Quantifying multiple burdens of dairy cattle production diseases and reproductive inefficiency: current knowledge and proposed metrics.

The economic burden of diseases and reproductive inefficiency in dairy cattle is evident and has been quantified. Dairy diseases and reproductive inefficiency are however associated with other issues as well, including animal welfare, environmental pressure, and public health risks. Quantifying these other issues is becoming important to help farmers making decisions. Quantification of the non-economic burdens of diseases and reproductive inefficiency is rare and lacks an overview of approaches and metrics. The first aim of this paper is to provide trends for associating diseases and reproductive inefficiency with economic and non-economic burdens of disease. The second aim is to provide a review of approaches and metrics used to quantify the non-economic burdens of disease and reproductive inefficiency. For the economic burden of diseases and reproductive performance, only an overview of the approaches used to quantify the burden is provided. The final aim is to propose approaches and metrics for future quantification of non-economic burdens caused by individual diseases. A literature search was conducted in Web of Science to identify scientific articles on mastitis, lameness, metabolic disorders and reproductive inefficiency in dairy cows. The search was restricted to articles published between 1 January 2010 and 31 December 2022 and resulted in 7,565 articles. The total number of articles that mentioned the economic, animal welfare, public health, and environmental burden was 1,253, 428, 291, and 77, respectively. An increase in the percentage of articles mentioning the economic, animal welfare, and public health burden is observed between 2010 and 2022. Despite the 2,049 articles that mentioned one of the burdens, the results showed that approximately 10% of the articles quantified one or more of these burdens. The economic burden of diseases and reproductive inefficiency has been quantified in 154 articles and very few articles quantified the non-economic burdens (9 articles for environment, 29 articles for public health and 2 articles for animal welfare). Eleven articles were identified that quantified multiple burdens, and in all these studies the economic burden was combined with a non-economic burden through a modeling approach (mainly simulation). We propose to link the non-economic burdens to biological simulation models, and thus develop bio-burden simulation models. Well-established approaches and metrics can be used to quantify economic, environmental, and public health burdens. For the economic impact, costs per cow per year can be assessed. A life cycle assessment can be performed for environmental impact and the public health impact can be assessed by a defined daily dose for antimicrobial use and disability-adjusted life years for zoonotic diseases. Regarding animal welfare, approaches and metrics to quantify the welfare impact of a diseased animal are not well established. For animal welfare, we propose a welfare-adjusted life years approach. The mentioned approaches and metrics are a proposal, and it is up to the scientific community to use them or, based on empirics and research experience, propose changes so that we will end up with robust approaches and metrics that enable us to compare research results and provide more evidence for animal health decision makers.

The economic effect of cow-based reproductive management programs with a systematic use of reproductive hormones.

Hormone-based reproductive management programs can be beneficial to improve dairy cow's reproductive performance. This study aimed to compare the economic impact of reproductive management programs using systematic hormonal treatments to individual cows with a specific DIM range with a reproductive management program using cow-specific hormonal treatment based on a veterinary diagnosis of ovarian dysfunction during a fertility check. An existing individual cow-based, dynamic, and stochastic bio-economic simulation model, mimicking the production dynamics of a 200 cow-herd in daily time steps, was extended with ovarian dysfunction and fertility inputs. Four hormone-based reproductive management programs were modeled. In the default reproductive management program, reflecting the current reproductive management of Dutch herds, lactating dairy cows are inseminated based on detection of estrus and non-cyclic dairy cows are treated with hormones based on a veterinary diagnosis of ovarian dysfunction during a fertility check. Hormone treatments prescribed by the veterinarian for anestrus, cystic, and sub-estrus cows were an 8-d progesterone-releasing intravaginal device (PRID)-Synch protocol (PRIDsynch), an Ovsynch protocol, and a PGF2⍺ treatment, respectively. The 3 other reproductive management programs reflected systematic hormonal treatments to cows at specific DIM and included a 1) Double-Ovsynch protocol for TAI with nonpregnant cows submitted to a resynchronization protocol (FTAI), 2) Double-Ovsynch protocol for TAI with nonpregnant cows detected in estrus or submitted to a resynchronization protocol (FTAI+ED), and 3) detection of estrus with cows not detected submitted to a PRIDsynch protocol (ED+TAI). All nonpregnant cows were submitted to a resynchronization protocol based on the absence (PRIDsynch) or presence (Ovsynch protocol) of a corpus luteum (CL). The annual mean net economic return (NER) was calculated for all reproductive management programs. Compared with the default reproductive management program, the highest NER was observed for the FTAI+ED reproductive management program with €23,764 higher net revenues, followed by the FTAI and the ED+TAI reproductive management programs with €19,550 and €14,314 higher net revenues, respectively. Overall, systematic hormone-based reproductive management programs gave higher costs due to more hormones administered and higher calving and feed costs due to more pregnant cows. Nevertheless, the additional revenues of milk and calves in the systematic hormone-based reproductive management programs outweighed the total cost. For instance, the FTAI+ED reproductive management program gave €8,953 higher total cost per year compared with the default but with €32,654 higher revenues. In summary, reproductive management programs where hormones were systematically used gave economic advantages over the current default reproductive management program in which hormones are administered to individual cows based on a veterinary diagnosis of ovarian dysfunction during a fertility check.

Effects of flow-controlled vacuum on milking performance and teat condition in a rotary milking parlor.

The objective of this study was to compare a vacuum control system that increases milking system vacuum during the peak flow period of milking to conventional constant vacuum control technology regarding its effect on milk flowrate and milking duration. Further objectives were to study the effects of flow-controlled vacuum on milking parlor performance. An observational study was conducted on a commercial dairy farm milking from 848 to 896 cows per day over the study period using a 60-stall rotary milking parlor. The flow-controlled vacuum control system was applied for 3 wk. Milking performance and teat condition were compared with 3-wk periods prior and subsequent to the test period using conventional vacuum control. Statistical analysis was performed assuming a cross-sectional study design during each period. Flow-controlled vacuum increased peak milk flowrate by 12% and increased average milk flowrate by 4%. The decrease in individual cow milking duration was proportional to milk yield per milking. Postmilking teat condition was good during the entire study period. The occurrence of rough teat ends was slightly reduced during the flow-controlled vacuum period with no meaningful difference in the occurrence of teats with blue color, palpable rings, or petechia. The combination of reduced vacuum during the low flow period of milking and the decrease in milking duration are likely factors that are protective of teat tissues. Bioeconomic modeling of the use of flow-controlled vacuum on the performance of rotary milking parlors, using the data that were collected during the study, showed that the reduction in milking duration of individual cows allows a higher rotary parlor speed. Modeled parlor throughput increased by 5.0% to 419 cows/h, 6.8% to 407 cows/h, and 4.2% to 326 cows/h when 80%, 95%, and 99% of the cows were finished milking at the end of the rotation for a 60-stall parlor. Model results showed that increased parlor throughput resulted in increased labor efficiency, reduced labor costs for milking, and a positive benefit-cost ratio on the investment for all but the smallest herd and parlor sizes considered.

Reproductive hormone use and its association with herd-level factors on Dutch dairy farms.

We studied the use of the 3 commonly used reproductive hormones, namely prostaglandins, GnRH, and progesterone, and associated herd-level factors on 760 Dutch dairy farms from 5 veterinary clinics. From 2017 to 2019 we collected data on the sales of reproductive hormones, converted this data into the number of reproductive hormone doses conducted, and expressed this as the annual number of reproductive hormone doses per 100 adult dairy cows. Additional herd-level information was available for 2019. Due to the excess of zeros in the data set (i.e., a substantial number of farms did not use any hormones), we used a zero-inflated negative binomial model to identify related herd-level factors for the use of reproductive hormones. In the entire study period of 2017 to 2019, 5.8% of the dairy farms did not use any reproductive hormones, with the proportion of nonusers varying between 0.0 and 10.3% per veterinary clinic. This proportion was around 13.5% on an annual basis. Prostaglandins were the most frequently used reproductive hormone in Dutch dairy cows (62.9%), followed by GnRH (33.1%) and progesterone (4.0%). Furthermore, participating in a veterinary herd health management program had a significant effect on reproductive hormone use. These farms used more reproductive hormones than farms that did not participate in a herd health management program and were less represented in the group of nonuser farms. Technologies, such as pedometers and automatic milking systems, also had an effect on reproductive hormone use. The presence of pedometers or activity monitors did not reduce the use of the reproductive hormones but was associated with a greater frequency of users. Farms with an automatic milking system used more reproductive hormones than farms with a conventional milking system. With this study, we have made a first step in achieving transparency in the Dutch dairy industry by providing an objective overview of reproductive hormone use on Dutch dairy farms and identifying associations with some herd-level factors.

Quarter- and cow-level risk factors for intramammary infection with coagulase-negative staphylococci species in Swiss dairy cows.

Bacteriological status, evaluation of udder symmetry, udder hygiene, and teat end scores of 92 dairy cows were assessed on 3 Swiss dairy farms in a longitudinal 1-yr study to determine risk factors for intramammary infection (IMI) with coagulase-negative staphylococci (CNS) species. Farm visits were performed monthly including sterile quarter milk sampling and udder evaluation of all lactating cows. Milk samples were evaluated for the presence of staphylococci using selective agar plates. Species identification was performed using MALDI-TOF mass spectrometry. Intramammary infection was defined as milk samples having ≥100 cfu per mL of milk according to culture results. Overall, 3,151 quarter samples were included in the statistical analysis. Staphylococcus chromogenes, Staphylococcus haemolyticus, Staphylococcus xylosus, and a Staphylococcus warneri-like species were the 4 most prevalent CNS species found. Hierarchical multivariable logistic regression models were built to evaluate risk factors for species-specific CNS IMI. Risk factors for Staph. chromogenes IMI were presence in herd B, the period from June 2014 to August 2014 and December 2014 to February 2015, and presence of udder edema. For Staph. haemolyticus, the relevant risk factor included coinfection with Staph. xylosus coinfection with other than the above-mentioned CNS species ("others") and the period from June 2014 to November 2014. Coinfection with Staph. haemolyticus and "others," the periods from June 2014 to August 2014 and December 2014 to February 2015, early phase of lactation (1-60 d in milk), and belonging to herd B were significantly associated with Staph. xylosus IMI. Mid and late lactation, coinfection with Staph. xylosus, and the period September 2014 to May 2015 were identified as significant risk factors for Staph. warneri-like IMI. For Staph. chromogenes, 60.6 and 26% of the variance was observed at the quarter and cow level, respectively, whereas for the other investigated species the highest variance was observed at the sample level. The predominant species within herds differed and was most pronounced for the Staph. warneri-like species.

A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†.

BACKGROUND: Nitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cisplatin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. PATIENTS AND METHODS: In this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)-paclitaxel (200 mg/m(2))-bevacizumab 15 mg/kg on day 1 every 3 weeks with or without NTG patches 15 mg (day -2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at α = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. RESULTS: Between 1 January 2011 and 1 January 2013, a total of 223 patients were randomized; 112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6-7.3) and 5.1 months (4.2-5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96-1.67). Overall survival (OS) was 11.6 months (8.8-13.6) in control arm and 9.4 months (7.8-11.3) in experimental arm, HR 1.02 (95% CI 0.71-1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). CONCLUSION: Adding NTG to first-line carboplatin-paclitaxel-bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC.

A multiarm randomized field trial evaluating strategies for udder health improvement in Swiss dairy herds.

The aims of this study were to quantify the effectiveness of specialist advice about udder health in Swiss dairy herds and to compare 3 different udder health improvement strategies against a negative control group. In 2010, 100 Swiss dairy herds with a high (between 200,000 and 300,000 cells/mL) yield-corrected bulk milk somatic cell count (YCBMSCC) were recruited for a 1-yr multiarm randomized field trial. The herds were visited between September and December 2011 to evaluate udder health-management practices and then randomly allocated into 1 of 4 study arms containing 25 herds each. The negative control study arm received neither recommendations for improving udder health nor any active support. The remaining 75 farmers received a herd-specific report with recommendations to improve udder health management. The positive control study arm received no further active support during 2012. The veterinarian study arm received additional support in the form of monthly visits by their herd veterinarian. Finally, the study group study arm received support in the form of bimonthly study group meetings where different topics concerning udder health were discussed. One year later, implementation of recommendations and changes in udder health were assessed. Of the recommendations given, 44.3% were completely implemented, 23.1% partially, and 32.6% were not implemented. No differences in implementation of recommendations were noted between the 3 study arms. At study enrollment, farmers were asked for the study arm of their preference but were subsequently randomly assigned to 1 of the 4 study arms. Farmers that were assigned to the study arm of their preference implemented more recommendations than farmers assigned to a study arm not of their preference. No decrease in the within-herd prevalence of cows that had a high (≥200,000 cells/mL) composite somatic cell count was observed in herds that had a YCBMSCC ≥200,000 cells/mL at the start of intervention. However, the 3 study arms with intervention (positive control, the veterinarian, and the study groups) prevented an increase in the within-herd prevalence of cows that had a high somatic cell count in herds with a low YCBMSCC at the start of the intervention compared with the negative control study arm. In the year after sending the report, herds assigned to the study group study arm had a reduced incidence rate of treated mastitis cases in comparison with the year before sending the report.

Mediators of physical exercise for improvement in cancer survivors' quality of life.

OBJECTIVE: Mediating mechanisms of a 12-week group-based exercise intervention on cancer survivors' quality of life (QoL) were examined to inform future exercise intervention development. METHODS: Two hundred nine cancer survivors ≥ 3 months posttreatment (57% breast cancer) aged 49.5 (± 10.4) years were assigned to physical exercise (n = 147) or wait-list control (n = 62). QoL, fatigue, emotional distress, physical activity, general self-efficacy and mastery were assessed at baseline and post-intervention using questionnaires. Path analysis was conducted using Mplus to explore whether improved physical activity, general self-efficacy and mastery mediated the effects of exercise on fatigue and distress and consequently QoL. RESULTS: The intervention was associated with increased physical activity (ß = 0.46, 95% confidence interval (CI) = 0.14;0.59), general self-efficacy (ß = 2.41, 95%CI = 0.35;4.73), and mastery (ß = 1.75, 95%CI = 0.36;2.78). Further, the intervention had both a direct effect on fatigue (ß = -1.09, 95%CI = -2.12;0.01), and an indirect effect (ß = -0.54, 95%CI = -1.00;-0.21) via physical activity (ß = -0.29, 95%CI = -0.64;-0.07) and general self-efficacy (ß = -0.25, 95%CI = -0.61;-0.05). The intervention had a borderline significant direct effect on reduced distress (ß = -1.32, 95%CI = -2.68;0.11), and a significant indirect effect via increased general self-efficacy and mastery (ß = -1.06, 95%CI = -1.89;-0.38). Reductions in fatigue (ß = -1.33, 95%CI =-1.85;-0.83) and distress (ß = -0.86, 95%CI = -1.25;-0.52) were associated with improved QoL. Further, increased physical activity was directly associated with improved QoL (ß = 3.37, 95%CI = 1.01;5.54). CONCLUSION: The beneficial effect of group-based physical exercise on QoL was mediated by increased physical activity, general self-efficacy and mastery, and subsequent reductions in fatigue and distress. In addition to physical activity, future interventions should target self-efficacy and mastery. This may lead to reduced distress and fatigue, and consequently improved QoL of cancer survivors.

A longitudinal study investigating the prevalence of Staphylococcus aureus genotype B in seasonally communal dairy herds.

Staphylococcus aureus is a major mastitis-causing pathogen. Various genotypes have been recently identified in Switzerland but Staph. aureus genotype B (GTB) was the only genotype associated with high within-herd prevalence. The risk of introducing this Staph. aureus genotype into a herd may be increased by frequent animal movements. This may also be the case when cows from different herds of origin are commingled and share their milking equipment for a limited period of time. The aim of the present study was to determine the prevalence of Staph. aureus GTB in seasonally communal dairy herds before and after a summer period when dairy farming is characterized by mixing cows from different herds of origin in 1 communal operation. In addition, the environment was investigated to identify potential Staph. aureus GTB reservoirs relevant for transmission of the disease. A total of 829 cows from 110 herds of origin in 9 communal operations were included in the study. Composite milk samples were collected from all cows during the first or second milking after arrival at the communal operation and again shortly before the end of the season. Swab samples from the environment, involved personnel, and herding dogs present were collected before the cows arrived. At the end of the season, sampling of personnel was repeated. All samples were analyzed for the presence of Staph. aureus GTB using an established quantitative PCR. At the beginning of the season, Staph. aureus GTB-positive cows were identified in 7 out of 9 communal operations and the within-communal operation prevalence ranged from 2.2 to 38.9%. At the second sampling, all communal operations were Staph. aureus GTB positive, showing within-communal operation prevalence from 1 to 72.1%. The between-herd of origin prevalence increased from 27.3 to 56.6% and the cow-level prevalence increased from 11.2% at the beginning of the season to 29.6% at the end of the season. On 3 different communal operations, Staph. aureus GTB-positive swabs from seasonally employed personnel were identified at the end of the season. The results indicate that Staph. aureus GTB can easily spread in communal operations when cows from different herds of origin are mixed during the summer season. Effective management measures need to be designed to prevent the spread of Staph. aureus GTB in seasonally communal herds.

Genotype-specific risk factors for Staphylococcus aureus in Swiss dairy herds with an elevated yield-corrected herd somatic cell count.

Bovine mastitis is a frequent problem in Swiss dairy herds. One of the main pathogens causing significant economic loss is Staphylococcus aureus. Various Staph. aureus genotypes with different biological properties have been described. Genotype B (GTB) of Staph. aureus was identified as the most contagious and one of the most prevalent strains in Switzerland. The aim of this study was to identify risk factors associated with the herd-level presence of Staph. aureus GTB and Staph. aureus non-GTB in Swiss dairy herds with an elevated yield-corrected herd somatic cell count (YCHSCC). One hundred dairy herds with a mean YCHSCC between 200,000 and 300,000cells/mL in 2010 were recruited and each farm was visited once during milking. A standardized protocol investigating demography, mastitis management, cow husbandry, milking system, and milking routine was completed during the visit. A bulk tank milk (BTM) sample was analyzed by real-time PCR for the presence of Staph. aureus GTB to classify the herds into 2 groups: Staph. aureus GTB-positive and Staph. aureus GTB-negative. Moreover, quarter milk samples were aseptically collected for bacteriological culture from cows with a somatic cell count ≥150,000cells/mL on the last test-day before the visit. The culture results allowed us to allocate the Staph. aureus GTB-negative farms to Staph. aureus non-GTB and Staph. aureus-free groups. Multivariable multinomial logistic regression models were built to identify risk factors associated with the herd-level presence of Staph. aureus GTB and Staph. aureus non-GTB. The prevalence of Staph. aureus GTB herds was 16% (n=16), whereas that of Staph. aureus non-GTB herds was 38% (n=38). Herds that sent lactating cows to seasonal communal pastures had significantly higher odds of being infected with Staph. aureus GTB (odds ratio: 10.2, 95% CI: 1.9-56.6), compared with herds without communal pasturing. Herds that purchased heifers had significantly higher odds of being infected with Staph. aureus GTB (rather than Staph. aureus non-GTB) compared with herds without purchase of heifers. Furthermore, herds that did not use udder ointment as supportive therapy for acute mastitis had significantly higher odds of being infected with Staph. aureus GTB (odds ratio: 8.5, 95% CI: 1.6-58.4) or Staph. aureus non-GTB (odds ratio: 6.1, 95% CI: 1.3-27.8) than herds that used udder ointment occasionally or regularly. Herds in which the milker performed unrelated activities during milking had significantly higher odds of being infected with Staph. aureus GTB (rather than Staph. aureus non-GTB) compared with herds in which the milker did not perform unrelated activities at milking. Awareness of 4 potential risk factors identified in this study guides implementation of intervention strategies to improve udder health in both Staph. aureus GTB and Staph. aureus non-GTB herds.

[Cost-benefit analysis of an intervention to improve udder health in Swiss dairy farms]. / Kosten-Nutzen-Analyse einer Intervention zur Verbesserung der Eutergesundheit in Schweizer Milchviehbetrieben.

The objective of this study was to calculate the national costs associated with udder health in Switzerland and to estimate the cost effectiveness of an udder health intervention program. In 49 farms, yearly mastitis associated costs before and during an intervention were collected at herd level. Costs were calculated for each lactating cow being present in the herd. At the beginning of the intervention, 24 farms received a report with recommendations to improve the udder health. In the following year, those herds were followed-up by their veterinarian at a monthly basis. The other 25 farms were used as a negative control group and neither received any recommendations nor any follow-up. In the first year of analysis (2010), the median udder health associated costs were 209.- Swiss Francs for each lactating cow, regardless of the intervention group. During the intervention period (2012), mastitis associated costs were 191.- Swiss Francs for control farms and 396.- Swiss Francs for farms with veterinary intervention on a monthly basis. The median additional costs for herds with intervention were 159.- Swiss Francs per lactating cow. At the national level, mastitis associated costs were estimated at 129.4 millions of Swiss Francs per year. The cost effectiveness of future mastitis control programs can be evaluated with the help of the deterministic model developed during this study.

Le but du présent travail était de calculer les coûts de la santé de la mamelle dans des exploitations laitières suisses et d'estimer l'efficacité économique d'une intervention en vue de l'améliorer. Pour cela on a relevé les coûts liés aux mammites sur une année dans 49 exploitations, et cela durant l'année précédant l'intervention puis dans l'année de l'intervention et on l'a divisé par le nombre de vaches en lactation. Vingt-quatre exploitations ont reçu au début de l'étude des recommandations en vue d'améliorer la santé de la mamelle et ont ensuite été suivies mensuellement durant une année par leur vétérinaire d'exploitation. Les 25 autres exploitations n'ont reçu aucune recommandation et ont été utilisées comme groupe de contrôle. Dans la première année d'analyse (2 ans avant l'intervention, 2010), les coûts moyens de la santé de la mamelle, indépendamment du groupe s'élevaient à CHF 209.­ par vache en lactation. Durant l'année de l'intervention, ils se montaient à CHF 191.­ pour les exploitations de contrôle contre CHF 396.- pour les exploitations suivies. Les dépenses supplémentaires durant l'intervention s'élevaient en moyenne à CHF 159.­ par vache en lactation. Au niveau national, on estime les coûts liés aux mammites à CHF 129.4 millions. Les modèles de calcul utilisés dans la présente étude permettent de juger à l'avenir de la rentabilité des programmes de contrôle des mammites.

Development and Portability of a Text Mining Algorithm for Capturing Disease Progression in Electronic Health Records of Patients With Stage IV Non-Small Cell Lung Cancer.

PURPOSE: The objective was to develop and evaluate the portability of a text mining algorithm for prospectively capturing disease progression in electronic health record (EHR) data of patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunochemotherapy. METHODS: This study used EHR data from patients with mNSCLC receiving immunochemotherapy (between October 1, 2018, and December 31, 2022) in four Dutch hospitals. A text mining algorithm for capturing disease progression was developed in hospitals 1 and 2 and then transferred to hospitals 3 and 4 to evaluate portability. Performance metrics were calculated by comparing its outcomes with manual chart review. In addition, data were simulated to come available over time to assess performance in real-time applications. Median progression-free survival (PFS) was calculated using the Kaplan-Meier method to compare text mining with manual chart review. RESULTS: During development and portability, the text mining algorithm performed well in capturing disease progression, with all performance scores >90%. When real-time performance was simulated, the performance scores in all four hospitals exceeded 90% from week 15 after the start of follow-up. Although the exact progression dates varied in 46 patients of 157 patients with progressive disease, the number of patients labeled with progression too early (n = 24) and too late (n = 22) was well balanced with discrepancies ranging from -116 to 384 days. Nevertheless, the PFS curves constructed with text mining and manual chart review were highly similar for each hospital. CONCLUSION: In this study, an accurate text mining algorithm for capturing disease progression in the EHR data of patients with mNSCLC was developed. The algorithm was portable across different hospitals, and the performance over time was good, making this an interesting approach for prospective follow-up of multicenter cohorts.

Improving bovine udder health: a national mastitis control program in the Netherlands.

Because of increasing bulk milk somatic cell counts and continuous clinical mastitis problems in a substantial number of herds, a national mastitis control program was started in 2005 to improve udder health in the Netherlands. The program started with founding the Dutch Udder Health Centre (UGCN), which had the task to coordinate the program. The program consisted of 2 parts: a research part and a knowledge-transfer part, which were integrated as much as possible. The knowledge-transfer part comprised 2 communication strategies: a central and a peripheral approach. The central approach was based on educating farmers using comprehensive science-based and rational argumentation about mastitis prevention and included on-farm study group meetings. Comprehensive education materials were developed for farmers that were internally motivated to improve udder health. In the peripheral approach it was tried to motivate farmers to implement certain management measures using nontechnical arguments. Mass media campaigns were used that focused on one single aspect of mastitis prevention. These communication strategies, as well as an integrated approach between various stakeholders and different scientific disciplines were used to reach as many farmers as possible. It should be noted that, because this intervention took place at a national level, no control group was available, as it would be impossible to isolate farmers from all forms of communication for 5 years. Based on several studies executed during and after the program, however, the results suggest that udder health seemed to have improved on a national level during the course of the program from 2005 to 2010. Within a cohort of dairy herds monitored during the program, the prevalence of subclinical mastitis did not change significantly (23.0 in 2004 vs. 22.2 in 2009). The incidence rate of clinical mastitis, however, decreased significantly, from 33.5 to 28.1 quarter cases per 100 cow years at risk. The most important elements of the farmers' mindset toward mastitis control also changed favorably. The simulated costs of mastitis per farm were reduced compared with a situation in which the mastitis would not have changed, with € 400 per year. When this amount is extrapolated to all Dutch farms, the sector as a whole reduced the total costs of mastitis by € 8 million per year. It is difficult to assign the improved udder health completely to the efforts of the program due to the lack of a control group. Nevertheless, investing € 8 million by the Dutch dairy industry in a 5-yr national mastitis control program likely improved udder health and seemed to pay for itself financially.

[Mastitis management in Swiss dairy farms with udder health problems]. / Mastitis-Management in Schweizer Milchviehbetrieben mit Eutergesundheitsproblemen.

The objective of this study was to describe the udder health management in Swiss dairy herds with udder health problems. One hundred dairy herds with a yield-corrected somatic cell count of 200'000 to 300'000 cells/ml during 2010 were selected. Data concerning farm structure, housing system, milking technique, milking procedures, dry-cow and mastitis management were collected during farm visits between September and December 2011. In addition, quarter milk samples were collected for bacteriological culturing from cows with a composite somatic cell count ≥ 150'000 cells/ml. The highest quarter level prevalence was 12.3 % for C. bovis. Eighty-two percent of the pipeline milking machines in tie-stalls and 88 % of the milking parlours fulfilled the criteria for the vacuum drop, and only 74 % of the pipeline milking machines met the criteria of the 10-l-water test. Eighty-five percent of the farms changed their milk liners too late. The correct order of teat preparation before cluster attachment was carried out by 37 % of the farmers only. With these results, Swiss dairy farmers and herd health veterinarians can be directed to common mistakes in mastitis management. The data will be used for future information campaigns to improve udder health in Swiss dairy farms.

Le but de cette étude était de décrire la gestion de la santé de la mamelle dans des exploitations connaissant des problèmes en la matière. Pour cela, on a sélectionné 100 exploitations laitières présentant, en 2010, un nombre théorique de cellules dans le lait de mélange compris entre 200'000 et 300'000 cellules/ml. Les données relatives à la structure de l'exploitation, à la détention des animaux, à la technique et au travail de traite ainsi qu' à la gestion du tarissement et des mammites ont été relevées lors d'une visite d'exploitation dans la période allant de septembre à décembre 2011.En outre des échantillons de lait des vaches avec un nombre de cellules ≥ 150'000/ml ont été analysés bactériologiquement. La prévalence la plus élevée au niveau des quartiers était celle de C. bovis avec 12.3 %. Lors du test des machines à traire relatif à la chute du vacuum, 82 % des installations des stabulations entravées et 88 % des salles de traites étaient dans la zone normale et seules 74 % des installations réussissaient le «test des 10 l d'eau¼. Le changement des manchons était effectué trop tard dans 85 % des exploitations. Seul 37 % des exploitants se tenaient, lors de la préparation des mamelles, à un ordre correct des phases de travail. Ces résultats doivent rendre les producteurs de lait et les vétérinaires d'exploitations attentifs aux erreur de gestion les plus fréquentes. Ces données serviront de bases pour les campagnes d'information futures, dans le but d'améliorer la santé de la mamelle dans les exploitations laitières suisses.

The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer.

INTRODUCTION: Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations. MATERIALS AND METHODS: This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m2 (normal weight and reference), 25.0-29.9 kg/m2 (overweight) or ≥30.0 kg/m2 (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR]. RESULTS: Overweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90). CONCLUSION: This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m2, and to verify calculated dosing of carboplatin for appropriateness.

Baseline survey of health prophylaxis and management practices on Swiss dairy farms.

Health prophylaxis management practices have acquired a major role in the success of dairy herd health programs, however, little is known about the scope and level of implementation on Swiss dairy farms. The main objective of this study was therefore to provide a general overview of the most important preventive measures which are currently being used on these farms. In March 2011, an online survey with 75 questions was sent to 2'285 randomly selected Swiss dairy farmers. Response rate by question ranged from 35 to 53 %. Within this study, answers were compared between dairy farms with a tie-stall (n = 739) and farms with a free-stall (n = 458). Homeopathic treatments were used by 51 % of the dairy farmers and antibiotic dry cow treatments by 94 %. Farmers with a tie-stall tended to carry out more prophylactic treatments against external parasites, vaccinated their cows more frequently against Clostridium chauvoei and Moraxella bovis, and carried out claw trimming more frequently than dairy farmers with a free-stall. A higher proportion of dairy farmers with a free-stall had a written feeding plan, carried out regular feed analysis, wore an apron and rubber gloves during milking, and carried out post milking teat disinfection more frequently than dairy farmers with a tie-stall. The data collected in this survey could assist in improving future dairy health communication campaigns in Switzerland.

Multi-Criteria Decision Analysis in Food Safety Risk Management: The Case of Dioxins in Baltic Fish.

The Swedish risk management case of Baltic fatty fishes, in which dioxin levels may be too high, is a typical multidimensional food safety decision problem involving public health, economic, environmental and socio-cultural aspects. To effectively address the dioxin food safety problem, the multiple dimensions and conflicting interests of stakeholders have to be considered systematically when evaluating competing risk management options. The objectives of this study were to illustrate the applicability of the Multi-Criteria Decision Analysis (MCDA) method for multidimensional food safety risk management problems, and to evaluate the Swedish dioxin risk management using MCDA. The results show that the MCDA method is indeed a relevant tool for modelling the multifactorial Swedish dioxin problem and for initiating discussions amongst stakeholders to increase the acceptance of chosen strategies. Abolishing the derogation from the European Commission's maximum limits for the presence of dioxins in Swedish fish is the dominant strategy for risk assessors, whereas the preferences provided by the other stakeholders would suggest a continuation of the derogation without providing consumer information. However, the preferences of female consumers match with the 2011 decision of the Swedish government to ask for a derogation in combination with consumer information. The conclusion drawn from our MCDA analysis is comparable to the government's decision that-given the gradual reduction in dioxin concentrations in Baltic fish-the decision to continue providing consumer information or not mainly depends on how risk managers balance the preferences of the different stakeholders.

Social integration of people with intellectual disability: insights from a social psychological research programme.

BACKGROUND: Social integration of people with intellectual disability (ID) moving into regular neighbourhoods tends to be studied and evaluated without detailed knowledge about the social psychological aspects of everyday interaction between neighbours with and without ID. The goal of the present paper is to show how the authors' social psychological research programme may contribute to this field of inquiry. METHODS: The different ways in which societies respond to features and behaviours that may be perceived as deviant are theoretically analysed. Results of empirical studies are reported to clarify how social responses to people with ID are special in terms of perceptions, emotions and interaction desires of people with and without ID during a pre-contact and contact phase. RESULTS: On the basis of the theoretical analysis, it is concluded that regular neighbouring in modern Western society often takes the form of benevolent tolerance, rather than stigmatisation and prejudice. However, empirical studies reveal that, prior to getting people with ID as new neighbours, prospective neighbours without ID experience a specific pattern of emotions that are associated with specific desires (e.g. with respect to information supply or a caring relationship). These anticipatory reactions are dependent on the expected size of the group moving in and on the severity of ID. Furthermore, while actually engaging in neighbouring, neighbours with and without ID appear to have experiences related to behaviour of residents, staff and features of housing facilities that are perceived as (in)congruent with regular neighbouring. CONCLUSIONS: It is concluded that interpersonal relationships between neighbours with and without ID should not be simplified in terms of attitudes that would be primarily prejudiced/stigmatising versus entirely accepting. Rather, our studies paint a more complex picture of sometimes ambivalent thoughts, feelings and interaction needs that all should be taken into account to make social integration a success.

Interactions between risk assessors and risk managers during three major food incidents in Europe.

Risk analysis consists of risk assessment (RA), risk management (RM), and risk communication (RC). In most countries, RA and RM of food safety are separated to achieve a high scientific integrity, and typically occur in sequential order. However, in case of a food safety incident, even though being separate processes, RA and RM are performed simultaneously due to great time pressure and expected high impacts. The aim of this study was to analyze and evaluate the observed interactions between RA and RM processes, during three major food incidents in Europe, and to provide suggestions for possible improvement. Based on the differences observed between the three cases, strengths and weaknesses of each system have been identified. The enterohemorrhagic Escherichia coli (EHEC) crisis in 2011 in Germany, the horsemeat scandal in 2013 in Ireland, and the fipronil incident in 2017 in the Netherlands were used as case studies. Timelines of these incidents and crisis management procedures in place in each of the three countries provided the basis for further analysis. First, results showed that details of the communication processes between RA and RM bodies were frequently lacking in crisis management protocols. Second, RA, RM, and RC processes differed for each incident, due to differences in estimated risk for public health, but also due to differences in the organization within a country. Based on our results, we recommend that crisis management protocols should contain a section on communication between RA, RM, and on communication between member states in the EU.

Therapeutic effects of antimicrobial treatment during lactation of recently acquired bovine subclinical mastitis: two linked randomized field trials.

Two linked randomized field trials were performed on 39 herds in the Netherlands to 1) determine therapeutic effects of antimicrobial treatment of recently acquired subclinical mastitis (RASCM) during lactation, 2) evaluate the effect of duration of subclinical mastitis on therapeutic outcome, and 3) identify factors related to the therapeutic success of RASCM. Cows with a first elevated composite somatic cell count (CSCC) after 2 consecutive low CSCC measurements were eligible for enrollment in trial 1 (treatment at the first elevated CSCC). Quarter milk samples were collected to determine bacteriological status for major pathogens and coagulase-negative staphylococci. Cows with one or more culture-positive quarters with a quarter somatic cell count (QSCC) >or=100,000 cells/mL were defined to have RASCM and were randomly assigned treatment or control (no treatment). Untreated cows from trial 1 that had a second elevated CSCC at the next milk recording were eligible for enrollment in trial 2 (treatment at the second elevated CSCC). In trial 2, staphylococci-positive cows (Staphylococcus aureus and coagulase-negative staphylococci) were randomly assigned to treatment or control. Farmers used their own treatment protocols to treat quarters in both trials. Bacteriological cure was defined as absence of the pathogen identified pre-intervention in 2 samples post-intervention; QSCC, CSCC, and milk yield were also analyzed. Hierarchical logistic and linear models were used to determine therapeutic effects and to identify factors related to therapy outcome. Treated quarters had a higher bacteriological cure rate than control quarters for all pathogens in both trials. Treatment resulted in lower QSCC and CSCC, whereas milk yield was not affected by treatment. Bacteriological cure of RASCM was better in quarters with a low QSCC pre-intervention and in coagulase-negative staphylococci-positive quarters. Control quarters with a single culture-positive sample pre-intervention also had a higher bacteriological cure than control quarters with >or=2 culture-positive samples. Time of antimicrobial treatment affected bacteriological cure for penicillin-sensitive Staph. aureus. Bacteriological cure tended to be higher for Staph. aureus after treatment at the first elevated CSCC compared with treatment at the second elevated CSCC. Thus, early treatment of Staph. aureus might be more effective than later treatment.