The Symptomatology and Diagnosis of Tuberculous Spinal Caries in Adults

I have attempted throughout this work to consider the symptoms and signs of Pott's disease, in the adult, with reference to its early diagnosis. The length of time which elapses between the onset of symptoms and the diagnosis, especially in cases under supervision -in my series the average time was over two years -indicates a very unsatisfactory state of affairs. I have dealt in some detail with the production of the symptom of pain, as pain is, in the majority of patients, the first cause of complaint. The character of the pain in spinal caries, and its situation, do not definitely distinguish the disease from other causes of pain in the back; but they are at least suggestive of Pott's disease and this should always be excluded before pain is attributed to some other cause. This refers more particularly to the pain situated in the anti-gravity muscles of the back. In order that an early diagnosis may be made in cases of spinal caries in the adult, it is essential that signs and symptoms such as I have described, and pointing to the possibility of spinal disease, should always lead to an examination of the stripped back; and it is also necessary that the examiner should realise that, when tuberculous spinal caries is present in an adult, the spine itself is seldom painful. Should any doubt exist after the clinical examination, resort should be had to radiographic examination. The following conclusions may be drawn from the investigations I have made:- 1. Tuberculous spinal caries in the adult tends especially to affect the vertebrae from the 11th. thoracic to the 4th. lumbar. 2. Trauma is seldom present as a predisposing or contributory cause. 3. Pain, felt in the muscles of the back, is the most common initial symptom. It is less likely to be a prominent feature of the disease in muscular subjects, engaged in heavy work, than in those who lead sedentary lives. 4. The pain is the expression of inadequate postural tone in the anti-gravity muscles of the back. This tone, though inadequate, is relatively greater than the normal, and so produces rigidity; in consequence the pain is more constantly associated with the movements throwing a strain on the rigid muscles, than is the pain due to inadequacy of postural tone, arising from other causes. 5. The production of so-called' root pains', associated with spinal caries, is not always confined to the nerve roots themselves. In many cases they are the result of involvement of a peripheral nerve by a psoas abscess. Hyper-irritability of the nerve roots resulting from interference with their blood supply by an abscess, is the essential factor in the production of true root pains. 6. Pain in the back on jarring of the spine is not necessarily diagnostic of spinal caries. 7. The prevertebral abscess, in connection with disease of the thoracic region, does not tend to track away from the spine to the same extent as in other regions of the spine, and this may account for the greater frequency with which paraplegia and root pains are observed when the thoracic vertebrae are diseased; and also for the more marked deformities encountered in this part of the spine. S. Stiffness of the back is not a frequent cause of complaint inpatients suffering from Pott's disease. 9. Deformity is, in the majority of cases, present in some degree, usually very slight but detectable, at the time of onset of symptoms. 10. Muscular rigidity in the region of the spinal lesion is the most constant clinical sign of Pott's disease, and is always present so long as the disease is active. 11. Tenderness of the spine is uncommon in adult cases of spinal caries. 12. A patient, complaining of symptoms attributable to spinal disease, should always be examined with the back stripped, particular attention being paid to the signs of deformity and rigidity; and finally; X-ray examination of the spine should be made the deciding factor in cases of doubt. In this way, only, will it be possible to obtain cases for treatment at an early stage of the disease

Geophysical characteristics and crustal structure of greenstone terranes: Canadian Shield

Geophysical studies in the Canadian Shield have provided some insights into the tectonic setting of greenstone belts. Greenstone belts are not rooted in deep crustal structures. Geophysical techniques consistently indicate that greenstones are restricted to the uppermost 10 km or so of crust and are underlain by geophysically normal crust. Gravity models suggest that granitic elements are similarly restricted, although magnetic modelling suggests possible downward extension to the intermediate discontinuity around approx. 18 km. Seismic evidence demonstrates that steeply-dipping structure, which can be associated with the belts in the upper crust, is not present in the lower crust. Horizontal intermediate discontinuities mapped under adjacent greenstone and granitic components are not noticeably disrupted in the boundary zone. Geophysical evidence points to the presence of discontinuities between greenhouse-granite and adjacent metasedimentary erranes. Measured stratigraphic thicknesses of greenstone belts are often twice or more the vertical thicknesses determined from gravity modelling. Explantations advanced for the discrepancy include stratigraphy repeated by thrust faulting and/or listric normal faulting, mechanisms which are consistent with certain aspects of conceptual models of greenstone development. Where repetition is not a factor the gravity evidence points to removal of the root zones of greenstone belts. For one region, this has been attributed to magmatic stopping during resurgent caldera activity

Implementation of Bayesian methods in the pharmaceutical industry

This thesis is concerned primarily with the practical implementation of Bayesian methodology within the context of the pharmaceutical industry. The implementation includes the development, where appropriate, of analytic approximations to the posterior distributions of interest and graphical methods for mapping prior assumptions to posterior inference. Two critical areas within pharmaceutical research, critical in the sense of the controversy which they have aroused, have been investigated. First, Bayesian methods for the analysis of two-treatment crossover designs which fell in to disfavour in the late 1970's and early 1980's because of the US Food and Drug Administration's published view that the two-treatment two-period design was not the design of first choice if unequivocal evidence of a treatment effect was required were developed. Each type of design considered and for which methods are developed are illustrated with examples from clinical trials which have already been reported in the medical literature. Second, a Bayesian method is developed whose purpose is to classify test compounds into one of several toxicity classes on the basis of an LD50 estimate. The method is generalised to deal with a non-standard LD50 problem related to the prediction of results from a future LD50 experiment. Both of these applications arose out of a practical consultancy session within the context of a statistics group in the chemical/pharmaceutical industry. As part of the methods required for carrying out these analyses the zeros and weights associated with some non-standard orthogonal polynomial are developed as a result of which a new asymptotic expansion of the Behrens-Fisher density is developed. Further applications of the polynomials orthogonal to t-kernels are developed including problems associated with prediction in clinical trials. A FORTRAN program which has been implemented at a laboratory level within the pharmaceutical toxicology department at CIBA-GEIGY in Switzerland is provided SAS programs for a variety of the analyses developed for the two-treatment crossover designs are provided as are SAS programs for determining the zeros and weights of a number of different classes of orthogonal polynomials

Anti-trypanosomal antibodies in sequentially collected sera of N'Dama cattle under natural trypanosomiasis risk in The Gambia

Investigates the time of appearance and the persistence of antibodies in N'Dama cattle bitten by infected tsetse flies under controlled conditions, the serology of village animals exposed to natural trypanosomiasis risk and the time of appearance and duration of anti-trypanosomal antibodies through the monthly collection of serum samples from calves following birth

The impact of internet-based cognitive behaviour therapy for perfectionism on different measures of perfectionism: a randomised controlled trial

The current study investigated the impact of an 8-module internet-based cognitive behaviour therapy for perfectionism (ICBT-P) across a variety of perfectionism subscales. Undergraduate students who identified as having a problem with perfectionism were randomized to receive the intervention (n = 41), and were free to choose the number of treatment modules they completed over a 4-week period, while the control group (N = 48) received access to treatment 8 weeks post-randomisation. Secondary measures included depression, anxiety, stress, body image and self-compassion. Assessments occurred at baseline, 2-, 4- and 8-week time points. A mean of 3.12 (SD = 2.67) modules were completed; 7 participants (17%) completed none and 6 (15%) completed all. Linear mixed modelling (with baseline observation included as a covariate) showed significant Bonferroni-adjusted post-hoc between-group differences for 5 of the 6 perfectionism measures, favouring the intervention group; the most robust between group effect sizes were for the Concern over Mistakes (d = −0.82), High Standards (d = −0.69), and Perfectionistic Standards (d = −0.47) subscales. There were no between-group differences for our secondary measures. ICBT-P was found to be an effective intervention for reducing different components of perfectionism compared to a control group. The relatively low use of modules may have contributed to a lack of effect on secondary measures

Economic evaluation of integrated new technologies for health and social care: Suggestions for policy makers, users and evaluators

With an ageing population there is a move towards the use of assisted living technologies (ALTs) to provide social care and health care services, and to improve service processes. These technologies are at the forefront of the integration of health and social care. However, economic evaluations of ALTs, and indeed economic evaluations of any interventions providing both health benefits and benefits beyond health are complex. This paper considers the challenges faced by evaluators and presents a method of economic evaluation for use with interventions where traditional methods may not be suitable for informing funders and decision makers. We propose a method, combining economic evaluation techniques, that can accommodate health outcomes and outcomes beyond health through the use of a common numeraire. Such economic evaluations can benefit both the public and private sector, firstly by ensuring the efficient allocation of resources. And secondly, by providing information for individuals who, in the market for ALTs, face consumption decisions that are infrequent and for which there may be no other sources of information. We consider these issues in the welfarist, extra-welfarist and capabilities framework, which we link to attributes in an individual production model. This approach allows for the valuation of the health component of any such intervention and the valuation of key social care attributes and processes. Finally, we present a set of considerations for evaluators highlighting the key issues that need to be considered in this type of economic evaluation

The effect of site practices on the integrity of large diameter bored piles

In South Africa, concrete in large diameter bored piles is generally placed by discharging a high flow concrete mix directly from the truck mixer and allowing the concrete to fall freely to the base of the pile hole. While certain site practices have been used by piling contractors for years, many engineers are not convinced of their acceptability. This paper discusses the results of an investigation which assessed the effect of site practices on the integrity of cast in-situ bored piles. Such practices include the method of concrete placement and the amount of water and/or loose spoil in the pile hole at the time of casting. The results of this investigation dispel the myth that the free fall placement of concrete in clean, dry pile holes has a detrimental effect on the degree of compaction and compressive strength of the concrete

The value of repeated lumbar puncture to test for xanthochromia, in patients with clinical suspicion of subarachnoid haemorrhage, with CT-negative and initial traumatic tap.

OBJECTIVES: For the diagnosis of subarachnoid haemorrhage (SAH), the presence of cerebrospinal fluid (CSF) xanthochromia is still considered the gold standard for patients with a thunderclap headache, in the absence of blood on brain CT scan. However, a traumatic lumbar puncture (LP) typically results in high concentrations of oxyhaemoglobin in CSF, impairing the detection of xanthochromia and preventing the reliable exclusion of SAH. In this context, the value of a repeat lumbar puncture has not yet been described. MATERIALS AND METHODS: A retrospective case series of suspected SAH patients, with a negative CT scan and initial traumatic LP, managed with a repeat LP to assess for CSF xanthochromia. Clinical notes, laboratory and imaging results were reviewed. RESULTS: Between August 2011 and January 2020, 31 patients with suspected SAH were referred to our neurosurgical unit following negative CT and traumatic LP. A repeat LP was performed in 7 of the 31 patients, 2.4 days (±0.79 SD) after the first traumatic LP. CSF spectrophotometry analysis from repeated LP in all 7 patients was negative for xanthochromia. No adverse clinical events were recorded on average 18 months following discharge. CONCLUSION: A repeat LP performed following a traumatic tap can still yield xanthochromia-negative CSF, thereby, excluding SAH, avoiding unnecessary invasive angiography and overall promoting the safer management of these patients

Implementation of Bayesian methods in the pharmaceutical industry

This thesis is concerned primarily with the practical implementation of Bayesian methodology within the context of the pharmaceutical industry. The implementation includes the development, where appropriate, of analytic approximations to the posterior distributions of interest and graphical methods for mapping prior assumptions to posterior inference. Two critical areas within pharmaceutical research, critical in the sense of the controversy which they have aroused, have been investigated. First, Bayesian methods for the analysis of two-treatment crossover designs which fell in to disfavour in the late 1970's and early 1980's because of the US Food and Drug Administration's published view that the two-treatment two-period design was not the design of first choice if unequivocal evidence of a treatment effect was required were developed. Each type of design considered and for which methods are developed are illustrated with examples from clinical trials which have already been reported in the medical literature. Second, a Bayesian method is developed whose purpose is to classify test compounds into one of several toxicity classes on the basis of an LD50 estimate. The method is generalised to deal with a non-standard LD50 problem related to the prediction of results from a future LD50 experiment. Both of these applications arose out of a practical consultancy session within the context of a statistics group in the chemical/pharmaceutical industry. As part of the methods required for carrying out these analyses the zeros and weights associated with some non-standard orthogonal polynomial are developed as a result of which a new asymptotic expansion of the Behrens-Fisher density is developed. Further applications of the polynomials orthogonal to t-kernels are developed including problems associated with prediction in clinical trials. A FORTRAN program which has been implemented at a laboratory level within the pharmaceutical toxicology department at CIBA-GEIGY in Switzerland is provided SAS programs for a variety of the analyses developed for the two-treatment crossover designs are provided as are SAS programs for determining the zeros and weights of a number of different classes of orthogonal polynomials

Risk Adjustment In Neurocritical care (RAIN)--prospective validation of risk prediction models for adult patients with acute traumatic brain injury to use to evaluate the optimum location and comparative costs of neurocritical care: a cohort study.

OBJECTIVES: To validate risk prediction models for acute traumatic brain injury (TBI) and to use the best model to evaluate the optimum location and comparative costs of neurocritical care in the NHS. DESIGN: Cohort study. SETTING: Sixty-seven adult critical care units. PARTICIPANTS: Adult patients admitted to critical care following actual/suspected TBI with a Glasgow Coma Scale (GCS) score of < 15. INTERVENTIONS: Critical care delivered in a dedicated neurocritical care unit, a combined neuro/general critical care unit within a neuroscience centre or a general critical care unit outside a neuroscience centre. MAIN OUTCOME MEASURES: Mortality, Glasgow Outcome Scale - Extended (GOSE) questionnaire and European Quality of Life-5 Dimensions, 3-level version (EQ-5D-3L) questionnaire at 6 months following TBI. RESULTS: The final Risk Adjustment In Neurocritical care (RAIN) study data set contained 3626 admissions. After exclusions, 3210 patients with acute TBI were included. Overall follow-up rate at 6 months was 81%. Of 3210 patients, 101 (3.1%) had no GCS score recorded and 134 (4.2%) had a last pre-sedation GCS score of 15, resulting in 2975 patients for analysis. The most common causes of TBI were road traffic accidents (RTAs) (33%), falls (47%) and assault (12%). Patients were predominantly young (mean age 45 years overall) and male (76% overall). Six-month mortality was 22% for RTAs, 32% for falls and 17% for assault. Of survivors at 6 months with a known GOSE category, 44% had severe disability, 30% moderate disability and 26% made a good recovery. Overall, 61% of patients with known outcome had an unfavourable outcome (death or severe disability) at 6 months. Between 35% and 70% of survivors reported problems across the five domains of the EQ-5D-3L. Of the 10 risk models selected for validation, the best discrimination overall was from the International Mission for Prognosis and Analysis of Clinical Trials in TBI Lab model (IMPACT) (c-index 0.779 for mortality, 0.713 for unfavourable outcome). The model was well calibrated for 6-month mortality but substantially underpredicted the risk of unfavourable outcome at 6 months. Baseline patient characteristics were similar between dedicated neurocritical care units and combined neuro/general critical care units. In lifetime cost-effectiveness analysis, dedicated neurocritical care units had higher mean lifetime quality-adjusted life-years (QALYs) at small additional mean costs with an incremental cost-effectiveness ratio (ICER) of £14,000 per QALY and incremental net monetary benefit (INB) of £17,000. The cost-effectiveness acceptability curve suggested that the probability that dedicated compared with combined neurocritical care units are cost-effective is around 60%. There were substantial differences in case mix between the 'early' (within 18 hours of presentation) and 'no or late' (after 24 hours) transfer groups. After adjustment, the 'early' transfer group reported higher lifetime QALYs at an additional cost with an ICER of £11,000 and INB of £17,000. CONCLUSIONS: The risk models demonstrated sufficient statistical performance to support their use in research but fell below the level required to guide individual patient decision-making. The results suggest that management in a dedicated neurocritical care unit may be cost-effective compared with a combined neuro/general critical care unit (although there is considerable statistical uncertainty) and support current recommendations that all patients with severe TBI would benefit from transfer to a neurosciences centre, regardless of the need for surgery. We recommend further research to improve risk prediction models; consider alternative approaches for handling unobserved confounding; better understand long-term outcomes and alternative pathways of care; and explore equity of access to postcritical care support for patients following acute TBI. FUNDING: The National Institute for Health Research Health Technology Assessment programme