-
The Cochrane Database of Systematic... Sep 2019Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA...
BACKGROUND
Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
OBJECTIVES
To assess the effectiveness and safety of topical CsA in the treatment of dry eye.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 16 February 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
DATA COLLECTION AND ANALYSIS
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD -0.35, 95% CI -0.69 to -0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses.
AUTHORS' CONCLUSIONS
Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non-serious, treatment-related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer-term disease-modifying effects. Well-planned, long-term, large clinical trials are needed to better assess CsA on long-term dry eye-modifying effects. A core outcome set, which ideally includes both biomarkers and patient-reported outcomes in the field of dry eye, is needed.
Topics: Cyclosporine; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Randomized Controlled Trials as Topic
PubMed: 31517988
DOI: 10.1002/14651858.CD010051.pub2 -
The Cochrane Database of Systematic... Jun 2019Lipid emulsions (LE) form a vital component of infant nutrition for critically ill, late preterm or term infants, particularly for those with gastrointestinal failure.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lipid emulsions (LE) form a vital component of infant nutrition for critically ill, late preterm or term infants, particularly for those with gastrointestinal failure. Conventionally used soybean oil-based LE (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols, which may contribute to adverse effects including parenteral nutrition-associated liver disease (PNALD).
OBJECTIVES
To compare the safety and efficacy of all LE for parenteral nutrition (PN) in term and late preterm infants (between 34 weeks' gestation and 36 weeks' and six days' gestation) with or without surgical conditions or PNALD within first six months of life, using all possible direct comparisons.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 June 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and the WHO's Trials Registry), and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised or quasi-randomised controlled studies in term and late preterm infants, with or without surgical conditions or PNALD.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting the conventional statistical significance of results.
MAIN RESULTS
The review included nine randomised studies (n = 273). LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soy oil-LE (MFS-LE) and olive-fish-soy-LE (OFS-LE)); 2. conventional pure S-LE; 3. alternative-LE (e.g. MCT-soy-LE (MS-LE), olive-soy-LE (OS-LE) and borage oil-based LE).We considered four broad comparisons: 1. all fish oil LE versus non-fish oil LE (6 studies; n = 182); 2. fish oil LE versus another fish oil LE (0 studies); 3. alternative-LE versus S-LE (3 studies; n = 91); 4. alternative-LE versus another alternative-LE (0 studies) in term and late preterm infants (0 studies), term and late preterm infants with surgical conditions (7 studies; n = 233) and term and late preterm infants with PNALD/cholestasis (2 studies; n = 40).PNALD/cholestasis was defined as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. We put no restriction on timing of PNALD detection. There was heterogeneity in definitions and time points for detecting PNALD in the included studies.We found one study each in surgical infants and in infants with cholestasis, showing no evidence of difference in incidence or resolution of PNALD/cholestasis (Cbil cut-off: 2 mg/dL) with use of fish oil-containing LE compared to S-LE.We considered an outcome allowing for any definition of PNALD (different Cbil cut-off levels). In infants with surgical conditions and no pre-existing PNALD, meta-analysis showed no difference in the incidence of PNALD/cholestasis (any definition) with use of fish oil-containing LE compared to S-LE (typical risk ratio (RR) 1.20, 95% confidence interval (CI) 0.38 to 3.76; typical risk difference (RD) 0.03, 95% CI -0.14 to 0.20; 2 studies; n = 68; low-quality evidence). In infants with PNALD/cholestasis (any definition), use of fish oil-LEs was associated with significantly less cholestasis compared to the S-LE group (typical risk ratio (RR) 0.54, 95% confidence interval (CI) 0.32 to 0.91; typical risk difference (RD) -0.39, 95% CI -0.65 to -0.12; number needed to treat for additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). This outcome had very low number of participants from two small studies with differences in study methodology and early termination in one study, which increased uncertainty about the effect estimates.One study in infants with cholestasis reported significantly better weight gain with a pure fish oil LE compared to a 10% S-LE (45 g/week, 95% CI 15.0 to 75.0; n = 16; very low-quality evidence). There were no significant differences in growth parameters in studies with surgical populations.For the secondary outcomes, in infants with cholestasis, one study (n = 24) reported significantly lower conjugated bilirubin levels but higher gamma glutamyl transferase levels with MOFS-LE (SMOFlipid) versus S-LE (Intralipid) and another study (n = 16), which was terminated early, reported significantly higher rates of rise in alanine aminotransferase (ALT) and conjugated bilirubin levels in the S-LE group compared to pure F-LE (Omegaven).In surgical infants, two studies each reported on hypertriglyceridaemia and Cbil levels with one study in each outcome showing significant benefit with use of a F-LE and the other study showing no difference between the groups. Meta-analysis was not performed for either of these outcomes as there were only two studies showing conflicting results with high heterogeneity between the studies.There was no evidence of differences in death, sepsis, alkaline phosphatase and ALT levels in infants with surgical conditions or cholestasis (very low-quality evidence).One study reported neurodevelopmental outcomes at six and 24 months in infants with surgical conditions (n = 11) with no evidence of difference with use of pure F-LE versus S-LE. Another study in infants with cholestasis (n = 16) reported no difference in head growth velocity between pure F-LE versus S-LE.GRADE quality of evidence ranged from low to very low as the included studies were small single-centre studies. Three of the six studies that contributed data to the review were terminated early for various reasons.
AUTHORS' CONCLUSIONS
Based on the current review, there is insufficient data from randomised studies to determine with any certainty, the potential benefit of any LE including fish oil-containing LEs over another LE, for prevention or resolution of PNALD/cholestasis or any other outcomes in term and late preterm infants with underlying surgical conditions or cholestasis. There were no studies in infants without surgical conditions or cholestasis.Further research is required to establish role of fish oil or lipids from other sources in LEs to improve PNALD/cholestasis, and other clinical outcomes in parenterally fed term and late preterm infants.
Topics: Bilirubin; Chemical and Drug Induced Liver Injury; Cholestasis; Emulsions; Fish Oils; Humans; Infant; Infant, Newborn; Infant, Premature; Olive Oil; Parenteral Nutrition; Phospholipids; Randomized Controlled Trials as Topic; Soybean Oil; Surgical Procedures, Operative; Term Birth
PubMed: 31158920
DOI: 10.1002/14651858.CD013171.pub2 -
The Cochrane Database of Systematic... Jun 2019Conventionally used soybean oil-based lipid emulsion (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols that may contribute to adverse effects... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conventionally used soybean oil-based lipid emulsion (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols that may contribute to adverse effects in preterm infants. The newer lipid emulsions (LE) from different lipid sources are currently available for use in preterm infants.
OBJECTIVES
To compare the safety and efficacy of all LE for parenteral nutrition (PN) in preterm infants (less than 37 weeks' gestation) including preterm infants with surgical conditions or parenteral nutrition-associated liver disease (PNALD)/cholestasis using direct comparisons and pair-wise meta-analyses.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 July 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and WHO's Trials Registry and Platform), and reference lists of retrieved articles.
SELECTION CRITERIA
Randomised or quasi-randomised controlled studies in preterm infants with or without surgical conditions or PNALD within the first six months of life.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting statistical significance of results.
MAIN RESULTS
We included 29 studies (n = 2037) in this review. LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil-LE (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soybean oil-LE (MFS-LE) and olive-fish-soybean oil-LE (OFS-LE); 2. conventional S-LE; 3. alternative-LE (e.g. MCT-soybean oil-LE (MS-LE), olive-soybean oil-LE and borage oil-based LE).We considered the following broad comparisons: fish oil LE versus non-fish oil LE; fish oil LE versus another fish oil LE; alternative-LE versus S-LE; alternative-LE versus another alternative-LE in preterm infants less than 37 weeks' gestation, preterm infants with surgical conditions and preterm infants with PNALD/cholestasis. Separate subgroup comparisons of each LE preparation were included within these broader groups.Most studies in preterm infants used PN for mean duration of four weeks or less and for longer duration in infants with cholestasis or surgical conditions.We defined the primary outcome of PNALD/cholestasis as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. There was heterogeneity in definitions used by the included studies with Cbil cut-offs ranging from 17.1 μmol/L (1 mg/dL) up to 50 μmol/L (about 3 mg/dL).In preterm infants, meta-analysis found no evidence of a difference in the incidence of PNALD/cholestasis (Cbil cut-off: 2 mg/dl) between fish oil-LEs and all non-fish oil LEs (typical risk ratio (RR) 0.61, 95% confidence interval (CI) 0.24 to 1.56; typical risk difference (RD) -0.03, 95% CI -0.08 to 0.02; 4 studies; n = 328; low-quality evidence).We also considered an outcome allowing for any definition of PNALD (different Cbil cutoffs). In the meta-analysis for PNALD/cholestasis, using any definition and restricted to low or unclear risk of bias studies, there was no evidence of a difference between fish oil LE and all non-fish oil LE for incidence of cholestasis (typical RR 0.80, 95% CI 0.53 to 1.21; typical RD -0.02, 95% CI -0.05 to 0.02; 10 studies; n = 1024; low-quality evidence). There was no evidence of difference in subgroup meta-analyses of individual LE types in any comparison.In preterm infants with surgical conditions or cholestasis, there was only one small study each reporting no evidence of a difference in incidence or resolution of cholestasis respectively with use of a pure F-LE versus S-LE (using a Cbil cut-off of 2 mg/dL).In preterm infants with PNALD/cholestasis (using any definition), the meta-analysis showed significantly less cholestasis with the use of fish oil-LE compared to S-LE (typical RR 0.54, 95% CI 0.32 to 0.91; typical RD -0.39, 95% CI -0.65 to -0.12; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). However, this outcome had a very low number of participants from two small studies with methodological differences, one of which was terminated early, increasing the uncertainty about effect estimates.There were no differences between LE types in pair-wise meta-analyses for growth in preterm infants. There was paucity of studies in preterm infants with surgical conditions or cholestasis to perform meta-analyses for growth and most other outcomes.In the secondary outcomes for preterm infants, there was no difference between fish-oil LE and non-fish oil LE in meta-analysis for severe retinopathy of prematurity (ROP) (stage 3 or greater, or requiring surgery: typical RR 0.80, 95% CI 0.55 to 1.16; typical RD -0.03, 95% CI -0.07 to 0.02; 7 studies; n = 731; very low-quality evidence). There were no differences in the LE types in pair-wise meta-analyses for death, bronchopulmonary dysplasia (BPD), ventilation duration, patent ductus arteriosus, sepsis, necrotising enterocolitis, intraventricular haemorrhage, periventricular leukomalacia, jaundice, hyperglycaemia, hypertriglyceridaemia, intrahepatocellular lipid content and conjugated bilirubin levels in any comparison.In surgical infants, one study (n = 19) reported no differences in death, sepsis rates, Cbil and neurodevelopmental outcomes with pure F-LE versus S-LE.In infants with cholestasis, there were no evidence of differences in death or sepsis in meta-analyses between fish oil-LE and S-LE; (2 studies; n = 40; very low-quality evidence).
AUTHORS' CONCLUSIONS
In the current review, we did not find any particular LE with or without fish oil to be better than another LE in preterm infants for prevention of PNALD/cholestasis, growth, mortality, ROP, BPD and other neonatal outcomes.In preterm infants with surgical conditions or cholestasis, there is currently insufficient evidence from randomised studies to determine with any certainty if fish oil LEs offer advantage in prevention or resolution of cholestasis or in any other clinical outcome.Further research, with larger well-designed trials, is warranted to evaluate the ideal composition of LE in preterm infants and the role of fish oil-containing and other LEs in the prevention and resolution of PNALD, ROP and other clinical outcomes.
Topics: Bilirubin; Bronchopulmonary Dysplasia; Chemical and Drug Induced Liver Injury; Cholestasis; Emulsions; Fish Oils; Humans; Infant, Newborn; Infant, Premature; Parenteral Nutrition; Plant Oils; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Soybean Oil; Surgical Procedures, Operative; gamma-Linolenic Acid
PubMed: 31158919
DOI: 10.1002/14651858.CD013163.pub2 -
The Cochrane Database of Systematic... Apr 2019Guttate psoriasis displays distinctive epidemiological and clinical features, making it a separate entity within the heterogeneous group of cutaneous psoriasis types. It...
BACKGROUND
Guttate psoriasis displays distinctive epidemiological and clinical features, making it a separate entity within the heterogeneous group of cutaneous psoriasis types. It is associated with genetic, immune, and environmental factors (such as stress and infections) and usually arises in younger age groups (including children, teenagers, and young adults). There is currently no cure for psoriasis, but various treatments can help to relieve the symptoms and signs. The objectives of treatment when managing an acute flare of guttate psoriasis are to reduce time to clearance and induction of long-term remission after resolution. This is an update of a Cochrane Review first published in 2000; since then, new treatments have expanded the therapeutic spectrum of systemic treatments used for psoriasis.
OBJECTIVES
To assess the effects of non-antistreptococcal interventions for acute guttate psoriasis or an acute guttate flare of chronic psoriasis.
SEARCH METHODS
We searched the following databases up to June 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials. We checked the proceedings of key dermatology conferences from 2004 to 2018, and also searched for trials in the US Food and Drug Administration (FDA) database for drug registration.
SELECTION CRITERIA
All randomised controlled trials assessing the effects of treatments for acute guttate psoriasis or an acute guttate flare of chronic psoriasis clinically diagnosed in children and adults. This included all topical and systemic drugs, biological therapy, phototherapy (all forms: topical and systemic), and complementary and alternative therapies. We compared these treatments against placebo or against another treatment. We did not include studies on drugs that aim to eradicate streptococcal infection. We did not include studies when separate results for guttate psoriasis participants were not available.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study eligibility and methodological quality and extracted data. We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'percentage of participants clear or almost clear (i.e. obtaining Psoriasis Area Severity Index (PASI) 100/90 and/or Physician's Global Assessment (PGA) of 0 or 1)' and 'percentage of participants with adverse effects and severe adverse effects'. Our secondary outcomes were 'number of relapses of guttate psoriasis or flares within a period of six months after the treatment has finished', 'percentage of participants achieving a PASI 75 or PGA of 1 or 2', and 'improvement in participant satisfaction measures and quality of life assessment measures'. We used GRADE to assess the quality of the evidence for each outcome.
MAIN RESULTS
This review included only one trial (21 participants), which compared fish oil-derived (n-3) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (10 participants) to soya oil-derived (n-6) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (11 participants) administered intravenously twice daily for 10 days, with a total follow-up of 40 days. The study was conducted in a single centre in Germany in 18 men and three women, aged between 21 and 65 years, who were in hospital with acute guttate psoriasis and had mean total body surface involvement of 25.7% ± 20.4% (range 10 to 90). The study was funded by a company that produces the oil emulsions. We found no other evidence regarding non-antistreptococcal interventions used in clinical practice for guttate psoriasis, such as topical treatments (corticosteroids, vitamin D₃ analogues), systemic drugs, biological therapy, and phototherapy.The primary outcomes of the review were not measured, and only one of our secondary outcomes was measured: improvement in participant satisfaction measures and quality of life assessment measures. However, the study authors did report that there was rare skin irritation at the site of peripheral intravenous route, but the number of affected participants was not provided.Improvement between baseline and day 10, using a non-validated score assessed by participants themselves daily based on five items (appearance of lesions, impairment of daily life, pruritus, burning, and pain), was greater in the group that received the fish oil-derived (n-3) fatty acid-based lipid emulsion (75%) than in the group receiving the soya oil-derived (n-6) fatty acid-based lipid emulsion (18%) (one trial, 21 participants). However, these results are uncertain as they are based on very low-quality evidence.
AUTHORS' CONCLUSIONS
There is no evidence regarding topical and systemic drugs, biotherapy, or phototherapy in guttate psoriasis (we did not consider drugs that aimed to eradicate streptococcal infection because these are assessed in another Cochrane Review). We are uncertain of the effect of intravenously administered lipid emulsion on guttate psoriasis because the quality of the evidence is very low, due to risk of bias (unclear risk of bias for all domains), indirectness (the trial only included adults, and the follow-up from baseline was only 10 days), and imprecision (small number of participants).This review highlights the need for trials assessing the efficacy and safety of phototherapy and topical and systemic drugs for guttate psoriasis. There is also a need for studies that clearly distinguish the specific population with guttate psoriasis from the larger group of people with chronic plaque psoriasis, and children and young adults should be assessed as a distinct group.
Topics: Administration, Oral; Administration, Topical; Biological Therapy; Humans; Immunosuppressive Agents; Phototherapy; Psoriasis; Treatment Outcome
PubMed: 30958563
DOI: 10.1002/14651858.CD011541.pub2 -
The Ocular Surface Jul 2019Dry eye disease (DED) is a multifactorial and complex disease of the ocular surface, with a high prevalence in adults. We systematically reviewed efficacy and safety...
Dry eye disease (DED) is a multifactorial and complex disease of the ocular surface, with a high prevalence in adults. We systematically reviewed efficacy and safety data from published articles reporting results from prospective, controlled trials of topical ophthalmic drugs for DED. PubMed was searched for articles from January 1997 to October 2017. Twenty-six unique trials investigating 13 ophthalmic drugs were identified, including trials of the approved drugs cyclosporine A, cyclosporine A cationic emulsion, diquafosol, rebamipide and lifitegrast. All identified studies provided level 1 evidence. None of the large (N > 100) studies demonstrated statistical significance of primary endpoints for both a sign and a symptom endpoint versus a control treatment in the same published trial. Publications on lifitegrast reported statistical superiority in a symptom or sign endpoint versus the control group in a large (N > 200), multicenter trial, with results repeated in trials of similar design. The most common adverse events associated with the approved drugs related to ocular discomfort upon instillation, especially burning/stinging and ocular irritation. The trial design and endpoints used across the studies varied considerably, highlighting the importance of standardization in clinical trials for DED. Recent advances in drug delivery and improved understanding of DED should contribute to new ophthalmic drug approvals.
Topics: Dry Eye Syndromes; Humans; Ophthalmic Solutions; Visual Acuity
PubMed: 30844466
DOI: 10.1016/j.jtos.2019.02.012 -
Journal of Alternative and... May 2019This meta-analysis aimed to assess the clinical effectiveness and safety of Javanica oil emulsion injection (JOEI) combined with the radiotherapy (RT) for treating... (Meta-Analysis)
Meta-Analysis
This meta-analysis aimed to assess the clinical effectiveness and safety of Javanica oil emulsion injection (JOEI) combined with the radiotherapy (RT) for treating esophageal cancer (EC). A literature search was conducted for collecting the randomized controlled trials (RCTs) on EC treated by JOEI in the Cochrane Library, PubMed, Embase, the Chinese Biomedical Literature Database (SinoMed), the China National Knowledge Infrastructure Database, the China Science and Technology Journal Database (VIP), and the Wanfang Database from inception to February 4, 2017. The quality of the RCTs was evaluated by the Cochrane risk of bias assessment tool, and objective remission rate, performance status, adverse drug reactions (ADRs), 1-year survival rate, and 2-year survival rate were analyzed by Review Manager 5.3 and Stata 13.0 software. A total of 11 RCTs with 909 participants were involved in this meta-analysis. The results showed that in comparison with RT alone, the JOEI combined with RT was associated with the better effects on improving objective remission rate (relative risk [RR] = 1.33, 95% confidence interval [CI 1.17-1.52], = 4.44, < 0.00001), performance status (RR = 1.52, 95% CI [1.25-1.85], = 4.24, < 0.00001), 1-year survival rate (RR = 1.37, 95% CI [1.17-1.60], = 3.86, < 0.0001), and 2-year survival rate (RR = 1.36, 95% CI [1.09-1.70], = 2.68, = 0.007). The differences between the two groups in objective remission rate, performance status, 1-year survival rate, and 2-year survival rate were statistically significant. Besides, the JOEI combined with RT could reduce the incidence of ADRs. Specifically, the statistically significant difference was detected between these two groups about leukopenia (RR = 0.39, 95% CI [0.25-0.61], = 4.19, < 0.0001), radiation esophagitis (RR = 0.68, 95% CI [0.50-0.93], = 2.42, = 0.02), thrombocytopenia (RR = 0.92, 95% CI [0.12-0.66], = 2.95, = 0.003), and hemoglobin reduction (RR = 0.53, 95% CI [0.35-0.79], = 3.14, = 0.002); however, there was no statistically significant difference for the outcome of nausea and vomiting (RR = 0.61, 95% CI [0.36-1.03], = 1.85, = 0.06) between two groups. This meta-analysis indicated that the combination of JOEI and RT was associated with the more beneficial treatment for patients with EC compared with only receiving RT. However, more well-designed and multicenter RCTs should be carried out to confirm this finding because of the limitations of enrolled 11 RCTs.
Topics: Adult; Aged; Aged, 80 and over; Chemoradiotherapy; Drugs, Chinese Herbal; Esophageal Neoplasms; Female; Humans; Male; Middle Aged
PubMed: 30785303
DOI: 10.1089/acm.2018.0096 -
The British Journal of Dermatology Jul 2019Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
BACKGROUND
Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
OBJECTIVES
To update our systematic review on interventions for rosacea.
METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index and ongoing trials registers (March 2018) for randomized controlled trials. Study selection, data extraction, risk-of-bias assessment and analyses were carried out independently by two authors. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess certainty of evidence.
RESULTS
We included 152 studies (46 were new), comprising 20 944 participants. Topical interventions included brimonidine, oxymetazoline, metronidazole, azelaic acid, ivermectin and other topical treatments. Systemic interventions included oral antibiotics, combinations with topical treatments or other systemic treatments. Several studies evaluated laser or light-based treatment. We present the most current evidence for rosacea management based on a phenotype-led approach.
CONCLUSIONS
For reducing temporarily persistent erythema there was high-certainty evidence for topical brimonidine and moderate certainty for topical oxymetazoline; for erythema and mainly telangiectasia there was low-to-moderate-certainty evidence for laser and intense pulsed light therapy. For reducing papules/pustules there was high-certainty evidence for topical azelaic acid and topical ivermectin; moderate-to-high-certainty evidence for doxycycline 40 mg modified release (MR) and isotretinoin; and moderate-certainty evidence for topical metronidazole, and topical minocycline and oral minocycline being equally effective as doxycycline 40 mg MR. There was low-certainty evidence for tetracycline and low-dose minocycline. For ocular rosacea, there was moderate-certainty evidence that oral omega-3 fatty acids were effective and low-certainty evidence for ciclosporin ophthalmic emulsion and doxycycline.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Brimonidine Tartrate; Combined Modality Therapy; Dermatologic Agents; Dermatology; Drug Therapy, Combination; Evidence-Based Medicine; Facial Dermatoses; Humans; Intense Pulsed Light Therapy; Low-Level Light Therapy; Oxymetazoline; Randomized Controlled Trials as Topic; Rosacea; Severity of Illness Index; Treatment Outcome
PubMed: 30585305
DOI: 10.1111/bjd.17590 -
Evidence-based Complementary and... 2018This meta-analysis sought to assess the efficacy and safety of oil emulsion injection (BJOEI) combined with chemotherapy for treating gastric cancer (GC). (Review)
Review
OBJECTIVE
This meta-analysis sought to assess the efficacy and safety of oil emulsion injection (BJOEI) combined with chemotherapy for treating gastric cancer (GC).
METHOD
Randomized controlled trials (RCTs) regarding BJOEI to treat GC were searched in PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure Database (CNKI), the Wan-Fang Database, China Science and Technology Journal Database (VIP), and the Chinese Biomedical Literature Database (SinoMed) up to January 9, 2017. The clinical total effective rate, performance status, adverse drug reactions (ADRs), and other outcomes were analyzed with Review Manager 5.3 and Stata12.0 software.
RESULTS
13 RCTs involving 912 patients were included in the present meta-analysis. The results demonstrated that, compared with receiving chemotherapy alone, BJOEI combined with chemotherapy was more effective in improving clinical total effective rate (RR = 1.38, 95% CI: 1.22~1.56, < 0.00001), performance status (RR = 1.63, 95% CI: 1.30~2.04, < 0.00001), and relieving ADRs such as myelosuppression, neutropenia, thrombopenia, and liver damage. Statistically significant difference was observed between the experimental group and control group.
CONCLUSION
The pooled analysis showed that using BJOEI on the basis of the chemotherapy had a remarkable therapeutic effect for patients with GC, whereas more evidence-based medical researches were required to further support our study.
PubMed: 29853964
DOI: 10.1155/2018/6350782 -
Scientific Reports Oct 2017Corneal endothelium morphological abnormalities result in fluid imbalance, stromal swelling, and loss of transparency, thus impairing visual function. Recently, growing... (Meta-Analysis)
Meta-Analysis
Corneal endothelium morphological abnormalities result in fluid imbalance, stromal swelling, and loss of transparency, thus impairing visual function. Recently, growing number of studies have focused on diabetic corneal abnormalities after cataract surgery and its comparison with non-diabetic patients, the results remain conflicting. Thus, to evaluate the effect of phacoemulsification on the corneal properties in diabetic and non-diabetic patients, prospective studies were comprehensively searched through PubMed, EMBASE, and Cochrane databases updated to Jan 2017. A meta-analysis of the 13 identified studies was performed using weighted mean difference (WMD) and 95% confidence interval (CI). For the dynamic changes between preoperative and postoperative values, significant differences were identified between the two groups in endothelial cell density (ECD) and hexagon cells (HC%) at 1 day, 1 week, 1 month, and 3 months postoperatively, in central corneal thickness (CCT) at 1 month postoperatively, and in coefficient variation (CV) at 1 week and 1 month postoperatively. However, no significant differences were observed in CCT at 1 day, 1 week and 3 months postoperatively or in CV at 1 day and 3 months postoperatively. Diabetic corneas are more vulnerable to stress and trauma, resulting in greater morphological abnormalities and longer recovery time.
Topics: Cataract; Cornea; Diabetes Complications; Emulsions; Humans
PubMed: 29074989
DOI: 10.1038/s41598-017-14656-7 -
The Cochrane Database of Systematic... Aug 2016Various hormone therapies (HT) are available to treat menopausal vasomotor symptoms. Bioidentical hormones are chemically identical to those produced by the human body,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Various hormone therapies (HT) are available to treat menopausal vasomotor symptoms. Bioidentical hormones are chemically identical to those produced by the human body, and several types are well-tested and available on prescription. Many women have opted for bioidentical hormone therapy (BHT) on the assumption that it is safer than other forms of HT. We evaluated the evidence.
OBJECTIVES
To determine the effectiveness and safety of bioidentical hormones compared to placebo or non-bioidentical hormones for the relief of vasomotor symptoms.
SEARCH METHODS
In July 2015 we searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), registers of ongoing trials and the reference lists of articles retrieved.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing bioidentical hormone therapy (BHT) versus placebo or non-bioidentical hormones.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane Collaboration. Our primary outcome was vasomotor symptoms (hot flushes and night sweats). We evaluated the overall quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation criteria (GRADE).
MAIN RESULTS
We included 23 RCTs (5779 participants). Most studies (20/23) included only women with moderate to severe hot flushes. All studies compared unopposed 17 beta-estradiol (beta-estradiol) versus placebo or conjugated equine estrogens (CEE). None of the studies reported night sweats as a separate outcome. BHT patch versus placebo Frequency of hot flushesFour RCTs reported data suitable for analysis. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.68, 95% CI -0.83 to -0.53, four RCTs, 793 women, I(2) = 67%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Seven RCTs reported data unsuitable for analysis; all reported a benefit in the intervention group. Symptom intensityTwo RCTs reported analysable data. Measured on a 0-100 visual analogue scale (VAS), hot flush intensity was lower in the BHT group (MD -19.94 points, 95% CI -24.86 to -15.02, two RCTs, 393 women, I(2) = 54%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Adverse effectsAdverse events (such as headache, vaginal bleeding, breast tenderness and skin reactions) were more common in the intervention group (odds ratio (OR) 2.14, 95% CI 1.29 to 3.54, 9 RCTs, 1822 women, I(2) = 73%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. In one study, five women in the intervention group developed endometrial hyperplasia. BHT gel versus placebo Hot flush frequencyThree RCTs reported this outcome, but the data were unsuitable for analysis. All reported a benefit in the BHT group. Adverse effectsAdverse events were more common in the BHT group (OR 1.41, 95% CI 1.09 to 1.83, 3 RCTs, 1086 women, I(2) = 0%, moderate quality evidence). Oral BHT versus placebo Hot flush frequencyTwo studies reported analysable data. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.80, 95% CI -1.03 to -0.57, two RCTs, 356 women, I(2) = 14%, low quality evidence). Adverse effectsThere was no evidence of a difference between the groups (OR 1.28, 95% CI 0.84 to 1.96, 3 RCTs, 433 women, I(2) = 0%, low quality evidence). Topical BHT emulsion versus placebo Hot flush frequencyOne study with data unsuitable for analysis reported a benefit in the intervention group. Adverse effectsThere was no evidence of a difference between the groups (OR 1.46, 95% CI 0.80 to 2.66, one RCT, 200 women, low quality evidence). Intranasal BHT versus placebo Hot flush frequencyOnly one study reported analysable data. There were fewer hot flushes per day in the BHT group (MD -3.04 95% CI -4.05 to -2.03, one study, 458 women, moderate quality evidence) Adverse effectsAdverse events (such as headache, breast tenderness, arthralgia and nausea) were more common in the intervention group (OR 1.96, 95% CI 1.26 to 3.03, one RCT, 458 women, moderate quality evidence). Subgroup analysesSubgroup analyses by dose of BHT suggested that higher doses of BHT may be associated with more effectiveness but also higher risk of adverse effects. BHT patch versus 0.625 mg CEETwo RCTs reported this comparison, but the data were unsuitable for analysis. Hot flush frequencyBoth RCTs reported no evidence of a difference between the groups. Adverse effectsFindings were inconsistent. In one comparison (0.1 mg BHT versus CEE), breast pain and vaginal bleeding were more frequent in the BHT group. Oral BHT versus 0.625 mg CEE Hot flush frequencyOne study with data unsuitable for analysis reported no evidence of a difference between the groups. Adverse effectsThere was no evidence of a difference between the groups (OR 1.20, 95% CI 0.50 to 2.87, one RCT, 103 women, very low quality evidence).
AUTHORS' CONCLUSIONS
There was low to moderate quality evidence that BHT in various forms and doses is more effective than placebo for treating moderate to severe menopausal hot flushes. There was low to moderate quality evidence of higher rates of adverse effects such as headache, vaginal bleeding, breast tenderness and skin reactions in the BHT group. There was some evidence to suggest that higher doses of BHT are associated with greater effectiveness but also with higher risk of adverse effects. Although all the included studies used unopposed estrogen, it is recommended best practice to use progestogen therapy in women with a uterus taking estrogen in order to avoid endometrial hyperplasia, regardless of the source of the estrogen. No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack, stroke and breast cancer.There was no good evidence of a difference in effectiveness between BHT and CEE, and findings with regard to adverse effects were inconsistent. The quality of the evidence was too low to reach any firm conclusions.The main limitations in the quality of the evidence were study risk of bias (mainly due to poor reporting of methods), imprecision and lack of data suitable for analysis.
Topics: Estradiol; Estrogens; Estrogens, Conjugated (USP); Female; Hot Flashes; Humans; Randomized Controlled Trials as Topic
PubMed: 27479272
DOI: 10.1002/14651858.CD010407.pub2