Neutral and Charged Polymers at Interfaces

Chain-like macromolecules (polymers) show characteristic adsorption properties due to their flexibility and internal degrees of freedom, when attracted to surfaces and interfaces. In this review we discuss concepts and features that are relevant to the adsorption of neutral and charged polymers at equilibrium, including the type of polymer/surface interaction, the solvent quality, the characteristics of the surface, and the polymer structure. We pay special attention to the case of charged polymers (polyelectrolytes) that have a special importance due to their water solubility. We present a summary of recent progress in this rapidly evolving field. Because many experimental studies are performed with rather stiff biopolymers, we discuss in detail the case of semi-flexible polymers in addition to flexible ones. We first review the behavior of neutral and charged chains in solution. Then, the adsorption of a single polymer chain is considered. Next, the adsorption and depletion processes in the many-chain case are reviewed. Profiles, changes in the surface tension and polymer surface excess are presented. Mean-field and corrections due to fluctuations and lateral correlations are discussed. The force of interaction between two adsorbed layers, which is important in understanding colloidal stability, is characterized. The behavior of grafted polymers is also reviewed, both for neutral and charged polymer brushes.Comment: a review: 130 pages, 30 ps figures; final form, added reference

The baculovirus Ac108 protein is a per os infectivity factor and a component of the ODV entry complex

Wild-type ODVs (Wt) have an intact ODV entry complex in their envelope and are orally infectious towards insect larvae (left panel). In the absence of Ac108 (mut ac108), the stable core is still present but nevertheless fails to form an entry complex, affecting the ODV oral infectivity (right panel). The components of the core complex are depicted in yellow and the loosely associated components are depicted in red. PIF7 is depicted in green as its affinity with the complex is currently not known.Baculoviruses orally infect insect larvae when they consume viral occlusion bodies (OBs). OBs consist of a crystalline protein matrix in which the infectious virus particles, the occlusion-derived viruses (ODVs), are embedded. The protein matrix dissolves in the alkaline environment of the insect's midgut lumen. The liberated ODVs can then infect midgut endothelial cells through the action of at least nine different ODV-envelope proteins, called per os infectivity factors (PIFs). These PIF proteins mediate ODV oral infectivity, but are not involved in the systemic spread of the infection by budded viruses (BVs). Eight of the known PIFs form a multimeric complex, named the ODV entry complex. In this study, we show for Autographa californica multiple nucleopolyhedrovirus that mutation of the ac108ORF abolishes the ODV oral infectivity, while production and infectivity of the BVs remains unaffected. Furthermore, repair of the ac108 mutant completely recovered oral infectivity. With an HA-tagged repair mutant, we were able to demonstrate by Western analysis that the Ac108 protein is a constituent of the ODV entry complex, where the formation was abolished in the absence of this protein. Based on these results, we conclude that ac108 encodes a per os infectivity factor (PIF9) that is also an essential constituent of the ODV entry complex.</p

Computerized advice on drug dosage to improve prescribing practice

International audienceComputerized advice on drug dosage to improve prescribing practice (Review) 1 Copyright © 2013 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Data collection and analysis Two review authors independently extracted data and assessed study quality.We grouped the results from the included studies by drug used and the effect aimed at for aminoglycoside antibiotics, amitriptyline, anaesthetics, insulin, anticoagulants, ovarian stimulation, anti-rejection drugs and theophylline. We combined the effect sizes to give an overall effect for each subgroup of studies, using a random-effects model. We further grouped studies by type of outcome when appropriate (i.e. no evidence of heterogeneity). Main results Forty-six comparisons (from 42 trials) were included (as compared with 26 comparisons in the last update) including a wide range of drugs in inpatient and outpatient settings. All were randomized controlled trials except two studies. Interventions usually targeted doctors, although some studies attempted to influence prescriptions by pharmacists and nurses. Drugs evaluated were anticoagulants, insulin, aminoglycoside antibiotics, theophylline, anti-rejection drugs, anaesthetic agents, antidepressants and gonadotropins. Although all studies used reliable outcome measures, their quality was generally low. This update found similar results to the previous update and managed to identify specific therapeutic areas where the computerized advice on drug dosage was beneficial compared with routine care: 1. it increased target peak serum concentrations (standardized mean difference (SMD) 0.79, 95% CI 0.46 to 1.13) and the proportion of people with plasma drug concentrations within the therapeutic range after two days (pooled risk ratio (RR) 4.44, 95% CI 1.94 to 10.13) for aminoglycoside antibiotics; 2. it led to a physiological parameter more often within the desired range for oral anticoagulants (SMD for percentage of time spent in target international normalized ratio +0.19, 95% CI 0.06 to 0.33) and insulin (SMD for percentage of time in target glucose range: +1.27, 95% CI 0.56 to 1.98); 3. it decreased the time to achieve stabilization for oral anticoagulants (SMD -0.56, 95% CI -1.07 to -0.04); 4. it decreased the thromboembolism events (rate ratio 0.68, 95% CI 0.49 to 0.94) and tended to decrease bleeding events for anticoagulants although the difference was not significant (rate ratio 0.81, 95%CI 0.60 to 1.08). It tended to decrease unwanted effects for aminoglycoside antibiotics (nephrotoxicity: RR 0.67, 95% CI 0.42 to 1.06) and anti-rejection drugs (cytomegalovirus infections: RR 0.90, 95% CI 0.58 to 1.40); 5. it tended to reduce the length of time spent in the hospital although the difference was not significant (SMD -0.15, 95% CI -0.33 to 0.02) and to achieve comparable or better cost-effectiveness ratios than usual care; 6. there was no evidence of differences in mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, antirejection drugs and antidepressants. For all outcomes, statistical heterogeneity quantified by I2 statistics was moderate to high. Authors’ conclusions This review update suggests that computerized advice for drug dosage has some benefits: it increases the serum concentrations for aminoglycoside antibiotics and improves the proportion of people for which the plasma drug is within the therapeutic range for aminoglycoside antibiotics. It leads to a physiological parameter more often within the desired range for oral anticoagulants and insulin. It decreases the time to achieve stabilization for oral anticoagulants. It tends to decrease unwanted effects for aminoglycoside antibiotics and anti-rejection drugs, and it significantly decreases thromboembolism events for anticoagulants. It tends to reduce the length of hospital stay compared with routine care while comparable or better cost-effectiveness ratios were achieved. However, there was no evidence that decision support had an effect on mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, anti-rejection drugs and antidepressants. In addition, there was no evidence to suggest that some decision support technical features (such as its integration into a computer physician order entry system) or aspects of organization of care (such as the setting) could optimize the effect of computerized advice. Taking into account the high risk of bias of, and high heterogeneity between, studies, these results must be interpreted with caution. P L A I N L A N G U A G E S U M M A R Y Computerized advice on drug dosage to improve prescribing practice (Review) 2 Copyright © 2013 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Computerized advice on drug dosage to improve prescribing practice Background Physicians and other healthcare professionals often prescribe drugs that will only work at certain concentrations. These drugs are said to have a narrow therapeutic window. This means that if the concentration of the drug is too high or too low, they may cause serious side effects or not provide the benefits they should. For example, blood thinners (anticoagulants) are prescribed to thin the blood to prevent clots. If the concentration is too high, people may experience excessive bleeding and even death. In contrast, if the concentration is too low, a clot could form and cause a stroke. For these types of drugs, it is important that the correct amount of the drug be prescribed. Calculating and prescribing the correct amount can be complicated and time-consuming for healthcare professionals. Sometimes determining the correct dose can take a long time since healthcare professionals may not want to prescribe high doses of the drugs initially because they make mistakes in calculations. Several computer systems have been designed to do these calculations and assist healthcare professionals in prescribing these types of drugs. Study characteristics We sought clinical trial evidence from scientific databases to evaluate the effectiveness of these computer systems. The evidence is current to January 2012. We found data from 42 trials (40 randomized controlled trials (trials that allocate people at random to receive one of a number of drugs or procedures) and two non-randomized controlled trials). Key results Computerized advice for drug dosage can benefit people taking certain drugs compared with empiric dosing (where a dose is chosen based on a doctor’s observations and experience)without computer assistance.When using the computer system, healthcare professionals prescribed appropriately higher doses of the drugs initially for aminoglycoside antibiotics and the correct drug dose was reached more quickly for oral anticoagulants. It significantly decreased thromboembolism (blood clotting) events for anticoagulants and tended to reduce unwanted effects for aminoglycoside antibiotics and anti-rejection drugs (although not an important difference). It tended to reduce the length of hospital stay compared with routine care with comparable or better cost-effectiveness. There was no evidence of effects on death or clinical side events for insulin (low blood sugar (hypoglycaemia)), anaesthetic agents, anti-rejection drugs (drugs taken to prevent rejection of a transplanted organ) and antidepressants. Quality of evidence The quality of the studies was low so these results must be interpreted with caution

Overview of Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) is the clinical practice of measuring specific drugs at designated intervals to maintain a constant concentration in a patient's bloodstream, thereby optimizing individual dosage regimens. It is unnecessary to employ TDM for the majority of medications, and it is used mainly for monitoring drugs with narrow therapeutic ranges, drugs with marked pharmacokinetic variability, medications for which target concentrations are difficult to monitor, and drugs known to cause therapeutic and adverse effects. The process of TDM is predicated on the assumption that there is a definable relationship between dose and plasma or blood drug concentration, and between concentration and therapeutic effects. TDM begins when the drug is first prescribed, and involves determining an initial dosage regimen appropriate for the clinical condition and such patient characteristics as age, weight, organ function, and concomitant drug therapy. When interpreting concentration measurements, factors that need to be considered include the sampling time in relation to drug dose, dosage history, patient response, and the desired medicinal targets. The goal of TDM is to use appropriate concentrations of difficult-to-manage medications to optimize clinical outcomes in patients in various clinical situations

Why has model-informed precision dosing not yet become common clinical reality?:Lessons from the past and a roadmap for the future

Patient groups prone to polypharmacy and special subpopulations are susceptible to suboptimal treatment. Refined dosing in special populations is imperative to improve therapeutic response and/or lowering the risk of toxicity. Model-informed precision dosing (MIPD) may improve treatment outcomes by achieving the optimal dose for an individual patient. There is, however, relatively little published evidence of large-scale utility and impact of MIPD, where it is often implemented as local collaborative efforts between academia and healthcare. This article highlights some successful applications of bringing MIPD to clinical care and proposes strategies for wider integration in healthcare. Considerations are brought up herein that will need addressing to see MIPD become "widespread clinical practice," among those, wider interdisciplinary collaborations and the necessity for further evidence-based efficacy and cost-benefit analysis of MIPD in healthcare. The implications of MIPD on regulatory policies and pharmaceutical development are also discussed as part of the roadmap

Cost-effectiveness of ward-based pharmacy care in surgical patients: protocol of the SUREPILL (Surgery & Pharmacy In Liaison) study

<p>Abstract</p> <p>Background</p> <p>Preventable adverse drug events (pADEs) are widely known to be a health care issue for hospitalized patients. Surgical patients are especially at risk, but prevention of pADEs in this population is not demonstrated before. Ward-based pharmacy interventions seem effective in reducing pADEs in medical patients. The cost-effectiveness of these preventive efforts still needs to be assessed in a comparative study of high methodological standard and also in the surgical population. For these aims the SUREPILL (Surgery & Pharmacy in Liaison) study is initiated.</p> <p>Methods/Design</p> <p>A multi-centre controlled trial, with randomisation at ward-level and preceding baseline assessments is designed. Patients admitted to the surgical study wards for elective surgery with an expected length of stay of more than 48 hours will be included. Patients admitted to the intervention ward, will receive ward-based pharmacy care from the clinical pharmacy team, i.e. pharmacy practitioners and hospital pharmacists. This ward-based pharmacy intervention includes medication reconciliation in consultation with the patient at admission, daily medication review with face-to-face contact with the ward doctor, and patient counselling at discharge. Patients admitted in the control ward, will receive standard pharmaceutical care.</p> <p>The primary clinical outcome measure is the number of pADEs per 100 elective admissions. These pADEs will be measured by systematic patient record evaluation using a trigger tool. Patient records positive for a trigger will be evaluated on causality, severity and preventability by an independent expert panel. In addition, an economic evaluation will be performed from a societal perspective with the costs per preventable ADE as the primary economic outcome. Other outcomes of this study are: severity of pADEs, number of patients with pADEs per total number of admissions, direct (non-)medical costs and indirect non-medical costs, extra costs per prevented ADE, number and type of pharmacy interventions, length of hospital stay, complications registered in a national complication registration system for surgery, number of readmissions within three months after initial admission (follow-up), quality of life and number of non-institutionalized days during follow-up.</p> <p>Discussion</p> <p>This study will assess the cost-effectiveness of ward-based pharmacy care on preventable adverse drug events in surgical patients from a societal perspective, using a comparative study design.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2258">NTR2258</a></p

Some international approaches to aminoglycoside monitoring in the extended dosing interval era

Aminoglycosides have rightly remained a cost-effective anti-microbial strategy for the treatment of Gram-positive infections for some 25 years. However, in recent years there has been a review of the traditional thrice-daily administration regimen in favor of an extended dosing interval strategy that takes into account the individual patient's renal function. The general recommendations that have been provided to date have been adopted in various ways internationally. These approaches were a matter of discussion for the Clinical Pharmacokinetics Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology at its congress (Vancouver, Canada; November 1997), and will again be a workshop issue at the Cairns (Australia) congress of the Association (September 1999). The present report provides examples of how these practices have been applied at a group of centers from Canada (2 centers), The Netherlands, Egypt, and Australia. These reports demonstrate a variety of approaches and highlight the need for further research for assessing clinical outcomes from different dosing strategies.Raymond G. Morris, Benedetta C. Sallustio, Alexander A. T. M. M. Vinks, Donald F. LeGatt, Zulfikarali H. Verjee, Ehab El Desok