Advancing Proficiencies for Health Professionals in the Treatment of Tobacco Use Among Marginalized Communities: Development of a Competency-Based Curriculum and Virtual Workshop.

BACKGROUND: Tobacco-related disparities are a leading contributor to health inequities among marginalized communities. Lack of support from health professionals is one of the most cited barriers to tobacco cessation reported by these communities. Improving the proficiencies with which health professionals incorporate social and cultural influences into therapeutic interactions has the potential to address this critical barrier. In general, training to improve these proficiencies has shown promise, but the specific proficiencies required for treating tobacco use among marginalized communities are unknown. This project aimed to develop a competency-based curriculum to improve these proficiencies among health professionals with experience and training in the evidence-based treatment of tobacco use, and then pilot test the content delivered via an expert review of a virtual, self-paced workshop. METHODS: We used the Delphi Technique to systematically identify the specific competencies and corresponding knowledge and skill sets required to achieve these proficiencies. Educational content was developed to teach these competencies in a virtual workshop. The workshop was evaluated by 11 experts in the field by examining pre- and post-training changes in perceived knowledge, skill, and confidence levels and other quantitative and qualitative feedback. Repeated measures analysis of variance and paired sample t-tests were used to examine pre-post training differences. RESULTS: Six competencies and corresponding skill sets were identified. After exposure to the virtual workshop, the experts reported significant increases in the overall proficiency for each competency as well as increases in nearly all levels of knowledge, skill, and confidence within the competency skill sets. Qualitative and quantitative findings indicate that content was relevant to practice. CONCLUSIONS: These findings provide preliminary support for 6 competencies and skills sets needed to improve therapeutic interpersonal interactions that recognize the importance of social and cultural influences in the treatment of tobacco use.

Incorporating Intersectionality as a Framework for Equity-Minded Tobacco Control Research: A Call for Collective Action Toward a Paradigm Shift.

INTRODUCTION: To eliminate tobacco-related disparities, tobacco control research would benefit from a paradigm shift. Intersectionality, a framework pioneered by Kimberlé Crenshaw in late 1980s, has the potential to improve our understanding of why and how certain social groups are disproportionately harmed by commercial tobacco use, and improve our ability to address persistent tobacco-related health disparities. AIMS AND METHODS: In this commentary, we outline the rationale and recommendations for incorporating intersectionality into equity-minded tobacco control research. These recommendations arose from intersectionality webinars organized by the Health Disparities (now Health Equity) Network of the Society for Research on Nicotine & Tobacco (SRNT) in 2019 and 2020. RESULTS: Specifically, we propose that eliminating tobacco-related disparities through intersectionality-informed research requires a multilevel, multipronged approach. We summarize priority actions for the tobacco control research field to achieve health equity through the intersectionality framework including acknowledging that structural factors, racism and power dynamics shape lived experiences, integrating critical theoretical frameworks and intersectionality scholarship into research questions, and embracing collaborative community-based approaches at every level of the research process. CONCLUSIONS: Through these actions, our field can take concrete steps to fundamentally improve our approach to conducting research to achieve health equity. IMPLICATIONS: Intersectionality is a valuable tool to align our field with our pursuit of health equity. The recommendations aim to improve methods of equity-focused tobacco control, prompt ongoing dialogue on the utility of this tool, and shift paradigms in how the research process is conducted at every level among stakeholders, including researchers, journal editors and reviewers, funders, practitioners, and policy makers.

Menthol Cigarette Use Among Adults Who Smoke Cigarettes, 2008-2020: Rapid Growth and Widening Inequities in the United States.

INTRODUCTION: In April 2021, the U.S. Food and Drug Administration announced its intention to issue a product standard banning menthol as a characterizing flavor in cigarettes. Given the potential relevance of national estimates of menthol use to pending legislation, this study estimated the prevalence of menthol use among U.S. adults who smoke cigarettes in 2020 and investigated changes in menthol use from 2008 to 2019 by sociodemographics, mental health, and substance use. AIMS AND METHODS: Nationally representative annual, cross-sectional data from the National Survey on Drug Use and Health, which included participants ages 18 years and older residing in the United States from 2008 to 2019 and the 2020. Data were analyzed using logistic and linear regression models to estimate trends in menthol use among adults who smoke cigarettes by sociodemographic, mental health and substance use variables (total analytic sample 2008-2019 n = 128 327). RESULTS: In 2020, 43.4% of adults who smoked cigarettes in the past month used menthol. Menthol use was most common among black adults (80%) and over 50% of those Hispanic, female, young (ages 18-34 years), lesbian/gay, with serious psychological distress, and with cigar use used menthol. Menthol use increased among adults who used cigarettes from 2008 to 2019, overall, and grew more rapidly among adults ages 26-34 years, Hispanic, light cigarette use (1-5 per day), and those who smoked cigars. CONCLUSIONS: Menthol use has increased among U.S. adults who smoke cigarettes over the past decade. Enacting menthol bans could have a widespread public health impact, especially among younger and minoritized groups. IMPLICATIONS: Menthol cigarette use increased among individuals who smoke cigarettes from 2008 to 2019 in the United States. In 2020, over 40% of smokers used menthol, and menthol use was considerably higher among adult smokers from racial/ethnic minoritized groups, who were younger and who reported mental health problems. The U.S. Food and Drug Administration seeks to ban menthol as a characterizing flavor in cigarettes; our results suggest that such a ban is likely to have a wide-ranging impact on public health.

Atmospheric deposition of particulate matter from beef cattle feedlots is a likely contributor of pyrethroid occurrence in isolated wetland sediment: Source apportionment and ecological risk assessment.

Industrial cattle feeding operations (feedlots) have been subject to public scrutiny in recent decades regarding environmental impacts of site runoff and aerial dispersion of agrochemical-laden particulate matter (PM). However, source apportionment of multi-use pesticides is challenging in mixed agricultural settings. Beef cattle on feed and row crop production are heavily concentrated in the Southern Great Plains of North America, where playa wetlands are vulnerable to agrochemical inputs and sedimentation from surrounding land use. In the current study, playa basin sediment (n = 33) was analyzed via UHPLC-MS for 21 agrochemicals spanning eight classes (macrocyclic lactones, neonicotinoids, organophosphates, pyrethroids, triazoles, ß-methoxyacrylates, a carboximide, and phenylpyrazole). Pyrethroids were detected most frequently (75.8% of basins). Sediment pyrethroid concentrations were also significantly correlated (R2 = 0.178, p = 0.007) with feedlot proximity (<1-50 km). Principal component analysis (PCA) of land use metrics extracted three principal components (74.3% of total variance), with principal component regression (PCR) showing the greatest agrochemical occurrence in basins heavily weighted by cropland buffer acreage (≤1 km) and feedlot proximity. Sediment toxicity benchmarks protective of two benthic invertebrates (Hyallela azteca and Chironomus spp.) identified λ-cyhalothrin, fenvalerate, and esfenvalerate as individual compounds exceeding levels of acute (RQ > 0.5) and chronic (RQ > 1) concern in >5% and >50% of cases, respectively. However, additive toxicity of co-occurring pyrethroids represents an acute high risk (RI > 1; median RI; acute = 2.4, chronic = 38.6) to benthic invertebrates in >75% of cases, which may threaten higher-order wetland taxa via bioaccumulation and trophic transfer.

The SWIS trial: Protocol of a pragmatic cluster randomised controlled trial of school based social work.

BACKGROUND: Child and family social workers in the UK work closely with other agencies including schools and the police, and typically they are based in local authority offices. This study will evaluate the effectiveness of placing social workers in schools (SWIS) on the need for social care interventions. SWIS was piloted in three local authorities in 2018-2020, and findings from a feasibility study of the pilots suggests SWIS may operate through three key pathways: (1) by enhancing schools' response to safeguarding issues, (2) through increased collaboration between social workers, school staff, and parents, and (3) by improving relationships between social workers and young people. METHODS: The study is a two-arm pragmatic cluster randomised controlled trial building on three feasibility studies which found SWIS to be promising. Social workers will work within secondary schools across local authorities in England. 280 mainstream secondary schools will be randomly allocated with a 1:1 ratio to SWIS or a comparison arm, which will be schools that continue as normal, without a social worker. The primary outcome will be the rate of Child Protection (Section 47) enquiries. Secondary outcomes will comprise rate of referrals to children's social care, rate of Child in Need (Section 17) assessments, days spent in care, and educational attendance and attainment. The study also includes an economic evaluation, and an implementation and process evaluation. Social care outcomes will be measured in July 2022, and educational outcomes will be measured in July 2023. Days in care will be measured at both time points. DISCUSSION: Findings will explore the effectiveness and cost-effectiveness of SWIS on the need for social care interventions. A final report will be published in January 2024. TRIAL REGISTRATION: The study was registered retrospectively with the International Standard Randomised Controlled Trial Number registry on 13.11.2020 (ISRCTN90922032).

Assessment of pleural pressure during sleep in Marfan syndrome.

STUDY OBJECTIVES: Patients with Marfan syndrome (MFS) have a high risk for aortic aneurysms. They are also susceptible to sleep-disordered breathing that may expose them to highly negative intrathoracic pressures known to increase aortic transmural pressure, which may accelerate aortic dilatation. Our objective was to quantify overnight intrathoracic pressure changes during sleep in snoring patients with MFS and the therapeutic effect of continuous positive airway pressure (CPAP). METHODS: We used a questionnaire to identify self-reported snoring patients with MFS. In these patients, we monitored intrathoracic pressure using esophageal pressure (Pes) during overnight baseline and CPAP sleep studies. We defined a peak-inspiratory Pes (Pespeak-insp) < - 5 cm H2O as greater than normal and examined the distribution of Pespeak-insp during baseline and CPAP studies. RESULTS: In our sample of 23 snorers with MFS, we found that 70% of sleep breaths exhibited Pespeak-insp < -5 cm H2O, with apnea/hypopneass accounting for only 12%, suggesting prevalent stable flow-limited breathing and snoring. In a subset (n = 12) with Pes monitoring during a CPAP night, CPAP lowered the mean proportion of breaths with Pespeak-insp < -5 cm H2O from 83.7% ± 14.9% to 3.6% ± 3.0% (P < .001). In addition, contemporaneous aortic root diameter was associated with the mean Pespeak-insp during inspiratory flow-limited breathing and apneas/hypopneas (ß = -0.05, r = .675, P = .033). CONCLUSIONS: The sleep state in MFS revealed prolonged exposure to exaggerated negative inspiratory Pes, which was reversible with CPAP. Since negative intrathoracic pressure can contribute to thoracic aortic stress and aortic dilatation, snoring may be a reversible risk factor for progression of aortic pathology in MFS. CITATION: Sowho M, Jun J, Sgambati F, et al. Assessment of pleural pressure during sleep in Marfan syndrome. J Clin Sleep Med. 2022;18(6):1583-1592.

Lamotrigine versus levetiracetam or zonisamide for focal epilepsy and valproate versus levetiracetam for generalised and unclassified epilepsy: two SANAD II non-inferiority RCTs.

BACKGROUND: Levetiracetam (Keppra®, UCB Pharma Ltd, Slough, UK) and zonisamide (Zonegran®, Eisai Co. Ltd, Tokyo, Japan) are licensed as monotherapy for focal epilepsy, and levetiracetam is increasingly used as a first-line treatment for generalised epilepsy, particularly for women of childbearing age. However, there is uncertainty as to whether or not they should be recommended as first-line treatments owing to a lack of evidence of clinical effectiveness and cost-effectiveness. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of lamotrigine (Lamictal®, GlaxoSmithKline plc, Brentford, UK) (standard treatment) with levetiracetam and zonisamide (new treatments) for focal epilepsy, and to compare valproate (Epilim®, Sanofi SA, Paris, France) (standard treatment) with levetiracetam (new treatment) for generalised and unclassified epilepsy. DESIGN: Two pragmatic randomised unblinded non-inferiority trials run in parallel. SETTING: Outpatient services in NHS hospitals throughout the UK. PARTICIPANTS: Those aged ≥ 5 years with two or more spontaneous seizures that require anti-seizure medication. INTERVENTIONS: Participants with focal epilepsy were randomised to receive lamotrigine, levetiracetam or zonisamide. Participants with generalised or unclassifiable epilepsy were randomised to receive valproate or levetiracetam. The randomisation method was minimisation using a web-based program. MAIN OUTCOME MEASURES: The primary outcome was time to 12-month remission from seizures. For this outcome, and all other time-to-event outcomes, we report hazard ratios for the standard treatment compared with the new treatment. For the focal epilepsy trial, the non-inferiority limit (lamotrigine vs. new treatments) was 1.329. For the generalised and unclassified epilepsy trial, the non-inferiority limit (valproate vs. new treatments) was 1.314. Secondary outcomes included time to treatment failure, time to first seizure, time to 24-month remission, adverse reactions, quality of life and cost-effectiveness. RESULTS: Focal epilepsy. A total of 990 participants were recruited, of whom 330 were randomised to receive lamotrigine, 332 were randomised to receive levetiracetam and 328 were randomised to receive zonisamide. Levetiracetam did not meet the criteria for non-inferiority (hazard ratio 1.329) in the primary intention-to-treat analysis of time to 12-month remission (hazard ratio vs. lamotrigine 1.18, 97.5% confidence interval 0.95 to 1.47), but zonisamide did meet the criteria (hazard ratio vs. lamotrigine 1.03, 97.5% confidence interval 0.83 to 1.28). In the per-protocol analysis, lamotrigine was superior to both levetiracetam (hazard ratio 1.32, 95% confidence interval 1.05 to 1.66) and zonisamide (hazard ratio 1.37, 95% confidence interval 1.08 to 1.73). For time to treatment failure, lamotrigine was superior to levetiracetam (hazard ratio 0.60, 95% confidence interval 0.46 to 0.77) and zonisamide (hazard ratio 0.46, 95% confidence interval 0.36 to 0.60). Adverse reactions were reported by 33% of participants starting lamotrigine, 44% starting levetiracetam and 45% starting zonisamide. In the economic analysis, both levetiracetam and zonisamide were more costly and less effective than lamotrigine and were therefore dominated. Generalised and unclassifiable epilepsy. Of 520 patients recruited, 260 were randomised to receive valproate and 260 were randomised to receive to levetiracetam. A total of 397 patients had generalised epilepsy and 123 had unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the primary intention-to-treat analysis of time to 12-month remission (hazard ratio 1.19, 95% confidence interval 0.96 to 1.47; non-inferiority margin 1.314). In the per-protocol analysis of time to 12-month remission, valproate was superior to levetiracetam (hazard ratio 1.68, 95% confidence interval 1.30 to 2.15). Valproate was superior to levetiracetam for time to treatment failure (hazard ratio 0.65, 95% confidence interval 0.50 to 0.83). Adverse reactions were reported by 37.4% of participants receiving valproate and 41.5% of those receiving levetiracetam. Levetiracetam was both more costly (incremental cost of £104, 95% central range -£587 to £1234) and less effective (incremental quality-adjusted life-year of -0.035, 95% central range -0.137 to 0.032) than valproate, and was therefore dominated. At a cost-effectiveness threshold of £20,000 per quality-adjusted life-year, levetiracetam was associated with a probability of 0.17 of being cost-effective. LIMITATIONS: The SANAD II trial was unblinded, which could have biased results by influencing decisions about dosing, treatment failure and the attribution of adverse reactions. FUTURE WORK: SANAD II data could now be included in an individual participant meta-analysis of similar trials, and future similar trials are required to assess the clinical effectiveness and cost-effectiveness of other new treatments, including lacosamide and perampanel. CONCLUSIONS: Focal epilepsy - The SANAD II findings do not support the use of levetiracetam or zonisamide as first-line treatments in focal epilepsy. Generalised and unclassifiable epilepsy - The SANAD II findings do not support the use of levetiracetam as a first-line treatment for newly diagnosed generalised epilepsy. For women of childbearing potential, these results inform discussions about the benefit (lower teratogenicity) and harm (worse seizure outcomes and higher treatment failure rate) of levetiracetam compared with valproate. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30294119 and EudraCT 2012-001884-64. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 75. See the NIHR Journals Library website for further project information.

BACKGROUND AND METHODS: The SANAD II trial was a clinical trial designed to identify the most clinically effective and cost-effective treatment for adults and children aged > 5 years with newly diagnosed epilepsy. There are two main epilepsy types: focal and generalised. In focal epilepsy, seizures start at a single place in the brain (a focus), whereas in generalised epilepsy seizures start in both sides of the brain at the same time. Anti-seizure medications are the main treatment. For people with newly diagnosed epilepsy, the first anti-seizure medication should control the seizures as quickly as possible while avoiding side effects. The first-choice treatments are lamotrigine (Lamictal®, GlaxoSmithKline plc, Brentford, UK) for focal epilepsy and valproate (Epilim®, Sanofi SA, Paris, France) for generalised epilepsy (however, the latter should be avoided in women who could become pregnant). A number of newer anti-seizure medications have been approved for NHS use, but it is unclear whether or not they should be used as first-line treatments. The SANAD II trial focused on the new medicines levetiracetam (Keppra®, UCB Pharma Ltd, Slough, UK) and zonisamide (Zonegran®, Eisai Co. Ltd, Tokyo, Japan). We recruited 1510 people aged ≥ 5 years with newly diagnosed epilepsy: 990 with focal epilepsy and 520 with generalised or unclassified epilepsy. FINDINGS: FOCAL EPILEPSY: People starting treatment with levetiracetam or zonisamide were significantly less likely to have a 12-month remission from seizures than people starting treatment with lamotrigine, unless they were changed to another anti-seizure medication. Side effects that were thought to be caused by anti-seizure medications were reported by 33% of participants starting lamotrigine, 44% of those starting levetiracetam and 45% of those starting zonisamide. The cost-effectiveness analyses showed that neither levetiracetam nor zonisamide is value for money for the NHS when compared with lamotrigine. The SANAD II findings do not support the use of levetiracetam or zonisamide as first-line treatments in focal epilepsy. FINDINGS: GENERALISED AND UNCLASSIFIABLE EPILEPSY: People starting treatment with levetiracetam were significantly less likely to have a 12-month remission from seizures than people starting valproate, unless they were changed to another anti-seizure medication. Side effects that were thought to be caused by anti-seizure medications were reported by 37% of participants starting valproate and 42% of participants starting levetiracetam. The cost-effectiveness analyses showed that levetiracetam is not good value for money for the NHS when compared with valproate. The SANAD II findings do not support the use of levetiracetam as a first-line treatment for newly diagnosed generalised epilepsy. Importantly, our results will inform treatment decisions for women, who may choose a less effective treatment that is safer in pregnancy.

Assessment of risks to listed species from the use of atrazine in the USA: a perspective.

Atrazine is a triazine herbicide used predominantly on corn, sorghum, and sugarcane in the US. Its use potentially overlaps with the ranges of listed (threatened and endangered) species. In response to registration review in the context of the Endangered Species Act, we evaluated potential direct and indirect impacts of atrazine on listed species and designated critical habitats. Atrazine has been widely studied, extensive environmental monitoring and toxicity data sets are available, and the spatial and temporal uses on major crops are well characterized. Ranges of listed species are less well-defined, resulting in overly conservative designations of "May Effect". Preferences for habitat and food sources serve to limit exposure among many listed animal species and animals are relatively insensitive. Atrazine does not bioaccumulate, further diminishing exposures among consumers and predators. Because of incomplete exposure pathways, many species can be eliminated from consideration for direct effects. It is toxic to plants, but even sensitive plants tolerate episodic exposures, such as those occurring in flowing waters. Empirical data from long-term monitoring programs and realistic field data on off-target deposition of drift indicate that many other listed species can be removed from consideration because exposures are below conservative toxicity thresholds for direct and indirect effects. Combined with recent mitigation actions by the registrant, this review serves to refine and focus forthcoming listed species assessment efforts for atrazine.Abbreviations: a.i. = Active ingredient (of a pesticide product). AEMP = Atrazine Ecological Monitoring Program. AIMS = Avian Incident Monitoring SystemArach. = Arachnid (spiders and mites). AUC = Area Under the Curve. BE = Biological Evaluation (of potential effects on listed species). BO = Biological Opinion (conclusion of the consultation between USEPA and the Services with respect to potential effects in listed species). CASM = Comprehensive Aquatic System Model. CDL = Crop Data LayerCN = field Curve Number. CRP = Conservation Reserve Program (lands). CTA = Conditioned Taste Avoidance. DAC = Diaminochlorotriazine (a metabolite of atrazine, also known by the acronym DACT). DER = Data Evaluation Record. EC25 = Concentration causing a specified effect in 25% of the tested organisms. EC50 = Concentration causing a specified effect in 50% of the tested organisms. EC50RGR = Concentration causing a 50% reduction in relative growth rate. ECOS = Environmental Conservation Online System. EDD = Estimated Daily Dose. EEC = Expected Environmental Concentration. EFED = Environmental Fate and Effects Division (of the USEPA). EFSA = European Food Safety Agency. EIIS = Ecological Incident Information System. ERA = Environmental Risk Assessment. ESA = Endangered Species Act. ESU = Evolutionarily Significant UnitsFAR = Field Application RateFIFRA = Federal Insecticide, Fungicide, and Rodenticide Act. FOIA = Freedom of Information Act (request). GSD = Genus Sensitivity Distribution. HC5 = Hazardous Concentration for ≤ 5% of species. HUC = Hydrologic Unit Code. IBM = Individual-Based Model. IDS = Incident Data System. KOC = Partition coefficient between water and organic matter in soil or sediment. KOW = Octanol-Water partition coefficient. LC50 = Concentration lethal to 50% of the tested organisms. LC-MS-MS = Liquid Chromatograph with Tandem Mass Spectrometry. LD50 = Dose lethal to 50% of the tested organisms. LAA = Likely to Adversely Affect. LOAEC = Lowest-Observed-Adverse-Effect Concentration. LOC = Level of Concern. MA = May Affect. MATC = Maximum Acceptable Toxicant Concentration. NAS = National Academy of Sciences. NCWQR = National Center of Water Quality Research. NE = No Effect. NLAA = Not Likely to Adversely Affect. NMFS = National Marine Fisheries Service. NOAA = National Oceanic and Atmospheric Administration. NOAEC = No-Observed-Adverse-Effect Concentration. NOAEL = No-Observed-Adverse-Effect Dose-Level. OECD = Organization of Economic Cooperation and Development. PNSP = Pesticide National Synthesis Project. PQ = Plastoquinone. PRZM = Pesticide Root Zone Model. PWC = Pesticide in Water Calculator. QWoE = Quantitative Weight of Evidence. RGR = Relative growth rate (of plants). RQ = Risk Quotient. RUD = Residue Unit Doses. SAP = Science Advisory Panel (of the USEPA). SGR = Specific Growth Rate. SI = Supplemental Information. SSD = Species Sensitivity Distribution. SURLAG = Surface Runoff Lag Coefficient. SWAT = Soil & Water Assessment Tool. SWCC = Surface Water Concentration Calculator. UDL = Use Data Layer (for pesticides). USDA = United States Department of Agriculture. USEPA = United States Environmental Protection Agency. USFWS = United States Fish and Wildlife Service. USGS = United States Geological Survey. WARP = Watershed Regressions for Pesticides.

The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

BACKGROUND: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. METHODS: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. INTERPRETATION: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. FUNDING: National Institute for Health Research Health Technology Assessment programme.

The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

BACKGROUND: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. METHODS: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5-12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0-94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96-1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of -0·040 (95% central range -0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years. INTERPRETATION: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Feasibility, Utility, and Limitations of a Rapid Community Behavioral Diagnosis for Social Distancing During the 2020 Coronavirus Pandemic.

PURPOSE: To evaluate the feasibility, utility, and limitations of a rapid community behavioral diagnosis (RCBD) for social distancing behaviors to prevent coronavirus transmission during a global coronavirus pandemic. DESIGN: Using social media for recruitment, we partnered with a local community task force to administer a brief online survey. SETTING: Residential urban community. SAMPLE: Eighty-four community members, the majority of whom were white, female, college educated completed the survey. MEASURES: Theory of planned behavior constructs: behavioral intentions, attitudes, perceived norms, and perceived behavioral control for 3 social distancing behaviors: maintaining a 6-foot distance, avoiding places people congregate, and staying home as much as possible. ANALYSIS: Path analyses were conducted to understand significant determinants of intentions for each behavior to guide the development of locally tailored health promotion messages. RESULTS: The RCBD was implemented, and results were communicated to the community within 1 week. Intentions were high across the 3 behaviors but lowest for staying home as much as possible. Younger participants had lower intentions of maintaining a 6-foot distance than older participants. For each behavior, specific recommendations for health promotion messaging emerged based on how attitudes, norms, and perceived behavioral control related to intentions. CONCLUSION: In a situation where local community action is paramount for reducing coronavirus transmission, this RCBD process is feasible and useful for informing local health promotion.

Vision for the blind: visual psychophysics and blinded inference for decision models.

Evidence accumulation models like the diffusion model are increasingly used by researchers to identify the contributions of sensory and decisional factors to the speed and accuracy of decision-making. Drift rates, decision criteria, and nondecision times estimated from such models provide meaningful estimates of the quality of evidence in the stimulus, the bias and caution in the decision process, and the duration of nondecision processes. Recently, Dutilh et al. (Psychonomic Bulletin & Review 26, 1051-1069, 2019) carried out a large-scale, blinded validation study of decision models using the random dot motion (RDM) task. They found that the parameters of the diffusion model were generally well recovered, but there was a pervasive failure of selective influence, such that manipulations of evidence quality, decision bias, and caution also affected estimated nondecision times. This failure casts doubt on the psychometric validity of such estimates. Here we argue that the RDM task has unusual perceptual characteristics that may be better described by a model in which drift and diffusion rates increase over time rather than turn on abruptly. We reanalyze the Dutilh et al. data using models with abrupt and continuous-onset drift and diffusion rates and find that the continuous-onset model provides a better overall fit and more meaningful parameter estimates, which accord with the known psychophysical properties of the RDM task. We argue that further selective influence studies that fail to take into account the visual properties of the evidence entering the decision process are likely to be unproductive.

Evaluation of the CareStart™ glucose-6-phosphate dehydrogenase (G6PD) rapid diagnostic test in the field settings and assessment of perceived risk from primaquine at the community level in Cambodia.

BACKGROUND: Primaquine is an approved radical cure treatment for Plasmodium vivax malaria but treatment can result in life-threatening hemolysis if given to a glucose-6-phosphate dehydrogenase deficient (G6PDd) patient. There is a need for reliable point-of-care G6PD diagnostic tests. OBJECTIVES: To evaluate the performance of the CareStart™ rapid diagnostic test (RDT) in the hands of healthcare workers (HCWs) and village malaria workers (VMWs) in field settings, and to better understand user perceptions about the risks and benefits of PQ treatment guided by RDT results. METHODS: This study enrolled 105 HCWs and VMWs, herein referred to as trainees, who tested 1,543 healthy adult male volunteers from 84 villages in Cambodia. The trainees were instructed on G6PD screening, primaquine case management, and completed pre and post-training questionnaires. Each trainee tested up to 16 volunteers in the field under observation by the study staff. RESULTS: Out of 1,542 evaluable G6PD volunteers, 251 (16.28%) had quantitative enzymatic activity less than 30% of an adjusted male median (8.30 U/g Hb). There was no significant difference in test sensitivity in detecting G6PDd between trainees (97.21%), expert study staff in the field (98.01%), and in a laboratory setting (95.62%) (p = 0.229); however, test specificity was different for trainees (96.62%), expert study staff in the field (98.14%), and experts in the laboratory (98.99%) (p < 0.001). Negative predictive values were not statistically different for trainees, expert staff, and laboratory testing: 99.44%, 99.61%, and 99.15%, respectively. Knowledge scores increased significantly post-training, with 98.7% willing to prescribe primaquine for P.vivax malaria, an improvement from 40.6% pre-training (p < 0.001). CONCLUSION: This study demonstrated ability of medical staff with different background to accurately use CareStart™ RDT to identify G6PDd in male patients, which may enable safer prescribing of primaquine; however, pharmacovigilance is required to address possible G6PDd misclassifications.

Effect of Travel Time for Thyroid Surgery on Treatment Cost and Morbidity.

Regionalizing surgical care to high-volume centers has improved outcomes for endocrine surgery. This shift is associated with increased travel time, costs, and morbidity within certain patient populations. We examined travel time-related differences in demographics, health-care utilization, thyroid-specific disease, and cost for patients undergoing thyroid surgery at a single high-volume center. Data were extracted from the 2005 to 2014 ACS-NSQIP and clinical data repository for patients undergoing thyroid surgery. Travel times between patients' home address and the hospital were calculated using Google Earth under assumptions of standard road conditions and speed restrictions. Travel time was divided into <2 hours versus ≥2 hours. Primary outcomes were hospital cost and 30-day morbidity. Factors associated with travel time and primary outcomes were analyzed using appropriate bivariate tests and multivariable regression modeling. A total of 1046 thyroid procedures were included, with median (IQR) travel time of 68.8 (40.1-107.2) minutes. Eight hundred forty-seven (80.9%) patients traveled <2 hours compared with 199 (19.1%) traveled ≥2 hours. Patients traveling ≥2 hours were more likely to have complex thyroid disease (37.7% vs 27.6%, P = 0.005), uninsured status (31.1% vs 11.8%, P < 0.001), lower preoperative morbidity risk (2.3% vs 2.7%, P = 0.02), and longer length of stay (1.21 vs 1.07 days, P = 0.04), but similar median operative times (163 vs 165 minutes, P = 0.89). Average cost was higher for patients traveling ≥2 hours ($7300 vs $6846 [2014 USD], P = 0.05). Despite observed patient differences, hospital costs and postoperative morbidity did not differ after adjustment. Existing management practices and the nature of the disease process may be protective against the potential negative effects of regionalization.

Mobile sexual health services for adolescents: investigating the acceptability of youth-directed mobile clinic services in Cape Town, South Africa.

BACKGROUND: The Human Immunodeficiency Virus (HIV) epidemic is growing rapidly among South African adolescents and young adults (AYA). Although HIV counselling and testing, HIV prevention and treatment options are widely available, many AYA delay health-seeking until illness occurs, demonstrating a need for youth responsive, integrated sexual and reproductive health services (SRHS). While feasibility and cost-effectiveness have been evaluated, acceptability of mobile clinics among AYA has yet to be established. The objective of this study was to investigate patient acceptability of mobile AYA SRHS and compare mobile clinic usage and HIV outcomes with nearby conventional clinics. METHODS: Patients presenting to a mobile clinic in Cape Town were invited to participate in an acceptability study of a mobile clinic after using the service. A trained researcher administered an acceptability questionnaire. Mobile clinic medical records during the study period were compared with the records of AYA attending four clinics in the same community. RESULTS: Three hundred three enrolled participants (16-24 years, 246 (81.2%) female) rated mobile AYA SRHS acceptability highly (median = 4,6 out of 5), with 90% rating their experience as better or much better than conventional clinics. The mobile clinic, compared to conventional clinics, attracted more men (26% v 13%, p < 0,000), younger patients (18 v 19 years, p < 0,000), and yielded more HIV diagnoses (4% v 2%, p < 0,000). CONCLUSIONS: Given the high ratings of acceptability, and the preference for mobile clinics over conventional primary health clinics, the scalability of mobile clinics should be investigated as part of a multipronged approach to improve the uptake of SRHS diagnostic, prevention and treatment options for AYA.

A review of the atomoRapid HIV self-testing device: an acceptable and easy alternative to facilitate HIV testing.

Introduction:HIV testing is the gateway to both HIV prevention and treatment, and increased HIV testing and linkage to services is vital for an effective HIV response. HIV testing has progressed significantly from a lengthy laboratory process conducted by specialist medical staff to rapid point of care testing performed by trained lay staff. Despite HIV testing services being widely available, testing rates remain suboptimal among young people and men. Alternative delivery strategies that complement conventional testing services are needed to reach these priority groups. Areas covered:This article reviewed the AtomoRapid HIV self-testing (HIVST) device as an innovative alternative to conventional testing. Expert commentary:HIVST complements traditional HIV testing options and can be used to overcome major barriers to testing by catering for testing outside of conventional settings and by allowing individuals to test themselves privately, and at their own discretion and frequency. We conclude that the high sensitivity, specificity, acceptability, usability, and fidelity of this device makes it an appropriate option for the enhancement of HIV testing strategies for harder to reach populations, such as young people and men.

Gametocyte Carriage, Antimalarial Use, and Drug Resistance in Cambodia, 2008-2014.

Gametocytes are the malaria parasite stages responsible for transmission from humans to mosquitoes. Gametocytemia often follows drug treatment, especially as therapies start to fail. We examined Plasmodium falciparum gametocyte carriage and drug resistance profiles among 824 persons with uncomplicated malaria in Cambodia to determine whether prevalent drug resistance and antimalarial use has led to a concentration of drug-resistant parasites among gametocyte carriers. Although report of prior antimalarial use increased from 2008 to 2014, the prevalence of study participants presenting with microscopic gametocyte carriage declined. Gametocytemia was more common in those reporting antimalarial use within the past year, and prior antimalarial use was correlated with higher IC50s to piperaquine and mefloquine, as well as to increased pfmdr1 copy number. However, there was no association between microscopic gametocyte carriage and parasite drug resistance. Thus, we found no evidence that the infectious reservoir, marked by those carrying gametocytes, is enriched with drug-resistant parasites.

A Conditional Economic Incentive Fails to Improve Linkage to Care and Antiretroviral Therapy Initiation Among HIV-Positive Adults in Cape Town, South Africa.

Interventions to improve antiretroviral therapy (ART) access are urgently needed to maximize the multiple benefits from ART. This pilot study examined the effect of a conditional economic incentive on linkage to care and uptake of treatment following ART referral by a mobile health clinic. Between April 2015 and May 2016, 86 individuals (≥18 years old) referred for ART in a resource-limited setting were randomized (1:1) to a control group or to an incentive: R300 cash (∼$23, or 3.5 days minimum wage in the domestic worker sector), conditional upon starting ART within 3 months. Outcome data were obtained from clinic records. The incentive effects on linkage to care (first clinic visit within 3 months) and ART initiation (treatment uptake within 3 months) were assessed using logistic regression. Overall, 67% linked to care and 42% initiated ART within 3 months after referral. No significant differences were found between the incentive and non-incentive group in terms of linkage to care [adjusted odds ratio (aOR): 0.70, 95% confidence interval (CI): 0.26-1.91] and initiation of ART (aOR: 0.67, 95% CI: 0.26-1.78). Ordinary least-squares regression analysis showed that incentivized individuals linked to care in fewer days (-7.9, 95% CI: -18.09 to 2.26) and started treatment in fewer days (-7.3, 95% CI: -27.01 to 12.38), but neither result was statistically significant. Our findings demonstrate poor treatment uptake by both the intervention and control participants and further highlight the challenge in achieving universal early treatment access. Further research is required to understand how economic incentives, which have been shown to have many benefits, can be applied to improve linkage to HIV care and treatment.