Parameter Estimation for Mixed-Mechanism Tear Film Thinning.

Etiologies of tear breakup include evaporation-driven, divergent flow-driven, and a combination of these two. A mathematical model incorporating evaporation and lipid-driven tangential flow is fit to fluorescence imaging data. The lipid-driven motion is hypothesized to be caused by localized excess lipid, or "globs." Tear breakup quantities such as evaporation rates and tangential flow rates cannot currently be directly measured during breakup. We determine such variables by fitting mathematical models for tear breakup and the computed fluorescent intensity to experimental intensity data gathered in vivo. Parameter estimation is conducted via least squares minimization of the difference between experimental data and computed answers using either the trust-region-reflective or Levenberg-Marquardt algorithm. Best-fit determination of tear breakup parameters supports the notion that evaporation and divergent tangential flow can cooperate to drive breakup. The resulting tear breakup is typically faster than purely evaporative cases. Many instances of tear breakup may have similar causes, which suggests that interpretation of experimental results may benefit from considering multiple mechanisms.

Psychosocial burden and out-of-pocket costs in patients with atopic dermatitis in Ireland.

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases in the developed world, affecting 1-3% of the adult population in Europe. This inflammatory disease can have a marked impact on affected individuals, leading to significant impairment in physical wellbeing and quality of life (QoL). The aim of this study was to investigate the psychosocial impact and financial burden of AD on patients in Ireland. To increase our understanding of the psychosocial and financial aspects of AD disease burden in the Irish population, an online survey was designed. The survey was launched by the Irish Skin Foundation, and included questions focusing on disease severity, disease control, psychosocial impact, interrupted sleep, missed work and school days, and financial cost. The survey showed that the impact of AD on QoL was profound. The survey demonstrated that 85% of adults described interrupted sleep, 70% reported social anxiety, 65% avoid exercise and sports, 52% avoid social activities, 52% avoid sexual intimacy and 43% feel they are depressed as a result of their AD. Approximately one-quarter of those surveyed can spend up to €2300 annually on over-the-counter, prescription and alternative treatments. This study has shown the significant impact AD has on patients living in Ireland. It also highlights that out-of-pocket costs for patients is higher compared with previous studies across European countries.

A qualitative analysis of psychological distress in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) can negatively impact on patients' quality of life and is associated with a higher risk of depression, as well as difficulties in employment and relationships. OBJECTIVES: This study sought to evaluate the lived experience of psychological distress in HS. METHODS: Structured interviews were conducted with 12 participants. These were later transcribed and analysed using thematic analysis. The transcripts and analysis were reviewed by an independent researcher. RESULTS: The results indicated that there were three main themes: shame, pain and coping mechanisms. Participants indicated that their feelings of shame were due to disgust at their symptoms. They feared that others would be disgusted if their symptoms were obvious. Participants reported feeling invalidated when others did not understand the severity of their pain. Additionally, they reported that pain left them with a sense of powerlessness over their own bodies. Regarding coping mechanisms, adaptive strategies included social support while maladaptive strategies included social withdrawal. CONCLUSIONS: These findings are discussed in the context of the existing research on shame, chronic pain and psoriasis. The implications for psychological support for individuals with HS are evaluated. Additionally, the limitations of this study are considered and recommendations for future research are given. This study has highlighted that feelings of shame and physical pain are associated with psychological distress in HS. What's already known about this topic? Hidradenitis suppurativa (HS) has been shown to be associated with physical pain, a higher risk of depression, difficulties in sustaining employment and difficulties in relationships. Additionally, studies using quality-of-life measures have found more impairment in HS than in other dermatological conditions. What does this study add? Although the research to date has determined that there are negative social and emotional consequences associated with HS, the psychological processes underlying these impairments have not yet been looked at. This study aims to get a deeper understanding of the lived experience of psychological distress in HS and how individuals with HS attempt to manage this distress. What are the clinical implications of the work? This study has identified shame as a key feature that underlies the psychological difficulties experienced as a consequence of HS. When deciding upon appropriate psychological interventions for HS, approaches that specifically focus on reducing feelings of shame should be considered.

Parameter Estimation for Evaporation-Driven Tear Film Thinning.

Many parameters affect tear film thickness and fluorescent intensity distributions over time; exact values or ranges for some are not well known. We conduct parameter estimation by fitting to fluorescent intensity data recorded from normal subjects' tear films. The fitting is done with thin film fluid dynamics models that are nonlinear partial differential equation models for the thickness, osmolarity and fluorescein concentration of the tear film for circular (spot) or linear (streak) tear film breakup. The corresponding fluorescent intensity is computed from the tear film thickness and fluorescein concentration. The least squares error between computed and experimental fluorescent intensity determines the parameters. The results vary across subjects and trials. The optimal values for variables that cannot be measured in vivo within tear film breakup often fall within accepted experimental ranges for related tear film dynamics; however, some instances suggest that a wider range of parameter values may be acceptable.

Investigation of the skin microbiome: swabs vs. biopsies.

BACKGROUND: Human skin is populated by diverse bacteria and there is increasing evidence that resident bacteria play a key role initiating immune responses in cutaneous diseases such as atopic dermatitis, psoriasis and hidradenitis suppurativa. Bacteria are present at all layers of the skin but many studies have relied on swabs to profile the skin microbiota. OBJECTIVES: As the pathogenesis of many skin conditions is dermal, we wanted to compare the microbiota obtained in swabs (surface) and biopsies (dermis). METHODS: Using 16S rRNA gene sequencing we established the microbial profiles of skin swabs and skin biopsies in 16 patients. RESULTS: We found differences in both diversity and taxonomic composition of the microbiome obtained from swabs and biopsies of the same individual. Several taxa were found to be more abundant in the swabs, which displayed significantly higher community richness, but Clostridiales and Bacteroidetes were significantly enriched in the biopsies. Most published research on cutaneous microbiota has been based on skin swabs, which represent the surface of the skin. CONCLUSIONS: Our study demonstrated a clear difference between the microbiome observed from skin swabs and skin biopsies. These findings may be highly relevant in disorders such as psoriasis where pathogenesis arises in the dermis. What's already known about this topic? 16S RNA gene sequencing has facilitated study of the skin microbiome. Several studies have sequenced the microbiome sampled by skin swabs. What does this study add? The microbiome data obtained using swabs and biopsies were different. Diseases that are predominantly dermal should be studied using both swabs and biopsies.

Could isotretinoin flare hidradenitis suppurativa? A case series.

We report eight cases of patients with severe acne who were treated with isotretinoin and developed painful nodules in the axillae and groin, consistent with hidradenitis suppurativa (HS). The pathogenesis of HS is still not completely understood; recent research from a study in 2011 of biopsies from HS lesions showed a reduction or absence of sebaceous glands compared with normal skin in patients with HS, with the report suggesting that this contributes to the pathogenesis of the disease. Interestingly, the main effect of isotretinoin is to decrease the size and action of sebaceous glands, so hypothetically, as isotretinoin acts by reducing the sebaceous glands further it could potentially aggravate HS. Our experience has instilled caution in our prescribing of isotretinoin, and we question patients, particularly those with acne conglobata, about symptoms of HS prior to and during treatment.

A cross-sectional epidemiological study of hidradenitis suppurativa in an Irish population (SHIP).

BACKGROUND: Hidradenitis suppurativa (HS), a chronic inflammatory disease that affects apocrine gland-bearing skin, has a significant impact on patients' quality of life. Estimates of the epidemiologic prevalence of HS are highly variable, and clinical data on disease characteristics and patient burden of disease remain limited. OBJECTIVE: The primary objective of this study was to determine the number of patients with HS attending dermatology clinics in a hospital setting in Ireland (within a 6-month time period). Secondary objectives included the assessment of disease characteristics and the collection of patient responses on disease burden and work productivity. METHODS: This was an epidemiologic, non-interventional, cross-sectional study across four dermatology clinics in Ireland over a 6-month time period. The disease prevalence was estimated by calculating the percentage of total patients with a diagnosis of HS (the primary population) across the selected sites. Secondary analyses were performed using the full analysis set, which consisted of eligible adults (≥18 years of age) from the primary population who provided informed consent. Data from these analyses are presented as descriptive summary statistics, with the use of an analysis of covariance for continuous endpoints. RESULTS: The prevalence of HS across the four selected sites was estimated at 1.4% (95% CI, 1.24-1.62). One hundred and fifty eligible patients comprised the full analysis set. The majority of participants were white (95.3%), female (70.0%), cigarette smokers (56.0%) and overweight or obese (body mass index ≥25 kg/m2 , 81.8%). Most patients for whom data were available presented with Hurley stage II (50.4%), and more than a third of the full analysis set had a relative with HS (34.7%). Questionnaire responses revealed a profound impact on quality of life, including diminished work productivity and various psychological comorbidities. CONCLUSION: This study offers insight into the clinical features and disease burden of hidradenitis suppurativa in an Irish population.

Natural killer cells from psoriasis vulgaris patients have reduced levels of cytotoxicity associated degranulation and cytokine production.

Psoriasis vulgaris is a chronic inflammatory disease of the skin with a strong genetic component and immune system involvement. Although some evidence suggests that Natural Killer (NK) cells may play a part in psoriasis, their role is relatively unstudied and results are controversial. In this current study, NK cells from psoriasis patients exhibited reduced degranulation and produced lower levels of the pro-inflammatory cytokines IFN-γ and TNF-α. Further investigation found that NK cells from psoriasis patients and healthy controls expressed similar levels of activation markers, NK cell receptors and apoptosis-inducing molecules. In addition, comparable levels of several cytokines important in NK cell biology were found in the serum of psoriasis patients and healthy controls. Genotyping analysis revealed that HLA-C2, which provides a ligand for killer-cell immunoglobulin-like receptors (KIR) expressed by NK cells, was strongly associated with psoriasis susceptibility. However, no link between the KIR genes themselves and disease was found.

Trends and outcomes of chronic kidney disease in intensive care: a 5-year study.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing in Australia and is independently associated with a higher risk of hospitalisation and death. Australian data may be useful in guiding improved hospital management of this growing cohort of patients. AIM: To assess and compare the trends and outcomes of CKD patients requiring hospital and intensive care unit (ICU) admission at a tertiary referral hospital and state public hospitals. METHODS: We conducted a retrospective analysis of all acute care admissions to St Vincent's Hospital Melbourne and all Victorian public hospitals using the Victorian Admitted Episodes Data Set (VAED) for the years 2010-2014 to determine CKD prevalence, demographic and outcome associations. The Elixhauser ICD-10 comorbidity classification of renal failure was used to identify CKD (ElixRF). Chi-squared test, Kruskal-Wallis test and logistic regression were used for analysis. RESULTS: A total of 101 817 patients was included from our institution, with 6.4% classified as having ElixRF. ELixRF increased from 5.2% in 2010 to 8.6% in 2014 for all hospital admissions and from 8.3% to 13.3% for ICU admissions. ElixRF was associated with longer hospital and ICU length of stay, male gender, older age, higher comorbidity and independently with increased mortality. The VAED contained 2 044 507 episodes for the same period with similar trends and associations. CONCLUSIONS: CKD prevalence amongst patients admitted to hospital and ICU is increasing and is associated with worse outcomes. ElixRF may be a useful administrative flag for nephrologist involvement in care and for prompting consideration of advanced care planning.

Hidradenitis Suppurativa and Crohn's Disease: A Case Series.

Hidradenitis Suppurativa (HS) is characterized by chronic recurrent abscesses, nodules and draining sinus tracts with scar formation. Cutaneous Crohn's Disease (CD) may also present similarly. We wished to identify and describe an Irish cohort with combined HS and CD, with a view to a better recognition of clinical manifestations and understanding of the pathophysiology underlying these two overlapping conditions. Cases were identified using the HIPE Code at Tallaght Hospital from 1990-2014 and retrospective review was performed. Seven patients with both HS and CD were identified, 5(71%) female. The median age of diagnosis with both conditions was 37 years. In all cases, CD had preceded the diagnosis of HS. All patients smoked. Six had an increased BMI and 43% had additional autoimmune conditions. All patients required treatment with a TNF-alpha inhibitor for HS with 5 of 6 subjects having reduced frequency of flare ups and clinically less active HS on follow up.

Diet-tissue discrimination factors and turnover of carbon and nitrogen stable isotopes in tissues of an adult predatory coral reef fish, Plectropomus leopardus.

RATIONALE: Stable isotope ratios (δ(13)C and δ(15)N values) provide a unique perspective into the ecology of animals because the isotope ratio values of consumers reflect the values in food. Despite the value of stable isotopes in ecological studies, the lack of species-specific experimentally derived diet-tissue discrimination factors (DTDFs) and turnover rates limits their application at a broad scale. Furthermore, most aquatic feeding experiments use temperate, fast-growing fish species and few have considered medium- to large-sized adults with low growth rates from tropical ecosystems. METHODS: A controlled-diet stable isotope feeding trial was conducted over a 196-day period for the adult predatory reef fish leopard coralgrouper (Plectropomus leopardus). This study calculated δ(13)C and δ(15)N DTDFs and turnover rates in five tissues (liver, plasma, red blood cells (RBC), fin, and muscle) using a continuous flow isotope ratio mass spectrometer equipped with an elemental analyzer. In addition, the effect of chemical lipid extraction (LE) on stable isotope values was examined for each tissue. RESULTS: Turnover was mainly influenced by metabolism (as opposed to growth) with LE δ(15)N half-life values lowest in fin (37 days) and plasma (66 days), and highest in RBC (88 days) and muscle (126 days). The diet-tissue discrimination factors for δ(15)N values in all tissues (Δ(15)N: -0.15 to 1.84‰) were typically lower than commonly reported literature values. Lipid extraction altered both δ(15) N and δ(13)C values compared with untreated samples; however, for the δ(15)N values, the differences were small (mean δ(15)N(LE-Bulk) <0.46‰ in all tissues). CONCLUSIONS: This study informs future interpretation of stable isotope data for medium- to large-sized fish and demonstrates that DTDFs developed for temperate fish species, particularly for δ(15)N values, may not apply to tropical species. Sampling of muscle and/or RBC is recommended for a relatively long-term representation of feeding habits, while plasma and/or fin should be used for a more recent indication of diet.

Epidemiology of in-hospital mortality in acute patients admitted to a tertiary-level hospital.

BACKGROUND: Healthcare professionals may have difficulty in recognising the dying patient in acute care settings, and yet, this is essential if timely end-of-life care is to be provided. While approximately one-third of patients who pass away in-hospital are reviewed by the rapid response team (RRT), there is limited available research on other factors associated with mortality within the hospital setting. AIMS: To describe the epidemiology of in-hospital mortality within a tertiary-level hospital, particularly in the context of RRT activation. METHODS: We utilised the database extraction of demographic, admission and RRT activation data on acute patients discharged from an Australian acute tertiary hospital between 1 January 2009 and 31 December 2013. Analyses included simple descriptors, Chi-squared and non-parametric Kruskal-Wallis tests as appropriate. RESULTS: Of the 44,297 patients discharged from our hospital, 1603 died during admission. The general medical, haematology/oncology and intensive care teams provided care for the majority of the patients who died. A small number of diagnoses had in-patient mortality rates of greater than 25%. These included respiratory failure, alcoholic liver disease, vascular disorders of the intestine, sepsis and aspiration pneumonia. Over 75% of patients who received a RRT call survived to hospital discharge; however, patients who received four or more RRT calls during admission had an in-hospital mortality rate of over 40%. CONCLUSION: Acute in-patient mortality is unequally distributed throughout the hospital, and a small number of diagnoses has large associated in-patient mortality rates. Repeated involvement of the RRT is associated with in-patient mortality.