148 research outputs found
Neuroimaging pain and analgesia mechanisms in experimental and chronic pain states
Chronic pain is a common and debilitating condition, affecting up to half of the UK population. Despite the use of both pharmacological and psychological/cognitive interventions, it is difficult to treat, and there is a clear need for new, effective therapies. The subjective nature of pain reporting makes the discovery and validation of new treatments challenging, but this could be improved by the presence of an objective biomarker of analgesic efficacy.
In this thesis I looked at the use of functional magnetic resonance imaging (fMRI) as such a biomarker, and as a technique for understanding the mechanisms by which interventions might achieve therapeutic effects. This was achieved through the investigation of two novel treatments for pain, the first being a pharmacological agent, and the second a cognitive therapy.
A randomised controlled trial was set up comparing ABX-1431, a first-in-class pharmacological agent that acts on the endocannabinoid system, with both placebo and nothing. Although it was not possible to show analgesic efficacy using behavioural outcomes, the presence of sedation in the active drug arm indicated a likely pharmacodynamic effect. It was possible to confirm this effect using functional magnetic resonance imaging (fMRI). Since the mechanism of action did not match that of existing analgesic agents, it was not possible to confirm analgesic efficacy, but the presence of altered activity in and connectivity between regions known to have a key role in descending pain modulation, including the lateral prefrontal cortex and right amygdala, indicates that ABX-1431 could impact chronic pain through these mechanisms, and that further trials are warranted.
Next, a prospective study of mindfulness-based cognitive therapy for irritable bowel syndrome (MBCT-IBS) was performed, in which behavioural data showed that it was an effective therapy for chronic visceral pain. Imaging showed that like ABX-1431, MBCT-IBS led to altered activity in regions of the brain known to have a role in descending pain modulation, including the right amygdala and dorsolateral prefrontal cortex. There was evidence of modulated functional connectivity between these regions and other cortical and subcortical regions important for pain perception. Activity and connectivity within the default mode network (DMN) was also affected, as was connectivity between the DMN and sensory cortices, indicating that MBCT-IBS might act by modulating intrinsic attentional networks as well as by influencing the top-down control of pain.
In combination, these studies have shown that fMRI is a valuable tool for elucidating the mechanisms of novel analgesic therapies across both pharmacological and cognitive modalities. The fact that neither intervention produced the imaging pattern seen in classical analgesia meant that fMRI was unable to provide an objective biomarker of efficacy on this occasion, but in both cases it was possible to show clear mediation of neural function in regions relating to descending pain control. It may be that in chronic pain, an objective biomarker of efficacy will look different to that seen in acute pain, and this is something worthy of further investigation
A snapshot of loss : a case study of one bereaved nine-year old boy's view of the world through his art and photographs
A child who has experienced the death of a parent may be traumatized by the loss. The nature of the child's reaction depends on a combination of several factors, including the circumstances surrounding the death, the nature of the child's relationship to the deceased parent and the existence of remaining, supportive, family members. The creative arts therapies have been successfully employed as a means of therapeutic intervention with bereaved children. One medium in the field of the creative arts therapies is the use of photography, or phototherapy. This research paper explores the use of photography, in conjunction with other forms of creative arts therapies with a parentally bereaved child. A combination of clinical examples and the writer's personal experiences and observations are employed to develop the notion that the camera (and photographs in general) can be used as a research tool, a therapeutic medium and as a metaphoric parallel in relation to working therapeutically with traumatically bereaved children
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Coccidioidomycosis Complement Fixation Titer Trends in the Age of Antifungals.
Coccidioidomycosis is associated with a broad spectrum of illness severity, ranging from asymptomatic or self-limited pulmonary infection to life-threatening manifestations of disseminated disease. Serologic studies before the widespread availability of antifungals established current understanding of serologic kinetics and dynamics. Chart histories and complement fixation (CF) titer trends were analyzed for 434 antifungal-treated coccidioidomycosis patients, who were classified by three infectious disease physicians as having either pulmonary uncomplicated coccidioidomycosis (PUC) (n = 248), pulmonary chronic coccidioidomycosis (PCC) (n = 64), disseminated coccidioidomycosis (DC) not including meningitis (n = 86), or coccidioidal meningitis (CM) (n = 36). The median maximal CF titers were 1:4 for PUC patients, 1:24 for PCC patients, 1:128 for DC patients, and 1:32 for CM patients. Approximately 25.4% of PUC patients, 6.2% of PCC patients, 2.3% of DC patients, and 8.3% of CM patients did not develop detectable titers during the study period. Maximal titers developed a mean of 31 days (95% confidence interval [CI], 13 to 50 days) after initial serologic positivity, with no significant differences between groups. Serologic recurrence occurred in 9% of PUC patients, 36% of PCC patients, 50% of DC patients, and 52% of CM patients. Median titer improvement rates were 91 days/dilution for PUC patients, 112 days/dilution for PCC patients, 136 days/dilution for DC patients, and 146 days/dilution for CM patients. Receiver operating characteristic (ROC) analysis revealed that CF testing retains moderate classification value for disseminated infections (area under the curve [AUC], 0.82 [95% CI, 0.78 to 0.87]) and complicated infections (AUC, 0.82 [95% CI, 0.77 to 0.86]). A suitable cutoff value for complicated infections is â„1:32. Findings update serologic parameters that are relevant for clinical assessment of coccidioidomycosis patients in the triazole era
A survey of physician receptivity to molecular diagnostic testing and readiness to act on results for early-stage colon cancer patients.
BACKGROUND: We sought to assess physician interest in molecular prognosic testing for patients with early stage colon cancer, and identify factors associated with the likelihood of test adoption.
METHODS: We identified physicians who care for patients with early-stage (pN0) colon cancer patients, mailed them a survey, and analyzed survey responses to assess clinician receptivity to the use of a new molecular test (GUCY2C) that identifies patients at risk for recurrence, and clinician readiness to act on abnormal test results.
RESULTS: Of 104 eligible potential respondents, 41 completed and returned the survey. Among responding physicians, 56 % were receptive to using the new prognostic test. Multivariable analyses showed that physicians in academic medical centers were significantly more receptive to molecular test use than those in non-academic settings. Forty-one percent of respondents were ready to act on abnormal molecular test results. Physicians who viewed current staging methods as inaccurate and were confident in their capacity to incorporate molecular testing in practice were more likely to say they would act on abnormal test results.
CONCLUSIONS: Physician receptivity to molecular diagnostic testing for early-stage colon cancer patients is likely to be influenced by practice setting and perceptions related to delivering quality care to patients.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01972737
Meat safety in northern Tanzania : inspectors' and slaughter workers' risk perceptions and management
This research was funded by the Biotechnology and Biological Sciences Research Council, the Department for International Development, the Economic and Social Research Council, the Medical Research Council, the Natural Environment Research Council, and the Defense Science and Technology Laboratory, under the UK Zoonoses and Emerging Livestock Systems Initiative (BB/L017679/1 and BB/L018926/1).Through a social scientific lens, this paper considers the risk perceptions and ârisk-based decision-makingâ of two key groups in a northern Tanzanian context: (1) frontline government meat inspectors and health officers charged with ensuring that red meat sold commercially is safe for people to consume, and (2) the workers who slaughter and process cattle and red meat prior to its sale in rural butcheries. In contrast to techno-scientific understandings of disease risk and ârationalâ approaches to its management, this paper foregrounds the role of social, economic and institutional context in shaping the perceptions and practices around meat safety of these actors whose daily, close proximity to meat means they play a significant role in mitigating potential meat-borne disease. We show how limited resources, and a combination of scientific and local knowledge and norms result in âsituated expertiseâ and particular forms of risk perception and practice which both enhance and compromise meat safety in different ways. Actors' shared concerns with what is visible, ensures that visibly unsafe or abnormal meat is excluded from sale, and that infrastructure and meat is kept âcleanâ and free of certain visible contaminants such as soil or, on occasion, feces. While such contaminants serve as a good proxy for pathogen presence, meat inspectors and especially slaughter workers were much less aware of or concerned with invisible pathogens that may compromise meat safety. The role of process and meat handling did not figure very strongly in their concerns. Microorganisms such as Salmonella and Campylobacter, which can easily be transferred onto meat and persist in slaughter and meat sale environments, went unacknowledged. Although health officers expressed more concern with hygiene and meat handling, their influence over slaughter process and butchery operations was unclear. Ultimately, recognizing the perceptions and practices of frontline actors who engage with meat, and the ways in which social, material and institutional realities shape these, is important for understanding how decisions about risk and meat safety are made in the complexity and context of everyday life, and thus for finding effective ways to support them to further enhance their work.Publisher PDFPeer reviewe
Rim lesions are demonstrated in early relapsingâremitting multiple sclerosis using 3Â T-based susceptibility-weighted imaging in a multi-institutional setting
PURPOSE: Rim lesions, characterised by a paramagnetic rim on susceptibility-based MRI, have been suggested to reflect chronic inflammatory demyelination in multiple sclerosis (MS) patients. Here, we assess, through susceptibility-weighted imaging (SWI), the prevalence, longitudinal volume evolution and clinical associations of rim lesions in subjects with early relapsingâremitting MS (RRMS). METHODS: Subjects (nâ=â44) with recently diagnosed RRMS underwent 3Â T MRI at baseline (M0) and 1Â year (M12) as part of a multi-centre study. SWI was acquired at M12 using a 3D segmented gradient-echo echo-planar imaging sequence. Rim lesions identified on SWI were manually segmented on FLAIR images at both time points for volumetric analysis. RESULTS: Twelve subjects (27%) had at least one rim lesion at M12. A linear mixed-effects model, with âsubjectâ as a random factor, revealed mixed evidence for the difference in longitudinal volume change between rim lesions and non-rim lesions (pâ=â0.0350 and pâ=â0.0556 for subjects with and without rim lesions, respectively). All 25 rim lesions identified showed T1-weighted hypointense signal. Subjects with and without rim lesions did not differ significantly with respect to age, disease duration or clinical measures of disability (pâ>â0.05). CONCLUSION: We demonstrate that rim lesions are detectable in early-stage RRMS on 3Â T MRI across multiple centres, although their relationship to lesion enlargement is equivocal in this small cohort. Identification of SWI rims was subjective. Agreed criteria for defining rim lesions and their further validation as a biomarker of chronic inflammation are required for translation of SWI into routine MS clinical practice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00234-021-02768-x
Mental Health Status Among Ethnic Albanians Seeking Medical Care in an Emergency Department Two Years After the War in Kosovo: A Pilot Project
Study objective: The long-term psychological effects of war are underappreciated
in clinical settings. Describing the postwar psychosocial burden on medical care can
help direct public health interventions. We performed an emergency department
(ED)âbased assessment of the mental health status of ethnic Albanian patients 2
years after the North Atlantic Treaty Organizationâled bombing of Serbia and Kosovo
in 1999.
Methods: This study was conducted July 30, 2001, to August 30, 2001, in the ED of a
hospital in Pristina, Kosovo. Investigators collected data through systematic sampling
of every sixth nonacute ED patient presenting for care; 87.7% of patients agreed to
participate. Respondents completed a structured questionnaire, including demographic
characteristics, the Short Form-36, and the Harvard Trauma Questionnaire.
Results: All 306 respondents were ethnic Albanians; mean age was 39 years (SD
17.9 years). Of respondents, 58% had become refugees during the war. Two hundred
ninety-six (97%) reported experiencing at least one traumatic event during the war;
the average number of traumatic events encountered by participants was 6.6. Fortythree
(14%) reported symptoms that met Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition criteria for posttraumatic stress disorder; mean Short Form-
36 Mental Component Summary score was 42.1 (SD 12.5). Separate multivariable linear
regression models confirmed our belief that older age, female sex, less than a
high school education, and having experienced a greater number of traumatic events
would be associated with more posttraumatic stress disorder symptoms and lower
Mental Component Summary scores.
Conclusion: Mental health problems among ED patients in Kosovo, particularly
among specific vulnerable populations, are a significant public health concern 2
years after the conflict.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40378/2/Fernandez_Mental Health Status Among Ethnic Albanians_2004.pd
Meat safety in Tanzaniaâs value chain : experiences, explanations and expectations in butcheries and eateries
This research was funded by the Biotechnology and Biological Sciences Research Council, the Department for International Development, the Economic and Social Research Council, the Medical Research Council, the Natural Environment Research Council, and the Defence Science and Technology Laboratory, under the UK Zoonoses and Emerging Livestock Systems Initiative (Grant Numbers BB/L017679/1 and BB/L018926/1).Urbanisation is associated with changes in consumption patterns and food production processes. These patterns and processes can increase or decrease the risks of outbreaks of foodborne diseases and are generally accompanied by changes in food safety policies and regulations about food handling. This affects consumers, as well as people economically engaged in the food value chain. This study looks at Tanzaniaâs red meat value chainâwhich in its totality involves about one third of the populationâand focuses on the knowledge, attitudes and reported practices of operators of butcheries and eateries with regards to meat safety in an urban and in a rural environment. We interviewed 64 operators about their experiences with foodborne diseases and their explanations and expectations around meat safety, with a particular emphasis on how they understood their own actions regarding food safety risks vis-Ă -vis regulations. We found operators of eateries emphasising their own agency in keeping meat safe, whereas operators of butcheriesâwhose products are more closely inspectedârelied more on official inspections. Looking towards meat safety in the future, interviewees in rural areas were, relative to their urban counterparts, more optimistic, which we attribute to rural operatorsâ shorter and relatively unmediated value chains.Publisher PDFPeer reviewe
Street-Level Diplomacy and Local Enforcement for Meat Safety in Northern Tanzania: Kowledge, Pragmatism and Trust
With increasing demand for red meat in Tanzania comes heightened potential for zoonotic infections
in animals and humans that disproportionately affect poor communities. A range of frontline government employees work to protect public health, providing services for people engaged in animal-based livelihoods (livestock owners and butchers), and enforcing meat safety and food premises standards. In contrast to literature which emphasises the inadequacy of extension support and food safety policy implementation in low- and middle-income countries, this paper foregrounds the âstreet-level diplomacyâ deployed by frontline actors operating in challenging contexts
Investigating the brainâs neurochemical profile at midlife in relation to dementia risk factors
Changes in the brainâs physiology in Alzheimerâs disease are thought to occur early in the diseaseâs trajectory. In this study our aim was to investigate the brainâs neurochemical profile in a midlife cohort in relation to risk factors for future dementia using single voxel proton magnetic resonance spectroscopy. Participants in the multi-site PREVENT-Dementia study (age range 40â59 year old) underwent 3T magnetic resonance spectroscopy with the spectroscopy voxel placed in the posterior cingulate/precuneus region. Using LCModel, we quantified the absolute concentrations of myo-inositol, total N-acetylaspartate, total creatine, choline, glutathione and glutamate-glutamine for 406 participants (mean age 51.1; 65.3% female). Underlying partial volume effects were accounted for by applying a correction for the presence of cerebrospinal fluid in the magnetic resonance spectroscopy voxel. We investigated how metabolite concentrations related to apolipoprotein É4 genotype, dementia family history, a risk score (Cardiovascular Risk Factors, Aging and Incidence of Dementia -CAIDE) for future dementia including non-modifiable and potentially-modifiable factors and dietary patterns (adherence to Mediterranean diet). Dementia family history was associated with decreased total N-acetylaspartate and no differences were found between apolipoprotein É4 carriers and non-carriers. A higher Cardiovascular Risk Factors, Aging, and Incidence of Dementia score related to higher myo-inositol, choline, total creatine and glutamate-glutamine, an effect which was mainly driven by older age and a higher body mass index. Greater adherence to the Mediterranean diet was associated with lower choline, myo-inositol and total creatine; these effects did not survive correction for multiple comparisons. The observed associations suggest that at midlife the brain demonstrates subtle neurochemical changes in relation to both inherited and potentially modifiable risk factors for future dementia
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