Do patient characteristics matter when calculating sample size for eczema clinical trials?

Background: The Patient-Oriented Eczema Measure (POEM) is the core outcome instrument recommended for measuring patient-reported atopic eczema symptoms in clinical trials. To ensure that the statistical significance of clinical trial results is meaningful, trials are often designed by specifying the target difference in the primary outcome as part of the sample size calculation. One method used to specify the target difference is a score that corresponds to a standardized effect size. Objectives: to assess how the standardized effect size of POEM scores vary across age, gender, ethnicity and disease severity. Methods: This study combined data from five UK-based randomized clinical trials of eczema treatments in order to assess differences in self-reported eczema symptoms (POEM) corresponding to a standardized effect size (0.5 SD of baseline POEM scores) across age, gender, ethnicity and disease severity. Results: POEM scores corresponding to 0.5 SD(baseline) were remarkably consistent across participants of varying ages, gender, ethnicity and disease severity from datasets of five UK trials in children (range 2.99-3.45). Conclusions: This study provides information that can support those designing clinical trials to determine their sample size and can aid individuals interpreting trial results. Further exploration of differences in populations beyond the United Kingdom is needed.

Risk of complications and mortality following recurrent and non-recurrent Clostridioides difficile infection: a retrospective observational database study in England.

BACKGROUND: Clostridioides difficile infection (CDI) increases the risk of complications and mortality. We assessed the magnitude of these outcomes in a large cohort of English patients with initial and recurrent CDI. AIM: To compare the risk of complications and all-cause mortality, within 12 months, among hospitalized patients ≥18 years old with hospital-associated- (HA-) CDI and recurrent CDI. METHODS: Patients with HA-CDI during 2002-2013 were identified using inpatient hospital data linked to primary care and death data. Each HA-CDI case was frequency matched to two hospitalized patients without CDI on age group, sex, calendar year of admission, admission method and number of hospital care episodes. A second CDI episode starting on days 13-56 was defined as recurrence. Risks of mortality and complications at 12 months were analysed using Cox proportional hazard models. FINDINGS: We included 6862 patients with HA-CDI and 13,724 without CDI. Median age was 81.0 years (IQR 71.0-87.0). Patients with HA-CDI had more comorbidities than those without CDI, and significantly higher risks of mortality (adjusted hazard ratio (95% confidence interval) 1.77 (1.67-1.87)) and complications (1.66 (1.46-1.88)) within 12 months from hospital admission. Of those with HA-CDI, 1140 (16.6%) experienced CDI recurrence. Patients with recurrent versus non-recurrent CDI also had significantly increased risk of mortality (1.32 (1.20-1.45)) and complications (1.37 (1.01-1.84)) in the 12 months from the initial CDI. CONCLUSIONS: HA-CDI (versus no CDI) and recurrent CDI are both associated with significantly higher risks of complications or death within 12 months of the initial CDI episode.

What the public think about participation in medical research during an influenza pandemic: an international cross-sectional survey.

OBJECTIVES: The public and patients are primary contributors and beneficiaries of pandemic-relevant clinical research. However, their views on research participation during a pandemic have not been systematically studied. We aimed to understand public views regarding participation in clinical research during a hypothetical influenza pandemic. STUDY DESIGN: This is an international cross-sectional survey. METHODS: We surveyed the views of nationally representative samples of people in Belgium, Poland, Spain, Ireland, the United Kingdom, Canada, Australia and New Zealand, using a scenario-based instrument during the 2017 regional influenza season. Descriptive and regression analyses were conducted. RESULTS: Of the 6804 respondents, 5572 (81.8%) thought pandemic-relevant research was important, and 5089 (74.8%) thought 'special rules' should be applied to make this research feasible. The respondents indicated willingness to take part in lower risk (4715, 69.3%) and higher risk (3585, 52.7%) primary care and lower risk (4780, 70.3%) and higher risk (4113, 60.4%) intensive care unit (ICU) study scenarios. For primary care studies, most (3972, 58.4%) participants preferred standard enrolment procedures such as prospective written informed consent, but 2327 (34.2%) thought simplified procedures would be acceptable. For ICU studies, 2800 (41.2%) preferred deferred consent, and 2623 (38.6%) preferred prospective third-party consent. Greater knowledge about pandemics, trust in a health professional, trust in the government, therapeutic misconception and having had ICU experience as a patient or carer predicted increased willingness to participate in pandemic-relevant research. CONCLUSIONS: Our study indicates current public support for pandemic-relevant clinical research. Tailored information and initiatives to advance research literacy and maintain trust are required to support pandemic-relevant research participation and engagement.

Levels of wound calprotectin and other inflammatory biomarkers aid in deciding which patients with a diabetic foot ulcer need antibiotic therapy (INDUCE study).

AIMS: Deciding if a diabetic foot ulcer is infected in a community setting is challenging without validated point-of-care tests. Four inflammatory biomarkers were investigated to develop a composite algorithm for mildly infected diabetic foot ulcers: venous white cell count, C-reactive protein (CRP) and procalcitonin, and a novel wound exudate calprotectin assay. Calprotectin is a marker of neutrophilic inflammation. METHODS: In a prospective study, people with uninfected or mildly infected diabetic foot ulcers who had not received oral antibiotics in the preceding 2 weeks were recruited from community podiatry clinics for measurement of inflammatory biomarkers. Antibiotic prescribing decisions were based on clinicians' baseline assessments and participants were reviewed 1 week later; ulcer infection was defined by clinicians' overall impression from their two assessments. RESULTS: Some 363 potential participants were screened, of whom 67 were recruited, 29 with mildly infected diabetic foot ulcers and 38 with no infection. One participant withdrew early in each group. Ulcer area was 1.32 cm2 [interquartile range (IQR) 0.32-3.61 cm2 ] in infected ulcers and 0.22 cm2 (IQR 0.09-1.46 cm2 ) in uninfected ulcers. Baseline CRP for mild infection was 9.00 mg/ml and 6.00 mg/ml for uninfected ulcers; most procalcitonin levels were undetectable. Median calprotectin level in infected diabetic foot ulcers was 1437 ng/ml and 879 ng/ml in uninfected diabetic foot ulcers. Area under the receiver operating characteristic curve for a composite algorithm incorporating calprotectin, CRP, white cell count and ulcer area was 0.68 (95% confidence intervals 0.52-0.82), sensitivity 0.64, specificity 0.81. CONCLUSIONS: A composite algorithm including CRP, calprotectin, white cell count and ulcer area may help to distinguish uninfected from mildly infected diabetic foot ulcers. Venous procalcitonin is unhelpful for mild diabetic foot ulcer infection.

Views of oral antibiotics and advice seeking about acne: a qualitative study of online discussion forums.

BACKGROUND: Acne vulgaris is common and can significantly impair quality of life, yet little is known about patients' understanding of acne and its treatments. Oral antibiotics are widely used for acne despite concerns about antibiotic resistance. People are increasingly turning to online discussion forums for advice, and information on these sites may influence health beliefs and treatment adherence. OBJECTIVES: To explore understandings about the use of oral antibiotics for acne and advice shared among messages posted on online forums. METHODS: We systematically searched for online forums and identified four where acne was frequently discussed. Discussion threads relating to oral antibiotics were analysed thematically. RESULTS: We extracted 136 pages of data comprising 65 discussions among 294 participants. We found a wide range of perceptions around effectiveness of antibiotics for acne and concerns about adverse effects. The delayed onset of action of antibiotics was a source of frustration and compounded dissatisfaction with healthcare providers, who were perceived by people as 'fobbing them off' with prolonged courses of ineffective treatment. Advice ranged from when to ask for or insist on referral to use of costly cleansers. Forum posts related to a wide range of severities, from 'spots' to severe acne, which may make it confusing for users to assess appropriateness of information. CONCLUSIONS: Online forums offer opinions that could confuse patients, or lead to early abandonment of treatments, challenging consultations and patient dissatisfaction. Users expressed frustration about the delayed onset of action of antibiotics for acne, perceptions of only temporary effectiveness and adverse effects.

The management of acne vulgaris in primary care: a cohort study of consulting and prescribing patterns using the Clinical Practice Research Datalink.

BACKGROUND: Effective management of acne vulgaris in primary care involves support (usually provided over a number of consultations) and prescription of effective treatments. However, consulting and prescribing patterns for acne in primary care are not well described. OBJECTIVES: To describe the rate of primary-care consultations and follow-up consultations; prescribing patterns, including overall use of acne-related medications (ARMs); and initial and follow-up prescription for acne vulgaris in the U.K. METHODS: U.K. primary-care acne consultations and prescriptions for ARMs were identified in the Clinical Practice Research Datalink. Annual consultation rates (between 2004 and 2013) by age and sex, new consultations and consultations in the subsequent year were calculated, along with prescribing trends - during a new consultation and over the subsequent 90 days and year - using the number of registered patients as the denominator. RESULTS: Two-thirds (66·1%) of patients who had a new acne consultation had no further acne consultations in the subsequent year. Overall 26·7%, 24·9%, and 23·6% and 2·8% of patients were prescribed no ARM, an oral antibiotic, a topical antibiotic or an oral plus topical antibiotic, respectively, during a new acne consultation. In total 60·1% and 38·6% of patients prescribed an ARM received no further ARM prescriptions in the following 90 days and 1 year, respectively, despite most prescriptions being for 2 months or less. Prescribing rates for lymecycline and topical combined clindamycin and benzoyl peroxide increased substantially between 2004 and 2013. There were no important changes in consultation rates between 2004 and 2013. CONCLUSIONS: These data suggest that patients with acne are receiving a suboptimal initial choice of ARMs, longitudinal care and prescribing.

Quality of life impact of childhood skin conditions measured using the Children's Dermatology Life Quality Index (CDLQI): a meta-analysis.

BACKGROUND: The Children's Dermatology Life Quality Index (CDLQI) is the most widely used instrument for measuring the impact of skin disease on quality of life (QoL) in children. OBJECTIVES: To provide a meta-analysis of all published QoL scores for a range of childhood skin conditions. METHODS: Studies using the CDLQI questionnaire to measure QoL in skin conditions were identified by searching Medline and Embase from January 1995 (CDLQI creation) to December 2014. Studies were grouped according to condition and baseline scores were combined using meta-analysis. RESULTS: Sixty-seven studies using the CDLQI met the inclusion criteria. The overall estimated CDLQI scores for conditions reported more than once were [point estimate (95% confidence interval, CI), number of studies (n), score range]: atopic eczema [8·5 (7·1-9·8), n = 38, 0-29], acne [5·3 (1·9-8·5), n = 5, 0-30], alopecia [3·1 (0-7·7), n = 2, 0-6], molluscum contagiosum [3·5 (0·6-6·7), n = 5, 0-27], psoriasis [8·0 (3·9-12·1), n = 6, 0-29], scabies [9·2 (0·0-20·3), n = 2, 1-26], urticaria [7·1 (0-15·4), n = 2, 0-22], vitiligo [6·5 (0·7-12·2), n = 2, 0-20] and warts [2·9 (0-5·8), n = 4, 0-16]. Overall, the mean effect on QoL [weighted average CDLQI score 4·6 (95% CI 3·9-5·4)] for children with these conditions was small. However, many children were found to experience a very large impact on QoL (34% of children with atopic eczema, 10% with molluscum contagiosum and 1-5% with acne) in studies where the distributions of scores were provided. CONCLUSIONS: Most skin conditions in children have a 'small' mean effect on QoL. However, the range is large and a significant proportion of children with many common skin conditions will experience a very large effect on quality of life.

General dental practitioners' perceptions of antimicrobial use and resistance: a qualitative interview study.

BACKGROUND: Dentists are responsible for 9-10% of all antibiotics dispensed in primary care in the UK, many of which may be provided contrary to clinical guidelines. Since antibiotic consumption has been identified as a major cause of antibiotic resistance, dental prescribing may be a significant contributor to this important public health problem.Objective This study aims to explore general dental practitioners' (GDPs) perceptions and attitudes towards antibiotic use and resistance. METHOD: Qualitative interview study with 19 purposively sampled GDPs working in Wales. A set of open-ended questions were developed and amended during semi-structured telephone interviews. Interviews were recorded, transcribed verbatim and codes were developed using thematic analysis. RESULTS: Perceptions of antibiotic use and resistance varied widely between practitioners, particularly with respect to the prevalence and impact of resistant strains on the management of dentoalveolar infection, and the impact of dental prescribing on the emergence of resistance. GDPs reported that their antibiotic prescribing decisions were driven by both clinical pressures and wider public health considerations. CONCLUSIONS: Interventions to enhance the quality of antibiotic prescribing in primary care dentistry should address issues associated with inappropriate prescribing as well as providing education about the causes, prevalence and impact of antibiotic resistance.