An Evaluation of the Bighorn Sheep Population in Badlands National Park

Within the last century, bighorn sheep (Ovis canadensis) in the badlands ecosystem of western South Dakota have been subjected to complete extirpation, reintroduction, disease die-offs, genetic bottlenecking, and population augmentation. Subsequently, the population in Badlands National Park (BNP) appears to have recovered, but it was unknown to what degree past events had influenced the population. From 2017-2019, we conducted research on 5 subherds within 2 management units in BNP to 1) survey for the presence of respiratory pathogens and estimate the prevalence of other potentially infectious diseases; 2) assess adult and lamb survival and cause-specific mortality; 3) estimate population size and growth; 4) evaluate the risk of disease exposure from domestic livestock operations within 8 km of the North Unit of BNP; and 5) evaluate genetic variation and population structuring and differentiation. We sampled (n = 83) individuals for the presence of respiratory pathogens including Mycoplasma ovipneumoniae (Movi). Movi results were PCR negative and serology positive (18% prevalence). Bacteriology results indicated additional respiratory pathogens (e.g., Bibersteinia trehalosi, Pasteurella species, Mannheimia species, Trueperella pyogenes) were present within the population. We radio-collared 49 adults and 53 lambs to monitor survival and cause-specific mortality. Overall adult and lamb survival was 96% (95% credible interval [CI] = 89%, 99%) and 82% (CI = 65%, 92%), respectively, with predation accounting for 56% of lamb mortalities. We documented 5 domestic sheep and goat operations within 8 km of the North Unit of BNP. Two goat operations were sampled for respiratory pathogens, one of which testing PCR positive for Movi (77% prevalence). We estimated population growth of = 1.17 in 2016-2017 and = 1.22 in 2017-2018 with a minimum population size count of 233 in 2018. Genetic analysis was conducted at 15 microsatellite loci from 75 individual samples. Overall genetic variation for the BNP population was consistent with other native and translocated populations of bighorn sheep across their range. We found averages of 5.80 and 0.65 for allelic diversity and heterozygosity levels, respectively. We identified three genetically distinct clusters recognized as the three source herds used to establish and supplement the BNP population between 1967 and 2014. Disease and genetic variation were not impacting the growth and survival of the BNP population. As the population continues to have high survival and growth, disease exposure from contact with domestic livestock operations appears to be the greatest risk to the population in the future

Post-infectious headache: a reactive headache?

Post-infectious disease syndrome includes both neurological and non-neurological disorders. However, headache as an isolated or a presenting complaint of post-infectious illness has not been well acknowledged in the literature. In this retrospective observation, patients having daily headache of more than 1 week and <4 weeks duration were included. We divided this group into patients having headache with preceding history of febrile illness in the recent past and patients without such history of febrile illness. We compared clinical features and therapeutic responses of various drugs between the groups. There were no significant differences in demographic features in these groups. However, associated neck pain, nausea, photophobia and meningeal signs were more prevalent in patients having history of preceding infection. A relatively lower proportion of subjects showed complete response to drugs at 3 months in post-infectious group. Good responses were noted to steroids in post-infectious group. In conclusion, a subset of patients with daily headache may be because of post-infectious pathology and treatment in the early stage may prevent it from becoming chronic. Large prospective studies are required to confirm these observations

Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions : A Systematic Review

BACKGROUND: We performed a systematic review to assess whether we can quantify the underreporting of adverse events (AEs) in the published medical literature documenting the results of clinical trials as compared with other nonpublished sources, and whether we can measure the impact this underreporting has on systematic reviews of adverse events. METHODS AND FINDINGS: Studies were identified from 15 databases (including MEDLINE and Embase) and by handsearching, reference checking, internet searches, and contacting experts. The last database searches were conducted in July 2016. There were 28 methodological evaluations that met the inclusion criteria. Of these, 9 studies compared the proportion of trials reporting adverse events by publication status. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. A total of 11 studies compared the numbers of adverse events in matched published and unpublished documents. The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were undertaken. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published documents. Additionally, 2 other studies demonstrated that there are substantially more types of adverse events reported in matched unpublished than published documents. There were 20 meta-analyses that reported the odds ratios (ORs) and/or risk ratios (RRs) for adverse events with and without unpublished data. Inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. The main limitations of this review are that the included case examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby substantial differences between published and unpublished data are more likely to be published. CONCLUSIONS: There is strong evidence that much of the information on adverse events remains unpublished and that the number and range of adverse events is higher in unpublished than in published versions of the same study. The inclusion of unpublished data can also reduce the imprecision of pooled effect estimates during meta-analysis of adverse events

The use of clinical study reports to enhance the quality of systematic reviews: a survey of systematic review authors

Background: Clinical study reports (CSRs) are produced for marketing authorisation applications. They often contain considerably more information about, and data from, clinical trials than corresponding journal publications. Use of data from CSRs might help circumvent reporting bias, but many researchers appear to be unaware of their existence or potential value. Our survey aimed to gain insight into the level of familiarity, understanding and use of CSRs, and to raise awareness of their potential within the systematic review community. We also aimed to explore the potential barriers faced when obtaining and using CSRs in systematic reviews. Methods: Online survey of systematic reviewers who (i) had requested or used CSRs, (ii) had considered but not used CSRs and (iii) had not considered using CSRs was conducted. Cochrane reviewers were contacted twice via the Cochrane monthly digest. Non-Cochrane reviewers were reached via journal and other website postings. Results: One hundred sixty respondents answered an open invitation and completed the questionnaire; 20/ 160 (13%) had previously requested or used CSRs and other regulatory documents, 7/160 (4%) had considered but not used CSRs and 133/160 (83%) had never considered this data source. Survey respondents mainly sought data from the European Medicines Agency (EMA) and/or the Food and Drug Administration (FDA). Motivation for using CSRs stemmed mainly from concerns about reporting bias 11/20 (55%), specifically outcome reporting bias 11/20 (55%) and publication bias 5/20 (25%). The barriers to using CSRs noted by all types of respondents included current limited access to these documents (43 respondents), the time and resources needed to obtain and include these data in evidence syntheses (n = 25) and lack of guidance about how to use these sources in systematic reviews (n = 26). Conclusions: Most respondents (irrespective of whether they had previously used them) agreed that access to CSRs is important, and suggest that further guidance on how to use and include these data would help to promote their use in future systematic reviews. Most respondents who received CSRs considered them to be valuable in their systematic review and/or meta-analysis

Increasing value and reducing waste in stroke research

Stroke represents a major burden to patients and society, and resources spent on stroke research must be used efficiently and produce good value in terms of improvements in human health. However, there are many examples of poor value from stroke research funding, which result from the way in which stroke research has been chosen, designed, conducted, analysed, regulated, managed, disseminated, or reported. In a project including a survey and a symposium and involving stroke researchers in the European Stroke Organisation we have sought to identify sources of inefficiency and waste, recommended approaches to increase value, and highlighted examples of best practice in stroke research. Recent evidence suggests that progress has been made, but there is room for much improvement, and stroke researchers, funders and other stakeholders might consider our recommendations when planning new research

Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64 years: cohort study using a primary care database

Background: Epilepsy is a serious condition which can profoundly affect an individual’s life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years. Methods: Data on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox’s proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables. Results: In the first 5 years of follow-up, 878 (0.37 %) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95 % confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95 % CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95 % CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95 % CI 1.52 to 4.91, NNH 166). Conclusions: Risk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies

Improvement of the Trivalent Inactivated Flu Vaccine Using PapMV Nanoparticles

Commercial seasonal flu vaccines induce production of antibodies directed mostly towards hemaglutinin (HA). Because HA changes rapidly in the circulating virus, the protection remains partial. Several conserved viral proteins, e.g., nucleocapsid (NP) and matrix proteins (M1), are present in the vaccine, but are not immunogenic. To improve the protection provided by these vaccines, we used nanoparticles made of the coat protein of a plant virus (papaya mosaic virus; PapMV) as an adjuvant. Immunization of mice and ferrets with the adjuvanted formulation increased the magnitude and breadth of the humoral response to NP and to highly conserved regions of HA. They also triggered a cellular mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain (WSN/33). Thus, seasonal flu vaccine adjuvanted with PapMV nanoparticles can induce universal protection to influenza, which is a major advancement when facing a pandemic

A low cortisol response to stress is associated with musculoskeletal pain combined with increased pain sensitivity in young adults: A longitudinal cohort study

Background: In this study, we investigated whether an abnormal hypothalamic-pituitary-adrenal (HPA) axis response to psychosocial stress at 18 years of age is associated with musculoskeletal (MS) pain alone and MS pain combined with increased pain sensitivity at 22 years of age. Methods: The study sample included 805 participants from the Western Australian Pregnancy Cohort (Raine) Study who participated in the Trier Social Stress Test (TSST) at age 18 years. Number of pain sites, pain duration, pain intensity and pain frequency were assessed at age 22 to measure severity of MS pain. Cold and pressure pain thresholds were determined at age 22. Group-based trajectory modeling was applied to establish cortisol response patterns based on the TSST. Logistic regression was used to study the association of TSST patterns with MS pain alone and MS pain combined with increased cold or pressure pain sensitivity, adjusted for relevant confounding factors. All analyses were stratified by sex. Results: The mean (standard deviation) age during the TSST was 18.3 (0.3) years, and during MS pain assessment it was 22.2 (0.6). Forty-five percent of the participants were female. Three cortisol response patterns were identified, with cluster 1 (34 % of females, 21 % of males) reflecting hyporesponse, cluster 2 (47 %, 54 %) reflecting intermediate response and cluster 3 (18 %, 24 %) reflecting hyperresponse of the HPA axis. MS pain was reported by 42 % of females and 33 % of males at age 22 years. Compared with females in cluster 2, females in cluster 1 had an increased likelihood of having any MS pain (odds ratio 2.3, 95 % confidence interval 1.0-5.0) and more severe MS pain (2.8, 1.1-6.8) if their cold pain threshold was above the median. In addition, females in cluster 1 had an increased likelihood (3.5, 1.3-9.7) of having more severe MS pain if their pressure pain threshold was below the median. No statistically significant associations were observed in males. Conclusions: This study suggests that a hyporesponsive HPA axis at age 18 years is associated with MS pain at 22 years in young females with increased pain sensitivity