Gabapentin versus dexchlorpheniramine as treatment for uremic pruritus: a randomised controlled trial

Background

Uremic pruritus is acommonsymptom in chronic renal failure patients with undefined pathophysiology. Initial treatment involves topical therapy mainly in the form of moisturizers, however, in many cases, this is not sufficient to relieve itching. Systemic adjuvant therapy is therefore necessary, which commonly includes oral antihistamines, with limited success. Positive effects have been reported for gabapentin.

Objectives

To evaluate the efficacy and safety of gabapentin vs. dexchlorpheniramine in reducing uremic pruritus.

Materials & Methods

A randomized, controlled, double-blinded clinical trial for haemodialysis patients with persistent pruritus was performed. Pre-randomisation, cold cream was used for 15 days by 71 participants. Those with pruritus who remained in the study (60 patients) were randomised to receive gabapentin (30 patients; GABA group) or dexchlorpheniramine (30 patients;DEXgroup) for 21 days. The primary outcomewas the decrease in pruritus score and improvement in quality of life.

Results

After cold cream use, the participants demonstrated a 37.5% median reduction in Visual Analogue Scale (p<0.01) and a 50% reduction in Quality of Life in Dermatology (DLQI) score (p<0.01). There was an additional reduction of pruritus in both groups (p<0.01), with no difference between the two (p>0.7). The median DLQI was reduced from 2 to 1 in the GABA group and from 2 to 0 in the DEX group. Nineteen patients (32%) reported mild/moderate side effects without differences between the groups.

Conclusions

Uremic pruritus was reduced upon treatment with gabapentin or dexchlorpheniramine with good safety profiles; no difference was observed between the two treatments.

     

Outcome measures for vulval skin conditions: a systematic review of randomized controlled trials

Symptoms and signs of vulval skin disorders are common. These conditions can have a considerable impact on quality of life, restricting physical activities and causing difficulty in everyday activities and may also affect social, psychosexual and psychological well‐being. There are no standardized measures routinely used to assess the impact of vulval disease on daily life. To report outcome measures used in clinically based randomized controlled trials (RCTs) investigating therapeutic interventions in vulval disease. The Medline, EMBASE and CENTRAL databases were searched to identify RCTs of vulval skin conditions written in English. Studies with laboratory tests or survival rates as the primary outcome, or those investigating menopausal symptoms or infections were excluded. Twenty‐eight published RCTs were included. The vulval conditions represented were vulvodynia (n = 14), lichen sclerosus (n = 9), vulval intraepithelial neoplasia (n = 2), vulval pruritus (n = 2) and lichen planus (n = 1). The 28 RCTs measured 25 different outcomes, using 49 different scales. The method of outcome assessment was lacking on nine occasions. Only 21% (six of 28) of included trials had a clearly stated primary outcome. Patient‐reported outcomes were more commonly reported than clinician‐related outcome measures. The most commonly reported patient‐rated outcome measure was a reduction in pain (measured 15 times) and an overall improvement in symptoms using a patient global assessment (measured 11 times). The most commonly reported clinician‐rated outcome was an overall assessment of the appearance of affected sites (measured 13 times). There were no agreed standard scales used for the global assessments. Only nine of the recorded outcome measure tools were designed to assess vulval disease or sexual functioning, the remainder were general measures. There is heterogeneity in the outcome measures used when reporting therapeutic interventions in vulval disease. This field of dermatology would benefit from development of a vulval‐specific outcome measure and the establishment of a core outcome measure set.     

Topical herbal medicines for atopic eczema: a systematic review of randomized controlled trials

Despite the availability of medicines with proven efficacy, many patients use complementary or alternative medicines (CAMs) to manage atopic eczema (AE). Due to the lack of objective information on topical CAMs, this systematic review evaluates the current evidence for the efficacy and safety of topical herbal preparations in AE. Using Cochrane systematic review methodology, PubMed, the Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (via EBSCO), MEDLINE (via EBSCO), Proquest Health and Medical Complete, GREAT and CAM‐QUEST were searched from inception until June 2014. Bibliographies of retrieved studies were hand searched for further relevant trials. All controlled clinical trials of topical herbal medicines for AE in humans of any age were included regardless of the control intervention or randomization. Only English‐language publications were considered. Eight studies met the inclusion criteria. Seven investigated extracts of single plants and one an extract from multiple plants. Only two studies that showed a positive effect were considered to have a low risk of bias across all domains (those of liquorice gel and Hypericum perforatum). In these two, the test product was reported to be superior to placebo. Despite variations in diagnostic criteria and lack of validated tools for outcome assessments in one of these, the promising results may warrant continued research in better‐designed studies. No meta‐analysis was performed due to heterogeneity in all studies. There is currently insufficient evidence of efficacy for any topical herbal extract in AE. Many studies had methodological flaws and even those showing efficacy were single trials with small patient cohorts.     

Reporting of outcomes in randomized controlled trials on nail psoriasis: a systematic review

One of the important complications of the skin disease, psoriasis, is the appearance of changes in the nails. These range from the formation of small pits across the surface of the nail to painful separation of the nail plate from the underlying nail bed and disfiguring enlargement and thickening of the nail itself. Given this wide range of changes in appearance it is important that, in assessing the results of treatment, researchers can use simple, but accurate, criteria for measuring changes in psoriatic nails under treatment; these are known as core outcome sets. This study, organised by investigators from the departments of dermatology in the Universities of Amsterdam and Nijmegen in the Netherlands, surveyed 65 clinical trials focussing on nail psoriasis, all of which used assessment measures for nail changes in psoriasis, the commonest of which is called the nail psoriasis severity index. However, they found that several different methods were used in the various studies. A detailed analysis of these studies has identified a number of variations in the methods used which make the results of different treatments difficult to compare. This is particularly because there was no standard way of expressing the final scores of the severity of nail disease found in these studies and also that the different aspects of severity were rated differently. Some of these assessment scoring systems have not been validated (substantiated) either. The authors call for a rethink of the use of nail assessments in psoriasis and highlight the need to develop new methods which are sufficiently robust to stand up to close scrutiny. These should allow investigators to assess the different changes seen in the diseased nails in a standardised way, so that results of different studies can be compared. They suggest that a consensus group should be established to carry out this work.     

Reporting of symptoms in randomized controlled trials of atopic eczema treatments: a systematic review

‘Symptoms’ is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand‐alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms‐only data from most published studies. Future trials should report symptom scores to permit meta‐analysis of the core outcomes.     

Homeopathy for eczema: a systematic review of controlled clinical trials

Background Homeopathy is often advocated for patients with eczema. Objectives This article systematically reviews the evidence from controlled clinical trials of any type of homeopathic treatment for any type of eczema. Methods Electronic searches were conducted in Medline, Embase and the Cochrane Library with no restrictions on time or language. In addition, the bibliographies of the retrieved articles and our departmental files were hand searched. All controlled trials of homeopathy in patients with eczema were considered. Their methodological quality was estimated using the Jadad score. Results One randomized and two nonrandomized clinical trials met the inclusion criteria. All were methodologically weak. None demonstrated the efficacy of homeopathy. Conclusions The evidence from controlled clinical trials therefore fails to show that homeopathy is an efficacious treatment for eczema.     

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials

OBJECTIVE: To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. DATA SOURCES: Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. STUDY SELECTION: Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). DATA EXTRACTION: Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. DATA SYNTHESIS: Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. CONCLUSIONS: Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.     

A systematic review of randomized controlled trials of treatments for inherited forms of epidermolysis bullosa

Background.  Many interventions have been described for inherited epidermolysis bullosa (EB), but it is unclear which are beneficial.
Aims.  A systematic review of randomized controlled trials (RCTs) was performed to inform practice and highlight research gaps.
Methods.  The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and the Cochrane Skin Group specialist library, from inception until 1 April 2007, were searched. Primary outcomes were healing of lesions or prevention of new lesions. Trials were assessed for quality of reporting and data were extracted.
Results.  Five randomized double-blind placebo-controlled crossover studies were identified ( n  = 102). Two studies assessed oral tetracyclines in EB simplex (EBS). In one study ( n  = 12), 4/6 patients improved and 2/6 deteriorated on a dose of 1500 mg of tetracycline daily; only two patients completed the study. In the second study ( n  = 21), 6/18 and 7/18 improved on oxytetracycline 1 g and placebo, respectively. Two RCTs assessed topical interventions for EBS: aluminium chloride hexahydrate solution 20% ( n  = 23) and bufexamac cream 5% ( n  = 8). Neither showed a benefit over placebo. One RCT of 36 patients with recessive dystrophic EB compared phenytoin with placebo and failed to show any difference in mean lesion counts (difference = 0, 95% CI −11 to 4).
Conclusions.  There is no reliable trial evidence for interventions in inherited EB. In future, it may be that gene treatment becomes the best treatment approach for these diseases.     

Homoeopathic remedies in dermatology: a systematic review of controlled clinical trials

Background Homoeopathic therapies are routinely used for the management of skin diseases. However, there is a lack of evidence‐based data on their effectiveness. Objectives To assess the evidence for the efficacy of homoeopathic treatments in dermatology. Methods We designed a systematic review of the controlled clinical trials (January 1962–April 2011) investigating homoeopathic therapies for the treatment of cutaneous diseases. We collected data from MEDLINE, PubMed, Current Contents, HomInform (Glasgow), reference lists, specialist textbooks and contacts with homoeopathic manufacturers. There was no restriction on language. Subsets were defined according to treated skin disease/condition. For each subset, two reviewers extracted data for information on study quality, type of remedy, population and outcomes. Results After an extensive search, we isolated a very limited number of trials investigating homoeopathic treatments for cutaneous diseases. Overall, of the 12 trials with interpretable results, nine trials indicated no positive effects of homoeopathy. The three trials showing a positive effect were of low methodological quality. Conclusions Reviewed trials of homoeopathic treatments for cutaneous diseases were highly variable in methods and quality. We did not find sufficient evidence from these studies that homoeopathy is clearly efficacious for any single dermatological condition.     

Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials

BACKGROUND: The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest. OBJECTIVES: The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population. METHODS: Three electronic databases were searched for relevant trials: MEDLINE (1966-October 2003), EMBASE (1980-week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi-randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and abstracts found by the search strategy were independently reviewed by two researchers for inclusion into the review. RESULTS: Eighty-one abstracts were identified through the electronic databases for consideration. Review of the abstracts identified three eligible trials. One cross-over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug-free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow-up. CONCLUSIONS: The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the risk-benefit ratio.     

Acupuncture plus moxibustion for herpes zoster: A systematic review and meta‐analysis of randomized controlled trials

Herpes zoster is an acute inflammatory condition which can have a significant impact on quality of life. Antiviral therapies are effective, but do not meet patients' expectations of symptomatic relief. Acupuncture and moxibustion have been used for herpes zoster; this systematic review evaluated their efficacy and safety. Nine English and Chinese databases were searched from their inceptions to March 2016. Randomized controlled trials evaluating the combination of acupuncture plus moxibustion in adult herpes zoster were included. Outcomes included pain intensity and duration, quality of life and adverse events. Meta‐analysis was performed using RevMan software (version 5.3). Nine studies (945 participants) were included. Studies were of low to moderate methodological quality based on risk of bias assessment. Pain intensity (visual analogue scale) was lower among those who received acupuncture plus moxibustion compared with pharmacotherapy (one study; MD ?8.25 mm, 95% CI ?12.36 to ?4.14). The clinical significance of this result is yet to be established. Some benefits were seen for other pain and cutaneous outcomes, and global improvement in symptoms. Mild adverse events were reported in the intervention groups. Acupuncture plus moxibustion may improve pain and cutaneous outcomes, although current evidence is limited by the number of studies and methodological shortcomings.     

他克莫司软膏治疗特应性皮炎疗效和安全性评价

目的：系统评价外用他克莫司软膏治疗特应性皮炎（AD）的临床疗效及安全性。方法：计算机检索Cochrane图书馆、Cochrane协作网皮肤病专业试验数据库、Medline、OVID数据库和中文生物医学期刊数据库．收集所有外用他克莫司与安慰剂、氢化可的松的随机对照试验（RCT）,对其进行系统评价。结果：共纳入RCT13篇论文,共5320例患者。Meta分析治疗有效率,结果显示：0．03％和0．1％他克莫司在12周疗程内疗效均优于安慰剂;0．03％和0．1％他克莫司3周疗程均高于1％醋酸氢化可的松,均不高于0．1％丁酸氢化可的松,但0．1％他克莫司在6个月疗程时疗效优于合用1％醋酸氢化可的松（用于头面部）和0．1％丁酸氢化可的松（用于躯干和四肢）;0．1％他克莫司在疗程12周内疗效优于0．03％他克莫司。最常见的不良反应是皮肤刺激和烧灼感。结论：他克莫司软膏治疗AD效果优于安慰剂及弱效糖皮质激素,长期疗效可能超过中强效糖皮质激素。目前外用他克莫司临床上是安全的,但尚需进行更多长期的RCT。