A rare partnership: patient community and industry collaboration to shape the impact of real-world evidence on the rare disease ecosystem.

People with rare lysosomal storage diseases face challenges in their care that arise from disease complexity and heterogeneity, compounded by many healthcare professionals being unfamiliar with these diseases. These challenges can result in long diagnostic journeys and inadequate care. Over 30 years ago, the Rare Disease Registries for Gaucher, Fabry, Mucopolysaccharidosis type I and Pompe diseases were established to address knowledge gaps in disease natural history, clinical manifestations of disease and treatment outcomes. Evidence generated from the real-world data collected in these registries supports multiple stakeholders, including patients, healthcare providers, drug developers, researchers and regulators. To maximise the impact of real-world evidence from these registries, engagement and collaboration with the patient communities is essential. To this end, the Rare Disease Registries Patient Council was established in 2019 as a partnership between the Rare Disease Registries and global and local patient advocacy groups to share perspectives on how registry data are used and disseminated. The Patient Council has resulted in a number of patient initiatives including patient representation at Rare Disease Registries advisory boards; development of plain language summaries of registry publications to increase availability of real-world evidence to patient communities; and implementation of digital innovations such as electronic patient-reported outcomes, and patient-facing registry reports and electronic consent (in development), all to enhance patient engagement. The Patient Council is building on the foundations of industry-patient advocacy group collaboration to fully integrate patient communities in decision-making and co-create solutions for the rare disease community.

Concerning emergence of a new vancomycin-resistant Enterococcus faecium strain ST1299/CT1903/vanA at a tertiary university centre in South Germany.

BACKGROUND: vanB-carrying vancomycin-resistant Enterococcus faecium (VREfm) of the sequence types 80 (ST80) and ST117 have dominated Germany in the past. In 2020, our hospital witnessed a sharp increase in the proportion of vanA-positive VREfm. AIM: To attempt to understand these dynamics through whole-genome sequencing (WGS) and analysis of nosocomial transmissions. METHODS: At our hospital, the first VREfm isolate per patient, treated during 2020, was analysed retrospectively using specific vanA/vanB PCR, WGS, multi-locus sequence typing (MLST), and core-genome (cg) MLST. Epidemiologic links between VRE-positive patients were assessed using hospital occupancy data. FINDINGS: Isolates from 319 out of 356 VREfm patients were available for WGS, of which 181 (56.7%) fulfilled the ECDC definition for nosocomial transmission. The high load of nosocomial cases is reflected in the overall high clonality rate with only three dominating sequence (ST) and complex types (CT), respectively: the new emerging strain ST1299 (100% vanA, 77.4% CT1903), and the well-known ST80 (90.0% vanB, 81.0% CT1065) and ST117 (78.0% vanB, 65.0% CT71). The ST1299 isolates overall, and the subtype CT1903 in particular, showed high isolate clonality, which demonstrates impressively high spreading potential. Overall, 152 out of 319 isolates had an allelic cgMLST difference of ≤3 to another, including 91 (59.6%) ST1299. Occupancy data identified shared rooms (3.7%), shared departments (6.2%), and VRE-colonized prior room occupants (0.6%) within 30 days before diagnosis as solid epidemiological links. CONCLUSION: A new emerging VREfm clone, ST1299/CT1903/vanA, dominated our institution in 2020 and has been an important driver of the increasing VREfm rates.

An emotion-eliciting version of the Hayling Sentence Completion Test.

INTRODUCTION: Executive functions comprise a suite of higher-order cognitive processes, which interact with other processes, such as emotion, to drive goal-directed behavior. The Hayling Sentence Completion Test is a widely used standard neuropsychological tool to measure executive functions, namely verbal initiation and suppression. The current studies aimed to establish and validate an emotion-eliciting version of the Hayling Sentence Completion Test, in order to examine the executive processes of initiation and suppression in an emotional context. Study 1 aimed to provide a quantitative evaluation of the emotional content of the Emotional Hayling Test. Study 2 investigated the differences between the Standard and Emotional Hayling Tests, and explored how performance relates to specific emotional properties of the sentences within the Emotional Hayling. METHODS: Study 1 included N = 100 participants, who were asked to rate each Emotional Hayling Sentence stem in terms of valence (pleasant-unpleasant) and arousal (intensity: low-high). Study 2 included N = 204 participants who completed the Emotional Hayling Test, along with other neuropsychological measures of cognitive and affective functioning. RESULTS: As designed, the sentence stimuli in the Emotional Hayling were rated as significantly higher in absolute emotional valence and arousal, compared to the Standard Hayling (Study 1). Overall, initiation and suppression on the Emotional Hayling were significantly poorer than on the Standard Hayling (Study 2). Finally, within the Emotional Hayling, participants made more suppression errors in response to negative sentences compared to positive sentences, and this effect was present in younger but not older adults. CONCLUSIONS: Reduced performance on the Emotional Hayling Test, particularly in response to negative sentences, is consistent with the emotional content placing increased demands on the executive function system. We present the Emotional Hayling Test as a promising clinical tool, with the potential to capture disruptions in emotional processing.

Rare lysosomal disease registries: lessons learned over three decades of real-world evidence.

Lysosomal storage disorders (LSD) are rare diseases, caused by inherited deficiencies of lysosomal enzymes/transporters, that affect 1 in 7000 to 1 in 8000 newborns. Individuals with LSDs face long diagnostic journeys during which debilitating and life-threatening events can occur. Clinical trials and classical descriptions of LSDs typically focus on common manifestations, which are not representative of the vast phenotypic heterogeneity encountered in real-world experience. Additionally, recognizing that there was a limited understanding of the natural history, disease progression, and real-world clinical outcomes of rare LSDs, a collaborative partnership was pioneered 30 years ago to address these gaps. The Rare Disease Registries (RDR) (for Gaucher, Fabry, Mucopolysaccharidosis type I, and Pompe), represent the largest observational database for these LSDs. Over the past thirty years, data from the RDRs have helped to inform scientific understanding and the development of comprehensive monitoring and treatment guidelines by creating a framework for data collection and establishing a standard of care, with an overarching goal to improve the quality of life of affected patients. Here, we highlight the history, process, and impact of the RDRs, and discuss the lessons learned and future directions.

Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers.

The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.

An online Sexual Health and Rehabilitation eClinic (TrueNTH SHAReClinic) for prostate cancer patients: a feasibility study.

PURPOSE: The primary objective was to determine the feasibility of implementing the TrueNTH SHAReClinic as a pan-Canadian sexual health and rehabilitation intervention for patients treated for localized prostate cancer. METHODS: The feasibility study was designed to evaluate the accessibility and acceptability of the intervention. Participants from five institutions across Canada were enrolled to attend one pre-treatment and five follow-up online clinic visits over 1 year following their prostate cancer (PC) treatment. RESULTS: Sixty-five patients were enrolled in the intervention. Website analytics revealed that 71% completed the intervention in its entirety, including the educational modules, with an additional 10% completing more than half of the intervention. Five thousand eighty-three views of the educational modules were made along with 654 views of the health library items. Over 1500 messages were exchanged between participants and their sexual health coaches. At 12 months, the intervention received an overall average participant rating of 4.1 out of 5 on a single item satisfaction measure. CONCLUSION: Results support the TrueNTH SHAReClinic as highly acceptable to participants as defined by intervention adherence and engagement. The TrueNTH SHAReClinic demonstrated promise for being a feasible and potentially resource-efficient approach to effectively improving the sexual well-being of patients after PC treatment.

Radiofrequency ablation alters the microstructural organization of healthy and enzymatically digested porcine mitral valves.

BACKGROUND: Myxomatous mitral valve degeneration is a common cause of mitral regurgitation and is often associated with mitral valve prolapse. With no known targets to pharmacologically treat mitral valve prolapse, surgery is often the only treatment option. Recently, radiofrequency ablation has been proposed as a percutaneous alternative to surgical resection for the reduction of mitral valve leaflet area. OBJECTIVE: Using an in vitro model of porcine mitral valve anterior leaflet enlargement following enzymatic digestion, we sought to investigate mechanisms by which radiofrequency ablation alters the geometry, microstructural organization, and mechanical properties of healthy and digested leaflets. METHODS: Paired measurements before and after ablation revealed the impact of radiofrequency ablation on leaflet properties. Multiphoton imaging was used to characterize changes in the structure and organization of the valvular extracellular matrix; planar biaxial mechanical testing and constitutive modeling were used to estimate mechanical properties of healthy and digested leaflets. RESULTS: Enzymatic digestion increased leaflet area and thickness to a similar extent as clinical mitral valve disease. Radiofrequency ablation altered extracellular matrix alignment and reduced the area of digested leaflets to that of control. Additionally, enzymatic digestion resulted in fiber alignment and reorientation toward the radial direction, causing increased forces during ablation and a structural stiffening which was improved by radiofrequency ablation. CONCLUSION: Radiofrequency ablation induces radial extracellular matrix alignment and effectively reduces the area of enlarged mitral valve leaflets. Hence, this technique may be a therapeutic approach for myxomatous mitral valve disease and is thus an avenue for future study.

Effects of the macroalga Asparagopsis taxiformis and oregano leaves on methane emission, rumen fermentation, and lactational performance of dairy cows.

Asparagopsis taxiformis (AT) is a source of multiple halogenated compounds and, in a limited number of studies, has been shown to decrease enteric CH4 emission in vitro and in vivo. Similarly, oregano has been suggested as a potential CH4 mitigating agent. This study consisted of 2 in vitro and 2 in vivo experiments. Experiment (Exp.) 1 was aimed at establishing the effect of AT on CH4 emission in vitro. Two experiments (Exp. 2 and 3) with lactating dairy cows were conducted to determine the antimethanogenic effect of AT and oregano (Exp. 3) in vivo. Another experiment (Exp. 4) was designed to investigate stability of bromoform (CHBr3) in AT over time. In Exp. 3, 20 Holstein cows were used in a replicated 4 × 4 Latin square design with four 28-d periods. Treatments were basal diet (control) or basal diet supplemented with (dry matter basis) 0.25% AT (LowAT), 0.50% AT (HighAT), or 1.77% oregano (Origanum vulgare L.) leaves. Enteric gas emissions were measured using the GreenFeed system (C-Lock Inc., Rapid City, SD), and rumen samples were collected for fermentation analysis using the ororuminal technique. In Exp.1 (in vitro), relative to the control, AT (at 1% dry matter basis, inclusion rate) decreased CH4 yield by 98%. In Exp. 3, HighAT decreased average daily CH4 emission and CH4 yield by 65% and 55%, respectively, in experimental periods 1 and 2, but had no effect in periods 3 and 4. The differential response to AT among experimental periods was likely a result of a decrease in CHBr3 concentration in AT over time, as observed in Exp. 4 (up to 84% decrease in 4 mo of storage). In Exp. 3, H2 emission was increased by AT and, as expected, the proportion of acetate in the total volatile fatty acids in the rumen was decreased and those of propionate and butyrate were increased by HighAT compared with the control. Compared with the control, HighAT decreased dry matter intake, milk yield, and energy-corrected milk yield in Exp. 3. Milk composition was not affected by treatment, except lactose percentage and yield were decreased by HighAT. Concentrations of iodine and bromide in milk were increased by HighAT compared with the control. Milk CHBr3 concentration and its organoleptic characteristics were not different between control and HighAT. Oregano had no effect on CH4 emission or lactational performance of the cows in Exp. 3. Overall, AT included at 0.50% in the ration of dairy cows can have a large mitigation effect on enteric CH4 emission, but dry matter intake and milk production may also decrease. There was a marked decrease in the CH4 mitigation potential of AT in the second half of Exp. 3, likely resulting from CHBr3 decay over time.

Comparing noninvasive sampling techniques with standard cannula sampling method for ruminal microbial analysis.

Rumen microbes play an important role in the conversion of indigestible plant material to energy and protein in dairy cows. Sampling for ruminal contents via cannula is considered the gold standard technique for microbial analysis, but the technique requires ruminally cannulated animals and specialized animal facilities. The purpose of this study was to determine whether other sampling methods and locations along the digestive tract may serve as noninvasive proxies to the cannula method for microbial analysis. Six ruminally cannulated lactating Holstein dairy cows were adapted to a standard total mixed ration for 2 wk and sampled during the third week. Sampling locations and methods included salivary content, rumination bolus (regurgitated digesta collected from the cow's mouth), feces, and rumen contents via stomach tube and cannula. Stomach tube and cannula samples differ in proportions of solid and liquid material and were therefore separated into whole (as collected), liquid, and solid fractions. Samples were collected at 0 (before feeding), 2, 4, 6, 8, and 12 h after feeding over 2 d. All samples were extracted for total genomic DNA and selected samples for metabolically active DNA (RNA), PCR-amplified for the V1-V2 region of the 16S rRNA bacterial gene, and analyzed for bacterial diversity using the QIIME2 pipeline followed by statistical analysis in R (https://www.R-project.org/). In DNA-based analysis, at the community level, saliva, rumination bolus, and fecal samples clustered in separate groups, whereas all fractions of stomach tube and cannula samples clustered together, indicating that microbial communities of stomach tube and cannula samples were homogeneous. Rumination bolus samples at 6, 8, and 12 h after feeding clustered with stomach tube and cannula samples, indicating that rumination bolus samples may be an alternative for cannula samples; however, time of sampling is critical for sampling of bolus digesta. Results of the RNA-based analysis of rumination bolus samples and solid samples from cannula and stomach tube at 0 and 6 h after feeding were similar. We concluded that the solid fraction of samples obtained via the stomach tube method may serve as a proxy for the solid fraction of whole ruminal contents obtained via cannula for DNA-based microbial investigations. Both rumination bolus and stomach tube solid samples may serve as proxies for cannula solid samples for RNA-based microbial analysis.

Characterization of on-target adverse events caused by TRK inhibitor therapy.

BACKGROUND: The tropomyosin receptor kinase (TRK) pathway controls appetite, balance, and pain sensitivity. While these functions are reflected in the on-target adverse events (AEs) observed with TRK inhibition, these AEs remain under-recognized, and pain upon drug withdrawal has not previously been reported. As TRK inhibitors are approved by multiple regulatory agencies for TRK or ROS1 fusion-positive cancers, characterizing these AEs and corresponding management strategies is crucial. PATIENTS AND METHODS: Patients with advanced or unresectable solid tumors treated with a TRK inhibitor were retrospectively identified in a search of clinical databases. Among these patients, the frequency, severity, duration, and management outcomes of AEs including weight gain, dizziness or ataxia, and withdrawal pain were characterized. RESULTS: Ninety-six patients with 15 unique cancer histologies treated with a TRK inhibitor were identified. Weight gain was observed in 53% [95% confidence interval (CI), 43%-62%] of patients and increased with time on TRK inhibition. Pharmacologic intervention, most commonly with glucagon-like peptide 1 analogs or metformin, appeared to result in stabilization or loss of weight. Dizziness, with or without ataxia, was observed in 41% (95% CI, 31%-51%) of patients with a median time to onset of 2 weeks (range, 3 days to 16 months). TRK inhibitor dose reduction was the most effective intervention for dizziness. Pain upon temporary or permanent TRK inhibitor discontinuation was observed in 35% (95% CI, 24%-46%) of patients; this was more common with longer TRK inhibitor use. TRK inhibitor reinitiation was the most effective intervention for withdrawal pain. CONCLUSIONS: TRK inhibition-related AEs including weight gain, dizziness, and withdrawal pain occur in a substantial proportion of patients receiving TRK inhibitors. This safety profile is unique relative to other anticancer therapies and warrants careful monitoring. These on-target toxicities are manageable with pharmacologic intervention and dose modification.

A core competency framework for prostate cancer peer navigation.

PURPOSE: Trained peer navigators can offer valuable peer support and mentorship to cancer patients and caregivers due to their highly relevant and unique perspective about the disease experience. In order to define the role of prostate cancer (PC) peer navigators within the cancer care system, it is important to establish the essential competencies of a PC peer navigator. We systematically identified and verified a set of core competencies for PC peer navigators and present a competency framework for PC peer navigators. METHODS: In phase 1, we conducted formative research consisting of a literature review and environmental scan as well as a secondary analysis of qualitative interviews. In phase 2, we drafted and mapped competencies. Finally in phase 3, expert stakeholders completed an anonymous survey to indicate whether they endorsed the competencies and to rank the importance of each competency to the peer navigator role. Open-ended feedback was also provided for each competency. RESULTS: Six core competency domains emerged: (1) self as navigator, (2) communication, (3) knowledge/information, (4) facilitate patient-centred care, (5) eHealth/technology, and (6) caregiver needs. Forty-seven core competency statements were mapped to these domains. Expert stakeholders (n = 27) included cancer survivors, caregivers, and healthcare providers. Most (89%) of core competency statements were endorsed by stakeholders and received high priority ratings, whereas only five of the competencies were less uniformly endorsed. CONCLUSIONS: This is the first attempt to list core competencies for PC peer navigators and may offer guidance for standardizing the PC peer navigator role and training.

Personalizing post-treatment cancer care: a cross-sectional survey of the needs and preferences of well survivors of breast cancer.

Background: Improved treatments resulting in a rising number of survivors of breast cancer (bca) calls for optimization of current specialist-based follow-up care. In the present study, we evaluated well survivors of bca with respect to their supportive care needs and attitudes toward follow-up with various care providers, in varying settings, or mediated by technology (for example, videoconference or e-mail). Methods: A cross-sectional paper survey of well survivors of early-stage pT1-2N0 bca undergoing posttreatment follow-up was completed. Descriptive and univariable logistic regression analyses were performed to examine associations between survivor characteristics, supportive care needs, and perceived satisfaction with follow-up options. Qualitative responses were analyzed using conventional content analysis. Results: The 190 well survivors of bca who participated (79% response rate) had an average age of 63 ± 10 years. Median time since first follow-up was 21 months. Most had high perceived satisfaction with in-person specialist care (96%, 177 of 185). The second most accepted model was shared care involving specialist and primary care provider follow-up (54%, 102 of 190). Other models received less than 50% perceived satisfaction. Factors associated with higher perceived satisfaction with non-specialist care or virtual follow-up by a specialist included less formal education (p < 0.01) and more met supportive care needs (p < 0.05). Concerns with virtual follow-up included the perceived impersonal nature of virtual care, potential for inadequate care, and confidentiality. Conclusions: Well survivors of bca want specialists involved in their follow-up care. Compared with virtual follow-up, in-person follow-up is perceived as more reassuring. Certain survivor characteristics (for example, met supportive care needs) might signal survivor readiness for virtual or non-specialist follow-up. Future work should examine multi-stakeholder perspectives about barriers to and facilitators of shared multimodal follow-up care.

Animal movement drives variation in seed dispersal distance in a plant-animal network.

Frugivores play differing roles in shaping dispersal patterns yet seed dispersal distance is rarely quantified across entire communities. We model seed dispersal distance using gut passage times and bird movement for the majority (39 interactions) of known bird-tree interactions on the island of Saipan to highlight differences in seed dispersal distances provided by the five avian frugivores. One bird species was found to be a seed predator rather than a disperser. The remaining four avian species dispersed seeds but differences in seed dispersal distance were largely driven by interspecific variation in bird movement rather than intraspecific variation in gut passage times. The median dispersal distance was at least 56 m for all species-specific combinations, indicating all species play a role in reducing high seed mortality under the parent tree. However, one species-the Micronesian Starling-performed 94% of dispersal events greater than 500 m, suggesting this species could be a key driver of long-distance dispersal services (e.g. linking populations, colonizing new areas). Assessing variation in dispersal patterns across this network highlights key sources of variation in seed dispersal distances and suggests which empirical approaches are sufficient for modelling how seed dispersal mutualisms affect populations and communities.

Developing a risk management framework to improve public health outcomes by enumerating Salmonella in ground turkey.

Salmonella spp. continue to be a leading cause of foodborne morbidity worldwide. To assess the risk of foodborne disease, current national regulatory schemes focus on prevalence estimates of Salmonella and other pathogens. The role of pathogen quantification as a risk management measure and its impact on public health is not well understood. To address this information gap, a quantitative risk assessment model was developed to evaluate the impact of pathogen enumeration strategies on public health after consumption of contaminated ground turkey in the USA. Public health impact was evaluated by using several dose-response models for high- and low-virulent strains to account for potential under- or overestimation of human health impacts. The model predicted 2705-21 099 illnesses that would result in 93-727 reported cases of salmonellosis. Sensitivity analysis predicted cooking an unthawed product at home as the riskiest consumption scenario and microbial concentration the most influential input on the incidence of human illnesses. Model results indicated that removing ground turkey lots exceeding contamination levels of 1 MPN/g and 1 MPN in 25 g would decrease the median number of illnesses by 86-94% and 99%, respectively. For a single production lot, contamination levels higher than 1 MPN/g would be needed to result in a reported case to public health officials. At contamination levels of 10 MPN/g, there would be a 13% chance of detecting an outbreak, and at 100 MPN/g, the likelihood of detecting an outbreak increases to 41%. Based on these model prediction results, risk management strategies should incorporate pathogen enumeration. This would have a direct impact on illness incidence linking public health outcomes with measurable food safety objectives.

Exposure to antimicrobials through the milk diet or systemic therapy is associated with a transient increase in antimicrobial resistance in fecal Escherichia coli of dairy calves.

The objective of this prospective cohort study was to describe the relationship between exposure to antimicrobials, through both the milk diet and systemic therapy, and to describe antimicrobial resistance of fecal Escherichia coli in dairy calves pre- and postweaning. A convenience sample of 15 Minnesota dairy farms was chosen, representing 3 equal cohorts of milk diet fed to preweaned calves: medicated milk replacer (MMR), nonmedicated milk replacer (NMR), or pasteurized nonsaleable milk (PNM). Five newborn calves were enrolled on each farm, with fecal samples collected from each calf at 1, 3, 5, and 16 wk of age. After isolation, 3 colonies of E. coli were randomly selected from each sample to determine antimicrobial susceptibility by minimum inhibitory concentration (Sensititer, Thermo Scientific, Waltham, MA) to 8 antimicrobials in 8 classes. The isolate was given an antimicrobial resistance score (ARS) according to the number of antimicrobial classes to which it was resistant. Any isolate resistant to 3 or more antimicrobials was defined as being multidrug resistant (MDR). Relationships between ARS and MDR (dependent variables) and possible explanatory variables were analyzed using mixed multivariable linear and logistic regression models, respectively, with critical P-values adjusted for multiple contrasts. Seventy percent of isolates were resistant to sulfadimethoxine. For wk 1 and 3, the mean ARS values were greatest for fecal E. coli from calves fed MMR or PNM compared with NMR, with no difference in ARS values between the MMR and PNM groups at either time point. At wk 5, the mean ARS value was greatest for fecal E. coli from calves fed MMR (3.56 ± 0.45; mean ± SE), intermediate for calves fed PNM (2.64 ± 0.45), and lowest for calves fed NMR (1.54 ± 0.45). However, by wk 16, the mean ARS values were ≤1.0 and did not differ among milk diets. Evaluation of the proportion of isolates with MDR mirrored the results of the ARS analysis (MDR more prevalent in MMR and PNM groups preweaning; no difference among milk diets at 16 wk). There was a tendency for an increase in ARS at wk 5 (1.28 ± 0.70), and the odds for MDR in fecal E. coli were estimated to be 5.2 (95% confidence interval = 0.67, 35.7) and 101.1 (95% confidence interval = 1.15, >999.9) higher at wk 3 and 5 if the calf was treated with a systemic antimicrobial within the 14-d period before sampling. These findings suggest that exposure to antimicrobials through the milk diet or systemic therapy may result in a transient increase in resistance in fecal E. coli, but once the antimicrobial pressure is removed, susceptible E. coli are able to flourish again, resulting in an overall decrease in resistance.

Risk factors associated with highly pathogenic avian influenza subtype H5N8 outbreaks on broiler duck farms in South Korea.

Highly Pathogenic Avian Influenza (HPAI) subtype H5N8 outbreaks occurred in poultry farms in South Korea in 2014 resulting in significant damage to the poultry industry. Between 2014 and 2016, the pandemic disease caused significant economic loss and social disruption. To evaluate the risk factors for HPAI infection in broiler duck farms, we conducted a retrospective case-control study on broiler duck farms. Forty-three farms with confirmed laboratories on premises were selected as the case group, and 43 HPAI-negative farms were designated as the control group. Control farms were matched based on farm location and were within a 3-km radius from the case premises. Spatial and environmental factors were characterized by site visit and plotted through a geographic information system (GIS). Univariable and multivariable logistic regression models were developed to assess possible risk factors associated with HPAI broiler duck farm infection. Four final variables were identified as risk factors in a final multivariable logistic model: "Farms with ≥7 flocks" (odds ratio [OR] = 6.99, 95% confidence interval [CI] 1.34-37.04), "Farm owner with ≥15 years of raising poultry career" (OR = 7.91, 95% CI 1.69-37.14), "Presence of any poultry farms located within 500 m of the farm" (OR = 6.30, 95% CI 1.08-36.93) and "Not using a faecal removal service" (OR = 27.78, 95% CI 3.89-198.80). This highlights that the HPAI H5N8 outbreaks in South Korea were associated with farm owner education, number of flocks and facilities and farm biosecurity. Awareness of these factors may help to reduce the spread of HPAI H5N8 across broiler duck farms in Korea during epidemics. Greater understanding of the risk factors for H5N8 may improve farm vulnerability to HPAI and other subtypes and help to establish policies to prevent re-occurrence. These findings are relevant to global prevention recommendations and intervention protocols.

Seroprevalence of brucellosis in goats and sheep in Thailand: Results from the Thai National Brucellosis Surveillance System from 2013 to 2015.

In Thailand, brucellosis re-emerged in humans in 2003 and is considered a public health risk to goat farmers as the disease is endemic in small ruminants. The Thai Department of Livestock Development (DLD) established a nationwide surveillance system for brucellosis in goats and sheep in 1997. Using data from this surveillance system, we describe the seroprevalence of brucellosis from 2013 to 2015 in small ruminants and the spatial distribution of the disease throughout Thailand. Surveillance data collected included the number of animals and herds tested, the province of the animal and herd and the laboratory results. Seroprevalence was estimated at both the animal and herd levels. During the 3-year period, 443,561 goats and sheep were tested for brucellosis by the DLD throughout Thailand using the Rose Bengal Plate Test (RBPT) and the enzyme-linked immunosorbent assay test for Brucella. Among the 3 years, 2013 had the highest proportion of herds that tested positive for brucellosis at 13.80% (95% CI, 12.52, 15.16). Overall, this study found that brucellosis seroprevalence in small ruminants is decreasing throughout Thailand. However, there is variability in the spread of the disease with provinces in the eastern and western regions of Thailand having higher proportions of animals and herds testing positive. Overall provinces in the south had the lowest proportion of animals and herds testing positive for brucellosis. Periodic review of surveillance data documents the impact of the current brucellosis control programme and supports a targeted response in higher prevalence regions when there are limited financial resources for control measures.

A biopsy of Breast Cancer mobile applications: state of the practice review.

BACKGROUND: Breast cancer is the most common cancer in women. The use of mobile software applications for health and wellbeing promotion has grown exponentially in recent years. We systematically reviewed the breast cancer apps available in today's leading smartphone application stores and characterized them based on their features, evidence base and target audiences. METHODS: A cross-sectional study was performed to characterize breast cancer apps from the two major smartphone app stores (iOS and Android). Apps that matched the keywords "breast cancer" were identified and data was extracted using a structured form. Reviewers independently evaluated the eligibility and independently classified the apps. RESULTS: A total of 1473 apps were a match. After removing duplicates and applying the selection criteria only 599 apps remained. Inter-rater reliability was determined using Fleiss-Cohen's Kappa. The majority of apps were free 471 (78.63%). The most common type of application was Disease and Treatment information apps (29.22%), Disease Management (19.03%) and Awareness Raising apps (15.03%). Close to 1 out of 10 apps dealt with alternative or homeopathic medicine. The majority of the apps were intended for patients (75.79%). Only one quarter of all apps (24.54%) had a disclaimer about usage and less than one fifth (19.70%) mentioned references or source material. Gamification specialists determined that 19.36% contained gamification elements. CONCLUSIONS: This study analyzed a large number of breast cancer-focused apps available to consumers. There has been a steady increase of breast cancer apps over the years. The breast cancer app ecosystem largely consists of start-ups and entrepreneurs. Evidence base seems to be lacking in these apps and it would seem essential that expert medical personnel be involved in the creation of medical apps.

Epidemiologic Investigation of Highly Pathogenic H5N2 Avian Influenza Among Upper Midwest U.S. Turkey Farms, 2015.

In 2015, an outbreak of H5N2 highly pathogenic avian influenza (HPAI) occurred in the United States, severely impacting the turkey industry in the upper midwestern United States. Industry, government, and academic partners worked together to conduct a case-control investigation of the outbreak on turkey farms in the Upper Midwest. Case farms were confirmed to have HPAI-infected flocks, and control farms were farms with noninfected turkey flocks at a similar stage of production. Both case and control farms were affiliated with a large integrated turkey company. A questionnaire administered to farm managers and supervisors assessed farm biosecurity, litter handling, dead bird disposal, farm visitor and worker practices, and presence of wild birds on operations during the 2 wk prior to HPAI confirmation on case premises and the corresponding time frame for control premises. Sixty-three farms, including 37 case farms and 26 control farms were included in the analysis. We identified several factors significantly associated with the odds of H5N2 case farm status and that may have contributed to H5N2 transmission to and from operations. Factors associated with increased risk included close proximity to other turkey operations, soil disruption (e.g., tilling) in a nearby field within 14 days prior to the outbreak, and rendering of dead birds. Observation of wild mammals near turkey barns was associated with reduced risk. When analyses focused on farms identified with H5N2 infection before April 22 (Period 1), associations with H5N2-positive farm status included soil disruption in a nearby field within 14 days prior to the outbreak and a high level of visitor biosecurity. High level of worker biosecurity had a protective effect. During the study period after April 22 (Period 2), factors associated with HPAI-positive farm status included nonasphalt roads leading to the farm and use of a vehicle wash station or spray area. Presence of wild birds near dead bird disposal areas was associated with reduced risk. Study results indicated that the initial introduction and spread of H5N2 virus likely occurred by both environmental and between-farm pathways. Transmission dynamics appeared to change with progression of the outbreak. Despite enhanced biosecurity protocols, H5N2 transmission continued, highlighting the need to review geographic/topologic factors such as farm proximity and potential dust or air transmission associated with soil disruption. It is likely that biosecurity improvements will reduce the extent and speed of spread of future outbreaks, but our results suggest that environmental factors may also play a significant role in farms becoming infected with HPAI.