ...built up by exhaustive searching. The CONSORT statement aims to encourage better reporting, and hence indexing, of RCTs. Our aim was to assess whether developments in the CENTRAL database, and the CONSORT statement, mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic reviews of health care interventions.
RCTs used in the Cochrane reviews were identified. A brief RCT search strategy (BRSS), consisting of a search of CENTRAL, and then for variants of the word random across all fields (random$.af.) in MEDLINE and EMBASE, was devised and run. Any trials included in the meta-analyses, but missed by the BRSS, were identified. The meta-analyses were then re-run, with and without the missed RCTs, and the differences quantified. The proportion of trials with variants of the word random in the title or abstract was calculated for each year. The number of RCTs retrieved by searching with "random$.af." was compared to the highly sensitive search strategy (HSSS).
The BRSS had a sensitivity of 94%. It found all journal RCTs in 47 of the 57 reviews. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five reviews, but no important differences in conclusions resulted. In the post-CONSORT years, 1997-2003, the percentage of RCTs with random in the title or abstract was 85%, a mean increase of 17% compared to the seven years pre-CONSORT (95% CI, 8.3% to 25.9%). The search using random$.af. reduced the MEDLINE retrieval by 84%, compared to the HSSS, thereby reducing the workload of checking retrievals.
A brief RCT search strategy is now sufficient to locate RCTs for systematic reviews in most cases. Exhaustive searching is no longer cost-effective, because in effect it has already been done for CENTRAL.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Patients with type 1 diabetes are known to have a higher hospital admission rate than the underlying population and may also be admitted for procedures that would normally be carried out on a day ...surgery basis for non-diabetics. Emergency admission rates have sometimes been used as indicators of quality of diabetes care. In preparation for a study of hospital admissions, a systematic review was carried out on hospital admissions for children diagnosed with type 1 diabetes, whilst under the age of 15. The main thrust of this review was to ascertain where there were gaps in the literature for studies investigating post-diagnosis hospitalisations, rather than to try to draw conclusions from the disparate data sets.
A systematic search of the electronic databases PubMed, Cochrane LibrarMEDLINE and EMBASE was conducted for the period 1986 to 2006, to identify publications relating to hospital admissions subsequent to the diagnosis of type 1 diabetes under the age of 15.
Thirty-two publications met all inclusion criteria, 16 in Northern America, 11 in Europe and 5 in Australasia. Most of the studies selected were focussed on diabetic ketoacidosis (DKA) or diabetes-related hospital admissions and only four studies included data on all admissions. Admission rates with DKA as primary diagnosis varied widely between 0.01 to 0.18 per patient-year as did those for other diabetes-related co-morbidity ranging from 0.05 to 0.38 per patient year, making it difficult to interpret data from different study designs. However, people with Type 1 diabetes are three times more likely to be hospitalised than the non-diabetic populations and stay in hospital twice as long.
Few studies report on all admissions to hospital in patients diagnosed with type 1 diabetes whilst under the age of 15 years. Health care costs for type 1 patients are higher than those for the general population and information on associated patterns of hospitalisation might help to target interventions to reduce the cost of hospital admissions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Screening for hyperglycaemia in pregnancy: Consensus and controversy Waugh, Norman, MRCP(UK), MPH; Pearson, Donald, BSc (Hons), FRCPG, FRCPE; Royle, Pamela, MSc, PhD
Best Practice & Research Clinical Endocrinology & Metabolism,
08/2010, Letnik:
24, Številka:
4
Journal Article
Recenzirano
Policy decisions on whether to implement screening programmes depend on whether the proposed programmes meet a set of criteria laid down by the World Health Organization. Screening for hyperglycaemia ...in pregnancy (HGP) does not meet all the criteria. However the case for screening has been strengthened by a number of recent developments, including: rising prevalence of HGP because of increasing maternal age and BMI; the results of the Hyperglycaemia and Adverse Pregnancy Outcomes study, showing that adverse effects of HGP are seen over a wider range of plasma glucose levels than previously thought; two large trials which showed the benefits of treating lesser degrees of HGP; trials showing that metformin and glibenclamide were effective and safe alternatives to immediate insulin in those without good control on lifestyle measures alone. However uncertainties remain around the threshold for treatment, and on the best screening strategy.
Methodological research to support searching for those doing systematic reviews of epidemiological studies is a relatively neglected area. Our aim was to determine how many databases it is necessary ...to search to ensure a comprehensive coverage of the literature in diabetes epidemiology, with the aim of examining the efficiency of searching in support of systematic reviews of the epidemiology of diabetes
Three approaches were used. First, we defined a set of English language diabetes journals and examined their coverage in bibliographic databases. Second, we searched extensively for diabetes epidemiology articles (in all languages) to determine which are the most useful databases; and third, we analysed the scattering of these articles to determine the core journals in the area.
The overlap between MEDLINE and Embase for diabetes journals was 59%. A search for diabetes epidemiology articles across both MEDLINE and Embase, showed that MEDLINE alone retrieved about 94% of the total articles. Searching for diabetes epidemiology studies beyond MEDLINE and Embase retrieved no additional English language journal articles. The only diabetes epidemiology studies found by searching beyond MEDLINE and Embase were found in LILACS, and were Spanish or Portuguese language studies from Latin America; no additional English language studies were found. Only 30% of the meeting abstracts were converted to full publication after three years. One third of journal articles were published in just six journals, with Diabetes Care contributing 14.3% of the articles, followed by Diabetic Medicine (5.0%); Diabetes Research & Clinical Practice (4.1%); Diabetologia (4.0%); Diabetes & Metabolism (2.4%) and Diabetes (2.0%).
Our results show that when searching for articles on diabetes epidemiology, MEDLINE and Embase would suffice for English language papers, with LILACS giving some additional non-English articles from Latin America. Although a MEDLINE-only search will retrieve the vast majority of the relevant literature, Embase and LILACs should also be searched to ensure the search is comprehensive. Searching for meeting abstracts is recommended to alert reviewers to unpublished work. The low rate of full publication of meeting abstracts has the danger of producing bias in reviews. Our findings on scattering show that the core literature in this field is concentrated in just six journals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Disease of the cardiovascular system is the main cause of long-term complications and mortality in patients with type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. ...Cerebrovascular mortality rates have been shown to be raised in patients with type II diabetes but have not previously been reported by age and sex in patients with type I diabetes.
A cohort of 23 751 patients with insulin-treated diabetes, diagnosed under the age of 30 years from throughout the United Kingdom, was identified during 1972 to 1993 and followed up for mortality until the end of December 2000. Age- and sex-specific mortality rates and standardized mortality ratios (SMRs) were calculated.
There were 1437 deaths during the follow-up, 80 due to cerebrovascular disease. Overall, the cerebrovascular mortality rates in the cohort were higher than the corresponding rates in the general population, and the SMRs were 3.1 (95% CI, 2.2 to 4.3) for men and 4.4 (95% CI, 3.1 to 6.0) for women. When stratified by age, the SMRs were highest in the 20- to 39-year age group. After subdivision of cause of death into hemorrhagic and nonhemorrhagic origins, there remained a significant increase in mortality from stroke of nonhemorrhagic origin.
Analyses of mortality from this cohort, essentially one of patients with type I diabetes, has shown for the first time that cerebrovascular mortality is raised at all ages in these patients. Type I diabetes is at least as great a risk factor for cerebrovascular mortality as type II diabetes.
ObjectiveBecause of the lack of head-to-head trials, the aim was to indirectly compare sodium glucose transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes.DesignSystematic review and ...network meta-analysis.Data sourcesMEDLINE and EMBASE were searched from January 2005 to January 2015.Eligibility criteriaRandomised controlled trials assessing the efficacy of SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with diet and exercise alone or metformin monotherapy. Minimum duration 24 weeks. Indirect comparison was undertaken using Bayesian methods.ResultsIn monotherapy, a greater proportion of patients achieved a glycated haemoglobin (HbA1c) level of <7% on canagliflozin 300 mg than on canagliflozin 100 mg (risk ratio (RR) 0.72%, 95% credible intervals (CrI) 0.59% to 0.87%) and dapagliflozin 10 mg (RR 0.63, 95% CrI 0.48 to 0.85) but there were no significant differences compared with either dose of empagliflozin. In monotherapy, canagliflozin 300 mg reduced HbA1c more than other SGLT-2 inhibitors (mean difference ranged from 0.20% to 0.64%). There were no significant differences in weight reduction. All the flozins reduced systolic blood pressure (SBP) more than placebo, ranging from a reduction of 6 mm Hg with canagliflozin 300–2.6 mm Hg with empagliflozin 10 mg. In dual therapy with metformin, all flozins were more effective than placebo for achieving HbA1c <7%, and reducing HbA1c, weight and SBP. The proportions achieving HbA1c level of <7% were mostly similar. Canagliflozin 300 mg reduced HbA1c more than the other drugs but this just reached statistical significance only against canagliflozin 100 mg (MD 0.15, CrI 0.04 to 0.26).ConclusionsThere were few differences among the SGLT-2 inhibitors, but in monotherapy, the glucose-lowering effect of canagliflozin 300 mg is slightly greater than most other SGLT-2 inhibitors.
Background
Glucagon‐like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes that mimic the endogenous hormone glucagon‐like peptide 1 (GLP‐1). GLP‐1 is an incretin, a ...gastrointestinal hormone that is released into the circulation in response to ingested nutrients. GLP‐1 regulates glucose levels by stimulating glucose‐dependent insulin secretion and biosynthesis, and by suppressing glucagon secretion, delayed gastric emptying and promoting satiety.
Objectives
To assess the effects of glucagon‐like peptide analogues in patients with type 2 diabetes mellitus.
Search methods
Studies were obtained from electronic searches of The Cochrane Library (last search issue 1, 2011), MEDLINE (last search March 2011), EMBASE (last search March 2011), Web of Science (last search March 2011) and databases of ongoing trials.
Selection criteria
Studies were included if they were randomised controlled trials of a minimum duration of eight weeks comparing a GLP‐1 analogue with placebo, insulin, an oral anti‐diabetic agent, or another GLP‐1 analogue in people with type 2 diabetes.
Data collection and analysis
Data extraction and quality assessment of studies were done by one reviewer and checked by a second. Data were analysed by type of GLP‐1 agonist and comparison treatment. Where appropriate, data were summarised in a meta‐analysis (mean differences and risk ratios summarised using a random‐effects model).
Main results
Seventeen randomised controlled trials including relevant analyses for 6899 participants were included in the analysis. Studies were mostly of short duration, usually 26 weeks.
In comparison with placebo, all GLP‐1 agonists reduced glycosylated haemoglobin A1c (HbA1c) levels by about 1%. Exenatide 2 mg once weekly and liraglutide 1.8 mg reduced it by 0.20% and 0.24% respectively more than insulin glargine. Exenatide 2 mg once weekly reduced HbA1c more than exenatide 10 μg twice daily, sitagliptin and pioglitazone. Liraglutide 1.8 mg reduced HbA1c by 0.33% more than exenatide 10 μg twice daily. Liraglutide led to similar improvements in HbA1c compared to sulphonylureas but reduced it more than sitagliptin and rosiglitazone.
Both exenatide and liraglutide led to greater weight loss than most active comparators, including in participants not experiencing nausea. Hypoglycaemia occurred more frequently in participants taking concomitant sulphonylurea. GLP‐1 agonists caused gastrointestinal adverse effects, mainly nausea. These adverse events were strongest at the beginning and then subsided. Beta‐cell function was improved with GLP‐1 agonists but the effect did not persist after cessation of treatment.
None of the studies was long enough to assess long‐term positive or negative effects.
Authors' conclusions
GLP‐1 agonists are effective in improving glycaemic control.
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