bluuebunny/crossref_metadata_2025_split huggingface dataset:
Don't rush to crush: audit of modification to oral medicines for patients with swallowing difficulties
Authors: Downey Catherine E. , Thakerar Arti , Kirsa Sue 
Published: June 2015

AbstractBackgroundOral medicines are frequently modified prior to administration for patients with swallowing difficulties or enteral tubes. The current Australian guideline, the Don't Rush to Crush (
DRTC
) Handbook has been available since 2011, and this study compares practice with its recommendations.AimTo assess compliance with Australian guidelines for the preparation of medications in patients who are unable to swallow solid oral medicines, and to provide nursing education as necessary to improve practice.MethodAn observational audit was undertaken during morning medication rounds in an 18‐bed medical oncology ward over 4 weeks. For each occasion that an oral medicine was modified, the preparation method was assessed against recommendations in the
DRTC
Handbook for appropriateness. A number of education strategies were implemented with support and input from senior nursing staff focusing on medication modification for patients with fine‐bore nasogastric tubes. A re‐audit was undertaken to assess practice improvement.ResultsEducation improved the proportion of medications prepared safely from 45% (37/82) to 91% (68/75) and those prepared according to the optimal method of preparation from 33% (27/82) to 60% (45/75). In the initial audit, 52% (43/82) of medications modified were strained prior to patient administration. Practical and collaborative education eliminated the straining of medications, and guidelines for difficult medications for patients with nasogastric tubes were developed.ConclusionCollaborative education that is practical and targeted can improve how oral medicines are modified for patients with swallowing difficulties and enteral tubes.
Methaemoglobinaemia associated with trimethoprim/sulfamethoxazole treatment on a background of leflunomide‐induced pneumonitis
Authors: Klusak Anna , Truloff Natasha 
Published: June 2015

AbstractBackgroundImmunomodulating drugs such as leflunomide are known to be associated with immunosuppression and infection. Off‐label use of such agents may place patients at increased risk of potentially unforeseen adverse effects not commonly observed in clinical trials.AimTo describe a case of leflunomide‐induced pneumonitis, which may have contributed to the development of Pneumocystis jirovecii pneumonia (PJP). Treatment of the infection with trimethoprim/sulfamethoxazole (TMP‐SMX) in this case was associated with the development of methaemoglobinaemia, a relatively rare adverse effect associated with this agent.Clinical detailsA 72‐year‐old female presented with a 2‐week history of progressive dyspnoea and orthopnoea with a background of newly diagnosed, biopsy proven, membranous glomerulonephropathy. She had recently started leflunomide and prednisolone for resistant proteinuria. Soon after admission, her respiratory status deteriorated with tachypnoea (30–40/min) and hypoxia requiring large amounts of supplemental oxygen (oxygen saturation (SaO2) 95%, partial pressure of oxygen (PO2) 68 mmHg with 10 L/min of oxygen). A chest X‐ray and computed tomography revealed diffuse bilateral ground glass opacities with multimodal consolidation. Sputum polymerase chain reaction testing was positive for P. jirovecii, and a diagnosis of PJP was made. Subsequent treatment with primaquine and TMP‐SMX was linked to the development of drug‐induced methaemoglobinaemia (MeHb).OutcomeThe antimicrobial regime was changed to intravenous (IV) pentamidine as an alternative treatment for P. jirovecii pneumonia. Despite this, there was further deterioration associated with a suspected secondary bacterial pneumonia. Additional IV antibiotics were added, including piperacillin/tazobactam and vancomycin. Following failure to respond to this treatment, active interventions were withdrawn after family discussions. Palliative care measures were implemented and she died 4 days later.ConclusionPharmacists should be aware of the potential for serious, rare adverse effects associated with immunomodulating drugs. Patients must be informed of the risks associated with treatment and the evidence for benefit when these drugs are prescribed for off‐label use. PJP pneumonia prophylaxis should be considered for patients commencing high dose, chronic corticosteroid therapy. Methaemoglobin should be measured for patients who become significantly hypoxic after treatment with trimethoprim/sulfamethoxazole.
Concomitant roxithromycin use among elderly patients taking warfarin resulting in significant over‐anti‐coagulation
Authors: Rotella Joe‐Anthony , Taylor David M. 
Published: June 2015

AbstractBackgroundThere is a paucity of literature regarding the potential association between roxithromycin and excessive anti‐coagulation in patients taking warfarin. An interaction may have important health implications for these patients, particularly the elderly, who are at greater risk of bleeding events due to falls and consequent injuries, as well as major gastrointestinal haemorrhage.AimTo report five cases of a possible roxithromycin–warfarin drug interaction, all resulting in extreme elevations of the international normalised ratio (INR) and requiring admission and intervention with vitamin K.Clinical detailsA retrospective medical record review of patients presenting to the emergency department of a tertiary‐level, university‐affiliated hospital was undertaken. Patients treated with warfarin and who had an excessively elevated international normalised ratio at presentation were identified. Of 102 525 cases screened, 72 cases were selected for further analysis. In five cases, elderly patients were taking roxithromycin for treatment of a lower respiratory tract infection and had a recorded international normalised ratio in the range of 10.1–14.5. Three of these five patients had impaired renal function.OutcomesNo patient had bleeding complications but all required admission and treatment with vitamin K. One patient died during admission but the cause of death was not related to bleeding. In each case, a potential roxithromycin–warfarin interaction was rated as probable using a commonly employed scale.ConclusionThe elevation of the international normalised ratio observed with these patients was most likely to have been caused by a drug interaction. Each patient required admission and considerable clinical intervention in order to correct the over‐anti‐coagulation. Hence, the clinician needs to be aware of the potential consequences of this drug interaction.
Impact of altered administrative processes for clozapine supply in a large‐scale Australian mental health shared‐care program
Authors: Bjorksten Cecilia E. , Berry Sherman 
Published: June 2015

AbstractClozapine is an effective antipsychotic agent that is associated with a range of serious adverse effects. Changes in the administrative processes for claiming reimbursement for the costs associated with clozapine through the Australian Pharmaceutical Benefits Scheme have been associated with significant clinical, financial and logistic challenges. This practice report illustrates the impact of the administrative changes upon consumers, doctors, pharmacists and other staff associated with a large Australian mental health service. It is noteworthy that the implementation of the changes had cross‐jurisdictional impact, with the introduction of changes in a federally funded programme creating major impacts upon a service funded and run by a state‐based management. Implementing change of this type can have a major negative impact upon consumers and staff: it is essential that such changes should be achieved in the context of genuine consultation and cooperative efforts.
Comprehensive analysis of sequences of a protein switch
Authors: Chen Szu‐Hua , Meller Jaroslaw , Elber Ron 
Published: June 2015

AbstractSwitches form a special class of proteins that dramatically change their three‐dimensional structures upon a small perturbation. One possible perturbation that we explore is that of a single point mutation. Building on the pioneering experimental work of Alexander et al. (Alexander et al. PNAS, 2007; 104,11963–11968) that determines switch sequences between α and α+β folds we conduct a comprehensive sequence sampling by a Markov Chain with multiple fitness criteria to identify new switches given the experimental folds. We screen for switch sequences using a combination of contact potential, secondary structure prediction, and finally molecular dynamics simulations. Statistical properties of switch sequences are discussed and illustrated to be most sensitive to mutation at the N‐ and C‐ termini of the switch protein. Based on this analysis, a particularly stable putative switch pair is identified and proposed for further experimental analysis.
Comparison of topological clustering within protein networks using edge metrics that evaluate full sequence, full structure, and active site microenvironment similarity
Authors: Leuthaeuser Janelle B. , Knutson Stacy T. , Kumar Kiran , Babbitt Patricia C. , Fetrow Jacquelyn S. 
Published: June 2015

AbstractThe development of accurate protein function annotation methods has emerged as a major unsolved biological problem. Protein similarity networks, one approach to function annotation via annotation transfer, group proteins into similarity‐based clusters. An underlying assumption is that the edge metric used to identify such clusters correlates with functional information. In this contribution, this assumption is evaluated by observing topologies in similarity networks using three different edge metrics: sequence (BLAST), structure (TM‐Align), and active site similarity (active site profiling, implemented in DASP). Network topologies for four well‐studied protein superfamilies (enolase, peroxiredoxin (Prx), glutathione transferase (GST), and crotonase) were compared with curated functional hierarchies and structure. As expected, network topology differs, depending on edge metric; comparison of topologies provides valuable information on structure/function relationships. Subnetworks based on active site similarity correlate with known functional hierarchies at a single edge threshold more often than sequence‐ or structure‐based networks. Sequence‐ and structure‐based networks are useful for identifying sequence and domain similarities and differences; therefore, it is important to consider the clustering goal before deciding appropriate edge metric. Further, conserved active site residues identified in enolase and GST active site subnetworks correspond with published functionally important residues. Extension of this analysis yields predictions of functionally determinant residues for GST subgroups. These results support the hypothesis that active site similarity‐based networks reveal clusters that share functional details and lay the foundation for capturing functionally relevant hierarchies using an approach that is both automatable and can deliver greater precision in function annotation than current similarity‐based methods.
Pharmacokinetic study of metopimazine by oral route in children
Authors: Mallet Eric , Bounoure Frederic , Skiba Mohamed , Saussereau Elodie , Goullé Jean‐Pierre , Castanet Mireille 
Published: June 2015

AbstractMetopimazine (MPZ) is an antiemetic considered as a currently used drug. In France, it has become the leading antiemetic mediator due to its good tolerance, however, its pharmacokinetics has never previously been studied in children. MPZ was administered by oral route to 8 children with a single dose of 0.33 mg/kg during an endocrine exploration using stimuli well known for its adverse emetic effects. We used biological remnants from sera following an hGH test in order to obtain the MPZ pharmacokinetics. Plasmatic concentrations of MPZ and the active acid metabolite AMPZ, were quantified by HPLC‐MS/MS during a 270 min test period. MPZ is quickly absorbed with a median Cmax of 17.2 ng/mL at one hour and its half‐life is 2.18 h. The plasmatic concentrations of AMPZ were higher than MPZ with a median Cmax of 76.3 ng/mL, a Tmax to 150 min and its concentration was approximately maintained at 50 ng/mL from 1 to 4 h. The plasmatic concentrations in children are similar to those observed in adults. No adverse effects, nausea or vomiting occurred during the trial. Therefore, these results confirm the MPZ dosage that should be used in children under 15 kg administered as 0.33 mg/kg up to 3 times a day.
The discovery of a selective and potent A2a agonist with extended lung retention
Authors: Åstrand Annika B. M. , Lamm Bergström Eva , Zhang Hui , Börjesson Lena , Söderdahl Therese , Wingren Cecilia , Jansson Anne‐Helene , Smailagic Amir , Johansson Camilla , Bladh Håkan , Shamovsky Igor , Tunek Anders , Drmota Tomas 
Published: June 2015

AbstractAlthough the anti‐inflammatory role of the A2a receptor is well established, controversy remains with regard to the therapeutic value for A2a agonists in treatment of inflammatory lung diseases, also as a result of unwanted A2a‐mediated cardiovascular effects. In this paper, we describe the discovery and characterization of a new, potent and selective A2a agonist (compound 2) with prolonged lung retention and limited systemic exposure following local administration. To support the lead optimization chemistry program with compound selection and profiling, multiple in vitro and in vivo assays were used, characterizing compound properties, pharmacodynamics (PD), and drug concentrations. Particularly, pharmacokinetic‐PD modeling was applied to quantify the effects on the cardiovascular system, and an investigative toxicology study in rats was performed to explore potential myocardial toxicities. Compound 2, in comparison to a reference A2a agonist, UK‐432,097, demonstrated higher solubility, lower lipophilicity, lower plasma protein binding, high rat lung retention (28% remaining after 24 h), and was efficacious in a lung inflammatory rat model following intratracheal dosing. Despite these properties, compound 2 did not provide a sufficient therapeutic index, that is, separation of local anti‐inflammatory efficacy in the lung from systemic side effects in the cardiovascular system. The plasma concentration that resulted in induction of hypotension (half maximal effective concentration; EC50 0.5 nmol/L) correlated to the in vitro A2a potency (rIC50 0.6 nmol/L). Histopathological lesions in the heart were observed at a dose level which is threefold above the efficacious dose level in the inflammatory rat lung model. In conclusion, compound 2 is a highly potent and selective A2a agonist with significant lung retention after intratracheal administration. Despite its local anti‐inflammatory efficacy in rat lung, small margins to the cardiovascular effects suggested limited therapeutic value of this compound for treatment of inflammatory lung disease by the inhaled route.
Sulfonamide inhibitors of α2β1 integrin reveal the essential role of collagen receptors in in vivo models of inflammation
Authors: Nissinen Liisa , Ojala Marika , Langen Barbara , Dost Rita , Pihlavisto Marjo , Käpylä Jarmo , Marjamäki Anne , Heino Jyrki 
Published: June 2015

AbstractSmall molecule inhibitors of α2β1 integrin, a major cellular collagen receptor, have been reported to inhibit platelet function, kidney injury, and angiogenesis. Since α2β1 integrin is abundantly expressed on various inflammation‐associated cells, we tested whether recently developed α2β1 blocking sulfonamides have anti‐inflammatory properties. Integrin α2β1 inhibitors were shown to reduce the signs of inflammation in arachidonic acid‐induced ear edema, PAF stimulated air pouch, ovalbumin‐induced skin hypersensitivity, adjuvant arthritis, and collagen‐induced arthritis. Thus, these sulfonamides are potential drugs for acute and allergic inflammation, hypersensitivity, and arthritis. One sulfonamide with potent anti‐inflammatory activity has previously been reported to be selective for activated integrins, but not to inhibit platelet function. Thus, the experiments also revealed fundamental differences in the action of nonactivated and activated α2β1 integrins in inflammation when compared to thrombosis.
Analysis of drug combinations: current methodological landscape
Authors: Foucquier Julie , Guedj Mickael 
Published: June 2015

AbstractCombination therapies exploit the chances for better efficacy, decreased toxicity, and reduced development of drug resistance and owing to these advantages, have become a standard for the treatment of several diseases and continue to represent a promising approach in indications of unmet medical need. In this context, studying the effects of a combination of drugs in order to provide evidence of a significant superiority compared to the single agents is of particular interest. Research in this field has resulted in a large number of papers and revealed several issues. Here, we propose an overview of the current methodological landscape concerning the study of combination effects. First, we aim to provide the minimal set of mathematical and pharmacological concepts necessary to understand the most commonly used approaches, divided into effect‐based approaches and dose–effect‐based approaches, and introduced in light of their respective practical advantages and limitations. Then, we discuss six main common methodological issues that scientists have to face at each step of the development of new combination therapies. In particular, in the absence of a reference methodology suitable for all biomedical situations, the analysis of drug combinations should benefit from a collective, appropriate, and rigorous application of the concepts and methods reviewed here.
Reduced activity of SKCa and Na‐K ATPase underlies the accelerated impairment of EDH‐type relaxations in mesenteric arteries of aging spontaneously hypertensive rats
Authors: Kong Billy W. C. , Man Ricky Y. K. , Gao Yuansheng , Vanhoutte Paul M. , Leung Susan W. S. 
Published: June 2015

AbstractAging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium‐dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH‐type relaxation due to aging. EDH‐type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH‐type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small‐conductance calcium‐activated potassium channels (SKCa) and sodium‐potassium ATPase (Na‐K ATPase). EDH‐type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKCa and Na‐K ATPase and activation of adenosine monophosphate‐activated protein kinase and silent information regulator T1 (sirtuin‐1; SIRT1) in mesenteric arteries of 12‐week‐old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH‐type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKCa and Na‐K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats.
Effects of Early U.S. Compulsory Schooling Laws on Educational Assortative Mating: The Importance of Context
Authors: Rauscher Emily 
Published: June 2015

Abstract
Modernization theory predicts that rising education should increase assortative mating by education and decrease sorting by race. Recent research suggests that effects of educational expansion depend on contextual factors, such as economic development. Using log-linear and log-multiplicative models of male household heads ages 36 to 75 in the 1940 U.S. census data—the first U.S. census with educational attainment information—I investigate how educational assortative mating changed with one instance of educational expansion: early U.S. compulsory school attendance laws. To improve on existing research and distinguish effects of expansion from changes due to particular years or cohorts, I capitalize on state variation in the timing of these compulsory laws (ranging from 1852 to 1918). Aggregate results suggest that compulsory laws had minimal impact on assortative mating. However, separate analyses by region (and supplemental analyses by race) reveal that assortative mating by education decreased with the laws in the South but increased in the North. Whether due to economic, legal, political, or other differences, results suggest that the implications of educational expansion for marital sorting depend on context. Contemporary implications are discussed in light of President Obama’s 2012 suggested extension of compulsory schooling to age 18.
Asymmetries of the central sulcus in young adults: Effects of gender, age and sulcal pattern
Authors: Sun Bo , Ge Haitao , Tang Yuchun , Hou Zhongyu , Xu Junhai , Lin Xiangtao , Liu Shuwei 
Published: June 2015

AbstractIn this study, we clarified the gender and age‐related asymmetries of the central sulcus (CS) in early adulthood using a parametric ribbon method. The CS was reconstructed and parameterized automatically from 3D MR images of 112 healthy right‐handed subjects. The 3D anatomic morphology of the CS was presented using 5 sulcal parameters, including sulcal depth position‐based profile (DPP), average depth (AD), average width (AW), top length (TL) and bottom length (BL). Asymmetry differences in DPPs were found in the medial and lateral part of the CS. In addition, significant gender differences were observed in the medial and middle parts of the right CS DPPs but scattered in the left side. We found leftward asymmetries of TL in males, but rightward asymmetries of AW in females. Males had a greater AW than females in the right hemisphere. Moreover, the females had bilateral longer TL and a longer left BL than did males. We also found significant age‐related reductions in bilateral TL and increases in bilateral AW, with males presenting more obvious age‐related change than females. There were sexual differences of the CS patterns, in which Type b was the most dominant sulcal pattern in males, whereas Type a was dominant in females. Three‐way ANOVA revealed sexual and asymmetry changes of TL and BL among different CS patterns. Our findings indicate that the lateralization performances of the CS manifest as sexually and regionally different. In addition, it is suggested that males may undergo a faster progress of aging compared to females.
Couple years protection lost, a new tool for family planning programs to prioritize stockout interventions
Authors: Schwandt Hilary M. , Saad Abudulmumin 
Published: June 2015

AbstractObjectiveTo develop and evaluate a new measure—couple years protection lost (CYPL)—to identify facilities with the most damaging contraceptive stockouts and therefore direct program response.MethodsAs part of a prospective descriptive study, data were gathered on stocks of contraceptives (oral contraceptive pill, intrauterine device, and two types of implant) at 10 family planning facilities in Abuja, Nigeria, between January and August 2012. CYPL values—a summation of average client volume across contraceptive methods multiplied by the number of stockouts and the USAID couple years of protection value for each method—were calculated for each facility.ResultsOver the 8‐month study period, the 10 facilities had CYPL values ranging from 15.7 to 588.7. Two facilities had a similarly high number of stockouts (9 vs 8), but completely different CYPL values (462.1 vs 15.7).ConclusionBy utilizing the CYPL measure, health programs can target family planning facilities with the most damaging stockouts first and thus strategically reduce the negative impact of contraceptive stockouts.