The Rate of Re-treatment in Patients Treated with Teprotumumab: A Multicenter Study of 119 Patients with 1 Year of Follow-up.

PURPOSE: To determine the rate of re-treatment in patients who receive a full course of teprotumumab therapy for thyroid eye disease (TED) and drivers of re-treatment. DESIGN: Multicenter retrospective study. PARTICIPANTS: All patients who received a full course of treatment and had available data at 1 year after initial treatment were included. METHODS: Charts were reviewed for the following information: age, sex, months since diagnosis of TED, smoking status, and prior treatments. Further, the clinical activity score (CAS), proptosis, and the Gorman diplopia score were reviewed at baseline, at the end of the first course, and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of re-treatment. MAIN OUTCOME MEASURES: Rate of re-treatment and the drivers of re-treatment. RESULTS: One hundred nineteen patients were included from 3 centers across the United States. The overall re-treatment rate was 24% (29/119). No difference was found among the 3 sites (P = 0.6). In univariable analyses, at baseline, no difference was found in proptosis (P = 0.07), diplopia score (P = 0.4), or duration of TED (P = 0.4) between patients who were re-treated and those not re-treated. From the re-treated group, 82% showed a significant proptosis response (≥ 2-mm reduction from baseline) after the initial course, whereas 68% of patients who were not re-treated showed a clinically significant proptosis response (P = 0.16). The mean ± standard deviation difference between the end of the first treatment and at baseline before the second treatment (in those who received it) was 2 ± 2 for CAS, 2 ± 4 mm for proptosis, and 1 ± 1 for diplopia score. Age was the only significant driver of re-treatment (P < 0.05). Re-treated patients were 7 years older than patients who were not re-treated (60 years vs. 53 years; P < 0.05). CONCLUSIONS: In patients receiving a full course of teprotumumab therapy, the rate of re-treatment was 24%. Age was the only driver of re-treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Support Provided by Stop-Smoking Practitioners to Co-users of Tobacco and Cannabis: A Qualitative Study.

INTRODUCTION: Co-use of tobacco and cannabis is highly prevalent among cannabis users and is associated with poorer tobacco cessation outcomes. This study explored the barriers and enablers influencing stop-smoking practitioners' ability to provide optimal support to co-users. AIMS AND METHODS: Online semi-structured interviews were audio recorded. Interviewees (n = 20) were UK-based certified stop-smoking practitioners. An interview schedule informed by the "capability", "opportunity", "motivation" (COM-B) model was designed to explore participants' perceived barriers and enablers in better supporting co-users to achieve abstinence of both substances or tobacco harm reduction. The transcripts were analyzed using framework analysis. RESULTS: Capability: Practitioners' lack of knowledge and skills undermines their delivery of smoking cessation interventions to co-users. Interestingly, when cannabis is used for medicinal reasons, practitioners feel unable to provide adequate support. Opportunity: Service recording systems play an important role in screening for co-use and supporting co-users. When responding to clients' specific needs and practitioners' uncertainties, a positive therapeutic relationship and a support network of peers and other healthcare professionals are needed. Motivation: supporting co-users is generally perceived as part of practitioners' roles but there are concerns that co-users are less likely to successfully stop smoking. CONCLUSIONS: Practitioners are willing to support co-users, but their lack of knowledge and access to an appropriate recording system are barriers to doing so. Having a supportive team and a positive therapeutic relationship is perceived as important. Identified barriers can be mostly addressed with further training to improve tobacco cessation outcomes for co-users.

A Novel Deep Learning Algorithm for Human Papillomavirus Infection Prediction in Head and Neck Cancers Using Routine Histology Images.

The etiology of head and neck squamous cell carcinoma (HNSCC) involves multiple carcinogens, such as alcohol, tobacco, and infection with human papillomavirus (HPV). Because HPV infection influences the prognosis, treatment, and survival of patients with HNSCC, it is important to determine the HPV status of these tumors. In this article, we propose a novel deep learning pipeline for HPV infection status prediction with state-of-the-art performance in HPV detection using only whole-slide images of routine hematoxylin and eosin-stained HNSCC sections. We show that our Digital-HPV score generated from hematoxylin and eosin slides produces statistically significant patient stratifications in terms of overall and disease-specific survival. In addition, quantitative profiling of the spatial tumor microenvironment and analysis of the immune profiles show relatively high levels of lymphocytic infiltration in tumor and tumor-associated stroma. High levels of B cells and T cells and low macrophage levels were also identified in HPV-positive patients compared to HPV-negative patients, confirming different immune response patterns elicited by HPV infection in patients with HNSCC.

Photoreceptive Ganglion Cells Drive Circuits for Local Inhibition in the Mouse Retina.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) exhibit melanopsin-dependent light responses that persist in the absence of rod and cone photoreceptor-mediated input. In addition to signaling anterogradely to the brain, ipRGCs signal retrogradely to intraretinal circuitry via gap junction-mediated electrical synapses with amacrine cells (ACs). However, the targets and functions of these intraretinal signals remain largely unknown. Here, in mice of both sexes, we identify circuitry that enables M5 ipRGCs to locally inhibit retinal neurons via electrical synapses with a nonspiking GABAergic AC. During pharmacological blockade of rod- and cone-mediated input, whole-cell recordings of corticotropin-releasing hormone-expressing (CRH+) ACs reveal persistent visual responses that require both melanopsin expression and gap junctions. In the developing retina, ipRGC-mediated input to CRH+ ACs is weak or absent before eye opening, indicating a primary role for this input in the mature retina (i.e., in parallel with rod- and cone-mediated input). Among several ipRGC types, only M5 ipRGCs exhibit consistent anatomical and physiological coupling to CRH+ ACs. Optogenetic stimulation of local CRH+ ACs directly drives IPSCs in M4 and M5, but not M1-M3, ipRGCs. CRH+ ACs also inhibit M2 ipRGC-coupled spiking ACs, demonstrating direct interaction between discrete networks of ipRGC-coupled interneurons. Together, these results demonstrate a functional role for electrical synapses in translating ipRGC activity into feedforward and feedback inhibition of local retinal circuits.SIGNIFICANCE STATEMENT Melanopsin directly generates light responses in intrinsically photosensitive retinal ganglion cells (ipRGCs). Through gap junction-mediated electrical synapses with retinal interneurons, these uniquely photoreceptive RGCs may also influence the activity and output of neuronal circuits within the retina. Here, we identified and studied an electrical synaptic circuit that, in principle, could couple ipRGC activity to the chemical output of an identified retinal interneuron. Specifically, we found that M5 ipRGCs form electrical synapses with corticotropin-releasing hormone-expressing amacrine cells, which locally release GABA to inhibit specific RGC types. Thus, ipRGCs are poised to influence the output of diverse retinal circuits via electrical synapses with interneurons.

Evaluation of saliva self-collection devices for SARS-CoV-2 diagnostics.

BACKGROUND: There is an urgent need to expand testing for SARS-CoV-2 and other respiratory pathogens as the global community struggles to control the COVID-19 pandemic. Current diagnostic methods can be affected by supply chain bottlenecks and require the assistance of medical professionals, impeding the implementation of large-scale testing. Self-collection of saliva may solve these problems, as it can be completed without specialized training and uses generic materials. METHODS: We observed 30 individuals who self-collected saliva using four different collection devices and analyzed their feedback. Two of these devices, a funnel and bulb pipette, were used to evaluate at-home saliva collection by 60 individuals. SARS-CoV-2-spiked saliva samples were subjected to temperature cycles designed to simulate the conditions the samples might be exposed to during the summer and winter seasons and sensitivity of detection was evaluated. RESULTS: All devices enabled the safe, unsupervised self-collection of saliva. The quantity and quality of the samples received were acceptable for SARS-CoV-2 diagnostic testing, as determined by human RNase P detection. There was no significant difference in SARS-CoV-2 nucleocapsid gene (N1) detection between the freshly spiked samples and those incubated with the summer and winter profiles. CONCLUSION: We demonstrate inexpensive, generic, buffer free collection devices suitable for unsupervised and home saliva self-collection.

Access to Pediatric Eye Care by Practitioner Type, Geographic Distribution, and US Population Demographics.

Importance: Investigating disparities in service coverage of pediatric optometrists and pediatric ophthalmologists in relation to patient demographics will illuminate vulnerable populations and inform future interventions. Objective: To characterize the geographic distribution of pediatric eye care practitioners and analyze its association with population demographics. Design, Setting, and Participants: In this cross-sectional study, 4 public databases were used to identify the addresses of pediatric optometrists and pediatric ophthalmologists in the US in April 2023. Addresses were geocoded, and population demographic data were collected. Pediatric optometrists and pediatric ophthalmologists listed in the public databases, as well as respondents to the 2020 US census, were included in this study. Data were analyzed from April to July 2023. Exposures: Public databases and US census data of eye practitioners and their practice locations. Main Outcomes and Measures: Geographic distribution of pediatric optometrists and pediatric ophthalmologists as listed in public databases and correlations between service coverage and US population demographics. Results: A total of 586 pediatric optometrists (302 female [51.5%]) and 1060 pediatric ophthalmologists (590 male [55.7%]) were identified. Among US counties, 203 (6.5%) had at least 1 pediatric optometrist, and 308 (9.7%) had at least 1 pediatric ophthalmologist, showing substantial geographic overlap (odds ratio, 12.7; 95% CI, 9.4-17.4; P < .001). In the 2834 counties without pediatric ophthalmologists, 2731 (96.4%) lacked pediatric optometrists. There were more pediatric ophthalmologists per million people (3.3) compared with pediatric optometrists per million people (2.5) across all states (difference, 0.8; 95% CI, 0-1.9; P = .047). Among counties with practitioners, the median (IQR) number of pediatric optometrists per million people was 7.8 (0.4-245.0), surpassing the median (IQR) number of pediatric ophthalmologists per million people, 5.5 (1.0-117.0). Counties with pediatric ophthalmologists had higher mean (SD) household incomes than counties with pediatric optometrists ($76 126.87 [$21 879.23] vs $68 681.77 [$18 336.40]; difference, -$7445.10; 95% CI, $2519.51-$12 370.69; P = .003) and higher mean (SD) population with bachelor's degrees than counties with pediatric optometrists (79 016 [82 503] vs 23 076 [44 025]; difference, -55 940; 95% CI, -73 035 to -38 845; P < .001), whereas counties with neither specialist type had the lowest mean (SD) household income ($57 714.03 [$2731.00] vs $78 388.67 [$18 499.21]; difference, -$20 675.00; 95% CI, -$21 550.90 to -$19 799.10; P < .001) and mean (SD) population with bachelor's degrees (5113 [12 875] vs 167 015 [216 486]; difference, -161 902; 95% CI, -170 388.9 to -153 415.1; P < .001) compared with counties with practitioners. Conclusions and Relevance: Geographic disparities in pediatric eye care access, compounded by socioeconomic differences, underscore the urgency of augmenting practitioner support in underserved areas.

Demystifying oral epithelial dysplasia: a histological guide.

Oral epithelial dysplasia is a histologically diagnosed potentially premalignant disorder of the oral mucosa, which carries a risk of malignant transformation to squamous cell carcinoma. The diagnosis and grading of oral epithelial dysplasia is challenging, with cases often referred to specialist oral and maxillofacial pathology centres for second opinion. Even still there is poor inter-examiner and intra-examiner agreement in a diagnosis. There are a total of 28 features of oral epithelial dysplasia listed in the 5th edition of World Health Organization classification of tumours of the head and neck. Each of these features is poorly defined and subjective in its interpretation. Moreover, how these features contribute to dysplasia grading and risk stratification is even less well defined. This article discusses each of the features of oral epithelial dysplasia with examples and provides an overview of the common mimics, including the normal histological features of the oral mucosa which may mimic atypia. This article also highlights the paucity of evidence defining these features while offering suggested definitions. Ideally, these definitions will be refined, and the most important features identified to simplify the diagnosis of oral epithelial dysplasia. Digital whole slide images of the figures in this paper can be found at: https://www.pathogenesis.co.uk/r/demystifying-dysplasia-histology-dataset.

Geographic disparities and surgical trends of strabismus surgery among Medicare beneficiaries (2016-2021).

This study highlights the disparity between the prevalence of adult strabismus in the United States and the limited number of surgeons performing adult strabismus surgery on Medicare beneficiaries. Only 12.2% of pediatric ophthalmologists billed Medicare for adult strabismus procedures during the study period. Additionally, geographic disparities of surgeons performing adult strabismus surgery were evident, with drastically different surgeon-to-patient ratios by state. Overall, the study raises concerns about the adequacy of the surgeon supply to meet the demand for adult strabismus cases.

The Value of Labial Gland Biopsies as a Diagnostic Test for Sjögren's Syndrome.

PURPOSE: There are a number of diagnostic criteria that can be used to support a diagnosis of Sjögren's syndrome (SS), a chronic autoimmune condition often characterised by xerostomia and xerophthalmia. Of the available investigations, the most invasive is the labial gland biopsy (LGB) for histopathology, which is associated with a risk of long-term altered sensation to the lip. A positive histological diagnosis is currently considered to be one of the most objective criteria, however there is debate about the interobserver agreement between pathologists, as well as the sensitivity and specificity of this test. We aim to determine if the diagnostic value of the LGB is significant enough to warrant the surgical procedure and its associated risks. METHODS: This study involved assessing the degree of agreement between members of a pathology team for a cohort of 50 LGBs taken for the purpose of confirming or excluding SS. The Tarpley system was used, which involves the allocation of a 'focus score'. Additionally, the histological diagnoses were compared to the relevant serological findings where available. RESULTS: All cases within the cohort had adequate tissue for assessment. 84% agreement (Cohen's Kappa = 0.585) was seen between the current team's consensus and the original reporting pathologist on whether the appearance was supportive of SS. However, only 58% agreement was seen for focus scores (Weighted Kappa = 0.496). The agreement between the serology result and whether the histology was supportive of SS was 79% (Cohen's Kappa = 0.493). CONCLUSION: The findings raise the possibility that undue emphasis is placed on the value of a histological SS diagnosis. The current system for assessing and grading these biopsies is ambiguous in nature, with a low threshold considered indicative of SS. Due to the risk of complications associated with a LGB, alternative minimally invasive investigations should always be considered. The histological findings in isolation, particularly when a low focus score is seen, may not be predictive of a diagnosis of SS.

Burn-Induced Cicatricial Eyelid Retraction: A Challenging Case and Review of Management Principles.

Thermal and chemical burns can result in cicatricial eyelid retraction, characterized by an abnormal resting position of the eyelid margin and increased palpebral fissure height. Eyelid retraction often leads to exposure keratopathy, which can cause complications ranging from mild dry eye to globe-threatening ulceration and perforation. Prompt intervention includes aggressive lubrication, moisture chambers, eyelid tarsorrhaphy, and retraction repair surgery. Discussed here is a burn patient that developed severe cicatricial eyelid retraction and ectropion, leading to severe exposure keratopathy and infectious corneal ulceration with perforation. The patient required aggressive medical intervention, as well as 2 surgeries to restore the normal eyelid anatomy to protect the globe.

Neurosyphilis is characterized by a compartmentalized and robust neuroimmune response but not by neuronal injury.

BACKGROUND: Neurosyphilis is increasing in prevalence but its pathophysiology remains incompletely understood. This study assessed for CNS-specific immune responses during neurosyphilis compared to syphilis without neurosyphilis and compared these immune profiles to those observed in other neuroinflammatory diseases. METHODS: Participants with syphilis were categorized as having neurosyphilis if their cerebrospinal fluid (CSF)-venereal disease research laboratory (VDRL) test was reactive and as having syphilis without neurosyphilis if they had a non-reactive CSF-VDRL test and a white blood cell count <5/µL. Neurosyphilis and syphilis without neurosyphilis participants were matched by rapid plasma reagin titer and HIV status. CSF and plasma were assayed for markers of neuronal injury and glial and immune cell activation. Bulk RNA sequencing was performed on CSF cells, with results stratified by the presence of neurological symptoms. FINDINGS: CSF neopterin and five CSF chemokines had levels significantly higher in individuals with neurosyphilis compared to those with syphilis without neurosyphilis, but no markers of neuronal injury or astrocyte activation were significantly elevated. The CSF transcriptome in neurosyphilis was characterized by genes involved in microglial activation and lipid metabolism and did not differ in asymptomatic versus symptomatic neurosyphilis cases. CONCLUSIONS: The CNS immune response observed in neurosyphilis was comparable to other neuroinflammatory diseases and was present in individuals with neurosyphilis regardless of neurological symptoms, yet there was minimal evidence for neuronal or astrocyte injury. These findings support the need for larger studies of the CSF inflammatory response in asymptomatic neurosyphilis. FUNDING: This work was funded by the National Institutes of Health, grants K23MH118999 (S.F.F.) and R01NS082120 (C.M.M.).

A Fibroblastic Reticular Cell Tumour Arising in the Oral Cavity: A Case Report and Review of the Literature.

BACKGROUND: Tumours of dendritic or histiocytic lineage are amongst the rarest tumours and probably account for < 1% of tumours affecting the lymph nodes or soft tissue. Because several of these entities were poorly recognised until recently, the true incidence is not determined. METHODS: We present what we believe is the first reported case report of a fibroblastic reticular cell tumour arising in the oral cavity as well as reviewing the current literature regarding this rare subset of tumours. RESULTS: We discuss the clinical and histopathological findings of our reported case and examine the literature regarding this entity. We discuss the key differential diagnoses to consider when making this diagnosis. CONCLUSION: Histiocytic and dendritic cell derived tumours are exceptionally rare within the head and neck region although a number of these tumours have been reported within the oral cavity. We present what we believe is the first reported case of a fibroblastic reticular cell tumour arising within the oral cavity.

Access to Pediatric Ophthalmological Care by Geographic Distribution and US Population Demographic Characteristics in 2022.

Importance: The geographic distribution of pediatric ophthalmological care has not been reported on since 2007; understanding this distribution could shed light on potential avenues to increase access, which is a necessary first step in addressing the pediatric ophthalmological needs of underserved areas. Objective: To analyze the number and location (ie, geographic distribution) of pediatric ophthalmologists in relation to US population demographic characteristics. Design, Setting, and Participants: In this cross-sectional study, public databases from the American Academy of Ophthalmology and American Association for Pediatric Ophthalmology and Strabismus were used to identify pediatric ophthalmologists in the US as of March 2022. Main Outcomes and Measures: Geographic distribution of pediatric ophthalmologists listed in public databases and any association between pediatric ophthalmologist distribution and US population demographic characteristics. Addresses were geocoded using ArcGIS Pro (Esri). Results: A total of 1056 pediatric ophthalmologists (611 men [57.9%]) were identified. States with the most pediatric ophthalmologists were California (n = 116 [11.0%]), New York (n = 97 [9.2%]), Florida (n = 69 [6.5%]), and Texas (n = 62 [5.9%]), the 4 most populous states. A total of 2828 of 3142 counties (90.0%) and 4 of 50 states (8.0%) had 0 pediatric ophthalmologists. In 314 counties (10.0%) with 1 or more pediatric ophthalmologists, the mean (range) pediatric ophthalmologists per million persons was 7.7 (0.4-185.5). The range of practitioner to million persons has increased since 2007. Counties with 1 or more pediatric ophthalmologists had a higher median (SD) household income compared with counties with 0 pediatric ophthalmologists ($70 230.59 [$18 945.05] vs $53 263.62 [$12 786.07]; difference, -$16 966.97; 95% CI, -$18 544.57 to -$14 389.37; P < .001). Additionally, the proportion of families in each county without internet service (8.0% vs 4.7%; difference, 3.4%; 95% CI, 3.0%-3.7%; P < .001), the proportion of persons younger than 19 years without health insurance (5.7% vs 4.1%; difference, 1.6%; 95% CI, 1.1%-2.2%; P < .001), and the proportion of households without vehicle access (2.1% vs 1.8%; difference, 0.3%; 95% CI, 0.6%-5.2%; P = .001) were greater in counties with 0 compared with counties with 1 or more pediatric ophthalmologists. Conclusion and Relevance: This cross-sectional study found that disparities in access to pediatric ophthalmological care have increased over the past 15 years and are associated with lower socioeconomic status. As patients may rely on online sources to identify the nearest pediatric ophthalmologist, accurate publicly available databases are important.

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART.

People with HIV (PWH) on antiretroviral therapy (ART) experience elevated rates of neurological impairment, despite controlling for demographic factors and comorbidities, suggesting viral or neuroimmune etiologies for these deficits. Here, we apply multimodal and cross-compartmental single-cell analyses of paired cerebrospinal fluid (CSF) and peripheral blood in PWH and uninfected controls. We demonstrate that a subset of central memory CD4+ T cells in the CSF produced HIV-1 RNA, despite apparent systemic viral suppression, and that HIV-1-infected cells were more frequently found in the CSF than in the blood. Using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we show that the cell surface marker CD204 is a reliable marker for rare microglia-like cells in the CSF, which have been implicated in HIV neuropathogenesis, but which we did not find to contain HIV transcripts. Through a feature selection method for supervised deep learning of single-cell transcriptomes, we find that abnormal CD8+ T cell activation, rather than CD4+ T cell abnormalities, predominated in the CSF of PWH compared with controls. Overall, these findings suggest ongoing CNS viral persistence and compartmentalized CNS neuroimmune effects of HIV infection during ART and demonstrate the power of single-cell studies of CSF to better understand the CNS reservoir during HIV infection.

Congenital Cytomegalovirus and Human Immunodeficiency Virus: Effects on Hearing, Speech and Language Development, and Clinical Outcomes in Children.

Prenatal infections can have adverse effects on an infant's hearing, speech, and language development. Congenital cytomegalovirus (CMV) and human immunodeficiency virus (HIV) are two such infections that may lead to these complications, especially when left untreated. CMV is commonly associated with sensorineural hearing loss in children, and it can also be associated with anatomical abnormalities in the central nervous system responsible for speech, language, and intellectual acquisition. In terms of speech, language, and hearing, HIV is most associated with conductive and/or sensorineural hearing loss and expressive language deficits. Children born with these infections may benefit from cochlear implantation for severe to profound sensorineural hearing losses and/or speech therapy for speech/language deficits. CMV and HIV simultaneously present in infants has not been thoroughly studied, but one may hypothesize these speech, language, and hearing deficits to be present with potentially higher severity. Early identification of the infection in combination with early intervention strategies yields better results for these children than no identification or intervention. The purpose of this review was to investigate how congenital CMV and/or HIV may affect hearing, speech, and language development in children, and the importance of early identification for these populations.

Cannabis use and co-use in tobacco smokers and non-smokers: prevalence and associations with mental health in a cross-sectional, nationally representative sample of adults in Great Britain, 2020.

BACKGROUND AND AIMS: In Great Britain, cannabis and tobacco are commonly used substances, both independently and together. Use of either substance is associated with mental health problems, but prevalence of co-use within these populations is unknown. We aimed to (1) estimate prevalence of cannabis use, frequency of use and routes of administration (ROA) among tobacco smokers and non-smokers and (2) investigate mental health problems among non-users, tobacco-only, cannabis-only and co-users of both substances. DESIGN: Cross-sectional national on-line survey (Action on Smoking and Health) fielded in February-March 2020. SETTING: Great Britain. PARTICIPANTS: Adults in Great Britain aged ≥ 18 years (n = 12 809) MEASUREMENTS: Tobacco use status [smoker (daily or non-daily) or non-smoker (never or ex-smoker)], cannabis use frequency (never to daily), detailed ROAs of cannabis, self-reported treatment for mental health disorders (depression, anxiety and any). Statistically weighted prevalence estimates were computed to ensure representativeness. Correlates were assessed using χ2 tests and logistic regression. FINDINGS: In Great Britain in 2020, 7.1% of the sample had used cannabis in the past year. Tobacco smokers had greater odds of using cannabis in the past year (21.9%) and using cannabis daily (8.7%) than non-smokers [past-year: 4.7%; adjusted odds ratio (aOR) = 10.07, 95% confidence interval (CI) = 8.4-12.0; daily: 0.7%; aOR = 24.6, 95% CI = 18.0-33.6)]. Co-administration with tobacco was common (46.2% of non-smokers, 80.8% of tobacco smokers). Co-users reported the highest prevalence of any treatment for mental health problems (54.2%) in comparison to cannabis-only (45.8%), tobacco-only (33.2%) and non-users (22.7%; all P ≤ 0.05). CONCLUSION: Approximately one in 13 adults in Great Britain reports having used cannabis in the past year, approximately four times as many among cigarette smokers as non-smokers. Co-administration of cannabis and tobacco, via smoking, appears to be common, including among self-identified non-smokers. Mental health problems appear to be particularly common among dual users.

Hypothermia induced by therapeutic doses of antipyretics: misdiagnosis of cold sepsis.

Fever is a natural and almost universal mammalian response to infection. There exists a fear amongst general public and healthcare providers regarding fever being harmful leading to its overzealous management with antipyretics. Although the National Institute for Health and Care Excellence (NICE) guidelines suggest the use of single antipyretic agent for management of fever, combination therapy with paracetamol, and ibuprofen is common in paediatric practice in the United Kingdom. These antipyretics at times can cause significant adverse events even when administered at regular therapeutic doses. We describe a young boy who presented with significant hypothermia (34.1°C) and was initially treated as cold sepsis. Once the boy got warmed up and as blood results became subsequently available, it became clearer that the hypothermia was secondary to therapeutic doses of antipyretics. In conclusion, we hope to improve awareness regarding this condition in clinical practice and educate health care professionals and caregivers with recommended NICE guidelines.