Tertiary hypothyroidism in a dog

<p/> <p>A nine-year-old male entire Labrador was diagnosed with pituitary dependent hyperadrenocorticism. Following seven months of successful mitotane therapy, the dog presented with marked weight gain, seborrhoea and alopecia. Routine clinicopathological analyses revealed marked hypercholesterolaemia. Serum total and free thyroxine (T4) concentrations were below their respective reference ranges. Serum thyroid stimulating hormone (cTSH) concentration was within reference range. TSH and thyrotropin releasing hormone (TRH) response tests revealed adequate stimulation of total T4 in both, and cTSH in the latter test. Magnetic resonance imaging revealed a mass arising from the pituitary fossa, with suprasellar extension. A diagnosis of tertiary hypothyroidism was made. Following four weeks of levothyroxine therapy, circulating cholesterol concentration had declined, weight loss had ensued and dermatological abnormalities had improved. Euthanasia was performed four months later due to the development of neurological signs. A highly infiltrative pituitary adenoma, with effacement of the overlying hypothalamus was identified on post mortem examination. Tertiary hypothyroidism has not been previously reported in dogs.</p

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio

Sticky knowledge: A possible model for investigating implementation in healthcare contexts

<p>Abstract</p> <p>Background</p> <p>In health care, a well recognized gap exists between what we know should be done based on accumulated evidence and what we actually do in practice. A body of empirical literature shows organizations, like individuals, are difficult to change. In the business literature, knowledge management and transfer has become an established area of theory and practice, whilst in healthcare it is only starting to establish a firm footing. Knowledge has become a business resource, and knowledge management theorists and practitioners have examined how knowledge moves in organisations, how it is shared, and how the return on knowledge capital can be maximised to create competitive advantage. New models are being considered, and we wanted to explore the applicability of one of these conceptual models to the implementation of evidence-based practice in healthcare systems.</p> <p>Methods</p> <p>The application of a conceptual model called sticky knowledge, based on an integration of communication theory and knowledge transfer milestones, into a scenario of attempting knowledge transfer in primary care.</p> <p>Results</p> <p>We describe Szulanski's model, the empirical work he conducted, and illustrate its potential applicability with a hypothetical healthcare example based on improving palliative care services. We follow a doctor through two different posts and analyse aspects of knowledge transfer in different primary care settings. The factors included in the sticky knowledge model include: causal ambiguity, unproven knowledge, motivation of source, credibility of source, recipient motivation, recipient absorptive capacity, recipient retentive capacity, barren organisational context, and arduous relationship between source and recipient. We found that we could apply all these factors to the difficulty of implementing new knowledge into practice in primary care settings.</p> <p>Discussion</p> <p>Szulanski argues that knowledge factors play a greater role in the success or failure of a knowledge transfer than has been suspected, and we consider that this conjecture requires further empirical work in healthcare settings.</p

Decline in Health-Related Quality of Life reported by more than half of those waiting for joint replacement surgery: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>In many healthcare systems, people with severe joint disease wait months to years for joint replacement surgery. There are little empirical data on the health consequences of this delay and it is unclear whether people with substantial morbidity at entry to the waiting list continue to deteriorate further while awaiting surgery. This study investigated changes in Health-Related Quality of Life (HRQoL), health status and psychological distress among people waiting for total hip (THR) and knee replacement (TKR) surgery at a major metropolitan Australian public hospital.</p> <p>Methods</p> <p>134 patients completed questionnaires including the Assessment of Quality of Life (AQoL) instrument, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kessler Psychological Distress Scale after entering an orthopaedic waiting list (baseline) and before surgery (preadmission). To quantify potential decline in wellbeing, we calculated the proportion of people experiencing clinically important deterioration using published guidelines and compared HRQoL and psychological distress outcomes with population norms.</p> <p>Results</p> <p>Most participants (69%) waited ≥6 months for surgery (median 286 days, IQR 169-375 days). Despite poor physical and psychological wellbeing at baseline, there was an overall deterioration in HRQoL during the waiting period (mean AQoL change -0.04, 95%CI -0.08 to -0.01), with 53% of participants experiencing decline in HRQoL (≥0.04 AQoL units). HRQoL prior to surgery remained substantially lower than Australian population norms (mean sample AQoL 0.37, 95%CI 0.33 to 0.42 vs mean population AQoL 0.83, 95%CI 0.82 to 0.84). Twenty-five per cent of participants showed decline in health status (≥9.6 WOMAC units) over the waiting period and prevalence of high psychological distress remained high at preadmission (RR 3.5, 95%CI 2.8 to 4.5). Most participants considered their pain (84%), fatigue (76%), quality of life (73%) and confidence in managing their health (55%) had worsened while waiting for surgery.</p> <p>Conclusions</p> <p>Despite substantial initial morbidity, over half of the participants awaiting joint replacement experienced deterioration in HRQoL during the waiting period. These data provide much-needed evidence to guide health professionals and policymakers in the design of care pathways and resource allocation for people who require joint replacement surgery.</p

Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function

<p>Abstract</p> <p>Background</p> <p>Asthma is a chronic inflammatory disease of the airway that is characterized by a Th2-type of immune response with increasing evidence for involvement of Th17 cells. The role of IL-6 in promoting effector T cell subsets suggest that IL-6 may play a functional role in asthma. Classically IL-6 has been viewed as an inflammatory marker, along with TNFα and IL-1β, rather than as regulatory cytokine.</p> <p>Objective</p> <p>To investigate the potential relationship between IL-6 and other proinflammatory cytokines, Th2/Th17 cytokines and lung function in allergic asthma, and thus evaluate the potential role of IL-6 in this disease.</p> <p>Methods</p> <p>Cytokine levels in induced sputum and lung function were measured in 16 healthy control and 18 mild-moderate allergic asthmatic subjects.</p> <p>Results</p> <p>The levels of the proinflammatory biomarkers TNFα and IL-1β were not different between the control and asthmatic group. In contrast, IL-6 levels were specifically elevated in asthmatic subjects compared with healthy controls (p < 0.01). Hierarchical regression analysis in the total study cohort indicates that the relationship between asthma and lung function could be mediated by IL-6. Among Th2 cytokines only IL-13 (p < 0.05) was also elevated in the asthmatic group, and positively correlated with IL-6 levels (r_S= 0.53, p < 0.05).</p> <p>Conclusions</p> <p>In mild-moderate asthma, IL-6 dissociates from other proinflammatory biomarkers, but correlates with IL-13 levels. Furthermore, IL-6 may contribute to impaired lung function in allergic asthma.</p

Long-term impact of the COVID-19 pandemic on the quality of life of people with dementia and their family carers

\ua9 The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. INTRODUCTION: Few studies have longitudinally mapped quality of life (QoL) trajectories of newly diagnosed people with dementia and their carers, particularly during coronavirus disease-2019 (COVID-19). METHODS: In a UK cohort study, 261 newly diagnosed people with dementia and 206 family carers were assessed prior to the pandemic (July 2019-March 2020), followed up after the first lockdown (July-October 2020) and then again a year and 2 years later. Latent growth curve modelling examined the level and change of QoL over the four time-points using dementia-specific QoL measures (DEMQOL and C-DEMQOL). RESULTS: Despite variations in individual change scores, our results suggest that generally people with dementia maintained their QoL during the pandemic and experienced some increase towards the end of the period. This contrasted with carers who reported a general deterioration in their QoL over the same period. \u27Confidence in future\u27 and \u27Feeling supported\u27 were the only carer QoL subscales to show some recovery post-pandemic. DISCUSSION: It is positive that even during a period of global disruption, decline in QoL is not inevitable following the onset of dementia. However, it is of concern that carer QoL declined during this same period even after COVID-19 restrictions had been lifted. Carers play an invaluable role in the lives of people with dementia and wider society, and our findings suggest that, post-pandemic, they may require greater support to maintain their QoL