bluuebunny/crossref_metadata_2025_split huggingface dataset:
A public-health approach to site-specific formulary management: addressing deficient drug supplies in Malawi†
Authors: Lauffenburger Julie C , Jonkman Lauren J , Lange C Elliott , Connor Sharon E , Sibale Chakunja 
Published: April 2011

Abstract

Objectives
Maintaining a well-stocked dispensary at a private non-profit clinic in a developing country can often be challenging due to limited financial and human resources. Organizations face frequent drug shortages, excesses of unnecessary medications and potentially inappropriate international donations. To promote adherence to international recommendations and enable targeted requests for international drug donations, this paper describes a process using a public-health approach to create a site-specific pharmacy formulary in a resource-poor setting using the World Health Organization's (WHO) Model List of Essential Medicines (‘Model List’).

Methods
The study site was a Malawian-run non-profit private clinic serving over 3000 people annually. The organization focuses on providing community support for orphans from the HIV/AIDS crisis in sub-Saharan Africa. While using the Model List as a backbone, we incorporated the clinic's drug inventory, patient needs, clinician prescribing patterns, and the country's national drug list into the final formulary. After analyzing site-specific factors, we determined which WHO Model List therapeutic classes were necessary for the clinic to address in the final formulary.

Key findings
Of the drug products currently available in the inventory, 65.6% were expired, 29.8% of which were international donations. After removing expired medications from the inventory, seven Model List priority categories remained unaddressed by the clinic's initial inventory. Based on the results of a structured needs assessment, 54 products were selected for the final simplified formulary.

Conclusions
Conscious selection of pharmaceuticals, resulting in a systematic formulary for drug distribution management, is critical so that a clinic can focus on procuring and prescribing the most needed medications. This selection process using the WHO Model List and a public-health approach to drug management could serve as a private clinic model for pharmaceutical optimization and targeted international drug donations in sub-Saharan Africa and other resource limited settings.
Severity and probability of harm of medication errors intercepted by an emergency department pharmacist
Authors: Patanwala Asad E , Hays Daniel P , Sanders Arthur B , Erstad Brian L 
Published: April 2011

Abstract

Objectives
The objective of this study was to evaluate the severity and probability of harm of medication errors (MEs) intercepted by an emergency department pharmacist. The phases of the medication-use process where MEs were most likely to be intercepted were determined.

Methods
The emergency department was staffed with a full-time pharmacist during the 7-month study period. The MEs that were intercepted by the pharmacist were recorded in a database. Each ME in the database was independently scored for severity and probability of harm by two pharmacists and one physician investigator who were not involved in the data collection process.

Key findings
There were 237 ME interceptions by the pharmacist during the study period. The final classification of MEs by severity was as follows: minor (n = 42; 18%), significant (n = 160; 67%) and serious (n = 35; 15%). The final classification of MEs by probability of harm was as follows: none (n = 13; 6%), very low (n = 96; 41%), low (n = 84; 35%), medium (n = 41; 17%) and high (n = 3; 1%). Inter-rater reliability for classification was as follows: error severity (agreement = 75.5%, kappa = 0.35) and probability of harm (agreement = 76.8%, kappa = 0.42). The MEs were most likely to be intercepted during the prescribing phase of the medication-use process (n = 236; 90.1%).

Conclusions
A high proportion of MEs intercepted by the emergency department pharmacist are considered to be significant or serious. However, a smaller percentage of these errors are likely to result in patient harm.
Integrated Multilevel Surveillance of the World's Infecting Microbes and Their Resistance to Antimicrobial Agents
Authors: O'Brien Thomas F. , Stelling John 
Published: April 2011

SUMMARY
Microbial surveillance systems have varied in their source of support; type of laboratory reporting (patient care or reference); inclusiveness of reports filed; extent of microbial typing; whether single hospital, multihospital, or multicountry; proportion of total medical centers participating; and types, levels, integration across levels, and automation of analyses performed. These surveillance systems variably support the diagnosis and treatment of patients, local or regional infection control, local or national policies and guidelines, laboratory capacity building, sentinel surveillance, and patient safety. Overall, however, only a small fraction of available data are under any surveillance, and very few data are fully integrated and analyzed. Advancing informatics and genomics can make microbial surveillance far more efficient and effective at preventing infections and improving their outcomes. The world's microbiology laboratories should upload their reports each day to programs that detect events, trends, and epidemics in communities, hospitals, countries, and the world.
Microbiology of Animal Bite Wound Infections
Authors: Abrahamian Fredrick M. , Goldstein Ellie J. C. 
Published: April 2011

SUMMARYThe microbiology of animal bite wound infections in humans is often polymicrobial, with a broad mixture of aerobic and anaerobic microorganisms. Bacteria recovered from infected bite wounds are most often reflective of the oral flora of the biting animal, which can also be influenced by the microbiome of their ingested prey and other foods. Bacteria may also originate from the victim's own skin or the physical environment at the time of injury. Our review has focused on bite wound infections in humans from dogs, cats, and a variety of other animals such as monkeys, bears, pigs, ferrets, horses, sheep, Tasmanian devils, snakes, Komodo dragons, monitor lizards, iguanas, alligators/crocodiles, rats, guinea pigs, hamsters, prairie dogs, swans, and sharks. The medical literature in this area has been made up mostly of small case series or case reports. Very few studies have been systematic and are often limited to dog or cat bite injuries. Limitations of studies include a lack of established or inconsistent criteria for an infected wound and a failure to utilize optimal techniques in pathogen isolation, especially for anaerobic organisms. There is also a lack of an understanding of the pathogenic significance of all cultured organisms. Gathering information and conducting research in a more systematic and methodical fashion through an organized research network, including zoos, veterinary practices, and rural clinics and hospitals, are needed to better define the microbiology of animal bite wound infections in humans.
HIV and Tuberculosis: a Deadly Human Syndemic
Authors: Kwan Candice K. , Ernst Joel D. 
Published: April 2011

SUMMARYA syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB. Moreover, multidisciplinary approaches that consider HIV and TB together, rather than as separate problems and diseases, will be necessary to prevent further worsening of the HIV-TB syndemic. This review examines current knowledge of the state and impact of the HIV-TB syndemic and reviews the epidemiological, clinical, cellular, and molecular interactions between HIV and TB.
Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination
Authors: Bousema Teun , Drakeley Chris 
Published: April 2011

SUMMARYMalaria remains a major cause of morbidity and mortality in the tropics, withPlasmodium falciparumresponsible for the majority of the disease burden andP. vivaxbeing the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infectAnophelesmosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity ofP. falciparumandP. vivaxgametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.
Mucormycosis Caused by Unusual Mucormycetes, Non-Rhizopus, -Mucor, and -Lichtheimia Species
Authors: Gomes Marisa Z. R. , Lewis Russell E. , Kontoyiannis Dimitrios P. 
Published: April 2011

SUMMARYRhizopus,Mucor, andLichtheimia(formerlyAbsidia) species are the most common members of the order Mucorales that cause mucormycosis, accounting for 70 to 80% of all cases. In contrast,Cunninghamella,Apophysomyces,Saksenaea,Rhizomucor,Cokeromyces,Actinomucor, andSyncephalastrumspecies individually are responsible for fewer than 1 to 5% of reported cases of mucormycosis. In this review, we provide an overview of the epidemiology, clinical manifestations, diagnosis of, treatment of, and prognosis for unusual Mucormycetes infections (non-Rhizopus, -Mucor, and -Lichtheimiaspecies). The infections caused by these less frequent members of the order Mucorales frequently differ in their epidemiology, geographic distribution, and disease manifestations.Cunninghamella bertholletiaeandRhizomucor pusillusaffect primarily immunocompromised hosts, mostly resulting from spore inhalation, causing pulmonary and disseminated infections with high mortality rates.R. pusillusinfections are nosocomial or health care related in a large proportion of cases. WhileApophysomyces elegansandSaksenaea vasiformisare occasionally responsible for infections in immunocompromised individuals, most cases are encountered in immunocompetent individuals as a result of trauma, leading to soft tissue infections with relatively low mortality rates. Increased knowledge of the epidemiology and clinical presentations of these unusual Mucormycetes infections may improve early diagnosis and treatment.
Hormones and the Resistance of Women to Paracoccidioidomycosis
Authors: Shankar Jata , Restrepo Angela , Clemons Karl V. , Stevens David A. 
Published: April 2011

SUMMARY

Paracoccidioidomycosis, one of the most important endemic and systemic mycoses in Latin America, presents several clinical pictures. Epidemiological studies indicate a striking rarity of disease (but not infection) in females, but only during the reproductive years. This suggested a hormonal interaction between female hormones and the etiologic dimorphic fungus
Paracoccidioides brasiliensis
. Many fungi have been shown to use hormonal (pheromonal) fungal molecules for intercellular communication, and there are increasing numbers of examples of interactions between mammalian hormones and fungi, including the specific binding of mammalian hormones by fungal proteins, and suggestions of mammalian hormonal modulation of fungal behavior. This suggests an evolutionary conservation of hormonal receptor systems. We recount studies showing the specific hormonal binding of mammalian estrogen to proteins in
P. brasiliensis
and an action of estrogen to specifically block the transition from the saprophytic form to the invasive form of the fungus
in vitro
. This block has been demonstrated to occur
in vivo
in animal studies. These unique observations are consistent with an estrogen-fungus receptor-mediated effect on pathogenesis. The fungal genes responsive to estrogen action are under study.
Specifications and testing of self-consolidating mortar designated for annular space grouting
Authors: Hwang Soo-Duck , Khayat Kamal H. , Morin Richard 
Published: April 2011

An experimental program was undertaken to evaluate the performance of self-consolidating mortar designed for filling small annular spaces for the rehabilitation of underground water line or sewage pipelines. The study also intended to establish a testing protocol to validate the workability of repair grout. All the investigated mixtures had good filling and passing ability with adequate retention of workability over 3 h. The repair mortars exhibited high stability with bleeding lower than 0.3% compared to 3% bleeding in the case of the reference neat cement grout. The reference grout had a lower plastic viscosity and higher slump flow values than the sanded repair grouts. A V-funnel with 30 mm × 30 mm overture and a flow cone with 12.7 mm overture are recommended for mortar made with concrete sand with a 5 mm nominal size and micro mortar with fine sand with a nominal size up to 3 mm, respectively.
THE ALIGNED K-CENTER PROBLEM
Authors: BRASS PETER , KNAUER CHRISTIAN , NA HYEON-SUK , SHIN CHAN-SU , VIGNERON ANTOINE 
Published: April 2011

In this paper we study several instances of the alignedk-center problem where the goal is, given a set of points S in the plane and a parameter k ⩾ 1, to find k disks with centers on a line ℓ such that their union covers S and the maximum radius of the disks is minimized. This problem is a constrained version of the well-known k-center problem in which the centers are constrained to lie in a particular region such as a segment, a line, or a polygon. We first consider the simplest version of the problem where the line ℓ is given in advance; we can solve this problem in time O(n log 2 n). In the case where only the direction of ℓ is fixed, we give an O(n2 log 2 n)-time algorithm. When ℓ is an arbitrary line, we give a randomized algorithm with expected running time O(n4 log 2 n). Then we present (1+ε)-approximation algorithms for these three problems. When we denote T(k, ε) = (k/ε2+(k/ε) log k) log (1/ε), these algorithms run in O(n log k + T(k, ε)) time, O(n log k + T(k, ε)/ε) time, and O(n log k + T(k, ε)/ε2) time, respectively. For k = O(n1/3/ log n), we also give randomized algorithms with expected running times O(n + (k/ε2) log (1/ε)), O(n+(k/ε3) log (1/ε)), and O(n + (k/ε4) log (1/ε)), respectively.
OUT-LICENSING IN MARKETS WITH ASYMMETRIC INFORMATION: THE CASE OF THE PHARMACEUTICAL INDUSTRY
Authors: REEPMEYER GERRIT , GASSMANN OLIVER , RÜTHER FRAUKE 
Published: April 2011

Few large pharmaceutical companies have recently discovered out-licensing of terminated R&D results as a way to recoup some of the significant investments made in R&D and to improve R&D productivity. Our empirical investigation reveals that the licensing partners are preferably young, small and highly specialized companies. This reverses the traditional logic of out-licensing. While out-licensing is usually done because of downstream concerns, our analysis shows that the company which owns the necessary assets for further development (the large pharmaceutical company) sells the license to a firm (the small partner company) which has — at the time of deal closure — no track record to prove its ability to successfully develop the compound. As the lack of a track record does not allow the pharmaceutical company to distinguish between the partner firms based on their development capabilities, these out-licensing deals are characterized by an asymmetric distribution of information. The application of the theory of adverse selection allows deriving managerial recommendations along three dimensions of the out-licensing deal: product coverage, price setting and performance presumption. By making changes along these dimensions, R&D managers are able to reduce the information asymmetry and approximate an equilibrium in the out-licensing market.
Update on lipids, inflammation and atherothrombosis
Authors: Storey Robert , Vilahur Gemma , Badimon Lina 
Published: April 2011

SummaryAtherosclerosis is an inflammatory disease that involves the arterial wall and is characterised by the progressive accumulation of lipids in the vessel wall. The first step is the internalisation of lipids (LDL) in the intima with endothelial activation which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. These events increase LDL particles accumulation in the extracellular matrix where they aggregate/fuse, are retained by proteoglycans and become targets for oxidative and enzymatic modifications. In turn, retained pro-atherogenic LDLs enhance selective leukocyte recruitment and attachment to the endothelial layer inducing their transmigration across the endothelium into the intima. While smooth muscle cell numbers decline with the severity of plaque progression, monocytes differentiate into macrophages, a process associated with the upregulation of pattern recognition receptors including scavenger receptors and Toll-like receptors leading to foam cell formation. Foamcells release growth factors, cytokines, metalloproteinases and reactive oxygen species all of which perpetuate and amplify the vascular remodelling process. In addition, macrophages release tissue factor that, upon plaque rupture, contributes to thrombus formation. Smooth muscle cells exposed in eroded lesions are also able to internalise LDL through LRP-1 receptors acquiring a pro-thrombotic phenotype and releasing tissue factor. Platelets recognise ligands in the ruptured or eroded atherosclerotic plaque, initiate platelet activation and aggregation leading to thrombosis and to the clinical manifestation of the atherothrombotic disease. Additionally, platelets contribute to the local inflammatory response and may also participate in progenitor cell recruitment.
Platelets, inflammation and tissue regeneration
Authors: Nurden Alan 
Published: April 2011

SummaryBlood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from α-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.
Inflammation and thrombosis in diabetes
Authors: Hess Katharina , Grant Peter 
Published: April 2011

SummaryPatients with diabetes mellitus are at increased risk of cardiovascular morbidity and mortality. Atherothrombosis, defined as atherosclerotic lesion disruption with superimposed thrombus formation, is the most common cause of death among these patients. Following plaque rupture, adherence of platelets is followed by local activation of coagulation, the formation of a cross-linked fibrin clot and the development of an occlusive platelet rich fibrin mesh. Patients with diabetes exhibit a thrombotic risk clustering which is composed of hyper-reactive platelets, up regulation of pro-thrombotic markers and suppression of fibrinolysis. These changes are mainly mediated by the presence of insulin resistance and dysglycaemia and an increased inflammatory state which directly affects platelet function, coagulation factors and clot structure. This prothrombotic state is related to increased cardiovascular risk and may account for the reduced response to antithrombotic therapeutic approaches, underpinning the need for adequate antithrombotic therapy in patients with diabetes to reduce their cardiovascular mortality.
Bleeding manifestations of congenital and drug-induced defects of the platelet P2Y12 receptor for adenosine diphosphate
Authors: Cattaneo Marco 
Published: April 2011

SummaryP2Y12, one of the two platelet receptors for adenosine diphosphate (ADP), plays a central role in platelet function. Defects of P2Y12 should be suspected when ADP, even at high concentrations (≥10 μM), is unable to induce full, irreversible platelet aggregation. Patients with congenital P2Y12 defects display a mild-to-moderate bleeding diathesis of variable severity, characterised by mucocutaneous bleeding and excessive post-surgical and post-traumatic blood loss. Drugs that inhibit P2Y12 are potent antithrombotic drugs, attesting the central role played by P2Y12 in platelet thrombus formation. Clopidogrel, the most widely used drug that inhibits P2Y12, is effective both in monotherapy and in combination with acetylsalicylic acid (ASA). Its most important drawback is the inability to inhibit adequately P2Y12-dependent platelet function in about 1/3 of patients, at the recommended therapeutic doses. The incidence of bleeding events is similar in ASA-treated and clopidogrel-treated patients; however, the combination of ASA and clopidogrel causes more bleeding than each drug in monotherapy. Compared to clopidogrel, new drugs inhibiting P2Y12, such as prasugrel and ticagrelor, decrease the risk of cardiovascular events and increase the risk of bleeding complications, because they adequately inhibit P2Y12-dependent platelet function in the vast majority of treated patients.
Pharmacology and clinical trials of reversibly-binding P2Y12 inhibitors
Authors: Storey Robert 
Published: April 2011

SummaryThe important role of the P2Y12 receptor in amplification of platelet activation and associated responses and the limitations associated with clopidogrel therapy have led to the development of novel inhibitors of this receptor. Three reversibly-binding P2Y12 inhibitors are in phase 3 development, ticagrelor, cangrelor and elinogrel. The pharmacology and clinical trial data for each of these inhibitors are discussed and compared with relevant data for the thienopyridines clopidogrel and prasugrel.