Prevalence and assessment of frailty in interstitial lung disease - a systematic review and meta-analysis.

BACKGROUND: Frailty is a multisystem dysregulation that challenges homeostasis and increases vulnerability towards stressors. In patients with interstitial lung diseases (ILD) frailty is associated with poorer lung function, greater physical impairment, and higher symptom burden. Our understanding of the prevalence of frailty in ILD and consequently its impact on the ILD population is limited. OBJECTIVE AND METHODS: We aimed to systematically review frailty assessment tools and to determine frailty prevalence across different ILD cohorts. Meta-analyses were used to calculate the pooled prevalence of frailty in the ILD population. RESULTS: We identified 26 studies (15 full-texts, 11 conference abstracts) including a total of 4614 patients with ILD. The most commonly used frailty assessment tools were the Fried Frailty Phenotype (FFP), the Short Physical Performance Battery (SPPB), and the cumulative Frailty Index (FI). Data allowed for meta-analyses of FFP and SPPB prevalence. The pooled prevalence of frailty was 35% (95% CI 25%-45%) by FFP, and 19% (95% CI 12%-28%) by SPPB. CONCLUSIONS: Frailty is common in ILD, with considerable variability of frailty prevalence depending on the frailty assessment tool used. These findings highlight the importance of frailty in ILD and the need for a standardized approach to frailty assessment in this population.

Occupational Safety and Health and Illicit Opioids: State of the Research on Protecting Against the Threat of Occupational Exposure.

The nationwide opioid crisis continues to affect not only people who use opioids but also communities at large by increasing the risk of accidental occupational exposure to illicit opioids. In addition, the emergence of highly potent synthetic opioids such as fentanyl and carfentanil increases the need to protect workers who may encounter unknown drug substances during job activities. To support the National Institute for Occupational Safety and Health Opioids Research Gaps Working Group, we examined the state of the literature concerning methods to protect workers against accidental occupational exposure to illicit opioids, and have identified unmet research needs concerning personal protective equipment, decontamination methods, and engineering controls. Additional studies are needed to overcome gaps in technical knowledge about personal protective equipment, decontamination, and control methods, and gaps in understanding how these measures are utilized by workers. Increasing our knowledge of how to protect against exposure to illicit opioids has the potential to improve occupational health across communities.

VANGUARD®crLyme: A next generation Lyme disease vaccine that prevents B. burgdorferi infection in dogs.

Lyme disease, a public health threat of significance to both veterinary and human medicine, is caused by the tick (Ixodes) transmitted spirochete, Borreliella burgdorferi. Here we report on the immunogenicity and efficacy of VANGUARD®crLyme (Zoetis), the most recent canine Lyme disease vaccine to be approved by the United States Department of Agriculture. VANGUARD®crLyme is a subunit vaccine consisting of outer surface protein A (OspA) and a recombinant outer surface protein C (OspC) based-chimeric epitope protein (chimeritope) that consists of at least 14 different linear epitopes derived from diverse OspC proteins. The combination of OspA and the OspC chimeritope (Ch14) in the vaccine formulation allows for the development of humoral immune responses that work synergistically to target spirochetes in both ticks and in mammals. Immunogenicity was assessed in purpose-bred dogs. A two-dose vaccination protocol resulted in high antibody titers to OspA and Ch14 and vaccinal antibody reacted with 25 different recombinant OspC variants. Efficacy was demonstrated using an Ixodes scapularis -purpose bred dog challenge model. Vaccination with VANGUARD®crLyme provided protection against infection and prevented the development of clinical manifestations and histopathological changes associated with Lyme disease.

Detection of an avian lineage influenza A(H7N2) virus in air and surface samples at a New York City feline quarantine facility.

BACKGROUND: In December 2016, an outbreak of low pathogenicity avian influenza (LPAI) A(H7N2) occurred in cats at a New York City animal shelter and quickly spread to other shelters in New York and Pennsylvania. The A(H7N2) virus also spread to an attending veterinarian. In response, 500 cats were transferred from these shelters to a temporary quarantine facility for continued monitoring and treatment. OBJECTIVES: The objective of this study was to assess the occupational risk of A(H7N2) exposure among emergency response workers at the feline quarantine facility. METHODS: Aerosol and surface samples were collected from inside and outside the isolation zones of the quarantine facility. Samples were screened for A(H7N2) by quantitative RT-PCR and analyzed in embryonated chicken eggs for infectious virus. RESULTS: H7N2 virus was detected by RT-PCR in 28 of 29 aerosol samples collected in the high-risk isolation (hot) zone with 70.9% on particles with aerodynamic diameters >4 µm, 27.7% in 1-4 µm, and 1.4% in <1 µm. Seventeen of 22 surface samples from the high-risk isolation zone were also H7N2 positive with an average M1 copy number of 1.3 × 103 . Passage of aerosol and surface samples in eggs confirmed that infectious virus was present throughout the high-risk zones in the quarantine facility. CONCLUSIONS: By measuring particle size, distribution, and infectivity, our study suggests that the A(H7N2) virus had the potential to spread by airborne transmission and/or direct contact with viral-laden fomites. These results warranted continued A(H7N2) surveillance and transmission-based precautions during the treatment and care of infected cats.

Evaluation of personal inhalable aerosol samplers with different filters for use during anthrax responses.

Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. While a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. The goal of this study was to determine the best sampler-filter combination(s) for the collection and extraction of B. anthracis spores. The study was designed to (1) evaluate the performance of four filter types (one mixed cellulose ester, MCE (pore size = 3 µm), two polytetrafluoroethylene, PTFE (1 and 3 µm), and one polycarbonate, PC (3 µm)); and (2) evaluate the best performing filters in two commercially available inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki [Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The filters were assessed based on criteria such as ability to maintain low pressure drop over an extended sampling period, filter integrity under various environmental conditions, spore collection and extraction efficiencies, ease of loading and unloading the filters into the samplers, cost, and availability. Three of the four tested collection filters-except MCE-were found suitable for efficient collection and recovery of Bt(k) spores sampled from dry and humid as well as dusty and clean air environments for up to 8 hr. The PC (3 µm) filter was identified as the best performing filter in this study. The PTFE (3 µm) demonstrated a comparable performance, but it is more expensive. Slightly higher concentrations were measured with the IOM inhalable sampler which is the preferred sampler's performance criterion when detecting a highly pathogenic agent with no established "safe" inhalation exposure level. Additional studies are needed to address the effects of environmental conditions and spore concentration. The data obtained in this investigation are crucial for future efforts on the development and optimization of a method for assessing inhalation exposure to B. anthracis.

Evaluation of standardized sample collection, packaging, and decontamination procedures to assess cross-contamination potential during Bacillus anthracis incident response operations.

Sample collection procedures and primary receptacle (sample container and bag) decontamination methods should prevent contaminant transfer between contaminated and non-contaminated surfaces and areas during bio-incident operations. Cross-contamination of personnel, equipment, or sample containers may result in the exfiltration of biological agent from the exclusion (hot) zone and have unintended negative consequences on response resources, activities and outcomes. The current study was designed to: (1) evaluate currently recommended sample collection and packaging procedures to identify procedural steps that may increase the likelihood of spore exfiltration or contaminant transfer; (2) evaluate the efficacy of currently recommended primary receptacle decontamination procedures; and (3) evaluate the efficacy of outer packaging decontamination methods. Wet- and dry-deposited fluorescent tracer powder was used in contaminant transfer tests to qualitatively evaluate the currently-recommended sample collection procedures. Bacillus atrophaeus spores, a surrogate for Bacillus anthracis, were used to evaluate the efficacy of spray- and wipe-based decontamination procedures. Both decontamination procedures were quantitatively evaluated on three types of sample packaging materials (corrugated fiberboard, polystyrene foam, and polyethylene plastic), and two contamination mechanisms (wet or dry inoculums). Contaminant transfer results suggested that size-appropriate gloves should be worn by personnel, templates should not be taped to or removed from surfaces, and primary receptacles should be selected carefully. The decontamination tests indicated that wipe-based decontamination procedures may be more effective than spray-based procedures; efficacy was not influenced by material type but was affected by the inoculation method. Incomplete surface decontamination was observed in all tests with dry inoculums. This study provides a foundation for optimizing current B. anthracis response procedures to minimize contaminant exfiltration.

Efficacy of sarolaner in the prevention of Borrelia burgdorferi and Anaplasma phagocytophilum transmission from infected Ixodes scapularis to dogs.

The efficacy of sarolaner (Simparica™, Zoetis) to prevent transmission primarily of Borrelia burgdorferi and secondarily of Anaplasma phagocytophilum from infected wild-caught Ixodes scapularis to dogs was evaluated in a placebo-controlled laboratory study. Twenty-four purpose-bred laboratory Beagles seronegative for B. burgdorferi and A. phagocytophilum antibodies were allocated randomly to one of three treatment groups: placebo administered orally on Days 0 and 7, or sarolaner at 2mg/kg administered orally on Day 0 (28 days prior to tick infestation) or on Day 7 (21 days prior to tick infestation). On Day 28, each dog was infested with approximately 25 female and 25 male wild caught adult I. scapularis that were determined to have prevalence of 57% for B. burgdorferi and 6.7% for A. phagocytophilum by PCR. In situ tick counts were conducted on Days 29 and 30. On Day 33, all ticks were counted and removed. Acaricidal efficacy was calculated based on the reduction of geometric mean live tick counts in the sarolaner-treated groups compared to the placebo-treated group for each tick count. Blood samples collected from each dog on Days 27, 49, 63, 77, 91 and 104 were tested for the presence of B. burgdorferi and A. phagocytophilum antibodies using the SNAP(®) 4Dx(®) Plus Test, and quantitatively assayed for B. burgdorferi antibodies using an ELISA test. Skin biopsies collected on Day 104 were tested for the presence of B. burgdorferi by bacterial culture and PCR. Geometric mean live tick counts for placebo-treated dogs were 14.8, 12.8, and 19.1 on Days 29, 30, and 33, respectively. The percent reductions in mean live tick counts at 1, 2, and 5 days after infestation were 86.3%, 100%, and 100% for the group treated with sarolaner 21 days prior to infestation, and 90.9%, 97.1%, and 100% for the group treated with sarolaner 28 days prior to infestation. Geometric mean live tick counts for both sarolaner-treated groups were significantly lower than those for the placebo group on all count days (P<0.0001). There were no adverse reactions to treatment with sarolaner. Transmission of B. burgdorferi to all eight placebo-treated dogs was confirmed by positive antibody (6 of 8 dogs), PCR (7 of 8 dogs), and/or culture (7 of 8 dogs). Similarly, transmission of A. phagocytophilum was confirmed by the presence of antibodies in four placebo-treated dogs. In contrast, treatment with a single dose of sarolaner prevented transmission of B. burgdorferi from infected ticks to dogs infested 21 or 28 days after treatment as demonstrated by negative antibody, PCR, and culture results. Prevention of transmission of A. phagocytophilum was demonstrated by negative antibody results in all sarolaner-treated dogs.

H-ras dependent estrogenic effects of epidermal growth factor in the estrogen-independent breast cancer cell line MDA-MB-231.

A crosstalk between cellular estrogen response and receptor tyrosine kinase signaling has been shown in a variety of estrogen receptor (ER)-positive cell lines. We intended to examine the presence of estrogenic growth factor effects in an ER alpha-negative breast cancer cell line. By means of reporter gene assays, we investigated the activation of estrogen response elements (EREs) by epidermal growth factor (EGF) in the estrogen-unresponsive cell line MDA-MB-231. Our results demonstrate the H-ras-dependent activation of EREs after EGF treatment in this estrogen-unresponsive cell line, an effect which was not observed in the ERalpha/beta-positive breast cancer cell line MCF-7. In MDA-MB-231 cells, the transcriptional activity of an ERE-containing promotor was enhanced dose dependently by all tested EGF concentrations. This effect could be blocked by co-treatment with the epidermal growth factor receptor (EGFR) inhibitors AG1478 and ZD1839, as well as by co-transfection with a vector coding for a dominant negative H-ras mutant, but not by co-treatment with the pure antiestrogen ICI182,780. Furthermore, expression of constitutively active H-ras was shown to be sufficient to activate EREs in MDA-MB-231 cells. Our results suggest alternative utilization of ERE-mediated gene regulation in an estradiol-unresponsive breast cancer cell line in response to an EGF stimulus. This mechanism was shown to be dependent on EGFR and H-ras activity, but independent of the presence of functional ERalpha.