Development and evaluation of a hand held computer based on-call pack for health protection out of hours duty: A pilot study

BACKGROUND: The on call service for health protection in most parts of the UK is provided by general public health consultants, registrars and nurses as the first tier of response backed up by medical consultants in health protection. The first tier responder usually carries a large bag of papers containing both local and national guidance on the management of common cases/incidents. An electronic on call pack may provide a suitable practical alternative to large paper based systems and help professionals deliver out of hours health protection advice and response to incidents. METHODS: We developed and piloted an electronic on call pack in Hertfordshire for use at the health protection unit level containing key local and national guidelines, contact information and useful references. The on-call pack was initially piloted using a laptop and more recently using a personal digital assistant (PDA). The use of the on-call pack was evaluated. RESULTS: Key advantages of the electronic system include reduced size, faster access to information that is clearly indexed and the relative ease of updating information. As part of the pilot, the electronic on call pack was presented to a local and regional training meeting with good response from participants using qualitative and quantitative methods. CONCLUSION: It is anticipated that with suitable evaluation this system can be adapted and utilised by other health protection practitioners. This system provides a fast, reliable and easily maintained source of information for the public health on-call team

Immediate continuous passive motion after internal fixation of an ankle fracture

Surgical treatment is usually mandatory in displaced bimalleolar and trimalleolar fractures. Some authors have recommended early mobilization of the ankle joint after surgical treatment of these lesions. In this study, we evaluate the effect of immediate postoperative continuous passive motion in the management of displaced bimalleolar and trimalleolar fractures treated surgically

Group differences in physician responses to handheld presentation of clinical evidence: a verbal protocol analysis

<p>Abstract</p> <p>Background</p> <p>To identify individual differences in physicians' needs for the presentation of evidence resources and preferences for mobile devices.</p> <p>Methods</p> <p>Within-groups analysis of responses to semi-structured interviews. Interviews consisted of using prototypes in response to task-based scenarios. The prototypes were implemented on two different form factors: a tablet style PC and a pocketPC. Participants were from three user groups: general internists, family physicians and medicine residents, and from two different settings: urban and semi-urban. Verbal protocol analysis, which consists of coding utterances, was conducted on the transcripts of the testing sessions. Statistical relationships were investigated between staff physicians' and residents' background variables, self-reported experiences with the interfaces, and verbal code frequencies.</p> <p>Results</p> <p>47 physicians were recruited from general internal medicine, family practice clinics and a residency training program. The mean age of participants was 42.6 years. Physician specialty had a greater effect on device and information-presentation preferences than gender, age, setting or previous technical experience. Family physicians preferred the screen size of the tablet computer and were less concerned about its portability. Residents liked the screen size of the tablet, but preferred the portability of the pocketPC. Internists liked the portability of the pocketPC, but saw less advantage to the large screen of the tablet computer (F[2,44] = 4.94, p = .012).</p> <p>Conclusion</p> <p>Different types of physicians have different needs and preferences for evidence-based resources and handheld devices. This study shows how user testing can be incorporated into the process of design to inform group-based customization.</p

Physiological dynamics of chemosynthetic symbionts in hydrothermal vent snails

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Breusing, C., Mitchell, J., Delaney, J., Sylva, S. P., Seewald, J. S., Girguis, P. R., & Beinart, R. A. Physiological dynamics of chemosynthetic symbionts in hydrothermal vent snails. Isme Journal, (2020), doi:10.1038/s41396-020-0707-2.Symbioses between invertebrate animals and chemosynthetic bacteria form the basis of hydrothermal vent ecosystems worldwide. In the Lau Basin, deep-sea vent snails of the genus Alviniconcha associate with either Gammaproteobacteria (A. kojimai, A. strummeri) or Campylobacteria (A. boucheti) that use sulfide and/or hydrogen as energy sources. While the A. boucheti host–symbiont combination (holobiont) dominates at vents with higher concentrations of sulfide and hydrogen, the A. kojimai and A. strummeri holobionts are more abundant at sites with lower concentrations of these reductants. We posit that adaptive differences in symbiont physiology and gene regulation might influence the observed niche partitioning between host taxa. To test this hypothesis, we used high-pressure respirometers to measure symbiont metabolic rates and examine changes in gene expression among holobionts exposed to in situ concentrations of hydrogen (H2: ~25 µM) or hydrogen sulfide (H2S: ~120 µM). The campylobacterial symbiont exhibited the lowest rate of H2S oxidation but the highest rate of H2 oxidation, with fewer transcriptional changes and less carbon fixation relative to the gammaproteobacterial symbionts under each experimental condition. These data reveal potential physiological adaptations among symbiont types, which may account for the observed net differences in metabolic activity and contribute to the observed niche segregation among holobionts.We thank the Schmidt Ocean Institute, the crew of the R/V Falkor and the pilots of the ROV ROPOS for facilitating the sample collections and shipboard experiments, and the Broad Institute Microbial ‘Omics Core for preparing and sequencing the transcriptomic libraries. This material is based in part upon work supported by the National Science Foundation under Grant Numbers NSF OCE-1536653 (to PRG), OCE-1536331 (to RAB and JSS), OCE-1819530 and OCE-1736932 (to RAB)

Influence of pharmacogenetic variability on the pharmacokinetics and toxicity of the aurora kinase inhibitor danusertib

Objectives Danusertib is a serine/threonine kinase inhibitor of multiple kinases, including aurora-A, B, and C. This explorative study aims to identify possible relationships between single nucleotide polymorphisms in genes coding for drug metabolizing enzymes and transporter proteins and clearance of danusertib, to clarify the interpatient variability in exposure. In addition, this study explores the relationship between target receptor polymorphisms and toxicity of danusertib. Methods For associations with clearance, 48 cancer patients treated in a phase I study were analyzed for ABCB1, ABCG2 and FMO3 polymorphisms. Association analyses between neutropenia and drug target receptors, including KDR, RET, FLT3, FLT4, AURKB and AURKA, were performed in 30 patients treated at recommended phase II dose-levels in three danusertib phase I or phase II trials. Results No relationships between danusertib clearance and drug metabolizing enzymes and transporter protein polymorphisms were found. Only, for the one patient with FMO3 18281AA polymorphism, a significantly higher clearance was noticed, compared to patients carrying at least 1 wild type allele. No effect of target receptor genotypes or haplotypes on neutropenia was observed. Conclusions As we did not find any major correlations between pharmacogenetic variability in the studied enzymes and transporters and pharmacokinetics nor toxicity, it is unlikely that danusertib is highly susceptible for pharmacogenetic variation. Therefore, no dosing alterations of danusertib are expected in the future, based on the polymorphisms studied. However, the relationship between FMO3 polymorphisms and clearance of danusertib warrants further research, as we could study only a small group of patients

Microalbuminuria among Type 1 and Type 2 diabetic patients of African origin in Dar Es Salaam, Tanzania

BACKGROUND: The prevalences and risk factors of microalbuminuria are not full described among black African diabetic patients. This study aimed at determining the prevalence of microalbuminuria among African diabetes patients in Dar es Salaam, Tanzania, and relate to socio-demographic features as well as clinical parameters. METHODS: Cross sectional study on 91 Type 1 and 153 Type 2 diabetic patients. Two overnight urine samples per patient were analysed. Albumin concentration was measured by an automated immunoturbidity assay. Average albumin excretion rate (AER) was used and were categorised as normalbuminuria (AER < 20 ug/min), microalbuminuria (AER 20–200 ug/min), and macroalbuminuria (AER > 200 ug/min). Information obtained also included age, diabetes duration, sex, body mass index, blood pressure, serum total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides, serum creatinine, and glycated hemoglobin A(1c). RESULTS: Overall prevalence of microalbuminuria was 10.7% and macroalbuminuria 4.9%. In Type 1 patients microalbuminuria was 12% and macroalbuminuria 1%. Among Type 2 patients, 9.8% had microalbuminuria, and 7.2% had macroalbuminuria. Type 2 patients with abnormal albumin excretion rate had significantly longer diabetes duration 7.5 (0.2–24 yrs) than those with normal albumin excretion rate 3 (0–25 yrs), p < 0.001. Systolic and diastolic blood pressure among Type 2 patients with abnormal albumin excretion rate were significantly higher than in those with normal albumin excretion rate, (p < 0.001). No significant differences in body mass index, glycaemic control, and cholesterol levels was found among patients with normal compared with those with elevated albumin excretion rate either in Type 1 or Type 2 patients. A stepwise multiple linear regression analysis among Type 2 patients, revealed AER (natural log AER) as the dependent variable to be predicted by [odds ratio (95% confidence interval)] diabetes duration 0.090 (0.049, 0.131), p < 0.0001, systolic blood pressure 0.012 (0.003–0.021), p < 0.010 and serum creatinine 0.021 (0.012, 0.030). CONCLUSION: The prevalence of micro and macroalbuminuria is higher among African Type 1 patients with relatively short diabetes duration compared with prevalences among Caucasians. In Type 2 patients, the prevalence is in accordance with findings in Caucasians. The present study detects, however, a much lower prevalence than previously demonstrated in studies from sub-Saharan Africa. Abnormal AER was significantly related to diabetes duration and systolic blood pressure

Clinical pharmacy activities in chronic kidney disease and end-stage renal disease patients: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent worldwide health problems with an epidemic extent. Therefore, attention must be given to the optimisation of patient care, as gaps in the care of CKD and ESRD patients are well documented. As part of a multidisciplinary patient care strategy, clinical pharmacy services have led to improvements in patient care. The purpose of this study was to summarise the available evidence regarding the role and impact of clinical pharmacy services for these patient populations.</p> <p>Methods</p> <p>A literature search was conducted using the <it>Medline</it>, <it>Embase </it>and <it>International Pharmaceutical Abstracts </it>databases to identify relevant studies on the impact of clinical pharmacists on CKD and ESRD patients, regarding disease-oriented and patient-oriented outcomes, and clinical pharmacist interventions on drug-related problems.</p> <p>Results</p> <p>Among a total of 21 studies, only four (19%) were controlled trials. The majority of studies were descriptive (67%) and before-after studies (14%). Interventions comprised general clinical pharmacy services with a focus on detecting, resolving and preventing drug-related problems, clinical pharmacy services with a focus on disease management, or clinical pharmacy services with a focus on patient education in order to increase medication knowledge. Anaemia was the most common comorbidity managed by clinical pharmacists, and their involvement led to significant improvement in investigated disease-oriented outcomes, for example, haemoglobin levels. Only four of the studies (including three controlled trials) presented data on patient-oriented outcomes, for example, quality of life and length of hospitalisation. Studies investigating the number and type of clinical pharmacist interventions and physician acceptance rates reported a mean acceptance rate of 79%. The most common reported drug-related problems were incorrect dosing, the need for additional pharmacotherapy, and medical record discrepancies.</p> <p>Conclusions</p> <p>Few high-quality trials addressing the benefit and impact of clinical pharmacy services in CKD and ESRD patients have been published. However, all available studies reported some positive impact resulting from clinical pharmacist involvement, including various investigated outcome measures that could be improved. Additional randomised controlled trials investigating patient-oriented outcomes are needed to further determine the role of clinical pharmacists and the benefits of clinical pharmacy services to CKD and ESRD patients.</p

Sodium Chloride Inhibits the Growth and Infective Capacity of the Amphibian Chytrid Fungus and Increases Host Survival Rates

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0–5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1–4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation

The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study

<p>Abstract</p> <p>Background</p> <p>Tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) are the three components of the once-daily, single tablet regimen (Atripla) for treatment of HIV-1 infection. Previous cell culture studies have demonstrated that the double combination of tenofovir (TFV), the parent drug of TDF, and FTC were additive to synergistic in their anti-HIV activity, which correlated with increased levels of intracellular phosphorylation of both compounds.</p> <p>Results</p> <p>In this study, we demonstrated the combinations of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV synergistically inhibit HIV replication in cell culture and synergistically inhibit HIV-1 reverse transcriptase (RT) catalyzed DNA synthesis in biochemical assays. Several different methods were applied to define synergy including median-effect analysis, MacSynergy^®II and quantitative isobologram analysis. We demonstrated that the enhanced formation of dead-end complexes (DEC) by HIV-1 RT and TFV-terminated DNA in the presence of FTC-triphosphate (TP) could contribute to the synergy observed for the combination of TFV+FTC, possibly through reduced terminal NRTI excision. Furthermore, we showed that EFV facilitated efficient formation of stable, DEC-like complexes by TFV- or FTC-monophosphate (MP)-terminated DNA and this can contribute to the synergistic inhibition of HIV-1 RT by TFV-diphosphate (DP)+EFV and FTC-TP+EFV combinations.</p> <p>Conclusion</p> <p>This study demonstrated a clear correlation between the synergistic antiviral activities of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV combinations and synergistic HIV-1 RT inhibition at the enzymatic level. We propose the molecular mechanisms for the TFV+FTC+EFV synergy to be a combination of increased levels of the active metabolites TFV-DP and FTC-TP and enhanced DEC formation by a chain-terminated DNA and HIV-1 RT in the presence of the second and the third drug in the combination. This study furthers the understanding of the longstanding observations of synergistic anti-HIV-1 effects of many NRTI+NNRTI and certain NRTI+NRTI combinations in cell culture, and provides biochemical evidence that combinations of anti-HIV agents can increase the intracellular drug efficacy, without increasing the extracellular drug concentrations.</p