Modeling suggests gene editing combined with vaccination could eliminate a persistent disease in livestock

Recent breakthroughs in gene-editing technologies that can render individual animals fully resistant to infections may offer unprecedented opportunities for controlling future epidemics in farm animals. Yet, their potential for reducing disease spread is poorly understood as the necessary theoretical framework for estimating epidemiological effects arising from gene-editing applications is currently lacking. Here, we develop semistochastic modeling approaches to investigate how the adoption of gene editing may affect infectious disease prevalence in farmed animal populations and the prospects and time scale for disease elimination. We apply our models to the porcine reproductive and respiratory syndrome (PRRS), one of the most persistent global livestock diseases to date. Whereas extensive control efforts have shown limited success, recent production of gene-edited pigs that are fully resistant to the PRRS virus have raised expectations for eliminating this deadly disease. Our models predict that disease elimination on a national scale would be difficult to achieve if gene editing was used as the only disease control. However, from a purely epidemiological perspective, disease elimination may be achievable within 3 to 6 y, if gene editing were complemented with widespread and sufficiently effective vaccination. Besides strategic distribution of genetically resistant animals, several other key determinants underpinning the epidemiological impact of gene editing were identified

Too Smart to Fail: Guide for the Struggling Medical Student

Medicine is a vocation of perpetual independent learning; long-term success is critically dependent on finding the right resources and establishing effective study methods and test-taking strategies. Students who struggle with the academic transition in medical school have common risk factors and characteristics. We highlight key resources that are available for struggling medical students with an emphasis on West Virginia\u27s HELP, ASPIRE, and STAT programs

Smartphone Medical Applications Useful for the Rural Practitioner

Like other similarly situated rural states, West Virginia’s patients and practitioners often experience access barriers to current medical expertise for multiple disciplines. This article was generated to help bridge this gap and highlights the best-rated mobile medical applications (Apps) for smartphone use. From finding drug interactions and dosing schedules to discussing patients in HIPAA-compliant formats, Apps are becoming integral to the practice of 21st Century medicine. The increased use of these Apps by physicians-in-training and established practitioners highlights the shift from reliance upon the medical library to the easy to use mobile-based technology platforms. This article provides our practitioners, physician extenders, medical trainees, and office staff a guide to access and assess the utility of some of the best rated medical and HIPAA compliant Apps

Improving Rural Bone Health and Minimizing Fracture Risk in West Virginia: Validation of the World Health Organization FRAX® Assessment Tool as a Phone Survey for Osteoporosis Detection

West Virginia ranks second nationally in population ≥ 65 years old placing our state at greater risk for osteoporosis and fracture. The gold standard for detecting osteoporosis is dual X-ray absorptiometry (DXA), yet over half of West Virginia’s counties do not have this machine. Due to access barriers, a validated phone-administered fracture prediction tool would be beneficial for osteoporosis screening. The World Health Organization’s FRAX® fracture prediction tool was administered as a phone survey to 45 patients; these results were compared to DXA bone mineral density determination. Results confirmed that the FRAX® phone survey is as reliable as DXA in detecting osteoporosis or clinically significant osteopenia: 92% positive predictive value, 100% negative predictive value, 100% sensitivity and 91% specificity when compared to the gold standard. These promising results allow for the development of telephone-based protocols to improve osteoporosis detection, referral and treatment especially in areas with health care access barriers

Teen perception of texting and driving in rural West Virginia

In the last decade, texting and driving has evolved into a serious problem among the adolescent population. The goal of this study was to determine if education can effectively raise awareness of the dangers of texting and driving and positively influence the behavior of rural West Virginia teens. A 25 question survey designed to asses teen driving behavior was administered to 143 rural West Virginia high school students before and after and educational session. The educational session was designed to explain how texting and driving impairs driving ability and show graphic images of accidents and injuries that resulted from this behavior. Pre and post-lecture survey responses were then analyzed. The survey results revealed that texting and driving is highly prevalent among rural West Virginia teens, with 57% of teens admitting to this behavior. Around 73% of teens agreed that texting and driving was very dangerous, but many continued to do so regardless. Additionally, 59% admitted to talking on the phone while driving, and 11% admitted to drinking and driving. A single lecture was not observed to reduce texting and driving behavior among the study population. More research is needed to establish an effective method to reduce this dangerous behavior

A Review of Mesenchymal Stem Cell Injections for Osteoarthritis

Mesenchymal stem cell (MSC) injections for osteoarthritis is reviewed. Methods- PubMed search identifying articles in English from 2003-2018 that used intra- articular injection (IA), cartilage repair, cartilage regeneration, chondral injury, adipose stem cells, bone marrow stem cells, mesenchymal stem cells, or autologous stem cells. Results – 388 patients receiving IA MSC injections are discussed with data obtained from 10 case reports or case series, 4 randomized clinical trials (RCT), 1 cohort study, and 3 case controlled therapeutic studies. Conclusions – MSC injections may be an effective adjunct in the management of osteoarthritis and a variety of cartilage related pathologies

Teen perception of texting and driving in rural West Virginia

In the last decade, texting and driving has evolved into a serious problem among the adolescent population. The goal of this study was to determine if education can effectively raise awareness of the dangers of texting and driving and positively influence the behavior of rural West Virginia teens. A 25 question survey designed to asses teen driving behavior was administered to 143 rural West Virginia high school students before and after and educational session. The educational session was designed to explain how texting and driving impairs driving ability and show graphic images of accidents and injuries that resulted from this behavior. Pre and post-lecture survey responses were then analyzed. The survey results revealed that texting and driving is highly prevalent among rural West Virginia teens, with 57% of teens admitting to this behavior. Around 73% of teens agreed that texting and driving was very dangerous, but many continued to do so regardless. Additionally, 59% admitted to talking on the phone while driving, and 11% admitted to drinking and driving. A single lecture was not observed to reduce texting and driving behavior among the study population. More research is needed to establish an effective method to reduce this dangerous behavior

Social recovery therapy for young people with emerging severe mental illness: the Prodigy RCT

Background Young people with social disability and non-psychotic severe and complex mental health problems are an important group. Without intervention, their social problems can persist and have large economic and personal costs. Thus, more effective evidence-based interventions are needed. Social recovery therapy is an individual therapy incorporating cognitive–behavioural techniques to increase structured activity as guided by the participant’s goals. Objective This trial aimed to test whether or not social recovery therapy provided as an adjunct to enhanced standard care over 9 months is superior to enhanced standard care alone. Enhanced standard care aimed to provide an optimal combination of existing evidence-based interventions. Design A pragmatic, single-blind, superiority randomised controlled trial was conducted in three UK centres: Sussex, Manchester and East Anglia. Participants were aged 16–25 years with persistent social disability, defined as < 30 hours per week of structured activity with social impairment for at least 6 months. Additionally, participants had severe and complex mental health problems, defined as at-risk mental states for psychosis or non-psychotic severe and complex mental health problems indicated by a Global Assessment of Functioning score ≤ 50 persisting for ≥ 6 months. Two hundred and seventy participants were randomised 1 : 1 to either enhanced standard care plus social recovery therapy or enhanced standard care alone. The primary outcome was weekly hours spent in structured activity at 15 months post randomisation. Secondary outcomes included subthreshold psychotic, negative and mood symptoms. Outcomes were collected at 9 and 15 months post randomisation, with maintenance assessed at 24 months. Results The addition of social recovery therapy did not significantly increase weekly hours in structured activity at 15 months (primary outcome treatment effect –4.44, 95% confidence interval –10.19 to 1.31). We found no evidence of significant differences between conditions in secondary outcomes at 15 months: Social Anxiety Interaction Scale treatment effect –0.45, 95% confidence interval –4.84 to 3.95; Beck Depression Inventory-II treatment effect –0.32, 95% confidence interval –4.06 to 3.42; Comprehensive Assessment of At-Risk Mental States symptom severity 0.29, 95% confidence interval –4.35 to 4.94; or distress treatment effect 4.09, 95% confidence interval –3.52 to 11.70. Greater Comprehensive Assessment of At-Risk Mental States for psychosis scores reflect greater symptom severity. We found no evidence of significant differences at 9 or 24 months. Social recovery therapy was not estimated to be cost-effective. The key limitation was that missingness of data was consistently greater in the enhanced standard care-alone arm (9% primary outcome and 15% secondary outcome missingness of data) than in the social recovery therapy plus enhanced standard care arm (4% primary outcome and 9% secondary outcome missingness of data) at 15 months. Conclusions We found no evidence for the clinical superiority or cost-effectiveness of social recovery therapy as an adjunct to enhanced standard care. Both arms made large improvements in primary and secondary outcomes. Enhanced standard care included a comprehensive combination of evidence-based pharmacological, psychotherapeutic and psychosocial interventions. Some results favoured enhanced standard care but the majority were not statistically significant. Future work should identify factors associated with the optimal delivery of the combinations of interventions that underpin better outcomes in this often-neglected clinical group. Trial registration Current Controlled Trials ISRCTN47998710. 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. 70. See the NIHR Journals Library website for further project information

Hip fracture evaluation with alternatives of total hip arthroplasty versus hemiarthroplasty (HEALTH): protocol for a multicentre randomised trial

Introduction: Hip fractures are a leading cause of mortality and disability worldwide, and the number of hip fractures is expected to rise to over 6 million per year by 2050. The optimal approach for the surgical management of displaced femoral neck fractures remains unknown. Current evidence suggests the use of arthroplasty; however, there is lack of evidence regarding whether patients with displaced femoral neck fractures experience better outcomes with total hip arthroplasty (THA) or hemiarthroplasty (HA). The HEALTH trial compares outcomes following THA versus HA in patients 50 years of age or older with displaced femoral neck fractures. Methods and analysis: HEALTH is a multicentre, randomised controlled trial where 1434 patients, 50 years of age or older, with displaced femoral neck fractures from international sites are randomised to receive either THA or HA. Exclusion criteria include associated major injuries of the lower extremity, hip infection(s) and a history of frank dementia. The primary outcome is unplanned secondary procedures and the secondary outcomes include functional outcomes, patient quality of life, mortality and hiprelated complications—both within 2 years of the initial surgery. We are using minimisation to ensure balance between intervention groups for the following factors: age, prefracture living, prefracture functional status, American Society for Anesthesiologists (ASA) Class and centre number. Data analysts and the HEALTH Steering Committee are blinded to the surgical allocation throughout the trial. Outcome analysis will be performed using a χ2 test (or Fisher’s exact test) and Cox proportional hazards modelling estimate. All results will be presented with 95% CIs. Ethics and dissemination: The HEALTH trial has received local and McMaster University Research Ethics Board (REB) approval (REB#: 06-151). Results: Outcomes from the primary manuscript will be disseminated through publications in academic journals and presentations at relevant orthopaedic conferences. We will communicate trial results to all participating sites. Participating sites will communicate results with patients who have indicated an interest in knowing the results. Trial registration number: The HEALTH trial is registered with clinicaltrials.gov (NCT00556842)

Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10(-8)), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10(-12)) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10(-10)). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants;thirteen of the chronotype signals remained associated at P<5x10(-8) on meta-analysis and eleven of these reached P< 0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10(-8)). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10(-16)) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10(-9);and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10(-9)). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05);undersleeping and BMI (rG = 0.147, P = 1x10(-5)) and over-sleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans