Laboratory tests in patients treated with isotretinoin: occurrence of liver and muscle abnormalities and failure of AST and ALT to predict liver abnormality.

Current laboratory monitoring may not be optimal. A retrospective chart review was performed on thelaboratory results of 246 patients who were treated with isotretinoin for acne over a 9-year period. Tests obtained were CBC, lipid panel, AST, ALT, CK, GGT,and C-reactive protein. Thirty-five patients had an elevated AST and 35 of these had an elevated CK; 32 had an elevated ALT and 11 of these had an elevated CK. Thirteen patients had an elevated GGT; in 5 this was the only abnormality, whereas 8 had a GGT elevation accompanied by an elevated AST or ALT. Two had an elevated GGT and an elevated CK with normal AST and ALT. Fifty-two patients had a single episode of elevated CK, of which 22 were female. However, 57 had multiple CK elevations and only one was female. Thirty-five patients had CK elevationsnormal; 38 had levels between 2 and 3 times normal, 18 had levels between 3 and 4 times normal, and 18 had levels greater than 4 times normal. We suggest that ALT and AST are not useful for monitoring isotretinoin therapy and that GGT and CK may be of greater value in managing patients

Prophylactic dressing to minimize sacral pressure injuries in high-risk hospitalized patients: A pilot study

Aim: In this paper, we describe a trial protocol used to assess feasibility related to: study administration (recruitment, randomization, retention, compliance, eligibility criteria, suitability of protocol instructions and data collection questionnaires); resource and data management (suitability of site, time and budget allocation, management of personnel and data); intervention fidelity (treatment dose, violations); and effect size. Background: Pressure injury can lead to increases in hospital length of stay and cost. The sacrum is identified as one of the most common anatomical pressure injury sites for hospitalized patients. Silicone foam border dressings have been proposed as one strategy to reduce pressure injury incidence; however, rigorous testing of benefit in a general medical-surgical population is required. Design: Randomized controlled trial. Methods: Eighty patients will be recruited after assessment of high risk of pressure injury in a large tertiary hospital in south-east Queensland, Australia. Eligible, consenting participants will be randomly allocated to either a control group (routine care) or an intervention group (routine care and a sacral prophylactic dressing). The primary outcomes comprise feasibility criteria as identified above. The secondary measure is the presence and severity of sacral pressure injury via blind assessment of digital photographs. Research ethics approval was received in October 2013. Discussion: Prophylactic dressings applied to the sacrum may be an effective method for reducing pressure injury in high-risk general medical-surgical patients. However, more rigorous studies to confirm benefit are required. This pilot study will determine the feasibility and effect size to inform a larger randomized controlled trial

Prevalence and predictors of verbal aggression in a secure mental health service:use of the HCR-20

Despite evidence about the negative effects of verbal aggression in mental health wards there is little research about its prevalence or about the factors that predict the behaviour among inpatients. This study aimed to determine the prevalence of verbal aggression in a secure mental health service, and to examine the relationship of verbal aggression with risk factors for aggression in the risk assessment tool HCR-20 in order to establish whether, and with which factors, the behaviour can be predicted. Verbal aggression was measured using the Overt Aggression Scale (OAS) over a 3-month period across a heterogeneous patient group (n = 613). Over half the patients (n = 341, 56%) engaged in 1594 incidents of verbal aggression. The HCR-20 total, clinical, and risk management subscale scores predicted verbal aggression, though effect sizes were not large. Item-outcome analysis revealed that impulsivity, negative attitudes, and non-compliance with medication were the best predictors of verbal aggression and, therefore, should be targeted for intervention. There are key synergies between factors predicting verbal aggression and the core mental health nursing role. Nurses, therefore, are in a prime position to develop and implement interventions that may reduce verbal aggression in mental health inpatients

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

An assessment of factors associated with quality of randomized controlled trials for smoking cessation

To reduce smoking-related diseases, a research priority is to develop effective interventions for smoking cessation, and evidence from randomized controlled trials (RCTs) is usually considered to be the most valid. However, findings from RCTs may still be misleading due to methodological flaws. This study aims to assess the quality of 1083 RCTs of smoking cessation interventions in 41 relevant Cochrane Systematic Reviews (CSRs). Logistic regression analysis was performed to identify significant variables associated with the quality of RCTs. It was found that evidence for smoking cessation from RCTs was predominantly from high income countries, and the overall quality was high in only 8.6% of the RCTs. High quality RCTs tended to have a larger sample size, to be more recently published, and conducted in multiple countries belonging to different income categories. In conclusion, the overall quality of RCTs of smoking cessation interventions is far from perfect, and more RCTs in less developed countries are required to generate high grade evidence for global tobacco control. Collaboration between researchers in developed and less developed countries should be encouraged

Philanthropy and COVID-19 in 2020: Measuring One Year of Giving

It has been a year since the global outbreak of COVID-19, and the world is still recovering and operating in what we have come to accept as the "new normal." In 2020, we saw funders react swiftly, not only directing emergency funds to organizations on the ground but also committing to changes in their grantmaking practices and priorities to better help nonprofits face the myriad challenges brought on by the pandemic. In this report, Candid and the Center for Disaster Philanthropy look at the global philanthropic response to COVID-19 in 2020

Investigating the origins of ivory recovered in the United Kingdom

Over recent years, mounting pressure has been placed on countries to assess their role in the ivory trade, with a view to tackling the rapidly declining numbers of elephants, due to poaching. The United Kingdom has been identified as a large re-exporter of ivory. Despite much of this trade being reported as legal or antique ivory, such provision of ivory to meet demand is known to fuel illegal markets and provide trade routes for modern ivory sales. Aside from ivory species and age, further analysis to evaluate geographic provenance, can inform where an elephant had lived, and so identify a source region or population where poaching occurred. The purpose of this study was to determine the age and species of ivory objects surrendered or seized in the UK and assess their likely geographic provenance through comparison of results from mitochondrial DNA and stable isotope analysis to publicly accessible georeferenced African elephant databases. The results demonstrated that the objects tested from an airport seizure were modern and matched existing haplotypes allowing for regional geographic inferences (supported by both techniques) to be obtained for most of these objects. In contrast, antique and modern ivory was detected amongst the amnesty objects, and several new mtDNA haplotypes were identified. Regional geographic inferences were achieved for some but not all of the objects tested. Our findings show this combination of methods provides a wealth of information which, could provide insight into targeted elephant populations and assist in disrupting international wildlife trade networks

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Tyrosine kinase signalling in breast cancer: Tyrosine kinase-mediated signal transduction in transgenic mouse models of human breast cancer

The ability of growth factors and their cognate receptors to induce mammary epithelial proliferation and differentiation is dependent on their ability to activate a number of specific signal transduction pathways. Aberrant expression of specific receptor tyrosine kinases (RTKs) has been implicated in the genesis of a significant proportion of sporadic human breast cancers. Indeed, mammary epithelial expression of activated RTKs such as ErbB2/neu in transgenic mice has resulted in the efficient induction of metastatic mammary tumours. Although it is clear from these studies that activation these growth factor receptor signalling cascades are directly involved in mammary tumour progression, the precise interaction of each of these signalling pathways in mammary tumourigenesis and metastasis remains to be elucidated. The present review focuses on the role of several specific signalling pathways that have been implicated as important components in RTK-mediated signal transduction. In particular, it focuses on two well characterized transgenic breast cancer models that carry the polyomavirus middle T(PyV mT) and neu oncogenes