Development and internal validation of a model for postoperative morbidity in adults undergoing major elective colorectal surgery: the peri-operative quality improvement programme (PQIP) colorectal risk model.

Over 1.5 million major surgical procedures take place in the UK NHS each year and approximately 25% of patients develop at least one complication. The most widely used risk-adjustment model for postoperative morbidity in the UK is the physiological and operative severity score for the enumeration of mortality and morbidity. However, this model was derived more than 30 years ago and now overestimates the risk of morbidity. In addition, contemporary definitions of some model predictors are markedly different compared with when the tool was developed. A second model used in clinical practice is the American College of Surgeons National Surgical Quality Improvement Programme risk model; this provides a risk estimate for a range of postoperative complications. This model, widely used in North America, is not open source and therefore cannot be applied to patient populations in other settings. Data from a prospective multicentre clinical dataset of 118 NHS hospitals (the peri-operative quality improvement programme) were used to develop a bespoke risk-adjustment model for postoperative morbidity. Patients aged ≥ 18 years who underwent colorectal surgery were eligible for inclusion. Postoperative morbidity was defined using the postoperative morbidity survey at postoperative day 7. Thirty-one candidate variables were considered for inclusion in the model. Death or morbidity occurred by postoperative day 7 in 3098 out of 11,646 patients (26.6%). Twelve variables were incorporated into the final model, including (among others): Rockwood clinical frailty scale; body mass index; and index of multiple deprivation quintile. The C-statistic was 0.672 (95%CI 0.660-0.684), with a bootstrap optimism corrected C-statistic of 0.666 at internal validation. The model demonstrated good calibration across the range of morbidity estimates with a mean slope gradient of predicted risk of 0.959 (95%CI 0.894-1.024) with an index-corrected intercept of -0.038 (95%CI -0.112-0.036) at internal validation. Our model provides parsimonious case-mix adjustment to quantify risk of morbidity on postoperative day 7 for a UK population of patients undergoing major colorectal surgery. Despite the C-statistic of < 0.7, our model outperformed existing risk-models in widespread use. We therefore recommend application in case-mix adjustment, where incorporation into a continuous monitoring tool such as the variable life adjusted display or exponentially-weighted moving average-chart could support high-level monitoring and quality improvement of risk-adjusted outcome at the population level.

Paediatric Psychiatry Admissions to Critical Care.

Aims Children and adolescents may require admission to PICU to manage significant episodes of psychiatric or behavioural disorders. The primary aim was to determine the number of paediatric psychiatry patients requiring PICU admission and the indications for admission. Methods Our patient information system was used to identify patients admitted with a psychiatric presentation. Results Fifteen patients were admitted during the study period. Ten (66%) patients were admitted at a weekend and 12 (80%) were admitted after 5pm. The admitting diagnosis was self-harm in 7 (46%), psychosis in five (33%) and an eating disorder in three (20%) patients. Conclusion The number of patients requiring PICU admission was small but represents a significant challenge to staff and resources. There is a need to establish a governance structure and pathway of care for these patients.

Cognitive functioning in systemic lupus erythematosus: a meta-analysis.

Cognitive deficits are common in patients with systemic lupus erythematosus (SLE) regardless of overt neuropsychiatric involvement; however, a clear neuropsychological profile of SLE has not emerged. This study undertook a literature search of the PubMed, Scopus and Ovid (PsychINFO) databases for studies investigating cognitive alterations in SLE, using standardized neuropsychological (NP) measures. The data were analysed using meta-analytical procedures. The results support the observation that relative to healthy controls, SLE (regardless of overt neuropsychiatric involvement) is associated with statistically significant, small effect-sized deficits in visual attention, cognitive fluency, immediate visual memory and visual reasoning. Moreover, the results support a gradient of cognitive disturbance in SLE with significantly greater cognitive impairment in NPSLE patients relative to non-NPSLE patients. Medium-sized deficits were observed in NPSLE patients relative to healthy controls across the domains of: complex attention, delayed verbal memory, language and verbal reasoning (with small or non-significant differences observed in non-NPSLE patients relative to healthy controls). These results are relevant to the understanding, assessment and rehabilitation of patients living with SLE, with or without overt neuropsychiatric involvement.

Cannabis Oil in an Irish Children's Critical Care Unit

Aims We present a case of a five-year-old female admitted postoperatively to the Paediatric Critical Care Unit with a history of refractory seizures for which her parents were administering cannabis oil. Methods We discuss the issues surrounding cannabis prescription in Ireland and the role of parental autonomy in medication selection and administration. Results An administration regime was agreed upon following discussion with the child's parents. Conslusion While this case raised ethical and legal issues, we must also consider parental autonomy and their role as advocate for their child during admission to critical care.

Organ and Tissue Donation in Irish Paediatric Intensive Care.

Aim Our aim was to present an overview of patterns of paediatric organ donation in the Republic of Ireland from January 2007 to January 2018. Methods We performed a retrospective audit of organ donation practice in paediatric intensive care units (PICU) in Ireland. Results Thirty-six children donated organs or tissue heart valves over the 11-year period. There were 13 paediatric organ donors between 2007 and 2012, this increased to 23 paediatric organ donors between 2013 and 2017. 2017 had the highest number of organ donors at 9 Conclusion Organ donation in Irish PICUs has increased over the last 11 years due to a combination of factors: improved resourcing and organization of Organ Donation Transplantation Ireland (ODTI), the establishment of clinical leads (both medical and nursing) in organ donation, a heightened awareness of organ donation and improved specialist Intensive Care dedicated consultant staffing. Finally organ donation is possible only through the generosity and altruism of bereaved families. Outcomes from donated organs have been excellent throughout the 11 year period audited.

Decreased levels of platelet-derived soluble glycoprotein VI detected prior to the first diagnosis of coronary artery disease in HIV-positive individuals.

HIV-positive patients are at increased risk for coronary artery disease (CAD); changes in platelet activation may play a role. This study was performed to determine if levels of soluble glycoprotein VI (sGPVI), a platelet-specific marker of activation, were different in HIV-positive patients compared with HIV-negative controls and further if levels were predictive of CAD in HIV. Twenty-four HIV-positive individuals (HIV cases) with CAD were compared with 46 age- and sex-matched HIV-positive controls without CAD and 41 HIV-negative controls (healthy controls). Platelet activation (represented by sGPVI level) was compared 12 months and 1 month prior to CAD diagnosis. sGPVI was quantified by ELISA. sGPVI levels were higher in HIV-positive subjects (combined) than healthy controls (122.5 ng/mL [interquartile ranges (IQR) 90.3-160.5] versus 84.7 ng/mL [IQR 48.6-119.5], p <0.001). Twelve months before the event, there was no difference in sGPVI between HIV cases and HIV controls (113.4 ng/mL [IQR 85.6-141.65] versus 128.0 ng/mL [IQR 96.6-179.4], p = 0.369). One month prior to the event, sGPVI was significantly lower in HIV cases compared with HIV controls (109.0 ng/mL [IQR 79.4-123.4] versus 133.9 ng/mL [IQR 112.7-171.9], p = 0.010). These results remained significant following adjustment for possible confounders. This work demonstrates that HIV infection is associated with higher sGPVI levels. A fall in sGPVI immediately prior to first coronary artery event may reflect a loss of negative-feedback mechanism and be an important pathological step in the development of symptomatic CAD, but further work is needed to confirm these findings and determine their clinical impact.

Vaccine-Preventable Admissions to an Irish Paediatric Intensive Care.

In the Republic of Ireland, the schedule of state-funded immunisation for children is comprehensive and includes diphtheria, pertussis, tetanus, pneumococcus, hepatitis B, meningococcus C, haemophilus B, polio, measles, rubella and mumps. Varicella and meningococcal B vaccines are commercially available but are not currently funded by the government. Each of the illnesses preventable by these vaccines can cause substantial morbidity, and rarely mortality, in infants and children. Our PICU continues to see serious illness due to avoidable infection. There were 39 admissions in a 4 year period, with 34 children surviving to discharge. Nine children were infected with pneumococcus, with 4 deaths. There was one case of pertussis, causing death. Most infections occurred in previously healthy children. These preventable conditions represent a significant burden on children, families, and on social and healthcare resources.

Vibriosis, not cholera: toxigenic Vibrio cholerae non-O1, non-O139 infections in the United States, 1984-2014.

Toxigenic strains of Vibrio cholerae serogroups O1 and O139 have caused cholera epidemics, but other serogroups - such as O75 or O141 - can also produce cholera toxin and cause severe watery diarrhoea similar to cholera. We describe 31 years of surveillance for toxigenic non-O1, non-O139 infections in the United States and map these infections to the state where the exposure probably originated. While serogroups O75 and O141 are closely related pathogens, they differ in how and where they infect people. Oysters were the main vehicle for O75 infection. The vehicles for O141 infection include oysters, clams, and freshwater in lakes and rivers. The patients infected with serogroup O75 who had food traceback information available ate raw oysters from Florida. Patients infected with O141 ate oysters from Florida and clams from New Jersey, and those who only reported being exposed to freshwater were exposed in Arizona, Michigan, Missouri, and Texas. Improving the safety of oysters, specifically, should help prevent future illnesses from these toxigenic strains and similar pathogenic Vibrio species. Post-harvest processing of raw oysters, such as individual quick freezing, heat-cool pasteurization, and high hydrostatic pressurization, should be considered.

Efficacy and safety of linagliptin according to patient baseline characteristics: A pooled analysis of three phase 3 trials.

BACKGROUND AND AIMS: We aimed to determine if patient baseline characteristics affect responses to linagliptin and identify relevant predictors of glycated hemoglobin (HbA1c) reduction in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Data were pooled from three 24-week, placebo-controlled trials of similar design (linagliptin, n = 1651; placebo, n = 607). Patients were categorized according to baseline characteristics: age, T2DM duration, gender, body mass index (BMI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and metabolic syndrome (MetS). Changes from baseline in HbA1c after 24 weeks were assessed with analysis of covariance (ANCOVA). The proportion of patients with baseline HbA1c >7% achieving HbA1c of ≤7% at week 24 were evaluated. Independent predictors of HbA1c response with linagliptin were analyzed in a multivariate analysis with ANCOVA. Linagliptin treatment led to significant mean (SE) placebo-corrected reductions from baseline in HbA1c across all subgroups (-0.42% [±0.11] to -0.79% [0.08]; all p < 0.001). Within subgroups, HbA1c reduction was more pronounced in patients without MetS (-0.74% [0.06]; treatment interaction p = 0.0489). The proportion of patients with baseline HbA1c >7% achieving a target HbA1c ≤7% was greater with linagliptin versus placebo (30.2% vs 11.5%; odds ratio 3.82; 95% CI 2.82 to 5.17; p < 0.001). Characteristics significantly predicting HbA1c reductions after 24 weeks were fasting plasma glucose and race (both p < 0.05). CONCLUSION: This post-hoc analysis supports that linagliptin achieved clinically meaningful improvements in hyperglycemia in patients with diverse clinical characteristics. These improvements were more pronounced in patients without MetS.

The stomach in health and disease.

The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.

HIV eradication symposium: will the brain be left behind?

On 18 July 2014, the National Institute of Mental Health in collaboration with ViiV Health Care and Boehringer Ingelheim supported a symposium on HIV eradication and what it meant for the brain. The symposium was an affiliated event to the 20th International AIDS Conference. The meeting was held in Melbourne, Australia, and brought together investigators currently working on HIV eradication together with investigators who are working on the neurological complications of HIV. The purpose of the meeting was to bring the two fields of HIV eradication and HIV neurology together to foster dialogue and cross talk to move the eradication field forward in the context of issues relating to the brain as a potential reservoir of HIV. The outcomes of the symposium were that there was substantive but not definitive evidence for the brain as an HIV reservoir that will provide a challenge to HIV eradication. Secondly, the brain as a clinically significant reservoir for HIV is not necessarily present in all patients. Consequently, there is an urgent need for the development of biomarkers to identify and quantify the HIV reservoir in the brain. Lastly, when designing and developing eradication strategies, it is critical that approaches to target the brain reservoir be included.

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes.

AIMS: To determine the effects of empagliflozin on blood pressure (BP) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks' empagliflozin (cohort 1, n = 823; cohort 2, n = 2477). BP was measured using 24-h BP monitoring (cohort 1) or seated office measurements (cohort 2). RESULTS: Empagliflozin reduced systolic BP (SBP) and diastolic BP in both cohorts (p < 0.001 vs placebo), without increasing heart rate. Empagliflozin reduced pulse pressure (PP; adjusted mean difference vs placebo cohort 1: -2.3 mmHg; cohort 2: -2.3 mmHg), mean arterial pressure (MAP; cohort 1, -2.3 mmHg; cohort 2, -2.1 mmHg) and double product (cohort 1, -385 mmHg × bpm; cohort 2, -369 mmHg × bpm) all p < 0.001 vs placebo. There was a trend towards a reduction in the ambulatory arterial stiffness index (AASI) with empagliflozin in cohort 1 (p = 0.059 vs placebo). AASI was not measured in cohort 2. Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 (p = 0.092). In cohort 2, greater reductions in MAP were achieved in patients with higher baseline SBP (p = 0.027) and greater reductions in PP were observed in older patients (p = 0.011). CONCLUSIONS: Empagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance.

Paediatric Early Warning Trigger--A Cry for Help.

In paediatrics, it is crucial to ensure that the child who is clinically deteriorating is rapidly recognised and treated. We implemented a Paediatric Early Warning Trigger (PEWT) in our unit to improve recognition of these patients. Our trigger was a series of physiological measurements with a PEWT call if any result was outside the accepted range. We retrospectively compared 12 months prior to the introduction of the trigger (January to December 2009) to the three years post the introduction of the trigger (January 2010 to December 2012). We compared the time from deterioration to involvement of senior staff during the two time periods. We also examined the rates of crash calls and PICU transfers in the two periods. We found that the time from deterioration to senior clinician involvement reduced from 312 minutes to 166 minutes and the rate of transfers to PICU among the triage category 1 & 2 patients reduced from 1:50 in 2009 to 1:129, 1:118 and 1:131 during the three years of the trial. The rate of cardiac arrest among this group reduced from 1:100 in 2009 to 1:129, 1:216 and 1:542 during the three years of the trial. This study demonstrates the effectiveness of a Paediatric Early Warning Trigger in an Irish setting. We have been able to maximise senior clinician input into our sickest children in a more timely fashion

Linagliptin treatment in subjects with type 2 diabetes with and without mild-to-moderate renal impairment.

AIMS: Renal disease is a frequent comorbidity of type 2 diabetes mellitus (T2DM) and an important factor complicating the choice of glucose-lowering drugs. The aim of this analysis was to evaluate the efficacy and safety of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin (5 mg/day) in mono, dual or triple oral glucose-lowering regimens in subjects with T2DM and mild or moderate renal impairment (RI). METHODS: In this pooled analysis of three 24-week, placebo-controlled, phase 3 trials, subjects with mild (estimated glomerular filtration rate (eGFR) 60-<90 ml/min/1.73 m(2) , n = 838) or moderate RI (30-<60 ml/min/1.73 m(2), n = 93) were compared with subjects with normal renal function (≥90 ml/min/1.73 m(2), n = 1212). RESULTS: Subjects with RI were older, had longer duration of diabetes, and increased prevalence of diabetes-related comorbidities. After 24 weeks, linagliptin achieved consistent placebo-corrected mean glycated haemoglobin (HbA1c) changes across the three renal function categories: normal (-0.63%; p < 0.0001), mild RI (-0.67%; p < 0.0001) and moderate RI (-0.53%; p < 0.01), with no inter-group difference (p = 0.74). Renal function with linagliptin remained stable across all categories. In linagliptin-treated subjects, overall adverse event (AE) rates and serious AE rates were similar to placebo. The incidence of hypoglycaemia with linagliptin and placebo was 11.1 versus 6.9%, 11.9 versus 9.0% and 15.9 versus 12.0% in the normal, mild RI and moderate RI categories, respectively. CONCLUSIONS: This pooled analysis provides evidence that linagliptin is an effective, well-tolerated and convenient treatment in subjects with T2DM and mild or moderate RI.

Cognitive control of attention is differentially affected in trauma-exposed individuals with and without post-traumatic stress disorder.

BACKGROUND: This study aimed to determine whether patients with post-traumatic stress disorder (PTSD) show difficulty in recruitment of the regions of the frontal and parietal cortex implicated in top-down attentional control in the presence and absence of emotional distracters. METHOD: Unmedicated individuals with PTSD (n = 14), and age-, IQ- and gender-matched individuals exposed to trauma (n = 15) and healthy controls (n = 19) were tested on the affective number Stroop task. In addition, blood oxygen level-dependent responses, as measured via functional magnetic resonance imaging, were recorded. RESULTS: Patients with PTSD showed disrupted recruitment of lateral regions of the superior and inferior frontal cortex as well as the parietal cortex in the presence of negative distracters. Trauma-comparison individuals showed indications of a heightened ability to recruit fronto-parietal regions implicated in top-down attentional control across distracter conditions. CONCLUSIONS: These results are consistent with suggestions that emotional responsiveness can interfere with the recruitment of regions implicated in top-down attentional control; the heightened emotional responding of patients with PTSD may lead to the heightened interference in the recruitment of these regions.

The Eczema Priority Setting Partnership: a collaboration between patients, carers, clinicians and researchers to identify and prioritize important research questions for the treatment of eczema.

BACKGROUND: Eczema is a common condition, yet there are uncertainties regarding many frequently used treatments. Knowing which of these uncertainties matter to patients and clinicians is important, because they are likely to have different priorities from those of researchers and funders. OBJECTIVES: To identify the uncertainties in eczema treatment that are important to patients who have eczema, their carers and the healthcare professionals (HCPs) who treat them. METHODS: An eczema Priority Setting Partnership was established, including patients, HCPs and researchers. Eczema treatment uncertainties were gathered from patients and clinicians, and then prioritized in a transparent process, using a methodology advocated by the James Lind Alliance. RESULTS: In the consultation stage 493 participants (including 341 patients/carers) made 1070 submissions, of which 718 were uncertainties relating to the treatment of eczema. Treatment uncertainties with more than one submission were grouped into 52 'indicative uncertainties', which were then ranked by 514 participants (including 399 patients/carers). The top 14 treatment uncertainties were prioritized for research. The first four were common to patients/carers and HCPs (shared uncertainties): (i) the best and safest way of using topical steroids (including frequency of application, potency, length of time, alternation with other topical treatments and age limits); (ii) the long-term safety of topical steroids; (iii) the role of food allergy tests; and (iv) the most effective and safe emollients in treating eczema. The remaining 10 of the top 14 uncertainties comprised the next five highest ranked uncertainties for patients and the next five highest ranked uncertainties for HCPs. At a workshop involving 40 participants (patients, HCPs and researchers), shared uncertainties were formulated into possible research questions. CONCLUSIONS: The top 14 treatment uncertainties around the treatment of eczema provide guidance for researchers and funding bodies to ensure that future research answers questions that are important to both clinicians and patients.

Setting research priorities for Type 1 diabetes.

AIMS: Research priorities are often set by academic researchers or the pharmaceutical industry. The interests of patients, carers and clinicians may therefore be overlooked and research questions that matter may be neglected. The aims of this study were to collect uncertainties about the treatment of Type 1 diabetes from patients, carers and health professionals, and to collate and prioritize these uncertainties to develop a top 10 list of research priorities, using a structured priority-setting partnership of patients, carers, health professionals and diabetes organizations, as described by the James Lind Alliance. METHODS: A partnership of interested organizations was set up, and from this a steering committee of 10 individuals was formed. An online and paper survey was used to identify uncertainties. These were collated, and the steering group carried out an interim priority-setting exercise with partner organizations. This group of uncertainties was then voted on to give a smaller list that went forward to the final priority-setting workshop. At this meeting, a final list of the top 10 research priorities was agreed. RESULTS: An initial 1141 uncertainties were described. These were reduced to 88 indicative questions, 47 of which went out for voting. Twenty-four were then taken forward to a final priority-setting workshop. This workshop resulted in a list of top 10 research priorities in Type 1 diabetes. CONCLUSION: We have shown that it is possible using the James Lind Alliance process to develop an agreed top 10 list of research priorities for Type 1 diabetes from health professionals, patients and carers.

Influenza vaccination can induce new-onset anticardiolipins but not ß2-glycoprotein-I antibodies among patients with systemic lupus erythematosus.

BACKGROUND: Antiphospholipid syndrome is characterized by autoantibodies against cardiolipins (aCL), lupus anticoagulant, and independent ß2-glycoprotein (ß2GPI). Controversy exists as to whether vaccination triggers the development of antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (101) and matched controls (101) were enrolled from 2005-2009 and received seasonal influenza vaccinations. Sera were tested by ELISA for aCL at baseline, 2, 6, and 12 weeks after vaccination. Vaccine responses were ranked according to an overall anti-influenza antibody response index. Individuals with positive aCL were further tested for ß2GPI antibodies. RESULTS: Patients with SLE and healthy controls can develop new-onset aCL post vaccination, although at rates which do not differ between patients and controls (12/101 cases and 7/101 controls, OR 1.81, p = 0.34). New-onset moderate aCL are slightly enriched in African American SLE patients (5/36 cases; p = 0.094). The optical density measurements for aCL reactivity in patients were significantly higher than baseline at 2 weeks (p < 0.05), 6 weeks (p < 0.05), and 12 weeks (p < 0.05) post vaccination. No new ß2GPI antibodies were detected among patients with new aCL reactivity. Vaccine response was not different between patients with and without new-onset aCL reactivity (p = 0.43). CONCLUSIONS: This study shows transient increases in aCL, but not anti-ß2GPI responses, after influenza vaccination.