Fall risk in people with MS: A Physiological Profile Assessment study.

INTRODUCTION: The Physiological Profile Assessment (PPA) is used in research and clinical practice for assessing fall risk. We compared PPA test performance between people with multiple sclerosis (MS) and healthy controls, determined the fall-risk profile for people with MS and developed a reference database for people with MS. METHODS: For this study, 416 ambulant people with MS (51.5 ± 12.0 years) and 352 controls (52.8 ± 12.2 years) underwent the PPA (tests of contrast sensitivity, proprioception, quadriceps strength, reaction time and sway) with composite fall-risk scores computed from these measures. MS participants were followed prospectively for falls for 3 months. RESULTS: The MS participants performed significantly worse than controls in each PPA test. The average composite fall-risk score was also significantly elevated, indicating a "marked" fall risk when compared with controls. In total, 155 MS participants (37.3%) reported 2 + falls in the follow-up period. Frequent fallers performed significantly worse than non-frequent fallers in the contrast sensitivity, reaction time and sway tests and had higher PPA composite scores. CONCLUSIONS: In line with poor PPA test performances, falls incidence in people with MS was high. This study provides comprehensive reference data for the PPA measures for people with MS that could be used to inform future research and clinical practice

Justice at Sea: Fishers’ politics and marine conservation in coastal Odisha, India

This is a paper about the politics of fishing rights in and around the Gahirmatha marine sanctuary in coastal Odisha, in eastern India. Claims to the resources of this sanctuary are politicised through the creation of a particularly damaging narrative by influential Odiya environmental actors about Bengalis, as illegal immigrants who have hurt the ecosystem through their fishing practices. Anchored within a theoretical framework of justice as recognition, the paper considers the making of a regional Odiya environmentalism that is, potentially, deeply exclusionary. It details how an argument about ‘illegal Bengalis’ depriving ‘indigenous Odiyas’ of their legitimate ‘traditional fishing rights’ derives from particular notions of indigeneity and territory. But the paper also shows that such environmentalism is tenuous, and fits uneasily with the everyday social landscape of fishing in coastal Odisha. It concludes that a wider class conflict between small fishers and the state over a sanctuary sets the context in which questions about legitimate resource rights are raised, sometimes with important effects, like when out at sea

Rethinking the Poverty-disease Nexus: the Case of HIV/AIDS in South Africa

While it is well-established that poverty and disease are intimately connected, the nature of this connection and the role of poverty in disease causation remains contested in scientific and social studies of disease. Using the case of HIV/AIDS in South Africa and drawing on a theoretically grounded analysis, this paper reconceptualises disease and poverty as ontologically entangled. In the context of the South African HIV epidemic, this rethinking of the poverty-disease dynamic enables an account of how social forces such as poverty become embodied in the very substance of disease to produce ontologies of HIV/AIDS unique to South Africa

Telling partners about chlamydia: how acceptable are the new technologies?

<p>Abstract</p> <p>Background</p> <p>Partner notification is accepted as a vital component in the control of chlamydia. However, in reality, many sexual partners of individuals diagnosed with chlamydia are never informed of their risk. The newer technologies of email and SMS have been used as a means of improving partner notification rates. This study explored the use and acceptability of different partner notification methods to help inform the development of strategies and resources to increase the number of partners notified.</p> <p>Methods</p> <p>Semi-structured telephone interviews were conducted with 40 people who were recently diagnosed with chlamydia from three sexual health centres and two general practices across three Australian jurisdictions.</p> <p>Results</p> <p>Most participants chose to contact their partners either in person (56%) or by phone (44%). Only 17% chose email or SMS. Participants viewed face-to-face as the "gold standard" in partner notification because it demonstrated caring, respect and courage. Telephone contact, while considered insensitive by some, was often valued because it was quick, convenient and less confronting. Email was often seen as less personal while SMS was generally considered the least acceptable method for telling partners. There was also concern that emails and SMS could be misunderstood, not taken seriously or shown to others. Despite these, email and SMS were seen to be appropriate and useful in some circumstances. Letters, both from the patients or from their doctor, were viewed more favourably but were seldom used.</p> <p>Conclusion</p> <p>These findings suggest that many people diagnosed with chlamydia are reluctant to use the new technologies for partner notification, except in specific circumstances, and our efforts in developing partner notification resources may best be focused on giving patients the skills and confidence for personal interaction.</p

A retrospective cohort study of stroke onset: implications for characterizing short term effects from ambient air pollution

<p>Abstract</p> <p>Background</p> <p>Case-crossover studies used to investigate associations between an environmental exposure and an acute health response, such as stroke, will often use the day an individual presents to an emergency department (ED) or is admitted to hospital to infer when the stroke occurred. Similarly, they will use patient's place of residence to assign exposure. The validity of using these two data elements, typically extracted from administrative databases or patient charts, to define the time of stroke onset and to assign exposure are critical in this field of research as air pollutant concentrations are temporally and spatially variable. Our a priori hypotheses were that date of presentation differs from the date of stroke onset for a substantial number of patients, and that assigning exposure to ambient pollution using place of residence introduces an important source of exposure measurement error. The objective of this study was to improve our understanding on how these sources of errors influence risk estimates derived using a case-crossover study design.</p> <p>Methods</p> <p>We sought to collect survey data from stroke patients presenting to hospital EDs in Edmonton, Canada on the date, time, location and nature of activities at onset of stroke symptoms. The daily mean ambient concentrations of NO₂and PM_2.5on the self-reported day of stroke onset was estimated from continuous fixed-site monitoring stations.</p> <p>Results</p> <p>Of the 336 participating patients, 241 were able to recall when their stroke started and 72.6% (95% confidence interval [CI]: 66.9 - 78.3%) experienced stroke onset the same day they presented to the ED. For subjects whose day of stroke onset differed from the day of presentation to the ED, this difference ranged from 1 to 12 days (mean = 1.8; median = 1). In these subjects, there were no systematic differences in assigned pollution levels for either NO₂or PM_2.5when day of presentation rather than day of stroke onset was used. At the time of stroke onset, 89.9% (95% CI: 86.6 - 93.1%) reported that they were inside, while 84.5% (95% CI: 80.6 - 88.4%) reported that for most of the day they were within a 15 minute drive from home. We estimated that due to the mis-specification of the day of stroke onset, the risk of hospitalization for stroke would be understated by 15% and 20%, for NO₂and PM_2.5, respectively.</p> <p>Conclusions</p> <p>Our data suggest that day of presentation and residential location data obtained from administrative records reasonably captures the time and location of stroke onset for most patients. Under these conditions, any associated errors are unlikely to be an important source of bias when estimating air pollution risks in this population.</p

Assessing Recent Smoking Status by Measuring Exhaled Carbon Monoxide Levels

The main expectations of applying proteomics technologies to clinical questions are the discovery of disease related biomarkers. Despite technological advancement to increase proteome coverage and depth to meet these expectations the number of generated biomarkers for clinical use is small. One of the reasons is that found potential biomarkers often are false discoveries. Small sample sizes, in combination with patient sample heterogeneity increase the risk of false discoveries. To be able to extract relevant biological information from such data, high demands are put on the experimental design and the use of sensitive and quantitatively accurate technologies. The overall aim of this thesis was to apply quantitative proteomics methods for biomarker discovery in clinical samples. A method for reducing bias by controlling for individual variation in smoking habits is described in paper I. The aim of the method was objective assessment of recent smoking in clinical studies on inflammatory responses. In paper II, the proteome of alveolar macrophages obtained from smoking subjects with and without the inflammatory lung disease chronic obstructive pulmonary disease (COPD) were quantified by two-dimensional gel-electrophoresis (2-DE). A gender focused analysis showed protein level differences within the female group, with down-regulation of lysosomal pathway and up-regulation of oxidative pathway in COPD patients. Paper III, a mass spectrometry based proteomics analysis of tumour samples, contributes to the molecular understanding of vulvar squamous cell carcinoma (VSCC) and we identified a high risk patient subgroup of HPV-negative tumours based on the expression of four proteins, further suggesting that this subgroup is characterized by an altered ubiquitin-proteasome signalling pathway. Paper III describes a data analysis workflow for the extraction of biological information from quantitative mass spectrometry based proteomics data. High patient-to-patient tumour proteome variability was addressed by using pathway profiling on individual tumour data, followed by comparison of pathway association ranks in a multivariate analysis. We show that pathway data on individual tumour level can detect subpopulations of patients and identify pathways of specific importance in pre-defined clinical groups by the use of multivariate statistics. In paper IV, the potentials and limits of quantitative mass spectrometry on clinical samples was evaluated by defining the quantitative accuracy of isobaric labels and label-free quantification. Quantification by isobaric labels in combination with pI pre-fractionation showed a lower limit of quantification (LOQ) than a label-free analysis without pI pre-fractionation, and 6-plex TMT were more sensitive than 8-plex iTRAQ. Precursor mixing measured by isolation interference (MS1 interference) is more linked to the quantitative accuracy of isobaric labels than reporter ion interference (MS2 interference). Based on that we could define recommendations for how much isolation interference that can be accepted; in our data <30% isolation interference had little effect the quantitative accuracy. In conclusion, getting biological knowledge from proteomics studies requires a careful study design, control of possible confounding factors and the use of clinical data to identify disease subtypes. Further, to be able to draw conclusions from the data, the analysis requires accurate quantitative data and robust statistical tools to detect significant protein alterations. Methods around these issues are developed and discussed in this thesis

Controlled human exposures to ambient pollutant particles in susceptible populations

Epidemiologic studies have established an association between exposures to air pollution particles and human mortality and morbidity at concentrations of particles currently found in major metropolitan areas. The adverse effects of pollution particles are most prominent in susceptible subjects, including the elderly and patients with cardiopulmonary diseases. Controlled human exposure studies have been used to confirm the causal relationship between pollution particle exposure and adverse health effects. Earlier studies enrolled mostly young healthy subjects and have largely confirmed the capability of particles to cause adverse health effects shown in epidemiological studies. In the last few years, more studies involving susceptible populations have been published. These recent studies in susceptible populations, however, have shown that the adverse responses to particles appear diminished in these susceptible subjects compared to those in healthy subjects. The present paper reviewed and compared control human exposure studies to particles and sought to explain the "unexpected" response to particle exposure in these susceptible populations and make recommendations for future studies. We found that the causes for the discrepant results are likely multifactorial. Factors such as medications, the disease itself, genetic susceptibility, subject selection bias that is intrinsic to many controlled exposure studies and nonspecificity of study endpoints may explain part of the results. Future controlled exposure studies should select endpoints that are more closely related to the pathogenesis of the disease and reflect the severity of particle-induced health effects in the specific populations under investigation. Future studies should also attempt to control for medications and genetic susceptibility. Using a different study design, such as exposing subjects to filtered air and ambient levels of particles, and assessing the improvement in biological endpoints during filtered air exposure, may allow the inclusion of higher risk patients who are likely the main contributors to the increased particle-induced health effects in epidemiological studies

Anticholinergic drug burden tools/scales and adverse outcomes in different clinical settings: a systematic review of reviews

Background: Cumulative anticholinergic exposure (anticholinergic burden) has been linked to a number of adverse outcomes. To conduct research in this area, an agreed approach to describing anticholinergic burden is needed. Objective: This review set out to identify anticholinergic burden scales, to describe their rationale, the settings in which they have been used and the outcomes associated with them. Methods: A search was performed using the Healthcare Databases Advanced Search of MEDLINE, EMBASE, Cochrane, CINAHL and PsycINFO from inception to October 2016 to identify systematic reviews describing anticholinergic burden scales or tools. Abstracts and titles were reviewed to determine eligibility for review with eligible articles read in full. The final selection of reviews was critically appraised using the ROBIS tool and pre-defined data were extracted; the primary data of interest were the anticholinergic burden scales or tools used. Results: Five reviews were identified for analysis containing a total of 62 original articles. Eighteen anticholinergic burden scales or tools were identified with variation in their derivation, content and how they quantified the anticholinergic activity of medications. The Drug Burden Index was the most commonly used scale or tool in community and database studies, while the Anticholinergic Risk Scale was used more frequently in care homes and hospital settings. The association between anticholinergic burden and clinical outcomes varied by index and study. Falls and hospitalisation were consistently found to be associated with anticholinergic burden. Mortality, delirium, physical function and cognition were not consistently associated. Conclusions: Anticholinergic burden scales vary in their rationale, use and association with outcomes. This review showed that the concept of anticholinergic burden has been variably defined and inconsistently described using a number of indices with different content and scoring. The association between adverse outcomes and anticholinergic burden varies between scores and has not been conclusively established

Can psychosocial and socio-demographic questions help identify sexual risk among heterosexually-active women of reproductive age? Evidence from Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Background: Contraceptive advice and supply (CAS) and sexually transmitted infection (STI) testing are increasingly provided in primary care. Most risk assessment tools are based on sexual risk behaviours and socio-demographics, for use online or in specialist services. Combining socio-demographic and psychosocial questions (e.g. religious belief and formative experience) may generate an acceptable tool for targeting women in primary care who would benefit from intervention. We aimed to identify psychosocial and socio-demographic factors associated with reporting key sexual risk behaviours among women in the British general population. Methods: We undertook complex survey analysis of data from 4,911 hetero-sexually active women aged 16-44 years, who participated in Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a national probability sample survey undertaken 2010-2012. We used multivariable regression to examine associations between the available psychosocial and socio-demographic variables in Natsal-3 and reports of 3 key sexual behaviours: a) 2+ partners in the last year (2PP); b) non-use of condoms with 2+ partners in the last year (2PPNC); c) non-use of condoms at first sex with most recent sexual partner (FSNC). We adjusted for key socio-demographic factors: age, ethnicity and socio-economic status (measured by housing tenure). Results: Weekly binge drinking (6+ units on one occasion), and first sex before age 16 were each positively associated with all three sexual behaviours after adjustment. Current relationship status, reporting drug use (ever), younger age and living in rented accommodation were also associated with 2+ partners and 2+partners without condoms after adjustment. Currently being a smoker, older age and respondent ethnicity were associated with FSNC after adjustment for all other variables. Current smoking status, treatment for depression (last year), and living at home with both parents until the age of 14 were each associated with 1 or more of the behaviours. Conclusions: Reported weekly binge drinking, early sexual debut, and age group may help target STI testing and/or CAS among women. Further research is needed to examine the proportion of sexual risk explained by these factors, the acceptability of these questions to women in primary care and the need to customise them for community and other settings

Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors.

BACKGROUND: Febrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Risk factors for FN have been reported, but risk models that include genetic variability have yet to be described. This study aimed to evaluate the predictive value of patient-related, chemotherapy-related, and genetic risk factors. METHODS: Data from consecutive breast cancer patients receiving chemotherapy with 4-6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) or three cycles of FEC and docetaxel were retrospectively recorded. Multivariable logistic regression was carried out to assess risk of FN during FEC chemotherapy cycles. RESULTS: Overall, 166 (16.7%) out of 994 patients developed FN. Significant risk factors for FN in any cycle and the first cycle were lower platelet count (OR = 0.78 [0.65; 0.93]) and haemoglobin (OR = 0.81 [0.67; 0.98]) and homozygous carriers of the rs4148350 variant T-allele (OR = 6.7 [1.04; 43.17]) in MRP1. Other significant factors for FN in any cycle were higher alanine aminotransferase (OR = 1.02 [1.01; 1.03]), carriers of the rs246221 variant C-allele (OR = 2.0 [1.03; 3.86]) in MRP1 and the rs351855 variant C-allele (OR = 2.48 [1.13; 5.44]) in FGFR4. Lower height (OR = 0.62 [0.41; 0.92]) increased risk of FN in the first cycle. CONCLUSIONS: Both established clinical risk factors and genetic factors predicted FN in breast cancer patients. Prediction was improved by adding genetic information but overall remained limited. Internal validity was satisfactory. Further independent validation is required to confirm these findings