Paediatric atopic dermatitis and treatment adherence: Exploring factors contributing to topical corticosteroid phobia as a contributor to poor treatment adherence

Atopic dermatitis (AD), also known as eczema or atopic eczema, is the most common chronic inflammatory dermatosis (skin condition) affecting paediatric patients in the western world. There continues to be a rapid rise in incidence of this condition worldwide with a doubling of prevalence in children under age five years in the past 30 years. It also remains one of the most treatable with correct management. Topical corticosteroids (TCS), which have a topical anti-inflammatory action, remain central to this management. However, parent and patient poor adherence to prescribed treatment plans often leads to less effective control of their AD. A review of the literature demonstrated that one of the commonly cited contributing factors to treatment non-adherence in paediatric AD is a fear or anxiety regarding the use of TCS, a condition termed ‘TCS phobia’ (Chapter 2). Although moderate to severe atopic dermatitis is disabling and highly disruptive for patients and their families, TCS phobia is a significant barrier to effective treatment. This thesis presents a body of work that aims to identify the sources of information or misinformation about the safety and efficacy of TCS, as well as assessing the impact of this information on parents’ and patients’ perception on the long term use of TCS to manage their AD. Previous research has identified that parents of children with AD highlight the role of family and friends, the Internet, pharmacists and general practitioners as key sources of information that contribute to fear and anxiety towards using TCS to manage AD. This can create conflicting information leading to confusion and ultimately poor or non-adherence to prescribed treatment plans. This is especially the case when the conflicting information comes from different members of the multidisciplinary treatment team. A multidisciplinary treatment team incorporates health care professionals from different disciplines who provide a specific service and associated health information to the patients, and in the setting of AD in Australia includes general practitioners, dermatologists, and pharmacists. Therefore, it is important to investigate the knowledge and attitudes of these health professionals about the safety and efficacy of TCS that forms the advice provided to parents and patients in paediatric AD. This is because treatment adherence is directly related to risk/benefit of treating a condition as well as the perception of disease severity. If the perceived risks associated with treatment, such as TCS in paediatric AD, out way the perceived benefits or perceived disease severity, then there is significant risk of treatment non-adherence. A consensus statement and systematic review of the adverse effects arising from the use of TCS in children with atopic dermatitis was performed (Chapter 3). The aim of the consensus meeting was to identify the potential and perceived adverse effects and systematically review the literature for each. Dermatologists play a key role as clinical educators around the use, safety and efficacy of TCS. A cross-sectional survey of all Australian dermatologists was performed to assess their attitudes towards the use and safety of TCS in paediatric AD (Chapter 4). Close to half (44%) of the 455 dermatologists in Australia completed the survey (n=198). Nearly all responders prescribed potent or super-potent TCS in the management of paediatric AD. The most common side-effect cited by over two-thirds of the respondents was peri-orificial dermatitis with only a minority (6%) citing cutaneous atrophy. Most dermatologists stated that pharmacists were the most common source of misinformation leading to TCS phobia. Of the respondents, 75% strongly agreed that TCS do not cause skin atrophy when used appropriately and under clinical supervision. Furthermore, 77% agreed or strongly agreed that the words ‘use sparingly’ should be removed from pharmacist labels on TCS prescriptions. This study indicates that dermatologists comfortably manage paediatric AD with potent or super-potent TCS and believe that TCS do not cause skin atrophy in paediatric AD. This is in keeping with the current up to date literature on the safety and efficacy of TCS in this setting and represents the baseline against which other healthcare professionals should refer to when providing advice about the treatment of paediatric AD. Parents and dermatologists commonly cite conflicting information provided by pharmacists on the safety and efficacy of TCS in paediatric AD as contributing to TCS phobia and serving as a major impediment to treatment adherence. Consequently, a study was conducted to assess pharmacists’ beliefs and information on the safety of TCS in paediatric AD treatment (Chapter 5). A cross-sectional survey to assess attitudes and knowledge on the use of TCS in paediatric AD was completed by Australian pharmacists (n=292) who attended a continuing professional development conference. The mean response rate for each question was 86% of the 292 surveyed. Of the responders, 64% recognised that treatment non-adherence was a major reason for treatment failure in paediatric AD. Only a quarter (27%) of the pharmacists would instruct parents/patients to apply TCS until the eczema is clear. Over half (54%) of the responders indicated they would instruct patients to use TCS sparingly. Nearly half (46%) of the responders believed that cutaneous atrophy was the commonest side-effect from use and over half (56%) indicated that side-effects would occur, even if used appropriately. This study demonstrated the existence of significant knowledge gaps about the use and safety of TCS in paediatric AD in Australian pharmacists. Furthermore, their advice to patients potentially contributes to poor treatment adherence because of this misinformation which can contribute to the fear and anxiety around using TCS. Parents cite general practitioners and pharmacists as a source of information that contributes to TCS phobia which can in turn affect treatment adherence. The previous study demonstrated the knowledge gap amongst Australian pharmacists. Therefore, a study was conducted to assess general practitioners’ beliefs and information on the safety of TCS in paediatric AD treatment (Chapter 6). A cross-sectional survey was performed on Australian general practitioners (n=257) participating in continuing professional development programs. Over a third (40.7%) instruct parents to apply TCS for two weeks or less. Nearly half (47.7%) instruct parents to apply TCS sparingly or with the smallest amount possible. Furthermore, nearly a third (30.2%) reported skin atrophy as the most common TCS side effect. Therefore, this study demonstrates that advice from their general practitioner may carry unintentional risk messages contributing to a fear and anxiety about using TCS and ultimately can lead to treatment non-adherence. The studies in chapters 4 to 6 demonstrate the potential for conflicting advice from healthcare professionals in a patient’s multi-disciplinary treatment team. However, an investigation was needed to assess the actual impact of the advice from healthcare professionals on patients and parents’ perception of the safety and efficacy of TCS in AD. Furthermore, it is important to assess the advice provided by pharmacists and general practitioners as related to and reported by patients and parents of patients using TCS on a long-term basis for AD (Chapter 7). A multi-centre cross-sectional survey was performed on a total of 123 adult patients and 78 parents (n=201). Of the total respondents, three quarters (76.6%) reported consistently (“Often” or “Always”) receiving one or more message(s) regarding TCS “risk” from a general practitioner (GP) and/ or pharmacist (n=192). Respondents reported being told to “try natural or complementary and alternative therapies before resorting to the use of TCS” significantly more often by pharmacists than by GPs (p=0.039). This study demonstrates that high rates of consistently delivered messages about TCS “risk” from GPs and pharmacists do affect patient/parent understanding about TCS safety. This “risk” messaging can contribute to fear and anxiety about using TCS and may lead to treatment non-adherence. Chapters 4 to 7 provide evidence that conflicting information from different healthcare professionals in the multi-disciplinary treatment team leads to the delivery of negative risk messaging to parents and patients with AD. This contributes to TCS phobia and can lead to poor treatment outcomes due to non-adherence. However, non-health professional such as parents, family and friends, and the Internet are others sources of knowledge about AD and its treatment. This was also investigated. The perception of TCS safety in the management of AD is influenced by family/friends of the patient or parent of children with AD. This means these are another potential source of misinformation on TCS which can negatively impact perceptions of TCS safety. A multicentre cross-sectional survey of patients (aged >18years old) and parents of patients (aged <18years old) with a history of a chronic inflammatory dermatosis was performed to assess information they receive from family/friends and the Internet about TCS use (Chapter 8). A total of 123 patients and 78 parents completed the survey (n=201). Parents/Patients reported that they were more likely to be informed by the Internet “[having] my [child’s] skin condition means that [I/he/she] will need to use topical corticosteroids” (p <0.001) and that “inflamed skin conditions will improve with the topical corticosteroids” (p = 0.007). On the other hand, family/friends were more likely to recommend parents/patients “try nonprescription creams/ointments before resorting to the use of prescription topical corticosteroids” (p = 0.014). This study highlights that high rates of messages about TCS ‘risk’ from family/friends and the Internet may affect patient/parent understanding about TCS safety. Furthermore, this may contribute to treatment non-adherence. Chapters 3 to 8 have demonstrated external influence that can deliver negative biases that contribute to fear and anxiety about TCS use and ultimately lead to non-adherence in the treatment of paediatric AD. However, a parent’s perception of disease severity, representing an ‘internal’ influence bias, can contribute to whether or not they treat their child’s AD. If a parent assesses their child’s AD to be less severe than it actually is, they are much more likely to undertreat and more likely to be non-adherent with the prescribed management plan. A study was performed comparing parent reported disease severity compared to physician assessed disease severity (Chapter 9). A prospective cohort study recruited fifty paediatric patients and their caregivers from an outpatient dermatology clinic. Two clinicians completed ratings on the Eczema Area and Severity Index (EASI) tool and caregivers completed ratings on the Self-Administered EASI (SA-EASI) and Dermatology Quality of Life Index (DLQI) tools. EASI scores between clinicians were compared and there was good inter-clinician reliability (p = 0.351 ). There was a strong, positive statistically significant correlation between EASI and SA-EASI (r = 0.865, p= <0.01). The EASI score mean was statistically significantly higher than the SA-EASI mean (p = <0.001) for a given patient. This study looked to establish a discrepancy between clinician and caregiver perception of atopic dermatitis severity. It showed that caregivers significantly underestimate the severity of their child’s atopic dermatitis. This provides the clinician with a greater understanding into poor treatment compliance commonly observed in clinical practice and highlights a need to provide parents with a greater understanding of their child’s disease. By establishing the severity of the eczema to the caregiver, the clinician is empowered to provide education about the expectations surrounding treatment, allowing greater insight into noncompliance. This can facilitate an approach to the fears and misconceptions that caregivers may have. Overall, the studies in this thesis contribute to an awareness of the sources of negative risk or misinformation about the safety and efficacy of TCS in the setting of paediatric AD. Furthermore, it demonstrates the direct impact of this information on patients and parents. These findings provide the basis for education programs to help educate the healthcare professional members of the multi-disciplinary treatment team. It is through consistent positive messaging from these healthcare professionals that patients and parents will be better equipped and supported to combat the negative risk messaging from non-healthcare professional sources such as family, friends and the Internet. Ultimately, this has the capacity to positively impact treatment adherence and outcomes for both the patient with AD and their entire family unit

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011