Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

The Gratitude Campaign: A Multihospital Evidence-Based Practice Project.

Nurse well-being and optimism were tested in the midst of COVID-19 patient surges and staffing challenges. Using the American Nurses Foundation Gratitude Toolkit, a health system implemented monthly gratitude practices at 4 hospitals. Validated survey measures indicated that nurses' scores of self-perceived gratitude, flourishing behaviors, and mindfulness were maintained during this challenging time but did not statistically increase. Although statistical significance increases were not demonstrated, the gratitude campaign offered clinical significance through positive feedback and was sustained through the distribution of a toolkit disseminated across the health system.

Breaking institutional barriers to enhance women's participation in and benefit from the Peste des Petits Ruminants and Newcastle Disease vaccine value chains for Sembabule district of Uganda.

This paper describes the institutional context that shapes the visibility and positioning of women along the Peste des Petits Ruminants (PPR) and Newcastle Disease (ND) vaccine value chains for Sembabule district of Uganda. It examines the institutional barriers and opportunities that affect women's empowerment derived from inclusion of women in the decision-making processes along the livestock vaccine value chain (LVVC) and that can support viable women-centered and owned enterprises, at the vaccine development, delivery, distribution and use level. Qualitative data analysis tools such as focus group discussions, focus meals, jar voices and key informant interviews were used. Using outcome mapping, a stakeholder analysis of the critical partners in the PPR and ND value chain was done involving the regulators, vaccine manufacturers, importers, distributors, agrovets, public and private veterinary service deliverers, local leaders, women groups, and farmers. The study concluded that training related to gender equality and livestock vaccines, infrastructural and technical support to the poultry and goat women and men farmers and other chain actors are inadequate in themselves to increase vaccine adoption and improve livestock productivity in Sembabule district. Strategies that promote gender-transformative collaborative efforts among the LVVC actors and build viable gender-transformed women groups and networks are critical to increase women's participation in and benefit from the livestock vaccine value chain.

Contributing Factors of Sugar-Sweetened Beverage Intake in the Latinx Population: A Narrative Review Using the Social-Ecological Model.

Sugar-sweetened beverage (SSB) consumption in the Latinx population has been a topic of increasing interest due to higher rates of consumption in this population, as well as higher prevalence of chronic health conditions, such as diabetes and obesity. SSB behaviors are influenced by multiple factors across the socio-ecological model. Understanding these factors can inform future intervention development and improve SSB consumption and overall health. Therefore, this narrative review identifies factors contributing to SSB consumption, as well as interventions conducted to address SSB consumption in the Latinx population residing in the United States. Contributing factors that are not currently addressed in published interventions are highlighted with the intent to inform the development of future comprehensive interventions.

Using Outcome Mapping to Mobilize Critical Stakeholders for a Gender Responsive Rift Valley Fever and Newcastle Disease Vaccine Value Chain in Rwanda.

Approximately 752 million of the world's poor keep livestock to produce food, generate income, and build assets. Women represent two-thirds (~400 million people) of low-income livestock keepers. Infectious diseases are a major issue in preventing livestock keepers from optimizing production earnings and improving food security. In Rwanda, highly contagious yet preventable diseases that affect animals that women manage, such as Rift Valley fever in goats and Newcastle disease in chickens have a high-mortality rate and can devastate their herds. Women are disproportionately affected because they bear primary responsibility for goats and chickens. These diseases are preventable through vaccination, but smallholder women farmers rarely benefit from livestock vaccines. Social norms and entrenched cultural stereotypes limit women's confidence and decision-making and restrict their access to resources and information. Women smallholder farmers find that there is little support for the small livestock they manage, because of the official preference given to cattle. They are also challenged by limited availability of livestock vaccines due to lack of a cold chain, inadequate extension, and veterinary services, especially for goats and chickens, and unreliable structures for vaccine delivery. To identify opportunities for women's engagement in the livestock vaccine value chain (LVVC) and reduce their barriers to accessing and using livestock vaccines, we used Outcome Mapping, a stakeholder engagement tool, and the Gender Equality Continuum Tool to classify and engage critical partners in the LVVC. We analyzed each critical partner's capacities, incentives, and drivers for engagement with women, challenges and barriers that hinder their support for women farmers, opportunities at systemic and programmatic levels for women's participation and benefit in the LVVC, and the gender capacities and perceptions of different stakeholders. Enhanced positioning and visibility of women in the LVVC can occur through a systemic engagement of all stakeholders, and recognition of the roles that women play. Women smallholder farmer involvement when determining and shaping the potential entry-points is critical to ensure support for their existing responsibilities in family food security, and future opportunities for generating income. Strengthening gender capacities of LVVC stakeholders, addressing identified barriers, and building on existing opportunities can increase women's participation in the LVVC.

Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial.

A randomized, double-blind, placebo-controlled, 52-week study (no. NCT03068468) evaluated gosuranemab, an anti-tau monoclonal antibody, in the treatment of progressive supranuclear palsy (PSP). In total, 486 participants dosed were assigned to either gosuranemab (n = 321) or placebo (n = 165). Efficacy was not demonstrated on adjusted mean change of PSP Rating Scale score at week 52 between gosuranemab and placebo (10.4 versus 10.6, P = 0.85, primary endpoint), or at secondary endpoints, resulting in discontinuation of the open-label, long-term extension. Unbound N-terminal tau in cerebrospinal fluid decreased by 98% with gosuranemab and increased by 11% with placebo (P < 0.0001). Incidences of adverse events and deaths were similar between groups. This well-powered study suggests that N-terminal tau neutralization does not translate into clinical efficacy.

Selection of individuals for lung cancer screening based on risk prediction model performance and economic factors - The Ontario experience.

INTRODUCTION: Randomized controlled trials have shown that screening with computed tomography reduces lung cancer mortality but is most effective when applied to high-risk individuals. Accurate lung cancer risk prediction models effectively select individuals for screening. Few pilots or programs have implemented risk models for enrolling individuals for screening in real-world, population-based settings. This report describes implementation of the PLCOm2012 risk prediction model in the Ontario Health (Cancer Care Ontario) lung cancer screening Pilot. METHODS: In the Pilot's Health Technology Assessment, 576 categorical age/pack-years/quit-years scenarios were evaluated using MISCAN microsimulation modeling and cost-effectiveness analyses. A preferred model was selected which provided the most life-years gained per cost. The PLCOm2012 was compared to the preferred MISCAN scenario at a threshold that yielded the same number eligible (risk ≥2.0 %/6-years). RESULTS: The PLCOm2012 had significantly higher sensitivity and predictive value (68.1 % vs 59.6 %, p < 0.0001; 4.90 % vs 4.29 %, p = 0.044), and an Expert Panel selected it for use in the Pilot. The Pilot cancer detection rate was significantly higher than in the NLST (p = 0.009) or NELSON (p = 0.003) and there was a significant shift to early stage compared to historical Ontario Cancer Registry statistics (p < 0.0001). Pre- and post-Pilot evaluations found that conducting quality risk assessments were not excessively time consuming or difficult, and participants' satisfaction was high. CONCLUSIONS: The PLCOm2012 was efficiently implemented in the Pilot in a real-world setting and is being used to transition into a provincial program. Compared to categorical age/pack-years/quit-years criteria, risk assessment using the PLCOm2012 can lead to effective and efficient screening.

Evaluation of the Potential Pharmacokinetic Interactions Between Vixotrigine and an Oral Contraceptive.

BACKGROUND AND OBJECTIVE: Vixotrigine is a voltage- and use-dependent sodium channel blocker in development for neuropathic pain management. This study evaluated the effect of coadministration of vixotrigine (metabolized primarily via uridine diphosphate-glucuronosyltransferases) and an oral contraceptive containing ethinyl estradiol (uridine diphosphate-glucuronosyltransferase inducer) and levonorgestrel on the pharmacokinetics and safety of all three compounds. METHODS: In this phase I, open-label, fixed-sequence, multiple-dose study, 36 healthy women received oral vixotrigine 150 mg three times daily for 6 days and once on day 7. This was followed by a washout period, days 8-11. The oral contraceptive was administered alone on days 12-25 and with vixotrigine 150 mg three times daily on days 26-32. Serial blood samples were collected for pharmacokinetic analysis. Safety was assessed. RESULTS: The geometric least-squares mean ratios (90% confidence intervals) for the area under the concentration-time curve over 8 h and maximum concentration of vixotrigine co-administered with an oral contraceptive vs vixotrigine alone were 0.85 (0.82-0.89) and 0.91 (0.87-0.96), respectively. The geometric least-squares mean ratios (90% confidence interval) for area under the concentration-time curve over 24 h and maximum concentration of ethinyl estradiol with vixotrigine vs ethinyl estradiol alone were 0.94 (0.91-0.97) and 0.89 (0.84-0.94), respectively; the ratios for levonorgestrel with vixotrigine vs levonorgestrel alone were 1.06 (0.98-1.16) and 1.05 (0.98-1.13), respectively. No adverse events occurring with vixotrigine alone were deemed related to the study drug by the investigators. CONCLUSIONS: Coadministration of vixotrigine and an oral contraceptive containing ethinyl estradiol and levonorgestrel had no clinically relevant effect on exposure of all three compounds. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT03324685 (registered 25 October, 2017).

MRI correlates of chronic symptoms in mild traumatic brain injury.

Some veterans with a history of mild traumatic brain injury (mTBI) have reported experiencing auditory and visual dysfunction that persist beyond the acute phase of the incident. The etiology behind these symptoms is difficult to characterize, since mTBI is defined by negative imaging findings on current clinical imaging. There are several competing hypotheses that could explain functional deficits; one example is shear injury, which may manifest in diffusion-weighted magnetic resonance (MR) imaging (DWI). Herein, we explore this alternative hypothesis in a pilot study of multi-parametric MR imaging. Briefly, we consider a cohort of 8 mTBI patients relative to 22 control subjects using structural T1-weighted imaging (T1w) and connectivity with DWI. 1,344 metrics were extracted per subject from whole brain regions and connectivity patterns in sensory networks. For each set of imaging-derived metrics, the control subject metrics were embedded in a low-dimensional manifold with principal component analysis, after which mTBI subject metrics were projected into the same space. These manifolds were employed to train support vector machines (SVM) to classify subjects as controls or mTBI. Two of the SVMs trained achieved near-perfect accuracy averaged across four-fold cross-validation. Additionally, we present correlations between manifold dimensions and 22 self-reported mTBI symptoms and find that five principal components from the manifolds (one component from the T1w manifold and four components from the DWI manifold) are significantly correlated with symptoms (p<0.05, uncorrected). The novelty of this work is that the DWI and T1w imaging metrics seem to contain information critical for distinguishing between mTBI and control subjects. This work presents an analysis of the pilot phase of data collection of the Quantitative Evaluation of Visual and Auditory Dysfunction and Multi-Sensory Integration in Complex TBI Patients study and defines specific hypotheses to be tested in the full sample.

Evaluation of the Pharmacokinetic Interaction Between the Voltage- and Use-Dependent Nav1.7 Channel Blocker Vixotrigine and Carbamazepine in Healthy Volunteers.

Vixotrigine is a voltage- and use-dependent Nav1.7 channel blocker under investigation for the treatment of peripheral neuropathic pain conditions, including trigeminal neuralgia. Vixotrigine is metabolized primarily via uridine diphosphate-glucuronosyltransferases (UGTs). Carbamazepine, a UGT and cytochrome P450 3A4 inducer, is a first-line treatment for trigeminal neuralgia. We conducted a double-blind, randomized, placebo-controlled, parallel-group, single-center phase 1 study to investigate the impact of coadministering vixotrigine and carbamazepine on their respective pharmacokinetics (PK) in healthy volunteers, the safety and tolerability of combined treatment, and PK recovery of vixotrigine following carbamazepine discontinuation. Randomly assigned treatments were carbamazepine (100 mg twice a day, days 1-3 and 200 mg twice a day, days 4-21) or placebo on days 1 to 21. All volunteers received vixotrigine 150 mg 3 times a day on days 16 to 28. At prespecified times, whole-blood samples were collected for PK assessment. Statistical analyses were performed on the log-transformed PK parameters area under the concentration-time curve within a dosing interval (AUC0-tau ) and maximum observed concentration (Cmax ) for vixotrigine, carbamazepine, and metabolites. Vixotrigine AUC0-tau and Cmax were reduced by 31.6% and 26.3%, respectively, when coadministered with carbamazepine compared with placebo. Seven days after carbamazepine discontinuation, vixotrigine AUC0-tau and Cmax remained 24.5% and 21.4% lower compared with placebo. Carbamazepine AUC0-tau and Cmax were <10% lower when coadministered with vixotrigine compared on days 15 and 21. Vixotrigine/carbamazepine coadministration was well tolerated. These results suggest that vixotrigine does not have an effect on carbamazepine PK, and although carbamazepine has an effect on the exposure of vixotrigine, the effect is not considered clinically relevant.

Current status of global dairy goat production: an overview.

The global goat population continues to grow and is now over one billion. The number of goats raised primarily for milk production is also growing, due to expanding demand. Most of the world dairy goat production and consumption is in Asia, but a global view of the dairy goat sector reveals important lessons about building successful modern dairy goat industries. The most organized market for goat milk is found in Europe, especially in France. The European goat sector is specialized for milk production, mostly for industrial cheesemaking, while also supporting traditional on-farm manufacturing. Government involvement is significant in sanitary regulation, research, extension, support for local producer organizations, and markets, and ensures safety and quality. Nonetheless, producers are still vulnerable to market fluctuations. New dairy goat industries are developing in countries without a long goat milk tradition, such as China, the United States, and New Zealand, due to rising consumer demand, strong prices, and climate change. The mix of policies, management and markets varies widely, but regardless of the country, the dairy goat sector thrives when producers have access to markets, and the tools and skills to sustainably manage their livestock and natural resources. These are most readily achieved through strong and inclusive producer organizations, access to technical services, and policies that enable the poor and marginalized groups to benefit from increasing demand.

Current status, challenges and prospects for dairy goat production in the Americas.

Dairy goat production continues to be a socially, economically and culturally important part of the livestock industry in North, Central and South America and the Caribbean islands. Goat milk, cheese and other dairy products offer consumers food products with nutritional, health and environmental benefits. In North America, Mexico produces the greatest volume of goat milk, but most is for family or local consumption that is typical of a mixed farming system adopted by subsistence farmers in dry areas. The United States is not yet a large global goat milk producer, but the sector has expanded rapidly, with dairy goat numbers doubling between 1997 and 2012. The number of dairy goats has also increased dramatically in Canada. Commercial farms are increasingly important, driven by rising demand for good quality and locally sourced goat cheese. In South America, Brazil has the most developed dairy goat industry that includes government assistance to small-scale producers and low-income households. As of 2017, FAO identified Haiti, Peru, Jamaica, and Bolivia as having important goat milk production in the Western Hemisphere. For subsistence goat producers in the Americas on marginal land without prior history of chemical usage, organic dairy goat production can be a viable alternative for income generation, with sufficient transportation, sanitation and marketing initiatives. Production efficiency, greenhouse gas emission, waste disposal, and animal welfare are important challenges for dairy goat producers in the Americas.

Development of a Measure of Barriers to Laparoscopic Adjustable Gastric Banding (LAGB) Aftercare Attendance.

BACKGROUND: Regular aftercare attendance following laparoscopic adjustable gastric banding (LAGB) is associated with greater weight loss and fewer post-surgical complications. Despite high reported rates of attrition from LAGB aftercare, the reasons for non-attendance have not been thoroughly explored. The aim of the current study was to describe the scale development, explore the factor structure and evaluate the psychometric properties of the Gastric Banding Aftercare Attendance Questionnaire (GBAAQ)-a tool that measures barriers to aftercare attendance in LAGB patients. METHODS: One hundred and eighty-three participants completed the GBAAQ; 107 regular attendees and 76 non-attendees. RESULTS: A factor analysis identified four factors (Treatment Approach, Time Constraints, Stress and Pressures, Uncomfortable Participating) that demonstrated good known-groups validity and internal consistency. CONCLUSIONS: Although further validation is needed, the results of the present study provide preliminary support for the validity of the GBAAQ. Knowledge about the barriers to LAGB aftercare attendance can be used to identify those most at risk of non-attendance and can inform strategies aimed at reducing non-attendance.

Measuring and reporting attrition from obesity treatment programs: A call to action!

The high attrition rates in obesity interventions are associated with poorer weight loss and maintenance for the individual and poorer overall treatment effectiveness and cost-effectiveness for the treatment provider. Increased knowledge about factors associated with attrition can facilitate the identification of individuals at risk of drop-out and inform treatment program improvements with the aim of maximising treatment retention. To date, a relatively small body of literature has explored attrition from weight-loss interventions using two methods of attrition assessment: identification of pre-treatment predictors of attrition and eliciting post-treatment reasons for attrition. A range of attrition rates have been reported and no reliable or consistent predictors of attrition have been found. It is unknown whether the lack of consistent findings reflects population or treatment differences, or if the discrepant findings simply reflect differences in definition and measurement of attrition. Further research is required to address these limitations. There is a need for a recognised definition of obesity treatment attrition, the consideration of predictors that are theoretically and empirically associated with attrition, the development of a well-validated and standardised measure of barriers to attendance, and assessment of both treatment completers and drop-outs. Understanding the factors that influence attrition can be used to inform the modification of treatment programs and to target those most at risk of drop-out so as to maximise the success of obesity interventions.

Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.

BACKGROUND: Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). METHODS AND RESULTS: We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. CONCLUSIONS: PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD.

ALCAPA Presents in an Adult with Exercise Intolerance but Preserved Cardiac Function.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly that usually manifests as severe left-sided heart failure and mitral valve insufficiency during the first one to two months of life. The majority of these cases die in infancy if not corrected early upon presentation. Adulthood presentation is rare and most of the untreated patients who reach adulthood present with left ventricular dysfunction, severe mitral regurgitation, and sometimes myocardial infarction. Here we report a case of a 20-year-old woman with a history of exercise intolerance since childhood that was misinterpreted as asthma until a 2D-Echo revealed ALCAPA with RCA collaterals to the left anterior descending artery, preserved LV ejection fraction, and absence of apparent mitral valve abnormality. One month after the ALCAPA diagnosis, she successfully underwent surgical reconstruction of left main and pulmonary artery without any major complications. She had normal left ventricular function without apparent ischemic cardiac symptoms eighteen months after procedure.

An experimental study of the role of weight bias in candidate evaluation.

Obese individuals are evaluated negatively and attributed negative trait characteristics in several contexts including employment, health care, and education. The current experimental study of college students examined the effect of body mass on the evaluation of political candidates and examined whether the gender of the candidate moderated the relationship. A series of ordinary least squares regression analyses found an interactive effect between candidate obesity and candidate gender for global evaluation and for several trait characteristics. Specifically, obese female candidates were evaluated more negatively than nonobese female candidates and nonobese male candidates were evaluated more negatively than were obese male candidates. This interaction persisted even after controlling for standard political and demographic characteristics of the evaluator. These findings suggest that weight bias exists for obese female political candidates, but that larger body size may be an asset for male candidates. The ability of candidates to be successful may depend less on their policy positions or even party affiliation and more on their physical attributes than has been previously assumed.