Optimal prandial timing of bolus insulin in diabetes management: a review.

The inability to achieve optimal diabetes glucose control in people with diabetes is multifactorial, but one contributor may be inadequate control of postprandial glucose. In patients treated with multiple daily injections of insulin, both the dose and timing of meal-related rapid-acting insulin are key factors in this. There are conflicting opinions and evidence on the optimal time to administer mealtime insulin. We performed a comprehensive literature search to review the published data, focusing on the use of rapid-acting insulin analogues in patients with Type 1 diabetes. Pharmacokinetic and pharmacodynamic studies of rapid-acting insulin analogues, together with postprandial glucose excursion data, suggest that administering these 15-20 min before food would provide optimal postprandial glucose control. Data from clinical studies involving people with Type 1 diabetes receiving structured meals and rapid-acting insulin analogues support this, showing a reduction in post-meal glucose levels of ~30% and less hypoglycaemia when meal insulin was taken 15-20 min before a meal compared with immediately before the meal. Importantly, there was also a greater risk of postprandial hypoglycaemia when patients took rapid-acting analogues after eating compared with before eating.

A Case of Autoimmune Pancreatitis Presenting as a Deterioration in Glycaemic Control in a Patient with Pre-Existing Type 2 Diabetes.

We report a case of Type 1 autoimmune pancreatitis presenting as a rare cause of worsening hyperglycaemia in a patient with Type 2 diabetes and discuss the difficulties in differentiating this disease from pancreatic cancer.

Modelling depression in animals: at the interface of reward and stress pathways.

RATIONALE: Despite substantial research efforts the aetiology of major depressive disorder (MDD) remains poorly understood, which is due in part to the heterogeneity of the disorder and the complexity of designing appropriate animal models. However, in the last few decades, a focus on the development of novel stress-based paradigms and a focus on using hedonic/anhedonic behaviour have led to renewed optimism in the use of animal models to assess aspects of MDD. OBJECTIVES: Therefore, in this review article, dedicated to Athina Markou, we summarise the use of stress-based animal models for studying MDD in rodents and how reward-related readouts can be used to validate/assess the model and/or treatment. RESULTS: We reveal the use and limitations of chronic stress paradigms, which we split into non-social (i.e. chronic mild stress), social (i.e. chronic social defeat) and drug-withdrawal paradigms for studying MDD and detail numerous reward-related readouts that are employed in preclinical research. Finally, we finish with a section regarding important factors to consider when using animal models. CONCLUSIONS: One of the most consistent findings following chronic stress exposure in rodents is a disruption of the brain reward system, which can be easily assessed using sucrose, social interaction, food, drug of abuse or intracranial self-stimulation as a readout. Probing the underlying causes of such alterations is providing a greater understanding of the potential systems and processes that are disrupted in MDD.

Patients safety incident reporting: the who, what, where, when and why?

The landscape of patient safety is changing nationally and internationally. Recently, the number of preventable deaths in the USA annually is estimated at between 200,000-400,000.Nationally and internationally under-reporting of patient safety incidents is an opportunity for improvement. In 2015, 58.6% of patient related claims received by the State Claims Agency (SCA) had no previous patient safety incident reported, despite the legal obligation to report adverse events to the SCA. A detailed, national survey of the acute hospitals identified that there is significant variation in the modes and patterns of incident reporting, including variation in the percentage of incidents reported to the SCA, who decides what is reported, how it is reported, the backlog of incidents not reported and the time delay before reporting. This knowledge confirms that currently, comparisons between hospitals of equal activity are inaccurate. Reduction in variation and increased standardisation of patient safety incident reporting is required.

Diagnosis and treatment of sleep related breathing disorders in children: 2007 to 2011.

Sleep related breathing disorders (SRBD) have historically been under-recognised and under-treated. Obstructive sleep apnoea (OSA) affects approximately 3% of children. In line with the increased recognition of SRBD there has been an increase in demand for diagnostic services. We determined the awareness of SRBD amongst Irish paediatricians, examined the provision of sleep services to children throughout the country between 2007 and 2011 and audited diagnostic sleep services in a tertiary centre in 2011. Amongst respondents there was an awareness of SRBD but a poor understanding of diagnostic evaluation with 31/46 (67) referring to inappropriate services. There has been a sharp increase in both diagnostic sleep tests (433-1793 [414]) and in the use of non-invasive ventilation (NIV) (31-186 [627]) for treatment of SRBD between 2007 and 2011. Paediatric sleep services are organized in an ad-hoc manner nationally with significant service variation. The use of domiciliary overnight oximetry reduced the requirement for more formal polysomnography by 70%.

Hippocampal plasticity during the peripartum period: influence of sex steroids, stress and ageing.

The peripartum period is accompanied by dramatic changes in hormones and a host of new behaviours in response to experience with offspring. Both maternal experience and maternal hormones can have a significant impact upon the brain and behaviour. This review outlines recent studies demonstrating modifications in hippocampal plasticity across the peripartum period, as well as the putative hormonal mechanisms underlying these changes and their modulation by stress. In addition, the impact of reproductive experience upon the ageing hippocampus is discussed. Finally, we consider how these changes in hippocampal structure may play a role in postpartum cognitive function and mood disorders, as well as age-related cognitive decline.

Outpatient parenteral antimicrobial therapy: a report of three years experience.

Although outpatient parenteral antimicrobial therapy (OPAT) is practiced internationally, there is a paucity of data regarding outcomes of paediatric OPAT. A retrospective analysis, of 3 years experience (January 2010 to 2013) was performed at a tertiary paediatric Respiratory unit. There were 362 OPAT courses administered to 32 children, of which 30 had cystic fibrosis and the remaining two had recurrent pneumonia. A total of 3,688 days of antibiotics were administered. The median age was 8.8 years (range 2.75 - 17.8 years). Sixteen (50%) were male. Each child received an average of 11 courses and median duration of OPAT was 10 days (range 2-21 days). Tobramycin was the commonest antimicrobial prescribed, with ceftazidime second. During this period, there was one readmission (0.3%) post discharge and 3 (2%) portocath infections. All patients attended for weekly review and laboratory monitoring. OPAT appears safe, effective and reduces the need for inpatient beds.

Impact of EWTD on teaching and training in Irish paediatric medicine: positive or negative?

The European working time directive (EWTD) was instituted in Children's University Hospital, Temple Street, Dublin, October 2010. This study aimed to assess the impact of the EWTD on teaching and training in hospital paediatric medicine. Research tools included questionnaire and focus group. Twenty out of a potential 52 non-consultant hospital doctors (NCHDs) completed the questionnaire. Sixty five percent (n = 13) of respondents stated the EWTD had an impact on teaching, with 75% (n = 15) stating it made it more difficult to attend hospital teaching sessions. The majority (95%, n = 19) felt it did not result in increased consultant or registrar teaching time. Thirty five percent (n=7) said the EWTD had decreased consultant supervised training time in specific procedures while 50% (n = 10) felt it had reduced registrar supervised training time. The EWTD enabled NCHDs to attend teaching sessions less tired (65%, n = 13) but they missed significant teaching due to enforced rest and cross cover arrangements.

Using animal models to study post-partum psychiatric disorders.

The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders.

The connective tissue and ligaments of the distal interphalangeal joint: a review and investigation using ultra-high field 16.4 Tesla magnetic resonance imaging.

This study reviews the literature on the anatomy of the connective tissues surrounding the distal interphalangeal joint and further characterizes the three-dimensional relationships of these structures with ultra-high field magnetic resonance imaging. Ten cadaver fingers, fixed in a solution of 5% agar and 4% formalin, were imaged utilising an ultrashield 16.4 Tesla ultra-high field magnetic resonance imaging, yielding a total of 4000 images. Images were analysed using Osirix™ (version 5.5.1 32 bit edition) for three-dimensional reconstruction. We found numerous conflicting descriptions of the connective tissue structures around the distal interphalangeal joint. Based upon our literature review and imaging studies we have defined precisely Cleland's ligaments, the oblique proximal septum, Grayson's ligaments, the dorsal plate, and the interosseous ligaments of the distal interphalangeal joint.

Animal models of depression and anxiety: What do they tell us about human condition?

While modern neurobiology methods are necessary they are not sufficient to elucidate etiology and pathophysiology of affective disorders and develop new treatments. Achievement of these goals is contingent on applying cutting edge methods on appropriate disease models. In this review, the authors present four rodent models with good face-, construct-, and predictive-validity: the Flinders Sensitive rat line (FSL); the genetically "anxious" High Anxiety-like Behavior (HAB) line; the serotonin transporter knockout 5-HTT(-/-) rat and mouse lines; and the post-traumatic stress disorder (PTSD) model induced by exposure to predator scent, that they have employed to investigate the nature of depression and anxiety.

Cumulative radiation exposure in children with cystic fibrosis.

This retrospective study calculated the cumulative radiation dose for children with cystic fibrosis (CF) attending a tertiary CF centre. Information on 77 children with a mean age of 9.5 years, a follow up time of 658 person years and 1757 studies including 1485 chest radiographs, 215 abdominal radiographs and 57 computed tomography (CT) scans, of which 51 were thoracic CT scans, were analysed. The average cumulative radiation dose was 6.2 (0.04-25) mSv per CF patient. Cumulative radiation dose increased with increasing age and number of CT scans and was greater in children who presented with meconium ileus. No correlation was identified between cumulative radiation dose and either lung function or patient microbiology cultures. Radiation carries a risk of malignancy and children are particularly susceptible. Every effort must be made to avoid unnecessary radiation exposure in these patients whose life expectancy is increasing.

Paediatric flexible bronchoscopy and its indications.

Paediatric flexible bronchoscopy (F.B.) with bronchoalveolar lavage (B.A.L.) is an increasingly important investigation. Retrospective review of 180 FB performed over a 5 year period by a single operator was undertaken. Common indications included recurrent lower respiratory tract infections (n = 92, 51%), persistent atelectasis (n = 43, 24%), persistent infiltrates (n = 18, 10%) and persistent consolidation (n = 17, 9%). Normal airway anatomy was identified in the majority (n = 154, 85.5%). Bronchomalacia was identified in 22 cases (12%). Thick purulent secretions were seen in 40 bronchoscopies (22%). Commonest organisms cultured on BAL were H. influenza (n = 22, 12.2%), Streptococcus Pneumoniae (n = 18, 10%) and Staph aureus (n = 9, 5%). Cytomegalo virus (C.M.V.), (n = 4, 2%), candida (n = 1, 0.5%) and aspergillus fumigatus were identified (n = 7, 4%). Bronchoscopic findings frequently guided management (n = 90, 51%). No significant complications occurred. Flexible bronchoscopy procedure, patient and equipment care were in adherence with best practice guidelines. Paediatric F.B. is a safe and useful procedure when clinically indicated.