Prioritizing treatment outcomes: How people with acne vulgaris decide if their treatment is working.

OBJECTIVE: To collect information about how people with acne make day-to-day decisions concerning the effectiveness of their treatment. METHODS: Between May and August 2013, an optional question was embedded in the James Lind Alliance Acne Priority Setting Partnership's online survey to collect treatment uncertainties. The question asked people with acne to "Tell us in your own words how you decide if your treatment has been effective." RESULTS: A total of 742 respondents specified at least one outcome or means of assessing change (outcome measure). Fewer spots were the most commonly cited outcome, identified by 272 respondents (36.7%). Other frequently mentioned outcomes were in descending order: less redness (19.4%), reduction in spot size (12.1%), and less pain/discomfort (11.4%). Signs were much more commonly used than symptoms and surrogate outcomes such as changes in aspects of life quality were infrequently mentioned. Visual inspection of the skin was the most widely adopted outcome measure (16.3%). CONCLUSIONS: Although the most frequently used methods map well onto the outcome measures adopted in the majority of acne trials, namely physician-assessed changes in lesion counts and global acne severity, people with acne often take into account several factors that cannot be assessed by a third party at a single point in time. The minimal use of changes in psychosocial wellbeing and mood may reflect that these are regarded as secondary consequences of improvements in appearance. The robustness of these findings now requires independent evaluation. If confirmed, they could form the basis of a new patient-reported outcome measure.

Oral Spironolactone for Acne Vulgaris in Adult Females: A Hybrid Systematic Review.

BACKGROUND: The management of acne in adult females is problematic, with many having a history of treatment failure and some having a predisposition to androgen excess. Alternatives to oral antibiotics and combined oral contraceptives (COCs) are required. OBJECTIVE: Our aim was to conduct a hybrid systematic review of the evidence for benefits and potential harms of oral spironolactone in the management of acne in adult females. METHODS: The review was conducted according to a previously published protocol. Three reviewers independently selected relevant studies from the search results, extracted data, assessed the risk of bias, and rated the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Ten randomized controlled trials (RCTs) and 21 case series were retrieved. All trials were assessed as being at a 'high risk' of bias, and the quality of evidence was rated as low or very low for all outcomes. Apart from one crossover trial that demonstrated statistical superiority of a 200 mg daily dose versus inflamed lesions compared with placebo, data from the remaining trials were unhelpful in establishing the degree of efficacy of lower doses versus active comparators or placebo. Menstrual side effects were significantly more common with the 200 mg dose; frequency could be significantly reduced by concomitant use of a COC. Pooling of results for serum potassium supported the recent recommendation that routine monitoring is not required in this patient population. CONCLUSION: This systematic review of RCTs and case series identified evidence of limited quality to underpin the expert endorsement of spironolactone at the doses typically used (≤100 mg/day) in everyday clinical practice.

Identifying acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership.

OBJECTIVES: The Acne Priority Setting Partnership (PSP) was set up to identify and rank treatment uncertainties by bringing together people with acne, and professionals providing care within and beyond the National Health Service (NHS). SETTING: The UK with international participation. PARTICIPANTS: Teenagers and adults with acne, parents, partners, nurses, clinicians, pharmacists, private practitioners. METHODS: Treatment uncertainties were collected via separate online harvesting surveys, embedded within the PSP website, for patients and professionals. A wide variety of approaches were used to promote the surveys to stakeholder groups with a particular emphasis on teenagers and young adults. Survey submissions were collated using keywords and verified as uncertainties by appraising existing evidence. The 30 most popular themes were ranked via weighted scores from an online vote. At a priority setting workshop, patients and professionals discussed the 18 highest-scoring questions from the vote, and reached consensus on the top 10. RESULTS: In the harvesting survey, 2310 people, including 652 professionals and 1456 patients (58% aged 24 y or younger), made submissions containing at least one research question. After checking for relevance and rephrasing, a total of 6255 questions were collated into themes. Valid votes ranking the 30 most common themes were obtained from 2807 participants. The top 10 uncertainties prioritised at the workshop were largely focused on management strategies, optimum use of common prescription medications and the role of non-drug based interventions. More female than male patients took part in the harvesting surveys and vote. A wider range of uncertainties were provided by patients compared to professionals. CONCLUSIONS: Engaging teenagers and young adults in priority setting is achievable using a variety of promotional methods. The top 10 uncertainties reveal an extensive knowledge gap about widely used interventions and the relative merits of drug versus non-drug based treatments in acne management.

A honey trap for the treatment of acne: manipulating the follicular microenvironment to control Propionibacterium acnes.

Today, as 40 years ago, we still rely on a limited number of antibiotics and benzoyl peroxide to treat inflammatory acne. An alternative way of suppressing the growth of Propionibacterium acnes is to target the environment in which it thrives. We conjecture that P. acnes colonises a relatively "extreme" habitat especially in relation to the availability of water and possibly related factors such as ionic strength and osmolarity. We hypothesise that the limiting "nutrient" within pilosebaceous follicles is water since native sebum as secreted by the sebaceous gland contains none. An aqueous component must be available within colonised follicles, and water may be a major factor determining which follicles can sustain microbial populations. One way of preventing microbial growth is to reduce the water activity (a w ) of this component with a biocompatible solute of very high water solubility. For the method to work effectively, the solute must be small, easily diffusible, and minimally soluble in sebaceous lipids. Xylose and sucrose, which fulfil these criteria, are nonfermentable by P. acnes and have been used to reduce water activity and hence bacterial colonisation of wounds. A new follicularly targeted topical treatment for acne based on this approach should be well tolerated and highly effective.

Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial.

BACKGROUND: We investigated the efficacy and cost-effectiveness of five antimicrobial regimens for mild to moderate facial acne and whether propionibacterial antibiotic resistance affects treatment response. METHODS: In this randomised, observer-masked trial, 649 community participants were allocated one of five antibacterial regimens. Primary outcomes were patients' self-assessed improvement and reduction in inflamed lesions at 18 weeks. Analyses were by intention to treat. FINDINGS: Moderate or greater improvement at 18 weeks was reported in 72 (55%) of 131 participants assigned oral oxytetracycline plus topical placebo, 70 (54%) of 130 assigned oral minocycline plus topical placebo, 78 (60%) of 130 assigned topical benzoyl peroxide plus oral placebo, 84 (66%) of 127 assigned topical erythromycin and benzoyl peroxide in a combined formulation plus oral placebo, and 82 (63%) of 131 assigned topical erythromycin and benzoyl peroxide separately plus oral placebo. Most improvement occurred in the first 6 weeks. Treatment differences for the proportion of people with at least moderate improvement were: minocycline versus oxytetracycline -1.2% (unadjusted 95% CI -13.3 to 10.9); combined erythromycin and benzoyl peroxide versus oxytetracycline 11.1% (-0.7 to 22.9) and versus minocycline 12.3% (0.4 to 24.2); erythromycin and benzoyl peroxide separately versus combined formulation -3.5% (-15.2 to 8.2); benzoyl peroxide versus oxytetracycline 5.0% (-7.0 to 17.0), versus minocycline 6.2% (-5.8 to 18.2), and versus combined formulation -6.1% (-17.9 to 5.7). Benzoyl peroxide was the most cost-effective treatment. Efficacy of both tetracyclines was reduced by pre-existing tetracycline resistance. INTERPRETATION: Topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations are similar in efficacy to oral oxytetracycline and minocycline and are not affected by propionibacterial antibiotic resistance.

Staphylococcal resistance revisited: community-acquired methicillin resistant Staphylococcus aureus--an emerging problem for the management of skin and soft tissue infections.

PURPOSE OF REVIEW: In the community non-localized or deep staphylococcal skin and soft tissue infections are typically managed with beta-lactamase stable penicillins. The aims of this review are (1) to evaluate the evidence for the emergence of new strains of community-acquired methicillin resistant Staphylococcus aureus (MRSA), (2) to identify the reasons for their significant association with cutaneous infections, and (3) to consider how they arose and how big a threat they pose to the management of such infections outside hospitals. RECENT FINDINGS: MRSA are emerging as significant community pathogens, especially in previously healthy children with no recognizable risk factors, and are predominantly associated with skin and soft tissue infections (especially abscesses and cellulitis). When present, risk factors are generally similar to those for infection with methicillin susceptible S. aureus. The MRSA isolates associated with such infections may not be entirely 'new', but could represent the displacement of some hospital clones (e.g. EMRSA-15 or variants thereof) to the community as well as the de-novo generation of novel MRSA clones by multiple horizontal transmissions of the mecA gene into methicillin susceptible S. aureus with different genetic backgrounds, some of which are already circulating globally. Community-acquired MRSA from diverse locations are non multiresistant and almost always contain the novel type IV SCCmec commonly found in coagulase-negative staphylococci, but also in hospital-associated gentamicin susceptible MRSA from France, the paediatric clone and in EMRSA-15. SUMMARY: More local data on CA-MRSA infections are needed so that dermatologists and community physicians can assess the risk of such infections amongst their patients and avoid the inappropriate administration of beta-lactams. No simple change in prescribing practices will entirely alleviate selective pressure for the spread of community-acquired MRSA and not exacerbate resistance in pyogenic streptococci, commonly found together with S. aureus in skin and soft tissue infections. The importance of hygiene in preventing the spread of community-acquired MRSA in the community must be reemphasized.

Detection of transposon Tn5432-mediated macrolide-lincosamide-streptogramin B (MLSB) resistance in cutaneous propionibacteria from six European cities.

Forty-five cutaneous propionibacterial isolates from six European cities were found to be highly resistant to all macrolide-lincosamide-streptogramin B antibiotics, including the ketolide telithromycin. This contrasts with previously documented phenotypes associated with 23S rRNA mutations. Sequencing of the resistance determinant showed it to be erm(X) of corynebacterial origin located on the composite transposon Tn5432.