Role of rhinovirus load in the upper respiratory tract and severity of symptoms in lung transplant recipients.

BACKGROUND: Rhinovirus is the most common cause of respiratory viral infections and leads to frequent respiratory symptoms in lung transplant recipients. However, it remains unknown whether the rhinovirus load correlates with the severity of symptoms. OBJECTIVES: This study aimed to better characterize the pathogenesis of rhinoviral infection and the way in which viral load correlates with symptoms. STUDY DESIGN: We assessed rhinovirus load in positive upper respiratory specimens of patients enrolled prospectively in a cohort of 116 lung transplant recipients. Rhinovirus load was quantified according to a validated in-house, real-time, reverse transcription polymerase chain reaction in pooled nasopharyngeal and pharyngeal swabs. Symptoms were recorded in a standardised case report form completed at each screening/routine follow-up visit, or during any emergency visit occurring during the 3-year study. RESULTS: Rhinovirus infections were very frequent, including in asymptomatic patients not seeking a specific medical consultation. Rhinovirus load ranged between 4.1 and 8.3 log copies/ml according to the type of visit and clinical presentation. Patients with highest symptom scores tended to have higher viral loads, particularly those presenting systemic symptoms. When considering symptoms individually, rhinovirus load was significantly higher in the presence of symptoms such as sore throat, fever, sputum production, cough, and fatigue. There was no association between tacrolimus levels and rhinovirus load. CONCLUSIONS: Rhinovirus infections are very frequent in lung transplant recipients and rhinoviral load in the upper respiratory tract is relatively high even in asymptomatic patients. Patients with the highest symptom scores tend to have a higher rhinovirus load.

Image quality in CT: From physical measurements to model observers.

Evaluation of image quality (IQ) in Computed Tomography (CT) is important to ensure that diagnostic questions are correctly answered, whilst keeping radiation dose to the patient as low as is reasonably possible. The assessment of individual aspects of IQ is already a key component of routine quality control of medical x-ray devices. These values together with standard dose indicators can be used to give rise to 'figures of merit' (FOM) to characterise the dose efficiency of the CT scanners operating in certain modes. The demand for clinically relevant IQ characterisation has naturally increased with the development of CT technology (detectors efficiency, image reconstruction and processing), resulting in the adaptation and evolution of assessment methods. The purpose of this review is to present the spectrum of various methods that have been used to characterise image quality in CT: from objective measurements of physical parameters to clinically task-based approaches (i.e. model observer (MO) approach) including pure human observer approach. When combined together with a dose indicator, a generalised dose efficiency index can be explored in a framework of system and patient dose optimisation. We will focus on the IQ methodologies that are required for dealing with standard reconstruction, but also for iterative reconstruction algorithms. With this concept the previously used FOM will be presented with a proposal to update them in order to make them relevant and up to date with technological progress. The MO that objectively assesses IQ for clinically relevant tasks represents the most promising method in terms of radiologist sensitivity performance and therefore of most relevance in the clinical environment.

Moderate glycemic control safe in critically ill adult burn patients: A 15 year cohort study.

INTRODUCTION: Hyperglycemia is a metabolic alteration in major burn patients associated with complications. The study aimed at evaluating the safety of general ICU glucose control protocols applied in major burns receiving prolonged ICU treatment. METHODS: 15year retrospective analysis of consecutive, adult burn patients admitted to a single specialized centre. EXCLUSION CRITERIA: death or length of stay <10 days, age <16years. VARIABLES: demographic variables, burned surface (TBSA), severity scores, infections, ICU stay, outcome. Metabolic variables: total energy, carbohydrate and insulin delivery/24h, arterial blood glucose and CRP values. Analysis of 4 periods: 1, before protocol; 2, tight doctor driven; 3, tight nurse driven; 4, moderate nurse driven. RESULTS: 229 patients, aged 45±20 years (mean±SD), burned 32±20% TBSA were analyzed. SAPSII was 35±13. TBSA, Ryan and ABSI remained stable. Inhalation injury increased. A total of 28,690 blood glucose samples were analyzed: the median value remained unchanged with a narrower distribution over time. After the protocol initiation, the normoglycemic values increased from 34.7% to 65.9%, with a reduction of hypoglycaemic events (no extreme hypoglycemia in period 4). Severe hyperglycemia persisted throughout with a decrease in period 4 (9.25% in period 4). Energy and glucose deliveries decreased in periods 3 and 4 (p<0.0001). Infectious complications increased during the last 2 periods (p=0.01). CONCLUSION: A standardized ICU glucose control protocol improved the glycemic control in adult burn patients, reducing glucose variability. Moderate glycemic control in burns was safe specifically related to hypoglycemia, reducing the incidence of hypoglycaemic events compared to the period before. Hyperglycemia persisted at a lower level.

Current and future trens in the quality control of pharmaceuticals and biopharmaticals : impacts on Cost of Goods Sold (COGS)

[Summary] 2. Roles of quality control in the pharmaceutical and biopharmaceutical industries. - 2.1. Pharmaceutical industry. - 2.2. Biopharmaceutical industry. - 2.3. Policy and regulatory. - 2.3.1. The US Food and Drug Administration (FDA). - 2.3.2. The European Medicine Agency (EMEA). - 2.3.3. The Japanese Ministry of Work, Labor and Welfare (MHLW). - 2.3.4. The Swiss Agency for Therapeutic Products (Swissmedic). - 2.3.5. The International Conference on Harmonization (ICH). - - 3. Types of testing. - 3.1. Microbiological purity tests. - 3.2. Physiochemical tests. - 3.3. Critical to quality steps. - 3.3.1. API starting materials and excipients. - 3.3.2. Intermediates. - 3.3.3. APIs (drug substances) and final drug product. - 3.3.4. Primary and secondary packaging materials fro drug products. - - 4. Manufacturing cost and quality control. - 4.1.1. Pharmaceutical manufacturing cost breakdown. - 4.1.2. Biopharmaceutical manufacturing cost breakdown. - 4.2. Batch failure / rejection / rework / recalls. - - 5. Future trends in the quality control of pharmaceuticals and biopharmaceuticals. - 5.1. Rapid and real time testing. - 5.1.1. Physio-chemicals testing. - 5.1.2. Rapid microbiology methods