Mask wearing in community settings reduces SARS-CoV-2 transmission.

The effectiveness of mask wearing at controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been unclear. While masks are known to substantially reduce disease transmission in healthcare settings [D. K. Chu et al., Lancet 395, 1973­1987 (2020); J. Howard et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2014564118 (2021); Y. Cheng et al., Science eabg6296 (2021)], studies in community settings report inconsistent results [H. M. Ollila et al., medRxiv (2020); J. Brainard et al., Eurosurveillance 25, 2000725 (2020); T. Jefferson et al., Cochrane Database Syst. Rev. 11, CD006207 (2020)]. Most such studies focus on how masks impact transmission, by analyzing how effective government mask mandates are. However, we find that widespread voluntary mask wearing, and other data limitations, make mandate effectiveness a poor proxy for mask-wearing effectiveness. We directly analyze the effect of mask wearing on SARS-CoV-2 transmission, drawing on several datasets covering 92 regions on six continents, including the largest survey of wearing behavior (n= 20 million) [F. Kreuter et al., https://gisumd.github.io/COVID-19-API-Documentation (2020)]. Using a Bayesian hierarchical model, we estimate the effect of mask wearing on transmission, by linking reported wearing levels to reported cases in each region, while adjusting for mobility and nonpharmaceutical interventions (NPIs), such as bans on large gatherings. Our estimates imply that the mean observed level of mask wearing corresponds to a 19% decrease in the reproduction number R. We also assess the robustness of our results in 60 tests spanning 20 sensitivity analyses. In light of these results, policy makers can effectively reduce transmission by intervening to increase mask wearing.

Surface-normal illuminated pseudo-planar Ge-on-Si avalanche photodiodes with high gain and low noise.

Germanium-on-Silicon (Ge-on-Si) avalanche photodiodes (APDs) are of considerable interest as low intensity light detectors for emerging applications. The Ge absorption layer detects light at wavelengths up to ≈ 1600 nm with the Si acting as an avalanche medium, providing high gain with low excess avalanche noise. Such APDs are typically used in waveguide configurations as growing a sufficiently thick Ge absorbing layer is challenging. Here, we report on a new vertically illuminated pseudo-planar Ge-on-Si APD design utilizing a 2 µm thick Ge absorber and a 1.4 µm thick Si multiplication region. At a wavelength of 1550 nm, 50 µm diameter devices show a responsivity of 0.41 A/W at unity gain, a maximum avalanche gain of 101 and an excess noise factor of 3.1 at a gain of 20. This excess noise factor represents a record low noise for all configurations of Ge-on-Si APDs. These APDs can be inexpensively manufactured and have potential integration in silicon photonic platforms allowing use in a variety of applications requiring high-sensitivity detectors at wavelengths around 1550 nm.

Harm Perceptions of E-cigarettes Among Smokers With and Without Mental Health Conditions in England: A Cross-Sectional Population Survey.

INTRODUCTION: E-cigarettes (ECs) may benefit smokers with mental health conditions who are more likely to smoke, and smoke more heavily, than those without mental health conditions. This could be undermined if harm misperceptions in this group are high as is the case in the general population. This study aimed to assess EC harm perceptions relative to cigarettes as a function of mental health status and a variety of characteristics. METHODS: Data were collected from 6531 current smokers in 2016/2017 in household surveys of representative samples of adults. The associations of mental health status (self-reported mental health condition and past year treatment), smoking and EC use characteristics, and characteristics relating to use of potential information sources with harm perceptions of ECs relative to cigarettes (measured by correct response "less harmful" vs. wrong responses "more harmful," "equally harmful," "don't know") were analyzed with logistic regression. RESULTS: A similar proportion of smokers without mental health conditions (61.5%, 95% CI 60.1-62.9) and with mental health conditions (both with [61.3%, 95% confidence interval [CI] 58.7-63.8] and without past year treatment [61.5%, 95% CI 58.1-64.7]) held inaccurate EC harm perceptions (all P > 0.05). Being female, nonwhite, aged 25-34 compared with 16-24, from lower social grades (C2, D, and E), not having post-16 qualifications, no EC experience, a daily smoker, unmotivated to quit <1 month, non-internet user and non-broadsheet reader were all associated with more inaccurate harm perceptions (all p < .05). CONCLUSIONS: The majority of smokers in England have inaccurate harm perceptions of ECs regardless of mental health status. IMPLICATIONS: This study is the first to use a nationally representative sample in order to investigate whether smokers with and without mental health conditions differ with regard to harm perceptions of ECs. Findings show that the majority of smokers in England hold inaccurate harm perceptions of ECs, and this does not differ as a function of mental health status. A number of characteristics associated with disadvantaged groups were significantly associated with inaccurate harm perceptions. These findings highlight the need to improve awareness and understanding among disadvantaged groups regarding the relative harms of ECs compared with tobacco.

Exploring mental health professionals' practice in relation to smoke-free policy within a mental health trust: a qualitative study using the COM-B model of behaviour.

BACKGROUND: Smoking has played a significant role in the historical culture of mental healthcare settings. Mental health professionals (MHPs) often hold dismissive attitudes regarding the importance of smoking cessation in the context of mental healthcare. In 2007, English mental health inpatient buildings were required by law to become smoke-free, and healthcare trusts have more recently begun to implement comprehensive policies (i.e. smoke-free grounds and buildings) and staff training in response to national guidance. It is therefore important to explore MHPs practice around smoking, smoking cessation, and smoke-free policy adherence. This study aimed to explore these issues by using the COM-B (capability, opportunity, motivation, behaviour) model to systematically identify barriers to, and facilitators for, MHPs addressing smoking with their patients. METHODS: Five focus groups with a total of 36 MHPs were conducted between March and August 2017. MHPs were recruited from one of the largest mental health trusts in Europe. Discussions were guided by a semi-structured guide. Responses were audio recorded, transcribed and coded using thematic analysis and the COM-B framework. RESULTS: Addressing smoking with patients was undermined by MHPs' 1) psychological capability to recall training content, misunderstand the potential benefits of addressing patient smoking and harm reduction approaches; 2) physical opportunity in terms of time constraints, and easy accessibility of tobacco in the community; 3) social opportunity in terms of increased cultural value of tobacco following inpatient smoke-free policy implementation, and lack of support from colleagues to enforce the smoke-free policy; 4) automatic motivation, including intrinsic biases regarding patients abilities and motivations to quit, and 5) reflective motivation, including perceived job role and decision making processes related to addressing behaviours deemed more important than smoking. The main facilitating factors identified were MHPs' having opportunity in the form of patients asking directly for support, and MHPs having access to resources such as stop smoking services and spirometers. CONCLUSION: Multiple barriers were identified across all key domains of the COM-B framework that undermine MHPs' practice regarding smoking cessation. Few facilitators were identified which may have implications for future smoke-free policy and clinical practice.

Factors Associated With the Mental Health and Satisfaction of Oral and Maxillofacial Surgery Residents in the United States: A Cross-Sectional Study and Analysis.

PURPOSE: Residents in training have reported high levels of stress and anxiety and have a greater risk of mental health problems compared with the general population. Mental health problems among residents have been correlated with decreased professional effectiveness, increased medical errors, emotional exhaustion, and depersonalization and could have significant negative effects on future practitioners. The purpose of the present study was to identify the factors that might be associated with the mental health and satisfaction of oral and maxillofacial surgery (OMS) residents and to determine the associations between these factors and OMS resident satisfaction as a surrogate of resident well-being. MATERIALS AND METHODS: We designed and implemented an online survey, which was e-mailed to all OMS residents in the 101 accredited training programs in the United States. The survey was designed to determine and assess the factors associated with OMS resident satisfaction. Differences between groups were tested using 1-way analysis of variance for continuous variables and χ2 tests for categorical variables. For each factor, we fit a logistic regression model to estimate the odds ratio of resident satisfaction for the factor, adjusting for gender, year in residency, and years of advanced training. RESULTS: Of the 1181 resident surveys sent out, 300 were completed (25.4% response rate). The satisfied OMS residents tended to be men, further along in their training program, and to have access to mental health resources. Dissatisfaction was associated with greater self-reported stress levels, working a greater number of hours per week, and believing one would be viewed differently for speaking to faculty about mental health. CONCLUSIONS: OMS resident satisfaction was associated with identifiable and potentially modifiable factors. These factors included workload characteristics, stress and coping ability, and mental health impact and resource availability. Evidence-based strategies for OMS resident well-being could lead to the development of best practice guidelines for promoting and optimizing resident mental health.

IQGAP2 is a novel interferon-alpha antiviral effector gene acting non-conventionally through the NF-κB pathway.

BACKGROUND & AIMS: Type I interferons (IFN) provide the first line of defense against invading pathogens but its mechanism of action is still not well understood. Using unbiased genome-wide siRNA screens, we recently identified IQ-motif containing GTPase activating protein 2 (IQGAP2), a tumor suppressor predominantly expressed in the liver, as a novel gene putatively required for IFN antiviral response against hepatitis C virus (HCV) infection. Here we sought to characterize IQGAP2 role in IFN response. METHODS: We used transient small interfering RNA knockdown strategy in hepatic cell lines highly permissive to JFH1 strain of HCV infection. RESULTS: We found that IQGAP2 acts downstream of IFN binding to its receptor, and independently of the JAK-STAT pathway, by physically interacting with RelA (also known as p65), a subunit of the NF-κB transcription factor. Interestingly, our data reveal a mechanism distinct from the well-characterized role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in IFN production. Indeed, IFN alone was sufficient to stimulate NF-κB-dependent transcription in the absence of viral infection. Finally, both IQGAP2 and RelA were required for the induction by IFN of a subset of IFN-stimulated genes (ISG) with known antiviral properties. CONCLUSIONS: Our data identify a novel function for IQGAP2 in IFN antiviral response in hepatoma cells. We demonstrate the involvement of IQGAP2 in regulating ISG induction by IFN in an NF-κB-dependent manner. The IQGAP2 pathway may provide new targets for antiviral strategies in the liver, and may have a wider therapeutic implication in other disease pathogeneses driven by NF-κB activation. LAY SUMMARY: In this study, we identify a novel mechanism of action of interferon involving the IQGAP2 protein and the NF-κB pathway that is ultimately protective against hepatitis C virus infection. This newly identified pathway functions independently of the well-known STAT pathway and may therefore provide new targets for antiviral strategies in the liver.

Megalocytivirus infection in cultured Nile tilapia Oreochromis niloticus.

Megalocytiviruses, such as infectious spleen and kidney necrosis virus (ISKNV), induce lethal systemic diseases in both ornamental and food fish species. In this study, we investigated an epizootic affecting Nile tilapia Oreochromis niloticus cultured in the US Midwest. Diseased fish displayed lethargy, gill pallor, and distension of the coelomic cavity due to ascites. Histopathological examination revealed a severe systemic abundance of intravascular megalocytes that were especially prominent in the gills, kidney, spleen, liver, and intestinal submucosa. Transmission electron microscopic examination revealed abundant intracytoplasmic polygonal virions consistent with iridovirus infection. Comparison of the full-length major capsid protein nucleotide sequences from a recent outbreak with a remarkably similar case that occurred at the same facility many years earlier revealed that both epizootics were caused by ISKNV. A comparison of this case with previous reports suggests that ISKNV may represent a greater threat to tilapia aquaculture than previously realized.

UK medical students' self-reported knowledge and harm assessment of psychedelics and their application in clinical research: a cross-sectional study.

OBJECTIVE: To capture UK medical students' self-reported knowledge and harm assessment of psychedelics and to explore the factors associated with support for changing the legal status of psychedelics to facilitate further clinical research. DESIGN: Cross-sectional, anonymous online survey of UK medical students using a non-random sampling method. SETTING: UK medical schools recognised by the General Medical Council. PARTICIPANTS: 132 medical students who had spent an average of 3.8 years (SD=1.4; range: 1-6) in medical school. RESULTS: Most students (83%) reported that they were aware of psychedelic research and only four participants (3%) said that they were not interested in learning more about this type of research. Although medical students' harm assessment of psychedelics closely aligned with that of experts, only 17% of students felt well-educated on psychedelic research. Teachings on psychedelics were only rarely encountered in their curriculum (psilocybin: 14.1 (SD=19.9), scale: 0 (never) to 100 (very often)). Time spent at medical schools was not associated with more knowledge about psychedelics (r=0.12, p=0.129). On average, this sample of medical students showed strong support for changing the legal status of psychedelics to facilitate further research into their potential clinical applications (psilocybin: 80.2 (SD=24.8), scale: 0 (strongly oppose) to 100 (strongly support)). Regression modelling indicated that greater knowledge of psychedelics (p<0.001), lower estimated harm scores (p<0.001), more time spent in medical school (p=0.024) and lower perceived effectiveness of non-pharmacological mental health treatments (p=0.044) were associated with greater support for legal status change. CONCLUSIONS: Our findings reveal a significant interest among UK medical students to learn more about psychedelic research and a strong support for further psychedelic research. Future studies are needed to examine how medical education could be refined to adequately prepare medical students for a changing healthcare landscape in which psychedelic-assisted therapy could soon be implemented in clinical practice.

Elicitation of Health State Utilities Associated with Progression from Bacillus Calmette-Guerin (BCG) Unresponsive Non-muscle Invasive Bladder Cancer (NMIBC).

OBJECTIVES: The treatments for high-grade non-muscle invasive bladder cancer (NMIBC) vary between bladder preserving intravesical approaches and radical cystectomy. The impact of these treatments on health-related quality of life may vary widely. The purpose of this study was to elicit the general public's perspective on quality of life, measured as utility scores associated with treatment for Bacillus Calmette-Guerin (BCG)-unresponsive NMIBC and disease progression, for supporting economic evaluation of newly developed treatments for NMIBC. MATERIALS AND METHODS: Part I involved the development and testing of health states describing NMIBC, which was informed by a rapid review, expert input and a patient advisor. Part II involved elicitation of societal utility values for the different health states. Time trade-off (TTO) interviews were conducted with members of the UK general public. Five health states described different NMIBC scenarios including disease recurrence and progression. Participants ranked each health state, followed by the TTO valuation exercise. Descriptors included NMIBC symptom severity, impact and treatment characteristics. RESULTS: In total, 202 members of the general public participated. The mean age was 46 (standard deviation [SD] 14.6) years. Sample mean (SD) EQ-5D-5L visual analogue scale (VAS) and index scores were 83.2 (12.3) and 0.89 (0.18), respectively. Mean utilities were 0.781 for No High-Grade Recurrence, 0.586 for High-Grade Recurrence, 0.572 for > 1-Year Post-cystectomy and 0.283 for metastatic disease. The First Year Post-cystectomy path health state had a mean utility of 0.288. Pairwise comparisons found statistically significant differences between utilities (p < 0.001), except between High-Grade Recurrence and > 1-Year Post-cystectomy (p = 0.524). There were significant differences in utility scores by age and employment status. CONCLUSION: This study provides utility scores for health states describing living with NMIBC, which is associated with a significant health-related quality-of-life burden. These values address an existing gap in available data and have the potential to be used in models evaluating the cost-effectiveness of both current and newly developed treatments for bladder cancer.

Lidocaine infusions in chronic pain management: A prospective case series analysis.

Chronic pain conditions are prevalent and cause a significant burden of disease. Intravenous lidocaine infusions have been reported to have an analgesic effect in patients with chronic neuropathic pain, but there is limited data supporting the efficacy of lidocaine across other chronic pain phenotypes. Our study aimed to evaluate the efficacy of a single infusion of intravenous lidocaine for pain relief and the impact on quality of life. We evaluated data from 74 patients with chronic pain who were treated with intravenous lidocaine at a specialist pain centre. Participants completed a questionnaire consisting of the Brief Pain Inventory (BPI) Short Form and additional EQ-5D quality of life metrics, before treatment and at follow-up. Data comparing pain severity did not demonstrate a statistically significant change after treatment when averaged across the entire patient cohort (6.15-5.88, p = .106), irrespective of gender or pain phenotype. Scores for pain interference showed statistically significant reductions following treatment (7.05-6.41, p = .023), which may have been driven through improvements in sleep (7.41-6.35, p = .001); however, these reductions are not clinically significant. The patient cohort was stratified into responders and non-responders based on >30% improvement in response to an overall impression of pain reduction question following treatment. In the 'responder' cohort, pain intensity scores showed a statistically significant reduction post-infusion (6.18-5.49, p = .0135), but no change was apparent for non-responders (6.07-6.09, p = .920). There were no differences between responders and non-responders for pain sub-types in our study. This study found no difference in pain outcomes in a cohort of patients with chronic pain, a mean of 63 days following a single lidocaine infusion. However, a specific subgroup of responders may show slight improvements in some pain outcomes that may warrant further exploration.

Patient Perspectives and Experiences of Preventive Treatments and Self-Injectable Devices for Migraine: A Focus Group Study.

BACKGROUND: Although several self-injectable preventive treatments for migraine have become available, they are not yet widely used. Thus, understanding patients' perceptions towards them is limited. OBJECTIVE: This study aimed to inform the design of a preference-elicitation instrument, which is being developed to quantify preventive treatment preferences of people with migraine. METHODS: We conducted a qualitative study involving nine in-person focus groups (three per country) in the United States, the United Kingdom, and Germany. Participants were adults (n = 47) with episodic or chronic migraine who were currently using or had used a prescription preventive treatment for migraine within the previous 5 years. During the focus groups, participants described their experiences of migraine and preventive treatments; handled and simulated self-injection using five different unbranded, fired demonstration auto-injectors and prefilled syringes; and ranked different aspects of preventive treatments by importance. Focus groups were analyzed with a focus on themes that would be feasible or meaningful to include in a subsequent preference-elicitation instrument. RESULTS: Reducing the frequency and severity of migraine attacks was consistently ranked as the most important aspect of preventive treatment. Participants expressed dissatisfaction with available daily oral preventive treatments for migraine they had previously used because they were ineffective or caused intolerable adverse events. Many participants were willing to self-inject a treatment that was effective and tolerable. When presented with devices for self-injecting a preventive treatment for migraine, participants generally preferred autoinjectors over prefilled syringes. Participants especially valued safety features such as the unlocking step and automated needle insertion, and audible and visual dose confirmation increased confidence in autoinjector use. Autoinjector needle protection mechanisms were also appreciated, especially by participants averse to needles, as the needles are not visible. CONCLUSIONS: This study highlights the fact that many people with migraine still lack access to a preventive treatment that is effective and tolerable. In addition to efficacy and safety considerations, treatment decisions may be guided by the mode of administration. In the case of self-injectable preventive treatments, key device characteristics affecting these decisions may be ease of use, comfort, and confidence in self-injection. Insights gained from this study were used to help develop a preliminary set of attributes and levels for a preference-elicitation instrument.

A dataset of non-pharmaceutical interventions on SARS-CoV-2 in Europe.

During the second half of 2020, many European governments responded to the resurging transmission of SARS-CoV-2 with wide-ranging non-pharmaceutical interventions (NPIs). These efforts were often highly targeted at the regional level and included fine-grained NPIs. This paper describes a new dataset designed for the accurate recording of NPIs in Europe's second wave to allow precise modelling of NPI effectiveness. The dataset includes interventions from 114 regions in 7 European countries during the period from the 1st August 2020 to the 9th January 2021. The paper includes NPI definitions tailored to the second wave following an exploratory data collection. Each entry has been extensively validated by semi-independent double entry, comparison with existing datasets, and, when necessary, discussion with local epidemiologists. The dataset has considerable potential for use in disentangling the effectiveness of NPIs and comparing the impact of interventions across different phases of the pandemic.

Understanding the effectiveness of government interventions against the resurgence of COVID-19 in Europe.

European governments use non-pharmaceutical interventions (NPIs) to control resurging waves of COVID-19. However, they only have outdated estimates for how effective individual NPIs were in the first wave. We estimate the effectiveness of 17 NPIs in Europe's second wave from subnational case and death data by introducing a flexible hierarchical Bayesian transmission model and collecting the largest dataset of NPI implementation dates across Europe. Business closures, educational institution closures, and gathering bans reduced transmission, but reduced it less than they did in the first wave. This difference is likely due to organisational safety measures and individual protective behaviours-such as distancing-which made various areas of public life safer and thereby reduced the effect of closing them. Specifically, we find smaller effects for closing educational institutions, suggesting that stringent safety measures made schools safer compared to the first wave. Second-wave estimates outperform previous estimates at predicting transmission in Europe's third wave.

Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England.

BACKGROUND: Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. METHODS: We examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021. FINDINGS: Across data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May. INTERPRETATION: The outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control efforts. FUNDING: National Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open Philanthropy, Academy of Medical Sciences Bill,Melinda Gates Foundation, Imperial College Healthcare NHS Trust, The Novo Nordisk Foundation, MRC Centre for Global Infectious Disease Analysis, Community Jameel, Cancer Research UK, Imperial College COVID-19 Research Fund, Medical Research Council, Wellcome Sanger Institute.

The N-terminus of Bunyamwera orthobunyavirus NSs protein is essential for interferon antagonism.

Bunyamwera virus NSs protein is involved in the inhibition of cellular transcription and the interferon (IFN) response, and it interacts with the Med8 component of Mediator. A spontaneous mutant of a recombinant NSs-deleted Bunyamwera virus (rBUNdelNSs2) was identified and characterized. This mutant virus, termed mBUNNSs22, expresses a 21 aa N-terminally truncated form of NSs. Like rBUNdelNSs2, mBUNNSs22 is attenuated in IFN-deficient cells, and to a greater extent in IFN-competent cells. Both rBUNdelNSs2 and mBUNNSs22 are potent IFN inducers and their growth can be rescued by depleting cellular IRF3. Strikingly, despite encoding an NSs protein that contains the Med8 interaction domain, mBUNNSs22 fails to block RNA polymerase II activity during infection. Overall, our data suggest that both the interaction of NSs with Med8 and a novel unidentified function of the NSs N-terminus, seem necessary for Bunyamwera virus to counteract host antiviral responses.

Cancer pain: part 2: physical, interventional and complimentary therapies; management in the community; acute, treatment-related and complex cancer pain: a perspective from the British Pain Society endorsed by the UK Association of Palliative Medicine and the Royal College of General Practitioners.

OBJECTIVE: This discussion document about the management of cancer pain is written from the pain specialists' perspective in order to provoke thought and interest in a multimodal approach to the management of cancer pain, not just towards the end of life, but pain at diagnosis, as a consequence of cancer therapies, and in cancer survivors. It relates the science of pain to the clinical setting and explains the role of psychological, physical, interventional and complementary therapies in cancer pain. METHODS: This document has been produced by a consensus group of relevant healthcare professionals in the United Kingdom and patients' representatives making reference to the current body of evidence relating to cancer pain. In the second of two parts, physical, invasive and complementary cancer pain therapies; treatment in the community; acute, treatment-related and complex cancer pain are considered. CONCLUSIONS: It is recognized that the World Health Organization (WHO) analgesic ladder, whilst providing relief of cancer pain towards the end of life for many sufferers world-wide, may have limitations in the context of longer survival and increasing disease complexity. To complement this, it is suggested that a more comprehensive model of managing cancer pain is needed that is mechanism-based and multimodal, using combination therapies including interventions where appropriate, tailored to the needs of an individual, with the aim to optimize pain relief with minimization of adverse effects.

Impact of prophylactic vaccination strategies on Ebola virus transmission: A modeling analysis.

Ebola epidemics constitute serious public health emergencies. Multiple vaccines are under development to prevent these epidemics and avoid the associated morbidity and mortality. Assessing the potential impact of these vaccines on morbidity and mortality of Ebola is essential for devising prevention strategies. A mean-field compartmental stochastic model was developed for this purpose and validated by simulating the 2014 Sierra Leone epidemic. We assessed the impacts of prophylactic vaccination of healthcare workers (HCW) both alone and in combination with the vaccination of the general population (entire susceptible population other than HCW). The model simulated 8,706 (95% confidence intervals [CI]: 478-21,942) cases and 3,575 (95%CI: 179-9,031) deaths in Sierra Leone, in line with WHO-reported statistics for the 2014 epidemic (8,704 cases and 3,587 deaths). Relative to this base case, the model then estimated that prophylactic vaccination of only 10% of HCW will avert 12% (95% CI: 6%-14%) of overall cases and deaths, while vaccination of 30% of HCW will avert 34% of overall cases (95% CI: 30%-64%) and deaths (95% CI: 30%-65%). Prophylactic vaccination of 1% and 5% of the general population in addition to vaccinating 30% of HCW was estimated to result in reduction in cases by 44% (95% CI: 39%-61%) and 72% (95% CI: 68%-84%) respectively, and deaths by 45% (95% CI: 40%-61%) and 74% (95% CI: 70%-85%) respectively. Prophylactic vaccination of even small proportions of HCW is estimated to significantly reduce incidence of Ebola and associated mortality. The effect is greatly enhanced by the additional vaccination even of small percentages of the general population. These findings could be used to inform the planning of prevention strategies.

Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity.

OBJECTIVE: To analyze a cluster of 30 industrial coworkers with Parkinson's disease and parkinsonism subjected to long-term (8-33 years) chronic exposure to trichloroethylene. METHODS: Neurological evaluations were conducted on the 30 coworkers, including a general physical and neurological examination and the Unified Parkinson's Disease Rating Scale. In addition, fine motor speed was quantified and an occupational history survey was administered. Next, animal studies were conducted to determine whether trichloroethylene exposure is neurotoxic to the nigrostriatal dopamine system that degenerates in Parkinson's disease. The experiments specifically analyzed complex 1 mitochondrial neurotoxicity because this is a mechanism of action of other known environmental dopaminergic neurotoxins. RESULTS: The three workers with workstations adjacent to the trichloroethylene source and subjected to chronic inhalation and dermal exposure from handling trichloroethylene-soaked metal parts had Parkinson's disease. Coworkers more distant from the trichloroethylene source, receiving chronic respiratory exposure, displayed many features of parkinsonism, including significant motor slowing. Neurotoxic actions of trichloroethylene were demonstrated in accompanying animal studies showing that oral administration of trichloroethylene for 6 weeks instigated selective complex 1 mitochondrial impairment in the midbrain with concomitant striatonigral fiber degeneration and loss of dopamine neurons. INTERPRETATION: Trichloroethylene, used extensively in industry and the military and a common environmental contaminant, joins other mitochondrial neurotoxins, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and some pesticides, as a risk factor for parkinsonism.

Individual-level behavioural smoking cessation interventions tailored for disadvantaged socioeconomic position: a systematic review and meta-regression.

BACKGROUND: Socioeconomic inequalities in smoking cessation have led to development of interventions that are specifically tailored for smokers from disadvantaged groups. We aimed to assess whether the effectiveness of interventions for disadvantaged groups is moderated by tailoring for socioeconomic position. METHODS: For this systematic review and meta-regression, we searched MEDLINE, PsycINFO, Embase, Cochrane Central Register, and Tobacco Addiction Register of Clinical Trials and the IC-SMOKE database from their inception until Aug 18, 2019, for randomised controlled trials of socioeconomic-position-tailored or non-socioeconomic-position-tailored individual-level behavioural interventions for smoking cessation at 6 months or longer of follow-up in disadvantaged groups. Studies measured socioeconomic position via income, eligibility for government financial assistance, occupation, and housing. Studies were excluded if they were delivered at the community or population level, did not report differential effects by socioeconomic position, did not report smoking cessation outcomes from 6 months or longer after the start of the intervention, were delivered at a group level, or provided pharmacotherapy with standard behavioural support compared with behavioural support alone. Individual patient-level data were extracted from published reports and from contacting study authors. Random-effects meta-analyses and mixed-effects meta-regression analyses were done to assess associations between tailoring of the intervention and effectiveness. Meta-analysis outcomes were summarised as risk ratios (RR). Certainty of evidence was assessed within each study using the Cochrane risk-of-bias tool version 2 and the grading of recommendations assessment, development, and evaluation approach. The study is registered with PROSPERO, CRD42018103008. FINDINGS: Of 2376 studies identified by our literature search, 348 full-text articles were retrieved and screened for eligibility. Of these, 42 studies (26 168 participants) were included in the systematic review. 30 (71%) of 42 studies were done in the USA, three (7%) were done in the UK, two (5%) each in the Netherlands and Australia, and one (2%) each in Switzerland, Sweden, Turkey, India, and China. 26 (62%) of 42 studies were trials of socioeconomic-position-tailored interventions and 16 (38%) were non-socioeconomic-position-tailored interventions. 17 (65%) of 26 socioeconomic-position-tailored interventions were in-person or telephone-delivered behavioural interventions, four (15%) were digital interventions, three (12%) involved financial incentives, and two (8%) were brief interventions. Individuals who participated in an intervention, irrespective of tailoring, were significantly more likely to quit smoking than were control participants (RR 1·56, 95% CI 1·39-1·75; I2=54·5%). Socioeconomic-position-tailored interventions did not yield better outcomes compared with non-socioeconomic-position-tailored interventions for disadvantaged groups (adjusted RR 1·01, 95% CI 0·81-1·27; ß=0·011, SE=0·11; p=0·93). We observed similar effect sizes in separate meta-analyses of non-socioeconomic-position-tailored interventions using trial data from participants with high socioeconomic position (RR 2·00, 95% CI 1·36-2·93; I2=82·7%) and participants with low socioeconomic position (1·94, 1·31-2·86; I2=76·6%), although certainty of evidence from these studies was graded as low. INTERPRETATION: We found evidence that individual-level interventions can assist disadvantaged smokers with quitting, but there were no large moderating effects of tailoring for disadvantaged smokers. Improvements in tailored intervention development might be necessary to achieve equity-positive smoking cessation outcomes. FUNDING: Cancer Research UK.

Mental health professionals' perceptions, judgements and decision-making practices regarding the use of electronic cigarettes as a tobacco harm reduction intervention in mental healthcare: A qualitative focus group study.

BACKGROUND: Smoking prevalence remains significantly higher among individuals with mental health conditions compared with the general population. Tobacco harm reduction (THR) in the form of replacing cigarettes for electronic cigarettes (ECs) is an alternative approach which may prove useful for these smokers who find it difficult to quit. Exploring how mental health professionals' (MHPs) perceive ECs, and how these influence decision making regarding their use in clinical settings is essential to determine the feasibility of incorporating ECs into the treatment pathway. METHODS: We conducted six focus groups between March and August 2017. A total of 39 MHPs were recruited from mental healthcare services in England. Discussions were guided by a semi-structured guide, and responses were recorded, transcribed and coded using thematic framework analysis. RESULTS: MHPs generally adopt a risk-averse approach when judging the safety and suitability of ECs. Risk-aversion was influenced by perceived obscurity surrounding ECs and THR, as well as high exposure to adverse and unreliable information regarding ECs, and perceived analogies between ECs and conventional cigarettes. Some MHPs adopt a pragmatic approach when making decisions based on THR and EC use in daily practice by considering the context of treatment and patient circumstances. However, this is often accompanied by a high degree of caution and misconceptions which limits the potential benefit this intervention could have in mental healthcare settings. CONCLUSION: Improved dissemination of national guidance and scientific literature regarding THR and ECs is essential in mental healthcare to eliminate misconceptions and better inform MHPs evidence-based decision-making practices.