Effects of increased grazing intensity during the early and late grazing periods on the welfare of spring-calving, pasture-based dairy cows.

The objective of this study was to identify potential effects of increased grazing intensity, characterized by differing pasture availability and stocking rate, on indicators of welfare during both early and late grazing periods. Seventy spring-calving, pasture-based Holstein-Friesian and cross-bred dairy cows, averaging 35 ± 16 d in milk on the first day of data collection, were assigned to 3 treatments (20-26 cows/treatment) representing a range in grazing intensity: LO (high pasture availability, 980 kg DM/ha opening cover, 2.75 cows/ha, 90:10% pasture:concentrate diet), MOD (medium pasture availability, 720 kg DM/ha opening cover, 2.75 cows/ha, 90:10% pasture:concentrate diet), and HI (low pasture availability, 570 kg DM/ha opening cover, 3.25 cows/ha, 80:20% pasture:concentrate diet); representative of current, best practice and proposed production levels respectively for this system. Welfare indicators were locomotion score, digital dermatitis and white line disease, rumen fill, ocular and nasal discharge, integument damage to the neck-back and hock regions, and lying time. Data were collected during a 5-wk early grazing period in spring (EG) and a 7-wk late grazing period in autumn (LG). Average daily lying time was recorded for 8 to 10 focal cows per treatment. Results demonstrated only minor treatment effects. Cows on MOD [odds ratio (OR) = 3.11] and HI (OR = 1.95) were more likely to display nasal discharge compared with LO. Cows on MOD tended to have more damage to the skin on the neck-back region than LO (OR = 4.26). Total locomotion score (maximum = 25) was greater on LOW (7.1 ± 0.20) compared with HI (6.5 ± 0.19). Average lame cow prevalence for EG and LG respectively was 15.3 ± 3.12% and 39.2 ± 3.00% (LO), 20.0 ± 2.58% and 24.2 ± 5.69% (MOD), and 14.9 ± 4.79% and 17.0 ± 3.44% (HI). Cows on HI were less likely to have impaired walking speed than either LO (OR = 0.24) or MOD (OR = 0.29). Cows on both HI (OR = 0.36) and MOD (OR = 0.40) were less likely to display impaired abduction or adduction compared with those on LO. An interaction between treatment and period revealed longer lying times for cows on LO (10.6 h/d ± 0.39) compared with both MOD and HI (8.7 ± 0.43 and 8.4 ± 0.41 h/d) during EG only. The greatest effects were across grazing periods, with all indicators except rumen fill and locomotion score demonstrating improvements from EG to LG. This suggests cows were able to cope well with increasing levels of grazing intensity, and that regardless of treatment, a greater number of days on pasture led to improvements in welfare indicators.

Hoof lesions in partly housed pasture-based dairy cows.

Lameness is a symptom of a painful disorder affecting the limbs, which impacts dairy cow welfare and productivity. Lameness is primarily caused by hoof lesions. The prevalence of different lesion types can differ depending on environmental conditions and farm management practices. The aims of this observational study were to establish the cow-level and herd-level lesion prevalence during both housing and grazing periods in a partly housed, pasture-based system, establish the prevalence of lesions always associated with pain ("alarm" lesion), identify the lesions associated with a higher lameness score, determine relationships between lesions, and identify risk factors for digital dermatitis. On 98 farms during the grazing period and on 74 of the same farms during the housing period, every cow was lameness scored (0-3 lameness scoring scale), and the hind hooves of lame cows (score 2 and 3) were examined (maximum 20 cows per visit) and the prevalence of each lesion type recorded. To gather data on potential predictors for the risk factor analysis, a questionnaire with the farmer was conducted on lameness management practices and infrastructure measurements were taken at each visit. Cow-level data were also collected (e.g., parity, breed, milk yield, and so on). Noninfectious lesions were found to be more prevalent than infectious lesions in this system type. The most prevalent lesion types during both grazing and housing periods were white line separation, sole hemorrhages and overgrown claws; all remaining lesions had a cow-level prevalence of less than 15%. The cow-level prevalence of alarm lesions was 19% during the grazing period and 25% during the housing period; the most prevalent alarm lesion was sole ulcers during both periods. We found significantly more foreign bodies within the hoof sole (grazing = 14%, housing = 7%) and overgrown claws (grazing = 71%, housing = 55%) during the grazing period compared with the housing period. Cows with foul of the foot, sole ulcer, white line abscess, toe necrosis or an amputated claw had higher odds of being more severely lame, compared with mildly lame. The strongest correlation between lesions were between toe necrosis and digital dermatitis (r = 0.40), overgrown claws and corkscrew claws (r = 0.33), and interdigital hyperplasia and digital dermatitis (r = 0.31) at herd level. At the cow level, the strongest correlation was between overgrown claws and corkscrew claws (r = 0.27), and digital dermatitis and heel erosion (r = 0.22). The farmers' perception of the presence of digital dermatitis (and lameness) was significantly correlated with the actual presence of digital dermatitis recorded. Additional risk factors for the presence of digital dermatitis were cow track and verge width near the collecting yard, and stone presence on the cow tracks. Results from this study help further our understanding of the causes of lameness in partly housed, pasture-based dairy cows, and can be used to guide prevention and treatment protocols.

Cow- and herd-level risk factors for lameness in partly housed pasture-based dairy cows.

Lameness in dairy cows is a major animal welfare concern and has substantial economic impact through reduced production and fertility. Previous risk factor analyses have focused on housed systems, rather than those where cows were grazed for the majority of the year and housed only for the winter period. Therefore, the aim of this observational study was to identify a robust set of cow-level and herd-level risk factors for lameness in a pasture-based system, based on predictors from the housing and grazing periods. Ninety-nine farms were visited during the grazing period (April 2019-September 2019), and 85 farms were revisited during the housing period (October 2019-February 2020). At each visit, all lactating cows were scored for lameness (0 = good mobility, 1 = imperfect mobility, 2 = impaired mobility, 3 = severely impaired mobility), and potential herd-level risk factors were recorded through questionnaires and infrastructure measurements. Routine cow-level management data were also collected. Important risk factors for lameness were derived though triangulation of results from elastic net regression, and from logistic regression model selection using modified Bayesian information criterion. Both selection methods were implemented using bootstrapping. This novel approach has not previously been used in a cow-level or herd-level risk factor analysis in dairy cows, to the authors' knowledge. The binary outcome variable was lameness status, whereby cows with a lameness score of 0 or 1 were classed as non-lame and cows with a score of 2 or 3 were classed as lame. Cow-level risk factors for increased lameness prevalence were age and genetic predicted transmitting ability for lameness. Herd-level risk factors included farm and herd size, stones in paddock gateways, slats on cow tracks near the collecting yard, a sharper turn at the parlor exit, presence of digital dermatitis on the farm, and the farmers' perception of whether lameness was a problem on the farm. This large-scale study identified the most important associations between risk factors and lameness, based on the entire year (grazing and housing periods), providing a focus for future randomized clinical trials.

Mechanical thrombectomy for acute ischaemic stroke during the COVID-19 pandemic: changes to UK practice and lessons learned.

AIM: To describe evolving practices in the provision of mechanical thrombectomy (MT) services across the UK during the COVID-19 pandemic, the responses of and impact on MT teams, and the effects on training. MATERIALS AND METHODS: The UK Neurointerventional Group (UKNG) and the British Society of Neuroradiologists (BSNR) sent out a national survey on 1 May 2020 to all 28 UK neuroscience centres that have the potential capability to perform MT. RESULTS: Responses were received from 27/28 MT-capable centres (96%). Three of the 27 centres do not currently provide MT services. There was a 27.7% reduction in MTs performed during April 2020 compared with the first 3 months of the year. All MT patients in 20/24 centres that responded were considered as COVID-19 suspicious/positive unless or until proven otherwise. Twenty-two of the 24 centres reported delays to the patient pathway. Seventeen of the 24 centres reported that the COVID-19 pandemic had reduced training opportunities for specialist registrars (SpR). Fourteen of the 24 centres reported that the pandemic had hampered their development plans for their local or regional MT service. CONCLUSION: The present survey has highlighted a trend of decreasing cases and delays in the patient pathway during the early stages of the COVID-19 pandemic across UK centres.

Factors impacting on technical success in stroke thrombectomy: experience of a UK neuro-interventional unit.

AIM: To investigate factors that could impact on recanalisation and reperfusion in patients undergoing mechanical thrombectomy and to assess the technical success over time. MATERIALS AND METHODS: Two hundred consecutive patients who underwent thrombectomy for a proximal anterior circulation occlusion were dichotomised into equal groups (groups 1 and 2) based on the date that immediate access to emergency general anaesthesia (GA) commenced. RESULTS: Recanalisation success using thrombolysis in cerebral infarction (TICI) 2b/3 or TICI 2c/3 significantly improved in group 2 (67% versus 93%, p<0.0001; 52% versus 78%, p=0.0002). Symptomatic haemorrhage also reduced from 9% to 4%. Despite similar presentation Alberta Stroke Program Early (computed tomography) CT Scores (ASPECTS), post-procedural ASPECTS was significantly increased in group 2 (7; [interquartile range {IQR} 4-9] versus 8 [IQR 7-9]; p=0.0034). The number of patients with a post procedural ASPECTS of 8-10 increased (46% versus 64%, p=0.0155) and the difference in ASPECTS between pre- and post-thrombectomy CT was significantly lower (2 [IQR 1-4] versus 1 [IQR 0-2], p<0.0001). GA use increased from 8% to 56% (p=0.0001) as did use of distal aspiration (59% versus 87%, p=0.0001) mostly in combination with a stent-retriever. Failed access fell from 8% to 3%. When GA was used, successful recanalisation (TICI 2b/3) was achieved more frequently (90.5% versus 76.7%; OR 3.04, 1.2-7.69, p=0.0187). CONCLUSION: Technical results for thrombectomy are improving over time. Technique modification, operator experience, and judicious use of GA may be contributing.

Mitigation of variability between competitively fed dairy cows through increased feed delivery frequency.

The objective of this study was to determine whether increased frequency of total mixed ration (TMR) delivery could mitigate the effects of feed bunk competition on the behavior and productivity of individual lactating dairy cows within a group. We hypothesized that, for competitively fed cows, a greater frequency of TMR delivery would improve access to feed, and reduce individual variability in behavior, meal patterns, and production between cows. Sixteen lactating Holstein dairy cows (first lactation = 4, second lactation = 5, ≥ third lactation = 7) averaging 72 ± 35 d in milk and producing 42 ± 6 kg of milk/d at the start of the trial, were categorized as either young (≤ second lactation) or mature (≥ third lactation) and paired to maximize difference in parity. Pairs were housed 4 at a time and competitively fed a TMR at a ratio of 2 cows:1 feed bin. Cow pairs were exposed, in a crossover design, to each of 2 feed delivery frequency treatments: low (2×/d) and high (6×/d) frequency. Treatments were applied for 10 d, with dry matter intake (DMI), feeding behavior (feeding time, feeding rate, and meal patterns), and replacement frequency for each cow recorded using an automated feed intake system on d 6 to 10 of each period. Rumination time, feed sorting, lying behavior, and productivity were also measured for this period. Variability in behavior within pairs of cows was determined by averaging the absolute difference within each pair over the recording period to provide 1 value per pair. Frequency of TMR delivery did not affect feeding time, feeding rate, DMI, replacement frequency, feed sorting, or productivity. At the high delivery frequency, there was a tendency for rumination time to increase [low = 519.3; high = 544.3 min/d; standard error of the difference (SED) = 11.32], and to be more variable within pairs (low = 38.0, high = 50.0 min/d; SED = 5.57). Cows also had longer lying bouts at the high delivery frequency (low = 53.0; high = 55.5 min/bout; SED = 1.00). No differences in daily meal patterns were found between treatments; however, the average first meal following each feeding indicated that cows under the high delivery frequency spent less time, consuming smaller meals during peak feeding periods. Comparing the young and mature individuals within each treatment pair revealed that feeding rate (young = 0.16; mature = 0.19 kg/min; SED = 0.014) and DMI (young = 25.6; mature = 28.6 kg of DM/d; SED = 1.36) were lower for the young cows on both treatments. Meal frequency was greater in young cows (young = 9.0; mature = 7.5 meals/d; SED = 0.71) and meal size was greater in mature cows (young = 3.2; mature = 4.2 kg of DM/meal; SED = 0.32) across treatments. These results suggest that for cows fed at a high level of competition, increasing TMR delivery frequency from 2 to 6×/d led to consumption of shorter, smaller meals during peak periods of feed consumption. However, under these conditions, the relative parity of competitively fed cows had a greater effect on feeding behavior, meal patterns, and production than did the frequency of feed delivery.

Social housing influences the behavior and feed intake of dairy calves during weaning.

We investigated the effect of social housing on the behavioral, intake, and physiological changes that occur at weaning for dairy calves fed milk ad libitum. These changes were evaluated during the weaning (d 40 to 48 of age) and postweaning (d 49 to 56 of age) stages. Twenty male Holstein calves were fed milk replacer ad libitum and weaned gradually by dilution over 9 d starting at d 40 of age. Calves were housed in pairs (10 calves) or individually (10 calves) from birth until the beginning of the postweaning phase, when all calves were paired. Feed and water intake were monitored daily. Feeding time was video-recorded, and blood ß-hydroxybutyrate concentration was measured on alternate days beginning on d 40 and ending on d 56 of age. Electronic accelerometers continuously recorded standing and lying behavior for the 17-d study. Solid feed consumption increased by more than 5-fold over the weaning phase in all calves; during this phase pair-housed calves consumed more than twice (0.96 vs. 0.50 kg/d on d 48) that of the individually housed calves. Postweaning all calves rapidly increased their solid feed intake, and to a greater extent for previously individually housed calves, such that intake was similar between treatments by d 56. Free water intake was stable during weaning; however, a decrease (of 6.6 L) occurred in the constituent milk replacer water intake across this phase. As result, total water intake (free water + milk replacer water content) decreased (by 6.0 L) over the weaning phase between d 40 (14.9 L/d) and d 48 (8.9 L/d). On the first day postweaning (d 49), total water intake for all calves increased sharply (to 19.0 L/d) and then returned to a lower baseline (13.2 L/d) the next day (d 50), and slowly increased over the following week. During the weaning phase, feeding time and feeding rate increased with time for all calves, whereas pair-housed calves had greater feeding rates than individually housed calves (13.4 vs. 6.6 g of DM/min). After weaning, calves previously housed individually spent more time feeding in the early hours of the day than calves housed in pairs. Lying time and lying bout frequency decreased with calf age during the weaning period across treatments, and pair-housed calves tended to spend less time lying than individually housed calves (1,015 vs. 1,039 min/d) during this time period. Blood ß-hydroxybutyrate increased across treatments over the weaning period, with the largest increase occurring between d 48 (0.05 mmol/L) and d 50 (0.2 mmol/L). These results show that calves alter their behavioral patterns during weaning and that housing calves in pairs may ease the transition from milk to solid feed.

Variability in behavior and production among dairy cows fed under differing levels of competition.

The objective of this study was to investigate the effects of differing levels of competition for feed access on group-housed dairy cows, and on variations in behavior and productivity between individuals within each group. Eighteen lactating Holstein cows, averaging 77 ± 20 d in milk with a production of 46 ± 7 kg/d at the start of the trial, were divided into subgroups of 3 and fed a total mixed ration 3×/d. Groups were exposed to each of 3 competition levels: high (3 cows:1 feed bin), moderate (3 cows:2 feed bins), and low (3 cows:3 feed bins). Treatments were assigned in random order according to a modified Latin-square design, and each was applied for 10 d. Using an automated feed intake system, feeding behavior data (dry matter intake, feeding time, feeding rate, and meal patterns) were recorded for each cow on d 6 to 10 of each treatment period. Additional behavioral [sorting, rumination, competitive interactions (replacements), lying time] and production (milk yield and components) data were collected. Greater competition resulted in a reduction in feeding time (low = 202.6, moderate = 194.9, high = 183.6 min/d; SE = 8.84), and an increased rate of feed intake (low = 0.16, moderate = 0.18, high = 0.20 kg of dry matter/min; SE = 0.01), especially following fresh feed delivery and milking. Dry matter intake was similar across treatments (average of 29.1 kg/d). Meal length increased under high competition (low = 37.0, moderate = 36.6, high = 47.3 min/meal; SE = 5.05) due to greater non-feeding time within meals, which was approximately twice as long under high competition (low = 10.0, moderate = 10.8, high = 20.3 min/meal; SE = 3.24). Daily lying time (low = 10.2, moderate = 10.2, high = 9.5 h/d; SE = 0.51) and milk protein yield (low = 1.41, mod = 1.42, high = 1.36 kg/d; SE = 0.05) were reduced under high competition. Analysis of individual within-group variability, calculated as the daily standard deviation of each group, averaged across 5 recording days, revealed greater variability in feeding time, feeding rate, meal length, non-feeding time within meals, milk yield, milk fat composition (%), and milk fat component yield (kg/d) under high competition. These results suggest that at elevated competition levels, cows modify their feeding behavior to consume feed in a shorter period and devote a large portion of their mealtime toward waiting to gain feed access, resulting in reduced daily lying time. Furthermore, meal patterns and milk production vary greatly within groups of cows at high levels of competition for feed access.

Impact of timing of feed delivery on the behavior and productivity of dairy cows.

The objective of this work was to assess the effect of timing of feed delivery on the behavior and productivity of cows milked 3 times per day. Twelve lactating Holstein dairy cows (4 primiparous and 8 multiparous), milked 3 times per day (at 1400, 2100, and 0700 h), were individually assigned and exposed to each of 2 treatments (over 21-d periods) in a replicated crossover design. Treatments were the manipulation of timing of TMR delivery, 2 times per day, in relation to milking time: (1) feeding at milking time (at 1400 and 0700 h), and (2) feeding halfway between milking times (at 1730 and 1030 h). Milk production, feeding, sorting, and rumination behavior were monitored for each animal for the last 7 d of each treatment period. Milk samples were collected for 2 of the last 4 d of each period for milk component analysis. With a feed delivery delay, dry matter intake (DMI) tended to be lower (26.5 vs. 27.2 kg/d). Although no difference was found in feeding time (224.2 min/d), cows fed with a delay consumed their feed more slowly (0.12 vs. 0.13 kg of dry matter/min) in more frequent meals (10.0 vs. 9.1 meals/d), which were smaller in size (2.8 vs. 3.1 kg/meal) and tended to be shorter in duration (26.7 vs. 30.1 min/meal). Cows fed at milking sorted for long particles (102.3%), whereas cows fed with a delay did not sort for or against those particles. Cows sorted for medium particles to a similar extent (102.5%) on each treatment. Cows did not sort for or against short particles on either treatment. Sorting against fine particles was observed, to a similar extent (97.1%), on both treatments. Rumination time (8.9 h/d) and lying time (9.5 h/d) were similar between treatments. Cows without fresh feed at the 1400 h milking tended to stand for less time following that milking (71.0 vs. 94.0 min), whereas cows without fresh feed at the 0700 h milking stood for less time following that milking (66.3 vs. 87.8 min). No difference in this latency to lie down was seen at the 2100 h milking. Milk yield (48.0 kg/d), milk fat content (3.64%), and milk protein content (2.86%) were similar between treatments. Given the tendency for a difference in DMI and no change in yield, efficiency of production was improved with a feed delay (1.93 vs. 1.80 kg of milk/kg of DMI). These data suggest that moving the timing of feed delivery resulted in cows consuming their feed more slowly in smaller, more frequent meals, contributing to an improvement in efficiency of production.

Initial experience using middle meningeal artery embolisation for patients with recurrent and high-recurrence-risk chronic subdural haematoma.

Recurrence rates following surgical management of chronic subdural haematoma (CSDH) range from 5 to 33 %. There is growing evidence which suggests middle meningeal artery embolisation (MMAe) may reduce recurrence rates when used as surgical adjunct or standalone treatment. In this study we described our experience of this new procedure in the our UK institution. Patients with recurrent CSDH or CSDH at high risk of recurrence were selected for MMAe on a case-by-case basis following MDT discussion. A departmental database was used to identify patients treated. 26 CSDH were embolised in 20 patients; 9 CSDH were de-novo and 17 were recurrent. 10/26 CSDH were treated with MMAe only. No procedural mortality, access site or thrombo-embolic complications occurred. One patient experienced symptomatic collection growth 12 h following MMAe and required surgical drainage. 15 (75 %) of patients were living at home at follow-up (mean 14 months). On imaging follow-up 15/18 showed CSDH volume reduction or resolution, 1/18 remained stable requiring no further treatment, 2/18 patients suffered recurrent CSDH requiring treatment. In both recurrent cases incomplete embolisation was noted on procedural imaging (posterior division of MMA not embolised). Persistent posterior MMA division filling was significantly associated with collection recurrence (p = 0.002). Our results suggest MMAe as a stand-alone or adjuvant therapy can be performed safely in a UK neuroscience setting and is associated with high rates of symptomatic CSDH size reduction or resolution in problematic CSDH that have either recurred or are prone to recurrence.

Characteristics of pain in hospitalized medical patients, surgical patients, and outpatients attending a pain management centre.

BACKGROUND: The characteristics and psychological impact of pain suffered by medical inpatients has been relatively under-investigated. The aim of this study was to compare the pain experience of medical, surgical inpatients, and patients attending a pain management centre. Some aspects of the quality of pain scoring and prescribing were also audited. METHODS: Medical inpatients with significant pain (moderate or severe pain on a verbal rating scale) were assessed using a battery of psychometric questionnaires. Comparator samples of surgical inpatients and patients attending the pain management centre were recruited. RESULTS: The prevalence of significant pain did not differ between the medical group (n=37) and the surgical group (n=38) (16.7% and 19.9%). Chronic pain was common in the medical group (54%) and the surgical group (50%). There were no differences in psychometric variables between the medical and surgical groups. Clinically significant scores for anxiety and depression (HADS ≥11) were common in all groups (30-38%). There was less concordance between patient-reported pain scores and nurse-recorded pain scores in the medical group than the surgical group and analgesic prescribing differed between the two groups. CONCLUSIONS: The characteristics of pain in the medical and surgical groups were similar, with high levels of anxiety and depression. The pain management group differed from the inpatient groups, with higher levels of psychopathology and poorer coping. These findings provide some insight into the complex nature of pain in hospital inpatients, and may inform where limited resources should be utilized to provide greatest patient benefit.

Risk factors associated with indicators of dairy cow welfare during the housing period in Irish, spring-calving, hybrid pasture-based systems.

In a dairy production system where cows are grazing for a large portion of their lactation, little attention has been afforded to investigating multiple indicators of welfare for risk factors associated with the housing period. Yet regardless of the length of the housing period, cows still experience the positive and negative welfare impacts of both indoor and outdoor environments in a hybrid system. Thus, the objective of this study was to identify risk factors for indicators of dairy cow welfare during the housing period in a spring-calving, hybrid pasture-based system. Herd-level scores for seven indicators of welfare (locomotion, body condition, ocular and nasal discharge, integument damage, tail injury and human avoidance response) were collected from 82 Irish dairy farms during the housing period (October - February). Data were analysed using multiple beta regression or zero-inflated beta regression to identify associations between these welfare indicators and measured herd-level housing, resource and management factors. Thirty-six unique risk factors were associated with one or more welfare indicators (P < 0.05). Analyses identified two risk factors for body condition < 3.0 and four for body condition > 3.5, the target range during the housing period. Four risk factors were identified for each of ocular discharge, nasal discharge and avoidance response of > 1 m from human approach. Six risk factors each were associated with the proportion of lame cows and integument damage to the head-neck-back or hindquarter regions. The greatest number of risk factors, 12, were associated with tail injury (broken, lacerated or incomplete tails). Risk factors associated with multiple indicators of welfare were cow comfort index (tail lacerations and hindquarter integument damage), cubicle width (broken and incomplete tails), shed floor slipperiness (lameness and head-neck-back integument damage), shed light-level (tail lacerations, avoidance response and below target body condition), shed passage width (broken tails and head-neck-back integument damage) and presence (incomplete tails) or absence (broken tails) of a collecting yard backing gate. With the large number of risk factors associated with tail injury, continued research is necessary to identify causes and determine prevention methods to contribute to improved overall welfare of dairy cows. Housing features meeting recommended guidelines from the literature were frequently associated with greater negative indicators of welfare. In light of this, housing guidelines may benefit from regular re-evaluation to ensure facilities meet the welfare needs of cows during the housing period.

Lameness prevalence and management practices on Irish pasture-based dairy farms.

BACKGROUND: Lameness is a painful disease, which negatively impacts dairy cow production and welfare. The aim of this observational study was to determine herd lameness prevalence, describe current lameness management practices and identify the presence of established risk factors for lameness on Irish pasture-based dairy farms. Farms were visited once during grazing (99 farms) and again during housing (85 farms). Lameness scoring was carried out at each visit (AHDB 0-3 scale); cows were classified as lame if they scored two or three. Farm management practices and infrastructure characteristics were evaluated via farmer questionnaires and direct measurements of farm infrastructure. RESULTS: Median herd-level lameness prevalence was 7.9% (interquartile range = 5.6 - 13.0) during grazing and 9.1% (interquartile range = 4.9 - 12.0) during housing; 10.9% of cows were lame at a single visit and 3.5% were lame at both visits (chronically lame or had a repeat episode of lameness). Fifty-seven percent of farmers were not familiar with lameness scoring and only one farm carried out lameness scoring. Only 22% of farmers kept records of lame cows detected, and 15% had a lameness herd health plan. Twenty-eight percent of farmers waited more than 48 h to treat a lame cow, and 21% waited for more than one cow to be identified as lame before treating. Six percent of farmers carried out routine trimming and 31% regularly footbathed (> 12 times per year). Twelve percent put severely lame cows in a closer paddock and 8% stated that they used pain relief to treat severely lame cows. Over 50% of farms had at least one cow track measurement that was classified as rough or very rough, and cow tracks were commonly narrow for the herd size. On 6% of farms, all cubicle beds were bare concrete (no matting or bedding) and on a further 6% of farms, there was a combination of cubicles with and without matting or bedding. On 56% of farms, all pens contained less than 1.1 cubicles per cow and on 28% of farms, a proportion of pens contained less than 1.1 cubicles per cow. CONCLUSIONS: Overall, this study identified infrastructure and management practices which could be improved upon. The comparatively low lameness prevalence demonstrated, compared to fully housed systems, also highlights the benefits of a pasture-based system for animal welfare; however, there remains scope for improvement.

Risk factors associated with the welfare of grazing dairy cows in spring-calving, hybrid pasture-based systems.

Large-scale investigation of risk factors for multiple welfare indicators in hybrid pasture-based dairy systems is scarce. Our objective was to identify grazing season welfare risk factors on spring-calving, hybrid pasture-based dairy farms where cows experience periods of both grazing and housing. Herd-level data were collected from visits to 93 farms in the primary dairy producing counties of Ireland. Zero-inflated beta regression analysis was used to assess potential associations between categorical management and resource factors, and commonly measured animal-based welfare indicators: locomotion, body condition, nasal and ocular discharge, tail injury, integument damage, and avoidance behaviour. To account for small sample size due to elimination of farms with missing data, analyses were conducted on both a dataset of complete cases, and a dataset where missing values had been substituted for the most common response through single imputation. Resulting risk factors from both methods of analysis were compared for each indicator. Analyses identified 14 risk factors associated with one or more welfare indicators. The proportion of lame cows was positively associated with a previous housing period of four months or more compared to three months, all cubicles being outside recommended lengths and repairing roadways every two to three years compared to either yearly or more than every four years to never. The proportion of cows below minimum target grazing body condition score of 2.75 was negatively associated with participation in elective herd disease-testing in the past year. The proportion of cows with tail lacerations was positively associated with using a single breeding method, not employing part-time staff and not using brisket boards in cubicles. Previous housing period length was significantly associated with the proportion of cows with integument damage, although the direction of association was unclear. Moderate to severe nasal discharge was positively associated with collecting yard holding times of ≤ 60 min compared to > 90 min. Ocular discharge was negatively associated with manual health record-keeping and a collecting yard below the recommended area of 1.4 m2/cow. The proportion of cows with an avoidance response distance > 1 m was positively associated with herding cows without a dog present and having no additional full-time staff. Multiple risk factors were related to the housing period, suggesting that potential carry-over effects of housing management on welfare persist into the grazing period. This emphasizes the need for research to consider both housing and grazing periods in the management of welfare in hybrid pasture-based systems.

Clinical safety and tolerance of mitoxantrone.

Mitoxantrone has been administered to more than 4000 patients worldwide. From this data base, a summary of the latest information is presented on the effect of mitoxantrone on bone marrow, on its nonmyelosuppressive acute toxicities, on its local tolerability, and on measurements of organ function. Most of these patients had solid tumors and were treated with an initial dose of mitoxantrone (12 to 14 mg/m2). Predictable leucopenia was dose limiting, but clinically significant suppression of RBC or platelet count was rare. Other hematologic or blood chemistry abnormalities were infrequent. The most common adverse clinical effects were nausea and vomiting, stomatitis, and alopecia, though the majority of these cases were mild. Many patients experienced no adverse reactions to mitoxantrone; there have been no reports of cellulitis, vesication, or tissue necrosis following extravasation. From the global experience with mitoxantrone, it seems that for patients who have not previously received anthracycline therapy, the risk of congestive heart failure is minimal up to a cumulative mitoxantrone dose of 160 mg/m2. In randomized, comparative clinical trials in advanced breast cancer, using mitoxantrone or doxorubicin either as single agents or in combination with other standard drugs, the incidence of moderate or severe acute toxic side effects was much lower for patients treated with mitoxantrone or mitoxantrone-containing combinations. From these data, it is clear that mitoxantrone has an exceptional safety profile, particularly with regard to acute nonmyelosuppressive toxicity and local tolerability. This offers the patient a better quality of life during antineoplastic chemotherapy.

Side effect and safety data for fenbufen.

The overall safety pattern of fenbufen has been evaluated in a total of 2,667 patients: 1,667 of them in domestic clinical studies and 1,000 in foreign pivotal studies. Comparisons of several hundred patients--each receiving aspirin, indomethacin, and placebo--were made. Detailed analysis of all reported adverse effects demonstrated that fenbufen is a relatively safe nonsteroidal anti-inflammatory drug. The incidence and severity of adverse gastrointestinal experiences in patients treated with fenbufen were less than those in patients treated with either aspirin or indomethacin. Life-table analysis showed that during the first three months of therapy, the overall incidence and severity of gastrointestinal reactions due to fenbufen therapy were similar to those observed with placebo therapy. Cutaneous disorders were reported in more fenbufen- than placebo-treated patients during the first month of therapy, thereafter, the incidence was the same. Clinical laboratory results were evaluated in the 1,667 patients who received fenbufen in domestic studies. Elevations of alkaline phosphatase and serum glutamic oxaloacetic transaminase levels, occurred occasionally with eosinophilia, particularly during the first four weeks of therapy with fenbufen. In the majority of cases, however, these abnormal values returned to normal or near-normal values with continuance of fenbufen therapy. No cases of drug-related jaundice have been reported either in clinical trials or from countries where fenbufen is marketed. No clinically significant changes were observed in other laboratory parameters including total bilirubin, blood urea nitrogen, white blood cell count, platelets, hematocrit, hemoglobin, and stool occult blood. In summary, fenbufen was well tolerated and provides a good therapeutic ratio, particularly in respect to gastrointestinal intolerance.

5,6,7,8-Tetrahydroquinolines. 5. Antiulcer and antisecretory activity of 5,6,7,8-tetrahydroquinolinethioureas and related heterocycles.

A series of thioureas derived from 5,6,7,8-tetrahydroquinoline, 1,5-, 1,6-, and 1,8-naphthyridiness, pyrido[2,3-b]azepine, and 7-azaindoline has been prepared and tested for antisecretory activity in the pylorus-ligated rat and protective activity against gastric erosions caused by cold-restraint stress. The thioureas exhibit different structure-activity relationships from the corresponding 5,6,7,8-tetrahydroquinoline-8-thiocarboxamides and these relationships are discussed. The activity of the thioureas is less affected by structural differences than the corresponding thioamides although they probably have the same mode of action.

Synthesis and antiinflammatory activity of certain 5,6,7,8-tetrahydroquinolines and related compounds.

Modification of some 8-benzylidene-5,6,7,8-tetrahydroquinolines, which have good antiulcer activity, led to three distinct classes of compounds with good in vivo antiinflammatory activity. Initial efforts led to a series of alkenes derived from 5,6,7,8-tetrahydroquinolines substituted at the 8-position. A second approach concentrated on replacing the CH linkage of these 8-benzylidene-substituted compounds with other spacer groups and increasing the size of the cycloalkyl ring from a six- to seven-membered ring, which provided 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine analogues. Finally, the substituent was switched from the cycloalkyl ring to the 2-position of the pyridine ring. Variation of the 2-substituent was also examined. Optimal antiinflammatory activity after oral administration was found in both the rat carrageenan paw edema and rat developing adjuvant arthritis models with 2-substituted 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridines, and of particular interest was 27 (WY-28342).