Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments.

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.

AGREE II assessments of recent acne treatment guidelines: how well do they reveal trustworthiness as defined by the U.S. Institute of Medicine criteria?

BACKGROUND: Up-to-date, trustworthy guidelines are a widely relied upon means of promoting excellent patient care. OBJECTIVES: To determine the quality of recently published acne treatment guidelines by utilizing the Appraisal of Guidelines for Research and Evaluation (AGREE) II Reporting Checklist, the U.S. Institute of Medicine's (IOM) criteria of trustworthiness, the red flags of Lenzer et al. and CheckUp. METHODS: Systematic searches were conducted in bibliographic databases, guideline depositories and using Google to identify acne treatment guidelines published since 2013. Six assessors independently scored each guideline using the AGREE II Reporting Checklist. Guidelines were concomitantly assessed for trustworthiness using the IOM criteria and for the red flags of Lenzer et al., indicative of potential bias. Updates were screened using CheckUp. RESULTS: Eight guidelines were identified, two of which were updates. Lowest scoring AGREE II domains across all guidelines were applicability (six poor, one fair, one average) and rigour (four poor, one fair, three average). Two of the three highest-scoring guidelines were developed using AGREE II. No guideline fully met each IOM criterion and all raised at least one red flag indicative of potential bias. One updated guideline did not address seven of 16 items on CheckUp and the other did not address four. Patient involvement in guideline development was minimal. CONCLUSIONS: Use of the AGREE II instrument during guideline development did not have as great an effect on guideline quality as might be expected. There is considerable room for improvement in acne treatment guidelines in order to satisfy the IOM trustworthiness criteria and avoid bias.

Emollients and moisturizers for eczema: abridged Cochrane systematic review including GRADE assessments.

Eczema is a chronic inflammatory skin disorder with considerable impact on quality of life. Emollients or moisturizers are widely recommended, but are these effective and safe? We searched for randomized controlled trials (RCTs) in the Cochrane Skin Group Specialised Skin Register, CENTRAL in The Cochrane Library, MEDLINE, Embase, LILACS, the GREAT database and five trial registers to December 2015. We included 77 RCTs with 6603 participants. Seven studies (9%) were at low risk of bias, 34 (44%) had unclear risk and 36 (47%) were at high risk. The quality of the evidence was mainly low or moderate for the prespecified outcomes. The most important comparison, 'moisturizer vs. no moisturizer', showed improved Scoring Atopic Dermatitis values in the moisturizer group compared with no moisturizer [mean difference -2·42, 95% confidence interval (CI) -4·55 to -0·28], but did not meet the minimal important difference of 8·7. Fewer flares were seen (risk ratio 0·40, 95% CI 0·23-0·70) and the rate of flares was reduced (hazard ratio 3·74, 95% CI 1·86-7·50). The groups applying moisturizer used less topical corticosteroids over 6-8 weeks (mean difference -9·30 g, 95% CI 15·3 to -3·27). Glycyrrhetinic acid-, urea- and glycerol-containing creams worked better than their controls (vehicle, placebo or no moisturizer) according to both participants and physicians. More flares were reported with moisturizer alone than when combined with twice-weekly fluticasone propionate (risk ratio 2·17, 95% CI 1·55-3·11). Adding moisturizers to topical anti-inflammatory treatment was more effective than anti-inflammatory treatment alone and resulted in fewer flares.

Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.

BACKGROUND: Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. PATIENTS AND METHODS: Patients with fixed cT3 or cT4 cancer were randomized either to 5 × 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. RESULTS: Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. CONCLUSIONS: No differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

Interventions for hirsutism excluding laser and photoepilation therapy alone: abridged Cochrane systematic review including GRADE assessments.

Hirsutism is a common disorder with a major impact on quality of life. The most frequent cause is polycystic ovary syndrome. Effects of interventions (except laser and light-based therapies) were evaluated, including Grading of Recommendations Assessment, Development and Evaluation assessments. Searches included Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, Medline, Embase and five trials registers to June 2014. We included 157 randomized controlled trials (RCTs) with 10 550 participants. The majority were assessed as having a 'high risk' of bias (123 of 157). The quality of evidence was rated moderate to very low for most outcomes. Pooled data for an oral contraceptive (OCP) (ethinyl oestradiol and cyproterone acetate) compared with another OCP (ethinyl oestradiol and desogestrel) demonstrated that both treatments were effective in reducing Ferriman-Gallwey scores, but the mean difference (MD) was not statistically significant [-1·84, 95% confidence interval (CI): -3·86-0·18]. Flutamide was more effective than placebo in two studies (MD -7·60, 95% CI: -10·53 to -4·67 and MD -7·20, 95% CI: -10·15 to -4·25), as was spironolactone (MD -7·69, 95% CI: -10·12 to -5·26). Spironolactone appeared to be as effective as flutamide (two studies) and finasteride (two studies). However, finasteride and the gonadotropin-releasing analogues showed discrepant results in several RCTs. Metformin was ineffective. Cyproterone acetate combined with OCPs demonstrated greater reductions in Ferriman-Gallwey scores. Lifestyle interventions reduced body mass index but did not show improvement in hirsutism, and although cosmetic measures are frequently used, no RCTs investigating cosmetic treatments were identified. RCTs investigating OCPs in combination with antiandrogens or finasteride vs. OCP alone, or the different antiandrogens and 5α-reductase inhibitors are warranted.

Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments.

Rosacea is a common chronic facial dermatosis. This update of our Cochrane review on interventions for rosacea summarizes the evidence, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group assessments, of the effects of the currently available treatments. Searches included the following: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and the Science Citation Index, and ongoing trials registries (July 2014). We included 106 randomized controlled trials (RCTs) with 13 631 participants, a more than 80% increase since the last update in 2011. Pooling of data was feasible for a few outcomes, for topical metronidazole and azelaic acid and both appeared to be more effective than placebo (moderate and high-quality evidence, respectively). Topical ivermectin was more effective than placebo based on two studies (high-quality evidence), and slightly more effective than metronidazole in one study. Brimonidine was more effective than vehicle in reducing erythema in rosacea (high-quality evidence). Ciclosporin ophthalmic emulsion was effective for ocular rosacea (low-quality evidence). For oral treatments there was moderate-quality evidence for the effectiveness of tetracycline based on two old studies, and high-quality evidence for doxycycline 40 mg compared with placebo according to physician assessments. One study at high risk of bias demonstrated equivalent effectiveness for azithromycin and doxycycline 100 mg. Minocycline 45 mg may be effective for papulopustular rosacea (low-quality evidence). Low-dose isotretinoin appeared to be slightly more effective than doxycycline 50-100 mg (high-quality evidence). Laser and light-based therapies for erythema in rosacea were effective (low-quality evidence). Further RCTs are required for ocular rosacea.

Omalizumab in patients with chronic spontaneous urticaria: a systematic review and GRADE assessment.

Chronic spontaneous urticaria (CSU) is characterized by the occurrence of hives, angio-oedema or both for a period of at least 6 weeks. Many patients remain symptomatic despite treatment with H1 antihistamines, even at higher doses. This systematic review assessed the quality of the evidence for the effects of omalizumab as treatment in patients with CSU. We searched PubMed, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials up to 7 August 2014. Three review authors independently carried out study selection, risk of bias assessment and data extraction. Two review authors analysed the data. Five randomized controlled trials (RCTs), which included 1116 participants, were evaluated. All the RCTs were judged as having a low risk of bias. There was a statistically significant improvement in measures of disease activity and quality of life following treatment with omalizumab when compared with placebo [mean difference (MD) -11·58, 95% confidence interval (CI) -13·39 to -9·77 and MD -13·12, 95% CI -16·30 to -9·95, respectively]. Complete response and partial response were more frequent after treatment with omalizumab [risk ratio (RR) 6·44, 95% CI 3·95-10·49 and RR 4·08, 95% CI 2·98-5·60, respectively]. There was no difference in the proportion of participants reporting adverse events between the omalizumab and placebo treatment groups (RR 1·05, 95% CI 0·96-1·16). There was high-quality evidence to support the effectiveness and safety of omalizumab 300 mg per month for the treatment of CSU for up to 6 months.

Evidence-based topical treatments for tinea cruris and tinea corporis: a summary of a Cochrane systematic review.

Tinea cruris and tinea corporis are common fungal infections. Most can be treated with a variety of topical antifungals. This review aimed to assess the evidence for the effectiveness and safety of topical treatments for tinea cruris and tinea corporis. Searches included the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, Medline, Embase, LILACS and ongoing trials registries (August 2013). One hundred and twenty-nine randomized controlled trials (RCTs) with 18 086 participants evaluated a range of interventions - mostly azoles. Pooling of data for several outcomes was only possible for two individual treatments. In five studies, terbinafine showed a statistically significant higher clinical cure rate compared with placebo [risk ratio (RR) 4·51, 95% confidence interval (CI) 3·10-6·56]. Data for mycological cure could not be pooled owing to substantial heterogeneity. Across three studies, mycological cure rates favoured naftifine (1%) compared with placebo (RR 2·38, 95% CI 1·80-3·14) but the quality of the evidence was low. Combinations of azoles with corticosteroids were slightly more effective than azoles for clinical cure, but there was no statistically significant difference with regard to mycological cure. Sixty-five studies were assessed as 'unclear' and 64 as being at 'high risk' of bias; many were over 20 years old, and most were poorly designed and inadequately reported. Although most active interventions showed sufficient therapeutic effect, this review highlights the need for further, high-quality, adequately powered RCTs to evaluate the effects of these interventions, which can ultimately provide reliable evidence to inform clinical decision making.

Evidence-based treatments for female pattern hair loss: a summary of a Cochrane systematic review.

Female pattern hair loss (FPHL) or androgenic alopecia is the most common type of hair loss affecting women with reduced hair density and can have a serious psychological impact. It is characterized by progressive replacement of slow cycling terminal hair follicles by miniaturized, rapidly cycling vellus hair follicles. The frontal hair line may or may not be preserved. The aim of this review was to assess the evidence for the effectiveness and safety of the treatments available for FPHL. Searches included: Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Clinical Trials in The Cochrane Library, MEDLINE, EMBASE, AMED, PsycINFO, LILACS and several ongoing trials registries (October 2011). Randomized controlled trials in women with FPHL were identified. Twenty-two trials, comprising 2349 participants, were included. A range of interventions was evaluated, with 10 studies examining varying concentrations of minoxidil. Pooled data from four studies indicated that a greater proportion of participants treated with minoxidil reported a moderate increase in their hair regrowth compared with placebo (relative risk 1·86, 95% confidence interval 1·42-2·43). There was no difference between the number of adverse events experienced in the twice daily minoxidil and the placebo intervention groups, except for a reported increase with minoxidil 5% twice daily. Single studies accounted for most of the other comparisons, which were assessed as either having high risk of bias and/or they did not address the prespecified outcomes for this review and provided limited evidence of either the effectiveness or safety of these interventions. Further well-designed, adequately powered randomized controlled trials investigating other treatment options are still required.

One health: perspectives on ethical issues and evidence from animal experiments.

Zoonoses constitute more than 60% of all known infectious diseases and 75% of emerging infectious diseases. Their impact is not monitored, prevented and treated in an integrated way. The efficacy of therapeutic interventions for zoonotic diseases is deemed to be comparable across species with scientifically valid results originating from a range of animal experiments. Ethical obligations limit the number of animals used in experiments as well as reduce repetition of studies. The evidence based on randomized controlled trails and systematic reviews for the effectiveness of health care interventions is often inconclusive. Subjecting human volunteers to risk in the absence of scientifically valid results from animal experiments is unethical. The One Health concept is a comparative, clinical approach directed towards zoonoses which present challenges to research workers and clinicians. Optimal health for all--One Health--should be underpinned by ethically conducted research in animals or humans and the results should be complementary to both.

One Health: perspectives on ethical issues and evidence from animal experiments

Zoonoses constitute more than 60% of all known infectious diseases and 75% of emerging infectious diseases. Their impact is not monitored, prevented and treated in an integrated way. The efficacy of therapeutic interventions for zoonotic diseases is deemed to be comparable across species with scientifically valid results originating from a range of animal experiments. Ethical obligations limit the number of animals used in experiments as well as reduce repetition of studies. The evidence based on randomized controlled trails and systematic reviews for the effectiveness of health care interventions is often inconclusive. Subjecting human volunteers to risk in the absence of scientifically valid results from animal experiments is unethical. The One Health concept is a comparative, clinical approach directed towards zoonoses which present challenges to research workers and clinicians. Optimal health for all-One Health-should be underpinned by ethically conducted research in animals or humans and the results should be complementary to both

Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review.

Rosacea is a common chronic skin disease affecting the face. There are numerous treatment options, but it is unclear which are the most effective. The aim of this review was to assess the evidence for the efficacy and safety of treatments for rosacea. Searches included the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and Ongoing Trials Registers (updated February 2011). Randomized controlled trials in people with moderate to severe rosacea were included. Fifty-eight trials, including 27 from the original review, comprising 6633 participants were included in this updated review. Interventions included topical metronidazole, oral antibiotics, topical azelaic cream or gel, topical benzoyl peroxide and/or combined with topical antibiotics, sulphacetamide/sulphur, and others. There was some evidence that topical metronidazole and azelaic acid were more effective than placebo. Two trials indicated that doxycycline 40mg was more effective than placebo. There was no statistically significant difference in effectiveness between doxycycline 40mg and 100mg but there were fewer adverse effects. One study reported that ciclosporin ophthalmic emulsion was significantly more effective than artificial tears for treating ocular rosacea. Although the majority of included studies were assessed as being at high or unclear risk of bias, there was some evidence to support the effectiveness of topical metronidazole, azelaic acid and doxycycline (40mg) in the treatment of moderate to severe rosacea, and ciclosporin 0·05% ophthalmic emulsion for ocular rosacea. Further well-designed, adequately powered randomized controlled trials are required.

Repair or replacement of restorations: do we accept built in obsolescence or do we improve the evidence?

INTRODUCTION: Controversy surrounds decisions on whether to repair or replace defective dental restorations. The concept of built-in obsolescence, ie periodic replacement of dental restorations, is largely accepted as the modus operandi if not the default mode in restorative care. In this article we examine the current best available evidence underpinning the effectiveness of replacement versus repair of direct amalgam and resin composite restorations. METHOD: This article builds on two recent Cochrane systematic reviews which have reported on the evidence base supporting the effectiveness of replacement versus repair of amalgam and direct resin composites and translates the results of their research conclusions into recommendations for the dental clinician. RESULTS: As no relevant randomised controlled trials (RCTs) were identified in either of these systematic reviews, the evidence regarding the effectiveness of repair versus replacement of amalgam and composite restorations is weak and incomplete. The evidence as it currently stands seems to favour repair over replacement, but this is insufficient to make firm recommendations. CONCLUSION: In view of the absence of high level evidence there is a need for further well designed RCTs. To add value to the evidence base these trials should be conducted in a general practice setting which will strengthen the generalisability and applicability of the research conclusions and enable dentists and patients to make informed decisions.