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The Cochrane Database of Systematic... Oct 2017Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A less invasive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A less invasive alternative to surgery in some people is enzymatic vitreolysis, using an intravitreal injection of ocriplasmin.
OBJECTIVES
To assess the efficacy and safety of ocriplasmin compared to no treatment, sham or placebo for the treatment of sVMA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 1), MEDLINE Ovid (1946 to 24 February 2017), Embase Ovid (1947 to 24 February 2017), PubMed (1946 to 24 February 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 24 February 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 24 February 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 24 February 2017. We did not use any date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people with sVMA. The intervention was intravitreal ocriplasmin 125 μg injection, and this was compared to placebo or sham injection (control). Placebo was defined as a single intravitreal injection of 0.10 mL placebo with identical drug vehicle diluted with saline. A sham injection was defined as the syringe hub or blunt needle touching the conjunctiva to simulate an injection.
DATA COLLECTION AND ANALYSIS
Two authors independently selected relevant trials, assessed methodological quality and extracted data. We graded the certainty of the evidence using the GRADE approach.
MAIN RESULTS
This review included four RCTs conducted in Europe and the USA with a total of 932 eyes of 932 participants. Participants were 18 to 97 years of age, with evidence of focal vitreomacular adhesion (VMA) on optical coherence tomography (OCT) imaging, with a best corrected visual acuity (BCVA) of 20/25 or worse in the study eye and 20/400 or better in the fellow eye. The interventions compared were intravitreal ocriplasmin versus sham (two RCTs) or placebo (two RCTs) injection. Both sham and placebo injection were classified as the control group. The main outcome measures were assessed at 28 days and six months. Overall, we judged the studies to have a low or unclear risk of bias. All four RCTs were sponsored by the manufacturers of ocriplasmin.Compared with control, ocriplasmin treatment was more likely to result in VMA release within 28 days (risk ratio (RR) 3.46, 95% confidence interval (CI) 2.00 to 6.00; 859 eyes, 4 RCTs, high-certainty evidence). Approximately 97/1000 eyes will have VMA release within 28 days without treatment. An additional 237 eyes will have VMA release within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 96 more to 482 more).Treatment with ocriplasmin was also more likely to result in macular hole closure (RR 2.87, 95% CI 1.50 to 5.51; 229 eyes, 3 RCTs, high-certainty evidence). Approximately 123/1000 eyes with macular holes will have closure with no treatment. An additional 231 eyes will have macular hole closure for every 1000 eyes treated with ocriplasmin (95% CI 62 more to 556 more).Eyes receiving ocriplasmin were also more likely to have complete posterior vitreous detachment (PVD) within 28 days (RR 2.94, 95% CI 1.39 to 6.24; 689 eyes, 3 RCTs, high-certainty evidence). Approximately 40/1000 eyes will have complete PVD within 28 days without treatment. An additional 78 eyes will have complete PVD within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 16 more to 210 more).Eyes receiving ocriplasmin were more likely to achieve 3-line or greater improvement in BCVA at six months (RR 1.95, 95% CI 1.07 to 3.53; 674 eyes, 3 RCTs, moderate-certainty evidence). Approximately 61/1000 eyes will have a 3-line or greater improvement in BCVA at six months without treatment. An additional 58 eyes will have 3-line or greater improvement in BCVA at six months for every 1000 eyes treated with ocriplasmin (95% CI 9 more to 154 more).Receiving ocriplasmin also reduced the requirement for vitrectomy at six months (RR 0.67, 95% CI 0.50 to 0.91; 689 eyes, 3 RCTs, moderate-certainty evidence). Approximately 265/1000 eyes will require vitrectomy at six months without treatment and 87 fewer eyes will require vitrectomy for every 1000 eyes treated with ocriplasmin (95% CI 24 fewer to 132 fewer).Treatment with ocriplasmin resulted in a greater improvement in validated Visual Function Questionnaire form score at six months (mean improvement difference 2.7 points, 95% CI 0.8 to 4.6; 652 eyes, 2 RCTs, moderate-certainty evidence).Eyes receiving ocriplasmin were more likely to have an adverse event (RR 1.22, 95% CI 1.09 to 1.37, 909 eyes, 4 RCTs, moderate-certainty evidence). Approximately 571/1000 eyes will have an adverse event with sham or placebo injection and 106 more eyes will have an adverse event for every 1000 eyes treated with ocriplasmin (95% CI 52 more to 212 more).
AUTHORS' CONCLUSIONS
Evidence from a limited number of RCTs suggests that ocriplasmin is useful in the treatment of sVMA. However, up to 20% of eyes treated with ocriplasmin will still require additional treatment with PPV within six months. There were more ocular adverse events in eyes treated with ocriplasmin than control (sham or placebo injection) treatment. Many of these adverse events, particularly vitreous floaters and photopsia, are known to be associated with posterior vitreous detachment. At present however, there is minimal published long-term safety data on eyes treated with ocriplasmin. Further large RCTs comparing ocriplasmin with other management options for sVMA would be beneficial.
Topics: Adult; Aged; Aged, 80 and over; Fibrinolysin; Fibrinolytic Agents; Humans; Intravitreal Injections; Middle Aged; Peptide Fragments; Randomized Controlled Trials as Topic; Retinal Diseases; Time Factors; Tissue Adhesions; Visual Acuity; Vitrectomy; Vitreous Body; Vitreous Detachment
PubMed: 29040800
DOI: 10.1002/14651858.CD011874.pub2 -
The Cochrane Database of Systematic... Dec 2014Myasthenia is a condition in which neuromuscular transmission is affected by antibodies against neuromuscular junction components (autoimmune myasthenia gravis, MG; and... (Review)
Review
BACKGROUND
Myasthenia is a condition in which neuromuscular transmission is affected by antibodies against neuromuscular junction components (autoimmune myasthenia gravis, MG; and neonatal myasthenia gravis, NMG) or by defects in genes for neuromuscular junction proteins (congenital myasthenic syndromes, CMSs). Clinically, some individuals seem to benefit from treatment with ephedrine, but its effects and adverse effects have not been systematically evaluated.
OBJECTIVES
To assess the effects and adverse effects of ephedrine in people with autoimmune MG, transient neonatal MG, and the congenital myasthenic syndromes.
SEARCH METHODS
On 17 November 2014, we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. We also searched reference lists of articles, conference proceedings of relevant conferences, and prospective trial registers. In addition, we contacted manufacturers and researchers in the field.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) and quasi-RCTs comparing ephedrine as a single or add-on treatment with any other active treatment, placebo, or no treatment in adults or children with autoimmune MG, NMG, or CMSs.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study design and quality, and extracted data. We contacted study authors for additional information. We collected information on adverse effects from included articles, and contacted authors.
MAIN RESULTS
We found no RCTs or quasi-RCTs, and therefore could not establish the effect of ephedrine on MG, NMG and CMSs. We describe the results of 53 non-randomised studies narratively in the Discussion section, including observations of endurance, muscle strength and quality of life. Effects may differ depending on the type of myasthenia. Thirty-seven studies were in participants with CMS, five in participants with MG, and in 11 the precise form of myasthenia was unknown. We found no studies for NMG. Reported adverse effects included tachycardia, sleep disturbances, nervousness, and withdrawal symptoms.
AUTHORS' CONCLUSIONS
There was no evidence available from RCTs or quasi-RCTs, but some observations from non-randomised studies are available. There is a need for more evidence from suitable forms of prospective RCTs, such as series of n-of-one RCTs, that use appropriate and validated outcome measures.
Topics: Adrenergic Agents; Adult; Child; Cholinesterase Inhibitors; Ephedrine; Humans; Infant, Newborn; Myasthenia Gravis; Myasthenia Gravis, Neonatal; Myasthenic Syndromes, Congenital
PubMed: 25515947
DOI: 10.1002/14651858.CD010028.pub2 -
The Lancet. Respiratory Medicine Jan 2023Influenza vaccines require annual readministration; however, several reports have suggested that repeated vaccination might attenuate the vaccine's effectiveness. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Influenza vaccines require annual readministration; however, several reports have suggested that repeated vaccination might attenuate the vaccine's effectiveness. We aimed to estimate the reduction in vaccine effectiveness associated with repeated influenza vaccination.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and CINAHL Complete databases for articles published from Jan 1, 2016, to June 13, 2022, and Web of Science for studies published from database inception to June 13, 2022. For studies published before Jan 1, 2016, we consulted published systematic reviews. Two reviewers (EJ-G and EJR) independently screened, extracted data using a data collection form, assessed studies' risk of bias using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) and evaluated the weight of evidence by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included observational studies and randomised controlled trials that reported vaccine effectiveness against influenza A(H1N1)pdm09, influenza A(H3N2), or influenza B using four vaccination groups: current season; previous season; current and previous seasons; and neither season (reference). For each study, we calculated the absolute difference in vaccine effectiveness (ΔVE) for current season only and previous season only versus current and previous season vaccination to estimate attenuation associated with repeated vaccination. Pooled vaccine effectiveness and ∆VE were calculated by season, age group, and overall. This study is registered with PROSPERO, CRD42021260242.
FINDINGS
We identified 4979 publications, selected 681 for full review, and included 83 in the systematic review and 41 in meta-analyses. ΔVE for vaccination in both seasons compared with the current season was -9% (95% CI -16 to -1, I=0%; low certainty) for influenza A(H1N1)pdm09, -18% (-26 to -11, I=7%; low certainty) for influenza A(H3N2), and -7% (-14 to 0, I=0%; low certainty) for influenza B, indicating lower protection with consecutive vaccination. However, for all types, A subtypes and B lineages, vaccination in both seasons afforded better protection than not being vaccinated.
INTERPRETATION
Our estimates suggest that, although vaccination in the previous year attenuates vaccine effectiveness, vaccination in two consecutive years provides better protection than does no vaccination. The estimated effects of vaccination in the previous year are concerning and warrant additional investigation, but are not consistent or severe enough to support an alternative vaccination regimen at this time.
FUNDING
WHO and the US National Institutes of Health.
Topics: Humans; Influenza, Human; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Vaccination; Seasons
PubMed: 36152673
DOI: 10.1016/S2213-2600(22)00266-1 -
Health Technology Assessment... May 2016Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for... (Review)
Review
Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model.
BACKGROUND
Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial.
OBJECTIVES
To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities.
DATA SOURCES
Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals.
REVIEW METHODS
A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model.
RESULTS
Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), AbbVie) or golimumab (GOL) (Simponi(®), MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8-32 and 32-52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8-32 weeks and GOL 50 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32-52 weeks was significant. The greatest effects were associated with GOL (at 8-32 weeks) and ADA (at 32-52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained.
LIMITATIONS
The health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review.
CONCLUSIONS
Adult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013006883.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adalimumab; Antibodies, Monoclonal; Biosimilar Pharmaceuticals; Colitis, Ulcerative; Cost-Benefit Analysis; Gastrointestinal Agents; Hospitalization; Humans; Infliximab; Models, Econometric; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; State Medicine
PubMed: 27220829
DOI: 10.3310/hta20390 -
Health Technology Assessment... Aug 2016End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival.
OBJECTIVES
To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation.
DATA SOURCES
Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost).
REVIEW METHODS
Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death.
RESULTS
Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC.
LIMITATIONS
The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.
CONCLUSIONS
TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42014013544.
FUNDING
The National Institute for Health Research HTA programme.
Topics: Abatacept; Antibodies, Monoclonal; Antilymphocyte Serum; Azathioprine; Basiliximab; Child; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Everolimus; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Models, Economic; Mycophenolic Acid; Recombinant Fusion Proteins; Sirolimus; Tacrolimus; Technology Assessment, Biomedical
PubMed: 27557331
DOI: 10.3310/hta20610 -
The Cochrane Database of Systematic... May 2016Nutritional support in the critically ill child has not been well investigated and is a controversial topic within paediatric intensive care. There are no clear... (Review)
Review
BACKGROUND
Nutritional support in the critically ill child has not been well investigated and is a controversial topic within paediatric intensive care. There are no clear guidelines as to the best form or timing of nutrition in critically ill infants and children. This is an update of a review that was originally published in 2009. .
OBJECTIVES
The objective of this review was to assess the impact of enteral and parenteral nutrition given in the first week of illness on clinically important outcomes in critically ill children. There were two primary hypotheses:1. the mortality rate of critically ill children fed enterally or parenterally is different to that of children who are given no nutrition;2. the mortality rate of critically ill children fed enterally is different to that of children fed parenterally.We planned to conduct subgroup analyses, pending available data, to examine whether the treatment effect was altered by:a. age (infants less than one year versus children greater than or equal to one year old);b. type of patient (medical, where purpose of admission to intensive care unit (ICU) is for medical illness (without surgical intervention immediately prior to admission), versus surgical, where purpose of admission to ICU is for postoperative care or care after trauma).We also proposed the following secondary hypotheses (a priori), pending other clinical trials becoming available, to examine nutrition more distinctly:3. the mortality rate is different in children who are given enteral nutrition alone versus enteral and parenteral combined;4. the mortality rate is different in children who are given both enteral feeds and parenteral nutrition versus no nutrition.
SEARCH METHODS
In this updated review we searched: the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2); Ovid MEDLINE (1966 to February 2016); Ovid EMBASE (1988 to February 2016); OVID Evidence-Based Medicine Reviews; ISI Web of Science - Science Citation Index Expanded (1965 to February 2016); WebSPIRS Biological Abstracts (1969 to February 2016); and WebSPIRS CAB Abstracts (1972 to February 2016). We also searched trial registries, reviewed reference lists of all potentially relevant studies, handsearched relevant conference proceedings, and contacted experts in the area and manufacturers of enteral and parenteral nutrition products. We did not limit the search by language or publication status.
SELECTION CRITERIA
We included studies if they were randomized controlled trials; involved paediatric patients, aged one day to 18 years of age, who were cared for in a paediatric intensive care unit setting (PICU) and had received nutrition within the first seven days of admission; and reported data for at least one of the pre-specified outcomes (30-day or PICU mortality; length of stay in PICU or hospital; number of ventilator days; and morbid complications, such as nosocomial infections). We excluded studies if they only reported nutritional outcomes, quality of life assessments, or economic implications. Furthermore, we did not address other areas of paediatric nutrition, such as immunonutrition and different routes of delivering enteral nutrition, in this review.
DATA COLLECTION AND ANALYSIS
Two authors independently screened the searches, applied the inclusion criteria, and performed 'Risk of bias' assessments. We resolved discrepancies through discussion and consensus. One author extracted data and a second checked data for accuracy and completeness. We graded the evidence based on the following domains: study limitations, consistency of effect, imprecision, indirectness, and publication bias.
MAIN RESULTS
We identified only one trial as relevant. Seventy-seven children in intensive care with burns involving more than 25% of the total body surface area were randomized to either enteral nutrition within 24 hours or after at least 48 hours. No statistically significant differences were observed for mortality, sepsis, ventilator days, length of stay, unexpected adverse events, resting energy expenditure, nitrogen balance, or albumin levels. We assessed the trial as having unclear risk of bias. We consider the quality of the evidence to be very low due to there being only one small trial. In the most recent search update we identified a protocol for a relevant randomized controlled trial examining the impact of withholding early parenteral nutrition completing enteral nutrition in pediatric critically ill patients; no results have been published.
AUTHORS' CONCLUSIONS
There was only one randomized trial relevant to the review question. Research is urgently needed to identify best practices regarding the timing and forms of nutrition for critically ill infants and children.
Topics: Burns; Child; Critical Illness; Enteral Nutrition; Humans; Infant; Intensive Care Units, Pediatric; Randomized Controlled Trials as Topic; Time Factors
PubMed: 27230550
DOI: 10.1002/14651858.CD005144.pub3 -
International Archives of Occupational... Jan 2017To conduct a systematic review of epidemiologic studies on risk of cancer from exposure to silicon carbide (SiC). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To conduct a systematic review of epidemiologic studies on risk of cancer from exposure to silicon carbide (SiC).
METHODS
We followed established guidelines to search electronic databases for studies on populations exposed to SiC. We conducted meta-analyses when the data justified it.
RESULTS
We identified two studies of SiC production workers and several studies of users. The studies of production workers indicated an increased risk of lung cancer. The increased risk was restricted to workers with elevated dust exposure and, in the most informative study from Norway, was linked to estimated cristobalite exposure, a form of crystalline silica. Increased risk was not linked to SiC particles, once cristobalite exposure was controlled for. Studies of SiC users in various industries did not reveal an increased risk of lung cancer.
CONCLUSIONS
The increased risk of lung cancer detected in the SiC production industry appears to be associated with high exposure levels to total dust, including crystalline silica and cristobalite which occurred in this industry in the past decades. It may not persist under current exposure circumstances, characterized by lower levels and use of personal protection equipment. Commercial users of SiC-based products were not affected.
Topics: Carbon Compounds, Inorganic; Dust; Humans; Lung Neoplasms; Manufacturing Industry; Occupational Diseases; Occupational Exposure; Risk Factors; Silicon Compounds; Silicon Dioxide
PubMed: 27628329
DOI: 10.1007/s00420-016-1169-8 -
PloS One 2016Bradford Hill's viewpoints were used to conduct a weight-of-the-evidence assessment of the association between Parkinson's disease (PD) and rural living, farming and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Bradford Hill's viewpoints were used to conduct a weight-of-the-evidence assessment of the association between Parkinson's disease (PD) and rural living, farming and pesticide use. The results were compared with an assessment based upon meta-analysis. For comparison, we also evaluated the association between PD and cigarette smoking as a "positive control" because a strong inverse association has been described consistently in the literature.
METHODS
PubMed was searched systematically to identify all published epidemiological studies that evaluated associations between Parkinson's disease (PD) and cigarette smoking, rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides or paraquat. Studies were categorized into two study quality groups (Tier 1 or Tier 2); data were abstracted and a forest plot of relative risks (RRs) was developed for each risk factor. In addition, when available, RRs were tabulated for more highly exposed individuals compared with the unexposed. Summary RRs for each risk factor were calculated by meta-analysis of Tier 1, Tier 2 and all studies combined, with sensitivity analyses stratified by other study characteristics. Indices of between-study heterogeneity and evidence of reporting bias were assessed. Bradford Hill's viewpoints were used to determine if a causal relationship between PD and each risk factor was supported by the weight of the evidence.
FINDINGS
There was a consistent inverse (negative) association between current cigarette smoking and PD risk. In contrast, associations between PD and rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides or paraquat were less consistent when assessed quantitatively or qualitatively.
CONCLUSION
The weight of the evidence and meta-analysis support the conclusion that there is a causal relationship between PD risk and cigarette smoking, or some unknown factor correlated with cigarette smoking. There may be risk factors associated with rural living, farming, pesticide use or well-water consumption that are causally related to PD, but the studies to date have not identified such factors. To overcome the limitations of research in this area, future studies will have to better characterize the onset of PD and its relationship to rural living, farming and exposure to pesticides.
Topics: Agriculture; Humans; Parkinson Disease; Pesticides; Risk Factors; Rural Population; Smoking; Water Wells
PubMed: 27055126
DOI: 10.1371/journal.pone.0151841 -
BMJ (Clinical Research Ed.) Oct 2016To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus. (Review)
Review
OBJECTIVE
To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus.
DESIGN
Systematic review of randomised controlled trials, cohort studies, and case-control studies.
DATA SOURCES
Embase, PubMed, Cochrane library, and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
All human studies reporting non-specific immunological effects after vaccination with standard childhood immunisations. Studies using recombinant vaccines, no vaccine at all, or reporting only vaccine specific outcomes were excluded. The primary aim was to systematically identify, assemble, and review all available studies and data on the possible non-specific or heterologous immunological effects of BCG; measles; mumps, measles, and rubella (MMR); diphtheria; tetanus; and pertussis vaccines.
RESULTS
The initial search yielded 11 168 references; 77 manuscripts met the inclusion criteria for data analysis. In most included studies (48%) BCG was the vaccine intervention. The final time point of outcome measurement was primarily performed (70%) between one and 12 months after vaccination. There was a high risk of bias in the included studies, with no single study rated low risk across all assessment criteria. A total of 143 different immunological variables were reported, which, in conjunction with differences in measurement units and summary statistics, created a high number of combinations thus precluding any meta-analysis. Studies that compared BCG vaccinated with unvaccinated groups showed a trend towards increased IFN-γ production in vitro in the vaccinated groups. Increases were also observed for IFN-γ measured after BCG vaccination in response to in vitro stimulation with microbial antigens from Candida albicans, tetanus toxoid, Staphylococcus aureas, lipopolysaccharide, and hepatitis B. Cohort studies of measles vaccination showed an increase in lymphoproliferation to microbial antigens from tetanus toxoid and C albicans Increases in immunogenicity to heterologous antigens were noted after diphtheria-tetanus (herpes simplex virus and polio antibody titres) and diphtheria-tetanus-pertussis (pneumococcus serotype 14 and polio neutralising responses) vaccination.
CONCLUSIONS
The papers reporting non-specific immunological effects had heterogeneous study designs and could not be conventionally meta-analysed, providing a low level of evidence quality. Some studies, such as BCG vaccine studies examining in vitro IFN-γ responses and measles vaccine studies examining lymphoproliferation to microbial antigen stimulation, showed a consistent direction of effect suggestive of non-specific immunological effects. The quality of the evidence, however, does not provide confidence in the nature, magnitude, or timing of non-specific immunological effects after vaccination with BCG, diphtheria, pertussis, tetanus, or measles containing vaccines nor the clinical importance of the findings.
Topics: BCG Vaccine; Case-Control Studies; Child, Preschool; Communicable Disease Control; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Female; Humans; Immunization; Infant; Male; Measles; Measles Vaccine; Measles-Mumps-Rubella Vaccine; Randomized Controlled Trials as Topic; Tetanus; Tuberculosis; United Kingdom; Vaccination; Whooping Cough
PubMed: 27737830
DOI: 10.1136/bmj.i5225 -
The Cochrane Database of Systematic... Jan 2021Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial.
OBJECTIVES
The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials.
SELECTION CRITERIA
Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.
MAIN RESULTS
We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all oral iron preparations showed that intravenous administration may lead to more responders (368/554 versus 205/373, RR 1.17, 95% CI 1.05 to 1.31, NNTB = 11, low-certainty due to risk of bias and inconsistency). Withdrawals due to adverse events may be greater in oral iron preparations vs intravenous (15/554 versus 31/373, RR 0.39, 95% CI 0.20 to 0.74, low-certainty due to risk of bias, inconsistency and imprecision).
AUTHORS' CONCLUSIONS
Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.
Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Bias; Colitis, Ulcerative; Crohn Disease; Disaccharides; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Fumarates; Hematinics; Humans; Iron Compounds; Maltose; Middle Aged; Placebos; Pyrones; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33471939
DOI: 10.1002/14651858.CD013529.pub2