Multimorbidity among persons aged 25-64 years: a population-based study of social determinants and all-cause mortality.

BACKGROUND: Despite increasing multimorbidity across the lifespan, little is known about the co-occurrence of conditions and risk factors among younger adults. This population-based study examines multimorbidity, social determinants and associated mortality among younger and middle-age adults. METHOD: Analysis was based on the Northern Ireland population aged 25-64 years enumerated in the 2011 Census (n = 878 345), with all-cause mortality follow-up to 2014 (8659 deaths). Logistic regression was used to examine social determinants and Cox proportional hazards models in the analysis of associated mortality. RESULTS: Prevalence of multimorbidity was 13.7% in females and 12.7% in males. There was a strong association between multimorbidity that included mental/cognitive illness and deprivation. Among those never married, multimorbid physical conditions were less likely [relative risk ratios (RRR) = 0.92: 95% confidence interval (CI) = 0.88, 0.95 for males; and RRR = 0.90: 0.87, 0.94 for females]. Rurality was associated with lower physical multimorbidity (RRR = 0.92: 0.89, 0.95) but higher mental/cognitive multimorbidity (RRR = 1.35: 1.12, 1.64) among females. All multimorbid categories were associated with elevated risk of mortality. CONCLUSION: The health and economic challenges created by multimorbidity should be addressed further 'upstream'. Future multimorbidity research should include younger adults to inform the development of preventative interventions and align health and social care services more closely with patients' needs.

Attitudes and Knowledge of Healthcare Professionals Regarding Organ Donation. A Survey of the Saolta University Health Care Group.

Organ donation saves lives and healthcare professionals (HCPs) play a vital role in that process. Therefore, the purpose of this study was to assess the attitudes and level of knowledge of HCPs regarding organ donation. An online anonymous self-administered questionnaire containing 40 questions on organ donation using google forms was created. The survey was distributed to HCPs working in the Saolta University Health Care Group. A hundred and thirty-nine responses were received giving a response rate of 11.8%. HCPs willingness to donate their organs was at 93% compared to 97% willing to receive a transplant. More HCPs understood or had knowledge of the term donation after brain death (64%) than donation after circulatory death (49%). HCPs working in intensive care knew more about the management of brain dead donors than other specialties (p<0.0001). Over 60% of HCPs when asked either disagreed or strongly disagreed with the adequacy of training in organ donation and transplant. Overall, HCPs surveyed had positive attitudes towards organ donation but there was a lack of knowledge particularly among non-intensive care professionals. This study highlights the need to increase awareness along with implementation of educational programmes among HCPs regarding organ donation and transplant.

Unmasking leading to a healthcare worker Mycobacterium tuberculosis transmission.

BACKGROUND: Mycobacterium tuberculosis is a major health burden worldwide. The disease may present as an individual case, community outbreak, or more rarely as a nosocomial outbreak. Even in countries with a low prevalence such as the UK, tuberculosis (TB) presents a risk to healthcare workers (HCWs). AIM: To report an outbreak which manifested 12 months after a patient with pulmonary tuberculosis was admitted to Queen Elizabeth Hospital Birmingham. METHODS: We present the epidemiological and outbreak investigations; the role of whole genome sequencing (WGS) in identifying the outbreak and control measures to prevent further outbreaks. FINDINGS: Subsequent to a diagnosis of open TB in a patient, transmission was confirmed in one HCW who had active TB; HCWs with latent TB infection (LTBI) were also identified among seven HCW contacts of the index patient. Of note, all the LBTI patients had other risk factors for TB. Routine use of WGS identified the outbreak link between the index patient and the HCW with active TB disease, and informed our investigations. CONCLUSION: Exposure most likely occurred during an aerosol-generating procedure (AGP) which was done in accordance with national guidance at that time without using respiratory protection. Enhanced control measures were implemented following the outbreak.

Videolaryngoscopy vs. fibreoptic bronchoscopy for awake tracheal intubation: a systematic review and meta-analysis.

Awake fibreoptic intubation is often considered the technique of choice when a difficult airway is anticipated. However, videolaryngoscopes are being used more commonly. We searched the current literature and performed a meta-analysis to compare the use of videolaryngoscopy and fibreoptic bronchoscopy for awake tracheal intubation. Our primary outcome was the time needed to intubate the patient's trachea. Secondary outcomes included: failed intubation; the rate of successful intubation at the first attempt; patient-reported satisfaction with the technique; and any complications resulting from intubation. Eight studies examining 429 patients were included in this review. The intubation time was shorter when videolaryngoscopy was used instead of fibreoptic bronchoscopy (seven trials, 408 participants, mean difference (95%CI) -45.7 (-66.0 to -25.4) s, p < 0.0001, low-quality evidence). There was no significant difference between the two techniques in the failure rate (six studies, 355 participants, risk ratio (95%CI) 1.01 (0.24-4.35), p = 0.99, low-quality evidence) or the first-attempt success rate (six studies, 391 participants, risk ratio (95%CI) 1.01 (0.95-1.06), p = 0.8, moderate quality evidence). The level of patient satisfaction was similar between both groups. No difference was found in two reported adverse events: hoarseness/sore throat (three studies, 167 participants, risk ratio (95%CI) 1.07 (0.62-1.85), p = 0.81, low-quality evidence), and low oxygen saturation (five studies, 337 participants, risk ratio (95%CI) 0.49 (0.22-1.12), p = 0.09, low-quality evidence). In summary, videolaryngoscopy for awake tracheal intubation is associated with a shorter intubation time. It also seems to have a success rate and safety profile comparable to fibreoptic bronchoscopy.

Not what it looks like: mate-searching behaviour, mate preferences and clutch production in wandering and territory-holding female fiddler crabs.

Risks inherent in mate-searching have led to the assumption that females moving sequentially through populations of courting males are sexually receptive, but this may not be true. We examined two types of fiddler crab females: wanderers moving through the population of courting males and residents that were occupying and defending their own territories. Sometimes residents leave territories to look for new burrows and we simulated this by displacing wanderers and residents and observing their behaviour while wandering. We predicted that the displaced wanderers would exhibit more mate-searching behaviours than resident females. However, wandering and resident females behaved nearly identically, displaying mate-searching behaviours and demonstrating matching mate preferences. Also, males behaved the same way towards both female types and similar proportions of wanderers and residents stayed in a male's burrow to mate. But more wanderers than residents produced egg clutches when choosing a burrow containing a male, suggesting females should be categorized as receptive and non-receptive. Visiting and rejecting several males is not the defining feature of female mate choice. Moving across the mudflat by approaching and leaving a succession of burrows (mostly occupied by males) is an adaptive anti-predator behaviour that is useful in the contexts of mate-searching and territory-searching.

Acceptability of temporary suspension of visiting during norovirus outbreaks: investigating patient, visitor and public opinion.

BACKGROUND: Noroviruses are a leading cause of outbreaks globally and the most common cause of service disruption due to ward closures. Temporary suspension of visiting (TSV) is increasingly a recommended public health measure to reduce exposure, transmission and impact during norovirus outbreaks; however, preventing patient-visitor contact may contravene the ethos of person-centred care, and public acceptability of this measure is not known. AIM: To investigate the acceptability of TSV during norovirus outbreaks from the perspectives of patients, visitors and the wider public. METHODS: Cross-sectional survey of patients (N = 153), visitors (N = 175) and the public (N = 224) in three diverse areas in Scotland. Health Belief Model constructs were applied to understand ratings of acceptability of TSV during norovirus outbreaks, and to determine associations between these levels and various predictor variables. FINDINGS: The majority (84.6%) of respondents indicated that the possible benefits of TSV are greater than the possible disadvantages. Conversely, the majority (70%) of respondents disagreed that TSV 'is wrong as it ignores people's rights to have contact with family and friends'. The majority (81.6%) of respondents agreed that TSV would be more acceptable if exceptions were made for seriously ill or dying patients. Correlational analysis demonstrated that overall acceptability was positively related to perceived severity (r = 0.65), identified benefits (r = 0.54) and implementing additional communication strategies (r = 0.60); acceptability was negatively related to potential barriers (r = -0.49). CONCLUSIONS: There is greater service user and public support for the use of TSV than concerns around impinging upon patients' rights to have visitors. TSV should be considered as an acceptable infection control measure that could be implemented consistently during norovirus outbreaks.

Temporary suspension of visiting during norovirus outbreaks in NHS Boards and the independent care home sector in Scotland: a cross-sectional survey of practice.

BACKGROUND: Norovirus outbreaks cause significant patient distress and adversely affect healthcare service delivery. Measures to manage outbreaks include controlling patient/staff movement and advising visitors of the risks of infection; temporary suspension of visiting (TSV) is advocated by some. Factors influencing the use of TSV have not previously been reported. AIM: To describe current practice in Scotland regarding TSV during norovirus outbreaks. METHODS: Cross-sectional survey of Scottish Health Boards [National Health Service (NHS)] Infection Prevention Leads (N = 22) and independent care home (ICH) managers (N = 107). FINDINGS: TSV practice is inconsistent across care settings. NHS findings: although 86.4% reported a recent norovirus outbreak, only 36.4% reported having criteria in place to guide TSV decisions and only 57.9% of those who had an outbreak implemented TSV. Conversely, 77.6% ICH respondents do have TSV criteria in place; 70.1% who had previously experienced an outbreak all reported that they would normally close to visitors. The majority of both NHS (81.8%) and ICH (84.2%) respondents reported making exceptions to TSV for individual cases. Despite variation in practice, 75% NHS and 81.8% ICH respondents agreed that TSV was helpful in controlling outbreaks. Factors influencing TSV implementation decisions included use of judgement in individual cases, perceived lack of evidence for the role of visitors in transmission, and belief in patients' rights to have visitors. CONCLUSION: Implementation of TSV in Scotland is inconsistent, with variation in the use of criteria, personal beliefs, and professional judgements. Further research on the role of visitors in transmission and service-user acceptability of TSV is required for policy development.

Historical outbreak of Salmonella hadar.

BACKGROUND: This article reports a historical outbreak of Salmonella hadar in a maternity setting. The outbreak occurred following admission of an infected index case, with transmission to 11 other individuals over a three-month period in a maternity and neonatal unit. METHODS: Despite rigorous assessment of clinical practices, screening of patients and staff, and review of disinfection and sterilization policies, the outbreak was difficult to control. This possibly reflects the capacity of S. hadar to survive well in the environment, and cause prolonged and asymptomatic carriage with intermittent shedding. FINDINGS: It is likely that the index case was a mother who had contracted infection after eating suspect food. Additionally, infection may have been perpetuated by shared use of tubes of yellow soft paraffin for lubrication of digital rectal thermometers. CONCLUSION: This outbreak emphasizes the difficulties in controlling outbreaks of S. hadar infection in an obstetric/neonatal setting, and also emphasizes the importance of early stool sampling in any patient with diarrhoeal symptoms.

Experimental Support for a Single Electron-Transfer Oxidation Mechanism in Firefly Bioluminescence.

Firefly luciferase produces light by converting substrate beetle luciferin into the corresponding adenylate that it subsequently oxidizes to oxyluciferin, the emitter of bioluminescence. We have confirmed the generally held notions that the oxidation step is initiated by formation of a carbanion intermediate and that a hydroperoxide (anion) is involved. Additionally, structural evidence is presented that accounts for the delivery of oxygen to the substrate reaction site. Herein, we report key convincing spectroscopic evidence of the participation of superoxide anion in a related chemical model reaction that supports a single electron-transfer pathway for the critical oxidative process. This mechanism may be a common feature of bioluminescence processes in which light is produced by an enzyme in the absence of cofactors.

A Photinus pyralis and Luciola italica chimeric firefly luciferase produces enhanced bioluminescence.

We report the enhanced bioluminescence properties of a chimeric enzyme (PpyLit) that contains the N-domain of recombinant Photinus pyralis luciferase joined to the C-domain of recombinant Luciola italica luciferase. Compared to the P. pyralis enzyme, the novel PpyLit chimera exhibited 1.8-fold enhanced flash-height specific activity, 2.0-fold enhanced integration-based specific activity, 2.9-fold enhanced catalytic efficiency (kcat/Km), and a 1.4-fold greater bioluminescence quantum yield. The results of this study provide an underlying basis of this unusual example of a chimeric enzyme with enhanced catalytic properties that are not simply the sum of the contributions of the two luciferases.

Chemical Analysis of the Luminous Slime Secreted by the Marine Worm Chaetopterus (Annelida, Polychaeta).

The marine annelid Chaetopterus variopedatus produces bioluminescence by an unknown and potentially novel mechanism. We have advanced the study of this fascinating phenomenon, which has not been investigated for nearly 60 years after initial studies were first reported for this species. Here, we show that the luminous slime produced by the worm exhibits blue fluorescence that matches the bioluminescence emission. This result suggests that the oxyluciferin emitter is present. However, while the blue fluorescence decays over time green fluorescence is increasingly revealed that is likely associated with products of the luminescence reaction. LC/MS and fluorescence analysis of harvested luminescent material revealed riboflavin as the major green fluorescent component. Riboflavin is usually associated with the mechanism of light production in bacteria, yet luminous bacteria were not found in the worm mucus, and accordingly were not reported to be directly responsible for the light emission, which is under nervous control in the worm. We therefore propose a hypothesis in which riboflavin or a structurally related derivative serves as the emitter in the worm's light producing reaction.

The outcome competency framework for practitioners in infection prevention and control: use of the outcome logic model for evaluation.

Healthcare is delivered in a dynamic environment with frequent changes in populations, methods, equipment and settings. Infection prevention and control practitioners (IPCPs) must ensure that they are competent in addressing the challenges they face and are equipped to develop infection prevention and control (IPC) services in line with a changing world of healthcare provision. A multifaceted Framework was developed to assist IPCPs to enhance competence at an individual, team and organisational level to enable quality performance and improved quality of care. However, if these aspirations are to be met, it is vital that competency frameworks are fit for purpose or they risk being ignored. The aim of this unique study was to evaluate short and medium term outcomes as set out in the Outcome Logic Model to assist with the evaluation of the impact and success of the Framework. This study found that while the Framework is being used effectively in some areas, it is not being used as much or in the ways that were anticipated. The findings will enable future work on revision, communication and dissemination, and will provide intelligence to those initiating education and training in the utilisation of the competences.

Novel heterocyclic analogues of firefly luciferin.

Five novel firefly luciferin analogues in which the benzothiazole ring system of the natural substrate was replaced with benzimidazole, benzofuran, benzothiophene, benzoxazole, and indole were synthesized. The fluorescence, bioluminescence, and kinetic properties of the compounds were evaluated with recombinant Photinus pyralis wild type luciferase. With the exception of indole, all of the substrates containing heterocycle substitutions produced readily measurable flashes of light with luciferase. Compared to that of luciferin, the intensities ranged from 0.3 to 4.4% in reactions with varying pH optima and times to reach maximal intensity. The heteroatom changes influenced both the fluorescence and bioluminescence emission spectra, which displayed maxima of 479-528 and 518-574 nm, respectively. While there were some interesting trends in the spectroscopic and bioluminescence properties of this group of structurally similar substrate analogues, the most significant findings were associated with the benzothiophene-containing compound. This synthetic substrate produced slow decay glow kinetics that increased the total light-based specific activity of luciferase more than 4-fold versus the luciferin value. Moreover, over the pH range of 6.2-9.4, the emission maximum is 523 nm, an unusual 37 nm blue shift compared to that of the natural substrate. The extraordinary bioluminescence properties of the benzothiophene luciferin should translate into greater sensitivity for analyte detection in a wide variety of luciferase-based applications.

Using a PDSA cycle of improvement to increase preparedness for, and management of, norovirus in NHS Scotland.

BACKGROUND: The 2009-2010 norovirus season was reported anecdotally by infection prevention and control teams (IPCTs) to be one of the worst seasons in Scotland. At its peak, Health Protection Scotland's (HPS) weekly point prevalence identified that 53 wards were closed. AIM: To develop an annual cycle of learning lessons and improving systems to reduce the impact and incidence of norovirus outbreaks in Scotland. METHODS: An analysis of two end-of-year norovirus season evaluations (2009-2010 and 2010-2011) by IPCTs in Scotland using a national Plan, Do, Study, Act (PDSA) model. FINDINGS: The first evaluation (2009-2010) identified that IPCTs responded well when outbreaks were reported, but were not optimally prepared for the season. In addition, IPCTs had little data to describe their particular problems in detail. HPS planned for the 2010-2011 season with tools to optimize preparedness and norovirus management. The second evaluation (2010-2011) identified much more proactive responses to both preparedness and norovirus management. CONCLUSION: This national PDSA cycle has led to system improvements designed to reduce the incidence and impact of norovirus in NHS Scotland. The incidence of norovirus was reduced in the 2011-2012 season; however, confounding from the variation in circulating viruses makes it difficult to measure any effect of the system improvements. As noroviruses challenge the health service every year, mainly in winter months, the end-of-season evaluations can be used to improve planning for subsequent seasons to share and demonstrate good practice. As more years of data become available for analysis, the impact of system improvements will become measurable.

Bioluminescence is produced from a trapped firefly luciferase conformation predicted by the domain alternation mechanism.

According to the domain alternation mechanism and crystal structure evidence, the acyl-CoA synthetases, one of three subgroups of a superfamily of adenylating enzymes, catalyze adenylate- and thioester-forming half-reactions in two different conformations. The enzymes accomplish this by presenting two active sites through an ~140° rotation of the C-domain. The second half-reaction catalyzed by another subgroup, the beetle luciferases, is a mechanistically dissimilar oxidative process that produces bioluminescence. We have demonstrated that a firefly luciferase variant containing cysteine residues at positions 108 and 447 can be intramolecularly cross-linked by 1,2-bis(maleimido)ethane, trapping the enzyme in a C-domain-rotated conformation previously undocumented in the available luciferase crystal structures. The cross-linked luciferase cannot adenylate luciferin but is nearly fully capable of bioluminescence with synthetic luciferyl adenylate because it retains the ability to carry out the oxidative half-reaction. The cross-linked luciferase is apparently trapped in a conformation similar to those adopted by acyl-CoA synthetases as they convert acyl adenylates into the corresponding CoA thioesters.

CD8+ lymphocyte depletion without SIV infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain.

BACKGROUND: Simian immunodeficiency virus (SIV) infection and persistent CD8(+) lymphocyte depletion rapidly leads to encephalitis and neuronal injury. The objective of this study is to confirm that CD8 depletion alone does not induce brain lesions in the absence of SIV infection. METHODS: Four rhesus macaques were monitored by proton magnetic resonance spectroscopy ((1) H-MRS) before and biweekly after anti-CD8 antibody treatment for 8 weeks and compared with four SIV-infected animals. Post-mortem immunohistochemistry was performed on these eight animals and compared with six uninfected, non-CD8-depleted controls. RESULTS: CD8-depleted animals showed stable metabolite levels and revealed no neuronal injury, astrogliosis or microglial activation in contrast to SIV-infected animals. CONCLUSIONS: Alterations observed in MRS and lesions in this accelerated model of neuroAIDS result from unrestricted viral expansion in the setting of immunodeficiency rather than from CD8(+) lymphocyte depletion alone.