Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections.     

A real-world study of user characteristics,safety and efficacy of open-source closed-loop systems and Medtronic 670G

We report a real-world evaluation of the first commercially approved automated insulin delivery (AID) system, MiniMed 670G (670G), and open source-automated insulin delivery (OS-AID) systems. This was undertaken as a retrospective observational study in adults with type 1 diabetes using AID systems for 6 months or longer in a publicly funded health service using clinically validated data. Sixty-eight adults (38 670G, 30 OS-AID systems) were included. OS-AID system users were younger, had a shorter diabetes duration and a higher education status. OS-AID systems displayed a significantly better change in HbA1c (median −0.9% [−0.4%, −1.1%] vs. −0.1% [IQR −0.7%, 0.2%], P = .004) and time in range 3.9-10 mmol/L (mean 78.5%, SD ± 12.0% vs. 68.2% ± 14.7%, P = .024) compared with 670G. Both systems showed minimal hypoglycaemia, with OS-AID systems revealing significantly improved secondary outcomes of mean glucose and percentage of time more than 10 mmol/L, with a higher percentage of time of less than 3 mmol/L. OS-AID system users displayed improved glycaemic outcomes with no clinical safety concerns compared with 670G, although higher weight-adjusted insulin dose and weight gain were noted. The study highlights key differences in OS-AID system user characteristics that are important for interpreting real-world findings from recent OS-AID system studies.     

A comparison of health care and blood supply system structures

There is great diversity in the practice of blood banking and transfusion medicine between countries. We sought to relate this to the variety of health care and blood supply systems in different countries. Questionnaires were completed by respondents from 15 countries selected from among those with higher Human Development Indices. These data were reviewed searching for correlations with blood banking and transfusion medicine practices. Wide varieties of health care and blood supply schemes were documented. There was no apparent relationship between their structure and organization nor their financing arrangements and their proclivity for the implementation of new methods or approaches such as pathogen inactivation and universal leucoreduction. The costs of the operation of the blood supply system as represented by their product fees and the rate of collection of red cells could also not be associated with the factors examined. The diversity of practice evident across developed countries is not explicable solely through their health care and blood supply system structures. Other factors are likely involved but are not easy to define or measure.     

A cost-benefit analysis of electronic medical records in primary care

Electronic medical record systems improve the quality of patient care and decrease medical errors, but their financial effects have not been as well documented. The purpose of this study was to estimate the net financial benefit or cost of implementing electronic medical record systems in primary care. We performed a cost-benefit study to analyze the financial effects of electronic medical record systems in ambulatory primary care settings from the perspective of the health care organization. Data were obtained from studies at our institution and from the published literature. The reference strategy for comparisons was the traditional paper-based medical record. The primary outcome measure was the net financial benefit or cost per primary care physician for a 5-year period. The estimated net benefit from using an electronic medical record for a 5-year period was 86,400 US dollars per provider. Benefits accrue primarily from savings in drug expenditures, improved utilization of radiology tests, better capture of charges, and decreased billing errors. In one-way sensitivity analyses, the model was most sensitive to the proportion of patients whose care was capitated; the net benefit varied from a low of 8400 US dollars to a high of 140,100 US dollars . A five-way sensitivity analysis with the most pessimistic and optimistic assumptions showed results ranging from a 2300 US dollars net cost to a 330,900 US dollars net benefit. Implementation of an electronic medical record system in primary care can result in a positive financial return on investment to the health care organization. The magnitude of the return is sensitive to several key factors.     

Predicting clonal self-renewal and extinction of hematopoietic stem cells

A single hematopoietic stem cell (HSC) can generate a clone, consisting of daughter HSCs and differentiated progeny, which can sustain the hematopoietic system of multiple hosts for a long time. At the same time, this massive expansion potential must be restrained to prevent abnormal, leukemic proliferation. We used an interdisciplinary approach, combining transplantation assays with mathematical and computational methods, to systematically analyze the proliferative potential of individual HSCs. We show that all HSC clones examined have an intrinsically limited life span. Daughter HSCs within a clone behaved synchronously in transplantation assays and eventually exhausted at the same time. These results indicate that each HSC is programmed to have a finite life span. This program and the memory of the life span of the mother HSC are inherited by all daughter HSCs. In contrast, there was extensive heterogeneity in life spans between individual HSC clones, ranging from 10 to almost 60 mo. We used model-based machine learning to develop a mathematical model that efficiently predicts the life spans of individual HSC clones on the basis of a few initial measurements of donor type cells in blood. Computer simulations predict that the probability of self-renewal decays with a logistic kinetic over the life span of a normal HSC clone. Other decay functions lead to either graft failure or leukemic proliferation. We propose that dynamical fate probabilities are a crucial condition that leads to self-limiting clonal proliferation.     

An expert system for the labeling and 3D reconstruction of the coronary arteries from two projections

Summary In this paper we present a rule-based expert system for the automatic delineation and 3D reconstruction of the left coronary artery on standard RAO and LAO angiographic projections. The approach is based on the application of a general blood vessel model and on anatomical models which take into account the normal variations of the coronary artery structure. In a first step, the arteries are delineated by detecting the maximum intensity on the centerline of the vessels. Then, we label the blood vessel segments according to an anatomical model of the left coronary artery. In general, only 1–2 labels remain for each blood vessel segment. Finally, these results are used for an automatic 3D reconstruction of the left coronary artery from two projections. Results from clinical RAO and LAO angiograms will be presented.     

Clinical evaluation of an electronic hand hygiene monitoring system

BackgroundWe aimed to test the accuracy of an electronic hand hygiene monitoring system (EHHMS) during daily clinical activities in different wards and with varying health care professions.MethodsThe accuracy of an EHHMS (Sani Nudge) was assessed during real clinical conditions by comparing events registered by two observers in parallel with events registered by the EHHMS. The events were categorized as true-positive, false-positive, and false-negative registrations. Sensitivity and positive predictive value (PPV) were calculated.ResultsA total of 103 events performed by 25 health care workers (9 doctors, 11 nurses, and 5 cleaning assistants) were included in the analyses. The EHHMS had a sensitivity of 100% and a PPV of 100% when measuring alcohol-based hand rub. When looking at the hand hygiene opportunities of all health care workers combined taking place in the patient rooms and working rooms, the sensitivity was 75% and the PPV 95%. For doctors’ and nurses’ taking care of patients in their beds the EHHMS had a sensitivity of 100% and a PPV of 94%.ConclusionsThe objective accuracy measures demonstrate that this EHHMS can capture hand hygiene behavior under clinical conditions in different settings with clinical health care workers but show less accuracy with cleaning assistants.     

Preferential protection of protein interaction network hubs in yeast: evolved functionality of genetic redundancy

The widely observed dispensability of duplicate genes is typically interpreted to suggest that a proportion of the duplicate pairs are at least partially redundant in their functions, thus allowing for compensatory affects. However, because redundancy is expected to be evolutionarily short lived, there is currently debate on both the proportion of redundant duplicates and their functional importance. Here, we examined these compensatory interactions by relying on a genome wide data analysis, followed by experiments and literature mining in yeast. Our data, thus, strongly suggest that compensated duplicates are not randomly distributed within the protein interaction network but are rather strategically allocated to the most highly connected proteins. This design is appealing because it suggests that many of the potentially vulnerable nodes that would otherwise be highly sensitive to mutations are often protected by redundancy. Furthermore, divergence analyses show that this association between redundancy and protein connectivity becomes even more significant among the ancient duplicates, suggesting that these functional overlaps have undergone purifying selection. Our results suggest an intriguing conclusion-although redundancy is typically transient on evolutionary time scales, it tends to be preserved among some of the central proteins in the cellular interaction network.     

Structural diversity in social contagion

The concept of contagion has steadily expanded from its original grounding in epidemic disease to describe a vast array of processes that spread across networks, notably social phenomena such as fads, political opinions, the adoption of new technologies, and financial decisions. Traditional models of social contagion have been based on physical analogies with biological contagion, in which the probability that an individual is affected by the contagion grows monotonically with the size of his or her "contact neighborhood"--the number of affected individuals with whom he or she is in contact. Whereas this contact neighborhood hypothesis has formed the underpinning of essentially all current models, it has been challenging to evaluate it due to the difficulty in obtaining detailed data on individual network neighborhoods during the course of a large-scale contagion process. Here we study this question by analyzing the growth of Facebook, a rare example of a social process with genuinely global adoption. We find that the probability of contagion is tightly controlled by the number of connected components in an individual's contact neighborhood, rather than by the actual size of the neighborhood. Surprisingly, once this "structural diversity" is controlled for, the size of the contact neighborhood is in fact generally a negative predictor of contagion. More broadly, our analysis shows how data at the size and resolution of the Facebook network make possible the identification of subtle structural signals that go undetected at smaller scales yet hold pivotal predictive roles for the outcomes of social processes.     

Correct biological timing in Arabidopsis requires multiple light-signaling pathways

Circadian oscillators provide rhythmic temporal cues for a range of biological processes in plants and animals, enabling anticipation of the day/night cycle and enhancing fitness-associated traits. We have used engineering models to understand the control principles of a plant’s response to seasonal variation. We show that the seasonal changes in the timing of circadian outputs require light regulation via feed-forward loops, combining rapid light-signaling pathways with entrained circadian oscillators. Linear time-invariant models of circadian rhythms were computed for 3,503 circadian-regulated genes and for the concentration of cytosolic-free calcium to quantify the magnitude and timing of regulation by circadian oscillators and light-signaling pathways. Bioinformatic and experimental analysis show that rapid light-induced regulation of circadian outputs is associated with seasonal rephasing of the output rhythm. We identify that external coincidence is required for rephasing of multiple output rhythms, and is therefore important in general phase control in addition to specific photoperiod-dependent processes such as flowering and hypocotyl elongation. Our findings uncover a fundamental design principle of circadian regulation, and identify the importance of rapid light-signaling pathways in temporal control.