Is there an association between low dose aspirin and anemia (without overt bleeding)?: narrative review

<p>Abstract</p> <p>Background</p> <p>Overt bleeding associated with low dose aspirin (LDA) is well-recognized, little attention is given to the possibility of association between LDA and occult bleeding, although this is known to occur in healthy volunteers. LDA is used increasingly in primary and secondary prevention of a number of medical conditions, many of which are common in older people, as is anemia. Anemia in older people is associated with adverse outcomes including disability, morbidity and mortality. The purpose of this study was to review the evidence that LDA might cause anemia without overt bleeding.</p> <p>Methods</p> <p>An extensive narrative review was carried out. Electronic searching (including database links) and reference lists of reports were used to identify studies reporting on use of aspirin ≤325 mg/day and anemia or change in hemoglobin (Hb) without overt bleeding. Data were extracted from reports of trials, adverse drug reactions (ADRs) and prevalence studies of adults aged ≥18 years, published since 1980.</p> <p>Results</p> <p>There are few relevant data, with considerable heterogeneity among trial designs, duration, and patient characteristics in studies of LDA. In five randomised trials (n = 5879) in (mostly secondary) prevention, the majority of patients were men without peptic ulcer disease aged 50-70 years and no consistent association between LDA and change in Hb was found. In two smaller studies (n = 609) of primary prevention in healthy patients aged ≥70 years, there was a small but statistically significant fall in Hb with LDA. Observational studies, and data from trials in which use of LDA was not a primary focus of the study, were inconclusive.</p> <p>Conclusions</p> <p>It is not clear whether there is an association between LDA and anemia in the absence of overt bleeding, but there may be an association between LDA and fall in Hb in (a subset of) older patients. The available evidence has significant limitations, which are discussed; studies including more older patients, and publication of individual patient data, would help clarify this important matter.</p

Is there evidence for a relationship between cognitive impairment and fatigue after acquired brain injury: a systematic review and meta-analysis

PurposeFatigue is a major symptom of ABI. Greater fatigue is associated with cognitive impairment. Our aim was to systematically review, describe and analyse the literature on the extent of this relationship.MethodsFive databases were searched from inception. Studies were included where: participants had a defined clinical diagnosis of ABI which included TBI, stroke or subarachnoid haemorrhage; a fatigue measure was included; at least one objective cognitive measure was used. Three reviewers individually identified studies and determined quality using the Quality Assessment Tool for Observational Cohort and Cross-sectional Studies.ResultsSixteen of the 412 identified studies, investigating the relationship between cognitive dysfunction and fatigue, comprising a total of 1,745 participants, were included. Quality ranged from fair to good. Meta-analysis found fatigue was significantly associated with an overall pattern of cognitive slowing on tasks of sustained attention. A narrative synthesis found weak associations with fatigue and information processing, attention, memory and executive function.ConclusionAnalysis found sustained attentional performance had stronger associations with fatigue after ABI. Whereas, weak associations were found between fatigue and information processing, attention and to some extent memory and executive function. More focused research on specific cognitive domains is needed to understand the mechanisms of fatigue.Implications for RehabilitationCognitive dysfunction is associated with higher fatigue levels after stroke, traumatic brain injury or subarachnoid haemorrhage.Management of cognitive dysfunction may improve fatigue and participation in meaningful activities after stroke, traumatic brain injury or subarachnoid haemorrhage.Intervention strategies that reduce cognitive load during everyday activities (e.g., grading the burden on attentional resources), may potentially be effective in managing post-ABI fatigue.Agreement on core measures could facilitate integration of findings into clinical practice

Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials

<p>Abstract</p> <p>Background</p> <p>Duloxetine hydrochloride is a reuptake inhibitor of 5-hydroxytryptamine and norepinephrine used to treat depression, generalized anxiety disorder, neuropathic pain, and stress incontinence in women. We investigated the efficacy of duloxetine in painful diabetic neuropathy and fibromyalgia to allow comparison with other antidepressants.</p> <p>Methods</p> <p>We searched PubMed, EMBASE (via Ovid), and Cochrane CENTRAL up to June 2008 for randomised controlled trials using duloxetine to treat neuropathic pain.</p> <p>Results</p> <p>We identified six trials with 1,696 patients: 1,510 were treated with duloxetine and 706 with placebo. All patients had established baseline pain of at least moderate severity. Trial duration was 12 to 13 weeks. Three trials enrolled patients with painful diabetic neuropathy (PDN) and three enrolled patients with fibromyalgia. The number needed to treat (NNT) for at least 50% pain relief at 12 to 13 weeks with duloxetine 60 mg versus placebo (1,211 patients in the total comparison) was 5.8 (95% CI 4.5 to 8.4), and for duloxetine 120 mg (1,410 patients) was 5.7 (4.5 to 5.7). There was no difference in NNTs between PDN and fibromyalgia. With all doses of duloxetine combined (20/60/120 mg) there were fewer withdrawals for lack of efficacy than with placebo (number needed to treat to prevent one withdrawal 20 (13 to 42)), but more withdrawals due to adverse events (number needed to harm (NNH) 15 (11 to 25)). Nausea, somnolence, constipation, and reduced appetite were all more common with duloxetine than placebo (NNH values 6.3, 11, 11, and 18 respectively). The results for duloxetine are compared with published data for other antidepressants in neuropathic pain.</p> <p>Conclusion</p> <p>Duloxetine is equally effective for the treatment of PDN and fibromyalgia, judged by the outcome of at least 50% pain relief over 12 weeks, and is well tolerated. The NNT of 6 for 50% pain relief suggests that this is likely to be a useful drug in these difficult-to-treat conditions, where typically only a minority of patients respond. Comparing duloxetine with antidepressants for pain relief in DPN shows inadequacies in the evidence for efficacy of antidepressants, which are currently recommended in PDN care pathways.</p

Reframing governance possibilities for urban biodiversity conservation through systemic co-inquiry

Despite decades of effort, biodiversity has not attracted effective political discourse, policies or action to halt its decline. In cities in particular, biodiversity conservation is challenged by short term approaches, separately focusing on biodiversity or community wellbeing rather than on their interconnection, and pervasive beliefs that urban citizenry lack the requisite ethic or skills for conservation action or biodiversity governance. We describe how a systemic co-inquiry in Victoria Australia, conducted by citizen and agency practitioners alongside policy developers and academic researchers, modified understandings, practices, and institutional arrangements (governance) for urban biodiversity conservation. The most impactful outcomes of the early co inquiry period were 1) start-up funding for a network to forge collaborations between community and local government actors that engage urban residents in supporting indigenous biodiversity in their gardens, and 2) empowered co-inquiry members driving the network’s development. These efforts have led to on-going social learning and long-term institutional arrangements for a burgeoning network of municipally based nature stewardship collaborations that are nurturing local human–nature relations. Key challenges include(d): maintaining the co inquiry, paradigms that undervalue urban biodiversity and the role of citizens, organisational inertia, and evaluation measures incommensurate with strengthening person-nature relationships. Our research shows how systemic co-inquiry involving citizen practitioners can surface misleading assumptions around biodiversity stewardship and governance, and help to empower citizen and agency actors to focus on nurturing sustainable human-nature relations in cities

Use of the Capability, Opportunity and Motivation Behaviour model (COM-B) to understand interventions to support physical activity behaviour in people with stroke : an overview of reviews

Objective. Physical activity in people with stroke remains low despite considerable research. This overview aimed to provide high-level synthesis and aid clinical decision-making. The Capability, Opportunity, Motivation-Behaviour (COM-B) model was used to classify interventions to understand which components improve physical activity behaviour in people with stroke. Data Sources. CINAHL, Cochrane Database, MEDLINE, PEDro, PsychINFO, SPORTDiscus Review. MethodsA systematic search was conducted (November 2023) to identify reviews of interventions to improve physical activity in people with stroke. Results were screened and assessed for eligibility. Participant characteristics, intervention classification using COM-B, and effect of intervention were extracted. Quality was assessed using AMSTAR2, and Corrected Cover Analysis for study overlap. Narrative synthesis was used to understand components of interventions to improve physical activity behaviour. Results. 1801 references were screened and 29 full-text references assessed for eligibility. Twenty reviews were included. Quality ranged from critically low (n = 3) to high (n = 10). Study overlap calculated using corrected cover area indicated slight overlap (0.028) and minimal reporting bias. The majority of participants were mobile with mild stroke and community dwelling. Twenty-three interventions were classified using COM-B. Three of twelve interventions classified to one aspect of the COM-B were effective. Fourteen of sixteen effective interventions combined at least two COM-B elements, ten of these combined capability and motivation. Conclusion. Interventions including at least two elements of the COM-B are most likely to improve physical activity in mobile stroke survivors. Further research is needed to understand physical activity behaviour in those with moderate to severe stroke

Hydromorphone for neuropathic pain in adults

BACKGROUND Opioid drugs, including hydromorphone, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for hydromorphone, at any dose, and by any route of administration. Other opioids are considered in separate reviews.This review is part of an update of a previous review, Hydromorphone for acute and chronic pain that was withdrawn in 2013 because it needed updating and splitting to be more specific for different pain conditions. This review focuses only on neuropathic pain. OBJECTIVES To assess the analgesic efficacy of hydromorphone for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), via the CRSO; MEDLINE via Ovid; and EMBASE via Ovid from inception to 17 November 2015, together with reference lists of retrieved papers and reviews, and two online study registries. SELECTION CRITERIA We included randomised, double-blind studies of two weeks' duration or longer, comparing hydromorphone (at any dose, by any route of administration, or in any formulation) with placebo or another active treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS Searches identified seven publications relating to four studies. We excluded three studies. One post hoc (secondary) analysis of a study published in four reports assessed the efficacy of hydromorphone in neuropathic pain, satisfied our inclusion criteria, and was included in the review. The single included study had an enriched enrolment, randomised withdrawal design with 94 participants who were successfully switched from oral morphine to oral hydromorphone extended release (about 60% of those enrolled). These participants were then randomised to continuing hydromorphone for 12 weeks or tapering down the hydromorphone dose to placebo. The methodological quality of the study was generally good, but we judged the risk of bias for incomplete outcome data as unclear, and for study size as high.Since we identified only one study for inclusion, we were unable to carry out any analyses. The included study did not report any of our prespecified primary outcomes, which relate to the number of participants achieving moderate or substantial levels of pain relief. It did report a slightly larger increase in average pain intensity for placebo in the randomised withdrawal phase than for continuing with hydromorphone. It also reported the number of participants who withdrew due to lack of efficacy in the randomised withdrawal phase, which may be an indicator of efficacy. However, in addition to using an enriched enrolment, randomised withdrawal study design, there was an unusual choice of imputation methods for withdrawals (about 50% of participants); the evidence was of very low quality and inadequate to make a judgement on efficacy. Adverse events occurred in about half of participants with hydromorphone, the most common being constipation and nausea. A similar proportion of participants experienced adverse events with placebo, the most common being opioid withdrawal syndrome (very low quality evidence). Most adverse events were mild or moderate in intensity. One in eight participants withdrew while taking hydromorphone during the conversion and titration phase, despite participants being opioid-tolerant (very low quality evidence).We downgraded the quality of the evidence to very low because there was only one study with few participants, it did not report clinically useful efficacy outcomes, and it was a post hoc analysis. AUTHORS' CONCLUSIONS There was insufficient evidence to support or refute the suggestion that hydromorphone has any efficacy in any neuropathic pain condition

Human-animal elision: a Darwinian universe in George Eliot’s novels

No abstract available

Prevalence of anaemia in older persons: systematic review

<p>Abstract</p> <p>Background</p> <p>Ageing populations will impact on healthcare provision, especially since extra years are not necessarily spent in good health. It is important to identify and understand the significance of common medical problems in older people. Anaemia may be one such problem. We report on the prevalence of anaemia in cohorts of elderly people in the general population. The presence of anaemia is associated with a worse prognosis for both morbidity and mortality.</p> <p>Methods</p> <p>Electronic searching and reference lists of published reports were used to identify studies that reported on prevalence of anaemia in cohorts of at least 100 individuals predominantly aged 65 years and over living in developed countries, together with criteria used to define anaemia. Studies of anaemia prevalence in specific disease groups or published before 1980 were excluded. Prevalence data for the entire cohort, for men and women separately and for different age bands were extracted.</p> <p>Results</p> <p>Forty-five studies contributed data. Thirty-four studies (n = 85,409) used WHO criteria to define anaemia. The weighted mean prevalence was 17% (3–50%) overall, and 12% (3–25%) in studies based in the community (27, n = 69,975), 47% (31–50%) in nursing homes (3, n = 1481), and 40% (40–72%) in hospital admissions (4, n = 13,953). Anaemia prevalence increased with age, was slightly higher in men than women, and was higher in black people than white. Most individuals classified as anaemic using WHO criteria were only mildly anaemic.</p> <p>Conclusion</p> <p>Anaemia, as defined by WHO criteria, is common in older people living in the community and particularly common in nursing home residents and hospital admissions. Predicted demographic changes underline the need to understand more about anaemia in older people.</p

Characterisation of a functional rat hepatocyte spheroid model.

Many in vitro liver cell models, such as 2D systems, that are used to assess the hepatotoxic potential of xenobiotics suffer major limitations arising from a lack of preservation of physiological phenotype and metabolic competence. To circumvent some of these limitations there has been increased focus on producing more representative 3D models. Here we have used a novel approach to construct a size-controllable 3D hepatic spheroid model using freshly isolated primary rat hepatocytes (PRH) utilising the liquid-overlay technique whereby PRH spontaneously self-assemble in to 3D microtissues. This system produces viable spheroids with a compact in vivo-like structure for up to 21 days with sustained albumin production for the duration of the culture period. F-actin was seen throughout the spheroid body and P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) transporters had polarised expression on the canalicular membrane of hepatocytes within the spheroids upon formation (day 3). The MRP2 transporter was able to functionally transport 5 μM 5-chloromethylfluorescein diacetate (CMFDA) substrates into these canalicular structures. These PRH spheroids display in vivo characteristics including direct cell-cell contacts, cellular polarisation, 3D cellular morphology, and formation of functional secondary structures throughout the spheroid. Such a well-characterised system could be readily exploited for pre-clinical and non-clinical repeat-dose investigations and could make a significant contribution to replace, reduce and refine the use of animals for applied research