Delirium in the elderly: Current problems with increasing geriatric age.

Delirium is an acute disorder of attention and cognition seen relatively commonly in people aged 65 yr or older. The prevalence is estimated to be between 11 and 42 per cent for elderly patients on medical wards. The prevalence is also high in nursing homes and long term care (LTC) facilities. The consequences of delirium could be significant such as an increase in mortality in the hospital, long-term cognitive decline, loss of autonomy and increased risk to be institutionalized. Despite being a common condition, it remains under-recognised, poorly understood and not adequately managed. Advanced age and dementia are the most important risk factors. Pain, dehydration, infections, stroke and metabolic disturbances, and surgery are the most common triggering factors. Delirium is preventable in a large proportion of cases and therefore, it is also important from a public health perspective for interventions to reduce further complications and the substantial costs associated with these. Since the aetiology is, in most cases, multfactorial, it is important to consider a multi-component approach to management, both pharmacological and non-pharmacological. Detection and treatment of triggering causes must have high priority in case of delirium. The aim of this review is to highlight the importance of delirium in the elderly population, given the increasing numbers of ageing people as well as increasing geriatric age.

Paediatric end-of-life care needs in Switzerland: current practices, and perspectives from parents and professionals. A study protocol.

AIM: To present a protocol for a multi-phase study about the current practice of end-of-life care in paediatric settings in Switzerland. BACKGROUND: In Switzerland, paediatric palliative care is usually provided by teams, who may not necessarily have specific training. There is a lack of systematic data about specific aspects of care at the end of a child's life, such as symptom management, involvement of parents in decision-making and family-centred care and experiences and needs of parents, and perspectives of healthcare professionals. DESIGN: This retrospective nationwide multicentre study, Paediatric End-of-LIfe CAre Needs in Switzerland (PELICAN), combines quantitative and qualitative methods of enquiry. METHODS: The PELICAN study consists of three observational parts, PELICAN I describes practices of end-of-life care (defined as the last 4 weeks of life) in the hospital and home care setting of children (0-18 years) who died in the years 2011-2012 due to a cardiac, neurological or oncological disease, or who died in the neonatal period. PELICAN II assesses the experiences and needs of parents during the end-of-life phase of their child. PELICAN III focuses on healthcare professionals and explores their perspectives concerning the provision of end-of-life care. CONCLUSION: This first study across Switzerland will provide comprehensive insight into the current end-of-life care in children with distinct diagnoses and the perspectives of affected parents and health professionals. The results may facilitate the development and implementation of programmes for end-of-life care in children across Switzerland, building on real experiences and needs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01983852.

Transcranial Direct Current Stimulation for the Treatment of Chronic Tinnitus: A Randomized Controlled Study.

BACKGROUND: Tinnitus is an often disabling condition for which there is no effective therapy. Current research suggests that tinnitus may develop due to maladaptive plastic changes and altered activity in the auditory and prefrontal cortex. Transcranial direct current stimulation (tDCS) modulates brain activity and has been shown to transiently suppress tinnitus in trials. OBJECTIVE: To investigate the efficacy and safety of tDCS in the treatment of chronic subjective tinnitus. METHODS: In a randomized, parallel, double-blind, sham-controlled study, the efficacy and safety of cathodal tDCS to the auditory cortex with anode over the prefrontal cortex was investigated in five sessions over five consecutive days. Tinnitus was assessed after the last session on day 5, and at follow-up visits 1 and 3 months post stimulation using the Tinnitus Handicap Inventory (THI, primary outcome measure), Subjective Tinnitus Severity Scale, Hospital Anxiety and Depression scale, Visual Analogue Scale, and Clinical Global Impression scale. RESULTS: 42 patients were investigated, 21 received tDCS and 21 sham stimulation. There were no beneficial effects of tDCS on tinnitus as assessed by primary and secondary outcome measures. Effect size assessed with Cohen's d amounted to 0.08 (95% CI: -0.52 to 0.69) at 1 month and 0.18 (95% CI: -0.43 to 0.78) at 3 months for the THI. CONCLUSION: tDCS of the auditory and prefrontal cortices is safe, but does not improve tinnitus. Different tDCS protocols might be beneficial.

Reciprocal preening and food sharing in colour-polymorphic nestling barn owls.

Barn owl (Tyto alba) siblings preen and offer food items to one another, behaviours that can be considered prosocial because they benefit a conspecific by relieving distress or need. In experimental broods, we analysed whether such behaviours were reciprocated, preferentially exchanged between specific phenotypes, performed to avoid harassment and food theft or signals of hierarchy status. Three of the results are consistent with the hypothesis of direct reciprocity. First, food sharing was reciprocated in three-chick broods but not in pairs of siblings, that is when nestlings could choose a partner with whom to develop a reciprocating interaction. Second, a nestling was more likely to give a prey item to its sibling if the latter individual had preened the former. Third, siblings matched their investment in preening each other. Manipulation of age hierarchy showed that food stealing was directed towards older siblings but was not performed to compensate for a low level of cooperation received. Social behaviours were related to melanin-based coloration, suggesting that animals may signal their propensity to interact socially. The most prosocial phenotype (darker reddish) was also the phenotype that stole more food, and the effect of coloration on prosocial behaviour depended upon rank and sex, suggesting that colour-related prosociality is state dependent.

Variation in Current Management of Term and Late-preterm Neonates at Risk for Early-onset Sepsis: An International Survey and Review of Guidelines.

BACKGROUND: Uncertainty about the presence of infection results in unnecessary and prolonged empiric antibiotic treatment of newborns at risk for early-onset sepsis (EOS). This study evaluates the impact of this uncertainty on the diversity in management. METHODS: A web-based survey with questions addressing management of infection risk-adjusted scenarios was performed in Europe, North America, and Australia. Published national guidelines (n = 5) were reviewed and compared with the results of the survey. RESULTS: 439 Clinicians (68% were neonatologists) from 16 countries completed the survey. In the low-risk scenario, 29% would start antibiotic therapy and 26% would not, both groups without laboratory investigations; 45% would start if laboratory markers were abnormal. In the high-risk scenario, 99% would start antibiotic therapy. In the low-risk scenario, 89% would discontinue antibiotic therapy before 72 hours. In the high-risk scenario, 35% would discontinue therapy before 72 hours, 56% would continue therapy for 5-7 days, and 9% for more than 7 days. Laboratory investigations were used in 31% of scenarios for the decision to start, and in 72% for the decision to discontinue antibiotic treatment. National guidelines differ considerably regarding the decision to start in low-risk and regarding the decision to continue therapy in higher risk situations. CONCLUSIONS: There is a broad diversity of clinical practice in management of EOS and a lack of agreement between current guidelines. The results of the survey reflect the diversity of national guidelines. Prospective studies regarding management of neonates at risk of EOS with safety endpoints are needed.

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

Lateral gene exchanges shape the genomes of amoeba-resisting microorganisms.

Based on Darwin's concept of the tree of life, vertical inheritance was thought to be dominant, and mutations, deletions, and duplication were streaming the genomes of living organisms. In the current genomic era, increasing data indicated that both vertical and lateral gene inheritance interact in space and time to trigger genome evolution, particularly among microorganisms sharing a given ecological niche. As a paradigm to their diversity and their survival in a variety of cell types, intracellular microorganisms, and notably intracellular bacteria, were considered as less prone to lateral genetic exchanges. Such specialized microorganisms generally have a smaller gene repertoire because they do rely on their host's factors for some basic regulatory and metabolic functions. Here we review events of lateral gene transfer (LGT) that illustrate the genetic exchanges among intra-amoebal microorganisms or between the microorganism and its amoebal host. We tentatively investigate the functions of laterally transferred genes in the light of the interaction with their host as they should confer a selective advantage and success to the amoeba-resisting microorganisms (ARMs).

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis.

Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called 'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.

Extracorporeal support for pulmonary resection: current indications and results.

Extracorporeal assistances are exponentially used for patients, with acute severe but reversible heart or lung failure, to provide more prolonged support to bridge patients to heart and/or lung transplantation. However, experience of use of extracorporeal assistance for pulmonary resection is limited outside lung transplantation. Airways management with standard mechanical ventilation system may be challenging particularly in case of anatomical reasons (single lung), presence of respiratory failure (ARDS), or complex tracheo-bronchial resection and reconstruction. Based on the growing experience during lung transplantation, more and more surgeons are now using such devices to achieve good oxygenation and hemodynamic support during such challenging cases. We review the different extracorporeal device and attempt to clarify the current practice and indications of extracorporeal support during pulmonary resection.