Trial Forge Guidance 4: a guideline for reporting the results of randomised Studies Within A Trial (SWATs).

BACKGROUND: Evidence to support decisions on trial processes is minimal. One way to generate this evidence is to use a Study Within A Trial (SWAT) to test trial processes or explore methodological uncertainties. SWAT evidence relies on replication to ensure sufficient power and broad applicability of findings. Prompt reporting is therefore essential; however, SWAT publications are often the first to be abandoned in the face of other time pressures. Reporting guidance for embedded methodology trials does exist but is not widely used. We sought therefore to build on these guidelines to develop a straightforward, concise reporting standard, which remains adherent to the CONSORT guideline. METHODS: An iterative process was used to develop the guideline. This included initial meetings with key stakeholders, development of an initial guideline, pilot testing of draft guidelines, further iteration and pilot testing, and finalisation of the guideline. RESULTS: We developed a reporting guideline applicable to randomised SWATs, including replications of previous evaluations. The guideline follows the Consolidated Standards for Reporting Trials (CONSORT) statement and provides example text to ensure ease and clarity of reporting across all domains. CONCLUSIONS: The SWAT reporting guideline will aid authors, reviewers, and journal editors to produce and review clear, structured reports of randomised SWATs, whilst also adhering to the CONSORT guideline. TRIAL REGISTRATION: EQUATOR Network - Guidelines Under Development ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#SWAT ). Registered on 25 March 2021.

Post-operative pain after laparoscopic right hemicolectomy for Crohn's disease: a case control study.

AIM: Surgery for Crohn's disease (CD) is characterized by an enhanced inflammatory response. While inflammation can induce hyperalgesia, post-operative pain following surgery for CD has not been characterized. This retrospective study compared a consecutive series of patients undergoing laparoscopic right hemicolectomy for CD and neoplasia performed by a single surgeon. METHOD: Elective resections performed between Jan-2016 and Aug-2017 managed in an enhanced recovery pathway were eligible for inclusion. Patients were excluded if open surgery was performed, an ileostomy was fashioned, no patient-controlled analgesia (PCA) was used or data were incomplete. Results : 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. RESULTS: 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. CONCLUSIONS: CD patients experience increased post-operative pain, require more post-operative analgesia and have an enhanced post-operative inflammatory response. Further studies to elucidate the mechanism of this hyperalgesia and strategies to obviate it are required.

Human Disease/Clinical Medical Sciences in Dentistry: Current state and future directions of undergraduate teaching in the UK and Ireland.

In March 2017, a group of teachers of human disease/clinical medical science (HD/CMSD) representing the majority of schools from around the UK and Republic of Ireland met to discuss the current state of teaching of human disease and also to discuss how the delivery of this theme might evolve to inform improved healthcare. This study outlines how the original teaching in medicine and surgery to dental undergraduate students has developed into the theme of HD/CMSD reflecting changing needs as well as guidance from the regulators, and how different dental schools have developed their approaches to reach their current state. Each school was also asked to share a strengths, weakness, opportunities and threats (SWOT) analysis of their programme and to outline how they thought their HD/CMSD programme may develop. The school representatives who coordinate the delivery and assessment of HD/CMSD in the undergraduate curriculum have extensive insight in this area and are well-placed to shape the HD/CMSD development for the future.

Oral manifestations of lupus.

INTRODUCTION: Mucosal involvement is commonly seen in patients with lupus; however, oral examination is often forgotten. Squamous cell carcinoma arising within oral lupoid plaques has been described, emphasizing the importance of identifying and treating oral lupus. METHODS: We undertook a retrospective single-centre study looking at oral findings in patients attending our multidisciplinary lupus clinic between January 2015 and April 2016. RESULTS: A total of 42 patients were included. The majority of patients were female (88%) and had a diagnosis of discoid lupus erythematosus (62%). Half of the patients had positive oral findings, 26% had no oral examination documented, and 24% had documented normal oral examinations. CONCLUSION: Our findings suggest that oral pathology is common in this cohort of patients. Regular oral examination is warranted to identify oral lupus and provide treatment. Associated diseases such as Sjogren's syndrome may also be identified. Patients should be encouraged to see their general dental practitioners on a regular basis for mucosal review. Any persistent ulcer that fails to respond to treatment or hard lump needs urgent histopathological evaluation to exclude malignant transformation to squamous cell carcinoma.

Liquid chromatography/mass spectrometry based detection and semi-quantitative analysis of INSL5 in human and murine tissues.

RATIONALE: Insulin-like peptide 5 (INSL5) is a hormone produced by enteroendocrine L-cells in the colon that has recently been implicated in the control of metabolic homeostasis. However, research into its physiology has been hindered by the reported unreliability of commercially available immunoassays and additional detection assays would benefit this emerging field. METHODS: Peptides from purified murine L-cells and homogenates from both human and mouse colonic tissues were extracted by precipitating larger proteins with acetonitrile. Untargeted liquid chromatography/tandem mass spectrometry (LC/MS/MS) analyses, followed by database searching, were used to detect and identify various INSL5 gene derived peptides and characterise their precise sequence. A similar approach was developed to quantify INSL5 levels in primary intestinal culture supernatants after purification and concentration by solid-phase extraction. RESULTS: Mass spectral analysis of purified enteroendocrine cells and tissue homogenates identified the exact sequence of A and B chains of INSL5 endogenously expressed in L-cells. Differences in the endogenously processed peptide and the Swissprot database entry were observed for murine INSL5, whereas the human sequence matched previous predictions from heterologous expression experiments. INSL5 was detected in the supernatant of human and mouse primary colonic cultures and concentrations increased after treatment with a known L-cell stimulus. CONCLUSIONS: The first LC/MS/MS-based method capable of the detection and semi-quantitative analysis of endogenous INSL5 using MS-based techniques has been demonstrated. The methodology will enable the identification of stimulants for INSL5 secretion from murine and human primary colonic epithelial cultures.

Dislocation loop formation by swift heavy ion irradiation of metals.

A coupled two-temperature, molecular dynamics methodology is used to simulate the structural evolution of bcc metals (Fe and W) and fcc metals (Cu and Ni) following irradiation by swift heavy ions. Electronic temperature dependent electronic specific heat capacities and electron-phonon coupling strengths are used to capture the full effects of the variation in the electronic density of states. Tungsten is found to be significantly more resistant to damage than iron, due both to the higher melting temperature and the higher thermal conductivity. Very interesting defect structures, quite different from defects formed in cascades, are found to be created by swift heavy ion irradiation in the bcc metals. Isolated vacancies form a halo around elongated interstitial dislocation loops that are oriented along the ion path. Such configurations are formed by rapid recrystallization of the molten cylindrical region that is created by the energetic ion. Vacancies are created at the recrystallization front, resulting in excess atoms at the core which form interstitial dislocation loops on completion of crystallization. These unique defect structures could, potentially, be used to create metal films with superior mechanical properties and interesting nanostructures.

The influence of the electronic specific heat on swift heavy ion irradiation simulations of silicon.

The swift heavy ion (SHI) irradiation of materials is often modelled using the two-temperature model. While the model has been successful in describing SHI damage in metals, it fails to account for the presence of a bandgap in semiconductors and insulators. Here we explore the potential to overcome this limitation by explicitly incorporating the influence of the bandgap in the parameterisation of the electronic specific heat for Si. The specific heat as a function of electronic temperature is calculated using finite temperature density functional theory with three different exchange correlation functionals, each with a characteristic bandgap. These electronic temperature dependent specific heats are employed with two-temperature molecular dynamics to model ion track creation in Si. The results obtained using a specific heat derived from density functional theory showed dramatically reduced defect creation compared to models that used the free electron gas specific heat. As a consequence, the track radii are smaller and in much better agreement with experimental observations. We also observe a correlation between the width of the band gap and the track radius, arising due to the variation in the temperature dependence of the electronic specific heat.

Cold atmospheric pressure plasma and decontamination. Can it contribute to preventing hospital-acquired infections?

Healthcare-associated infections (HCAIs) affect ∼4.5 million patients in Europe alone annually. With the ever-increasing number of 'multi-resistant' micro-organisms, alternative and more effective methods of environmental decontamination are being sought as an important component of infection prevention and control. One of these is the use of cold atmospheric pressure plasma (CAPP) systems with clinical applications in healthcare facilities. CAPPs have been shown to demonstrate antimicrobial, antifungal and antiviral properties and have been adopted for other uses in clinical medicine over the past decade. CAPPs vary in their physical and chemical nature depending on the plasma-generating mechanism (e.g. plasma jet, dielectric barrier discharge, etc.). CAPP systems produce a 'cocktail' of species including positive and negative ions, reactive atoms and molecules (e.g. atomic oxygen, ozone, superoxide and oxides of nitrogen), intense electric fields, and ultraviolet radiation (UV). The effects of these ions have been studied on micro-organisms, skin, blood, and DNA; thus, a range of possible applications of CAPPs has been identified, including surface decontamination, wound healing, biofilm removal, and even cancer therapy. Here we evaluate plasma devices, their applications, mode of action and their potential role specifically in combating HCAIs on clinical surfaces.

Oral hairy leukoplakia in healthy, immunocompetent individuals.

Oral hairy leukoplakia (OHL), while typically associated with HIV infection and immunosuppression, is rarely seen in HIV negative immunocompetent individuals. We report on two cases of OHL in immunocompetent patients.

Air and surface contamination patterns of meticillin-resistant Staphylococcus aureus on eight acute hospital wards.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) can be recovered from hospital air and from environmental surfaces. This poses a potential risk of transmission to patients. AIM: To investigate associations between MRSA isolates recovered from air and environmental surfaces with those from patients when undertaking extensive patient and environmental sampling. METHODS: This was a prospective observational study of patients and their environment in eight wards of a 700-bed tertiary care hospital during 2010 and 2011. Sampling of patients, air and surfaces was carried out on all ward bays, with more extended environmental sampling in ward high-dependency bays and at particular times of the day. The genetic relatedness of isolates was determined by DNA microarray profiling and spa typing. FINDINGS: MRSA was recovered from 30/706 (4.3%) patients and from 19/132 (14.4%) air samples. On 9/132 (6.8%) occasions both patient and air samples yielded MRSA. In 32 high-dependency bays, MRSA was recovered from 12/161 (7.4%) patients, 8/32 (25%) air samples, and 21/644 (3.3%) environmental surface samples. On 10/132 (7.6%) occasions, MRSA was isolated from air in the absence of MRSA-positive patients. Patient demographic data combined with spa typing and DNA microarray profiling revealed four likely transmission clusters, where patient and environmental isolates were deemed to be very closely related. CONCLUSION: Air sampling yielded MRSA on frequent occasions, especially in high-dependency bays. Environmental and air sampling combined with patient demographic data, spa typing and DNA microarray profiling indicated the presence of clusters that were not otherwise apparent.

The antimicrobial effects of helium and helium-air plasma on Staphylococcus aureus and Clostridium difficile.

UNLABELLED: Healthcare-associated infections (HCAI) affect 5-10% of acute hospital admissions. Environmental decontamination is an important component of all strategies to prevent HCAI as many bacterial causes survive and persist in the environment, which serve as ongoing reservoirs of infection. Current approaches such as cleaning with detergents and the use of chemical disinfectant are suboptimal. We assessed the efficacy of helium and helium-air plasma in killing Staphylococcus aureus and Clostridium difficile on a glass surface and studied the impact on bacterial cells using atomic force microscopy (AFM). Both plasma types exhibited bactericidal effects on Staph. aureus (log3·6 - >log7), with increased activity against methicillin-resistant strains, but had a negligible effect on Cl. difficile spores (<1log). AFM demonstrated cell surface disruption. The addition of air increased the microbicidal activity of the plasma and decreased the exposure time required for an equivalent log reduction. Further evaluation of cold plasma systems is warranted with, for example, different bacteria and on surfaces more reminiscent of the health care environment as this approach has potential as an effective decontaminant. SIGNIFICANCE AND IMPACT OF THE STUDY: Many bacterial causes of healthcare infection can survive in the inanimate environment for lengthy periods and be transmitted to patients. Furthermore, current methods of environmental decontamination such as detergents, chemical disinfectants or gaseous fumigation are suboptimal for a variety of reasons. We assessed the efficacy of helium and helium-air plasma as a decontaminant and demonstrated a significant reduction in bacterial counts of Staphylococcus aureus on a glass surface. Atomic force microscopy morphologically confirmed the impact on bacterial cells. This approach warrants further study as an alternative to current options for hospital hygiene.

Deprivation as an outcome determinant in emergency medical admissions.

BACKGROUND: Deprivation in the general population predicts mortality. We have investigated its relevance to an acute medical admission, using a database of all emergency admissions to St James' Hospital, Dublin, over a 10-year period (2002-11). METHODS: All emergency admissions, based on geocoding of residence, were allocated to a Small Area Health Research Unit division, with a corresponding deprivation index. We then examined this index as a univariate (unadjusted) and independent (adjusted) predictor of 30-day in-hospital mortality. RESULTS: The 30-day in-hospital mortality, over the 10-year period, was higher for those in the upper half of the deprivation distribution (9.6 vs. 8.6%; P = 0.002). Indeed, there was a stepwise increase in 30-day mortality over the quintiles of deprivation from 7.3% (Quintile 1) to 8.8, 10.0, 10.0 and 9.3%, respectively. Univariate logistic regression of the deprivation indices (quintiles) against outcome showed an increased risk (P = 0.002) of a 30-day death with odds ratios (ORs), respectively (compared with lowest deprivation quintile) of 1.39 [95% confidence intervals (CI) 1.21, 1.58], 1.47 (95% CI 1.29, 1.68), 1.44 (95% CI 1.26, 1.64) and 1.39 (95% CI 1.22, 1.59). The deprivation index was an independent predictor of outcome in a model when adjusted for illness severity and co-morbidity. The fully adjusted OR for a 30-day death was increased by 31% (P = 0.001) for patients in the upper half of the deprivation index distribution (OR 1.35; 95% CI 1.23, 1.48; P < 0.001). CONCLUSION: Deprivation, independent of co-morbidity or acute illness severity, is an independent predictor of 30-day mortality in acute medical admissions.

Microbial monitoring of the hospital environment: why and how?

BACKGROUND: The purpose of microbial monitoring of the inanimate environment surrounding a patient can be two-fold; to monitor hygiene standards and also to examine for the presence of specific nosocomial pathogens which may be the source of an outbreak. While both purposes involve routine culture of microorganisms, the methods used for each can differ in order to provide optimal results. The main difference between both purposes is the need for enumeration, site specificity for an aerobic colony count (ACC) for hygiene assessments, and the need to simply detect the presence or absence of multi-resistant nosocomial pathogens for infection control surveillance. AIM: To access current methods used in research studies and during outbreak investigations to detect nosocomial pathogens in the inanimate environment in the clinical setting. METHODS: A Pubmed search of published literature was performed. FINDINGS: Microbial monitoring of the environment can involve the use of swabs, sponges, contact plates and dip slides coupled with a variety of enrichment broths and selective media. The use of molecular methods such as polymerase chain reaction (PCR) can potentially provide a faster turnaround time, resulting in the quicker implementation of infection prevention and control cleaning and disinfection regimens. However, the optimal methods for performing a microbial hygiene evaluation or detecting specific bacterial pathogens are not generally agreed. CONCLUSION: There is a need for agreed standards on the optimal methods, frequency of environmental sampling and acceptable levels of surface contamination within the healthcare system.

Total arterial coronary artery bypass grafting in patients with diabetes: an 8-year experience.

OBJECTIVE: Coronary artery bypass grafting using arterial conduits may improve survival and minimise harvest site complications. However, in diabetes, the outcomes of coronary artery bypass grafting performed exclusively using arterial conduits are uncertain. We reviewed our experience with this approach. METHODS: From 1996 to 2008, 400 patients with diabetes (managed with oral hypoglycaemics, insulin or both) underwent primary isolated coronary artery bypass grafting for triple vessel coronary disease. In 246 (61.5%), total arterial revascularisation was achieved using single or bilateral internal thoracic arteries supplemented by one or more radial arteries (arterial group), while in the remaining 154 (38.5%), at least one venous conduit was used (mixed conduits group: mean 1.5 veins per patient). Propensity-score matching was used to adjust for bias. RESULTS: Total arterial revascularisation patients were more likely to be younger (arterial: 63 ± 10 years vs mixed: 67 ± 10 years, P < 0.0001), of elective priority (85% vs 75%, P = 0.018) and less likely to have moderate-severe left ventricular dysfunction (23% vs 36%, P = 0.024). Use of bilateral internal thoracic arteries was similar between groups (16% vs 11%, P = 0.19). There was a comparable in-hospital mortality (1.9% vs 2.0%, P > 0.99) and major morbidities, except the arterial group who experienced less stroke (0.4% vs 3.2% vs P = 0.04) and harvest site infections (0.4% vs 4%, P = 0.016). Mean follow was 7.8 ± 3.7 years. Estimated survival at 12-year survival in the arterial group was 80% ± 3.2% vs 54% ± 5.5% (P < 0.0001). Subsequently, 103 propensity-score-matched patient pairs were created between the two groups. After matching, in-hospital mortality (1% vs 2%, P > 0.99) and major morbidities were similar, as was an estimated 12-year survival (69% ± 6.1% vs 59% ± 6.5%, P > 0.99). CONCLUSIONS: The use of veins to supplement arterial conduits did not deleteriously affect survival. However, the significant number of patients receiving arterial grafts in both groups may have masked any potential difference. Greater numbers and longer follow-up will reveal the potential of this approach.

Evaluation of vaporized hydrogen peroxide, Citrox and pH neutral Ecasol for decontamination of an enclosed area: a pilot study.

Hydrogen peroxide, Ecasol and Citrox aerosols were each tested for their ability to kill a range of nosocomial pathogens. Hydrogen peroxide had the broadest microbicidal activity but operational issues limit its use. Ecasol was effective against all micro-organisms, except Clostridium difficile, while Citrox aerosols were not effective against Gram-negative bacilli.

Effects of age and coronary artery disease on cerebrovascular reactivity to carbon dioxide in humans.

Alterations in cerebrovascular reactivity to CO2, an index of cerebrovascular function, have been associated with increased risk of stroke. We hypothesised that cerebrovascular reactivity is impaired with increasing age and in patients with symptomatic coronary artery disease (CAD). Cerebrovascular and cardiovascular reactivity to CO2 was assessed at rest and during hypercapnia (5% CO2) and hypocapnia (hyperventilation) in subjects with symptomatic CAD (n=13) and age-matched old (n=9) and young (n=20) controls without CAD. Independent of CAD, reductions in middle cerebral artery blood velocity (transcranial Doppler) and cerebral oxygenation (near-infrared spectroscopy) were correlated with increasing age (r = -0.68, r = -0.51, respectively, P < 0.01). In CAD patients, at rest and during hypercapnia, cerebral oxygenation was lower (P < 0.05 vs. young). Although middle cerebral artery blood velocity reactivity was unaltered in the hypercapnic range, middle cerebral artery blood velocity reactivity to hypocapnia was elevated in the CAD and age-matched controls (P < 0.01 vs. young), and was associated with age (r = 0.62, P < 0.01). Transient drops in arterial PCO2 occur in a range of physiological and pathophysiological situations, therefore, the elevated middle cerebral artery blood velocity reactivity to hypocapnia combined with reductions in middle cerebral artery blood velocity may be important mechanisms underlying neurological risk with aging. In CAD patients, additional reductions in cerebral oxygenation may place them at additional risk of cerebral ischaemia.

Cocaine-related admissions to an intensive care unit: a five-year study of incidence and outcomes.

Cocaine misuse is increasing and it is evidently considered a relatively safe drug of abuse in Ireland. To address this perception, we reviewed the database of an 18-bed Dublin intensive care unit, covering all admissions from 2003 to 2007. We identified cocaine-related cases, measuring hospital mortality and long-term survival in early 2009. Cocaine-related admissions increased from around one annually in 2003-05 to 10 in 2007. Their median (IQR [range]) age was 25 (21-35 [17-47]) years and 78% were male. The median (IQR [range]) APACHE II score was 16 (11-27 [5-36]) and length of intensive care stay was 5 (3-9 [1-16]) days. Ten patients died during their hospital stay. A further five had died by the time of follow-up, a median of 24 months later. One was untraceable. Cocaine toxicity necessitating intensive care is increasingly common in Dublin. Hospital mortality in this series was 52%. These findings may help to inform public attitudes to cocaine.

Identical pattern of cerebral hypoperfusion during different types of syncope.

Syncope is caused by insufficient oxygen supply to the brain. There have been attempts to classify syncope on the basis of defects in the venous system, arterial system (that is impaired systemic vascular resistance) or a combination of the two (that is mixed). We examined the hypothesis that a comparable decrease in cerebral perfusion would be evident at pre-syncope irrespective of the category of dysfunction. Young healthy volunteers (N=37) participated. The protocol consisted of 15 min supine rest, followed by 60 degrees head-up tilt and lower body suction in increments of -10 mm Hg for 5 min each until pre-syncope. Beat-to-beat blood pressure (BP) (Finometer or intra-arterial), cardiac output (Finometer), middle cerebral artery blood velocity (MCAv), end-tidal CO(2) and cerebral oxygenation were monitored continuously. At pre-syncope, mixed dysfunction was common (21 out of 37 participants), followed by venular dysfunction (15 out of 37 participants). In the venular and mixed groups, comparable orthostatic tolerance and declines in BP (-37 vs -43% from baseline, respectively), end-tidal PCO(2), MCAv (-35 vs -38%) and cerebral oxygenation (-5 vs -7%) were evident despite distinct mechanisms purportedly being responsible for the hypotension. Although different determinants of hypotension do exist, cerebral hypoperfusion occurs to a similar extent.