Beyond 'find and fix': improving quality and safety through resilient healthcare systems.

OBJECTIVE: The aim was to develop a method based on resilient healthcare principles to proactively identify system vulnerabilities and quality improvement interventions. DESIGN: Ethnographic methods to understand work as it is done in practice using concepts from resilient healthcare, the Concepts for Applying Resilience Engineering model and the four key activities that are proposed to underpin resilient performance-anticipating, monitoring, responding and learning. SETTING: Accident and Emergency Department (ED) and the Older People's Unit (OPU) of a large teaching hospital in central London. PARTICIPANTS: ED-observations 104 h, and 14 staff interviews. OPU-observations 60 h, and 15 staff interviews. RESULTS: Data were analysed to identify targets for quality improvement. In the OPU, discharge was a complex and variable process that was difficult to monitor. A system to integrate information and clearly show progress towards discharge was needed. In the ED, patient flow was identified as a complex high-intensity activity that was not supported by the existing data systems. The need for a system to integrate and display information about both patient and organizational factors was identified. In both settings, adaptive capacity was limited by the absence of systems to monitor the work environment. CONCLUSIONS: The study showed that using resilient healthcare principles to inform quality improvement was feasible and focused attention on challenges that had not been addressed by traditional quality improvement practices. Monitoring patient and workflow in both the ED and the OPU was identified as a priority for supporting staff to manage the complexity of the work.

Inhaled nitric oxide use in preterm infants in California neonatal intensive care units.

OBJECTIVE: To describe inhaled nitric oxide (iNO) exposure in preterm infants and variation in neonatal intensive care unit (NICU) use. STUDY DESIGN: This was a retrospective cohort study of infants, 22 to 33+6/7 weeks of gestational age (GA), during 2005 to 2013. Analyses were stratified by GA and included population characteristics, iNO use over time and hospital variation. RESULTS: Of the 65 824 infants, 1718 (2.61%) received iNO. Infants, 22 to 24+6/7 weeks of GA, had the highest incidence of iNO exposure (6.54%). Community NICUs (n=77, median hospital use rate 0.7%) used less iNO than regional NICUs (n=23, median hospital use rate 5.8%). In 22 to 24+6/7 weeks of GA infants, the median rate in regional centers was 10.6% (hospital interquartile range 3.8% to 22.6%). CONCLUSION: iNO exposure varied with GA and hospital level, with the most use in extremely premature infants and regional centers. Variation reflects a lack of consensus regarding the appropriate use of iNO for preterm infants.

Photochemically modified diamond-like carbon surfaces for neural interfaces.

Diamond-like carbon (DLC) was modified using a UV functionalization method to introduce surface-bound amine and aldehyde groups. The functionalization process rendered the DLC more hydrophilic and significantly increased the viability of neurons seeded to the surface. The amine functionalized DLC promoted adhesion of neurons and fostered neurite outgrowth to a degree indistinguishable from positive control substrates (glass coated with poly-L-lysine). The aldehyde-functionalized surfaces performed comparably to the amine functionalized surfaces and both additionally supported the adhesion and growth of primary rat Schwann cells. DLC has many properties that are desirable in biomaterials. With the UV functionalization method demonstrated here it may be possible to harness these properties for the development of implantable devices to interface with the nervous system.

The cytoplasmic and nuclear populations of the eukaryote tRNA-isopentenyl transferase have distinct functions with implications in human cancer.

Mod5 is the yeast tRNA isopentenyl transferase, an enzyme that is conserved from bacteria to humans. Mod5 is primarily cytoplasmic where it modifies the A37 position of a few tRNAs, and the yeast enzyme has been shown capable of forming heritable, amyloid-like aggregates that confer a selective advantage in the presence of specific antifungal agents. A subpopulation of Mod5 is also found associated with nuclear tRNA genes, where it contributes tRNA-gene mediated (tgm) silencing of local transcription by RNA polymerase II. The tgm-silencing function of Mod5 has been observed in yeast and a Mod5-deletion in yeast can be complemented by the plant and human tRNA isopentenyl transferases, but not the bacterial enzymes, possibly due to the lack of an extended C-terminal domain found in eukaryotes. In light of this additional nuclear role for Mod5 we discuss the proposed role of the human homologue of Mod5, TRIT1, as a tumor suppressor protein.

Pulmonary hypertension predicts mortality in infants with omphalocele.

OBJECTIVE: The objective of this study was to identify predictors of mortality in infants with omphalocele. METHODS: Medical records of infants with omphalocele born between January 1992 and June 2012, with follow-up toDecember 2012, were retrospectively reviewed. Survivors and non-survivors were compared. Evidence for pulmonary hypertension was sought between the second and seventh day after birth. All included infants had increased right ventricular pressures (RVP >40 mmhg) on echocardiogram on the second day of life with increased oxygen requirements, therefore, the finding of increased pressure was not considered a result of the transitional circulation. Logistic regression was used to evaluate the importance and independence of various factors. RESULTS: Of 51 infants whose records were reviewed, 13 died (25%) and 38 survived (75%). The median time to death was 34 days (range: 4 -408 days). The median follow-up time for those who died was 1.5 years (range: 0.01-15 years) and for survivors was 2.6 years (range: 0.08-15 years). Logistic regression revealed that respiratory insufficiency at birth (OR: 14.8; 95% CI: 2.5-85.0) and pulmonary hypertension (OR: 6.4; 95% CI: 1.1-39.0) were independently associated with mortality. CONCLUSION: Respiratory insufficiency after birth and pulmonary hypertension are independent predictors of mortality in infants with omphalocele.

Amine functionalized nanodiamond promotes cellular adhesion, proliferation and neurite outgrowth.

In this study, we report the production of amine functionalized nanodiamond. The amine functionalized nanodiamond forms a conformal monolayer on a negatively charged surface produced via plasma polymerization of acrylic acid. Nanodiamond terminated surfaces were studied as substrates for neuronal cell culture. NG108-15 neuroblastoma-glioma hybrid cells were successfully cultured upon amine functionalized nanodiamond coated surfaces for between 1 and 7 d. Additionally, primary dorsal root ganglion (DRG) neurons and Schwann cells isolated from Wistar rats were also successfully cultured over a period of 21 d illustrating the potential of the coating for applications in the treatment of peripheral nerve injury.

Potential coeliac disease in Type 1 diabetes mellitus: does a positive antibody lead to increased complications?

BACKGROUND AND AIMS: Coeliac disease (CD) is more common in people with Type 1 diabetes and is associated with poorer glycaemic control, lipid profiles, nephropathy and retinopathy. Potential CD (positive serology but normal duodenal biopsy) is associated with neuropathy but patients with coexisting Type 1 diabetes were excluded. The aim was to determine whether potential CD is associated with increased microvascular complications in patients with Type 1 diabetes. METHODS AND RESULTS: Four groups were recruited; 1) patients with Type 1 diabetes and potential CD, 2) patients with Type 1 diabetes and newly identified CD, 3) patients with Type 1 diabetes alone and 4) patients with CD alone. Glycaemic control, quality of life, lipid profile and microvascular complication rates were examined. As many as 76 individuals were included in the study: 22 in group 1, 14 in group 2, 24 in group 3 and 16 in group 4. There were no differences in age, gender, BMI and diabetes duration between the groups. Patients in group 1 had significantly lower total cholesterol compared to group 3 (p = 0.003) but higher than group 2 (p = 0.027). There were no significant differences in HbA1c, HDL cholesterol, cholesterol:HDL ratio, creatinine, quality of life scores or prevalence of neuropathy between individuals in group 1 and the other groups. CONCLUSIONS: This is the first study to assess the effects of potential CD in patients with Type 1 diabetes. It appears that an enteropathy is required as well as antibody positivity in order to increase the risk of diabetes related complications. This pilot data requires further longitudinal validation.

Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary?

AIMS: Immunoglobulin A (IgA) measurement is advocated when case finding for coeliac disease in patients with Type 1 diabetes mellitus. Currently, there is a paucity of contemporary studies assessing IgA deficiency in Type 1 diabetes. This study evaluates the prevalence of IgA deficiency in individuals with Type 1 diabetes, compared with patients with coeliac disease and control subjects. In addition, we evaluate whether routine IgA measurement is justifiable when case finding for coeliac disease in patients with Type 1 diabetes. METHODS: All patients were assessed using IgA endomysial antibodies, IgA anti-tissue transglutaminase antibodies and total IgA levels. Altogether, 2434 individuals were tested: 1000 patients with Type 1 diabetes, 234 patients with coeliac disease and 1200 population control subjects. Definitive IgA deficiency was defined as total IgA levels < 0.07 g/l. RESULTS: The prevalence of IgA deficiency was significantly more common in patients with Type 1 diabetes (0.9%, n = 9/1000; P = 0.036) and coeliac disease (1.29%, n = 3/234; P = 0.041) when compared with population control subjects (prevalence of 0.17%, 2/1200). No statistical difference between Type 1 diabetes and coeliac disease for IgA deficiency was identified (P = 0.87). Of patients in the group with Type 1 diabetes, 3.3% (33/1000) had coeliac disease, and of those only one patient had IgA deficiency leading to an antibody-negative presentation. Both IgA-deficient individuals within the population control subjects had normal duodenal biopsies and no relevant symptoms. CONCLUSIONS: IgA deficiency is more common in Type 1 diabetes compared with population control subjects. Despite this, very few individuals with Type 1 diabetes and IgA deficiency appear to have villous atrophy on biopsy. These outcomes question the practice of routine IgA measurement when case finding for coeliac disease in patients with Type 1 diabetes.

Quality not quantity for transglutaminase antibody 2: the performance of an endomysial and tissue transglutaminase test in screening coeliac disease remains stable over time.

National Institute of Clinical Excellence (NICE) and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidance for the diagnosis of coeliac disease has been published. However, there is some controversy regarding the advice on the use of stratifying levels of immunoglobulin (IgA) tissue transglutaminase antibody (TG2) test positivity in the absence of test standardization and the vagueness of the indication to test equivocal samples. Using repeat service audit, we demonstrate that a combination of TG2 followed by IgA endomysial antibodies (EMA) is the best strategy for all degrees of mucosal abnormality using our test combination. Reliance upon immunoassay titre is not as effective, and cannot be applied consistently across populations in the absence of assay standardization. Guidelines advocating the use of tests should involve experts in laboratory diagnostics and external quality assurance to ensure that errors of generalization do not occur and that test performance is achievable in routine diagnostic use.

Use of propranolol for treatment of hemangiomas in PHACE syndrome.

We report the case of a 29-week preterm infant with PHACE (posterior fossa malformations, hemangionas, arterial anomalies, cardiac anomalies, eye anomalies) syndrome. PHACE syndrome is a neurocutaneous disorder with large facial segmental hemangionas associated with anomalies of the brain, eye, heart and aorta. The hemangiomas in our patient were problematic, distorting the airway and interfering with respirations to the point of requiring mechanical ventilation. Consultation with several different centers with medical expertize in treatment of congenital hemangiomas revealed different views on the best management strategy. In this infant, the hemangiomas progressed with failure to involute despite currently recommended therapy including corticosteroids and vincristine. Therefore, the infant was treated with propranolol and had significant regression of the hemangiomas. The use of propranolol for the treatment of infantile hemangiomas is reviewed.

Comparison of patients' needs and doctors' perceptions of information requirements related to a diagnosis of oesophageal or gastric cancer.

The aim of this study was to assess the information needs of patients diagnosed with oesophageal and gastric cancer and to compare these with their perceived information needs in the opinion of junior doctors. One hundred patients and 100 doctors responded to a questionnaire regarding the information needs of cancer patients. Seventy-nine per cent of patients wanted as much information as possible about their diagnosis, but only 35% of doctors were willing to give all the available information (P < 0.0001). Seventy-seven per cent of patients wanted to receive their diagnosis from a consultant whereas only 5% of doctors believed that patients should receive their diagnoses from a consultant (P < 0.0001). Eighty-four per cent of doctors were willing to communicate a serious illness with a good prognosis, yet only 43% would communicate a diagnosis with a poor prognosis (P < 0.0001). All 100 doctors had received formal training in breaking bad news, but 20 considered this inadequate. Socio-economic deprivation was associated with poor access to supplementary Internet derived information (P < 0.001). The majority of patients with a diagnosis of oesophagogastric cancer want a great deal of information regarding their illness, which contrasts with doctors' perceptions. Adequate training in information disclosure may help address this issue.

Autoimmune pancreatitis: an important diagnostic consideration in obstructive jaundice due to a pancreatic mass lesion.

Autoimmune or immunoglobulin G subtype (IgG4) pancreatitis is a newly recognised clinical entity and is an important differential diagnosis for patients presenting with obstructive jaundice. Knowledge of autoimmune pancreatitis (AIP) continues to evolve both for pathogenesis and management; however diagnosis is often not straightforward or even considered, therefore a high index of suspicion remains an important tool for the treating physician. The six cases presented illustrate both the difficulties in diagnosis as well as management of this condition.

A prospective study into the aetiology of lymphocytic duodenosis.

BACKGROUND: Lymphocytic duodenosis is defined by normal villous architecture and intraepithelial lymphocytes (IELs) >25 per 100 enterocytes. Such patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with lymphocytic duodenosis. AIM: To study prospectively the aetiology of lymphocytic duodenosis. METHODS: One hundred patients with lymphocytic duodenosis were investigated rigorously for coeliac disease and other known associations for lymphocytic duodenosis by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for lymphocytic duodenosis, 29 underwent repeat duodenal biopsies following a gluten challenge. RESULTS: Coeliac disease was present in 16% of patients with lymphocytic duodenosis. In the absence of a positive coeliac diagnosis, lymphocytic duodenosis was most commonly associated with drugs (21%), infection (19%), immune dysregulation (4%), inflammatory bowel disease (2%), microscopic colitis (2%), sarcoidosis (1%) and IgA deficiency (1%). Of 34 with no known associations, 18 had symptoms of irritable bowel syndrome (IBS), and in 29 patients investigated with repeat duodenal biopsies, the IEL count returned to normal in 22. CONCLUSIONS: In 66% of cases of lymphocytic duodenosis, a known association can be found by further investigations; importantly, 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count becomes normal on repeat biopsy in 76%.

Prospective comparison of endosonography, computed tomography, and histopathological stage of junctional oesophagogastric cancer.

AIMS: To assess the strength of agreement between the perceived preoperative stage of Siewert II (oesophagogastric junction) and Siewert III (proximal gastric tumours) as determined by computed tomography (CT) and endoscopic ultrasound (EUS), both alone and in combination, with histopathological stage. METHODS: Forty-four patients with Siewert II (n=18) and III (n=26) adenocarcinomas of the oesophagogastric junction underwent preoperative CT at their local hospitals followed by specialist EUS, and the strengths of the agreement between the radiological stages and the histopathological stages were determined by the weighted Kappa statistic (Kw). RESULTS: Kw for Siewert II T and N stages was 0.491 (p=0.016) and 0.4 (p=0.087) for CT compared with 0.852 (p=0.0001) and 1 (p=0.0001) for EUS. Kw for Siewert III T and N stages was 0.181 (p=0.206) and 0.121 (p=0.376) for CT compared with 0.173 (p=0.195) and 0.263 (p=0.031) for EUS. CONCLUSION: Siewert II tumour T and N stages were more accurately predicted by EUS than CT, but Siewert III tumour T and N stages were more difficult to assess, arguably because of anatomical constraints at the oesophagogastric junction. CT and EUS are complimentary techniques, and these results highlight the importance of multidisciplinary discussion in planning treatment.