Use of recombinant tissue plasminogen activator (rTPA) for treatment of fibrin in the anterior chamber of the horse.

BACKGROUND: Recombinant intracameral tissue plasminogen activator (rTPA) administration can aid clearance of fibrin from the anterior chamber. MATERIALS AND METHODS: In this retrospective multicentre case series, the effect of intracameral rTPA administration to treat fibrin in the anterior chamber resulting from trauma or inflammatory ocular disease was evaluated. Clinical data from 30 treatments in 29 horses were obtained from medical records from 2003 to 2022. Association between time from onset of clinical signs and time for rTPA treatment to effect was studied with regression analysis. RESULTS: Twenty-seven horses (93.1%) had no previous history of ophthalmic disease; one had an iridic cyst, and another had equine recurrent uveitis. The majority of cases were related to trauma (79.3%). Median time from the onset of clinical signs to treatment was 12 h (IQR = 4-48 h). rTPA (72% 20 µg; 24% 25 µg; 3.3% 40 µg) was administered once in all but one eye, which was treated twice. Resolution of fibrin was seen in 96.9% (29/30) of treatments. Fibrin accumulation recurred in one case but resolved 14 days after the second treatment. Complications were seen in four treatments (13.3%): moderate pain for 24 h, intracameral debris and mild intracameral haemorrhage in a horse that received 40 µg of tissue plasminogen activator. Recurrence of fibrin accumulation was absent in 96.7% of cases. Median time to effect was 20 min (IQR = 10-45 min). Time for rTPA treatment to effect was not associated with time from fibrin formation (R2 = 0.09; p = 0.11). CONCLUSION: Intracameral rTPA treatment can be considered at 20-25 µg in 0.1 mL solution to aid resolution of fibrin accumulation.

An objective study into the effects of an incline on naturally occurring lameness in horses.

BACKGROUND: The clinical examination of lame horses in real world settings often requires the use of sloped surfaces. OBJECTIVES: This pilot study aimed to evaluate the effects of uphill and downhill locomotion on asymmetry in horses with naturally occurring lameness affecting forelimbs and hindlimbs. METHODS: Ten horses (8-19 years) with forelimb lameness and eight horses (7-16 years) with hindlimb lameness were fitted with inertial sensors at the poll, withers, sacrum and both tuber coxae. Data were collected whilst the horses were trotted in hand on a level surface (<0.7%), as well as up and down a minor slope of 2.4%. Data were collected for a minimum of 25 strides at each incline type. Effect of incline was compared using a repeated measures ANOVA and, where significant, a subsequent Bonferroni's multiple comparisons. RESULTS: Of the horses with hindlimb lameness, there were reductions in asymmetry seen during downhill locomotion when compared with trotting on the flat (flat: 6.6 ± 4.4 mm to downhill: 1.9 ± 2.9 mm; p = 0.015) and when compared with uphill locomotion (8.4 ± 4.3 mm; p = 0.007). Horses with forelimb lameness showed no significant difference in asymmetry. However, there were considerable changes in poll asymmetry (>20 mm) among conditions in individual horses. Two horses with hindlimb lameness and two horses with forelimb lameness switched asymmetry between left and right by changing incline. CONCLUSIONS: These results confirm that incline can be an influential factor in the assessment of lame horses. Further work is justified to elucidate the types of pathology associated with the most relevant changes in asymmetry which would allow the use of an incline to prioritise a list of differential diagnoses.

Assessment of agreement using the equine glandular gastric disease grading system in 84 cases.

INTRODUCTION: Equine glandular gastric disease (EGGD) is a common condition causing signs of gastric pain although lesions are highly variable in their appearance. The only definitive method to diagnose EGGD ante-mortem is gastroscopy. The current recommended method for describing these lesions is the European College of Equine Internal Medicine (ECEIM) guidelines; however, repeatability between users is variable. This study aimed to validate the reliability of lesion descriptions using ECEIM consensus guidelines, using four blinded equine internal medicine diplomates. METHODS: Ninety-two horses with EGGD with pre- and post-treatment gastroscopy images were identified using the electronic record at a UK equine hospital between 2012 and 2019. Eight horses were excluded due to non-diagnostic images. Four blinded observers used the recommended grading system to describe images and outcomes. Intraclass correlation coefficients and Krippendorff's alpha were used to determine reliability and agreement, respectively. RESULTS: Intraclass correlation coefficient for severity was 0.782 (95% confidence interval [CI] 0.722-0.832), for distribution was 0.671 (95% CI 0.540-0.763), for the descriptor raised was 0.635 (95% CI 0.479-0.741), fibrinosuppurative was 0.745 (95% CI 0.651-0.812), haemorrhagic was 0.648 (95% CI 0.513-0.744), hyperaemic was 0.389 (95% CI 0.232-0.522) and for outcome was 0.677 (95% CI 0.559-0.770). Krippendorff's alpha for severity was 0.466 (95% CI 0.466-0.418), for distribution was 0.304 (95% CI 0.234-0.374), for the descriptor raised was 0.268 (95% CI 0.207-0.329), fibrinosuppurative was 0.406 (95% CI 0.347-0.463), haemorrhagic was 0.287 (95% CI 0.229-0.344), hyperaemic was 0.112 (95% CI 0.034-0.188) and for outcome was 0.315 (95% CI 0.218-0.408). There was moderate reliability determined between observers using intra-class correlation coefficients and unacceptable agreement determined between observers using Krippendorff's alpha. DISCUSSION: These results suggest that the current grading system is not comparable between observers, indicating the need to review the grading system or define more robust criteria.

Use of aminoglycoside antibiotics in equine clinical practice; a questionnaire-based study of current use.

Veterinary use of the aminoglycoside antibiotics is under increasing scrutiny. This questionnaire-based study aimed to document the use of aminoglycosides with a particular focus on gentamicin. An online questionnaire was delivered to generalist equine veterinary surgeons and specialists in internal medicine to determine the perceived importance, frequency of use and routes of administration of the aminoglycoside antibiotics. A series of hypothetical scenarios were also evaluated regarding gentamicin. Data were compared to evaluate the impact of the level of specialisation on prescribing practices for different antibiotics using Chi-squared and Fischer's exact tests. Data were analysed from 111 responses. Gentamicin was commonly used empirically without culture and susceptibility testing. Generalists were more likely to use gentamicin only after susceptibility testing than specialists in a variety of clinical presentations including respiratory diseases, septic peritonitis, acute febrile diarrhoea, cellulitis and contaminated limb wounds (p < 0.01). Intravenous administration of gentamicin was most common, although inhaled and regional administration of gentamicin and amikacin were also described. Amikacin was most commonly used by intra-articular administration. Gentamicin was more likely to be used in high-risk procedures or contaminated surgeries (86% and 74%, respectively) compared with clean surgery (32%; p < 0.0001). Gentamicin was often used perioperatively in horses undergoing exploratory celiotomy and more commonly used in horses undergoing an enterotomy (90%) than without and enterotomy (79%; p = 0.04). Most respondents (86%) used gentamicin at a dose of 6.6 mg/kg in adults, with few changing their dosing strategies based on the presence of sepsis, although higher doses were more reported in foals (7-15 mg/kg) irrespective of the presence of sepsis. Aminoglycosides are widely used in equine practice and use outside current EU marketing authorisations is common. Stewardship of the aminoglycoside antibiotics could be enhanced in both generalists and specialists through the more frequent use of susceptibility testing, regional administration and dose adjustment, especially in foals.

Real-time three-dimensional (3D) echocardiographic characterisation of an atrial septal defect in a horse.

Atrial septal defects have been well reported in humans and dogs and the principles of intervention have been well established. In contrast, there is very little information published about these congenital anomalies in horses. True ASDs are regarded as rare and little is known about the clinical significance of these defects in horses. An 11-year-old Thoroughbred gelding with a history of poor performance was diagnosed with an atrial septal defect, measuring approximately 2 cm in diameter, on 2D transthoracic echocardiography. Real-time three-dimensional (3D) echocardiography was used to map the structure of the defect and was useful in fully characterising the ASD in this case.

Cardiac Therapeutics in Horses.

Many cardiac therapeutics lack significant evidence of benefit in the horse, and in many cases their use is based on extrapolation of evidence from other species. In recent years there has been a push to develop a better understanding of both the pharmacodynamics and pharmacokinetics of these drugs. Recent data have described the use of antiarrhythmic agents including sotalol, flecainide, and amiodarone. Data about the use of ACE inhibitors in the management of congestive heart failure are encouraging and support their use in certain cases, wheras evidence for other medicines, such as pimobendan, remain speculative.

An evaluation of the psychometric properties of the Indicator of Relative Need (IoRN) instrument.

BACKGROUND: The Indicator of Relative Need (IoRN) instrument is designed for both health and social care services to measure function and dependency in older people. To date, the tool has not undergone assessment of validity. We report two studies aimed to evaluate psychometric properties of the IoRN. METHODS: The first study recruited patients receiving social care at discharge from hospital, those rehabilitating in intermediate care, and those in a rehabilitation at home service. Participants were assessed using the IoRN by a single researcher and by the clinical team at baseline and 8 weeks. Comparator instruments (Barthel ADL, Nottingham Extended ADL and Townsend Disability Scale) were also administered. Overall change in ability was assessed with a 7 point Likert scale at 8 weeks. The second study analysed linked routinely collected, health and social care data (including IoRN scores) to assess the relationship between IoRN category and death, hospitalisation and care home admission as a test of external validity. RESULTS: Ninety participants were included in the first study, mean age 77.9 (SD 12.0). Cronbach's alpha for IoRN subscales was high (0.87 to 0.93); subscales showed moderate correlation with comparator tools (r = 0.43 to 0.63). Cohen's weighted kappa showed moderate agreement between researcher and clinician IoRN category (0.49 to 0.53). Two-way intraclass correlation coefficients for IoRN subscales in participants reporting no change in ability were high (0.88 to 0.98) suggesting good stability; responsiveness coefficients in participants reporting overall change were equal to or better than comparator tools. 1712 patients were included in the second study, mean age 81.0 years (SD 7.7). Adjusted hazard ratios for death, care home admission and hospitalisation in the most dependent category compared to the least dependent IoRN category were 5.9 (95 % CI 2.0-17.0); 7.2 (95 % CI 4.4-12.0); 1.1 (95 % CI 0.5-2.6) respectively. The mean number of allocated hours of care 6 months after assessment was higher in the most dependent group compared to the least dependent group (5.6 vs 1.4 h, p = 0.005). CONCLUSIONS: Findings from these analyses support the use of the IoRN across a range of clinical environments although some limitations are highlighted.

Temporal trends and risk factors for readmission for infections, gastrointestinal and immobility complications after an incident hospitalisation for stroke in Scotland between 1997 and 2005.

BACKGROUND: Improvements in stroke management have led to increases in the numbers of stroke survivors over the last decade and there has been a corresponding increase of hospital readmissions after an initial stroke hospitalisation. The aim of this study was to examine the one year risk of having a readmission due to infective, gastrointestinal or immobility (IGI) complications and to identify temporal trends and any risk factors. METHODS: Using a cohort of first hospitalised for stroke patients who were discharged alive, time to first event (readmission for IGI complications or death) within 1 year was analysed in a competing risks framework using cumulative incidence methods. Regression on the cumulative incidence function was used to model the risks of having an outcome using the covariates age, sex, socioeconomic status, comorbidity, discharge destination and length of hospital stay. RESULTS: There were a total of 51,182 patients discharged alive after an incident stroke hospitalisation in Scotland between 1997-2005, and 7,747 (15.1%) were readmitted for IGI complications within a year of the discharge. Comparing incident stroke hospitalisations in 2005 with 1997, the adjusted risk of IGI readmission did not increase (HR = 1.00 95% CI (0.90, 1.11). However, there was a higher risk of IGI readmission with increasing levels of deprivation (most deprived fifth vs. least deprived fifth HR = 1.16 (1.08, 1.26). CONCLUSIONS: Approximately 15 in 100 patients discharged alive after an incident hospitalisation for stroke in Scotland between 1997 and 2005 went on to have an IGI readmission within one year. The proportion of readmissions did not change over the study period but those living in deprived areas had an increased risk.

Trends in incidence and in short term survival following a subarachnoid haemorrhage in Scotland, 1986-2005: a retrospective cohort study.

BACKGROUND: To examine age and sex specific incidence and 30 day case fatality for subarachnoid haemorrhage (SAH) in Scotland over a 20 year period. METHODS: A retrospective cohort study using routine hospital discharge data linked to death records. RESULTS: Between 1986 and 2005, 12,056 individuals experienced an incident SAH. Of these 10,113 (84%) survived to reach hospital. Overall age-standardised incidence rates were greater in women than men and remained relatively stable over the study period. In 2005, incidence in women was 12.8 (95% CI 11.5 to 14.2) and in men 7.9 (95% CI 6.9 to 9.1). 30 day case fatality in individuals hospitalised with SAH declined substantially, falling from 30.0% in men and 33.9% in women in 1986-1990 to 24.5% in men and 29.1% in women in 2001-2005. For both men and women, the largest reductions were observed in those aged between 40 to 59 years. After adjustment for age, socio-economic status and co-morbidity, the odds of death at 30 days in 2005 compared to odds of death in 1986 was 0.64 (0.54 to 0.76), p < 0.001 for those below 70 years, and 1.14 (0.83 to 1.56), p = 0.4 in those 70 years and above. CONCLUSIONS: Incidence rates for SAH remained stable between 1986 and 2005 suggesting that a better understanding of SAH risk factors and their reduction is needed. 30 day case fatality rates have declined substantially, particularly in middle-age. However, they remain high and it is important to ensure that this is not due to under-diagnosis or under-treatment.

Estimating the impact of stroke unit care in a whole population: an epidemiological study using routine data.

BACKGROUND AND PURPOSE: Randomised trials indicate that organised inpatient (stroke unit) care has an important impact on patient outcomes with an absolute risk difference (ARD) of 3% for survival and 5% for returning home. However, it is unclear what impact this complex intervention actually has in routine practice. A comprehensive national dataset was used to study the impact of stroke unit implementation. METHODS: The Scottish linked discharge database was used to identify all patients admitted to hospital with an incident stroke. Analyses compared case fatality and discharge home (adjusted for age, sex, deprivation and comorbidity) for hospitals with or without a stroke unit during four consecutive study periods: 1986-1990, 1991-1995, 1996-2000 and 2001-2005. RESULTS: During the study period, the percentage of admissions to hospitals that had a stroke unit increased from 0% to 87%, the 6 month case fatality decreased from 45% to 29% and discharges home increased from 46% to 59%. Adjusted ORs (95% CI) for case fatality (stroke unit versus no unit) in each study period were as follows: not calculable (no units before 1991), 0.83 (0.78-0.89), 0.90 (0.86-0.94) and 0.87 (0.82-0.91). These equate to an ARD of 3.0% over the whole study period. Equivalent data for discharge home indicated an increased odds of discharge home: not calculable, 1.23 (1.15-1.31), 1.15 (1.10-1.21) and 1.17 (1.11-1.23) with an overall ARD of 5%. CONCLUSIONS: These results indicate a positive impact of a policy of stroke unit care on case fatality and discharge home. The estimated impact, after adjusting for case mix, appears very similar to that calculated using clinical trial data.

Temporal trends in hospitalisation for stroke recurrence following incident hospitalisation for stroke in Scotland.

BACKGROUND: There are few studies that have investigated temporal trends in risk of recurrent stroke. The aim of this study was to examine temporal trends in hospitalisation for stroke recurrence following incident hospitalisation for stroke in Scotland during 1986 to 2001. METHODS: Unadjusted survival analysis of time to first event, hospitalisation for recurrent stroke or death, was undertaken using the cumulative incidence method which takes into account competing risks. Regression on cumulative incidence functions was used to model the temporal trends of first recurrent stroke with adjustment for age, sex, socioeconomic status and comorbidity. Complete five year follow-up was obtained for all patients. Restricted cubic splines were used to determine the best fitting relationship between the survival events and study year. RESULTS: There were 128,511 incident hospitalisations for stroke in Scotland between 1986 and 2001, 57,351 (45%) in men. A total of 13,835 (10.8%) patients had a recurrent hospitalisation for stroke within five years of their incident hospitalisation. Another 74,220 (57.8%) patients died within five years of their incident hospitalisation without first having a recurrent hospitalisation for stroke. Comparing incident stroke hospitalisations in 2001 with 1986, the adjusted risk of recurrent stroke hospitalisation decreased by 27%, HR = 0.73 95% CI (0.67 to 0.78), and the adjusted risk of death being the first event decreased by 28%, HR = 0.72 (0.70 to 0.75). CONCLUSIONS: Over the 15-year period approximately 1 in 10 patients with an incident hospitalisation for stroke in Scotland went on to have a hospitalisation for recurrent stroke within five years. Approximately 6 in 10 patients died within five years without first having a recurrent stroke hospitalisation. Using hospitalisation and death data from an entire country over a 20-year period we have been able to demonstrate not only an improvement in survival following an incident stroke, but also a reduction in the risk of a recurrent event.

Age- and sex-specific trends in fatal incidence and hospitalized incidence of stroke in Scotland, 1986 to 2005.

BACKGROUND: Temporal trends in stroke incidence are unclear. We aimed to examine age- and sex-specific temporal trends in incidence of fatal and nonfatal hospitalized stroke in Scotland from 1986 to 2005. METHODS AND RESULTS: Mean age at the time of first stroke was 70.8 (SD, 12.9) years in men and 76.4 (12.9) years in women. Between 1986 and 2005, rates fell in men from 235 (95% CI, 229 to 242) to 149 (144 to 154) and in women from 299 (292 to 306) to 182 (177 to 188). Poisson modeling showed that temporal trends were influenced by age with declines in incidence of hospitalized stroke starting later in younger than older age groups. In both men and women aged under 55 years, the overall incidence rate of stroke was significantly higher in 2005 than in 1986. CONCLUSIONS: We report in a whole country that the overall incidence of stroke declined steadily and substantially between 1986 and 2005, with a relative reduction in the risk of stroke of 31% in men and 42% in women. Reductions in rates of both hospitalized and nonhospitalized fatal stroke contributed to this overall decline. The increase in incident stroke rates in young people is of concern.

Coronary heart disease mortality among young adults in Scotland in relation to social inequalities: time trend study.

OBJECTIVE: To examine recent trends and social inequalities in age specific coronary heart disease mortality. DESIGN: Time trend analysis using joinpoint regression. SETTING: Scotland, 1986-2006. PARTICIPANTS: Men and women aged 35 years and over. MAIN OUTCOME MEASURES: Age adjusted and age, sex, and deprivation specific coronary heart disease mortality. RESULTS: Persistent sixfold social differentials in coronary heart disease mortality were seen between the most deprived and the most affluent groups aged 35-44 years. These differentials diminished with increasing age but equalised only above 85 years. Between 1986 and 2006, overall, age adjusted coronary heart disease mortality decreased by 61% in men and by 56% in women. Among middle aged and older adults, mortality continued to decrease fairly steadily throughout the period. However, coronary heart disease mortality levelled from 1994 onwards among young men and women aged 35-44 years. Rates in men and women aged 45-54 showed similar flattening from about 2003. Rates in women aged 55-64 may also now be flattening. The flattening of coronary heart disease mortality in younger men and women was confined to the two most deprived fifths. CONCLUSIONS: Premature death from coronary heart disease remains a major contributor to social inequalities. Furthermore, the flattening of the decline in mortality for coronary heart disease among younger adults may represent an early warning sign. The observed trends were confined to the most deprived groups. Marked deterioration in medical management of coronary heart disease seems implausible. Unfavourable trends in the major risk factors for coronary heart disease (smoking and poor diet) thus provide the most likely explanation for these inequalities.

Sex differences in incidence, mortality, and survival in individuals with stroke in Scotland, 1986 to 2005.

BACKGROUND AND PURPOSE: The aim of this study was to examine the effect of sex across different age groups and over time for stroke incidence, 30-day case-fatality, and mortality. METHODS: All first hospitalizations for stroke in Scotland (1986 to 2005) were identified using linked morbidity and mortality data. Age-specific rate ratios (RRs) for comparing women with men for both incidence and mortality were modeled with adjustment for study year and socioeconomic deprivation. Logistic regression was used to model 30-day case-fatality. RESULTS: Women had a lower incidence of first hospitalization than men and size of effect varied with age (55 to 64 years, RR=0.65, 95% CI 0.63 to 0.66; >or=85 years, RR=0.94, 95% CI 0.91 to 0.96). Women aged 55 to 84 years had lower mortality than men and again size of effect varied with age (65 to 74 years, RR=0.79, 95% CI 0.76 to 0.81); 75 to 84 years, RR=0.94, 95% CI 0.92 to 0.95). Conversely, women aged >or=85 years had 15% higher stroke mortality than men (RR=1.15, 95% CI 1.12 to 1.18). Adjusted risk of death within 30 days was significantly higher in women than men, and this difference increased over the 20-year period in all age groups (adjusted OR in 55 to 64 year olds 1.23, 95% CI 1.14 to 1.33 in 1986 and 1.51, 95% CI 1.39 to 1.63 in 2005). CONCLUSIONS: We observed lower rates of incidence and mortality in younger women than men. However, higher numbers of older women in the population mean that the absolute burden of stroke is greater in women. Short-term case-fatality is greater in women of all ages and, worryingly, these differences have increased from 1986 to 2005.

Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people.

BACKGROUND: We examined whether population-level hospitalization rates for heart failure (HF) and subsequent survival have continued to improve since the turn of the century. We also examined trends in the prescribing of evidence-based pharmacological treatment for HF. METHODS AND RESULTS: All patients in Scotland hospitalized with a first episode of HF between 1986 and 2003 were followed up until death or the end of 2004. Prescriptions of evidence-based treatments issued from 1997 to 2003 by a sample of primary care practices were also examined. A total of 116 556 individuals (52.6% women) had a first hospital discharge for HF. Age-adjusted first hospitalization rates for HF (per 100 000; 95% CI in parentheses) rose from 124 (119 to 129) in 1986 to 162 (157 to 168) in 1994 and then fell to 105 (101 to 109) in 2003 in men; in women, they rose from 128 (123 to 132) in 1986 to 160 (155 to 165) in 1993, falling to 101 (97 to 105) in 2003. Case-fatality rates fell steadily over the period. Adjusted 30-day case-fatality rates fell after discharge (adjusted odds [2003 versus 1986] 0.59 [95% CI 0.45 to 0.63] in men and 0.77 [95% CI 0.67 to 0.88] in women). Adjusted 1- and 5-year survival improved similarly. Median survival increased from 1.33 to 2.34 years in men and from 1.32 to 1.79 years in women. Age-adjusted prescribing rates for angiotensin-converting enzyme inhibitors, beta-blockers, and spironolactone increased from 1997 to 2003 (all P<0.0001 for trend). CONCLUSIONS: After rising between 1986 and 1994, rates of first hospitalization for HF declined. Case-fatality rates also fell. Prescribing rates for HF therapies increased from 1997 to 2003. These findings suggest that improvements in the prevention and treatment of HF may have had progressive, sustained effects on outcomes at the population level; however, prognosis remains poor in HF.

Discordant short- and long-term outcomes associated with diabetes in patients with heart failure: importance of age and sex: a population study of 5.1 million people in Scotland.

BACKGROUND: Diabetes and heart failure frequently coexist. Our aim was to assess the association between diabetes and short- and long-term outcomes in all patients admitted to the hospital for the first time with heart failure in Scotland between 1986 and 2003. METHODS AND RESULTS: A total of 116 556 patients were studied, of whom 13% (n=15 161) had a diagnosis of diabetes. At 30 days, diabetes was associated with a lower case fatality. By 1 year, the association between diabetes and better outcome was reversed, and diabetes was a significant independent predictor of higher case fatality. The longer term risk of death associated with diabetes was greatest in younger patients. In patients aged 65 years or younger, the hazard ratio for mortality at 5 years associated with diabetes was 1.41 (95% CI, 1.31 to 1.52) for men and 1.64 (1.50 to 1.79) for women. The risk associated with diabetes was less in patients aged 75 years or older: a hazard ratio in men 1.16 (1.10 to 1.22) and in women 1.15 (1.10 to 1.20). In the younger age group the risk associated with diabetes was significantly greater in women than in men (P=0.005 for diabetes-sex interaction). Diabetes was also a significant independent predictor of heart failure readmission, and again the risk was greatest in younger women. CONCLUSIONS: Although diabetes was associated with a lower case fatality at 30 days, by 1 year it was a significant independent predictor of higher case fatality. The risk associated with diabetes was greatest in young patients, and in young patients the risk was greatest in women.