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Summary: Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

Background: The current cervical cancer screening and diagnosis have limitations due to their subjectivity and lack of reproducibility. We describe the development of a deep learning (DL)-based diagnostic risk prediction model and evaluate its potential for clinical impact., Method: We developed and internally validated a DL model which accommodates both clinical data and colposcopy images in predicting the patients CIN2+ status using a retrospective cohort of 6356 cases of LEEP-conization/cone-biopsy (gold-standard diagnosis) following an abnormal screening result. The overall performance, discrimination, and calibration of the model were compared to expert clinician's colposcopic impression. The potential for clinical impact was assessed with rate of unnecessary conizations that could be avoided by using our model., Results: The model combining clinical history and colposcopy images demonstrated superior performance prediction of CIN2+(AUC-ROC = 95.3 %, accuracy = 90.8 %, PPV = 94.1 %, NPV = 87.9 %) and better calibration compared to models that used image or clinical history data alone and outperformed clinician's colposcopic impressions. Moreover, if a decision threshold of 10 % is applied to the predicted probability from this model to recommend conization, up to 35 % of conizations could be avoided without missing any true CIN2+ cases., Conclusion: We present a novel DL model to predict cervical neoplasia with potential for reducing unnecessary conization. External validation studies are warranted for assessing generalizability., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Early life factors for inflammatory bowel disease are likely to impact the gut microbiota., Aim: We investigated the associations between early exposures and inflammatory bowel disease., Methods: This case-control study was nested within the CO·MMUNITY cohort. Cases of Crohn's disease (CD) and ulcerative colitis (UC) were identified using validated algorithms. All cases and randomly selected controls were invited to complete a questionnaire including early life exposures. Analyses were conducted by logistic regression and causal mediation (direct/indirect effects for passive/active smoking)., Results: Early introduction of solid foods at 3-6 months tended to increase CD risk compared to later introduction (>6 months): OR = 1.23; 95 % CI: 0.96-1.56, but not of UC. Exclusive breastfeeding tended to decrease the risk of CD (OR = 0.77; 95 % CI: 0.55-1.08), less so for UC. Antibiotics tended to decrease CD (OR = 0.89; 95 % CI: 0.74-1.07) and UC (OR = 0.88; 95 % CI: 0.71-1.09). No association was found between pets and CD or UC. Passive smoking increased CD risk (OR = 1.23; 95 % CI: 1.00-1.51), 20 % of which was mediated by active smoking, but not UC., Conclusion: Differences were noticed in early risk factors for CD and UC. The impact of passive smoking was largely independent of active smoking, highlighting its importance for prevention., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Accurate diagnosis of oral lesions, early indicators of oral cancer, is a complex clinical challenge. Recent advances in deep learning have demonstrated potential in supporting clinical decisions. This paper introduces a deep learning model for classifying oral lesions, focusing on accuracy, interpretability, and reducing dataset bias. The model integrates three components: (i) a Classification Stream, utilizing a CNN to categorize images into 16 lesion types (baseline model), (ii) a Guidance Stream, which aligns class activation maps with clinically relevant areas using ground truth segmentation masks (GAIN model), and (iii) an Anatomical Site Prediction Stream, improving interpretability by predicting lesion location (GAIN+ASP model). The development dataset comprised 2765 intra-oral digital images of 16 lesion types from 1079 patients seen at an oral pathology clinic between 1999 and 2021. The GAIN model demonstrated a 7.2% relative improvement in accuracy over the baseline for 16-class classification, with superior class-specific balanced accuracy and AUC scores. Additionally, the GAIN model enhanced lesion localization and improved the alignment between attention maps and ground truth. The proposed models also exhibited greater robustness against dataset bias, as shown in ablation studies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Knowledge Transfer Statement: The topic discussed in this commentary could serve as an initial inquiry point that deeply probes into the trustworthiness of an AI solution that a user might consider applying in the field of dentistry., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Recent studies have identified significant gaps in equity, diversity, and inclusion (EDI) considerations within the lifecycle of artificial intelligence (AI), spanning from data collection and problem definition to implementation stages. Despite the recognized need for integrating EDI principles, there is currently no existing guideline or framework to support this integration in the AI lifecycle., Objective: This study aimed to address this gap by identifying EDI principles and indicators to be integrated into the AI lifecycle. The goal was to develop a comprehensive guiding framework to guide the development and implementation of future AI systems., Methods: This study was conducted in 3 phases. In phase 1, a comprehensive systematic scoping review explored how EDI principles have been integrated into AI in health and oral health care settings. In phase 2, a multidisciplinary team was established, and two 2-day, in-person international workshops with over 60 representatives from diverse backgrounds, expertise, and communities were conducted. The workshops included plenary presentations, round table discussions, and focused group discussions. In phase 3, based on the workshops' insights, the EDAI framework was developed and refined through iterative feedback from participants. The results of the initial systematic scoping review have been published separately, and this paper focuses on subsequent phases of the project, which is related to framework development., Results: In this study, we developed the EDAI framework, a comprehensive guideline that integrates EDI principles and indicators throughout the entire AI lifecycle. This framework addresses existing gaps at various stages, from data collection to implementation, and focuses on individual, organizational, and systemic levels. Additionally, we identified both the facilitators and barriers to integrating EDI within the AI lifecycle in health and oral health care., Conclusions: The developed EDAI framework provides a comprehensive, actionable guideline for integrating EDI principles into AI development and deployment. By facilitating the systematic incorporation of these principles, the framework supports the creation and implementation of AI systems that are not only technologically advanced but also sensitive to EDI principles., (©Samira Abbasgholizadeh Rahimi, Richa Shrivastava, Anita Brown-Johnson, Pascale Caidor, Claire Davies, Amal Idrissi Janati, Pascaline Kengne Talla, Sreenath Madathil, Bettina M Willie, Elham Emami. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.11.2024.)

Excess body fatness in late adulthood has been observed to increase ovarian cancer risk, but the association is relatively weak. Body fatness can change over time, and timing may differently influence risk. We used a life course epidemiology approach to identify whether the relation between body fatness and ovarian cancer risk is best described by a critical period, accumulation or sensitive period hypothesis. In a population-based case-control study of ovarian cancer in Montreal, Canada (2011-16), data on body mass index (BMI) at each decade starting at age 20 was available. Among 363 cases and 707 controls aged ≥ 50 years, we used a Bayesian relevant life course exposure model to estimate the relative importance of BMI for three pre-specified periods across the adult life course, i.e., early childbearing years, late childbearing years, and peri/postmenopause, on ovarian cancer risk. The accumulation hypothesis best described BMI in relation to ovarian cancer overall, with an odds ratio (OR) for the lifetime effect of BMI (per 5 kg/m 2 increase) of 1.10 (95% credible interval [CrI]: 0.90-1.35). For invasive ovarian cancer, the OR (95% CrI) for the lifetime effect was 1.16 (0.92-1.48), with BMI during early childbearing years showing the highest relative importance, suggesting this may be a sensitive period. For borderline cancer, the lifetime effect OR was not strongly supportive of an association (OR: 0.90, 95% CrI: 0.53-1.32). The results suggest that a sensitive period of early childbearing years is a candidate hypothesis for further investigation., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. The PROVAQ study was approved by the Research Ethics Committee of the Centre de recherche du CHUM as well as the participating hospitals. Consent to participate: All participants provided written informed consent. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. Springer Nature B.V.)

Introduction: Poor oral health has been suggested as a risk factor for cognitive decline. Yet, biologically plausible mechanisms explaining this relationship remain unknown., Objectives: We aimed (1) to identify oral and cognitive health clustering patterns among middle-aged to elderly Canadians and (2) to investigate the extent to which these patterns could be explained by bone mineral density (BMD), a proxy measure of the cholinergic neurons' activity., Methods: This cross-sectional study used baseline data from the Comprehensive cohort of the Canadian Longitudinal Study of Aging (CLSA). Oral health was assessed by a self-report questionnaire, and 7 task-based instruments measured cognitive health. We identified oral and cognitive health clusters, our outcome variables, using latent class analysis. Two sets of multivariate logistic regression and 95% confidence intervals were used to investigate whether BMD explains the odds of membership in a certain oral and cognitive health group. The final models were adjusted for socioeconomic, health, and lifestyle factors., Results: Our study sample (N = 25,444: 13,035 males, 12,409 females) was grouped into 5 and 4 clusters based on the oral health status and performance on the cognitive tasks, respectively. After adjusting for all potential covariates, increase in BMD was not associated with higher odds of membership in classes with better oral health (odds ratio [OR] = 1.58 [95% confidence interval {CI}: 0.85-2.92]) and cognitive health (OR = 1.61 [95% CI: 1-2.6]) compared with the groups with the least favorable oral and cognitive health status, respectively., Conclusion: Middle-aged and elderly Canadians show different oral and cognitive health profiles, based on their denture-wearing status and performance on cognitive tests. No evidence could be found to support BMD in place of cholinergic neurons' activity as the common explanatory factor behind the association between oral health and cognitive health., Knowledge Transfer Statement: This study is probably the first of its kind to shed light on the cholinergic system as a potential pathway influencing oral and cognitive health. Our findings may support the notion that any potential association between poor oral health and cognitive health might be explained by common contributors, helping clinicians to find the common risk factors for both conditions., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The opinions expressed in this manuscript are the authors' own and do not reflect the views of the Canadian Longitudinal Study on Aging.

Background: Due to the evolving nature of COVID-19, there is evidence that COVID-19-specific infection prevention and control guideline (IPCG) documents formulated for oral health care settings are also changing rapidly. To better inform future policies, a comprehensive review of all IPCG documents across different phases of restrictions for oral health care practitioners is required., Types of Studies Reviewed: A search was performed for documents shared from March 2020 through January 2022 on websites of oral health regulatory authorities in Canada's 10 provinces and 3 territories. The authors performed a narrative review of the identified IPCG documents for dentists (n = 78) and dental hygienists (n = 57)., Results: Overall findings from more than 100 IPCG documents distributed during a period of 23 months revealed that the frequency of these updates differed among jurisdictions and between the 2 oral health care practitioners (ie, dentists and dental hygienists) within the same jurisdiction. The most notable observation was the different face-covering recommendations for dentists and dental hygienists within the same jurisdiction during the same timeframe. A common document was sometimes observed for dentists and dental hygienists, however, most jurisdictions had separate IPCG documents., Conclusions and Practical Implications: The different approaches could have been justified on the basis of prevalence of COVID-19 and availability of personal protective equipment; however, there was a risk of creating confusion about IPCG best practices. The findings of this review will support decision makers when planning future development and dissemination of regulations for all oral health care practitioners., Competing Interests: Disclosure None of the authors reported any disclosures., (Copyright © 2023 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Objective: Prognostic risk prediction models estimate the probability of developing head and neck cancer (HNC), providing valuable information for managing the disease. While different prognostic HNC risk prediction models have been developed worldwide, a comprehensive evaluation of their methods is lacking. We conducted a scoping review with a critical assessment aiming to identify the methodological strengths and limitations of HNC risk prediction models., Method: We searched Medline, Embase, Scopus, Web of Science, and CAB Abstracts databases and included full-text-available peer-reviewed published papers on developing or validating a prognostic HNC risk prediction model. Study quality was appraised using the PROBAST tool., Results: Nine papers were included. Although all had a high risk of bias, mainly in the analysis domain, only two studies had high concerns about clinical applicability., Conclusion: Currently published studies provide insufficient information on methods, making it difficult to judge the models' quality and applicability. Future investigations should follow the guidelines in reporting the prediction modelling studies., (Copyright© 2023 Dennis Barber Ltd.)

Objectives: Using an established proxy measure of intra-utero testosterone and estrogen levels-the ratio of second- and fourth-digit lengths-we estimated its association with the oral cancer risk among a population from Southern India., Material and Methods: In a hospital-based case-control study, incident oral cancer cases (N = 350) and non-cancer controls (N = 371), frequency-matched by age and sex, were recruited from two major referral hospitals in Kerala, India. Structured interviews collected information on several domains of exposure via detailed life course questionnaires. Digit lengths were measured using a ruler in a standardized manner. Unconditional logistic regression was performed to estimate the odds ratios and 95% confidence intervals., Results: Second- and fourth-digit ratio lower than 1, which indicates relatively higher intra-utero level of testosterone and lower intra-utero level of estrogen, was associated with higher oral cancer risk (OR = 1.60, 95% CI: 1.02-2.52), after accounting for several confounders., Conclusion: Our findings suggest that intra-utero hormonal levels measured by second- and fourth-digit ratio are associated with oral cancer risk. Further studies in different population should confirm these results., (© 2022 Wiley Periodicals LLC.)

Introduction: Head and neck cancers (HNCs) are a significant health burden worldwide. Oral human papillomavirus (HPV) infection is a major risk factor for HNCs. Unfortunately, currently available prophylactic vaccines have limited coverage and potential for HPV type replacement. Carrageenan, a natural product extracted from marine red algae, has demonstrated potency as an HPV inhibitor and could offer a potential alternative to prevent HPV-related diseases, including oral HPV infection. However, there is a lack of clinical studies on the effect of carrageenan on oral HPV infections. As a first step to address this gap, we propose a randomised controlled trial (RCT) to evaluate the feasibility of conducting a larger multicentric RCT to investigate the effect of a carrageenan mouthwash on oral HPV infection., Methods and Analysis: We will conduct a placebo-controlled triple-blinded feasibility RCT with two parallel arms, each arm consisting of 20 participants. Participants will complete a single in-person visit at baseline and conduct biweekly follow-ups from home by completing a web-based questionnaire and sending saliva self-samples via mail. During the 6-month period trial, participants will gargle with the mouthwash morning and night, and around sexual activities. The study will evaluate several factors including recruitment and retention rates, the feasibility of data collection procedures, compliance with study procedures, acceptability of RCT procedures and intervention and safety data on carrageenan use in the oral cavity. We will estimate the standard deviation of outcome measures, including time to the incidence of oral HPV infection and time to clearance of prevalent oral HPV infection. The trial primary outcome is whether to proceed to a definitive trial based on prespecified progression criteria., Ethics and Dissemination: The protocol was approved by the McGill University institutional review board. Study results will be presented at scientific conferences and published in academic journals., Trial Registration Number: NCT05746988., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors declare no conflict of interest.

Background: Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene. This rarity contributes to misdiagnosis, delayed diagnosis and barriers to good care. There are no published national or international consensus guidelines for the diagnosis and management of patients with ASMD. For these reasons, we have developed clinical guidelines that defines standard of care for ASMD patients., Methods: The information contained in these guidelines was obtained through a systematic literature review and the experiences of the authors in their care of patients with ASMD. We adopted the Appraisal of Guidelines for Research and Evaluation (AGREE II) system as method of choice for the guideline development process., Results: The clinical spectrum of ASMD, although a continuum, varies substantially with subtypes ranging from a fatal infantile neurovisceral disorder to an adult-onset chronic visceral disease. We produced 39 conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. In addition, these guidelines have identified knowledge gaps that must be filled by future research., Conclusion: These guidelines can inform care providers, care funders, patients and their carers about best clinical practice and leads to a step change in the quality of care for patients with ASMD with or without enzyme replacement therapy (ERT)., (© 2023. The Author(s).)

Background: In Spring of 2020, due to the COVID-19 pandemic, Canadian provincial dental hygiene regulatory bodies implemented new practice guidelines. Reports of stress, anxiety and conflict experienced by dental hygienists have been linked to miscommunication between oral health regulators at this time. Limited data exists on the perceptions and experiences of dental hygienists navigating new guidelines for dental hygiene care during the pandemic. Therefore, the objective of our study was to explore via descriptive thematic analysis how dental hygienists experienced and perceived: i) dental hygiene practice during the COVID-19 pandemic, and ii) their regulatory body's COVID-19 guidelines., Methods: Participants were identified through provincial dental hygiene licensing bodies. Online bi-monthly questionnaires were administered to participants (n = 876) from December 2021 to January 2022. Two open-ended questions were asked in the questionnaire. A qualitative descriptive thematic analysis was applied to these two questions., Results: Major themes at baseline relayed challenges related to workplace compliance, patient treatment and communication of practice protocols. Across responses, hygienists confirmed conflicting messaging from regulators and guideline interpretations as stressors impacting their professional practice and satisfaction within the profession. Participant responses at endpoint cited increased satisfaction with regulatory guidelines as the pandemic evolved, yet inconsistencies in regulators' messaging was noted as a prevailing issue., Conclusion: Inconsistent guideline messaging reflects an increased need for collaboration amongst oral health care regulators to streamline protocols for practice and reduce interprofessional conflict in pandemic circumstances. A national unified approach is warranted in establishing guidelines for dental hygiene practice in Canada., (© 2022. The Author(s).)

Background: The ICECAP-Supportive Care Measure (SCM) is a self-complete measure developed to inform economic decision making at the end-of-life. Previous research has demonstrated its feasibility in hospice and nursing home settings. This is the first study of its use with patients on the organ failure trajectory., Aim: To determine the feasibility of using the ICECAP-SCM with patients experiencing end-stage organ failure in a hospital setting., Design: Participants were asked to 'think aloud' when completing the ICECAP-SCM, ICECAP-A and EQ-5D-5L measures. The interviews were transcribed verbatim and examined for errors in comprehension, retrieval, judgement, and response by five raters. Qualitative data were collected to explore reasons for errors in completing the measures and participants' views about the measures., Setting/participants: Sixty patients (with end-stage renal failure n  = 18; end-stage heart failure n  = 21; end-stage chronic obstructive pulmonary disease n  = 21) participated. Senior clinicians applied prognostic criteria to determine eligibility., Results: Participants reported that the measures were acceptable, clear, and easy to complete. Error rates in completing the measures were low (ICECAP-A = 3%,and ICECAP-SCM = 5.7% and EQ-5D-5L = 6.3%). There was some variation in responses between patients with different end-stage conditions, particularly those with symptom fluctuation. Some patients had not considered their end-of-life (i.e. advance care planning) and reported finding questions about this difficult to answer., Conclusion: It is feasible to use the ICECAP-SCM with patients with end-stage organ failure receiving care in hospital settings. This study provides evidence for researchers and policy makers involved in measuring end-of-life care globally. The ICECAP-SCM can be recommended for research with patients in end-stage organ failure to appropriately capture the broader benefits of end-of-life care.

Background: Oral health care settings potentially carry a high risk of cross-infection due to close contact and aerosol-generating procedures. There is limited evidence of the impact of COVID-19 among dental hygienists. This longitudinal study aimed to 1) estimate COVID-19 incidence rates among Canadian dental hygienists over a 1-year period; and 2) estimate vaccination rates among Canadian dental hygienists., Methods: A prospective cohort study design was used to collect self-reported COVID-19 status from 876 registered dental hygienists across Canada via an online baseline survey and then 6 follow-up questionnaires delivered between December 2020 and January 2022. Bayesian Poisson and binomial models were used to estimate the incidence rate and cumulative incidence of self-reported COVID-19., Results: The estimated cumulative incidence of COVID-19 in dental hygienists in Canada from December 2020 to January 2022 was 2.39% (95% CrI, 1.49%-3.50%), while the estimated cumulative incidence of COVID-19 in corresponding Canadian provinces was 5.12% (95% CrI, 5.12%-5.13%) during the same period. At last follow-up, 89.4% of participants self-reported that they had received at least 1 dose of a COVID-19 vaccine., Conclusion: The low infection rate observed among Canadian dental hygienists between December 2020 and January 2022 is reassuring to the dental hygiene and general community., Competing Interests: The authors declare no known conflicts of interest., (Copyright © 2022 CDHA | ACHD.)

Purpose: Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function., Methods: We conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP., Results: Nineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI - 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP., Conclusions: CPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered., (© 2022. The Author(s).)

Background: Oral health care settings carry a potentially high risk of causing cross-infection between dentists and patients and among dental staff members due to close contact and use of aerosol-generating procedures. The authors aimed to estimate COVID-19 incidence rates among Canadian dentists over a 6-month period., Methods: The authors conducted a prospective cohort study of 644 licensed dentists across Canada from July 29, 2020, through February 12, 2021. An online questionnaire, adapted from the World Health Organization's Unity Studies protocols for assessment of COVID-19 risk among health care workers, was used to collect data on self-reported severe acute respiratory syndrome coronavirus 2 infections every 4 weeks. A bayesian Poisson model was used to estimate the incidence rate and corresponding 95% credible intervals (CIs)., Results: Median age of participants was 47 years; most participants were women (56.4%) and general practitioners (90.8%). Median follow-up time was 188 days. Six participants reported COVID-19 infections during the study period, giving an incidence rate of 5.10 per 100,000 person-days (95% CI, 1.86 to 9.91 per 100,000 person-days). The incidence proportion was estimated to be 1,084 per 100,000 dentists (95% CI, 438 to 2,011 per 100,000 dentists) and 1,864 per 100,000 people (95% CI, 1,859 to 1,868 per 100,000 people) in the Canadian population during the same period., Conclusions: The low infection rate observed among Canadian dentists from July 29, 2020, through February 12, 2021, should be reassuring to the dental and general community., Practical Implications: Although the infection rates were low among Canadian dentists, it is important to continue to collect disease surveillance data., (Copyright © 2022 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: Tobacco smoking remains one of the major risk factors for oral cavity cancers (OCC), a subgroup of head and neck cancer (HNC) less attributed to human papillomavirus (HPV) infection. Although a strong dose-dependent association between tobacco smoking and OCC exists, several important questions on the age-dependent effects of this habit remain unanswered. We investigated which life course hypothesis best describes the association between tobacco smoking and HPV-negative (HPV - ve ) OCC in Canada and India., Methods: We used data from the HeNCe Life study, a hospital-based case-control study conducted in Canada and India, using similar protocols. Cases were newly diagnosed subjects with primary squamous cell carcinomas of the head and neck region. Control subjects were patients with non-cancer selected from various outpatient clinics in a hospital located in the same catchment area as the cases and frequency-matched to cases according to age and sex. We collected information on an array of life course exposures using a structured questionnaire with the help of a life grid. Tobacco exposure (pack-years) during three life periods (≤ 30, 31-50, and >50 years of age) was calculated from the entire life course history of smoking. We used CDx brushes to collect oral exfoliated cells. Alpha HPV DNA detection and genotyping were performed for 36 HPV genotypes using the linear array. Participants who tested positive for HPV were excluded from the analysis. We used the Bayesian relevant life course exposure model (BRLM) to identify the life course hypothesis that best described the relationship between tobacco smoking and HPV - ve OCC., Results: We show evidence for a late-life sensitive period (>50 years of age) for tobacco smoking in relation to the risk of HPV - ve OCC in both Canada and India. An increase of 1 pack-year of tobacco smoking increased the risk of OCC by ~3% in both countries., Conclusion: Our findings from the Canadian and Indian data suggest that smoking tobacco after 50 years of age may carry a higher risk of developing oral cancer than earlier in life. Further studies are warranted to confirm the results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Madathil, Rousseau, Durán, Alli, Joseph and Nicolau.)

Background: The Streptococcus anginosus group is known for its pathogenicity and tendency for abscess formation. The S anginosus group also causes brain abscesses, yet few studies describe this presentation in the pediatric neurology literature. We describe 5 patients with central nervous system infection due to S anginosus group evaluated by child neurologists at the University of Iowa from 2014 to 2020., Methods: We performed a retrospective case series review of electronic medical records detailing the clinical presentation and course of pediatric patients with S anginosus group-associated central nervous system infection., Results: We identified 4 males and 1 female (8, 11, 14, 16, and 21 years). Brain imaging showed abscesses in 4 cases and empyema in 1. All underwent neurosurgical intervention and antibiotic treatment. Cultures obtained during the neurosurgical procedure grew S anginosus group (4 cases with Streptococcus intermedius and 1 with Streptococcus constellatus ). An 8-year-old boy with a delayed diagnosis died from brain herniation., Conclusions: Central nervous system infections due to the S anginosus group can be life-threatening. Neuroimaging plays a key role in the early identification of abscesses. Prompt surgical intervention and timely initiation of antibiotics are critical for optimal outcomes.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies., Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure., Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021., Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475)., Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days., Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group., Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings., Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Background: The medium- and long-term effects of severe acute respiratory syndrome coronavirus 2 infection on survivors are unknown. In the current study, we assessed the medium-term effects of coronavirus disease 2019 (COVID-19) on survivors of severe disease., Methods: This is a retrospective, case series of 200 patients hospitalized across 3 large Birmingham hospitals with severe-to-critical COVID-19 infection 4-7 months from disease onset. Patients underwent comprehensive clinical, laboratory, imaging, lung function tests (LFTs), and quality of life and cognitive assessments., Results: At 4-7 months after disease onset, 63.2% of patients reported persistent breathlessness; 53.5%, significant fatigue; 37.5%, reduced mobility; and 36.8% pain. Serum markers of inflammation and organ injuries that persisted at hospital discharge had normalized on follow-up, indicating no sustained immune response causing chronic maladaptive inflammation. Chest radiographs showed complete resolution in 82.8%, and significant improvement or no change in 17.2%. LFTs revealed gas transfer abnormalities in 80.0% and abnormal spirometric values in 37.6% of patients. Compared with patients who did not experience breathlessness, those who did had significantly higher incidences of comorbid conditions and residual chest radiographic and LFT abnormalities (P < .01 to all). For all parameters assessed and persisting symptoms there were no significant differences between patients in hospital wards and those in intensive treatment units. All patients reported a significantly reduced quality of life in all domains of the EQ-5D-5L quality-of-life measures., Conclusions: A significant proportion of severely ill patients with COVID-19 still experience symptoms of breathlessness, fatigue, pain, reduced mobility, depression and reduced quality of life 4-7 months after disease onset. Symptomatic patients tend to have more residual chest radiographic and LFT abnormalities., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Algorithms for predicting retinopathy of prematurity (ROP) requiring treatment need to be validated in Indian settings to determine if the burden of screening can be reduced without compromising the sensitivity of existing gestation and weight-based cut offs., Objective: To evaluate the performance of the available algorithms namely, WINROP (Weight, Insulin-like growth factor I, Neonatal ROP), CHOP-ROP (Children's Hospital of Philadelphia ROP) and ROPScore in predicting type 1 ROP and time from alarm to treatment by each algorithm., Study Design: Ambispective observational., Setting: Tertiary care neonatal intensive care unit in India., Participants: Neonates less than 32 weeks or less than 1500 g born between July, 2013 to June, 2019 (N=578), who underwent ROP screening., Primary Outcome: Sensitivity, specificity and time from alarm to treatment by each algorithm., Results: The sensitivity and specificity of WINROP was 85% and 36%, for CHOP-ROP it was 54% and 71%, and for ROPScore it was 73% and 67%, respectively in detecting type 1 ROP. A total of 50/51 (98%) of neonates with type 1 ROP underwent treatment at median gestation of 9 weeks and median time from alarm to treatment by WINROP, CHOP-ROP and ROPScore was 7, 7 and 3 weeks, respectively., Conclusion: WINROP, CHOP-ROP and ROPScore were not sensitive enough to replace the gestational age, weight and risk factor-based screening criteria for type 1 ROP.

Objectives: To investigate if intravenous fentanyl or intravenous ketamine can provide adequate analgesia in preterm infants undergoing laser photocoagulation for retinopathy of prematurity (ROP)., Design: Open-label randomised trial., Setting: Tertiary care institution., Participants: Preterm infants who underwent laser photocoagulation for ROP., Interventions: Infants were randomised to receive fentanyl as intravenous bolus dose of 2 µg/kg, followed by an intravenous infusion of 1 µg/kg/hour increased to a maximum of 3 µg/kg/hour or intravenous ketamine as bolus dose of 0.5 mg/kg, followed by further intermittent intravenous bolus doses of 0.5 mg/kg to a maximum of 2 mg/kg in the initial phase and intravenous fentanyl (bolus of 2 µg/kg followed by infusion of 2 µg/kg/hour to a maximum of 5 µg/kg/hour) or intravenous ketamine (bolus dose of 1 mg/kg followed by intermittent bolus doses of 0.5 mg/kg to a maximum of 4 mg/kg) in the revised regimen phase., Main Outcome Measures: Proportion of infants with adequate analgesia defined as the presence of both: (1) all the Premature Infant Pain Profile-Revised scores measured every 15 min less than seven and (2) proportion of the procedure time the infant spent crying less than 5%.Secondary outcomes included apnoea, cardiorespiratory or haemodynamic instability, feed intolerance and urinary retention requiring catheterisation during and within 24 hours following the procedure., Results: A total of 97 infants were randomised (fentanyl=51, ketamine=46). The proportions of infants with adequate analgesia were 16.3% (95% CI 8.5% to 29%) with fentanyl and 4.5% (95% CI 1.3% to 15.1%) with ketamine. Ten infants (19.6%) in the fentanyl group and seven infants (15.2%) in the ketamine group had one or more side effects. In view of inadequate analgesia with both the regimens, the study steering committee recommended using a higher dose of intravenous fentanyl and intravenous ketamine. Consequently, we enrolled 27 infants (fentanyl=13, ketamine=14). With revised regimens, the proportions of infants with adequate analgesia were higher: 23.1% (95% CI 8.2% to 50.2%) with fentanyl and 7.1% (95% CI 1.3% to 31.5%) with ketamine. However, higher proportions of infants developed apnoea (n=4; 30.7%), need for supplemental oxygen (n=5, 38.4%) and change in cardiorespiratory scores (n=7; 53.8%) with fentanyl but none with ketamine., Conclusions: Fentanyl-based and ketamine-based drug regimens provided adequate analgesia only in a minority of infants undergoing laser photocoagulation for ROP. More research is needed to find safe and effective regimens that can be employed in resource constrained settings., Trial Registration Number: CTRI/2018/03/012878., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Late pulmonary valve replacement following repair of tetralogy of Fallot may become necessary in patients with chronic pulmonary insufficiency. There is limited information on the long-term outcome of these prostheses, which is the focus of this study., Methods: We conducted a retrospective study of patients with repaired tetralogy of Fallot who underwent pulmonary valve replacement from 1990 to 2015 in our institution. We investigated imaging and clinical parameters including mortality and late adverse events (reintervention [surgical or transcatheter]), infective endocarditis, or arrhythmias requiring device implantation or ablation., Results: There were 69 patients divided into 3 groups: Carpentier-Edwards (n = 14), Contegra (n = 40), and pulmonary homograft (n = 15). The mean age at the time of pulmonary valve replacement was 21 ± 12 years. The mean follow-up was 8.5 ± 4.7 years. The mean preoperative and postoperative right ventricular end-diastolic volume index was 210 ± 42 and 120 ± 24 mL/m 2 , respectively. There were no mortalities. Late adverse events were observed in 23 (33%) patients: 15 (22%) reintervention (surgical or transcatheter), 11 (16%) endocarditis, and 11 (16%) arrhythmias. Overall, 1-, 5-, and 10-year freedom from surgical reintervention was 98.5%, 93.6%, and 79.3%, respectively. The Contegra group had significantly higher pulmonary valve gradients, a higher risk of developing late adverse events compared to Carpentier-Edwards ( P = .046) and pulmonary homograft ( P = .055) in multivariate analysis and increased risk for reintervention in the univariate analysis (hazard ratio: 3.4; 95% CI: 0.92-13; P value.066)., Conclusion: Pulmonary valve replacement in patients with repaired tetralogy of Fallot has acceptable short- and intermediate-term outcomes. Contegra prosthesis had a higher risk of late adverse events with higher pulmonary valve gradients.

Introduction: Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers., Methods: A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP., Results: On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence., Discussion: Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The respiratory manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been extensively documented. There is emerging evidence that coronavirus disease 2019 (COVID-19) has number of other presenting features which might not be related to the severity of the respiratory disease. We have previously described a case of hypoactive delirium as the first manifestation of COVID-19 without profound lung disease. Here we present five cases of elderly patients, without a prior history of dementia and had no overt COVID-19-related pneumonia, who presented with the acute onset of delirium as the primary manifestation of COVID-19., Methods: This retrospective, single-center study performed a health informatics search to produce a list of patients who were admitted with acute confusion and tested positive for the SARS-CoV-2 virus between March 1 and June 30, 2020. The electronic medical admission notes were screened for all patients with confusion who tested positive for SARS-CoV-2. Patients with a history of dementia and a high risk of delirium were excluded, such as severe COVID-19-related pneumonia or any other infection, malignancy, drugs, or severe illness of any kind., Results: During the first wave of the COVID-19 pandemic our hospital experienced just over 3,000 SARS-CoV-2 positive patients, and 45 of them had documented confusion upon admission. Secondary causes for their acute confusion were excluded. Five patients were identified as having delirium as the initial presentation of COVID-19-related illness without significant COVID-19-related pneumonitis. None of them had overt chest symptoms or a previous history of confusion, and the 3 patients who underwent head CT scans had normal findings., Conclusions: This case series illustrates the importance of recognizing acute confusion as the first manifestation of COVID-19 in susceptible individuals., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 Korean Neurological Association.)

Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals., (© 2020 SSIEM.)

Coronavirus disease 2019 (COVID-19) is a novel infection of which we still have much to learn. Microvascular and macrovascular complications are increasingly recognised as being among the drivers of morbidity and mortality in patients with this condition. Here we present a case of a woman with COVID-19 who suffered massive and bilateral middle cerebral artery strokes, which presented as reduced consciousness several days into admission. Clinicians need to be aware of possible causes of reduced consciousness in COVID-19 patients, particularly as delirium appears to be a common complication, and revisit working diagnoses if the clinical picture does not fully fit. Studies into both anticoagulation and the management of stroke in the context of COVID-19 are urgently needed to help inform future practice., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Muscle contraction is regulated by the movement of end-to-end-linked troponin-tropomyosin complexes over the thin filament surface, which uncovers or blocks myosin binding sites along F-actin. The N-terminal half of troponin T (TnT), TNT1, independently promotes tropomyosin-based, steric inhibition of acto-myosin associations, in vitro. Recent structural models additionally suggest TNT1 may restrain the uniform, regulatory translocation of tropomyosin. Therefore, TnT potentially contributes to striated muscle relaxation; however, the in vivo functional relevance and molecular basis of this noncanonical role remain unclear. Impaired relaxation is a hallmark of hypertrophic and restrictive cardiomyopathies (HCM and RCM). Investigating the effects of cardiomyopathy-causing mutations could help clarify TNT1's enigmatic inhibitory property. We tested the hypothesis that coupling of TNT1 with tropomyosin's end-to-end overlap region helps anchor tropomyosin to an inhibitory position on F-actin, where it deters myosin binding at rest, and that, correspondingly, cross-bridge cycling is defectively suppressed under diastolic/low Ca 2+ conditions in the presence of HCM/RCM lesions. The impact of TNT1 mutations on Drosophila cardiac performance, rat myofibrillar and cardiomyocyte properties, and human TNT1's propensity to inhibit myosin-driven, F-actin-tropomyosin motility were evaluated. Our data collectively demonstrate that removing conserved, charged residues in TNT1's tropomyosin-binding domain impairs TnT's contribution to inhibitory tropomyosin positioning and relaxation. Thus, TNT1 may modulate acto-myosin activity by optimizing F-actin-tropomyosin interfacial contacts and by binding to actin, which restrict tropomyosin's movement to activating configurations. HCM/RCM mutations, therefore, highlight TNT1's essential role in contractile regulation by diminishing its tropomyosin-anchoring effects, potentially serving as the initial trigger of pathology in our animal models and humans., Competing Interests: The authors declare no competing interest.

Human papillomavirus (HPV) infection and tobacco smoking are well-known risk factors for head and neck cancers (HNC). Although an effect modification between oral HPV infection and tobacco smoking may exist, evidence is lacking on how they interact temporally. We investigated the latency and life course effects of tobacco smoking on risk of HNC among HPV-positive (HPV +ve ) and negative (HPV -ve ) individuals. We used data from 631 ever-smoker participants of a hospital-based case-control study conducted in four major hospitals in Montréal, Canada. Cases (n = 320), incident, histologically confirmed, primary squamous cell carcinomas, were frequency-matched to controls (n = 311) by age and sex. Sociodemographic and behavioral factors (e.g., tobacco and alcohol use and sexual history) were collected using a structured interview applying a life grid technique. Oral exfoliated cells were used for HPV DNA detection and genotyping. Latency effects were estimated flexibly using a Bayesian relevant exposure model and further extended with a life course approach. Retrospective smoking trajectories for HPV +ve cases and controls had similar shapes. Exposure to tobacco smoking even 40 years before diagnosis was associated with an increased HNC risk among both HPV +ve and HPV -ve participants. The effect of smoking before the start of sexual activity compared to afterwards was higher among HPV +ve individuals. This pattern of association was less profound among HPV -ve participants. Temporal interactions may exists between oral HPV infection and life course smoking trajectories in relation to HNC risk., (© 2019 UICC.)

Objective: To evaluate the clinical profile and outcome of neonates with non-immune hydrops (NIH)., Methods: Data of all the NIH cases admitted to neonatal intensive care unit at our center, New Delhi from January, 2010 to October, 2017 were extracted from hospital records, which included clinical profile and outcomes., Results: Of the 17,299 total births, 27 neonates were identified to have NIH. Antenatal interventions were undertaken in five (18.5%) cases. The most common etiology of NIH was cardiac (n=5; 18.5%). Two babies with chylothorax were successfully managed with octreotide infusions. Overall survival rate of NIH was 70.3% (n=19). All neonates with a suspected genetic syndrome died., Conclusions: Multidisciplinary team including obstetricians, pediatric surgeons, geneticists and neonatologists can improve outcome in neonates with NIH.