Science, Medicine, and Cytology: an educational program of the Diversity, Equity, and Inclusion Committee of the American Society of Cytopathology.

INTRODUCTION: As our field of pathology continues to grow, our trainee numbers are on the decline. To combat this trend, the ASC Diversity, Equity, and Inclusion Committee established the Science, Medicine, and Cytology SumMer Certificate program to improve exposure to pathology/cytopathology with a focus on diversity, equity, and inclusion. Herein, we report our findings of the first 2 years of the program. MATERIALS AND METHODS: An online course was developed targeting students who are underrepresented in medicine at the high school and college level. It consisted of several didactic sessions, presenting the common procedures involving cytopathologists and cytologists. Interviews with cytopathologists were also included. Participants were surveyed for demographic information and provided course evaluations. RESULTS: In the first year of the program (2021), 34 participants completed the program, which increased to 103 in 2022. In both years there was a diversity in participant demographic backgrounds; however, only a minority of participants self-identified as being underrepresented in medicine. A vast majority (>85%) of participants in both years were high school or college students. In 2021, 100% of participants stated that the program format was effective and 94% thought the content was appropriate for their level of education; in 2022 the results were similar. In 2021, 66% considered health care as a potential career; this value increased in 2022 to 83%. In 2021 and 2022, 31% and 38%, respectively, considered cytology as a career. CONCLUSIONS: Evaluations were excellent, generating interest in cytopathology. Barriers in reaching underrepresented minorities exist and additional work is needed. Expansion to a wider audience may increase outreach.

The current state of digital cytology and artificial intelligence (AI): global survey results from the American Society of Cytopathology Digital Cytology Task Force.

INTRODUCTION: The integration of whole slide imaging (WSI) and artificial intelligence (AI) with digital cytology has been growing gradually. Therefore, there is a need to evaluate the current state of digital cytology. This study aimed to determine the current landscape of digital cytology via a survey conducted as part of the American Society of Cytopathology (ASC) Digital Cytology White Paper Task Force. MATERIALS AND METHODS: A survey with 43 questions pertaining to the current practices and experiences of WSI and AI in both surgical pathology and cytology was created. The survey was sent to members of the ASC, the International Academy of Cytology (IAC), and the Papanicolaou Society of Cytopathology (PSC). Responses were recorded and analyzed. RESULTS: In total, 327 individuals participated in the survey, spanning a diverse array of practice settings, roles, and experiences around the globe. The majority of responses indicated there was routine scanning of surgical pathology slides (n = 134; 61%) with fewer respondents scanning cytology slides (n = 150; 46%). The primary challenge for surgical WSI is the need for faster scanning and cost minimization, whereas image quality is the top issue for cytology WSI. AI tools are not widely utilized, with only 16% of participants using AI for surgical pathology samples and 13% for cytology practice. CONCLUSIONS: Utilization of digital pathology is limited in cytology laboratories as compared to surgical pathology. However, as more laboratories are willing to implement digital cytology in the near future, the establishment of practical clinical guidelines is needed.

Digital cytology part 1: digital cytology implementation for practice: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytopathology laboratory. However, peer-reviewed real-world data and literature are lacking regarding the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper presented herein is a review and offers best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the results of a global survey regarding digital cytology are highlighted.

Digital cytology part 2: artificial intelligence in cytology: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytology laboratory. However, peer-reviewed real-world data and literature are lacking in regard to the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper is presented as a separate paper which details a review and best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper presented here provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the cytology global survey results highlighting current AI practices by various laboratories, as well as current attitudes, are reported.

How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review.

PURPOSE: To examine the reporting completeness of randomized controlled trials (RCTs) of non-pharmacological interventions following concussion. METHODS: We searched MEDLINE, Embase, PsycInfo, CINAHL, and Web of Science up to May 2022. Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication (TIDieR), Consensus on Exercise Reporting Template (CERT), and international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) checklists. Additional information was sought my study authors where reporting was incomplete. Risk of bias (ROB) was assessed with the Cochrane ROB-2 Tool. RCTs examining non-pharmacological interventions following concussion. RESULTS: We included 89 RCTs (n = 53 high ROB) examining 11 different interventions for concussion: sub-symptom threshold aerobic exercise, cervicovestibular therapy, physical/cognitive rest, vision therapy, education, psychotherapy, hyperbaric oxygen therapy, transcranial magnetic stimulation, blue light therapy, osteopathic manipulation, and head/neck cooling. Median scores were: TIDieR 9/12 (75%; interquartile range (IQR) = 5; range: 5-12), CERT 17/19 (89%; IQR = 2; range: 10-19), and i-CONTENT 6/7 (86%; IQR = 1; range: 5-7). Percentage of studies completely reporting all items was TIDieR 35% (31/89), CERT 24% (5/21), and i-CONTENT 10% (2/21). Studies were more completely reported after publication of TIDieR (t87 = 2.08; p = 0.04) and CERT (t19 = 2.72; p = 0.01). Reporting completeness was not strongly associated with journal impact factor (TIDieR: rs = 0.27; p = 0.01; CERT: rs = -0.44; p = 0.06; i-CONTENT: rs = -0.17; p = 0.48) or ROB (TIDieR: rs = 0.11; p = 0.31; CERT: rs = 0.04; p = 0.86; i-CONTENT: rs = 0.12; p = 0.60). CONCLUSION: RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness, but are often missing key components, particularly modifications, motivational strategies, and qualified supervisor. Reporting completeness improved after TIDieR and CERT publication, but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Stress-induced severe transient hypercortisolism with reversible bilateral adrenal enlargement after cardiogenic shock.

Summary: Acute illness-related stress can result in severe hypercortisolism and bilateral adrenal enlargement in certain patients. We report a case of stress-induced hypercortisolism and bilateral adrenal enlargement in a patient admitted for acute respiratory distress and cardiogenic shock. Bilateral adrenal enlargement and hypercortisolism found during hospitalization for acute illness resolved 3 weeks later following the resolution of acute illness. Acute illness can be a precipitating factor for stress-induced hypercortisolism and bilateral adrenal enlargement. We hypothesize that increased adrenocorticotrophic hormone mediated by corticotrophin-releasing hormone from physical stress resulted in significant adrenal hyperplasia and hypercortisolism. This mechanism is downregulated once acute illness resolves. Learning points: Adrenal enlargement with abnormal adrenal function after stress is uncommon in humans; however, if present, it can have self-resolution after the acute illness is resolved. Stress induces enlargement of the adrenals, and the degree of cortisol elevation could be very massive. This process is acute, and the absence of cushingoid features is expected. Treatment efforts should be focused on treating the underlying condition.

Human skeletal muscle mitochondrial responses to single-leg intermittent or continuous cycle exercise training matched for absolute intensity and total work.

There is renewed interest in the potential for interval (INT) training to increase skeletal muscle mitochondrial content including whether the response differs from continuous (CONT) training. Comparisons of INT and CONT exercise are impacted by the manner in which protocols are "matched", particularly with respect to exercise intensity, as well as inter-individual differences in training responses. We employed single-leg cycling to facilitate a within-participant design and test the hypothesis that short-term INT training would elicit a greater increase in mitochondrial content than work- and intensity-matched CONT training. Ten young healthy adults (five males and five females) completed 12 training sessions over 4 weeks with each leg. Legs were randomly assigned to complete either 30 min of CONT exercise at a challenging sustainable workload (~50% single-leg peak power output; Wpeak) or INT exercise that involved 10 × 3-min bouts at the same absolute workload. INT bouts were interspersed with 1 min of recovery at 10% Wpeak and each CONT session ended with 10 min at 10% Wpeak. Absolute and mean intensity, total training time, and volume were thus matched between legs but the pattern of exercise differed. Contrary to our hypothesis, biomarkers of mitochondrial content including citrate synthase maximal activity, mitochondrial protein content and subsarcolemmal mitochondrial volume increased after CONT (p < 0.05) but not INT training. Both training modes increased single-leg Wpeak (p < 0.01) and time to exhaustion at 70% of single-leg Wpeak (p < 0.01). In a work- and intensity-matched comparison, short-term CONT training increased skeletal muscle mitochondrial content whereas INT training did not.

Zinc toxicosis in a cat associated with ingestion of a metal screw nut.

Case summary: A 3-year-old female neutered domestic shorthair cat was presented for vomiting, inappetence and weight loss. The cat developed moderately regenerative anaemia, moderately increased alanine transaminase and alkaline phosphatase activities, hyperbilirubinaemia and prolonged activated partial thromboplastin time. Abdominal ultrasound identified gastric wall thickening and changes suggestive of pancreatitis. Gastroduodenoscopy identified a metal screw nut in the pylorus, which was removed with rat tooth forceps. Metal analysis and serum zinc concentration using leftover serum collected at admission were performed after screw nut removal. Serum zinc concentration was markedly elevated, confirming a diagnosis of zinc toxicosis. Metal analysis of the screw nut showed that the major metal component was zinc. The cat recovered after screw nut removal and supportive care. Clinical signs resolved and the serum zinc concentration reduced significantly after screw nut removal. Relevance and novel information: Reports of zinc toxicosis in cats are scarce, possibly due to the more discriminating eating habits of this species. To our knowledge, this is the first report of zinc toxicosis causing haemolytic anaemia, liver enzyme activity increases, gastrointestinal signs and pancreatitis in a cat associated with ingestion of a zinc-containing metal object.

Is early patent ductus arteriosus ligation helpful in premature neonates? A 10-year retrospective study.

BACKGROUND: To compare short and long outcomes between early (≤ 28 days) (EL) and late ligation (LL) groups. To explore factors predicting early extubation (≤ 7 days) after patent ductus arteriosus (PDA) ligation. METHODS: We conducted a single center, retrospective cohort study of preterm infants < 32 weeks who underwent surgical ligation over a 10-year period (2009-2019). RESULTS: A total of 133 infants underwent PDA ligation, in the study period. Both groups had similar short-term outcome such as bronchopulmonary dysplasia (BPD) or death (96% vs. 98%, P = 0.64) and long-term clinical outcomes including Bayley's assessment at 2 years corrected age. Fewer infants in the EL group developed severe BPD (63% vs. 81%, P = 0.02). Age at ligation had adjusted odds ratio of 1.04 with over lapping confidence interval (95% CI 1.0-1.1, P = 0.02) for severe BPD/death. There was no difference in day of extubation between the EL and LL group (8 days vs. 7 days, P = 0.85). Left atrium/aortic root ratio of ≥ 1.75 would give sensitivity of 41% and 80% specificity for early extubation (area under the curve of 0.61). There was marginal reduction of hospital stay in the EL group [113 (105-121) days vs. 115 (107-123) days; log rank P = 0.026]. CONCLUSION: EL can be delivered safely with a clinically important lower incidence of severe BPD and shorter duration of hospital stay compared to LL.

Caval foramen hernia in a cat.

CASE SUMMARY: A 3-year-old neutered female domestic shorthair cat presented for a 2-week history of hyporexia, lethargy and weight loss. Aspartate aminotransferase, alanine aminotransferase and cholesterol were mildly elevated. Thoracic radiographs identified a lobulated soft tissue opacity in the caudal thorax to the right of midline, with the border effacing the caudal vena cava and broad-based towards the diaphragm. The broad base was suggestive of diaphragmatic hernia, with the other radiographic features and location suggestive of caval foramen hernia. Ultrasound confirmed diaphragmatic hernia with liver herniation. CT showed the herniation of multiple liver lobes and the gallbladder through a defect at the caval foramen. Herniorrhaphy was performed via ventral midline coeliotomy. Following this procedure, the cat's clinical signs resolved and its weight has been regained. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of successful caval foramen herniorrhaphy in a cat. Caval foramen hernia is a type of congenital diaphragmatic hernia. The authors suggest that its embryopathology involves defective septum transversum development. The case was detected during the standard diagnostic investigation of non-specific clinical signs. Its radiographic findings may easily be mistaken for a pulmonary mass. Although not seen in our case, caval foramen hernia is commonly associated with caudal vena cava obstruction, which can potentially result in Budd-Chiari-like syndrome.

Peripartum clinical manifestations of a mesentericorenocaval shunt in a Burmese cat.

CASE SUMMARY: A 3-year-old entire female Burmese cat was presented for investigation of intermittent lethargy during gestation followed by persistent hypersalivation and ataxia postpartum. The cat had queened three litters in total, with clinical signs worsening during the most recent lactation period. Mild anaemia (26%), hypoglycaemia (2.4 mmol/l; reference interval [RI] 3.9-8.3 mmol/l) and increased postprandial serum bile acids (74 µmol/l; RI <25 µmol/l) were identified on initial bloodwork. Multiphase contrast-enhanced CT identified a mesentericorenocaval portosystemic shunt; this was attenuated surgically with an ameroid constrictor. Clinical signs resolved after surgery. Follow-up 3 months postoperatively revealed normal pre- and postprandial serum bile acids (2 µmol/l and 3 µmol/l, respectively) with repeat CT identifying evidence of shunt attenuation. The cat continued to be healthy and free of clinical signs 12 months postoperatively. RELEVANCE AND NOVEL INFORMATION: Mesentericorenocaval portosystemic shunt morphology has not been previously reported in the cat and should be considered as a differential diagnosis for cats presenting with peripartum onset of malaise, ptyalism or ataxia.

An international outreach from the American Society of Cytopathology: Worldvision Cytopathology Contest.

In an effort to be more inclusive and embrace the international cytology community, the American Society of Cytopathology formed the International Liaison and Membership (ILM). The Worldvision Cytopathology Contest was designed by the co-chairs of this committee (Drs. Güliz A. Barkan and Esther Diana Rossi) as an opportunity of scientific exchange in the international cytology community. The idea took its inspiration from the well-known song contest, the "Eurovision Song Contest" a competition among international singers, which started as a "light entertainment" in the 1950's to bring together a war-torn Europe. The goals of this session were to bring the worldwide cytology community together, to increase the international participation to the ASC, to attract a younger generation of pathology professionals to cytopathology, to provide education on interesting cases for the participants, and to provide training for international contestants on how to give good public presentations. The contest was successfully done at the 2019 annual meeting, and the winner was Dr. Elena Vigliar from Italy. The Worldvision Cytopathology Contest will be performed again in future meetings.

Catastrophic failure of the Accolade I hip arthroplasty stem: a retrieval analysis study.

PURPOSE: Modular Morse tapered femoral arthroplasty stems have been used for many years with great success and minimal complications. 1 stem, the Accolade by Stryker is noted to have increased failure when used in combination with LFIT V40 CoCr or the MITCH CoCr femoral heads. The failure has been in the form of corrosion, metallosis, fretting and trunnion fracture. This paper explores 10 cases with trunnion failure. METHODS: A retrospective retrieval analysis of ten femoral stems retrieved at four different centres across Western Australia over a 3-year time frame. Inclusion criteria for this analysis included the use of Accolade 1 TMZF femoral stem plus either a MITCH or LFIT modular head. RESULTS: 10 Accolade I (Stryker) stems were retrieved as part of the analysis, 6 with the LFIT V40 36-mm femoral head and 4 with a MITCH TRH femoral head. Average in situ time was 8.9 years. The hips were revised for either trunnion dislocation (6 cases) or trunnion fracture (4 cases). A characteristic destructive wear pattern of the femoral taper (trunnion) a "bird beak" appearance was present in all stems. This wear pattern created excessive movement and loosening resulting in a trunnion/head dislocation or brittle fracture of the trunnion. CONCLUSIONS: Catastrophic femoral neck fracture was likely due to a combination of material composition mismatch and mechanically assisted fretting corrosion at the head-neck junction leading to gross metallosis and failure. We suggest a recall on patients with an Accolade 1 stems in combination with a 36-mm or above LFIT or MITCH head, and for these patients to have clinical and radiological review.

Feline Parvovirus Seroprevalence Is High in Domestic Cats from Disease Outbreak and Non-Outbreak Regions in Australia.

Multiple, epizootic outbreaks of feline panleukopenia (FPL) caused by feline parvovirus(FPV) occurred in eastern Australia between 2014 and 2018. Most affected cats were unvaccinated.We hypothesised that low population immunity was a major driver of re-emergent FPL. The aim ofthis study was to (i) determine the prevalence and predictors of seroprotective titres to FPV amongshelter-housed and owned cats, and (ii) compare the prevalence of seroprotection between a regionaffected and unaffected by FPL outbreaks. FPV antibodies were detected by haemagglutinationinhibition assay on sera from 523 cats and titres ≥1:40 were considered protective. Socioeconomicindices based on postcode and census data were included in the risk factor analysis. The prevalenceof protective FPV antibody titres was high overall (94.3%), even though only 42% of cats wereknown to be vaccinated, and was not significantly different between outbreak and non-outbreakregions. On multivariable logistic regression analysis vaccinated cats were 29.94 times more likelyto have protective FPV titres than cats not known to be vaccinated. Cats from postcodes of relativelyless socioeconomic disadvantage were 5.93 times more likely to have protective FPV titres. Thepredictors identified for FPV seroprotective titres indicate targeted vaccination strategies in regionsof socioeconomic disadvantage would be beneficial to increase population immunity. The criticallevel of vaccine coverage required to halt FPV transmission and prevent FPL outbreaks should bedetermined.

B-type natriuretic peptide trumps other prognostic markers in patients assessed for coronary disease.

BACKGROUND: Risk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous markers have the potential to predict prognosis and guide management, but we currently lack robust 'real-world' evidence for their use. METHODS: Prospective, multicentre observational study of consecutive patients referred for elective coronary angiography. Clinicians were blinded to all risk assessments, consisting of conventional factors, radial artery pulse wave analysis, 5-minute heart rate variability, high-sensitivity C-reactive protein and B-type natriuretic peptide (BNP). Blinded, independent adjudication was performed for all-cause mortality and the composite of death, myocardial infarction or stroke, analysed with Cox proportional hazards regression. RESULTS: Five hundred twenty-two patients were assessed with median age 66 years and 21% prior revascularization. Median baseline left ventricular ejection fraction was 64%, and 62% had ≥ 50% stenosis on angiography. During 5.0 years median follow-up, 30% underwent percutaneous and 16% surgical revascularization. In multivariate analysis, only age and BNP were independently associated with outcomes. The adjusted hazard ratio per log unit increase in BNP was 2.15 for mortality (95% CI 1.45-3.19; p = 0.0001) and 1.27 for composite events (1.04-1.54; p = 0.018). Patients with baseline BNP > 100 pg/mL had substantially higher mortality and composite events (20.9% and 32.2%) than those with BNP ≤ 100 pg/mL (5.6% and 15.5%). BNP improved both classification and discrimination of outcomes (p ≤ 0.003), regardless of left ventricular systolic function. Conversely, high-sensitivity C-reactive protein, pulse wave analysis and heart rate variability were unrelated to prognosis at 5 years after risk modification and treatment of coronary disease. CONCLUSIONS: Conventional risk factors and other markers of arterial compliance, inflammation and autonomic function have limited value for prediction of outcomes in risk-modified patients assessed for coronary disease. BNP can independently identify patients with subtle impairment of cardiac function that might benefit from more intensive management. TRIAL REGISTRATION: Clinicaltrials.gov, NCT00403351 Registered on 22 November 2006.

Suspected adverse drug interaction between spinosad and milbemycin oxime in a cat.

CASE SUMMARY: A 12-year-old male neutered Tonkinese cat was presented for acute ataxia, weakness, altered mentation and generalised tremors. The cat had been administered oral spinosad (140 mg; 33.5 mg/kg) 48 h prior to the onset of clinical signs, and an oral anthelmintic containing milbemycin oxime (16 mg; 3.8 mg/kg) and praziquantel (40 mg; 9.6 mg/kg) 12 h before the onset of clinical signs. On physical examination, dull-to-obtunded mentation, tetraparesis, ataxia and mild tremors of facial, limb and trunk muscles were noted. Serum biochemical changes and urinalysis were consistent with haemoconcentration. The results of a complete blood count, urine culture and serology for feline leukaemia virus, feline immunodeficiency virus and cryptococcal antigen were negative. The patient was monitored in hospital and all clinical signs resolved within 24 h. RELEVANCE AND NOVEL INFORMATION: The neurological signs in this case were consistent with macrocyclic lactone neurotoxicity, which is suspected to have occurred from an adverse drug interaction between spinosad and milbemycin oxime. This report serves to highlight the potential for this adverse drug interaction between these commonly used prophylactic drugs.

Dental Abscess in Pediatric Patients: A Marker of Neglect.

OBJECTIVES: Neglect is defined as the persistent failure to meet a child or young person's basic physical or psychological needs. Dental caries is explicitly mentioned in guidance on child maltreatment. We discuss the link between dental caries and child abuse in patients presenting to the emergency department. METHODS: A review of patient medical records was undertaken within the Paediatric Emergency Department at Sunderland Royal Hospital, with the aim to determine whether neglect was considered as a possible contributory factor when a child or young person presented at triage with an "oral cavity" problem. RESULTS: Of the applicable cases with inferences of possible safeguarding concerns, 13% had these concerns documented. CONCLUSIONS: Child abuse recognition has become a prominent issue in recent years due to high profile cases. It is clear from this work, which resonates with the reported literature, that there is a lack of recognition of dental neglect being a possible indicator of more systemic abuse.There is likely underreporting of these cases to the relevant authorities.

The effect of brief intermittent stair climbing on glycemic control in people with type 2 diabetes: a pilot study.

We examined the effect of brief intermittent stair climbing exercise on glycemic control using continuous glucose monitoring in people with type 2 diabetes (n = 7, 5 men; 2 women; age, 21-70 years). The protocol involved three 60-s bouts of vigorously ascending and slowly descending a flight of stairs. Mean 24-h blood glucose was unchanged after an acute session (p = 0.43) and following 18 sessions over 6 weeks (p = 0.13). The protocol was well tolerated by participants but seemingly insufficient to alter glycemic control.

Is the Skin Absorption of Hydrocortisone Modified by the Variability in Dosing Topical Products?

Fingertip units have been proposed as a tool to standardize topical therapy with semisolid formulations. However, no studies to date have characterized the variability in dosing by patients using this concept and whether this variability ultimately affects the topical absorption of drugs. This work aimed to answer these two questions. A first study determined the dose measured, the area of spread and the area-normalized dose for a 1% hydrocortisone cream and ointment applied by members of the public using this dosing approach before and after brief counselling. Then, in vivo tape-stripping and in vitro permeation studies investigated whether the variability in the area-normalized dose altered the skin absorption of hydrocortisone. Participants applied greater doses and spread them over larger areas after a short counselling intervention leading to smaller area-normalized doses. In vivo hydrocortisone uptake by the stratum corneum was significantly greater for the higher normalized dose and the differences were further supported by the in vitro permeation studies. However, these differences were relatively small and not proportional to the increase in normalized dose. This work shows that, following brief advice, patients and carers can apply consistent and sufficient doses of corticosteroids whilst minimizing risks and variability in hydrocortisone absorption.