What are the important components of the clinical assessment of hand problems in older adults in primary care? Results of a Delphi study

<p>Abstract</p> <p>Background</p> <p>To identify clinical questions and assessments regarded by health care practitioners as important when assessing undifferentiated hand pain or problems in adults aged 50 years and over presenting to primary care.</p> <p>Methods</p> <p>A purposively selected panel of 26 UK-based Health Care Practitioners comprising occupational therapists, physiotherapists, rheumatologists and general practitioners, were invited to take part in a consensus study involving three postal rounds of a Delphi questionnaire with accompanying case scenarios. Participants were asked to generate questions and assessments (round 1), rate their importance (round 2), and vote on which items were most important (round 3).</p> <p>Results</p> <p>Sixteen Health Care Practitioners agreed to participate with 11 completing all three rounds. The first round of the Delphi study generated 156 questions and 143 assessments. After three rounds agreement was reached on the importance of 25 questions and 19 assessments. Questions were weighted towards current symptoms, but also included the history of previous hand problems, self-reported hand function, co-morbidity and general health. Observation and palpation of features predominated in the choice of assessment, but specific tests, grip strength, evaluation of sensation and hand function were also included.</p> <p>Conclusions</p> <p>A pool of clinical questions and assessments were generated by Health Care Practitioners, and those considered most important for assessing older adults presenting with undifferentiated hand pain and hand problems in primary care were identified. Further evaluation is required to establish the reliability and feasibility of using these questions and assessments in primary care. In particular, the relative contribution of these questions and assessments in evaluating the nature and severity of hand problems, assisting diagnosis, indicating appropriate management, and predicting future course requires further investigation.</p

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

The bii4africa dataset of faunal and floral population intactness estimates across Africa’s major land uses

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/ taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Batrachochytrium dendrobatidis in amphibians of Cameroon, including first records for caecilians

Amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has been hypothesised to be an indigenous parasite of African amphibians. In Cameroon, however, previous surveys in one region (in the northwest) failed to detect this pathogen, despite the earliest African Bd having been recorded from a frog in eastern Cameroon, plus one recent record in the far southeast. To reconcile these contrasting results, we present survey data from 12 localities across 6 regions of Cameroon from anurans (n = 1052) and caecilians (n = 85) of ca. 108 species. Bd was detected in 124 amphibian hosts at 7 localities, including Mt. Oku, Mt. Cameroon, Mt. Manengouba and lowland localities in the centre and west of the country. None of the hosts were observed dead or dying. Infected amphibian hosts were not detected in other localities in the south and eastern rainforest belt. Infection occurred in both anurans and caecilians, making this the first reported case of infection in the latter order (Gymnophiona) of amphibians. There was no significant difference between prevalence and infection intensity in frogs and caecilians. We highlight the importance of taking into account the inhibition of diagnostic qPCR in studies on Bd, based on all Bd-positive hosts being undetected when screened without bovine serum albumin in the qPCR mix. The status of Bd as an indigenous, cosmopolitan amphibian parasite in Africa, including Cameroon, is supported by this work. Isolating and sequencing strains of Bd from Cameroon should now be a priority. Longitudinal host population monitoring will be required to determine the effects, if any, of the infection on amphibians in Cameroon.http://www.int-res.com/abstracts/dao/v102/n3/http://www.int-res.com/journals/dao/dao-home/http://dx.doi.org/10.3354/dao0255

Figure 4 in Rediscovery, natural history, and conservation status of Idiocranium russeli Parker, 1936 (Amphibia: Gymnophiona: Indotyphlidae)

Figure 4. Size of newly collected sample of Idiocranium russeli. (A) Preserved length frequency distribution; (B) fresh total length versus mass.Published as part of Gower, David J., Kouete, Marcel T., Doherty-Bone, Thomas M., Ndeme, Echalle S. & Wilkinson, Mark, 2014, Rediscovery, natural history, and conservation status of Idiocranium russeli Parker, 1936 (Amphibia: Gymnophiona: Indotyphlidae), pp. 233-253 in Journal of Natural History 49 (3) on page 244, DOI: 10.1080/00222933.2014.939733, http://zenodo.org/record/400271

Figure 3 in Rediscovery, natural history, and conservation status of Idiocranium russeli Parker, 1936 (Amphibia: Gymnophiona: Indotyphlidae)

Figure 3. Photographs showing some habitats in the survey area, April 2012. (A) View approximately south from disturbed habitat on the outskirts of Kakpenyi to less disturbed forest in the nearby hills; (B) view approximately north along the Makamune valley from the northern edge of Tinta, the locality 'Tinta 4' is the recently burned patch at the centre of the picture; (C) digging fieldwork at 'Tinta 3'; (D) digging fieldwork at 'Makamune 4'.Published as part of &lt;i&gt;Gower, David J., Kouete, Marcel T., Doherty-Bone, Thomas M., Ndeme, Echalle S. &amp; Wilkinson, Mark, 2014, Rediscovery, natural history, and conservation status of Idiocranium russeli Parker, 1936 (Amphibia: Gymnophiona: Indotyphlidae), pp. 233-253 in Journal of Natural History 49 (3)&lt;/i&gt; on page 242, DOI: 10.1080/00222933.2014.939733, &lt;a href="http://zenodo.org/record/4002711"&gt;http://zenodo.org/record/4002711&lt;/a&gt

The systematics of Boulengerula fischeri (Amphibia: Gymnophiona: Caeciliidae) based on morphological and molecular data

Eight new specimens are reported for the caecilian amphibian Boulengerula fischeri, a species known in detail previously only from its holotype collected in 1987. The new material was collected at the type locality in Rwanda in 2009, and is used to expand and refine the morphological characterization of the species. Mitochondrial and nuclear gene sequences were used to assess the phylogenetic position of B. fischeri in the context of a recent molecular phylogeny of six of the seven other species of Boulengerula (from Kenya and Tanzania). Among nominal species, only B. denhardti remains to be included in molecular phylogenetic studies of Boulengerula. Boulengerula is recovered as monophyletic, with either B. fischeri or (more probably) B. boulengeri sister to all other sampled species. There are at least three deep lineages within Boulengerula: (1) B. boulengeri, (2) B. fischeri, and (3) all other Eastern Arc Mountain and Coastal Forest species from Kenya and Tanzania. The status of Afrocaecilia, a genus erected by Taylor in 1968 to contain all Boulengerula except B. boulengeri, is not yet resolved