COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2).

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways in Plasmodium vivax Hypnozoites.

Radical cure of Plasmodium vivax malaria must include elimination of quiescent 'hypnozoite' forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets for hypnozoites, we screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library and a collection of epigenetic inhibitors against P. vivax liver stages. From both libraries, we identified inhibitors targeting epigenetics pathways as selectively active against P. vivax and P. cynomolgi hypnozoites. These include DNA methyltransferase (DNMT) inhibitors as well as several inhibitors targeting histone post-translational modifications. Immunofluorescence staining of Plasmodium liver forms showed strong nuclear 5-methylcystosine signal, indicating liver stage parasite DNA is methylated. Using bisulfite sequencing, we mapped genomic DNA methylation in sporozoites, revealing DNA methylation signals in most coding genes. We also demonstrated that methylation level in proximal promoter regions as well as in the first exon of the genes may affect, at least partially, gene expression in P. vivax. The importance of selective inhibitors targeting epigenetic features on hypnozoites was validated using MMV019721, an acetyl-CoA synthetase inhibitor that affects histone acetylation and was previously reported as active against P. falciparum blood stages. In summary, our data indicate that several epigenetic mechanisms are likely modulating hypnozoite formation or persistence and provide an avenue for the discovery and development of improved radical cure antimalarials.

Assessing the use of minimally invasive self-sampling at home for long-term monitoring of the microbiota within UK families.

Monitoring the presence of commensal and pathogenic respiratory microorganisms is of critical global importance. However, community-based surveillance is difficult because nasopharyngeal swabs are uncomfortable and painful for a wide age range of participants. We designed a methodology for minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. Participants were invited to take part in an exit interview. Thirty-three families completed the study. Sampling using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Multi-niche self-sampling at home can be used by adults and children for longitudinal surveillance of respiratory microorganisms, providing key data for design of future studies.

Neuroimaging Features of Biotinidase Deficiency.

Biotinidase deficiency is an autosomal recessive condition caused by pathogenic variants in the BTD gene. Resultant deficiency of free biotin leads to impaired activity of the enzyme carboxylase and related neurologic, dermatologic, and ocular symptoms. Many of these are reversible on treatment, but early recognition and commencement of biotin supplementation are critical. This practice is especially important in countries where routine neonatal screening for biotinidase deficiency is not performed. In this report comprising 14 patients from multiple centers, we demonstrate the MR imaging patterns of this disorder at various age groups. Knowledge of these patterns in the appropriate clinical context will help guide early diagnosis of this treatable metabolic disorder.

Healthcare workers' experiences of caring for patients colonized with carbapenemase-producing Enterobacterales (CPE) in an acute hospital setting - a scoping review.

Carbapenemase-producing Enterobacterales (CPE) is an increasing public health concern; these bacteria are highly transmissible in hospital environments and the number of patients with these multidrug-resistant bacteria is rising. Healthcare workers caring for patients colonized with CPE offer insight into care delivery and processes in the hospital setting. The aim of this review was to explore healthcare workers' experiences of caring for patients colonized with CPE. A scoping review method was employed and seven electronic databases (CINAHL, Academic Search Complete, Cochrane, Embase, Medline, Web of Science and Scopus) and four grey literature databases (Open Grey, Grey Literature Report, Clinical trials. gov and WHO International Clinical Trials Registry Platform) were searched using specific search terms and inclusion/exclusion criteria. A PRISMA flow diagram was used to illustrate the process of article selection and thematic analysis used to form themes. Three studies met the criteria to be included in this review. Two main themes were identified from analysing the articles: 'Safeguarding' and 'Power of Knowledge'. The desire to protect themselves, their families and patients was evident from the studies. Healthcare workers were aware of the importance on infection prevention and control measures such as hand hygiene, in preventing the transmission of CPE, however barriers to these were identified, such as time constraints. In conclusion, healthcare workers have negative associations when it comes to caring for patients with CPE. Very little research has been conducted in the area and there is an opportunity to further explore the experience of healthcare workers caring for patients with CPE to identify opportunities for improvement and support of staff.

Automated detection of enteric tubes misplaced in the respiratory tract on chest radiographs using deep learning with two centre validation.

AIM: To develop and test a model based on a convolutional neural network that can identify enteric tube position accurately on chest radiography. MATERIALS AND METHODS: The chest radiographs of adult patients were classified by radiologists based on enteric tube position as either critically misplaced (within the respiratory tract) or not critically misplaced (misplaced within the oesophagus or safely positioned below the diaphragm). A deep-learning model based on the 121-layer DenseNet architecture was developed using a training and validation set of 4,693 chest radiographs. The model was evaluated on an external test data set from a separate institution that consisted of 1,514 consecutive radiographs with a real-world incidence of critically misplaced enteric tubes. RESULTS: The receiver operator characteristic area under the curve was 0.90 and 0.92 for the internal validation and external test data sets, respectively. For the external data set with a prevalence of 4.4% of critically misplaced enteric tubes, the model achieved high accuracy (92%), sensitivity (80%), and specificity (92%) for identifying a critically misplaced enteric tube. The negative predictive value (99%) was higher than the positive predictive value (32%). CONCLUSION: The present study describes the development and external testing of a model that accurately identifies an enteric tube misplaced within the respiratory tract. This model could help reduce the risk of the catastrophic consequences of feeding through a misplaced enteric tube.

Audit of cancer yields after prostate MRI using both the PI-RADS version 2 and Likert scoring systems.

AIM: To audit diagnostic yields of the updated magnetic resonance imaging (MRI)-directed prostate cancer diagnostic service according to Prostate Imaging - Reporting and Data System (PI-RADS) version 2 and Likert assessments, comparing outcomes of the two scoring systems. MATERIALS AND METHODS: Consecutive men with suspected cancer undergoing prostate MRI were included. Biopsy rates and histological diagnostic yields of all and International Society of Urological Pathology Grade Group (ISUP GG) ≥2 cancers according to PI-RADS and Likert assessment categories were documented and outcomes compared. RESULTS: Of 326 men (91% biopsy naive), 177 (54%) underwent transrectal (n=119) or transperineal (n=58) ultrasound-guided biopsies; 92% with negative MRI avoided immediate biopsies following multidisciplinary team (MDT) review. All cancer and ISUP GG ≥ 2 cancer-detection rates increased with increasing suspicion scores. Prospective paired PI-RADS and Likert scoring was undertaken in 323/326 studies, with 87% concordance rate. High concordance between PI-RADS and Likert scores was observed in negative MRI (99%) and score 5 (96%). High discordance was demonstrated in the PI-RADS 4 group (32% with PI-RADS 4 categories up-risked to Likert 5). All cancer and ISUP GG ≥ 2 cancer detection rates for MRI score ≥3 were 78% and 63%, and for MRI score ≥4 were 75% and 61%, respectively for both PI-RADS and Likert scoring systems. CONCLUSIONS: Most men with negative prostate MRI can avoid immediate biopsies following MDT review. Performance of PI-RADS and Likert scoring systems in clinically significant cancer detection after positive MRI is equivalent. Discordance between PI-RADS and Likert systems seems mostly confined to PI-RADS 4 categories.

Imaging of transcatheter aortic valve replacement complications.

Aortic stenosis is increasing in incidence and is now commonly managed with transcatheter aortic valve replacement (TAVR) in intermediate and high-risk patients. Radiologists are likely to encounter patients undergoing this procedure both pre- and postoperatively, and therefore, an understanding of procedural complications is essential. Complications may relate to the access site or approach, or the valve itself. This article will review the most common complications described in literature and focuses on the role of multidetector computed tomography (CT) in their evaluation either exclusively, or complementary to other imaging methods.

Autoimmune cortical encephalitis in two children with anti-myelin oligodendrocyte glycoprotein (MOG) antibody.

PURPOSE: Anti-myelin oligodendrocyte glycoprotein antibodies (anti-MOG), directed against a component of the myelin sheath, are sometimes detected in the blood or cerebrospinal fluid (CSF) of patients with acute demyelinating conditions. Cortical encephalitic presentations in anti-MOG-antibody-positive patients are recognized but rare, and few pediatric cases have been described. METHODS: We describe clinical, biochemical, and MRI findings in two children presenting with generalized seizures due to cortical encephalitis, and review potential underlying immunological processes. RESULTS: In both patients, anti-MOG antibodies were detected. Both underwent MRI scans which demonstrated bilateral cortical swelling and T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity with corresponding regions of reduced diffusion. CONCLUSION: Early detection of anti-MOG antibodies in patients with a similar presentation and imaging features would enable rapid institution of appropriate treatment, and potentially reduce the need for invasive diagnostic procedures such as brain biopsy.

Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.

BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. CONCLUSIONS: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. CLINICAL TRIALS REGISTRATION: NCT03341767.

Long-term follow-up of a randomized controlled trial of a text-message diabetes self-management support programme, SMS4BG.

AIMS: To determine the long-term effectiveness of an individually tailored text-message diabetes self-management support programme, SMS4BG, on glycaemic control at 2 years in adults with diabetes with an HbA1c concentration > 64 mmol/mol (8%). METHODS: We conducted a 2-year follow-up of a two-arm, parallel, randomized controlled trial across health services in New Zealand. Participants were English-speaking adults with type 1 or 2 diabetes and with an HbA1c >64 mmol/mol (8%). In the main trial participants randomized to the intervention group (N=183) received up to 9 months of an automated tailored text-message programme in addition to usual care. Participants in the control group (N=183) received usual care for 9 months. In this follow-up study, 293 (80%) of 366 randomized participants in the main trial were included. The primary outcome measure was change in glycaemic control (HbA1c ) from baseline to 2 years. Mixed-effect models were used to compare the group differences at 3, 6, 9 and 24 months, adjusted for baseline HbA1c and stratification factors (health district category, diabetes type and ethnicity). RESULTS: The decrease in HbA1c at 2 years was significantly greater in the intervention group [mean (sd) -10 (18) mmol/mol or -0.9 (1.6)%] compared with the control group [mean (sd) -1 (20) mmol/mol or -0.1 (1.8)%], with an adjusted mean difference of -9 mmol/mol (95% CI -14, -5) or -0.8% (95% CI -1.2, -0.4; P<0.0001). CONCLUSIONS: Improvements in glycaemic control resulting from a text-message diabetes self-management support programme were sustained at 2 years after randomization. These findings support the implementation of SMS4BG in current practice.

A Novel Piperazine-Based Drug Lead for Cryptosporidiosis from the Medicines for Malaria Venture Open-Access Malaria Box.

Cryptosporidiosis causes life-threatening diarrhea in children under the age of 5 years and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to the need for new drugs, better knowledge of drug properties that drive in vivo efficacy is needed to facilitate drug development. We report the identification of a piperazine-based lead compound for Cryptosporidium drug development, MMV665917, and a new pharmacodynamic method used for its characterization. The identification of MMV665917 from the Medicines for Malaria Venture Malaria Box was followed by dose-response studies, in vitro toxicity studies, and structure-activity relationship studies using commercial analogues. The potency of this compound against Cryptosporidium parvum Iowa and field isolates was comparable to that against Cryptosporidium hominis Furthermore, unlike nitazoxanide, clofazimine, and paromomycin, MMV665917 appeared to be curative in a NOD SCID gamma mouse model of chronic cryptosporidiosis. MMV665917 was also efficacious in a gamma interferon knockout mouse model of acute cryptosporidiosis. To determine if efficacy in this mouse model of chronic infection might relate to whether compounds are parasiticidal or parasitistatic for C. parvum, we developed a novel in vitro parasite persistence assay. This assay suggested that MMV665917 was parasiticidal, unlike nitazoxanide, clofazimine, and paromomycin. The assay also enabled determination of the concentration of the compound required to maximize the rate of parasite elimination. This time-kill assay can be used to prioritize early-stage Cryptosporidium drug leads and may aid in planning in vivo efficacy experiments. Collectively, these results identify MMV665917 as a promising lead and establish a new method for characterizing potential anticryptosporidial agents.

Age increases MCP-1 level in association with bariatric surgery operating time and metabolic risk severity.

OBJECTIVE: Assess the role of inflammation on operating time in younger vs. older bariatric surgery patients. METHODS: Fifty-five younger (F: 46, Age: 34.9 ± 4.0 years, body mass index [BMI]: 48.2 ± 1.0 kg m-2) and 48 older (F: 34, Age: 57.0 ± 5.1 years, BMI: 46.8 ± 1.0 kg m-2) adults were studied prior to surgery. Blood pressure, glycaemic control (fasting glucose/insulin, HbA1c), lipids (high-density lipoprotein and triglycerides) and inflammation (monocyte chemoattractant protein-1 [MCP-1]) were assessed. Metabolic risk severity z-scores were calculated from clinical outcomes. Omental adipose biopsies were collected at surgery for MCP-1 protein analysis. Operating time was used to characterize surgical difficulty. RESULTS: Older vs. younger adults had higher HbA1c (P = 0.03). There was no difference in BMI, lipids, metabolic risk severity or insulin between groups, but operating time was longer in older vs. younger individuals (P = 0.04). Circulating MCP-1 was also elevated in older vs. younger adults (P = 0.04) independent of HbA1c, although this was not explained by omental fat. Nevertheless, serum MCP-1 was associated with increased metabolic risk severity (R = 0.27, P = 0.01). In addition, operating time was linked to HbA1c (R = 0.30, P = 0.01) and omental MCP-1 protein (R = 0.31, P < 0.01). CONCLUSIONS: MCP-1 is associated with longer operating time and increased metabolic risk severity in older bariatric patients independent of glycaemic control. Pre-operative treatment of inflammation may be required to enhance surgery effectiveness.

Integrating habits and practices data for soaps, cosmetics and air care products into an existing aggregate exposure model.

In order to accurately assess aggregate exposure to a fragrance material in consumers, data are needed on consumer habits and practices, as well as the concentration of the fragrance material in those products. The present study describes the development of Phase 2 Creme RIFM model by expanding the previously developed Phase 1 model to include an additional six product types. Using subject-matching algorithms, the subjects in the Phase 1 Creme RIFM database were paired with subjects in the SUPERB and BodyCare surveys based on age and gender. Consumption of the additional products was simulated to create a seven day diary allowing full data integration in a consistent format. The inhalation route was also included for air care and other products where a fraction of product used is inhaled, derived from the RIFM 2-box model. The expansion of the Phase 1 Creme RIFM model has resulted in a more extensive and refined model, which covers a broader range of product categories and now, includes all relevant routes of exposure. An evaluation of the performance of the model has been carried out in an accompanying publication to this one.

Invasive cervical resorption and the oro-facial cleft patient: a review and case series.

Introduction Invasive cervical resorption (ICR) has an unknown aetiology, yet it exhibits very aggressive behaviour compared with typical external root resorption, posing a high risk of tooth loss.Aim To investigate the number of patients at the Dublin Cleft Prosthodontic Department with an oro-facial cleft who experienced ICR and to identify any possible aetiological factors.Materials and method A retrospective investigation of all oro-facial cleft patients treated at the Dublin Cleft Prosthodontic Department, St James's Hospital, Dublin. All patients' clinical and radiological records were reviewed. Patients where tooth loss became inevitable due to Class 4 ICR were analysed.Results From 588 oro-facial cleft patients, 14 (2.38%) patients with ICR were identified. Of these eight (57%) were female and six (43%) were male. Mean age at diagnosis was 28 years (range = 16-49 years). Cleft type: six (42.1%) unilateral cleft lip and palate, eight (57.9%) bilateral cleft lip and palate. Seventeen ICR affected teeth in total, with eleven (65%) maxillary central incisors, two (12%) maxillary lateral incisors, four (23%) maxillary canines, and one (7%) central, lateral and canine affected. Some, (N = 10, 71.4%) presented with ICR resulting in immediate tooth loss. Other patients (N = 4, 28.6%) developed ICR during or following prosthodontic treatment at the Cleft Centre. Tooth loss for this cohort, though not immediate, was inevitable. All had undergone fixed orthodontic appliance treatment and twelve had received dento-alveolar bone grafts. A number (N = 7, 50%) had undergone osteotomy, two (14%) had received night guard vital dental whitening and one had a history of trauma.Conclusions ICR, given its aggressive nature and ill-understood aetiology, poses significant treatment challenges. The most severe form of ICR (Class 4) leads inevitably to tooth loss. The slow-moderate progression of ICR may explain the late presentation found in this study, reinforcing the importance of long-term follow-up of this special dental care group.

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 2-Surveillance for Treatment Complications and Disease Progression.

An understanding of the new generation of MS drugs in conjunction with the key role MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse effects is of vital importance to the neuroradiologist. Part 1 of this review outlined the current treatment options available for MS and examined the mechanisms of action of the various medications. It also covered specific complications associated with each form of therapy. Part 2, in turn deals with the subject of pharmacovigilance and the optimal frequency of MRI monitoring for each individual patient, depending on his or her unique risk profile. Special attention is given to the diagnosing of progressive multifocal leukoencephalopathy in patients treated with natalizumab as this is a key area in which neuroradiologists can contribute to improved patient outcomes. This article also outlines the aims of treatment and reviews the possibility of "no evidence of disease activity" becoming a treatment goal with the availability of more effective therapies. Potential future areas and technologies including image subtraction, brain volume measurement and advanced imaging techniques such as double inversion recovery are also reviewed. It is anticipated that such advancements in this rapidly developing field will improve the accuracy of monitoring an individual patient's response to treatment.

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 1-Mechanisms, Efficacy, and Safety.

Imaging for the diagnosis and follow-up of patients with suspected or confirmed multiple sclerosis is a common scenario for many general radiologists and subspecialty neuroradiologists. The field of MS therapeutics has rapidly evolved with multiple new agents now being used in routine clinical practice. To provide an informed opinion in discussions concerning newer MS agents, radiologists must have a working understanding of the strengths and limitations of the various novel therapies. The role of imaging in MS has advanced beyond monitoring and surveillance of disease activity to include treatment complications. An understanding of the new generation of MS drugs in conjunction with the key role that MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse events is of vital importance to the radiologist and clinical physician alike. Radiologists are in a unique position to detect many of the described complications well in advance of clinical symptoms. Part 1 of this review outlines recent developments in the treatment of MS and discusses the published clinical data on the efficacy and safety of the currently approved and emerging therapies in this condition as they apply to the radiologist. Part 2 will cover pharmacovigilance and the role the neuroradiologist plays in monitoring patients for signs of opportunistic infection and/or disease progression.

Application of the expanded Creme RIFM consumer exposure model to fragrance ingredients in cosmetic, personal care and air care products.

As part of a joint project between the Research Institute for Fragrance Materials (RIFM) and Creme Global, a Monte Carlo model (here named the Creme RIFM model) has been developed to estimate consumer exposure to ingredients in personal care products. Details of the model produced in Phase 1 of the project have already been published. Further data on habits and practises have been collected which enable the model to estimate consumer exposure from dermal, oral and inhalation routes for 25 product types. . In addition, more accurate concentration data have been obtained which allow levels of fragrance ingredients in these product types to be modelled. Described is the use of this expanded model to estimate aggregate systemic exposure for eight fragrance ingredients. Results are shown for simulated systemic exposure (expressed as µg/kg bw/day) for each fragrance ingredient in each product type, along with simulated aggregate exposure. Highest fragrance exposure generally occurred from use of body lotions, body sprays and hydroalcoholic products. For the fragrances investigated, aggregate exposure calculated using this model was 11.5-25 fold lower than that calculated using deterministic methodology. The Creme RIFM model offers a very comprehensive and powerful tool for estimating aggregate exposure to fragrance ingredients.

Left cardiac sympathetic denervation: case series and technical report.

BACKGROUND: Left cardiac sympathetic denervation (LCSD) is a surgical procedure that has been shown to have an antiarrhythmic and antifibrillatory effect. Evidence indicating its antiarrhythmic effect has been available for over 100 years. It involves the removal of the lower half of the stellate ganglion and T2-T4 of the sympathetic ganglia and is carried out as either a unilateral or bilateral procedure. With advancements in thoracic surgery, it can be safely performed via a minimally invasive Video-Assisted Thoracoscopic Surgery (VATS) approach resulting in significantly less morbidity and a shortened inpatient stay. LCSD provides a valuable treatment option for patients with life-threatening channelopathies and cardiomyopathies. AIMS AND METHODS: This case series reports the preliminary paediatric and adult experience in the Republic of Ireland with LCSD and describes five cases recently treated in addition to an outline of the operative procedure employed. Of the five cases included, two were paediatric cases and three were adult cases. RESULTS: One of the paediatric patients had a diagnosis of the rare catecholaminergic polymorphic ventricular tachycardia (CPVT) and the other a diagnosis of long-QT syndrome. Both paediatric patients experienced excellent outcomes. Of the three adult patients, two benefitted greatly and remain well at follow-up (one inappropriate sinus tachycardia and one CPVT). One patient with idiopathic ventricular fibrillation unfortunately passed away from intractable VF despite all attempts at resuscitation. CONCLUSION: In this case series, we highlight that LCSD provides a critical adjunct to existing medical therapies and should be considered for all patients with life-threatening refractory arrhythmias especially those patients on maximal medical therapy.