Direct costs of interferon-based and interferon-free direct-acting antiviral regimens for the treatment of chronic hepatitis C infection.

Given the increasing budget impact of Hepatitis C virus (HCV) treatment, robust real-world cost data are essential for healthcare decision-makers to evaluate and understand the costs and benefits of these treatments. To determine the direct cost of treating HCV infection in a hospital-based ambulatory care setting in Ireland based on available data from the Irish national hepatitis C treatment registry. A microcosting study of the direct costs of patients with hepatitis C treated with interferon-based and interferon-free direct-acting antiviral regimens was conducted. Attendance at the outpatient clinic for clinical assessment, the quantity of resources used per patient, the medication prescribed and the identification and timing of staff involvement was measured and combined to establish a mean cost of treatment per patient and a cost per sustained virological response (SVR). One hundred and sixty-eight patients were included in the analysis; 119 treated with interferon-based direct-acting antiviral regimens and 47 treated with interferon-free regimens. The mean costs of treatment with the interferon-based regimens per patient were €38 286 (95% CI €35 305-€41 061). The cost per SVR was €62 457. The mean cost of treatment with interferon-free regimens per patient was €55 734 (95% CI €50 906-€60 880). The cost per SVR was €81 873. Real-world cost data provide valuable information to enhance reimbursement decisions. While the direct costs associated with hepatitis C treatment in Ireland are substantial, it is reasonable to expect that the mean cost of treatment and the cost per SVR will reduce as patients with less advanced disease are treated with interferon-free therapies.

The cost of the inpatient management of febrile neutropenia in cancer patients--a micro-costing study in the Irish healthcare setting.

The objective was to evaluate the resource use and cost of hospitalisation for febrile neutropenia (FN) from the health-payer's perspective. This was a single centre study. Adults undergoing chemotherapy, who were admitted for FN, were identified prospectively. Patient medical records were reviewed retrospectively. Demographics and resource utilisation data were obtained from a cohort of 32 patients (69% female, mean age = 58.8 years). Twenty-five per cent of patients had more than one FN episode. In total, 42 FN episodes were captured; 60% of episodes had occurred within the first two cycles of chemotherapy. The bootstrap estimation was used to determine mean hospital length of stay (LOS) with standard deviation (±SD) and mean costs ± SD. The mean LOS was 7.3 ± 0.5 days. The mean cost per FN episode was €8915 ± 718. The major cost driver was hospital bed-stay (mean cost of €6851 ± 549). Other cost drivers included antibacterial treatment at €760 ± 156, laboratory investigations at €538 ± 47 and the requirement for blood bank products at €525 ± 189. To our knowledge, this is the first investigation of the cost of chemotherapy induced FN within the context of the Irish healthcare setting.

Can accelerometer ear tags identify behavioural changes in sheep associated with parturition?

On-animal sensor systems provide an opportunity to monitor ewes during parturition, potentially reducing ewe and lamb mortality risk. This study investigated the capacity of machine learning (ML) behaviour classification to monitor changes in sheep behaviour around the time of lambing using ear-borne accelerometers. Accelerometers were attached to 27 ewes grazing a 4.4 ha paddock. Data were then classified based on three different ethograms: (i) detection of grazing, lying, standing, walking; (ii) detection of active behaviour; and (iii) detection of body posture. Proportion of time devoted to performing each behaviour and activity was then calculated at a daily and hourly scale. Frequency of posture change was also calculated on an hourly scale. Assessment of each metric using a linear mixed-effects model was conducted for the 7 days (day scale) or 12 h (hour scale) before and after lambing. For all physical movements, regardless of the ethogram, there was a change in the days surrounding lambing. This involved either a decrease (grazing, lying, active behaviour) or peak (standing, walking) on the day of parturition, with most values returning to either pre-partum or near-pre-partum levels (all P < 0.001). Hourly changes also occurred for all behaviours (all P < 0.001), the most marked being increased walking behaviour and frequency of posture change. These findings indicate ewes were more restless around the time of parturition. Further application of this research should focus on development of algorithms that can be used to identify onset of lambing and/or time of parturition in pasture-based ewes.

Epidemiology of sporting and recreational injuries in a paediatric orthopaedic outpatients department.

Knowledge of the number and type of injuries attending the paediatric orthopaedic outpatients is crucial in the future planning of any new paediatric hospital. We prospectively collected data on all new patients attending two paediatric orthopaedic out-patients departments, over a four month period. There were a total of 1,791 completed questionnaires. Sporting and recreational injuries represented 270% and 28% of the total attending, respectively. The new use of heelies represented 11% of the recreational injuries. The upper limb injuries represented 74% of the total, with the lower limb accounting for 25%. Treatment was nonoperative or operative. The number of patients, and the types of injuries presenting demonstrates the workload involved in diagnosing and treating these injuries. A total of 827 casts were applied. With almost half of those attending the clinic requiring a cast, the workload on the plaster technicians is substantial, and has implications for future service planning.

Epidemiology of major paediatric trauma.

In Europe injury is the leading cause of death in those aged between 1 and 14 years. In Ireland over 800,000 people are aged less than 14 years. There is currently no national trauma register to collect data on the morbidity and mortality associated with major trauma in the paediatric population in Ireland. We prospectively collected data on 153 patients admitted to our hospital with major trauma. There were 99 males and 54 females. The majority of patients were transported by ambulance (n= 138). Road traffic accidents (n=69) and thermal injuries (n=49) represented the majority of admissions. 68% (n=47) of the vehicle occupants in this study were either unrestrained or incorrectly restrained. Most patients (n=133) had an in patient stay of <50 days, with only 4 patients staying >100 days. 14 patients died. A paediatric trauma register as well as a level 1 paediatric trauma centre are required in Ireland.

Survival of Cryptosporidium parvum oocysts in calf housing facilities in the New York City watersheds.

Pathogen contamination of the public drinking water supply in the New York City watersheds is a serious concern. New York City's Watershed Agriculture Program is working with dairy farms in the watersheds to implement management practices that will reduce the risk of pathogens contaminating the water supply. Solar calf housing (SCH) was suggested as a best management practice (BMP) to control Cryptosporidium parvum, a common protozoan parasite that causes disease in humans. This BMP targets young calves because they are the primary source of C. parvum in dairy herds. The objective of this project was to assess and compare the survivability of C. parvum in SCH and in conventional calf housing (CCH), usually located in the main barn. C. parvum oocysts were secured in sentinel chambers and placed in SCH and CCH bedding on four farms. The chambers were in thermal, chemical, and moisture equilibrium with their microenvironments. An oocyst-filled control chamber, sealed from its surroundings, was placed near each chamber. Chambers and controls were sampled after 4, 6, and 8 wk. Oocyst viability in the chambers decreased to less than 10% in warm months and between 15 and 30% in the winter months. The viability of the control oocysts was similar to the chambers during warm months and generally higher during winter months. There was no significant (P > 0.05) difference in the viability decrease between SCH and CCH. Although oocyst viability was similar in both types of calf housing, SCH allow contaminated calf manure to be isolated from the main barn manure and potentially managed differently and in a way to decrease the number of viable oocysts entering the environment during field spreading.

Minor head injuries in children.

Traumatic head injury continues to be a major problem facing the pediatric specialists despite efforts to reduce its incidence. Aims of our study were assessment of the incidence of hospital admissions of children with minor head injuries, their treatment and outcome. In this prospective study we included 101 patient with head injury. We assessed the hospital admission criteria of children with minor head injuries, their length of stay, symptoms and neurological status, in-hospital imaging and consultations to other medical specialities, together with the outcome of patients on their discharge from the hospital. Of 101 patient 54 (53.46%) were male and 47 (46.53%) female. Average age was 3 years with age range from 5/52 to 12 years. Majority of patients (46.53%) were less than 1 year old. Fall was the most common mechanism of injury (92.07% of all patients). Injuries were witnessed in 51 case (50.49%), unwitnessed in 19 cases (18.81%) and unknown in 31 cases (30.69%). 95 patients did not have associated extracranial injuries, while 5 patients had associated lacerations and one had associated extracranial fracture. Length of stay was from 1 day in 80.19% of all cases to more than 2 days in 6.93%. GCS was recorded on admission and discharge and majority of patients were discharged with GCS of 15. 93% of admissions had no neurological deficit. 79% had 1 or more symptoms including vomiting, sleepiness, LOC and headaches. Over half of patients (55%) had no imaging done. 45 patients (45%) had skull x-ray. CT was performed in 7 (15%) patients and 7 fractures were found on x-ray and CT. 3 patients were admitted to ICU. All injuries were closed and all received conservative treatment. In less than 1 year old group of patients 95% of them were also seen by medical team and social worker. The outcome was good for all patients. We conclude that majority of patients with minor head injury could be supervised and observed at home by a competent care giver. Admitted patients need radiological evaluation, preferably a CT scan.

Adolescent idiopathic scoliosis: metric analysis of the deformity.

In order to explore the concept that scoliosis is fundamentally a loss of left-right symmetry. surface topography was used to measure asymmetry in three dimensions at three levels on the back surface. Statistical analysis of prospectively collected topographic, radiographic and clinical data, in girls with adolescent idiopathic scoliosis, was carried out and comparisons were made with theoretically perfect symmetry (test value of zero). All scoliosis showed statistically significant differences in coronal dimensions, index points on the convex side of the scoliosis being further from the mid-line than those on the concave side. Primary thoracic scoliosis differed from thoracolumbar and lumbar in that they showed directional asymmetry at all levels and in all directions, the side of the scoliosis convexity being broader, taller and thicker. This asymmetry is not due to posture, spinal balance or trunk rotation, as left and right sides are being compared independently of their orientation in space. The asymmetry is of size in three dimensions and size is determined by growth. Growth is a three dimensional process, but does not necessarily occur equally in all three. Differential growth is both directional and regional, particularly during the pubertal growth spurt, when proportions change substantially, and is controlled by many genes, as well as by hormones and signalling molecules. The implication is that scoliotic deformity is the result of asymmetric growth, not confined to the vertebrae, but affecting the entire trunk. This is a developmental, rather than pathological, phenomenon. It makes questions of aetiology redundant and natural history logical.

Handedness and spinal deformity.

Biological lateralisation is clearly manifest in scoliosis, yet its relevance is unclear. Goldberg et al. (Spine. 15(2):61-64. 1990) found an association between curve pattern and hand-preference in a screened population, but no increase in sinistrality. Milenkovic et al, (European Journal of Epidemiology, 19:969-972,2004) concluded left-handedness was a risk factor in a screened group. The database was reassessed to determine whether clinically significant scoliosis was associated with sinistrality or differed from the population norm of 10%. Patients attending the scoliosis clinic were asked their preferred writing hand. 1,636 patients were identified with complete data. Overall, left handedness occurred in 11.5%, greater than the general population (p=0.04) Left hand preference was found to be increased in boys with infantile idiopathic scoliosis and in girls with infantile, juvenile, congenital and syndromic scoliosis, but was reduced in girls with adolescent idiopathic scoliosis. Scoliosis lateralisation was random in infantile and congenital scoliosis, while left curve patterns were decreased in girls with juvenile idiopathic scoliosis and increased in boys with syndromic scoliosis. Curve pattern and handedness correlated in asymmetry in boys and girls and in girls with radiologically confirmed adolescent idiopathic scoliosis, but not in any other type. This study cannot confirm findings of left-handedness as a risk factor for spinal deformity. Its incidence is reduced in girls with adolescent idiopathic scoliosis, and the increased sinistrality in infantile scoliosis is not a new finding (Rauterberg & Tonnis Ger. Z.Orthop. 109(14):676-689. 1971). Lateralisation is undoubtedly a factor in scoliosis, but does not have a simple causal relationship, probably deriving from the underlying scoliotic process, rather than contributing to it.

Surface topography and vectors: a new measure for the three dimensional quantification of scoliotic deformity.

The monitoring of spinal deformity uses many techniques: clinical history and physical examination for patient status, radiography for precise spinal delineation and Cobb angle, topography to quantify cosmesis and to approximate the Cobb angle. Experience with a system based on Raster photography has shown that adequate correlation with the Cobb angle is achieved, but that the relationship between spinal curvature and cosmetic effect is not simple. A measure was developed to quantify the asymmetry of the back, making it available to statistical analysis, without expressing it in terms of the Cobb angle or referring to trunk balance or rotation. The calculation expresses symmetry about the median saggittal plane (first thoracic vertebra to natal cleft), reflecting the right half onto the left and measuring the three-dimensional displacement between corresponding fixed points on the trunk. Tolerance limits were calculated and correlation with Cobb angles using routine scans was analysed. There were statistically significant correlations between the Cobb angle and all vectors except the middle antero-posterior. All vectors correlated with each other, except again for the middle Z or anteroposterior which correlated only with the middle and lowermost sets. Applied to natural history and to surgical outcome, this new parameter provides a different quantification of back shape which can be used both for patient assessment and monitoring, for the evaluation of the cosmetic (as opposed to the radiological) effect of treatment, and for aetiology and natural history studies.

Cortical Map Plasticity as a Function of Vagus Nerve Stimulation Intensity.

BACKGROUND: Pairing sensory or motor events with vagus nerve stimulation (VNS) can reorganize sensory or motor cortex. Repeatedly pairing a tone with a brief period of VNS increases the proportion of primary auditory cortex (A1) responding to the frequency of the paired tone. However, the relationship between VNS intensity and cortical map plasticity is not known. OBJECTIVE/HYPOTHESIS: The primary goal of this study was to determine the range of VNS intensities that can be used to direct cortical map plasticity. METHODS: The rats were exposed to a 9 kHz tone paired with VNS at intensities of 0.4, 0.8, 1.2, or 1.6 mA. RESULTS: In rats that received moderate (0.4-0.8 mA) intensity VNS, 75% more cortical neurons were tuned to frequencies near the paired tone frequency. A two-fold effective range is broader than expected based on previous VNS studies. Rats that received high (1.2-1.6 mA) intensity VNS had significantly fewer neurons tuned to the same frequency range compared to the moderate intensity group. CONCLUSION: This result is consistent with previous results documenting that VNS is memory enhancing as a non-monotonic relationship of VNS intensity.

Guidelines for the medical management of Irish children and adolescents with Down syndrome.

Down syndrome (DS) is the most common chromosomal cause of developmental disability in Ireland. Children with DS have a high incidence of associated treatable medical disorders where early intervention carries a better outcome. Currently there are no agreed protocols for the screening and management of children and adults with DS in Ireland. A cross-sectional study of 394 children and adolescents was undertaken in the Eastern Regional Health Authority (ERHA) to assess the medical needs of children and adolescents with DS, in order to develop medical management guidelines. This study provides evidence-based data that children and adolescents with DS have a high incidence of treatable medical disorders, which supports the need for the medical management guidelines presented.

Discitis as a cause of abdominal pain in children.

The purpose of this study is to draw attention to inflammatory disease of lumbar intervertebral discs in children as a source of referred abdominal pain. For three children presenting with abdominal pain the eventual diagnosis was discitis of the lumbar spine. Failure to examine the patient's backs at the initial examinations resulted in a delay in diagnosis ranging from 66 to 2 days. Treatment with antibiotics and spinal jacket was effective in all cases.

Adolescent idiopathic scoliosis--early menarche, normal growth.

Growth has long been known to be relevant to the development and prognosis of spinal deformity and abnormalities have been considered in the etiology of idiopathic scoliosis. Age at menarche, as an indicator of puberty, in 303 girls with idiopathic scoliosis 10 degrees or more from the Dublin school screening program was 13.13 years, 0.39 years earlier than the national mean for Irish girls. This difference is statistically significant (P < 0.01). The heights of 214 of these girls aged 10-15.5 years at diagnosis and at least 14 years at follow-up, after a minimum 6 months, were compared with the national standards. It was found that, although those diagnosed at a younger age were generally taller than their peers, this was not true for those diagnosed at a later age or for anyone at final follow-up. This points to an early pubertal growth spurt in girls with adolescent idiopathic scoliosis but not to any outright abnormality of growth or development.

Left thoracic scoliosis configurations. Why so different?

STUDY DESIGN: Patients in the scoliosis screening database were analyzed with respect to curve convexity, severity, and outcome, using standard statistical methods. OBJECTIVES: This study assessed whether left thoracic scoliosis is always pathologic and inquired why this is the case. SUMMARY OF BACKGROUND DATA: Left thoracic scoliosis is more significant than the usual right thoracic pattern, but evidence in the literature is circumstantial. METHODS: Prospectively collected data from 1979-1990 was analyzed in the natural history database of the school screening program. RESULTS: Right thoracic pattern was observed in 421 girls, and left thoracic pattern was present in 125 girls. The minimum age at diagnosis was 10 years and the Cobb angle was > 4 degrees. Primary left thoracic patterns were statistically smaller and less progressive. CONCLUSIONS: The left pattern of scoliosis in the absence of overt neuropathology carries a benign prognosis. This contradictory observation is examined in the light of biological asymmetry.

Left thoracic curve patterns and their association with disease.

STUDY DESIGN: Analysis of clinical database material collected prospectively. OBJECTIVE: Examination of the association between lateralization of scoliotic curves and the existence of underlying disease. SUMMARY OF BACKGROUND DATA: It has been suggested that left thoracic scoliosis configurations are intrinsically pathologic, whereas the more usual right curve is, in a sense, "normal." METHODS: Research-based records were analyzed. Scoliosis configuration, patient gender, and diagnostic group were correlated. The results were interpreted within a biologic framework. RESULTS: Congenital and infantile idiopathic scoliosis showed a random right-left curve distribution. In older age groups, boys were more likely to have a left thoracic curve and to have underlying disease, but there was no association between the two. In girls, occurrence in childhood itself and left thoracic patterns within that group were associated with disease. Nevertheless, most curves were in the right thoracic pattern, regardless of cause. CONCLUSIONS: Although an association exists between left thoracic curves and disease, it is not strong enough to determine who should be intensively investigated, to the exclusion of other clinical findings, and it seems inappropriate for a different approach to be adopted on the basis of scoliosis pattern alone. Gender in males and age at occurrence in females are more important risk factors than in scoliosis configuration. All new cases of scoliosis treated by a physician warrant equally meticulous assessment, with more sophisticated investigative techniques where indicated by the complete clinical picture, of which curve lateralization is only a part. Biologic theories of left and right are more capable of dealing with the phenomenon of scoliosis lateralization than are simple mechanics or concepts of specific diseases.

Electro-spinal stimulation in children with adolescent and juvenile scoliosis.

A series of forty-one patients with adolescent or juvenile idiopathic scoliosis who were treated with electro-spinal stimulation is reported. Nineteen children were removed from the program because of curve progression or unacceptable deformity. Sixteen of these (39%) required surgery as a first alternative. Three were given a brace. Thirteen children have reached skeletal maturity without significant deterioration. Those who did well were in a lower risk category. The efficacy of this form of treatment has not been demonstrated in this series, and it is being discontinued.

School scoliosis screening and the United States Preventive Services Task Force. An examination of long-term results.

STUDY DESIGN: Analysis of scoliosis screening in Dublin (1979-1990) of patients who passed significant levels (25 degrees and 40 degrees) and received orthotic treatment or surgery. OBJECTIVES: To reexamine the basis of school scoliosis screening. SUMMARY OF BACKGROUND DATA: The United States Preventive Services Task Force questioned the validity of school screening for adolescent idiopathic scoliosis because there is insufficient scientific evidence to justify it. METHODS: New entrants (1986-87) to the screening program were used to test the validity of the screening methods. The total screened population, proportions reaching significant Cobb angles or undergoing treatment, were compared across the time period. RESULTS: The sensitivity of the forward bend test in detecting or predicting 40 degrees scoliosis was 0.83, the specificity was 0.99, and the predictive value was 0.08. The proportion prescribed braces declined significantly (P < 0.01), but there was no significant change in those with scoliosis greater than 24 degrees (0.18%) or 39 degrees (.08%) nor was there a significant change in the numbers needing surgery (.045%). CONCLUSIONS: The incidence of significant scoliosis and of surgery is low and independent of changes in bracing policy. The validity of screening to cause significant change in prevalence must be challenged.