PROTECTED-UK – Clinical pharmacist interventions in the UK critical care unit: exploration of relationship between intervention, service characteristics and experience level

PURPOSE: Clinical pharmacist (CP) interventions from the PROTECTED-UK cohort, a multi-site critical care interventions study, were further analysed to assess effects of: time on critical care, number of interventions, CP expertise and days of week, on impact of intervention and ultimately contribution to patient care. METHODS: Intervention data were collected from 21 adult critical care units over 14 days. Interventions could be error, optimisation or consults, and were blind-coded to ensure consistency, prior to bivariate analysis. Pharmacy service demographics were further collated by investigator survey. KEY FINDINGS: Of the 20 758 prescriptions reviewed, 3375 interventions were made (intervention rate 16.1%). CPs spent 3.5 h per day (mean, ±SD 1.7) on direct patient care, reviewed 10.3 patients per day (±SD 4.2) and required 22.5 min (±SD 9.5) per review. Intervention rate had a moderate inverse correlation with the time the pharmacist spent on critical care (P = 0.05; r = 0.4). Optimisation rate had a strong inverse association with total number of prescriptions reviewed per day (P = 0.001; r = 0.7). A consultant CP had a moderate inverse correlation with number of errors identified (P = 0.008; r = 0.6). No correlation existed between the presence of electronic prescribing in critical care and any intervention rate. Few centres provided weekend services, although the intervention rate was significantly higher on weekends than weekdays. CONCLUSIONS: A CP is essential for safe and optimised patient medication therapy; an extended and developed pharmacy service is expected to reduce errors. CP services should be adequately staffed to enable adequate time for prescription review and maximal therapy optimisation

Pharmacist's review and outcomes: Treatment-enhancing contributions tallied, evaluated, and documented (PROTECTED-UK)

The purpose was to describe clinical pharmacist interventions across a range of critical care units (CCUs) throughout the United Kingdom, to identify CCU medication error rate and prescription optimization, and to identify the type and impact of each intervention in the prevention of harm and improvement of patient therapy

Altered networks in bothersome tinnitus: a functional connectivity study

<p>Abstract</p> <p>Background</p> <p>The objective was to examine functional connectivity linked to the auditory system in patients with bothersome tinnitus. Activity was low frequency (< 0.1 Hz), spontaneous blood oxygenation level-dependent (BOLD) responses at rest. The question was whether the experience of chronic bothersome tinnitus induced changes in synaptic efficacy between co-activated components. Functional connectivity for seed regions in auditory, visual, attention, and control networks was computed across all 2 mm³brain volumes in 17 patients with moderate-severe bothersome tinnitus (<it>Tinnitus Handicap Index: average </it>53.5 ± 3.6 (range 38-76)) and 17 age-matched controls.</p> <p>Results</p> <p>In bothersome tinnitus, negative correlations reciprocally characterized functional connectivity between auditory and occipital/visual cortex. Negative correlations indicate that when BOLD response magnitudes increased in auditory or visual cortex they decreased in the linked visual or auditory cortex, suggesting reciprocally phase reversed activity between functionally connected locations in tinnitus. Both groups showed similar connectivity with positive correlations within the auditory network. Connectivity for primary visual cortex in tinnitus included extensive negative correlations in the ventral attention temporoparietal junction and in the inferior frontal gyrus and rostral insula - executive control network components. Rostral insula and inferior frontal gyrus connectivity in tinnitus also showed greater negative correlations in occipital cortex.</p> <p>Conclusions</p> <p>These results imply that in bothersome tinnitus there is dissociation between activity in auditory cortex and visual, attention and control networks. The reciprocal negative correlations in connectivity between these networks might be maladaptive or reflect adaptations to reduce phantom noise salience and conflict with attention to non-auditory tasks.</p

Pathogenesis of Scleroderma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65784/1/j.1365-4362.1984.tb05678.x.pd

Genetic Structure Among 50 Species of the Northeastern Pacific Rocky Intertidal Community

Comparing many species' population genetic patterns across the same seascape can identify species with different levels of structure, and suggest hypotheses about the processes that cause such variation for species in the same ecosystem. This comparative approach helps focus on geographic barriers and selective or demographic processes that define genetic connectivity on an ecosystem scale, the understanding of which is particularly important for large-scale management efforts. Moreover, a multispecies dataset has great statistical advantages over single-species studies, lending explanatory power in an effort to uncover the mechanisms driving population structure. Here, we analyze a 50-species dataset of Pacific nearshore invertebrates with the aim of discovering the most influential structuring factors along the Pacific coast of North America. We collected cytochrome c oxidase I (COI) mtDNA data from populations of 34 species of marine invertebrates sampled coarsely at four coastal locations in California, Oregon, and Alaska, and added published data from 16 additional species. All nine species with non-pelagic development have strong genetic structure. For the 41 species with pelagic development, 13 show significant genetic differentiation, nine of which show striking FST levels of 0.1–0.6. Finer scale geographic investigations show unexpected regional patterns of genetic change near Cape Mendocino in northern California for five of the six species tested. The region between Oregon and Alaska is a second focus of intraspecific genetic change, showing differentiation in half the species tested. Across regions, strong genetic subdivision occurs more often than expected in mid-to-high intertidal species, a result that may reflect reduced gene flow due to natural selection along coastal environmental gradients. Finally, the results highlight the importance of making primary research accessible to policymakers, as unexpected barriers to marine dispersal break the coast into separate demographic zones that may require their own management plans

Intermittent preventive treatment with sulphadoxine-pyrimethamine is effective in preventing maternal and placental malaria in Ibadan, south-western Nigeria

<p>Abstract</p> <p>Background</p> <p>Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPT-SP) is currently the recommended regimen for prevention of malaria in pregnancy in endemic areas. This study sets out to evaluate the effectiveness of IPT-SP in the prevention of maternal and placental malaria in parturient mothers in Ibadan, Nigeria, where the risk of malaria is present all year round.</p> <p>Method</p> <p>During a larger study evaluating the epidemiology of congenital malaria, the effect of malaria prophylaxis was examined in 983 parturient mothers. Five hundred and ninety eight mothers (60.8%) received IPT-SP, 214 (21.8%) received pyrimethamine (PYR) and 171 (17.4%) did not take any chemoprophylactic agent (NC).</p> <p>Results</p> <p>The prevalence of maternal parasitaemia in the IPT-SP, PYR and NC groups was 10.4%, 15.9% and 17% respectively (p = 0.021). The prevalence of placental parasitaemia was 10.5% in the IPT-SP, 16.8% PYR and 17% NC groups, respectively (p = 0.015). The prevalence of maternal anaemia (haematocrit <30%) was 5.7% vs. 8.9% vs. 13.4% among the IPT-SP, PYR and NC groups respectively (p < 0.0001) while that of pre-term delivery (GA <37 weeks) was 10.5%, 19.2% and 25.3% among IPT-SP, PYR and NC groups respectively (p < 0.0001). Babies born to mothers in the IPT-SP, PYR and NC groups had mean birth weights of 3204 ± 487.16, 3075 ± 513.24 and 3074 ± 505.92 respectively (ρ < 0.0001). There was a trend towards a lower proportion of low birth weight babies in the IPT-SP group (p = 0.095).</p> <p>Conclusion</p> <p>IPT-SP is effective in preventing maternal and placental malaria as well as improving pregnancy outcomes among parturient women in Ibadan, Nigeria. The implementation of the recently adopted IPT-SP strategy should be pursued with vigour as it holds great promise for reducing the burden of malaria in pregnancy in Nigeria.</p

cDNA Immunization of Mice with Human Thyroglobulin Generates Both Humoral and T Cell Responses: A Novel Model of Thyroid Autoimmunity

Thyroglobulin (Tg) represents one of the largest known self-antigens involved in autoimmunity. Numerous studies have implicated it in triggering and perpetuating the autoimmune response in autoimmune thyroid diseases (AITD). Indeed, traditional models of autoimmune thyroid disease, experimental autoimmune thyroiditis (EAT), are generated by immunizing mice with thyroglobulin protein in conjunction with an adjuvant, or by high repeated doses of Tg alone, without adjuvant. These extant models are limited in their experimental flexibility, i.e. the ability to make modifications to the Tg used in immunizations. In this study, we have immunized mice with a plasmid cDNA encoding the full-length human Tg (hTG) protein, in order to generate a model of Hashimoto's thyroiditis which is closer to the human disease and does not require adjuvants to breakdown tolerance. Human thyroglobulin cDNA was injected and subsequently electroporated into skeletal muscle using a square wave generator. Following hTg cDNA immunizations, the mice developed both B and T cell responses to Tg, albeit with no evidence of lymphocytic infiltration of the thyroid. This novel model will afford investigators the means to test various hypotheses which were unavailable with the previous EAT models, specifically the effects of hTg sequence variations on the induction of thyroiditis

Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome

<p>Abstract</p> <p>Background</p> <p>This study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous <b>s</b>tomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease.</p> <p>Methods</p> <p>A cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA.</p> <p>Results</p> <p>Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.</p> <p>Conclusions</p> <p>Identification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.</p

Effect of Testosterone on Insulin Stimulated IRS1 Ser Phosphorylation in Primary Rat Myotubes—A Potential Model for PCOS-Related Insulin Resistance

Polycystic ovary syndrome (PCOS) is characterized by a hyperandrogenic state and frequently develops skeletal muscle insulin resistance. We determined whether testosterone adversely affects insulin action by increasing serine phosphorylation of IRS-1(636/639) in differentiated rat skeletal muscle myotubes. The phosphorylation of Akt, mTOR, and S6K, downstream targets of the PI3-kinase-IRS-1 complex were also studied.Primary differentiated rat skeletal muscle myotubes were subjected to insulin for 30 min after 16-hour pre-exposure to either low (20 ng/ml) or high (200 ng/ml) doses of testosterone. Protein phosphorylation of IRS-1 Ser(636/639), Akt Ser(473), mTOR-Ser(2448), and S6K-Thr(389) were measured by Western blot with signal intensity measured by immunofluorescence.Cells exposed to 100 nM of insulin had increased IRS-1 Ser(636/639) and Akt Ser(473) phosphorylation. Cells pre-exposed to low-dose testosterone had significantly increased insulin-induced mTOR-Ser(2448) and S6K-Thr(389) phosphorylation (p<0.05), and further increased insulin-induced IRS-1 Ser(636/639) phosphorylation (p = 0.042) compared to control cells. High-dose testosterone pre-exposure attenuated the insulin-induced mTOR-Ser(2448) and S6K-Thr(389) phosphorylation.The data demonstrated an interaction between testosterone and insulin on phosphorylation of intracellular signaling proteins, and suggests a link between a hyperandrogenic, hyperinsulinemic environment and the development of insulin resistance involving serine phosphorylation of IRS-1 Ser(636/639). These results may guide further investigations of potential mechanisms of PCOS-related insulin resistance