RAGE: a new frontier in chronic airways disease

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.     

Oxidation of Therapeutic Proteins and Peptides: Structural and Biological Consequences

Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences of protein/peptide oxidation. Representative examples are discussed of specific products whose oxidation has been recently studied, including monoclonal antibodies, calcitonin, granulocyte colony-stimulating factor, growth hormone, insulin, interferon alpha and beta, oxytocin and parathyroid hormone. These examples illustrate that oxidation often leads to modifications of higher-order structures, including aggregate induction, and can generate products that are pharmacokinetically different, biologically less active and/or potentially more immunogenic than their native counterpart. It is therefore crucially important during the pharmaceutical development of therapeutic proteins and peptides to comprehensively characterize oxidation products and evaluate the impact of oxidation-induced structural modifications on the biological properties of the drug.     

The Impact of Food Assistance on Dietary Diversity and Food Consumption among People Living with HIV/AIDS

Little is known about the outcomes of food assistance targeted to food insecure people living with HIV/AIDS. Using primary data from Zambia, we estimated the impact of food assistance on the dietary diversity and consumption expenditures of households with HIV infected members receiving antiretroviral therapy. Propensity score matching estimates show that food assistance increased dietary diversity by 9.8 points (23%) mainly through the consumption of food items provided in the ration. Food assistance recipients were 20% points more likely to have acceptable food consumption and 15% points less likely to have poor food consumption than non-recipients. Food assistance also increased food consumption expenditures but had no significant impact on food purchases and total consumption expenditures. Overall, our findings demonstrate that food assistance can be an effective instrument for improving diets and enhancing the food security of people living with HIV/AIDS.     

Rasch analysis of the Patient and Observer Scar Assessment Scale (POSAS) in burn scars

Purpose  

The Patient and Observer Scar Assessment Scale (POSAS) is a questionnaire that was developed to assess scar quality. It consists of two separate six-item scales (Observer Scale and Patient Scale), both of which are scored on a 10-point rating scale. After many years of experience with this scale in burn scar assessment, it is appropriate to examine its psychometric properties using Rasch analysis.     

Hand‐foot‐skin reaction related to use of the multikinase inhibitor sorafenib and hard orthotics

Hand‐foot‐skin reaction is a distinct clinical condition arising in association with the use of multikinase inhibitors, including sorafenib. Because multikinase inhibitors are increasingly being used in children with cancer, recognition of this previously unfamiliar condition is of importance to pediatric dermatologists. We describe the diagnosis and successful treatment of a case of hand‐foot‐skin reaction in a child taking sorafenib for an unresectable desmoid tumor.     

Gonadal function recovery in very long-term male survivors of childhood cancer

BackgroundAlthough gonadal toxicity has been reported, no data are available on recovery of gonadal function in very long-term survivors of childhood cancer. Inhibin B is a novel reliable serum marker which has been shown to be of value in childhood cancer survivor studies to identify risk groups for impaired gonadal function, but consecutive long-term follow-up studies using serum inhibin B as a marker are not available.ObjectiveTo evaluate possible recovery of gonadal dysfunction over time in adult male survivors of childhood cancer.MethodsIn this retrospective study, adult male long-term childhood cancer survivors (n = 201) who visited our outpatient late effects clinic were included and we used inhibin B as a surrogate marker for gonadal function.ResultsMedian age at diagnosis was 5.9 years (range 0.0–17.5) and discontinuation of treatment was reached at a median age of 8.2 years (range 0.0–20.8). Inhibin B levels were first measured after a median follow-up time of 15.7 years (range 3.0–37.0). Median interval between the first (T1) and second measurement (T2) was 3.3 years (range 0.7–11.3). Median inhibin B level was 127 ng/L (range 5–366) at T1 and 155 ng/L (range 10–507) at T2. The prediction model suggests that inhibin B levels do not normalise in survivors with a very low Inhibin B level at T1.ConclusionsOur results suggest that recovery of gonadal function is possible even long after discontinuation of treatment. However, this recovery does not seem to occur in survivors who already reached critically low inhibin B levels after discontinuation of treatment.     

Exploring improvements in patient logistics in Dutch hospitals with a survey

ABSTRACT: BACKGROUND: Research showed that promising approaches such as benchmarking, operations research, lean management and six sigma, could be adopted to improve patient logistics in healthcare. To our knowledge, little research has been conducted to obtain an overview on the use, combination and effects of approaches to improve patient logistics in hospitals. We therefore examined the approaches and tools used to improve patient logistics in Dutch hospitals, the reported effects of these approaches on performance, the applied support structure and the methods used to evaluate the effects. METHODS: A survey among experts on patient logistics in 94 Dutch hospitals. The results were analysed using cross tables. RESULTS: Forty-eight percent of all hospitals participated. Ninety-eight percent reported to have used multiple approaches, 39% of them used five or more approaches. Care pathways were the preferred approach by 43% of the hospitals, followed by business process re-engineering and lean six sigma (both 13%). Flowcharts were the most commonly used tool, they were used on a regular basis by 94% of the hospitals. Less than 10% of the hospitals used data envelopment analysis and critical path analysis on a regular basis. Most hospitals (68%) relied on external support for process analyses and education on patient logistics, only 24% had permanent internal training programs on patient logistics. Approximately 50% of the hospitals that evaluated the effects of approaches on efficiency, throughput times and financial results, reported that they had accomplished their goals. Goal accomplishment in general hospitals ranged from 63% to 67%, in academic teaching hospitals from 0% to 50%, and in teaching hospitals from 25% to 44%. More than 86% performed an evaluation, 53% performed a post-intervention measurement. CONCLUSIONS: Patient logistics appeared to be a rather new subject as most hospitals had not selected a single approach, they relied on external support and they did not have permanent training programs. Hospitals used a combination of approaches and tools, about half of the hospitals reported goal accomplishment and no approach seemed to outperform the others. To make improvement efforts more successful, research should be conducted into the selection and application of approaches, their contingency factors, and goal-setting procedures.