The herd-level sensitivity of abattoir surveillance for bovine tuberculosis: Simulating the effects of current and potentially modified meat inspection procedures in irish cattle

The European Food Safety Authority (EFSA) has published a series of opinions to assess the impact of changing from the current meat inspection procedures (CMI) to visual-only inspection (VOI) procedures. Concern has been raised that changes from CMI to VOI would adversely affect the effectiveness of surveillance for bovine tuberculosis (bTB) in EU member states, both for countries with and without official status of bTB freedom (OTF and non-OTF countries, respectively). This study was conducted to estimate the impact of a change from CMI to VOI in abattoirs on herd-level detection sensitivity in Ireland, a non-OTF country. Using national Irish data, we identified all herds that sold at least one animal to slaughter during 2010–12 whilst unrestricted for bTB. For each of these herds, we calculated the number of cattle sent to slaughter whilst unrestricted, the number of factory lesion tests (FLT) that had been performed, and estimated the apparent within-herd prevalence (APwh). A FLT is a whole-herd test conducted in a herd following the confirmation of bTB in an animal at slaughter. We considered five different inspection scenarios, each based on meat inspection and bacteriology in series, including current meat inspection (CMI) and four visual-only inspection scenarios (VOI2, VOI3, VOI4, VOI5) with reducing inspection sensitivities. Separately for each inspection scenario, a simulation model was used to estimate the herd-level detection sensitivity and the number of bTB-herds (that is, herds that sent at least one animal detected with M. bovis to slaughter when unrestricted during 2010–12) that would and would not be detected. The simulated mean herd-level detection sensitivity estimates were 0.24 for CMI, and 0.16, 0.12, 0.10 and 0.08 for VOI2-5, assuming a 2-, 3-, 4- and 5-fold decrease, respectively, in the animal-level detection sensitivity of VOI relative to that of CMI. The estimated number of non-detected bTB-herds is substantial with CMI, and increases in the series of VOI scenarios with decreasing herd-level detection sensitivity. If VOI were introduced without alternative surveillance means to compensate for the decrease in animal-level inspection sensitivity, such changes might jeopardise bTB surveillance, control and eradication programmes in cattle herds of non-OTF countries, including Ireland

Ruxolitinib in patients with polycythemia vera resistant and/or intolerant to hydroxyurea:European observational study

Background: Hydroxyurea (HU) is a commonly used first-line treatment in patients with polycythemia vera (PV). However, approximately 15%–24% of PV patients report intolerance and resistance to HU. Methods: This phase IV, European, real-world, observational study assessed the efficacy and safety of ruxolitinib in PV patients who were resistant and/or intolerant to HU, with a 24-month follow-up. The primary objective was to describe the profile and disease burden of PV patients. Results: In the 350 enrolled patients, 70% were &gt;60 years old. Most patients (59.4%) had received ≥1 phlebotomy in the 12 months prior to the first dose of ruxolitinib. Overall, 68.2% of patients achieved hematocrit control with 92.3% patients having hematocrit &lt;45% and 35.4% achieved hematologic remission at month 24. 85.1% of patients had no phlebotomies during the study. Treatment-related adverse events were reported in 54.3% of patients and the most common event was anemia (22.6%). Of the 10 reported deaths, two were suspected to be study drug-related. Conclusion: This study demonstrates that ruxolitinib treatment in PV maintains durable hematocrit control with a decrease in the number of phlebotomies in the majority of patients and was generally well tolerated.</p

Further improvement in the control of bovine tuberculosis recurrence in Ireland

Ongoing objective assessment of national bovine tuberculosis (bTB) policy in Ireland is important to monitor efforts towards improved bTB control. The study objective was to investigate temporal trends in the risk of herd recurrence. The study included all herds derestricted following a bTB episode ending in 1998, 2008 or 2012. The respective \u27study periods\u27 were up to the end of 2001 for 1998-derestricted herds, to the end of 2011 for 2008-derestricted herds, and to the end of 2015 for 2012-derestricted herds. A multivariable Cox proportional-hazard model was developed to examine time to next restriction. The results from the model showed a continuing significant decreasing trend in herd recurrence of bTB in Ireland from 1998 until 2015: herds derestricted in 2008 were 0.75 (95 per cent CI 0.68 to 0.82) times as likely to develop a further restriction compared with 1998 herds, and herds derestricted in 2012 were 0.85 (95per cent CI 0.76 to 0.95) times as likely as 2008 herds. However, despite significant improvements, recurrence of bTB remains a concern, with 30.2 per cent (95 per cent CI 28.0 to 32.4 per cent) of herds derestricted in 2012 being re-restricted over the subsequent three years. Further work is needed to address the two key drivers of herd recurrence, namely residual infection and local reinfection

Further improvement in the control of bovine tuberculosis recurrence in Ireland

Ongoing objective assessment of national bovine tuberculosis (bTB) policy in Ireland is important to monitor efforts towards improved bTB control. The study objective was to investigate temporal trends in the risk of herd recurrence. The study included all herds derestricted following a bTB episode ending in 1998, 2008 or 2012. The respective 'study periods' were up to the end of 2001 for 1998-derestricted herds, to the end of 2011 for 2008-derestricted herds, and to the end of 2015 for 2012-derestricted herds. A multivariable Cox proportional-hazard model was developed to examine time to next restriction. The results from the model showed a continuing significant decreasing trend in herd recurrence of bTB in Ireland from 1998 until 2015: herds derestricted in 2008 were 0.75 (95 per cent CI 0.68 to 0.82) times as likely to develop a further restriction compared with 1998 herds, and herds derestricted in 2012 were 0.85 (95per cent CI 0.76 to 0.95) times as likely as 2008 herds. However, despite significant improvements, recurrence of bTB remains a concern, with 30.2 per cent (95 per cent CI 28.0 to 32.4 per cent) of herds derestricted in 2012 being re-restricted over the subsequent three years. Further work is needed to address the two key drivers of herd recurrence, namely residual infection and local reinfection

Further description of bovine tuberculosis trends in the United Kingdom and the Republic of Ireland, 2003–2015

Extending on earlier work, trends in bovine tuberculosis (bTB) from 2003 to 2015 are described for the countries of the UK and the Republic of Ireland using standardised definitions and measures. Based on measures of animal and herd incidence, there remains a stable situation of extremely low prevalence in Scotland and the Low Risk Area of England, and a higher but ongoing reduction in prevalence in the Republic of Ireland. In Northern Ireland, there has been a rising bTB trend during 2010-2015, although not to levels experienced during 2002-2004. In the High Risk Area and Edge Area of England during 2010-2015, the rising bTB trends have continued but with some recent evidence of stabilisation. In Wales, prevalence has fallen subsequent to a peak in 2008. The paper considers country-level differences in the light of key policy changes, which are presented in detail. This work is unique, and will assist policymakers when critically evaluating policy options for effective control and eradication. Ongoing updates of this analysis would be useful, providing an evidence base for country-level comparison of bTB trends into the future. The use of multivariable analytical methods should be considered, but will rely on substantial sharing of raw data across the five countries

The impact of removal of the seasonality formula on the eligibility of Irish herds to supply raw milk for processing of dairy products

Background: The dairy industry in Ireland is expanding rapidly, with a focus on the production of high quality milk. Somatic cell counts (SCC) are an important indicator both of udder health and milk quality. Milk sold by Irish farmers for manufacture must comply with EU regulations. Irish SCC data is also subject to a monthly seasonal adjustment, for four months from November to February, on account of the seasonality of milk production in Ireland. In a recent study, however, there was no evidence of a dilution effect on SCC with increasing milk yield in Irish dairy cattle. The aim of this paper is to estimate the impact of removal of the seasonality formula on the eligibility of Irish herds to supply raw milk for processing of dairy products. Methods: Bulk tank SCC data from 2013 were collected from 14 cooperatives in Ireland. The geometric mean of SCC test results was calculated for each calendar month. We then calculated the number of herds and volume of milk supplied falling in three SCC categories (400,000 cells/mL) in Ireland during 2013 based on their geometric mean SCC every month. Each herd was assigned an ‘eligibility to supply’ status (always compliant, under warning (first warning, second warning, third warning) and liable for suspension) each month based on their 3-month rolling geometric mean, using methods as outlined in EU and Irish legislation. Two methods were used to calculate the 3-month rolling geometric mean. We then determined the number of herds and volume of milk supplied by ‘eligibility to supply’ status in Ireland during 2013. All calculations were conducted with and without the seasonality adjustment. Results: The analyses were performed on 2,124,864 records, including 1,571,363 SCC test results from 16,740 herds. With the seasonality adjustment in place, 860 (5.1%) or 854 (5.1%) of herds should have been liable for suspension during 2013 if calculation method 1 or 2, respectively, had been used. If the seasonality adjustment were removed, it is estimated that the number of herds liable for suspension would increase from 860 to 974 (13.2% increase) using calculation method 1, or from 854 to 964 (12.9% increase) using calculation method 2. Conclusions: The modelled impact of such removal would be relatively minor, based on available data, regardless of the method used to calculate the 3-month rolling geometric mean. The focus of the current study was quite narrow, effectively from July to December 2013. Therefore, the results are an underestimate of the total number of herds liable for suspension during 2013. They may also underestimate the true percentage change in herds liable for suspension, with the removal of the seasonality formula. A national herd identifier was lacking from a sizeable percentage of the 2013 bulk tank SCC data, but will be needed if these data are to be meaningfully used for this or other purposes.Animal Health Irelan

Additional file 3: Figure S2. of The impact of removal of the seasonality formula on the eligibility of Irish herds to supply raw milk for processing of dairy products

The relative monthly change in the percentage of national volume under warning and liable for suspension following removal of the seasonality adjustment, using calculation method 1. (PDF 5 kb

The Herd-Level Sensitivity of Abattoir Surveillance for Bovine Tuberculosis: Simulating the Effects of Current and Potentially Modified Meat Inspection Procedures in Irish Cattle

The European Food Safety Authority (EFSA) has published a series of opinions to assess the impact of changing from the current meat inspection procedures (CMI) to visual-only inspection (VOI) procedures. Concern has been raised that changes from CMI to VOI would adversely affect the effectiveness of surveillance for bovine tuberculosis (bTB) in EU member states, both for countries with and without official status of bTB freedom (OTF and non-OTF countries, respectively). This study was conducted to estimate the impact of a change from CMI to VOI in abattoirs on herd-level detection sensitivity in Ireland, a non-OTF country. Using national Irish data, we identified all herds that sold at least one animal to slaughter during 2010-12 whilst unrestricted for bTB. For each of these herds, we calculated the number of cattle sent to slaughter whilst unrestricted, the number of factory lesion tests (FLT) that had been performed, and estimated the apparent within-herd prevalence (APwh). A FLT is a whole-herd test conducted in a herd following the confirmation of bTB in an animal at slaughter. We considered five different inspection scenarios, each based on meat inspection and bacteriology in series, including current meat inspection (CMI) and four visual-only inspection scenarios (VOI2, VOI3, VOI4, VOI5) with reducing inspection sensitivities. Separately for each inspection scenario, a simulation model was used to estimate the herd-level detection sensitivity and the number of bTB-herds (that is, herds that sent at least one animal detected with M. bovis to slaughter when unrestricted during 2010-12) that would and would not be detected. The simulated mean herd-level detection sensitivity estimates were 0.24 for CMI, and 0.16, 0.12, 0.10 and 0.08 for VOI2-5, assuming a 2-, 3-, 4-and 5-fold decrease, respectively, in the animal-level detection sensitivity of VOI relative to that of CMI. The estimated number of non-detected bTB-herds is substantial with CMI, and increases in the series of VOI scenarios with decreasing herd-level detection sensitivity. If VOI were introduced without alternative surveillance means to compensate for the decrease in animal-level inspection sensitivity, such changes might jeopardise bTB surveillance, control and eradication programmes in cattle herds of non-OTF countries, including Ireland.Department of Agriculture, Food and the Marin

Additional file 1: Appendix 1. of The impact of removal of the seasonality formula on the eligibility of Irish herds to supply raw milk for processing of dairy products

Pseudocode detailing the two methods for calculating the rolling geometric mean herd SCC and monthly herd compliance. (PDF 83 kb

Real-life safety of PD-1 and PD-L1 inhibitors in older patients with cancer: An observational study

Introduction: To compare the real-world safety profile of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors between younger and older patients. Materials and Methods: All patients receiving pembrolizumab, nivolumab, atezolizumab or durvalumab between September 2016 and September 2019 at Haga Teaching Hospital, The Hague, The Netherlands were included in this retrospective study. Immune-related adverse drug reactions (irADRs) were manually retrieved from the electronic patient files. The cumulative incidence of irADRs were compared between younger (<65 years) and older (≥65 years) patients using a Pearsons Chi-square test. Results: We identified 217 patients who were treated with at least one dose of PD-(L)1 inhibitor. 58% were 65 years or older at the start of immunotherapy. 183 patients (84.3%) received monotherapy PD-(L)1 inhibitors and 34 (15.7%) received chemo-immunotherapy. A total of 278 irADRs were registered. Cutaneous irADRs (53.9%), thyroid gland disorders (20.3%), and non-infectious diarrhoea/colitis (17.5%) were the most frequently reported irADRs. The majority of the irADRs were mild to moderate and no fatal irADRs were observed. 61 (21.9%) of the irADRs needed systemic treatment, of which 19 (6.8%) required treatment with corticosteroids. 18 irADRs (6.5%) were severe and resulted in hospitalisation. The cumulative incidence of cutaneous irADRs was different between the age groups: 45.7% of the patients <65 years and in 60.0% of the patients ≥65 years (p = 0.036). No statistical difference was found in the cumulative incidence of other irADRs between the two age groups. Discussion: Advanced age is not associated with immune-related adverse drug reactions of PD-1 and PD-L1 inhibitors