Three-year safety observation of subcutaneous administration of epoetin-zeta in patients with chronic renal anemia: Results from PASCO II study.

Epoetin has been used to treat patients with renal anemia since 1988. -Anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) has been associated with epoetin usage, and a PRCA incidence of 4.5 per 10,000 patient-years was observed for epoetin-α (Eprex) in 2002. The PASCO II study (post-authorization safety cohort observation of Retacrit and Silapo (epoetin-ζ) administered subcutaneously for the treatment of renal anemia) followed 6,346 patients (4,501 Retacrit (group R); 1,845 Silapo (group S)) for up to 3 years of subcutaneous treatment with the biosimilar epoetin-ζ. One PRCA in 1 (0.02%) patient in group R who tested positive for neutralizing antibodies was reported. Overall, 527 adverse events of special interest (AESI) including PRCA occurred in 418 (6.60%) patients, lack of efficacy occurred in 34 (0.54%), and thromboembolic events in 389 (6.14%) patients. 41 adverse drug reactions other than AESIs were reported in 28 (0.44%) patients. The exposure-adjusted incident rate of PRCA was 0.84 per 10,000 patient-years. This real-world study showed that among patients with renal anemia receiving subcutaneous administration of the biosimilar product epoetin-ζ, the incidence rate of PRCA was substantially below the risk observed in 2002 for Eprex and that there was no immunogenicity concern or other new safety concern.

Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study.

BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.

Valuing Citizen Access to Digital Health Services: Applied Value-Based Outcomes in the Canadian Context and Tools for Modernizing Health Systems.

BACKGROUND: In publicly funded health systems, digital health technologies are strategies that aim to improve the quality and safety of health care service delivery and enhance patient experiences and outcomes. In Canada, governments and health organizations have invested in digital health technologies such as personal health records (PHRs) and other electronic service functionalities and innovation across provincial and territorial health systems. OBJECTIVE: Patients' access to their own information via secure, Web-based PHRs and integrated virtual care services are promising mechanisms for supporting patient engagement in health care. We draw on current evidence to develop an economic model that estimates the demonstrated and potential value of these digital health initiatives. METHODS: We first synthesized results from a variety of Canadian and international studies on the outcomes for patients and service providers associated with PHRs across a continuum of services, ranging from viewing information (eg, laboratory results) on the Web to electronic prescription renewal to email or video conferencing with care teams and providers. We then developed a quantitative model of estimated value, grounded in these demonstrated benefits and citizen use (2016-2017). In addition to estimating the costs saved from patient and system perspectives, we used a novel application of a compensating differential approach to assess the value (independent of costs) to society of improved health and well-being resulting from PHR use. RESULTS: Patients' access to a range of digital PHR functions generated value for Canadians and health systems by increasing health system productivity, and improving access to and quality of health care provided. As opportunities increased to interact and engage with health care providers via PHR functions, the marginal value generated by utilization of PHR functionalities also increased. Web-based prescription renewal generated the largest share of the total current value from the patient perspective. From the health systems perspective, Canadians' ability to view their information on the Web was the largest value share. If PHRs were to be implemented with more integrated virtual care services, the value generated from populations with chronic illnesses such as severe and persistent mental illness and diabetes could amount to between Can $800 million and Can $1 billion per year across Canadian health systems. CONCLUSIONS: PHRs with higher interactivity could yield substantial potential value from wider implementation in Canada and increased adoption rates in certain target groups-namely, high-frequency health system users and their caregivers. Further research is needed to tie PHR use to health outcomes across PHR functions, care settings, and patient populations.

Alliance members' roles in collective field-building: an assessment of leadership and championship within the Population Health Intervention Research Initiative for Canada.

BACKGROUND: The Population Health Intervention Research Initiative for Canada (PHIRIC) is a multi-stakeholder alliance founded in 2006 to advance population health intervention research (PHIR). PHIRIC aimed to strengthen Canada's capacity to conduct and use such research to inform policy and practice to improve the public's health by building PHIR as a field of research. In 2014, an evaluative study of PHIRIC at organisational and system levels was conducted, guided by a field-building and collaborative action perspective. METHODS: The study involved 17 qualitative key informant interviews with 21 current and former PHIRIC Planning Committee and Working Group members. The interviews examined how individuals and organisations were acting as champions and exerting leadership in building the field of PHIR. RESULTS: Founding PHIRIC organisational members have been championing PHIR at organisational and system levels. While the PHIR field has progressed in terms of enhanced funding, legitimacy, profile and capacity, some members and organisations faced constraints and challenges acting as leaders and champions in their respective environments. Expectations about the future of PHIRIC and field-building of PHIR were mixed, where longer-term and founding members of PHIRIC expressed more optimism than recent members. All agreed on the need for incorporating perspectives of decision-makers into PHIR directions and initiatives. CONCLUSIONS: The findings contribute to understanding alliance members' roles in leadership and championship for field-building more generally, and for population health and PHIR specifically. Building this field requires multi-level efforts, collaborative action and distributed leadership to create the necessary conditions for PHIRIC members to both benefit from and contribute to advancing PHIR as a field. Lessons from this 'made in Canada' model may be of interest to other countries regarding the structures needed for PHIR field-building.

Work-related injuries to animal care workers, Washington 2007-2011.

BACKGROUND: For workers engaged in animal care, workplace hazards are common and may outnumber those experienced by human healthcare workers. METHODS: We used accepted Washington State workers' compensation claims for the period from January 1, 2007 and December 31, 2011 to compare injury rates and types of injuries across animal care occupations. RESULTS: Work-related injuries frequently affect veterinary support staff and those working in pet stores, shelters, grooming facilities and kennels. Animal-related injuries were the most commonly reported injury type experienced by all groups, though the animal source of injury appears to differ by work setting. CONCLUSIONS: Workplace related injuries among animal care workers are common and most often caused by physical insults resulting from worker-animal interaction.

The Effects of Web-Based Patient Access to Laboratory Results in British Columbia: A Patient Survey on Comprehension and Anxiety.

BACKGROUND: Web-based patient access to personal health information is limited but increasing in Canada and internationally. OBJECTIVE: This exploratory study aimed to increase understanding of how Web-based access to laboratory test results in British Columbia (Canada), which has been broadly available since 2010, affects patients' experiences. METHODS: In November 2013, we surveyed adults in British Columbia who had had a laboratory test in the previous 12 months. Using a retrospective cohort design, we compared reported wait-time for results, test result comprehension, and anxiety levels of "service users" who had Web-based access to their test results (n=2047) with those of a general population panel that did not have Web-based access (n=1245). RESULTS: The vast majority of service users (83.99%, 95% CI 82.31-85.67) said they received their results within "a few days", compared to just over a third of the comparison group (37.84%, 95% CI 34.96-40.73). Most in both groups said they understood their test results, but the rate was lower for service users than the comparison group (75.55%, 95% CI 73.58-77.49 vs 84.69%, 95% CI 82.59-86.81). There was no significant difference between groups in levels of reported anxiety after receiving test results. CONCLUSIONS: While most patients who received their laboratory test results online reported little anxiety after receiving their results and were satisfied with the service, there may be opportunities to improve comprehension of results.

Real-world observational cohort study of treatment patterns and safety outcomes of infliximab biosimilar CT-P13 for the treatment of inflammatory bowel disease (CONNECT-IBD).

BACKGROUND: The objective of this non-interventional, observational prospective cohort study (CONNECT-IBD) was to assess the use of CT-P13 (Inflectra®) in the treatment of patients with Crohn's disease (CD) and ulcerative colitis (UC) in the context of treatment with reference infliximab (IFX; Remicade®). METHODS: Patients (recruited April 2015 to October 2018) at 150 sites across 13 European countries were followed for up to 2 years. Primary outcomes were safety, population characteristics, and drug utilization patterns. Secondary outcomes included clinical assessment of disease activity. Data were analyzed descriptively. RESULTS: Overall, 2543 patients (CD, n = 1676; UC, n = 867) were included. In the CT-P13 cohort (n = 1522), median disease duration was 63 (0-579) months and 30% of patients were IFX naïve; median duration of prior IFX treatment was 5 months. During the observation period, median duration of drug exposure was 14 (0-28) months. 41% of patients reported 912 all-causality treatment-emergent adverse events (TEAEs); 24% experienced treatment-related TEAEs. Most TEAEs were of mild-to-moderate severity. Treatment-emergent serious adverse events were reported by 17% of patients. CONCLUSION: Safety information for CT-P13 in this large study was consistent with the known safety profile for IFX and did not alter the established benefit-risk profile of CT-P13.

Dairy Cattle Euthanasia-Focus Groups Exploring the Perspectives of Brazilians Working in the Dairy Cattle Industry.

The objective of this study was to explore perspectives and attitudes about euthanasia specific to the Brazilian dairy cattle industry. Twenty-five Brazilian citizens (13 veterinarians, 4 animal scientists, 3 professors, 3 researchers, 1 dairy owner, and 1 caretaker) participated in one of three focus groups conducted and recorded online (10, 8, and 7 participants per group). Questions regarding euthanasia were posed by a moderator, and the focus group discussions were then transcribed verbatim for analysis. After the initial data analysis, themes were evaluated and collapsed into three major categories: Euthanasia Training and Farm and Human Components. A complex interconnection between the three main themes and multiple subthemes specific to dairy cattle euthanasia was also revealed. The lack of nationally recognized euthanasia guidelines for dairy cattle paired with ineffective and inaccessible euthanasia tools makes it difficult for dairy veterinarians to implement humane protocols for on-farm euthanasia. In addition, logistical factors, particularly, the financial cost of euthanasia and the human-animal bond, play a role in the failure to perform euthanasia when warranted. Future studies should focus on the development of science-based standards and producer training to improve the consistency of on-farm euthanasia in Brazilian dairy operations.

Real-life drug persistence in patients with rheumatic diseases treated with CT-P13: a prospective observational cohort study (PERSIST).

OBJECTIVE: The aim was to report results from PERSIST, a real-life, observational, prospective cohort study of CT-P13, an infliximab (IFX) biosimilar, for treatment of patients with RA, AS or PsA who were biologic naïve or switched from an IFX reference product (IFX-RP; Remicade). METHODS: Adult patients were recruited during usual care at 38 sites in Europe and Canada and enrolled by their physicians after meeting eligibility criteria according to the country-approved label for CT-P13. Primary outcomes were to determine drug utilization and treatment persistence and to assess safety. Patients were followed for up to 2 years. Data were analysed and reported descriptively. RESULTS: Of 351 patients enrolled, 334 were included in the analysis (RA, 40.4%; AS, 34.7%; PsA, 24.9%). The safety analysis set comprised all 328 patients treated with CT-P13. The majority (58.2%) of patients received CT-P13 monotherapy, most (72.6%) by dosing every 6 or 8 weeks. The mean treatment persistence was 449.2 days; 62.3% of patients completed 2 years of treatment. In all, 214 treatment-emergent adverse events (TEAEs) were reported in 38.4% of patients. Most TEAEs were of mild or moderate intensity; 13 were severe. The most commonly reported TEAEs were drug ineffective (9.5%) and infusion-related reactions (5.2%). The most frequently reported infection-related TEAEs were upper respiratory tract infections (3.0%), nasopharyngitis (2.1%) and bronchitis (1.5%). No patients experienced tuberculosis. CONCLUSION: Drug utilization and treatment persistence with CT-P13 were consistent with historical reports of IFX-RP in this patient population. Safety findings did not identify new concerns for CT-P13 in the treatment of patients with RA, AS or PsA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605642.

Determination of Dairy Cattle Euthanasia Criteria and Analysis of Barriers to Humane Euthanasia in the United States: Dairy Producer Surveys and Focus Groups.

There are currently no clear guidelines in the US and some other countries regarding euthanasia decision making timelines for dairy cattle that become injured or ill to the extent that recovery is unlikely or impossible. Our study aimed to identify decision making criteria and the most common factors considered when making and carrying out euthanasia decisions. Dairy producers were recruited to participate in a mailed survey (Part I, 307 completed surveys were returned) or in one of three focus groups (Part II, 8-10 producers/group, n = 24). Part I (survey): Farm owners were most commonly responsible for on-farm euthanasia and most respondents would treat and monitor compromised cattle for a majority of 15 health conditions. Responses were highly variable; for example, 6.3% and 11.7% of respondents would never euthanize a non-ambulatory cow or calf, respectively. Part II (focus groups): Three main themes (animal, human, and farm operation) were identified from discussion which focused primarily on animal welfare (16% of the discussion) and human psychology (16%). Participants expressed a desire to eliminate animal suffering by euthanizing, alongside a wide range of emotional states. Development of specific standards for euthanasia is a critical next step and more research is needed to understand the human emotions surrounding euthanasia decision making.

Determination of Dairy Cattle Euthanasia Criteria and Analysis of Barriers to Humane Euthanasia in the United States: The Veterinarian Perspective.

When dairy cattle become ill or injured to the extent that recovery is unlikely or impossible, on-farm euthanasia should be used as a tool to eliminate pain and suffering. Our study aimed to identify decision-making criteria and the most common factors considered by veterinarians when making and carrying out euthanasia decisions. Dairy cattle veterinarians were recruited to participate in an online survey (Part I, 61 surveys collected) or in one of three focus groups (Part II, 4-10 veterinarians/group, n = 22). Part I (survey): Surveyed veterinarians varied regarding health condition management and demonstrated a strong proclivity to treat compromised cattle, mirroring trends amongst dairy producers identified in previous research. Sixty percent of respondents indicated that most facilities for which they serve as the primary veterinarian have a written euthanasia protocol in place. Part II (focus groups): Three main themes about euthanasia decision-making (logistical, animal, and human) were identified from focus group discussions. Discussions focused primarily on logistical factors such as financial considerations and client/public perceptions. Development of specific standards for euthanasia, alongside interactive training programs for dairy veterinarians and producers are vital next steps to improving cattle welfare and consistency in euthanasia decision-making across the United States dairy industry.

Strategic Priorities for Research on Antibiotic Alternatives in Animal Agriculture-Results From an Expert Workshop.

The emergence, spread, and expansion of antibiotic resistance and increasing restrictions on the use of antibiotics in animal agriculture have created a need for efficacious alternatives that remains unmet. Prioritizing research needs in the development of alternatives is key to ensuring that scarce research resources are dedicated to the most promising approaches. However, frameworks to enable a consistent, systematic, and transparent evaluation of antibiotic alternative candidates are lacking. Here, we present such an evaluation framework.

Pet owners' perceptions of veterinary safety practices.

Veterinary workers must care for their animal patients while simultaneously protecting their own health and safety. This process can be complicated by the presence and perception of pet owners who may not agree with a given tactic used to protect veterinary workers from injury. We conducted focus groups of pet owners in the Seattle area during November 2016 to gain a deeper understanding of their perceptions relating to veterinary worker safety practices. Focus group interviews were recorded and transcribed and study themes identified and summarised. Twenty pet owners participated in three focus groups. Study themes arising from the focus group discussions could be categorised into human, animal, behavioural and environmental domains as outlined in a One Health Occupational Safety and Health (OHOSH) model. Communication was a recurring study theme identified, suggesting that lacking or impaired veterinary personnel-client communication plays a key role in the safe delivery of veterinary services and can negatively impact the use of safety practices among veterinary personnel. Our study suggests that it is important for veterinary personnel to communicate to clients the reasons for policies related to worker safety. Such communication can help engage the veterinary client in order to effectively avoid situations that precipitate injury.

Distribution of Staphylococcus species in dairy cows, workers and shared farm environments.

Dairy farming involves frequent contact among animals, workers and farm environments. To explore the Staphylococcus spp. diversity that occurs on dairy farms, a pilot study sampled dairy workers, cows and the farm environments from five farms, two organic and three conventional farms, in Washington State. Samples were taken from the nares and hands of consenting workers (n = 24), udders and nares of selected cows (n = 25) and representative environmental surfaces (n = 96) from each farm. To increase diversity of the Staphylococcus spp. characterized, five distinct colonies were selected from each sample for identification with 16S analysis. A total of 198 staphylococci were characterized representing 19 different Staphylococcus spp. The diversity of species ranged from 9-15 Staphylococcus spp./farm with no difference between conventional and organic farms. S. haemolyticus [n = 60 isolates] was the most common species and was isolated from all farms and from cows, humans and environmental samples. Whole genome sequencing of selected S. haemolyticus found no genetically related isolates among human, animal and environmental samples within the same farm. S. epidermidis, S. saprophyticus, S. sciuri and S. xylosus were also found in ≥1 farms from human, animal and environmental samples.

Survey of occupational hazards in Minnesota veterinary practices in 2012.

OBJECTIVE: To identify the scope of occupational hazards encountered by veterinary personnel and compare hazard exposures between veterinarians and technicians working in small and large animal practices. DESIGN: Cross-sectional survey. POPULATION: Licensed veterinarians and veterinary staff in Minnesota. PROCEDURES: A survey of Minnesota veterinary personnel was conducted between February 1 and December 1, 2012. Adult veterinary personnel working in clinical practice for > 12 months were eligible to participate. Information was collected on various workplace hazards as well as on workplace safety culture. RESULTS: 831 eligible people responded, representing approximately 10% of Minnesota veterinary personnel. A greater proportion of veterinarians (93%; 368/394) reported having received preexposure rabies vaccinations than did veterinary technicians (54%; 198/365). During their career, 226 (27%) respondents had acquired at least 1 zoonotic infection and 636 (77%) had been injured by a needle or other sharps. Recapping of needles was reported by 87% of respondents; the most common reason reported by veterinarians (41%; 142/345) and veterinary technicians (71%; 238/333) was being trained to do so at school or work. Recent feelings of depression were reported by 204 (25%) respondents. A greater proportion of technicians (42%; 155/365) than veterinarians (21%; 81/394) indicated working in an environment in which employees experienced some form of workplace abuse. CONCLUSIONS AND CLINICAL RELEVANCE: Veterinary personnel in Minnesota were exposed to several work-related hazards. Practice staff should assess workplace hazards, implement controls, and incorporate instruction on occupational health into employee training.

Swine worker awareness and behavior regarding prevention of zoonotic influenza transmission.

ABSTRACT A convenience survey of swine workers on large and small commercial farms in the Northeast and Midwest United States regarding zoonotic influenza awareness and precautions was conducted. Workers reported low levels of concern regarding the risk of contracting influenza from swine, and were generally not aware of national guidelines for influenza prevention. Use of personal protective equipment (PPE) varied by task, N95 respirator use was rare, and no workers were enrolled in respirator programs. Reported influenza vaccination coverage was greater than the national average in 2009-2010, but declined in 2010-2011. Workers on large farms were more likely to use PPE in some tasks and to report using more precautions when pigs appeared ill. Although reporting low levels of concern regarding zoonotic influenza and low adherence to national influenza guidelines, swine workers reported making task-based and risk-based decisions about use of PPE, suggesting opportunities for enhanced prevention of zoonotic disease transmission.