Cross-sectional burden-of-illness study in atopic dermatitis (MEASURE-AD) in Australia and New Zealand reveals impacts on well-being.

OBJECTIVES: To describe disease burden in individuals with moderate-to-severe atopic dermatitis (AD) in Australia and New Zealand (ANZ) and compare it with other geographic regions. METHODS: This multicentre, cross-sectional, observational study (MEASURE-AD) recruited consecutive adolescent and adult patients attending dermatology clinics in 28 countries. Data collected included scores of pruritus, disease severity, sleep, pain, disease control, work and quality of life. RESULTS: This study included 112 ANZ participants (Australia n = 72; New Zealand n = 40) from December 2019 to December 2020. Treatments included topicals (85.7% of patients), non-biologic systemic therapy (28.6%), phototherapy (9.8%) and dupilumab (4.5%). Mean Eczema Area and Severity Index (EASI) score was 22.3 (95% CI 19.6-25.0) and Patient-Oriented Eczema Measurement (POEM) score was 18.4 (95% CI 16.8-20.0). Pruritus Numerical Rating Scale (NRS) was 6.0 (95% CI 5.5-6.6) (50% had severe pruritus) and Dermatology Life Quality Index (DLQI) 14.3 (95% CI 12.8-15.8). ADerm-Impact sleep domain score was 15.1 (95% CI 13.2-16.9). ADerm-Symptom Scale worst skin pain domain score was 5.0 (95% CI 4.3-5.6). Work Productivity and Activity Impairment (WPAI) percentages indicated work and productivity impairment. Inadequately controlled AD was self-reported by 41%, with 9.7 flares in the past 6 months. Scores of pruritus, disease severity, sleep, pain, disease control and quality of life in ANZ were often the highest of all the geographic regions studied. CONCLUSION: ANZ patients with AD have a high disease burden, which extends across multiple facets of daily life. Many are inadequately controlled with existing therapies.

Accuracy of intra-arterial line transducer levelling practice in a general intensive care unit.

BACKGROUND: The intra-arterial line is a common device intervention used in the intensive care environment to provide continuous blood pressure measurement. The transducer line is levelled to the patient's phlebostatic axis to provide accurate measurements. AIM: The aim of this study was to investigate registered nurses' accuracy at levelling the transducer to the correct anatomical position using visual judgement, compared to one done using a laser level. METHODS: Patient transducers were levelled by visual judgement and then by using a laser level. Time and mean arterial pressure (MAP) were recorded with each measurement along with any difference in transducer level between the two methods and subsequent changes in inotrope administration. RESULTS: A total of 577 MAP measurements were recorded from 178 patients; 70% of observations had a difference in transducer level, 30% of the time the inotrope rate was increased and 18% of the time the inotrope rate was reduced. The prevalence of clinically significant observations with an absolute difference of 50 mm or more in transducer placement was 25%. The mean difference in MAP measurements when a cut-off of 64 mmHg or more for laser was applied to the data was 0.22 (95% confidence interval: -0.14, 0.58, n = 513, p = 0.23), and for a cut-off of less than 64 for laser, a larger mean difference of 4.36 (95% confidence interval: 3.75, 5.28], n = 64, p < 0.001) was observed. CONCLUSIONS: Transducers were unable to be accurately levelled for haemodynamic monitoring using visual means alone. Over the range of patient MAP values examined, 25% of all observations had a clinically significant absolute difference of 50 mm or more in the transducer level position between the two methods. The visual method became increasingly inaccurate and unreliable at low MAP levels requiring medical intervention.

Proactive debriefing to promote wellbeing in intensive care nurses: A protocol.

BACKGROUND: The dynamic, rewarding, yet challenging environment of the intensive care unit is experienced in extremes by intensive care nurses. To ensure intensive care nurses can continue to fulfil their professional roles and responsibilities, careful consideration and promotion of collective and individual wellbeing is required. Regular proactive debriefing provides an opportunity to commune, connect, and reflect on the challenging nature of clinical work and is a potential intervention to aid in the promotion of wellbeing. AIM/OBJECTIVE: This study aims to collaboratively develop, implement, and evaluate a proactive debriefing intervention, which will target the promotion of nurses' wellbeing. STUDY PLAN: This hybrid effectiveness-implementation study will use a pretest/post-test design to test a codesigned proactive debriefing intervention on the wellbeing of nurses working in a large quaternary intensive care unit. This research will be conducted in two phases. Phase one will consist of focus groups and a codesign workshop. Phase two surrounds the implementation and analysis of the codesigned intervention.

Bullous pemphigoid: Its incidence, mortality and clinical outcome in New Zealand.

BACKGROUND/OBJECTIVES: Bullous pemphigoid (BP) is an uncommon autoimmune bullous disorder, with significant morbidity and mortality. Mortality may be as high as 23.5% in the first year after diagnosis. Clear epidemiologic data across Australasia are lacking. METHODS: A retrospective, multi-centred cohort study was designed to determine the incidence and mortality of bullous pemphigoid in New Zealand. Data from all histopathologically diagnosed patients with bullous pemphigoid between 2009 and 2015 from the Auckland region were obtained. Demographics, clinical characteristics and outcome 3 years from diagnosis (until 31 December 2018) were collected. Demographic data were compared against a denominator year-matched New Zealand Census population. RESULTS: One hundred sixty-one patients had confirmed bullous pemphigoid, with an incidence rate of 3.03/100 000 person-years [95% CI 2.58-3.54]; 70% were of European ethnicity; 12.4% were Pacific peoples; 11.2% were Asian; and 6.8% were Maori. 45.3% had associated cognitive impairment and/or stroke. In the 3-year follow-up, 25% had treatment complications mostly from prednisone therapy. The mortality rate was 40%, highest in the first year of diagnosis, with age at diagnosis a predictor. CONCLUSION: The incidence and mortality rates are comparable to the UK/Northern Europe. Knowledge of the epidemiology of bullous pemphigoid in New Zealand and within an international settling informs the provision of future care and treatments.

Immunotherapy for the treatment of penile intraepithelial neoplasia associated with human papilloma virus type 16 using topical imiquimod and human papilloma virus vaccination.

Penile intraepithelial neoplasia (PeIN) is frequently associated with human papilloma virus (HPV). Three cases of PeIN associated with HPV-type 16 were successfully treated with topical imiquimod and concurrent HPV vaccination. Human papilloma vaccine protects against oncogenic human papilloma viruses. In New Zealand, a decline in incidence of PeIN is anticipated with the recent funding of human papilloma vaccine for boys and young men aged 9-26 years. Therefore, HPV vaccination may have a role for treatment of PeIN and prophylaxis.

The Effects of Sensory Enrichment After a Laboratory Stressor on Human Skin Barrier Recovery in a Randomized Trial.

OBJECTIVE: Environmental enrichment (EE) can reduce stress, alter immunity, and speed wound healing in animals. However, it is not known whether these effects translate to humans. This study aimed to investigate whether sensory EE could improve wound healing after a stressor in humans. METHODS: A total of 105 participants underwent a tape-stripping procedure and were then stressed using a laboratory stress paradigm. After this, they were randomized to interact for 30 minutes with one of two possible sensory EE interventions (music as auditory enrichment or a Paro robot as multisensory enrichment) or to a control condition. Skin barrier recovery was measured using transepidermal water loss at baseline, after the stressor, and after the intervention. Stress was measured using self-report, heart rate, blood pressure, and salivary stress-related biological measures. Enjoyment during the intervention was measured by self-report as a possible mediator. RESULTS: The Paro condition had significantly improved skin barrier recovery (mean [M] = 44%, standard error [SE] = 1.92) compared with the control condition (M = 37% SE = 2.01, F(2,88) = 3.25, p = .043), both with and without controlling for covariates. The music condition did not significantly differ from the other conditions (M = 42%, SE = 1.95, p values > .05). Both objective and subjective stress measures did not significantly differ between conditions. Mediational analysis showed that enjoyment levels during the intervention period significantly mediated the relationship between condition and skin barrier recovery (z = 2.00, p = .046). CONCLUSIONS: Paro, or other companion robots, may be an effective form of enrichment to improve skin barrier recovery in humans after a laboratory stressor, and this effect may be due to enjoyment. Further research with patient groups is required to investigate whether Paro can help heal clinical wounds. TRIAL REGISTRATION: ACTRN12618000953235, registered at https://anzctr.org.au.

The epidemiology of subcutaneous panniculitis-like alpha-beta T-cell lymphoma in New Zealand.

BACKGROUND/OBJECTIVES: Subcutaneous panniculitis-like alpha-beta T-cell lymphoma is a rare disease, which comprises less than 1% of all non-Hodgkin lymphoma. The epidemiology of this disorder has not been established in New Zealand, particularly the ethnic variation. METHODS: A retrospective study was conducted from 2005 to 2017 in South Auckland, New Zealand. Patients with histopathologically confirmed subcutaneous panniculitis-like alpha-beta T-cell lymphoma, according to the WHO-EORTC classification, were included. Cases were identified from multiple data sources to ensure the study population was completely surveyed. Census data were used as the denominator. RESULTS: Ten cases were identified. Five were men and five women. The median age at diagnosis was of 38.5 years (range 17-73 years). Nine were Maori/Pacific, and one was European. The ethnic relative risk of subcutaneous panniculitis-like alpha-beta T-cell lymphoma in Maori/Pacific versus European was 11.1 (95% Cl 1.83-246.1, P = 0.005). CONCLUSION: Maori and Pacific have a higher relative risk of subcutaneous panniculitis-like alpha-beta T-cell lymphoma compared to non-Maori/Pacific.

Open-label Placebos for Wound Healing: A Randomized Controlled Trial.

Background: Open-label placebos are a novel treatment option, in which participants take placebos with full knowledge that they do not contain active medicine. Open-label placebo treatments have been shown to result in patient-reported symptom improvements, but they have not been tested on objectively measurable physiological outcomes such as wound healing. Purpose: The current study aimed to determine whether open-label placebos improved wound healing in punch biopsy wounds compared with no treatment. Methods: In a randomized controlled trial, 70 participants (mean age 27.6 ± 10.1, 58 female) were provided with information about the beneficial effects of placebos and given a 4 mm punch biopsy wound. Participants were then randomized to either an open-label placebo intervention (two placebo tablets twice a day for 10 days) or a no-treatment control group. Wounds were photographed at 7 days and 10 days to determine reepithelialization of the wound surface. Results: No significant differences were observed between the open-label placebo and control conditions in the percentage of wound area healed or for the number of participants with fully reepithelialized wounds at 7 days (placebo 7/32 wounds healed, control 10/33 wounds healed, (χ2[1, N = 65] = 0.60, p = .440, φ = 0.10) and 10 days after wounding (placebo 17/32, control 25/33 wounds healed (χ2[1, N = 65] = 3.64, p = .056, φ = 0.24). Conclusions: Open-label placebo treatment does not improve the healing rate of wounds. Open-label placebos may be beneficial for subjective patient-reported outcomes but do not influence wound healing. Australian New Zealand Clinical Trials Registration: ACTRN12616000411448.

Scabies is strongly associated with acute rheumatic fever in a cohort study of Auckland children.

AIM: This study sought to determine whether scabies infection is associated with acute rheumatic fever (ARF) or chronic rheumatic heart disease (CRHD). METHODS: A cohort study was undertaken using health records of children aged 3-12 years attending an oral health service for the first time. Subjects were then linked to hospital diagnoses of scabies and ARF or CRHD. RESULTS: A total of 213 957 children free of rheumatic heart disease at baseline were available for analysis. During a mean follow-up time of 5.1 years, 440 children were diagnosed with ARF or CRHD in hospital records. Children diagnosed with scabies during follow-up were 23 times more likely to develop ARF or CRHD, compared with children who had no scabies diagnosis. After adjustment for confounders in a Cox model, the association reduced but remained strong (adjusted hazard ratio: 8.98; 95% confidence interval: 6.33-20.2). In an analysis restricted to children hospitalised at least once during follow-up, the adjusted hazard ratio for the same comparison was 3.43 (95% confidence interval: 1.85-6.37). CONCLUSIONS: A recent diagnosis of scabies from hospital records is strongly associated with a subsequent diagnosis of ARF. Further investigation of the role that scabies infestation may play in the aetiology of ARF is warranted.

Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients.

The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h-1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h-1 A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.

The effects of expressive writing before or after punch biopsy on wound healing.

OBJECTIVE: Recent studies have shown that written emotional disclosure (expressive writing) performed in the two weeks prior to wounding improves healing of punch biopsy wounds. In many clinical settings, it would be more practical for patients to perform this intervention after wounding. The aim of this study was to investigate whether expressive writing could speed the healing of punch biopsy wounds if writing was performed after wounds were made. METHODS: One hundred and twenty-two healthy participants aged between 18 and 55years were randomly allocated to one of four groups in a 2 (intervention) by 2 (timing) design. Participants performed either expressive writing or neutral writing, either before or after receiving a 4mm punch biopsy wound. Wounds were photographed on day 10 (primary endpoint) and day 14 after the biopsy to measure epithelisation. Participants also completed questionnaires on stress and affect two weeks prior to the biopsy, on the day of biopsy and two weeks after biopsy. RESULTS: There was a significant difference in healing at day 10 between groups, χ2(3, N=97)=8.84, p=0.032. A significantly greater proportion of participants who performed expressive writing before the biopsy had fully reepithelialised wounds on day 10 compared to participants who performed neutral writing either before or after wounding, with no other significant differences between groups. Amongst people who wrote expressively after wounding, those who finished writing over the first 6days were significantly more likely to be healed at 14days than those who finished writing later. There were significant differences in positive and negative affect over the healing period between the pre and post expressive writing groups. CONCLUSIONS: Expressive writing can improve healing if it is performed prior to wounding. Performing expressive writing after wounding may be able to improve healing depending on the timing of writing and wound assessment. Expressive writing causes affect to worsen followed by subsequent improvement and it is important to consider this in the timing of intervention delivery. Further research with patient groups is required to determine the clinical relevance of these findings.

A short history of phototherapy, vitamin D and skin disease.

The earliest record between sun exposure and skin disease goes back five millennia to the ancient Egyptians. The modern scientific era of medical light therapy and skin diseases started in 1877 when Downs and Blunt reported that exposure to light inhibited fungal growth in test tubes. Continuing research generated a growing medical interest in the potential the effects of light to treat and cure skin diseases considered as parasitic. This culminated in the awarding of the 1903 Nobel Prize in Medicine to Niels Finsen for his pioneering work showing that light could successfully treat cutaneous mycobacterium tuberculosis (lupus vulgaris), a disfiguring disorder common at the time. Cod liver oil was used as a folk remedy to treat rickets prior to 1789 in Manchester, UK and sunlight was published as the cure for this disease in 1921. The work by Hess and Weinstock in 1925 showed that food irradiated with ultraviolet (UV) light prevented rickets in rats, which paved the way for the discovery of vitamin D. The range of skin diseases treated by light therapy increased in the following years, to the point where a 1932 review by the American Medical Association on the use of UV therapy in dermatology listed 34 skin conditions for which UV radiation may be useful. This period coincided with the development of sanatoria in Europe and North America which used heliotherapy for the treatment of tuberculosis. UV therapy and vitamin D continued to be used successfully for the treatment of tuberculosis up to the 1950s when it was superseded by more effective antibiotics. Modern phototherapy developed in the 1980s with the discovery of the action spectrum for psoriasis leading to the development of narrow band UVB. Subsequently a biological mechanism by which UV light and vitamin D treated tuberculosis was identified in 2006. This involves activation of human macrophages via toll-like receptors to upregulate the vitamin D receptor gene resulting in induction of the antimicrobial peptide cathelicidin. The role of UV light and vitamin D in the treatment of skin diseases is currently an active area of research.

Medical specialists' attitudes to prescribing biosimilars.

PURPOSE: Biosimilars are a cost-effective alternative to biologics that could improve patients' access to expensive biological medicines. Currently, there are little data on doctors' perceptions of biosimilars and in what situations they are comfortable prescribing biosimilars. In this study, we investigated medical specialists' perceptions of biosimilars and the factors associated with the acceptance of biosimilars. METHODS: A national sample of 110 of 327 medical specialists working in the areas of rheumatology, dermatology, gastroenterology, oncology and haematology completed an online questionnaire examining attitudes towards prescribing biosimilars, indication extrapolation and switching patients to a biosimilar. RESULTS: Most specialists held positive views of biosimilars, with between 54 and 74% confident in the safety, efficacy, manufacturing and pharmacovigilance of biosimilars. Seventy-one percent of specialists agreed that they would prescribe biosimilars for all or some conditions meeting relevant clinical criteria. Specialists were less confident about indication extrapolation and switching patients from an existing biologic. Acceptance of biosimilars was significantly associated with a lower perceived time to explain a biosimilar to a patient and lower number of weekly patient appointments. The most common situations that they would not prescribe a biosimilar was where there was a lack of clinical data supporting efficacy (32%), or evidence of adverse effects (17%). CONCLUSIONS: Medical specialists held generally positive attitudes towards biosimilars but were less confident in indication extrapolation and switching patients from a biologic. Providing clinicians with guidance on how to explain biosimilars to patients and written patient material may help overcome some of the barriers to the use of biosimilars. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of Obesity on the Population Pharmacokinetics of Meropenem in Critically Ill Patients.

Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m(2)), obese (30.0 to 39.9 kg/m(2)), and morbidly obese (≥40 kg/m(2)). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean ± standard deviation (SD) age, weight, and BMI were 49 ± 15.9 years, 95 ± 22.0 kg, and 33 ± 7.0 kg/m(2), respectively. A two-compartment model described the data adequately. The mean ± SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 ± 6.0 liters/h; volume of distribution in the central compartment (V1), 11.7 ± 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 ± 35.1 liters h(-1); and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 ± 12.24 liters h(-1) Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V1, dose adjustment based on CLCR appears to be more important than patient BMI.

Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients.

Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (≥40 kg/m2). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (n = 6) and morbidly obese (n = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m2, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (Vc) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m2 A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.

Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity.

OBJECTIVES: To measure tissue glucocorticoid sensitivity in patients with septic shock and determine its relationship to standard measurements of adrenal function and of outcome. DESIGN: Prospective observational trial. SETTING: Teaching hospital ICU. SUBJECTS: Forty-one patients and 20 controls were studied. INTERVENTIONS: Glucocorticoid sensitivity was measured by in vitro suppression of cytokine production from lipopolysaccharide-stimulated leukocytes. MEASUREMENTS AND MAIN RESULTS: There was no significant difference between the groups in the relative suppression of cytokine production, although there was a greater range and variance in the patient data. Patients in the lowest quartile of glucocorticoid sensitivity had higher Acute Physiology and Chronic Health Evaluation II scores (25 [24-28] vs 20 [14-23]; p = 0.02) and a trend toward higher mortality (30% vs 0%; p = 0.2) compared to those in the highest. The mRNA expression of the ß variant of the glucocorticoid receptor and the 11-ß hydroxysteroid dehydrogenase 2 isozyme were significantly higher in patients compared to controls (8.6-fold, p = 0.002 and 10.1-fold, p = 0.0002, respectively). Changes in mRNA expression of these genes did not correlate with measurements of glucocorticoid sensitivity. CONCLUSIONS: Patients with septic shock and controls do not differ in their median glucocorticoid sensitivity. However, patients exhibited a greater variability in glucocorticoid responsiveness and had evidence of association between increased sickness sensitivity and reduced glucocorticoid sensitivity. Sensitivity to glucocorticoids did not appear to be mediated by changes in the expression of the ß variant of the glucocorticoid receptor or the 11-ß hydroxysteroid dehydrogenase 2 isozyme.