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Introduction Experts recommend integrating smoking-cessation treatments within U.S. mental health settings, but the population health benefits of doing so have not been estimated. This study simulates the impact of widespread cessation treatment for patients with depression under best-case treatment and maximum potential cessation scenarios. Methods Cessation interventions were simulated for U.S. adult smokers seeing a health professional for depression from 2020 to 2100. Interventions included (1) Any Treatment (behavioral counseling, pharmacological, combination) and (2) Pharmacological Treatment (including counseling), combined with increased mental health service utilization each. These were compared with a maximum potential cessation scenario where all patients with major depression quit smoking. Analyses were conducted in 2016–2020. Results Widespread uptake of Any Treatment among patients with depression would avert 32,000 deaths and result in 138,000 life-years gained by 2100; Any Treatment combined with 100% mental health service utilization would result in 53,000 and 231,000, respectively. Pharmacological Treatment would avert 125,000 deaths, with 540,000 life-years gained. Pharmacological Treatment combined with 100% mental health service utilization would result in 203,000 deaths averted and 887,000 life-years gained. Health gains under best-case treatment scenarios represent modest fractions of those projected under maximum potential cessation scenarios at current mental health service utilization levels (835,000 deaths averted, 3.73 million life-years gained) and at 100% utilization (1.11 million deaths averted, 5.07 million life years gained). Conclusions Providing smoking-cessation treatment to patients with depression and increasing mental health service utilization would reduce the toll of tobacco on this population. These gains would be considerably larger if cessation treatments were more effective.

Objectives: To investigate how the symptoms of mucus and cough impact adults living with laryngotracheal stenosis, and to use this information to guide future research and treatment plans. Methods: A survey was developed with the support of patient advisors and distributed to people suffering with laryngotracheal stenosis. The survey comprised 15 closed and open questions relating to mucus and cough and included the Leicester Cough Questionnaire (LCQ). Descriptive statistics, X2 and thematic analyses were completed. Results: In total, 641 participants completed the survey, with 83.62% (n = 536) reporting problems with mucus; 79% having daily issues of varying severity that led to difficulties with cough (46.18%) and breathing (20.90%). Mucus affected voice and swallowing to a lesser degree. Respondents described a range of triggers; they identified smoky air as the worst environmental trigger. Strategies to manage mucus varied widely with drinking water (72.26%), increasing liquid intake in general (49.35%) and avoiding or reducing dairy (45.32%) the most common approaches to control symptoms. The LCQ showed a median total score of 14 (interquartile range 11-17) indicative of cough negatively affecting quality of life. Thematic analysis of free text responses identified 4 key themes—the Mucus Cycle, Social impact, Psychological impact, and Physical impact. Conclusion: This study shows the relevance of research focusing on mucus and cough and its negative impact on quality of life, among adults with laryngotracheal stenosis. It demonstrates the inconsistent advice and management strategies provided by clinicians for this issue. Further research is required to identify clearer treatment options and pathways.

Acquired laryngotracheal stenosis (LTS) is a rare condition causing dyspnea and stridor. Patients often require multiple surgical procedures with no guarantee of a definitive outcome. Difficulty swallowing is a recognised problem associated with LTS and the reconstructive surgeries required to manage the condition. The breathlessness patient’s experience impacts on swallowing, and the vulnerable structures of the larynx are implicated during complex surgeries. This leads to dysphagia post-surgery, with some patients experiencing more chronic symptoms depending on the biomechanical impact of the surgery, or a pre-existing dysphagia. Despite this there is limited observational research about the dysphagia associated with LTS, with no exploration of the patient experience. Our aim was to investigate patient experience of living with LTS focussing on dysphagia in order to guide clinical practice. A qualitative study was completed using focus groups and semi-structured interviews with 24 patients who have had reconstructive surgery for LTS. Thematic analysis was used to identify three over-arching themes: The Physical Journey, The Emotional Journey and The Medical Journey. Key sub-themes included the importance of self-management and control, presence of symptoms, benefits of therapy, living with a life-long condition, fear and anxiety, autonomy, medicalisation of normal processes and the dichotomy between staff expertise and complacency. Swallowing was connected to all themes. The results are reviewed with consideration of the wider literature of lived experience particularly in relation to other chronic conditions and those that carry a high symptom burden such as head and neck cancer. Future clinical and research recommendations have been made. Akin to other clinical groups, adults with LTS are keen that management of their swallowing is person-centred and holistic.

Self-assessment is the most common method for monitoring performance and safety in the workplace. However, discrepancies between subjective and objective measures have increased interest in physiological assessment of performance. In a double-blind placebo-controlled study, 23 healthy adults were randomly assigned to either a placebo (n = 11; 5 F, 6 M) or caffeine condition (n = 12; 4 F, 8 M) while undergoing 50 h (i.e. two days) of total sleep deprivation. In previous work, higher salivary alpha-amylase (sAA) levels were associated with improved psychomotor vigilance and simulated driving performance in the placebo condition. In this follow-up article, the effects of strategic caffeine administration on the previously reported diurnal profiles of sAA and performance, and the association between sAA and neurobehavioural performance were investigated. Participants were given a 10 h baseline sleep opportunity (monitored via standard polysomnography techniques) prior to undergoing sleep deprivation (total sleep time: placebo = 8.83 ± 0.48 h; caffeine = 9.01 ± 0.48 h). During sleep deprivation, caffeine gum (200 mg) was administered at 01:00 h, 03:00 h, 05:00 h, and 07:00 h to participants in the caffeine condition (n = 12). This strategic administration of caffeine gum (200 mg) has been shown to be effective at maintaining cognitive performance during extended wakefulness. Saliva samples were collected, and psychomotor vigilance and simulated driving performance assessed at three-hour intervals throughout wakefulness. Caffeine effects on diurnal variability were compared with previously reported findings in the placebo condition (n = 11). The impact of caffeine on the circadian profile of sAA coincided with changes in neurobehavioural performance. Higher sAA levels were associated with improved performance on the psychomotor vigilance test during the first 24 h of wakefulness in the caffeine condition. However, only the association between sAA and response speed (i.e. reciprocal-transform of mean reaction time) was consistent across both days of sleep deprivation. The association between sAA and driving performance was not consistent across both days of sleep deprivation. Results show that the relationship between sAA and reciprocal-transform of mean reaction time on the psychomotor vigilance test persisted in the presence of caffeine, however the association was relatively weaker as compared with the placebo condition. Refereed/Peer-reviewed

Objectives Mindfulness-based programs (MBPs) such as the ‘Soles of the Feet’ (SoF) meditation have been shown to be effective for reducing aggressive behavior in people with intellectual disabilities (ID). Research on SoF has shown promising results in the USA but there is an absence of evidence for the approach in the United Kingdom (UK). The aim of this research was to adapt SoF for the UK and to assess the feasibility and cost of implementing the SoF intervention in a UK healthcare setting (UK SoF). Methods The UK SoF intervention consisted of a manualized protocol delivered over a six-week period by National Health Service staff to people with ID and their carers. This was a single-arm study with three measurement time points (baseline and 2- and 6-month follow-ups). Results The UK SoF intervention was shown to be feasible, with recruitment, retention, and adherence figures exceeding the minimum cut-off of 50%. Costs were £2426 per participant, or £2766 when including set-up costs such as therapist training. Although not a primary aim, data suggest that at 6-month follow-up, there was a reduction in scores for anger and aggressive behavior, and depression and anxiety showed improvement. In addition, people with ID were able to self-report on their health-related quality of life. Conclusions This study has indicated areas where the protocol could be further improved, and it is recommended that the research should move to a pilot trial before the development of a full randomized control trial.

Rationale & Objective More than 50% of hemodialysis patients experience sleep disturbance and most have coexisting sleep apnea. However, how sleep apnea affects sleep and the overall experience of patients with chronic kidney disease treated by hemodialysis has not been evaluated. Study Design A mixed-methods design, incorporating cross-sectional observational and descriptive qualitative methodologies. Setting & Participants Patients receiving maintenance hemodialysis in Newcastle, New South Wales, Australia, with newly diagnosed sleep apnea (apnea-hypopnea index ≥ 5 per hour). Assessments In-laboratory polysomnography to assess sleep apnea and objective sleep parameters. Epworth Sleepiness Scale to assess daytime symptoms. A semi-structured qualitative interview to explore patient experience. Analytical Approach Descriptive and iterative thematic analysis. Results We analyzed 36 patients with newly diagnosed sleep apnea and interviewed 26 (mean age, 62 years, median apnea-hypopnea index, 32 per hour). Severity of sleep apnea did not affect patients’ sleep duration, sleep efficiency, or self-reported Epworth Sleepiness Scale score. From the qualitative interviews, 4 themes emerged: “broken sleep” related to short sleep duration, with waking and dozing off a common sleep cycle, caused by uncontrolled pain and dialysis. Many participants reported regularly “feeling unrefreshed” on waking. “Impact of sleep disturbance” included reduced physical, mental, and self-management capacity. Finally, interviewees described the need to use strategies to “soldier on” with symptoms. Limitations Participants’ views are only transferrable to hemodialysis patients with sleep apnea. Conclusions Our findings suggest that severity of sleep apnea does not affect sleep time or patient-reported daytime sleepiness; however, hemodialysis patients with sleep apnea report disturbed and unrefreshed sleep and the debilitating effects of sleep disturbance is profound. Broken and unrefreshed sleep were the dominant symptoms of sleep apnea and should be assessed routinely to identify patients with sleep apnea and improve quality of life in patients with chronic kidney disease treated with hemodialysis., Graphical abstract

PurposeRadiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inhibitors for diagnostic and radionuclide therapeutic applications. Here, we performed a systematic evaluation by varying the molar activity of [18F]olaparib and the injected mass of [TotalF]olaparib to investigate the effects on tumour and normal tissue uptake in two subcutaneous human glioblastoma xenograft models.Methods[18F]Olaparib uptake was evaluated in the human glioblastoma models: in vitro on U251MG and U87MG cell lines, and in vivo on tumour xenograft-bearing mice, after administration of [TotalF]olaparib (varying injected mass: 0.04-8.0 µg, and molar activity: 1-320 GBq/μmol).ResultsSelective uptake of [18F]olaparib was demonstrated in both models. Tumour uptake was found to be dependent on the injected mass of [TotalF]olaparib (µg), but not the molar activity per sé. An injected mass of 1 μg resulted in the highest tumour uptake (up to 6.9 ± 1.3%ID/g), independent of the molar activity. In comparison, both the lower and higher injected masses of [TotalF]olaparib resulted in lower relative tumour uptake (%ID/g; PEx vivo analysis of U87MG xenograft sections showed that the heterogeneity in [18F]olaparib intratumoural uptake correlated with PARP1 expression. Substantial upregulation of PARP1-3 expression was observed after administration of [TotalF]olaparib (>0.5 µg).Conclusion Our findings show that the injected mass of [TotalF]olaparib has significant effects on tumour uptake. Moderate injected masses of PARP inhibitor-derived radiopharmaceuticals may lead to improved relative tumour uptake and tumour-to-background ratio for cancer diagnosis and radionuclide therapy.

The consumption of caffeine has been linked to osteoporosis, believed to be due to enhanced bone resorption as a result of increased calcium excretion in the urine. However, the amount of calcium in the urine may not necessarily reflect the true effect of caffeine on calcium clearance. This study therefore examined the impact of high-dose, short-term caffeine intake on renal clearance of calcium, sodium and creatinine in healthy adults. In a double-blind clinical study, participants chewed caffeine (n = 12) or placebo (n = 12) gum for 5 minutes at 2-hour intervals over a 6-hour treatment period (800 mg total caffeine). Caffeine increased renal calcium clearance by 77%. Furthermore, the effect was positively correlated with sodium clearance and urine volume, suggesting that caffeine may act through inhibition of sodium reabsorption in the proximal convoluted tubule. This study confirmed that caffeine does increase renal calcium clearance and fosters further investigation into safe consumption of caffeine. Refereed/Peer-reviewed

SUMMARYSmoking rates in people with depression and anxiety are twice as high as in the general population, even though people with depression and anxiety are motivated to stop smoking. Most healthcare professionals are aware that stopping smoking is one of the greatest changes that people can make to improve their health. However, smoking cessation can be a difficult topic to raise. Evidence suggests that smoking may cause some mental health problems, and that the tobacco withdrawal cycle partly contributes to worse mental health. By stopping smoking, a person's mental health may improve, and the size of this improvement might be equal to taking antidepressants. In this article we outline ways in which healthcare professionals can compassionately and respectfully raise the topic of smoking to encourage smoking cessation. We draw on evidence-based methods such as cognitive–behavioural therapy (CBT) and outline approaches that healthcare professionals can use to integrate these methods into routine care to help their patients stop smoking.

OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.\ud \ud RESULTS:\ud The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively.\ud \ud CONCLUSIONS:\ud This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Objectives Airway reconstruction for laryngotracheal stenosis (LTS) encompasses several procedures. Dysphagia is a well-recognised sequela of LTS and airway surgery, however studies have employed mostly non-validated assessments post-operatively in small, heterogenous samples, perpetuating uncertainty around the contributions of LTS and its management to impaired deglutition. Consequently, considerable variation in LTS perioperative nutritional management exists. Our objective was to characterise baseline and post-operative dysphagia with instrumental assessment in an LTS cohort undergoing airway reconstruction and provide a gold-standard management framework for its management. Design, setting, participants and main outcome measures We performed a retrospective cohort study of adult airway reconstruction procedures from 2016-2020 at our quaternary centre. Patient background, LTS aetiology, procedure type, tube feeding duration, length of stay and serial Functional Oral Intake Scale (FOIS) and International Dysphagia Diet Standardisation Initiative (IDDSI) scores were noted. Baseline, post-operative day one and post-stent removal Fibreoptic Endoscopic Evaluation of Swallow (FEES) generated Penetration Aspiration Scale (PAS) scores. Results Forty-four patients underwent forty-six reconstructions. Baseline incidence of penetration-aspiration was considerably higher than the general population and worsened in the immediate post-operative period, however FOIS and PAS scores generally returned to baseline by discharge. Post-operative FOIS correlated negatively with tracheostomy or airway stent placement. At discharge, 80% tolerated soft or normal diet and 93% were feeding tube independent. Conclusions We present the largest adult airway reconstruction cohort with instrumental swallow assessment perioperatively. LTS patients have a higher incidence of underlying dysphagia but swallowing tends to return to baseline with appropriate postoperative rehabilitation. Such practice may avoid the complications, costs and morbidity of prolonged nutritional support.

Introduction Sarcoidosis is a chronic granulomatous disease of unknown aetiology and laryngeal involvement is seen in a small percentage of cases. Dysphagia is a common but under-reported symptom. Little is known about how dysphagia typically presents or is managed in the context of this fluctuating disease. We present our case series using an SLT-led model of assessment and management. Methods A literature search was conducted for any articles that reported both laryngeal sarcoidosis and dysphagia. We then analysed a case series of laryngeal sarcoidosis patients treated at Charing Cross Hospital. We report on multidimensional swallowing evaluation and rehabilitative interventions. Results Seventeen papers report both laryngeal sarcoidosis and dysphagia, with only one paper giving details on the nature of the dysphagia and the treatment provided. In our case series (n = 7), patients presented with FOIS Scores ranging from 5 to 7 pre-operatively (median = 6). Aspiration (median PAS Score = 6 and Range = 3–8) and pharyngeal residue were common. Sensory issues were also prevalent with most unaware of the extent of their difficulties. Management interventions included safe swallowing advice, compensatory strategies, exercises and close surveillance given their potential for repeated surgical interventions. Conclusion Laryngeal sarcoidosis is a rare condition. Dysphagia is under-reported and our experience highlights the need for specialist dysphagia intervention. Further research is required to understand dysphagia management requirements in the context of this fluctuating disease process.

BACKGROUND: The quality of case reports, which are often the first reported evidence for a disease, may be negatively affected by a rush to publication early in a pandemic. We aimed to determine the completeness of reporting (COR) for case reports published on coronavirus disease 2019 (COVID-19). METHODS: We conducted a systematic search of the PubMed database for all single-patient case reports of confirmed COVID-19 published from Jan. 1 to Apr. 24, 2020. All included case reports were assessed for adherence to the CARE (Case Report) 31-item checklist, which was used to create a composite COR score. The primary outcome was the mean COR score assessed by 2 independent raters. Secondary outcomes included whether there was a change in overall COR score with certain publication factors (e.g., publication date) and whether there was a linear relation between COR and citation count and between COR scores and social media attention. RESULTS: Our search identified 196 studies that were published in 114 unique journals. We found that the overall mean COR score was 54.4%. No one case report included all of the 31 CARE checklist items. There was no significant correlation between COR with either citation count or social media attention. INTERPRETATION: We found that the overall COR for case reports on COVID-19 was poor. We suggest that journals adopt common case-reporting standards to improve reporting quality.

PURPOSE OF REVIEW: Videofluoroscopy (VFSS) and fibreoptic endoscopic evaluation of swallowing (FEES) are established instrumental techniques to support differential diagnosis and treatment of oropharyngeal dysphagia. Whilst their value is undisputed, each tool is not without limitations. The COVID-19 pandemic has restricted access to VFSS and FEES leading clinicians to explore alternative or augmentative tools to support swallowing assessment. Ultrasound (US) is an established tool for visualisation of head and neck anatomy, including structures implicated in swallowing. While US has been utilised in swallowing research for many years, its application has not translated into common clinical practice. This review presents and debates the evidence for and against use of ultrasound for clinical swallowing assessment. RECENT FINDINGS: Evaluation of swallowing muscle morphometry and measurement of isolated swallowing kinematics are two primary uses of US in swallowing assessment that have been identified in the literature. Use of US to detect bolus flow, aspiration, and residues is in its early stages and needs further research. SUMMARY: US shows promise as an adjunctive modality to support assessment of swallowing. With standardisation, these measurements may have potential for transition into clinical care. Reliability and validity testing and development of normative data are imperative to ensure its use as an evidence-based instrumentation.

Background: There is a common perception that smoking generally helps people to manage stress, and may be a form of 'self‐medication' in people with mental health conditions. However, there are biologically plausible reasons why smoking may worsen mental health through neuroadaptations arising from chronic smoking, leading to frequent nicotine withdrawal symptoms (e.g. anxiety, depression, irritability), in which case smoking cessation may help to improve rather than worsen mental health. Objectives: To examine the association between tobacco smoking cessation and change in mental health. Search Methods: We searched the Cochrane Tobacco Addiction Group's Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, and the trial registries clinicaltrials.gov and the International Clinical Trials Registry Platform, from 14 April 2012 to 07 January 2020. These were updated searches of a previously‐conducted non‐Cochrane review where searches were conducted from database inception to 13 April 2012. Selection Criteria: We included controlled before‐after studies, including randomised controlled trials (RCTs) analysed by smoking status at follow‐up, and longitudinal cohort studies. In order to be eligible for inclusion studies had to recruit adults who smoked tobacco, and assess whether they quit or continued smoking during the study. They also had to measure a mental health outcome at baseline and at least six weeks later. Data Collection and Analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcomes were change in depression symptoms, anxiety symptoms or mixed anxiety and depression symptoms between baseline and follow‐up. Secondary outcomes included change in symptoms of stress, psychological quality of life, positive affect, and social impact or social quality of life, as well as new incidence of depression, anxiety, or mixed anxiety and depression disorders. We assessed the risk of bias for the primary outcomes using a modified ROBINS‐I tool. For change in mental health outcomes, we calculated the pooled standardised mean difference (SMD) and 95% confidence interval (95% CI) for the difference in change in mental health from baseline to follow‐up between those who had quit smoking and those who had continued to smoke. For the incidence of psychological disorders, we calculated odds ratios (ORs) and 95% CIs. For all meta‐analyses we used a generic inverse variance random‐effects model and quantified statistical heterogeneity using I2. We conducted subgroup analyses to investigate any differences in associations between sub‐populations, i.e. unselected people with mental illness, people with physical chronic diseases. We assessed the certainty of evidence for our primary outcomes (depression, anxiety, and mixed depression and anxiety) and our secondary social impact outcome using the eight GRADE considerations relevant to non‐randomised studies (risk of bias, inconsistency, imprecision, indirectness, publication bias, magnitude of the effect, the influence of all plausible residual confounding, the presence of a dose‐response gradient). Main Results: We included 102 studies representing over 169,500 participants. Sixty‐two of these were identified in the updated search for this review and 40 were included in the original version of the review. Sixty‐three studies provided data on change in mental health, 10 were included in meta‐analyses of incidence of mental health disorders, and 31 were synthesised narratively. For all primary outcomes, smoking cessation was associated with an improvement in mental health symptoms compared with continuing to smoke: anxiety symptoms (SMD −0.28, 95% CI −0.43 to −0.13; 15 studies, 3141 participants; I2 = 69%; low‐certainty evidence); depression symptoms: (SMD −0.30, 95% CI −0.39 to −0.21; 34 studies, 7156 participants; I2 = 69%' very low‐certainty evidence); mixed anxiety and depression symptoms (SMD −0.31, 95% CI −0.40 to −0.22; 8 studies, 2829 participants; I2 = 0%; moderate certainty evidence). These findings were robust to preplanned sensitivity analyses, and subgroup analysis generally did not produce evidence of differences in the effect size among subpopulations or based on methodological characteristics. All studies were deemed to be at serious risk of bias due to possible time‐varying confounding, and three studies measuring depression symptoms were judged to be at critical risk of bias overall. There was also some evidence of funnel plot asymmetry. For these reasons, we rated our certainty in the estimates for anxiety as low, for depression as very low, and for mixed anxiety and depression as moderate. For the secondary outcomes, smoking cessation was associated with an improvement in symptoms of stress (SMD −0.19, 95% CI −0.34 to −0.04; 4 studies, 1792 participants; I2 = 50%), positive affect (SMD 0.22, 95% CI 0.11 to 0.33; 13 studies, 4880 participants; I2 = 75%), and psychological quality of life (SMD 0.11, 95% CI 0.06 to 0.16; 19 studies, 18,034 participants; I2 = 42%). There was also evidence that smoking cessation was not associated with a reduction in social quality of life, with the confidence interval incorporating the possibility of a small improvement (SMD 0.03, 95% CI 0.00 to 0.06; 9 studies, 14,673 participants; I2 = 0%). The incidence of new mixed anxiety and depression was lower in people who stopped smoking compared with those who continued (OR 0.76, 95% CI 0.66 to 0.86; 3 studies, 8685 participants; I2 = 57%), as was the incidence of anxiety disorder (OR 0.61, 95% CI 0.34 to 1.12; 2 studies, 2293 participants; I2 = 46%). We deemed it inappropriate to present a pooled estimate for the incidence of new cases of clinical depression, as there was high statistical heterogeneity (I2 = 87%). Authors' Conclusions: Taken together, these data provide evidence that mental health does not worsen as a result of quitting smoking, and very low‐ to moderate‐certainty evidence that smoking cessation is associated with small to moderate improvements in mental health. These improvements are seen in both unselected samples and in subpopulations, including people diagnosed with mental health conditions. Additional studies that use more advanced methods to overcome time‐varying confounding would strengthen the evidence in this area.

BackgroundSmoking rates are significantly higher in people with mental health problems, compared to those without. Negative attitudes towards smoking cessation are widespread in inpatient settings towards patients with severe and enduring mental illness. It is not clear if the same attitudes operate in psychological services towards people with common mental illness. We aimed to understand the concerns and views that patients, therapists, and smoking cessation practitioners may have about integrating smoking cessation treatment into psychological treatment for common mental illness and how these concerns may be overcome.MethodsThematic analysis of 23 in-depth interviews. Interviews took place in Improving Access to Psychological Therapies (IAPT) and smoking cessation services in England. Participants were 11 psychological wellbeing practitioners (PWPs), six IAPT patients with common mental illness, and six smoking cessation advisors.OutcomesNone.FindingsIAPT patients reported psychological benefits from smoking, but also described smoking as a form of therapeutic self-harm. PWPs seem positive towards smoking cessation treatment for people with common mental illness. IAPT PWPs and patients accept evidence that smoking tobacco may harm mental health, and quitting might benefit mental health. PWPs report expertise in helping people with common mental illness to make behavioural changes in the face of mood disturbances and poor motivation. IAPT appears to be a natural environment for smoking cessation intervention. PWPs felt confident to offer smoking cessation treatments to IAPT patients, but thought that a reduction in caseload was required to deliver smoking cessation support in an already pressed service.

Caffeine is widely used to promote alertness and cognitive performance under challenging conditions, such as sleep loss. Non-digestive modes of delivery typically reduce variability of its effect. In a placebo-controlled, 50-h total sleep deprivation (TSD) protocol we administered four 200 mg doses of caffeine-infused chewing-gum during night-time circadian trough and monitored participants' drowsiness during task performance with infra-red oculography. In addition to the expected reduction of sleepiness, caffeine was found to disrupt its degrading impact on performance errors in tasks ranging from standard cognitive tests to simulated driving. Real-time drowsiness data showed that caffeine produced only a modest reduction in sleepiness (compared to our placebo group) but substantial performance gains in vigilance and procedural decisions, that were largely independent of the actual alertness dynamics achieved. The magnitude of this disrupting effect was greater for more complex cognitive tasks.

Tobacco-related health disparities disproportionately affect smokers with major depression (MD). Although tobacco simulation models have been applied to general populations, to date they have not considered populations with a comorbid mental health condition. We developed and calibrated a simulation model of smoking and MD comorbidity for the US adult population using the 2005–2018 National Surveys on Drug Use and Health. We use this model to evaluate trends in smoking prevalence, smoking-attributable mortality and life-years lost among adults with MD, and changes in smoking prevalence by mental health status from 2018 to 2060. The model integrates known interaction effects between smoking initiation and cessation, and MD onset and recurrence. We show that from 2018 to 2060, smoking prevalence will continue declining among those with current MD. In the absence of intervention, people with MD will be increasingly disproportionately affected by smoking compared to the general population; our model shows that the smoking prevalence ratio between those with current MD and those without a history of MD increases from 1.54 to 2.42 for men and from 1.81 to 2.73 for women during this time period. From 2018 to 2060, approximately 484,000 smoking-attributable deaths will occur among adults with current MD, leading to 11.3 million life-years lost. Ambitious tobacco control efforts could alter this trajectory. With aggressive public health efforts, up to 264,000 of those premature deaths could be avoided, translating into 7.5 million life years gained. This model can compare the relative health gains across different intervention strategies for smokers with MD.

BackgroundSmoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).MethodsWe conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.ResultsThere was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.ConclusionsThese findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.

Background: Ultrasound (US) is not widely used as part of the speech and language therapy (SLT) clinical toolkit The COVID-19 pandemic has intensified interest in US as an alternative to SLT instrumental tools such as the videofluoroscopic swallowing study (VFSS), fibreoptic endoscopic evaluation of swallowing (FEES) and endoscopic evaluation of the larynx (EEL) as a non-invasive, non-aerosol-generating procedure that can be delivered at the bedside to assess swallowing and/or laryngeal function To establish the appropriacy of routine US use, and in response to a national professional body request for a position statement, a group of expert SLTs conducted a rapid review of the literature Aim: To explore critically the clinical utility of US as an assessment tool for swallowing and laryngeal function in adults Methods & Procedures: A rapid review of four databases was completed to identify articles using US to assess swallowing and/or laryngeal function in adults compared with reference tests (VFSS/FEES/EEL/validated outcome measure) Screening was completed according to predefined inclusion/exclusion criteria and 10% of abstracts were rescreened to assess reliability Data were extracted from full texts using a predeveloped form The QUADAS-2 tool was used for quality ratings Information from included studies was summarized using narrative synthesis and visual illustration Outcomes & Results: Ten papers used US to assess swallowing, and 13 to assess laryngeal function All were peer-reviewed primary studies across a range of clinical populations and with a wide geographical spread Four papers had an overall low risk of bias, but the remaining 19 had at least one domain where risk of bias was judged as high or unclear Applicability concerns were identified in all papers The papers that used US to assess swallowing varied widely in terms of the anatomical structures assessed and methodology employed The papers assessing laryngeal function were more homogenous in their methodology Sensitivity and specificity data were provided for 12 of the laryngeal function papers with ranges of 64 3–100% and 48 5–100%, respectively Conclusions & Implications: There is burgeoning evidence to support the use of US as an adjunct to SLT clinical assessment of swallowing and laryngeal function However, the current literature does not support its use as a tool in isolation Further research is required to establish reliability in US assessment as well as clear SLT-driven protocols and training What this paper adds What is already known on the subject US has demonstrated potential as an assessment tool for objective parameters of swallowing Its use for laryngeal assessment (gross vocal fold movement) is also widely recognized within the literature This review appraised the literature related to US as an alternative or adjunctive tool for the assessment of swallowing and laryngeal function What this paper adds to existing knowledge This paper identifies that the current evidence base for US as a swallowing or laryngeal assessment tool is heterogenous and of variable quality No study combined the assessment of swallowing and laryngeal function, and only two studies assessed more than one parameter of swallowing, limiting the clinical application of the results What are the potential or actual clinical implications of this work? This review shows that US is a non-invasive accessible tool that can offer a detailed focal assessment of swallowing and laryngeal function, such as hyoid displacement and vocal fold mobility With the development of protocols, training packages and competency standards, US has the potential to be used as an adjunct to SLT assessment of swallowing and laryngeal function There is not currently enough evidence to support the use of US as a stand-alone tool for SLT assessment of swallowing or laryngeal function © 2020 Royal College of Speech and Language Therapists

Background:\ud A core outcome set (COS) is a standardised collection of outcomes to be collected and reported in all trials within a research area. A COS can reduce reporting bias and facilitate evidence synthesis. This is currently unavailable for use in community-based bipolar trials. This research aimed to develop such a COS, with input from a full range of stakeholders.\ud \ud Methods:\ud A co-production approach was used throughout. A longlist of outcomes was derived from focus groups with people with a bipolar diagnosis and carers, interviews with healthcare professionals and a rapid review of outcomes listed in bipolar trials on the Cochrane database. An expert panel with personal and/or professional experience of bipolar participated in a modified Delphi process and the COS was finalised at a consensus meeting.\ud \ud Results:\ud Fifty participants rated the importance of each outcome. Sixty-six outcomes were included in Round 1 of the questionnaire; 13 outcomes were added by Round 1 participants and were rated in Round 2. Seventy-six percent of participants (n = 38) returned to Round 2 and 60 outcomes, including 4 outcomes added by participants in Round 1, received a rating of 7–9 by >70% and 1–3 by

There are large inter-individual differences in slow wave sleep, which constitute a trait or phenotype. We investigated whether the manifestation of this trait is impacted by daytime sleeping after sleep deprivation, and to what extent it is robust to prior caffeine intake. N = 12 subjects underwent three 48 h periods of total sleep deprivation with different caffeine dosing regimens. There were significant, considerable, and robust inter-individual differences in slow wave sleep across nighttime sleep opportunities before, and daytime sleep after, total sleep deprivation, regardless of caffeine dosing. The robustness of this phenotype may have functional implications for individuals in around-the-clock operational settings.

Background The COVID-19 pandemic and the UK government's subsequent coronavirus action plan have fundamentally impacted on every aspect of healthcare. One area that is severely affected is ear, nose and throat (ENT)/laryngology where speech and language therapists (SLTs) engage in a diverse range of practice with patients with a range of conditions, including voice disorders, airway problems, and head and neck cancers (HNCs). A large majority of these patients are in high-risk categories, and many specialized clinical practices are vulnerable. In addition, workforce and research issues are challenged in both the immediate context and the future. Aims To discuss the threats and opportunities from the COVID-19 pandemic for SLTs in ENT/laryngology with specific reference to clinical practice, workforce and research leadership. Methods & procedures The relevant sections of the World Health Organisation's (WHO) health systems building blocks framework (2007) were used to structure the study. Expert agreement was determined by an iterative process of multiple-group discussions, the use of all recent relevant policy documentation, and other literature and shared documentation/writing. The final paper was verified and agreed by all authors. Main contribution The main threats to ENT/laryngology SLT clinical services include increased patient complexity related to COVID-19 voice and airway problems, delayed HNC diagnosis, reduced access to instrumental procedures and inequitable care provision. The main clinical opportunities include the potential for new modes of service delivery and collaborations, and harnessing SLT expertise in non-instrumental assessment. There are several workforce issues, including redeployment (and impact on current services), training implications and psychological impact on staff. Workforce opportunities exist for service innovation and potential extended ENT/SLT practice roles. Research is threatened by a reduction in immediate funding calls and high competition. Current research is affected by very limited access to participants and the ability to conduct face-to-face and instrumental assessments. However, research opportunities may result in greater collaboration, and changes in service delivery necessitate robust investigation and evaluation. A new national set of research priorities is likely to emerge. Conclusions & implications The immediate impact of the pandemic has resulted in major disruption to all aspects of clinical delivery, workforce and research for ENT/laryngology SLT. It is unclear when any of these areas will resume operations and whether permanent changes to clinical practice, professional remits and research priorities will follow. However, significant opportunity exists in the post-COVID era to re-evaluate current practice, embrace opportunities and evaluate new ways of working. What this paper adds What is already known on the subject ENT/laryngology SLTs manage patients with a range of conditions, including voice disorders, airway problems and HNCs. The diverse scope of clinical practice involves highly specialized assessment and treatment practices in patients in high-risk categories. A large majority of active research projects in this field are patient focused and involve instrumental assessment. The COVID-19 pandemic has created both opportunities and threats for ENT SLT clinical services, workforce and research. What this paper adds to existing knowledge This study provides a discussion of the threats and opportunities from the COVID-19 pandemic for ENT/laryngology SLT with specific reference to clinical practice, workforce and research leadership. What are the potential or actual clinical implications of this work? The COVID-19 pandemic has resulted in major disruption to all aspects of clinical delivery, workforce and research for ENT/laryngology SLT. Changes to clinical practice, professional remits and research priorities are of indeterminant duration at this time, and some components could be permanent. Significant clinical practice, workforce and research opportunities may exist in the post-COVID era.

Smoking is the leading avoidable cause of illness and premature mortality. The first-line treatments for smoking cessation are nicotine replacement therapy and varenicline. Meta-analyses of experimental studies have shown that participants allocated to the varenicline group were 1.57 times (95% confidence interval 1.29 to 1.91 times) as likely to be abstinent 6 months after treatment as those allocated to the nicotine replacement therapy group. However, there is limited evidence about the effectiveness of varenicline when prescribed in primary care. We investigated the effectiveness and rate of adverse events of these medicines in the general population.To estimate the effect of prescribing varenicline on smoking cessation rates and health outcomes.Clinical Practice Research Datalink.We conducted an observational cohort study using electronic medical records from the Clinical Practice Research Datalink. We extracted data on all patients who were prescribed varenicline or nicotine replacement therapy after 1 September 2006 who were aged ≥ 18 years. We investigated the effects of varenicline on smoking cessation, all-cause mortality and cause-specific mortality and hospitalisation for: (1) chronic lung disease, (2) lung cancer, (3) coronary heart disease, (4) pneumonia, (5) cerebrovascular disease, (6) diabetes, and (7) external causes; primary care diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression, or prescription for anxiety; weight in kg; general practitioner and hospital attendance. Our primary outcome was smoking cessation 2 years after the first prescription. We investigated the baseline differences between patients prescribed varenicline and patients prescribed nicotine replacement therapy. We report results using multivariable-adjusted, propensity score and instrumental variable regression. Finally, we developed methods to assess the relative bias of the different statistical methods we used.People prescribed varenicline were healthier at baseline than those prescribed nicotine replacement therapy in almost all characteristics, which highlighted the potential for residual confounding. Our instrumental variable analysis results found little evidence that patients prescribed varenicline had lower mortality 2 years after their first prescription (risk difference 0.67, 95% confidence interval -0.11 to 1.46) than those prescribed nicotine replacement therapy. They had similar rates of all-cause hospitalisation, incident primary care diagnoses of myocardial infarction and chronic obstructive pulmonary disease. People prescribed varenicline subsequently attended primary care less frequently. Patients prescribed varenicline were more likely (odds ratio 1.46, 95% confidence interval 1.42 to 1.50) to be abstinent 6 months after treatment than those prescribed nicotine replacement therapy when estimated using multivariable-adjusted for baseline covariates. Patients from more deprived areas were less likely to be prescribed varenicline. However, varenicline had similar effectiveness for these groups.Patients prescribed varenicline in primary care were more likely to quit smoking than those prescribed nicotine replacement therapy, but there was little evidence that they had lower rates of mortality or morbidity in the 4 years following the first prescription. There was little evidence of heterogeneity in effectiveness across the population.Future research should investigate the decline in prescribing of smoking cessation products; develop an optimal treatment algorithm for smoking cessation; use methods for using instruments with survival outcomes; and develop methods for comparing multivariable-adjusted and instrumental variable estimates.Not all of our code lists were validated, body mass index and Index of Multiple Deprivation had missing values, our results may suffer from residual confounding, and we had no information on treatment adherence.This trial is registered as NCT02681848.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inSmoking is the number one avoidable cause of ill health and death. Experiments suggest that more smokers will quit after being given the drug varenicline than with any other smoking cessation treatment. However, most of the experiments used to license varenicline had a relatively short follow-up ( 1 year) and did not necessarily recruit participants who were representative of smokers seen in a general practice in the UK, who tend to be older, are sicker and more likely to have neuropsychiatric illnesses. In this study, we investigated the outcomes of 287,079 patients prescribed varenicline or nicotine replacement therapy (e.g. nicotine patches and gum). We followed each patient for up to 4 years after they received their prescriptions and matched their data to information on deaths from the Office for National Statistics and hospital admissions. We investigated how often these patients subsequently attended their general practitioner, and how often they received a diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression or anxiety in primary care. We found that patients who were prescribed varenicline were much more likely to quit smoking up to 4 years after they received treatment and subsequently attended their general practitioner less frequently. These findings were robust across the three different analysis methods we used. We also found that patients prescribed varenicline were much less likely to be ill or to die than those prescribed nicotine replacement therapy. However, these results may be because the patients who were prescribed varenicline were much healthier before they received the prescription. Therefore, these differences in health are unlikely to be caused by taking varenicline or quitting smoking. In conclusion, varenicline helped patients quit smoking, but there was little causal evidence that prescribing patients varenicline causally reduced rates of mortality or morbidity compared with prescribing nicotine replacement therapy.

Whilst the goal of intensive care is to maintain life and ideally restore a person’s health through complex management of multiple bodily systems, an unintended consequence of these interventions is a loss of awareness and control of their unfamiliar environment. Our ability to speak enables us to manipulate and modify the information we receive, to help the process of adaptation. With technological advancements, many more people are surviving ICU although many report distorted memories and traumatic experiences often through the lack of being able to speak to the people around them, to verify their thoughts and allay their fears and anxieties. Facilitating communication is an important role for all healthcare staff, and the skill and expertise of speech and language therapists (SLT) can help to maximise opportunities for effective communication through either verbal or non-verbal means. In turn, this improves the quality of the experience of intensive care and aids psychological and emotional recovery alongside physical improvement. This chapter shares the importance of communication, the impact of communication impairment on the patient and those around them, and provides a range of methods to support communication.

Background and aimsVarenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care.DesignCase–cross‐over study.SettingUK‐based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality data sets.ParticipantsAdult smokers observed during periods when exposed and not exposed to either varenicline or NRT.MeasurementsMain outcomes included suicide, self‐harm, myocardial infarction (MI), all‐cause death and cause‐specific death [MI, chronic obstructive pulmonary disease (COPD)]. In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure during the risk period (90 days prior to the event) with the chance of exposure during an earlier single reference period (91–180 days prior to the event) or multiple 90‐day reference periods to increase statistical power.FindingsIn the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, while NRT was associated with MI [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.18–1.67]. Using multiple reference periods, varenicline was associated with an increased risk of self‐harm (OR = 1.32, 95% CI = 1.12–1.56) and suicide (OR = 3.56, 95% CI = 1.32–9.60) but a reduction in all‐cause death (OR = 0.75, 95% CI = 0.61–0.93). NRT was associated with MI (OR = 1.54, 95% CI = 1.36–1.74), self‐harm (OR = 1.30, 95% CI = 1.18–1.44) and deaths from MI (OR = 1.53, 95% CI = 1.11–2.10), COPD (OR = 1.33, 95% CI = 1.14–1.56) and all causes (OR = 1.28, 95% CI = 1.18–1.40) when using multiple reference periods.ConclusionsThere appear to be positive associations between (1) nicotine replacement therapy (NRT) and myocardial infarction, death and risk of self‐harm and (2) varenicline and increased risk of self‐harm and suicide, as well as a negative association between varenicline and all‐cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (nicotine replacement therapy is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self‐harm).

Rationale: Despite its widespread use in oncology, the PET radiotracer 18F-FDG is ineffectivefor improving early detection of pancreatic ductal adenocarcinoma (PDAC). An alternative strategy for early detection of pancreatic cancer involves visualisation of high-grade pancreatic intraepithelial neoplasias (PanIN-3), generally regarded as the non-invasive precursors of PDAC. The DNA damage response is known to be hyper-activated in late-stage PanINs. Therefore, we investigated whether the SPECT imaging agent, 111In-anti-γH2AX-TAT, allows visualisation of the DNA damage repair marker γH2AX in PanIN-3s in an engineered mouse model of PDAC, to facilitate early detection of PDAC. Methods: Genetically engineered KPC mice (KRasLSL.G12D/+; p53LSL.R172H/+; PdxCre) were imaged with 18F-FDG and 111In-anti-γH2AX-TAT. PanIN/PDAC presence visualised by histology was compared with autoradiography and immunofluorescence. Separately, the survival of KPC mice imaged with 111In-anti-γH2AX-TAT was evaluated. Results: In KPC mouse pancreata, γH2AX expression was increased in high-grade PanINs, but not in PDAC, corroborating earlier results obtained from human pancreas sections. Uptake of 111In-anti-γH2AX-TAT, but not 111In-IgG-TAT or 18F-FDG, within the pancreas was positively correlated with the age of KPC mice, which was correlated with the number of highgrade PanINs. 111In-anti-γH2AX-TAT localises preferentially in high-grade PanIN lesions, but not in established PDAC. Younger, non-tumour-bearing KPC mice that show uptake of 111Inanti-γH2AX-TAT in the pancreas survive significantly shorter than mice with physiological 111In-anti-γH2AX-TAT uptake. Conclusion: 111In-anti-γH2AX-TAT imaging allows non-invasive detection of DNA damage repair signalling upregulation in pre-invasive PanIN lesions and is a promising new tool to aid in the early detection and staging of pancreatic cancer.

This study aimed to determine the effectiveness and safety of varenicline versus NRT for smoking cessation in people with neurodevelopmental disorders, compared to those without, at up to four years after exposure. We analysed electronic medical records from the Clinical Practice Research Datalink using three different statistical approaches: multivariable logistic regression, propensity score matching (PSM), and instrumental variable analysis. Exposure was prescription of varenicline versus NRT and the primary outcome was smoking cessation at 2-years. We included 235,314 people aged 18 and above with eligible smoking cessation prescriptions in the effectiveness analysis. Smokers with neurodevelopmental disorders were 48% less likely (95% confidence interval: 42%, 54%) to be prescribed varenicline than NRT, compared to smokers without neurodevelopmental disorders. At 2-year follow-up, smokers with neurodevelopmental disorders prescribed varenicline were 38% more likely to quit smoking (95% confidence interval: 6%, 78%). Similar results were obtained using PSM and instrumental variable analyses. There was little evidence showing that varenicline increased the likelihood of mental health related adverse events in people with neurodevelopmental disorders. Varenicline is less likely to be prescribed to people with neurodevelopmental disorders despite results suggesting it is more effective than NRT and little evidence of increased likelihood of mental health related adverse events.

Objectives Laryngotracheal stenosis is a rare condition characterized by upper airway narrowing. Reconstructive surgical treatment aims to manage the area of stenosis to improve dyspnea and can impact voice and swallowing function. This article critically evaluates the literature about voice and swallowing outcomes in adults with laryngotracheal stenosis who undergo reconstructive surgery. Study design Systematic review. Methods Six databases were searched for articles referring to voice and swallowing outcome measures following reconstruction procedures in adults with laryngotracheal stenosis. Screening was completed using predefined inclusion/exclusion criteria. Results A total of 143 abstracts were reviewed, with 67 articles selected for full-text review. Twenty studies met the inclusion criteria. Data extraction was completed with the Strengthening Reporting of Observational Studies in Epidemiology checklist with Oxford Centre for Evidence-Based Medicine Level of Evidence used to indicate quality. Risk of bias was assessed using the Risk of Bias Assessment Tool for Non-Randomized Studies. All studies scored a high risk of bias in at least one of the domains. Selection and timing of outcome measures was heterogenous, and there was limited information provided about rationale or reliability. Conclusions The literature acknowledges the importance of voice and swallowing outcomes following airway reconstruction. Studies show correlation between reconstructive surgery and deterioration in vocal function; there are no consistent data about swallowing outcomes. The lack of a core outcome measures set for adults with laryngotracheal stenosis limits the findings of this review. Further research is needed to establish clear criteria for robust and clinically relevant outcome measurement. Laryngoscope, 131:146-157, 2021.

There are increasing numbers of children presenting to paediatric hospital settings in mental health crisis. Typically, non-mental health professionals are responsible for the initial assessment of these children and are required to identify immediate physical and emotional health needs. To ensure the safety of these children, immediate risk of suicide and self-harm should be assessed. However, no standardized assessment tool is used in clinical practice, and for those tools that are used, their validity and reliability is unclear. A scoping review was conducted to identify the existing assessment tools of immediate self-harm and suicide risk. Searches of electronic databases and relevant reference lists were undertaken. Twenty-two tools were identified and most assessed acute risk of suicide with only four tools incorporating a self-harm assessment. The tools varied in number of items (4–146), subscales (0–11) and total scores (16–192). Half incorporated Likert-type scales, and most were completed via self-report. Many tools were subject to limited psychometric testing, and no single tool was valid or reliable for use with children presenting in mental health crisis to non-mental health settings. As such, a clinically appropriate, valid and reliable tool that assesses immediate risk of self-harm and suicide in paediatric settings should be developed.

Aims To investigate whether smokers prescribed varenicline had lower risks of serious ill-health during the 4 years following treatment compared with those prescribed nicotine replacement therapy (NRT). Design Observational cohort study of electronic medical records. Setting A total of 370 UK general practices sampled from the Clinical Practice Research Datalink. Participants A total of 126 718 patients aged 18 and over who were issued smoking cessation prescriptions between 1 September 2006 and 31 March 2014. Measurements Our primary outcome was all-cause mortality within 2 years of first prescription as indicated by linked Office of National Statistics data. Our secondary outcomes were cause-specific mortality, all-cause, cause-specific hospitalization, primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease (COPD), body mass index and attendance rate to primary care within 2 years of first prescription. Risk differences and 95% confidence intervals were estimated by multivariable adjusted regression and propensity score matched regression. We used instrumental variable analysis to overcome residual confounding. Findings People prescribed varenicline were healthier at baseline than those prescribed NRT in almost all characteristics, highlighting the potential for residual confounding. Our instrumental variable analysis results found that people prescribed varenicline had a similar risk of mortality at 2 years [risk difference per 100 patients treated = 0.67, 95% confidence interval (CI) = -0.11 to 1.46)] to those prescribed NRT, and there were similar rates of all-cause hospitalization, incident primary-care diagnoses of myocardial infarction and COPD. People prescribed varenicline subsequently attended primary care less frequently. Conclusions Smokers prescribed varenicline in primary care in the United Kingdom do not appear to be less likely to die, be hospitalized or experience a myocardial infarction or chronic obstructive pulmonary disease during the following 2 years compared with smokers prescribed nicotine replacement therapy, but they gain more weight and attend primary care less frequently.

Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130–2.794), premature birth (OR 1.34; 95% CI 1.060–1.690), gestational diabetes (OR 1.24; 95% CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.

Introduction There is some evidence suggesting that patients with hypersomnia have delayed circadian timing, which could explain, at least in part, the excessive sleepiness and impaired daytime performance experienced by these individuals. This study investigated the effects of bright light treatment on improving daytime alertness in patients with idiopathic hypersomnia. Methods Participants were scheduled to two in-laboratory sessions (baseline and treatment) consisting of overnight sleep monitoring (polysomnography) followed by maintenance of wakefulness tests (MWT) and performance testing (10-min psychomotor vigilance task (PVT)). MWTs were performed at 10:00, 12:00, 14:00 and 16:00 and PVTs were performed at 11:00, 13:00, 15:00 and 15:00. In-laboratory sessions were separated by a two-week at-home treatment period during which participants were instructed to use commercially available light devices for 30-60 min each morning. Participants also completed the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) at baseline and after treatment. Paired t-tests were performed to assess differences in sleep architecture, sleep quality, performance (lapses; reaction time >500ms) and alertness (MWT mean sleep latency) between baseline and treatment. Results To date, three participants (2 male) aged 62.7±13.2 (mean±SD) years have completed the study. Lapses (baseline: 17.9±11.9; treatment: 6.3±5.4), ESS (baseline: 17.3±3.1; treatment 12.3±6.8) and PSQI (baseline: 7.7±3.8; treatment: 4.0±1.0) all improved with light treatment, although this did not reach statistical significance. There were no statistical differences between baseline and treatment with regards to sleep architecture or mean sleep latency. Conclusion Although preliminary, results suggest that bright light treatment may improve subjective sleepiness, subjective sleep quality and performance. There was some variability between individuals, indicating that this treatment may not offer the same benefits to all patients. Although ongoing, this study suggests that light therapy could be used as an alternative, non-pharmacological treatment option to improve waking functions and sleepiness in hypersomnia patients. Support This project is supported by a Hunter Medical Research Institute Research Project Grant

Background: Sleep apnoea is prevalent in dialysis patients. Previous studies identified excessive inflammation in ­patients with sleep apnoea. Online haemodiafiltration ­(OL-HDF) may reduce systematic inflammation through better clearance of middle molecules. We aimed to determine the feasibility of OL-HDF in sleep apnoea management. Methods: Eligible dialysis patients were screened for risk of sleep apnoea by nocturnal oximetry followed by a diagnostic sleep study to assess apnoea-hypopnea index (AHI). Patients with AHI ≥15/h were invited to a randomized crossover trial. The intervention was 2-month high-flux haemodialysis (HF-HD) followed by 2-month OL-HDF or vice versa with 1-month washout via HF-HD. Feasibility was assessed by patient recruitment and the primary outcome, severity of sleep apnoea (AHI). Secondary outcomes were pro-inflammatory cytokines, patient-reported daytime sleepiness, quality of sleep and health-related quality of life. Results: Of 65 participants at risk of sleep apnoea, only 15 were consented and randomized (mean age 70 years, 80% male, mean AHI 42.2/h). AHI was not statistically different between OL-HDF versus HF-HD (55.6/h vs. 48.3/h, p = 0.134); however, when sleep apnoea was stratified into obstructive and central apnoea, patients had less obstructive episodes after treated by OL-HDF (23.2/h vs. 18.6/h, p = 0.178); a sensitivity analysis was performed excluding outliers, and the treatment effect for obstructive episodes was found to be statistically significant (11.1 vs. 18.2/h, p = 0.019). Pro-inflammatory biomarkers and patient-reported outcomes were similar between OL-HDF and HF-HD. Conclusion: Patient recruitment was a major challenge in this feasibility study. OL-HDF may reduce obstructive sleep apnoea; however, the result needs to be confirmed by larger studies.

IntroductionSmoking among persons with a mental health disorder is associated with inequitable health, social and economic burden. Randomised controlled trials (RCTs) are considered the gold standard design for the assessment of healthcare intervention efficacy/effectiveness. However, many RCTs of smoking interventions for persons with a mental health disorder lack rigour due to low participant retention. No systematic review has pooled retention rates in randomised trials of smoking interventions for persons with a mental health disorder or explored associated factors. The aims of the systematic review will therefore be to: (1) summarise overall rates of participant retention in smoking cessation and reduction trials involving persons with a mental health disorder (including for experimental and control groups separately) and (2) determine if retention rates vary according to participant, environmental, researcher and study factors.Methods and analysisPsycINFO, EMBASE, MEDLINE, CENTRAL and The Cochrane Tobacco Addiction Review Group Specialised Register will be searched for reports of RCTs of outpatient smoking cessation or reduction interventions for adults with a mental health disorder. The search terms will include MeSH terms and free text words, and there will be no language or date restrictions. All databases will be searched from inception to present. Data will be analysed using the Mantel-Haenszel fixed-effect model, and where substantial heterogeneity (I2>50%) is detected, DerSimonian & Laird inverse-variance random effects model. Pooled estimates and 95% CIs will be calculated for overall participant retention rates and for intervention and control trial arms separately. Associations between participant retention and participant, environmental, researcher and study factors will be assessed via subgroup analyses and, where sufficient data are obtained, meta-regression.Ethics and disseminationThis study does not require ethical approval. The findings of this review will be disseminated via publication in a peer-reviewed open access medical journal and presentations at international scientific meetings.

ObjectivesOur primary objective was to estimate smoking prevalence and prescribing rates of varenicline and nicotine replacement therapy (NRT) in people with and without general practitioner (GP)-recorded dementia. Our secondary objective was to assess and compare quit rates of smokers with versus without GP-recorded dementia who were prescribed varenicline or NRT for smoking cessation.DesignA retrospective cohort study based on the analysis of electronic medical records within the Clinical Practice Research Datalink (2007–2015).Setting683 general practices in England.ParticipantsPeople with and without GP-recorded dementia, aged 18 years and have a code indicating that they are a current smoker.InterventionIndex prescription of varenicline or NRT (from 1 September 2006).Outcome measuresThe primary outcomes were smoking prevalence and prescribing rates of varenicline and NRT (2007–2015). The secondary outcome was smoking cessation at 2 years.ResultsAge and sex-standardised prevalence of smoking was slightly higher in people with GP-recorded dementia than in those without. There were 235 314 people aged 18 years and above prescribed NRT or varenicline. Among smokers with GP-recorded dementia (N=447), 409 were prescribed NRT and 38 varenicline. Smokers with GP-recorded dementia were 74% less likely (95% CI 64% to 82%) to be prescribed varenicline than NRT, compared with smokers without GP-recorded dementia. Compared with people without GP-recorded dementia, people with GP-recorded dementia had consistently lower prescribing rates of varenicline from 2007 to 2015. Two years after prescription, there was no clear evidence for a difference in the likelihood of smoking cessation after prescription of these medications between individuals with and without dementia (OR 1.0, 95% CI 0.8 to 1.2).ConclusionsBetween 2007 and 2015, people with GP-recorded dementia were less likely to be prescribed varenicline than those without dementia. Quit rates following prescription of either NRT or varenicline were similar in those with and without dementia.

Objective We conducted a prospective cohort study of the Clinical Practice Research Database to estimate rates of varenicline and nicotine replacement therapy (NRT) prescribing and the relative effects on smoking cessation, and mental health. Methods We used multivariable logistic regression, propensity score matched regression, and instrumental variable analysis. Exposure was varenicline or NRT prescription. Mental disorders were bipolar, depression, neurotic disorder, schizophrenia, or prescriptions of antidepressants, antipsychotics, hypnotics/anxiolytics, mood stabilizers. Outcomes were smoking cessation, and incidence of neurotic disorder, depression, prescription of antidepressants, or hypnotics/anxiolytics. Follow-ups were 3, 6, and 9 months, and at 1, 2, and 4 years. Results In all patients, NRT and varenicline prescribing declined during the study period. Seventy-eight thousand four hundred fifty-seven smokers with mental disorders aged ≥18 years were prescribed NRT (N = 59 340) or varenicline (N = 19 117) from September 1, 2006 to December 31, 2015. Compared with smokers without mental disorders, smokers with mental disorders had 31% (95% CI: 29% to 33%) lower odds of being prescribed varenicline relative to NRT, but had 19% (95% CI: 15% to 24%) greater odds of quitting at 2 years when prescribed varenicline relative to NRT. Overall, varenicline was associated with decreased or similar odds of worse mental health outcomes than NRT in patients both with and without mental disorders, although there was some variation when analyses were stratified by mental disorder subgroup. Conclusions Smoking cessation medication prescribing may be declining in primary care. Varenicline was more effective than NRT for smoking cessation in patients with mental disorders and there is not clear consistent evidence that varenicline is adversely associated with poorer mental health outcomes. Implications Patients with mental disorders were less likely to be prescribed varenicline than NRT. We triangulated results from three analytical techniques. We found that varenicline was more effective than NRT for smoking cessation in patients with mental disorders. Varenicline was generally associated with similar or decreased odds of poorer mental health outcomes (ie, improvements in mental health) when compared with NRT. We report these findings cautiously as our data are observational and are at risk of confounding.

ObjectiveTo examine the direction and magnitude of the relation between family meal frequency and dietary and family functioning outcomes in children (aged 2–18 years).DesignSystematic literature review with meta-analysis.MethodsIndependent electronic searches, 1 for each outcome of interest, were conducted across 5 databases: PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, and PsycINFO. Studies were included if they were peer-reviewed and published in English in the US through December 2018.Main Outcome MeasuresDiet and family functioning.ResultsDietary outcomes showed some evidence of a positive association between family meal frequency and fruits, vegetables, fruits and vegetables, sugar-sweetened beverages, and the Healthy Eating Index. There was less clear evidence of this relation in snacks, fast food, and desserts. A positive association was found between family meal frequency or dinner family meal frequency and family functioning outcomes. All studies included had cross-sectional and longitudinal study designs.Conclusions and ImplicationsThere is some evidence to show a positive relation between family meal frequency and dietary outcomes. There is stronger evidence for the relation with family functioning outcomes. Most articles included in the systematic reviews were excluded from meta-analysis owing to inadequate data and high methodological diversity across exposure and outcome variables.

Highlights • Beta rebound (PMBR) is reduced in recent-onset and established schizophrenia cases • In established cases, PMBR is negatively correlated with disorganisation symptoms • Hidden Markov model shows different transient pan-spectral bursts underlying PMBR., Magnetoencephalography (MEG) measures magnetic fields generated by synchronised neural current flow and provides direct inference on brain electrophysiology and connectivity, with high spatial and temporal resolution. The movement-related beta decrease (MRBD) and the post-movement beta rebound (PMBR) are well-characterised effects in magnetoencephalography (MEG), with the latter having been shown to relate to long-range network integrity. Our previous work has shown that the PMBR is diminished (relative to controls) in a group of schizophrenia patients. However, little is known about how this effect might differ in patients at different stages of illness and degrees of clinical severity. Here, we extend our previous findings showing that the MEG derived PMBR abnormality in schizophrenia exists in 29 recent-onset and 35 established cases (i.e., chronic patients), compared to 42 control cases. In established cases, PMBR is negatively correlated with severity of disorganization symptoms. Further, using a hidden Markov model analysis, we show that transient pan-spectral oscillatory ”bursts”, which underlie the PMBR, differ between healthy controls and patients. Results corroborate that PMBR is associated with disorganization of mental activity in schizophrenia.

A major barrier to clinicians referring service users with psychosis for psychological therapies is the belief that they will not engage. We investigated therapy receipt after discharge, in a sample of service users who had already demonstrated willingness to engage in psychological therapy during an inpatient admission. Only one-third of service users (33%; 16/48) received at least 1 session of evidence-based therapy at 6-month follow-up after discharge. Therapy receipt was more common for service users with (i) lower delusional distress at discharge, (ii) Black and Minority Ethnic (BME) background, and (iii) discharged to an Early Intervention (EI) service.

Introduction Heparin is commonly used after hemodialysis treatments as a locking solution to prevent catheter thrombosis. The comparative efficacy and safety of different heparin concentrations to maintain catheter patency has been previously reported in retrospective studies. We conducted a prospective, randomised, controlled study of 1000 U/mL heparin (low dose) versus 5000 U/mL heparin (high dose) locking solution to maintain patency of tunnelled catheters. Methods One hundred patients receiving chronic, unit-based hemodialysis with newly placed tunnelled hemodialysis catheters (less than 1 week) were randomly assigned to either a low dose (n = 48) or high dose heparin (n=52). The primary intention-to-treat analysis examined time to malfunction in both groups over a 90 day period. A secondary analysis compared baseline patient characteristics in relation to catheter malfunction. Findings Overall rate of catheter patency loss was 32% of catheters by 90 days. There was no significant difference in time to malfunction of catheters locked with low dose or high dose heparin (P = 0.5770). Time to catheter malfunction was not associated with diabetic, hypertensive or smoking status. There was no difference in mean delivered blood flow rate, venous and arterial pressure, and dialysis adequacy between low dose and high dose groups. No patient suffered a hemorrhagic complication requiring hospitalisation during the study period. Discussion Low dose heparin is adequate to maintain tunnelled hemodialysis catheter patency when compared with high dose heparin. The study also suggests that there is no relationship between catheter malfunction and diabetic, hypertensive or smoking status.

Purpose: This article presents a detailed review of the etiology of laryngotracheal stenosis, common surgical procedures, and typical pathophysiological changes affecting swallowing function. We describe the redundancy in airway protection and the possibility of safe swallowing in suboptimal conditions. Conclusion: Comprehensive understanding of unique patient factors and swallowing physiology in this complex population facilitates targeted and patient-specific rehabilitation.