Long-term costs and cost-effectiveness of adjunctive corticosteroids for patients with septic shock in New Zealand.

OBJECTIVE: The aim of the study was to determine whether adjunctive hydrocortisone reduced healthcare expenditure and was cost-effective compared with placebo in New Zealand patients in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. DESIGN: This is a health economic analysis using data linkage to New Zealand Ministry of Health databases to determine resource use, costs, and cost-effectiveness for a 24-month period. SETTING: The study was conducted in New Zealand. PARTICIPANTS AND INTERVENTION: Patients with septic shock were randomised to receive a 7-day continuous infusion of 200 mg of hydrocortisone or placebo in the ADRENAL trial. MAIN OUTCOME MEASURES: Healthcare expenditure was associated with all hospital admissions, emergency department presentations, outpatient visits, and pharmacy expenditure. Effectiveness outcomes included mortality at 6 months and 24 months and quality of life at 6 months. Cost-effectiveness outcomes were assessed with reference to quality-adjusted life years gained at 6 months and life years gained at 24 months. RESULTS: Of 3800 patients in the ADRENAL trial, 419 (11.0%) were eligible, and 405 (96.7% of those eligible) were included. The mean total costs per patient over 24 months were $143,627 ± 100,890 and $143,772 ± 97,117 for the hydrocortisone and placebo groups, respectively (p = 0.99). Intensive care unit costs for the index admission were $50,492 and $62,288 per patient for the hydrocortisone and placebo groups, respectively (p = 0.09). The mean number of quality-adjusted life years gained at 6 months and mean number of life years gained at 24 months was not significantly different by treatment group, and the probability of hydrocortisone being cost-effective was 55% at 24 months. CONCLUSIONS: In New Zealand, adjunctive hydrocortisone did not reduce total healthcare expenditure or improve outcomes compared with placebo in patients with septic shock.

COVID-19 et corticostéroïdes systémiques / COVID-19 and corticosteroids systemic

CONTEXTE: Le présent document ainsi que les constats qu'il énonce ont été rédigés en réponse à une interpellation du ministère de la Santé et des Services sociaux dans le contexte de l'urgence sanitaire liée à la maladie à coronavirus (COVID-19) au Québec. L'objectif est de réaliser une recension des données publiées et de mobiliser les savoirs clés afin d'informer les décideurs publics et les professionnels de la santé et des services sociaux. Bien que les constats reposent sur un repérage exhaustif des données scientifiques publiées, l'évaluation de la qualité méthodologique des études et une appréciation du niveau de preuve scientifique par paramètre clinique d'intérêt, le processus ne reposent pas sur une méthode systématique ni une validation externe selon les normes habituelles à l'INESSS. Par ailleurs, les positions ne découlent pas d'un processus de consultation élaboré. Dans les circonstances d'une telle urgence de santé publique, l'INESSS reste à l'affût de toutes nouvelles données, qu'elles soient de nature scientifique ou contextuelle, susceptibles de lui faire modifier cette réponse. P

The cost-effectiveness of adjunctive corticosteroids for patients with septic shock.

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.

Cost Analysis of Adjunctive Hydrocortisone Therapy for Septic Shock: U.S. Payer Perspective.

OBJECTIVES: To conduct a cost analysis of adjunctive hydrocortisone therapy for severe septic shock from the perspective of a third-party payer in the United States. DESIGN: Estimates of outcomes were aggregate data from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials. In these trials, the outcomes of interests were ICU length of stay, vasopressor-free days, ventilation-free days, and the proportion of patients receiving blood transfusion. Each outcome was monetized into a set of mutually exclusive components and was aggregated to estimate the cost-per-patient based on each trial. Cost inputs for each outcome were obtained from literature and adjusted based on the medical care consumer price index. To estimate the budget impact using adjunctive hydrocortisone therapy, per-patient avoided cost was multiplied by expected septic shock annual incidence. Deterministic one-way sensitivity analysis evaluated the robustness of the findings, and Monte Carlo simulation estimated 95% CI of the findings. SETTING: A total of 103 medical-surgical ICU (69 for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and 34 for Activated Protein C and Corticosteroids for Human Septic Shock). PATIENTS: Adults greater than or equal to 18 years old with septic shock. INTERVENTIONS: Adjunctive hydrocortisone therapy (hydrocortisone at a dose of 200 mg/d for 7 d for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and hydrocortisone at a 50 mg IV bolus every 6 hr and fludrocortisone as a 50 µg tablet once daily). MEASUREMENTS AND MAIN RESULTS: Per Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $8,111 (95% CI, $3,914-$12,307) per patient, driven by improvements in ICU-free days, vasopressor-free days, ventilation-free days, and blood transfusion proportion. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $750 million. Per Activated Protein C and Corticosteroids for Human Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $25,539 per patient (95% CI, $22,853-$28,224), driven by improvements in ICU free-days, vasopressor-free days, and ventilation-free days. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $2.3 billion. The deterministic one-way sensitivity analysis showed the cost of ICU stays to be the most influential factor in both analyses. The sensitivity analysis using the reported median showed a greater monetized benefit of $10,658 (Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock) and $30,911 (Activated Protein C and Corticosteroids for Human Septic Shock) per patient. CONCLUSIONS: Using adjunctive hydrocortisone therapy yields a significant monetized benefit based on inputs from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials.

Corticoides sistémicos en COVID-19 / Systemic corticosteroids in COVID-19

CONTEXTO CLÍNICO: La Enfermedad por el Coronavirus 2019 (COVID­19, por su sigla en inglés Coronavirus Disease 2019) es una enfermedad respiratoria de humanos producida por un nuevo coronavirus identificado con la sigla SARS-CoV-2. El 11 de marzo de 2020 la Organización Mundial de la Salud (OMS) declaro la COVID-19 como una pandemia. Desde ese momento hasta el 15 de junio su circulación se ha reportado en 205 países reportándose más de 7.800.000 casos y la muerte 430.000 personas. El período de incubación de la infección es de 2 a 14 días. La mayor parte de los contagios se producen persona a persona, siendo altamente transmisible.(3) La clínica varía desde casos asintomáticos a cuadros febriles con tos y dificultad respiratoria, neumonía y distrés respiratorio. También puede acompañarse de alteraciones gastrointestinales. En los casos con mal pronóstico, el paciente presenta un importante deterioro respiratorio en 4-8 días. Las imágenes radiológicas muestran generalmente neumonía focal o generalizada semejante al síndrome de distress respiratorio agudo. (3) La mayoría de los casos graves requieren ingreso hospitalario, siendo mayoritariamente casos primarios en pacientes de edad avanzada y con comorbilidades (diabetes, enfermedad crónica renal, hipertensión, enfermedad cardiaca y enfermedad pulmonar crónica). La tasa media de letalidad de los pacientes ingresados a UTI es cercana al 49%, siendo los valores más elevados en pacientes masculinos de más de 50 años con comorbilidades múltiples. Actualmente el tratamiento de la COVID­19 es sintomático y de sostén no existiendo hasta el momento tratamiento farmacológico específico curativo. Debido a la evidencia que sugiere que el daño pulmonar agudo observado en la infección por SARS-CoV-2 estaría asociada a la activación de las células inmunes circulantes, incluyendo células T y las citoquinas que conducen a un síndrome de liberación de citoquinas (similar al síndrome de activación macrofágica y hemofagocítico) por lo que se plantea que el uso de corticoides sistémicos podría disminuir la mortalidad y/o necesidad de soporte ventilatorio invasivo. TECNOLOGÍA: Los glucocorticoides (GCS) son una familia de medicamentos antiinflamatorios e inmunomoduladores que se utilizan en el tratamiento de diversas patologías cuyo principal componente etiopatogénico es la inflamación. Dentro de los mecanismos de acción propuestos se encuentran: inhibición de citoquinas inflamatorias (IL-1 y IL-2), inhibición de la migración de leucocitaria, inhibición de la desgranulación de mastocitos, depleción linfocitaria (principalmente linfocitos T), incremento de citoquinas anti-inflamatorias (IL-10). Dentro de las alternativas para la administración sistémica se pueden mencionar a la hidrocortisona, dexametasona, betametasona, prednisona, prednisolona, metilprednisolona y deflazacort. Todos ellos difieren principalmente en el grado de actividad mineralocorticorticoide y vida media. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de corticoides sistémicos en COVID­19. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y recomendaciones de diferentes organizaciones de salud. RESULTADOS: Se incluyeron un ECA, una RS, dos estudios observacionales, un documento de evaluación de tecnología sanitaria, 12 guías de práctica clínica, recomendaciones de organismos gubernamentales o sociedades científicas acerca del uso de corticoides sistémicos en pacientes con diagnóstico de COVID­19. CONCLUSIONES: Evidencia de alta calidad proveniente de los resultados de un ensayo clínico aleatorizado aún no publicado sugiere que el uso de corticoides sistémicos se asocia a una disminución en el riesgo de mortalidad principalmente en pacientes con requerimientos de oxigeno suplementario o asistencia mecánica invasiva. Evidencia de muy baja calidad también sugiere que podría tener el mismo beneficio en aquellos pacientes con COVID-19 que presentan síndrome de distrés respiratorio agudo. Múltiples ensayos clínicos aleatorizados en pacientes con cuadros moderados o severos se encuentran en curso. Las guías de práctica clínica de diferentes sociedades internacionales y organismos gubernamentales que lo recomiendan indican su utilización para el tratamiento de pacientes con criterios de síndrome de distrés respiratorio agudo. Si bien no se encontraron estudios de costo-efectividad en Latinoamérica, el costo total del tratamiento al igual que su impacto presupuestario sería muy bajo.

Informe diário de evidências COVID-19: busca realizada entre 24 e 26 de abril de 2020 / COVID-19 daily evidence report: search conducted between April 24 and 26, 2020

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 25 artigos e 47 protocolos.

A descriptive study of the effect of a disciplinary proceeding decision on medical practitioners' practice behaviour in the context of providing a hydrocortisone and lignocaine injection.

INTRODUCTION: We conducted a descriptive study to evaluate any changes in practice behaviour regarding the provision of hydrocortisone and lignocaine (H&L) injections among doctors and how an H&L injection is priced following a disciplinary proceeding decision. A doctor had been fined SGD 100,000 for failing to obtain informed consent before an H&L injection. METHODS: We performed a survey shortly after the disciplinary decision to ascertain: (a) the category of the respondent; (b) whether the respondent provided H&L injections and how much he charged before the decision; and (c) after the decision. All members of the Singapore Medical Association and College of Family Physicians Singapore are doctors and were invited to participate. RESULTS: 1,927 doctors responded to the survey. Prior to the decision, 804 doctors did not perform H&L injections; this increased by 20.4% to 968 after the decision. The number of doctors who gave H&L injections decreased by 164 (14.6%), from the previous 1,123. Pre-decision, doctors who determined their own price for H&L injections charged a median pricing ≤ SGD 100. Post-decision, the median charge rose to > SGD 100 to SGD 200. At higher price bands, the number of doctors who charged > SGD 1,000 increased eight-fold, from eight to 65. CONCLUSION: The study demonstrated how a disciplinary decision can affect practice behaviour, and specifically how doctors may choose to not offer a service, an example of defensive medicine through avoidance behaviour. It also showed how prices for a service can rise following such a decision, which demonstrates the concept of negative general deterrence in sentencing.

Acute Adrenal Insufficiency Precipitated by the Discontinuation of a Betamethasone and Dextrochlorpheniramine Combination: The Diagnostic Utility of an Echocardiographic Assessment of Systemic Vascular Resistance.

A 72-year-old woman with primary biliary cholangitis was admitted to our hospital with heart failure with a preserved ejection fraction. An accidental right ventricular perforation that occurred during an endomyocardial biopsy precipitated cardiogenic shock. Despite successful surgical treatment, she demonstrated progressive hemodynamic deterioration, which was resistant to the administration of high-dose catecholamines. She was diagnosed with acute adrenal insufficiency, which was attributed to the discontinuation of Celestamine® (betamethasone/dextrochlorpheniramine combination) just after the perforation. Prompt intravenous administration of hydrocortisone (150 mg/day) led to hemodynamic stabilization. The serial noninvasive assessment of systemic vascular resistance using transthoracic echocardiography was instrumental in detecting acute adrenal insufficiency in this case.

[Addisonian Crisis - Risk Assessment and Appropriate Treatment]. / Addison-Krise ­ Risiko erkennen und rasch behandeln.

An adrenal crisis (Addisonian crisis) is an acute life-threatening complication of adrenal insufficiency. It occurs when hydrocortisone demand is not met by supplementation in the context of an infection - often gastrointestinal, fever, trauma, acute psychological or physical stress. Symptoms of weakness, nausea, muscle/joint pain and drowsiness may develop out of robust health within few hours. If overlooked, treated too late, with insufficient dose or route of application, there exists a considerable risk of mortality. Treatment consists of immediate parenteral hydrocortisone (100 mg bolus) and subsequent continuous infusion until the underlying precipitating cause is cured and/or when regular supplementation can be continued. Physicians and nurses must not underestimate the condition, since diagnosis and treatment must not be delayed. Patients, relatives and spouses need to be trained in prevention and early recognition through educational programs and emergency cards.

Longitudinal Assessment of Illnesses, Stress Dosing, and Illness Sequelae in Patients With Congenital Adrenal Hyperplasia.

Context: Patients with congenital adrenal hyperplasia (CAH) are at risk for life-threatening adrenal crises. Management of illness episodes aims to prevent adrenal crises. Objective: We evaluated rates of illnesses and associated factors in patients with CAH followed prospectively and receiving repeated glucocorticoid stress dosing education. Methods: Longitudinal analysis of 156 patients with CAH followed at the National Institutes of Health Clinical Center over 23 years was performed. The rates of illnesses and stress-dose days, emergency room (ER) visits, hospitalizations, and adrenal crises were analyzed in relation to phenotype, age, sex, treatment, and hormonal evaluations. Results: A total of 2298 visits were evaluated. Patients were followed for 9.3 ± 6.0 years. During childhood, there were more illness episodes and stress dosing than adulthood (P < 0.001); however, more ER visits and hospitalizations occurred during adulthood (P ≤ 0.03). The most robust predictors of stress dosing were young age, low hydrocortisone and high fludrocortisone dose during childhood, and female sex during adulthood. Gastrointestinal and upper respiratory tract infections (URIs) were the two most common precipitating events for adrenal crises and hospitalizations across all ages. Adrenal crisis with probable hypoglycemia occurred in 11 pediatric patients (ages 1.1 to 11.3 years). Undetectable epinephrine was associated with ER visits during childhood (P = 0.03) and illness episodes during adulthood (P = 0.03). Conclusions: Repeated stress-related glucocorticoid dosing teaching is essential, but revised age-appropriate guidelines for the management of infectious illnesses are needed for patients with adrenal insufficiency that aim to reduce adrenal crises and prevent hypoglycemia, particularly in children.

Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomised trial.

BACKGROUND: Infliximab and ciclosporin are of similar efficacy in treating acute severe ulcerative colitis, but there has been no comparative evaluation of their relative clinical effectiveness and cost-effectiveness. METHODS: In this mixed methods, open-label, pragmatic randomised trial, we recruited consenting patients aged 18 years or older at 52 district general and teaching hospitals in England, Scotland, and Wales who had been admitted, unscheduled, with severe ulcerative colitis and failed to respond to intravenous hydrocortisone within about 5 days. Patients were randomly allocated (1:1) to receive either infliximab (5 mg/kg intravenous infusion given over 2 h at baseline, and again at 2 weeks and 6 weeks after the first infusion) or ciclosporin (2 mg/kg per day by continuous infusion for up to 7 days, followed by twice-daily tablets delivering 5·5 mg/kg per day for 12 weeks). Randomisation used a web-based password-protected site, with a dynamic algorithm to generate allocations on request, thus protecting against investigator preference or other subversion, while ensuring that each trial group was balanced by centre, which was the only stratification used. Local investigators and participants were aware of the treatment allocated, but the chief investigator and analysts were masked. Analysis was by treatment allocated. The primary outcome was quality-adjusted survival-ie, the area under the curve (AUC) of scores from the Crohn's and Ulcerative Colitis Questionnaire (CUCQ) completed by participants at baseline, 3 months, and 6 months, then every 6 months from 1 year to 3 years. This trial is registered with the ISRCTN Registry, number ISRCTN22663589. FINDINGS: Between June 17, 2010, and Feb 26, 2013, 270 patients were recruited. 135 patients were allocated to the infliximab group and 135 to the ciclosporin group. 121 (90%) patients in each group were included in the analysis of the primary outcome. There was no significant difference between groups in quality-adjusted survival (mean AUC 564·0 [SD 241·9] in the infliximab group vs 587·0 [226·2] in the ciclosporin group; mean adjusted difference 7·9 [95% CI -22·0 to 37·8]; p=0·603). Likewise, there were no significant differences between groups in the secondary outcomes of CUCQ scores, EQ-5D, or SF-6D scores; frequency of colectomy (55 [41%] of 135 patients in the infliximab group vs 65 [48%] of 135 patients in the ciclosporin group; p=0·223); or mean time to colectomy (811 [95% CI 707-912] days in the infliximab group vs 744 [638-850] days in the ciclosporin group; p=0·251). There were no differences in serious adverse reactions (16 reactions in 14 participants receiving infliximab vs ten in nine patients receiving ciclosporin); serious adverse events (21 in 16 patients vs 25 in 17 patients); or deaths (three in the infliximab group vs none in the ciclosporin group). INTERPRETATION: There was no significant difference between ciclosporin and infliximab in clinical effectiveness. FUNDING: NIHR Health Technology Assessment programme.

National Utilization and Forecasting of Ototopical Antibiotics: Medicaid Data Versus "Dr. Google".

OBJECTIVES: To forecast national Medicaid prescription volumes for common ototopical antibiotics, and correlate prescription volumes with internet user search interest using Google Trends (GT). STUDY DESIGN: National United States Medicaid prescription and GT user search database analysis. METHODS: Quarterly national Medicaid summary drug utilization data and weekly GT search engine data for ciprofloxacin-dexamethasone (CD), ofloxacin (OF), and Cortisporin (CS) ototopicals were obtained from January 2008 to July 2014. Time series analysis was used to assess prescription seasonality, Holt-Winter's method for forecasting quarterly prescription volumes, and Pearson correlations to compare GT and Medicaid data. RESULTS: Medicaid prescription volumes demonstrated sinusoidal seasonality for OF (r = 0.91), CS (r = 0.71), and CD (r = 0.62) with annual peaks in July, August, and September. In 2017, OF was forecasted to be the most widely prescribed ototopical, followed by CD. CS was the least prescribed, and volumes were forecasted to decrease 9.0% by 2017 from 2014. GT user search interest demonstrated analogous sinusoidal seasonality and significant correlations with Medicaid data prescriptions for CD (r = 0.38, p = 0.046), OF (r = 0.74, p < 0.001), CS (r = 0.49, p = 0.008). CONCLUSION: We found that OF, CD, and CS ototopicals have sinusoidal seasonal variation with Medicaid prescription volume peaks occurring in the summer. After 2012, OF was the most commonly prescribed ototopical, and this trend was forecasted to continue. CS use was forecasted to decrease. Google user search interest in these ototopical agents demonstrated analogous seasonal variation. Analyses of GT for interest in ototopical antibiotics may be useful for health care providers and administrators as a complementary method for assessing healthcare utilization trends.

Impaired health-related quality of life in Addison's disease--impact of replacement therapy, comorbidities and socio-economic factors.

OBJECTIVE: Patients with Addison's disease (AD) on conventional replacement therapy have impaired health-related quality of life (HRQoL). It is possible that lower hydrocortisone (HC) doses recommended by current guidelines could restore HRQoL. We compared HRQoL in AD patients treated according to current HC recommendations to that of the age- and gender-standardized general population. SUBJECTS, DESIGN AND MEASUREMENT: We assessed HRQoL in a cross-sectional setting with the 15D instrument in a Finnish AD cohort (n = 107) and compared the results with those of a large sample of general population (n = 5671). We examined possible predictors of HRQoL in AD. Within the patient group, HRQoL was also assessed by SF-36. RESULTS: Mean HC dose was 22 mg/d, corresponding to 12 ± 4 mg/m2. HRQoL was impaired in AD compared with the general population (15D score; 0·853 vs 0·918, P < 0·001). Within single 15D dimensions, discomfort and symptoms, vitality and sexual activity were most affected. Stepwise regression analysis demonstrated that Patient's Association membership (P = 0·02), female gender (P < 0·01), presence of other autoimmune or inflammatory comorbidity (P < 0·02), lower education (P < 0·02) and longer disease duration (P < 0·05) independently predicted impaired HRQoL, whereas replacement regimens, autoimmune-related comorbidities, total number of comorbidities or level of healthcare follow-up did not. In AD, HRQoL was impaired also as assessed by SF-36. CONCLUSIONS: HRQoL is significantly impaired in AD compared with the general population despite use of recommended HC doses. Patient's Association membership was the most significant predictor of impaired HRQoL. This finding should be explored in more detail in the future.

Conventional ultrasonography and sonoelastography in the assessment of plaque psoriasis under topical corticosteroid treatment - work in progress.

AIMS: The objective of the study was to compare the efficiency of 20 MHz skin ultrasonography and 40 MHz conventional ultrasonography in the assessment of plaque psoriasis and to assess the efficiency of 40 MHz real-time sonoelastography in the early detection of steroid-induced skin atrophy in psoriatic plaques. PATIENTS AND METHODS: Ultrasonographic blinded evaluation was performed on 16 plaques in three consecutive patients, at baseline and after hydrocortisone acetate 1% ointment six-week application. The parameters were epidermal and dermal thicknesses for gray-scale ultrasonography and strain ratio for sonoelastography. Strain ratio was computed between the dermis and the adjacent hypodermis. Student's t-test for paired samples was performed. A confidence level of p<.05 was considered significant. RESULTS: At follow-up, epidermal thickness was significantly reduced with 20 MHz (p = .002) and 40 MHz sonography (p = .032), while dermal thickness varied insignifcantly with 20 MHz (p = .35) and 40 MHz sonography (p = .33). Measurements at 40 MHz were significantly higher than their 20 MHz counterparts at baseline (epidermis: p < .001; dermis: p = .003) and at follow-up (epidermis: p < .001; dermis: p = .001). Strain ratio revealed no significant change of dermal elasticity (p = .96). CONCLUSIONS: Although epidermal and dermal measurements varied significantly with 20 MHz and 40 MHz ultrasonography, both techniques efficiently quantified treatment response by measuring the reduction of epidermal thickness. Sonoelastographic findings were consistent with the expected outcome of short-term use of low-potency corticosteroid. Further studies are recommended.

Assessment of salivary free cortisol levels by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in patients treated with mitotane.

OBJECTIVE: Mitotane is an adrenocytolytic agent used in adrenocortical carcinoma, inducing adrenal insufficiency, requiring replacement treatment. Such therapy is not easy to monitor because of mitotane interference. Salivary cortisol reflects a free fraction of plasma cortisol and may be useful in such patients. DESIGN: The aim of our study was to evaluate salivary cortisol by HPLC coupled to tandem-mass spectrometry (LC-MS/MS) and by an electrochemiluminescence immunoassay (ECLIA) in patients treated with mitotane. We enrolled 6 patients receiving mitotane and 2 Addison disease patients as negative controls and determined salivary cortisol rhythm. We also determined the salivary cortisol rhythm in 8 healthy subjects. Salivary samples (n=112) were assayed by ECLIA, using Roche Modular E170, and by LC-MS/MS. RESULTS: The mean values obtained by ECLIA were significantly higher than those obtained by LC-MS/MS in the mitotane group (p<0.001). In fact, in the group measured by LC-MS/MS, we observed several peaks eluting at a retention time different from the cortisol group, presumably due to cortisol-like analogues. In Addison disease, since steroidogenesis is absent, salivary cortisol values measured by the two methods did not show any significant difference (p=0.61). CONCLUSIONS: Salivary cortisol measured by LC-MS/MS is a selective method, excluding cortisol analogues accumulating in treated patients. Therefore, LC-MS/MS offers an effective system to monitor replacement therapy in mitotane treated patients.

New treatment strategy and assessment questionnaire for external auditory canal pruritus: topical pimecrolimus therapy and Modified Itch Severity Scale.

OBJECTIVE: We aimed to compare the efficacy of topical pimecrolimus versus hydrocortisone in treating external auditory canal pruritus, using the Modified Itch Severity Scale as an assessment tool. METHODS: We included in the study 40 patients with isolated itching of the external auditory canal who had not received any benefit from previous topical and systemic treatments. Topical 1 per cent pimecrolimus or topical hydrocortisone was applied to each patient's external auditory canal for three months. A Modified Itch Severity Scale was developed and used to assess treatment response. RESULTS: Compared with itching scores on initial assessment, the scores of patients receiving topical pimecrolimus had decreased by 52.3 per cent by the third week of treatment and by 77.6 per cent by the third month, whereas the scores of patients receiving topical hydrocortisone had decreased by 34.4 per cent by the third week and by 64.2 per cent by the third month. CONCLUSIONS: Topical pimecrolimus appears to be as effective as topical hydrocortisone in relieving external auditory canal pruritus. We used a novel scoring system, the Modified Itch Severity Scale, to evaluate external auditory canal pruritus; this is the first self-reporting questionnaire for the quantification of external auditory canal pruritus severity. Further studies are needed to validate this scoring system.

Risk analysis of early childhood eczema.

BACKGROUND: The increasing prevalence of eczema suggests the role of environmental factors triggering a genetic predisposition. OBJECTIVE: To analyze the effect of environmental exposures in early life and genetic predisposition on the development of eczema before age 3 years. METHODS: The Copenhagen Study on Asthma in Childhood is a prospective clinical study of a birth cohort of 411 children born of mothers with asthma. Eczema was diagnosed, treated, and monitored at the clinical research unit, and complete follow-up for the first 3 years of life was available for 356 children. Risk assessments included filaggrin loss-of-function mutation; parent's atopic disease; sex; social status; previous deliveries; third trimester complications and exposures; anthropometrics at birth; month of birth; duration solely breast-fed; introduction of egg, cow's milk, and fish; time spent in day care; cat and dog at home; feather pillow; nicotine in infant's hair; and temperature and humidity in bedroom. RESULTS: Eczema developed in 43.5% of the infants. Filaggrin mutation (odds ratio [OR], 3.20; 95% CI, 1.46-7.02; P = .004), mother's eczema (OR, 2.80; 95% CI, 1.70-4.63; P < .0001), and father's allergic rhinitis (OR, 1.91; 95% CI, 1.09-3.33; P = .02) were directly associated with risk of eczema. Risk of eczema was significantly reduced by birth length (OR per cm increase, 0.87; 95% CI, 0.78-0.97; P = .02), increased bedroom temperature (probably inverse causality; OR, 0.80; 95% CI, 0.66-0.97; P = .02), and dog living in the home (OR, 0.44; 95% CI, 0.23-0.87; P = .02). CONCLUSIONS: Dog exposure reduced the risk of eczema, whereas short length at birth, filaggrin mutation, and parental atopy increased the risk of eczema by age 3 years.

Snake bites in north east Sri Lanka.

INTRODUCTION: Snake bite is a major problem in Sri Lanka where recent decades of warfare and economic sanctions have complicated its management. RESULTS: A retrospective review of snake bites in north-east Sri Lanka was undertaken in 2005 to review management. Of 303 victims, 145 revealed a local response, 134 a prolonged clotting time, 46 ptosis and five respiratory failure. One died. Of 97 snakes identified: 42 were saw-scaled vipers, 14 Russell's vipers, 6 cobras and 6 kraits. Most bites occurred at the harvest and the median age of victims was 32 years. There was no difference in morbidity or mortality at any age. In total, 262 snake bite cases were treated within 3 hours of the bite, and 183 were given antivenom. Seventy victims reacted adversely, of whom 61 received hydrocortisone, chlorpheniramine and subcutaneous adrenaline. No significant side effects were noted. CONCLUSION: North-east Sri Lanka has endured two decades of civil disruption but public knowledge and an established protocol for management, including adrenaline, has compensated for shortages in medical staff and infrastructure. The resumption of economic sanctions in 2007 is likely to counter that success.