Trends in viable microbial bioburden on surfaces within a paediatric bone marrow transplant unit.

BACKGROUND: Despite their role being historically overlooked, environmental surfaces have been shown to play a key role in the transmission of pathogens causative of healthcare-associated infection. To guide infection prevention and control (IPC) interventions and inform clinical risk assessments, more needs to be known about microbial surface bioburdens. AIM: To identify the trends in culturable bacterial contamination across communal touch sites over time in a hospital setting. METHODS: Swab samples were collected over nine weeks from 22 communal touch sites in a paediatric bone marrow transplant unit. Samples were cultured on Columbia blood agar and aerobic colony counts (ACC) per 100 cm2 were established for each site. Individual colony morphologies were grouped and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or 16s rDNA sequencing. FINDINGS: Highest mean counts were observed for sites associated with ward management activity and computer devices (3.29 and 2.97 ACC/100 cm2 respectively). A nurses' station keyboard had high mean ACC/100 cm2 counts (10.67) and diversity, while laundry controls had high mean ACC/100 cm2 counts (4.70) and low diversity. Micrococcus luteus was identified in all sampling groups. Clinical staff usage sites were contaminated with similar proportions of skin and environmental flora (52.19-46.59% respectively), but sites associated with parental activities were predominantly contaminated by environmental microflora (86.53%). CONCLUSION: The trends observed suggest patterns in microbial loading based on site activities, surface types and user groups. Improved understanding of environmental surface contamination could help support results interpretation and IPC interventions, improving patient safety.

How long do nosocomial pathogens persist on inanimate surfaces? A scoping review.

Healthcare hygiene plays a crucial role in the prevention of healthcare-associated infections. Patients admitted to a room where the previous occupant had a multi-drug-resistant bacterial infection are at an increased risk of colonization and infection with the same organism. A 2006 systematic review by Kramer et al. found that certain pathogens can survive for months on dry surfaces. The aim of this review is to update Kramer et al.'s previous review and provide contemporary data on the survival of pathogens relevant to the healthcare environment. We systematically searched Ovid MEDLINE, CINAHL and Scopus databases for studies that described the survival time of common nosocomial pathogens in the environment. Pathogens included in the review were bacterial, viral, and fungal. Studies were independently screened against predetermined inclusion/exclusion criteria by two researchers. Conflicts were resolved by one of two senior researchers. A spreadsheet was developed for the data extraction. The search identified 1736 studies. Following removal of duplicates and application of the search criteria, the synthesis of results from 62 included studies were included. 117 organisms were reported. The longest surviving organism reported was Klebsiella pneumoniae which was found to have persisted for 600 days. Common pathogens of concern to infection prevention and control, can survive or persist on inanimate surfaces for months. This data supports the need for a risk-based approach to cleaning and disinfection practices, accompanied by appropriate training, audit and feedback which are proven to be effective when adopted in a 'bundle' approach.

Military service and alcohol use: a systematic narrative review.

BACKGROUND: Despite research highlighting the role of alcohol in military life, specifically in relation to mental health and certain combat experiences, there is no synthesised evidence looking at the relationship between military service and alcohol use. AIMS: To synthesize and examine evidence exploring the relationship between military service and alcohol use. METHODS: Six databases were examined across a 10-year period. Papers were included if they involved a military population and focused on alcohol use. From 4046 papers identified, 29 papers were included in the review. RESULTS: Military characteristics and experience were linked to high levels of alcohol use across military populations. Societal and cultural factors also played a role in alcohol use in military populations. Predatory behaviour of alcohol establishments, pressures to conform, an acceptance of alcohol use, and the role of religious services and military affiliated social networks were all considered. Excessive drinking impacted physical and mental health. Those diagnosed with PTSD and associated symptoms appeared to have greater alcohol use. CONCLUSIONS: This review identified certain characteristics and experiences of military service that are associated with higher levels of alcohol use. It is important to identify risk factors for alcohol misuse to develop appropriate policy, targeting prevention.

Review of decontamination protocols for shared non-critical objects in 35 policies of UK NHS acute care organizations.

BACKGROUND: Decontamination of non-critical objects shared by patients is key in reducing hospital-acquired infections (HAIs), but it is a complex process that needs precise guidance from UK National Health Service (NHS) acute care organizations (ACOs). AIM: To review the indications given by NHS ACOs' policies regarding the decontamination of shared non-critical devices. METHODS: Detailed lists of decontamination protocols for shared non-critical objects were retrieved from cleaning, disinfection and decontamination policies of 35 NHS ACOs. Three parameters were considered for each object: decontamination method, decontamination frequency, and person responsible for decontamination. FINDINGS: In total, 1279 decontamination protocols regarding 283 different shared non-critical objects were retrieved. Of these, 689 (54%) did not indicate the person responsible for decontamination, and only 425 (33%) were complete, giving indications for all three parameters analysed. Only 2.5% (32/1279) of decontamination protocols were complete and identical in two policies. In policies where cleaning represented the major decontamination method, chemical disinfection was rarely mentioned and vice versa. General agreement among policies was found for four main decontamination methods (detergent and water, detergent wipes, disinfectant wipes, and use of disposable items), two decontamination frequencies (between events and daily) and two responsible person designations (nurses and domestic staff). CONCLUSIONS: Decontamination protocol policies for shared non-critical objects had some similarities but did not concur on how each individual object should be decontaminated. The lack of clear indications regarding the person responsible for the decontamination process put at risk the ability of policies to serve as guidance.

Assessment of the microbial load of airway clearance devices used by a cohort of children with cystic fibrosis.

BACKGROUND: Positive expiratory pressure (PEP) devices are an important element of the management of cystic fibrosis, and of other respiratory diseases. Whereas there have been reports in the literature of contamination of airway clearance devices and their surfaces by microbial pathogens, there is little evidence available regarding such contamination and its contribution to respiratory infection. AIM: To establish whether pathogenic bacteria can contaminate PEP devices in the context of normal cleaning and maintenance practices. METHODS: Patients' home-use clearance devices were brought to a routine clinic appointment and collected for microbiology sampling and analysis. The patients were provided with replacement devices. Nineteen such devices were collected from 17 patients, reflecting use of multiple devices by some patients. Swabs were taken and cultured from each patient's used device, the patient's airway, as well as from new unopened and unused devices that acted as controls. RESULTS: Seven of 19 devices (37%) tested positive for presence of pathogenic bacteria. Device-cleaning methods varied among patients and non-sterilization methods were found to be ineffective at removing pathogens. Microbial species found on the devices did not correlate with those identified from airway swabs. CONCLUSION: This study demonstrates the presence of pathogens on positive expiratory pressure devices. The potential for transmission of these pathogens to the patient's airway and the risk of infection remains unclear and requires further study.

The cost-effectiveness of temporary single-patient rooms to reduce risks of healthcare-associated infection.

BACKGROUND: The use of single rooms for patient isolation often forms part of a wider bundle to prevent certain healthcare-associated infections (HAIs) in hospitals. Demand for single rooms often exceeds what is available and the use of temporary isolation rooms may help resolve this. Changes to infection prevention practice should be supported by evidence showing that cost-effectiveness is plausible and likely. AIM: To perform a cost-effectiveness evaluation of adopting temporary single rooms into UK National Health Service (NHS) hospitals. METHODS: The cost-effectiveness of a decision to adopt a temporary, single-patient, isolation room to the current infection prevention efforts of an NHS hospital was modelled. Primary outcomes are the expected change to total costs and life-years from an NHS perspective. FINDINGS: The mean expected incremental cost per life-year gained (LYG) is £5,829. The probability that adoption is cost-effective against a £20,000 threshold per additional LYG is 93%, and for a £13,000 threshold the probability is 87%. The conclusions are robust to scenarios for key model parameters. If a temporary single-patient isolation room reduces risks of HAI by 16.5% then an adoption decision is more likely to be cost-effective than not. Our estimate of the effectiveness reflects guidelines and reasonable assumptions and the theoretical rationale is strong. CONCLUSION: Despite uncertainties about the effectiveness of temporary isolation rooms for reducing risks of HAI, there is some evidence that an adoption decision is likely to be cost-effective for the NHS setting. Prospective studies will be useful to reduce this source of uncertainty.

Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy.

Reactivation of Human Endogenous Retrovirus K (HERV-K), subtype HML-2, has been associated with pathophysiology of amyotrophic lateral sclerosis (ALS). We aimed to assess the efficacy of antiretroviral therapy in inhibiting HML-2 in patients with ALS and a possible association between the change in HML-2 levels and clinical outcomes. We studied the effect of 24-weeks antiretroviral combination therapy with abacavir, lamivudine, and dolutegravir on HML-2 levels in 29 ALS patients. HML-2 levels decreased progressively over 24 weeks (P = 0.001) and rebounded within a week of stopping medications (P = 0.02). The majority of participants (82%), defined as "responders", experienced a decrease in HML-2 at week 24 of treatment compared to the pre-treatment levels. Differences in the evolution of some of the clinical outcomes could be seen between responders and non-responders: FVC decreased 23.69% (SE = 11.34) in non-responders and 12.71% (SE = 8.28) in responders. NPI score decreased 91.95% (SE = 6.32) in non-responders and 53.05% (SE = 10.06) in responders (P = 0.01). Thus, participants with a virological response to treatment showed a trend for slower progression of the illness. These findings further support the possible involvement of HML-2 in the clinical course of the disease.

A Compound Heterozygous Mutation in Calpain 1 Identifies a New Genetic Cause for Spinal Muscular Atrophy Type 4 (SMA4).

Spinal Muscular Atrophy (SMA) is a heterogeneous group of neuromuscular diseases characterized by degeneration of anterior horn cells of the spinal cord, leading to muscular atrophy and weakness. Although the major cause of SMA is autosomal recessive exon deletions or loss-of-function mutations of survival motor neuron 1 (SMN1) gene, next generation sequencing technologies are increasing the genetic heterogeneity of SMA. SMA type 4 (SMA4) is an adult onset, less severe form of SMA for which genetic and pathogenic causes remain elusive.Whole exome sequencing in a 30-year-old brother and sister with SMA4 identified a compound heterozygous mutation (p. G492R/p. F610C) in calpain-1 (CAPN1). Mutations in CAPN1 have been previously associated with cerebellar ataxia and hereditary spastic paraplegia. Using skin fibroblasts from a patient bearing the p. G492R/p. F610C mutation, we demonstrate reduced levels of CAPN1 protein and protease activity. Functional characterization of the SMA4 fibroblasts revealed no changes in SMN protein levels and subcellular distribution. Additional cellular pathways associated with SMA remain unaffected in the patient fibroblasts, highlighting the tissue specificity of CAPN1 dysfunction in SMA4 pathophysiology. This study provides genetic and functional evidence of CAPN1 as a novel gene for the SMA4 phenotype and expands the phenotype of CAPN1 mutation disorders.

Cortical inexcitability defines an adverse clinical profile in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis, studies using threshold-tracking transcranial magnetic stimulation (TMS) have identified corticomotoneuronal dysfunction as a key pathogenic mechanism. Some patients, however, display no motor response at maximal TMS intensities, termed here an 'inexcitable' motor cortex. The extent to which this cortical difference impacts clinical outcomes remains unclear. The aim of this study was to determine the clinical profile of patients with inexcitability to TMS. METHODS: Motor cortex excitability was evaluated using TMS. Patients in whom a motor evoked potential could not be recorded in one or more limbs at maximal TMS intensities were classified as four-limb or partially inexcitable. Demographic information, clinical variables and survival data were analysed. RESULTS: From 133 patients, 40 were identified with inexcitability. Patients with four-limb inexcitability were younger (P = 0.03) and had lower-limb disease onset (64%), greater functional disability (P < 0.001) and faster disease progression (P = 0.02), particularly if inexcitability developed within 1 year of symptoms (P < 0.01). Patients with partial inexcitability had higher resting motor thresholds compared to the excitable cohort (P < 0.01), but averaged short-interval intracortical inhibition was similar (P = 0.5). Mean survival was reduced if inexcitability involved all limbs within 12 months of symptom onset (P = 0.04). CONCLUSION: Amyotrophic lateral sclerosis patients with inexcitability of all four limbs to TMS have a distinct clinical profile of younger age and lower-limb onset. Importantly, these patients display a more malignant disease trajectory, with faster progression, greater functional disability and reduced survival when occurring in early disease. This measure may provide an important prognostic marker in amyotrophic lateral sclerosis.

Role of circulating fibrocytes in the diagnosis of acute appendicitis.

BACKGROUND: Improved diagnostic biomarkers are required for acute appendicitis. The circulating fibrocyte percentage (CFP) is increased in inflammatory states, but has not been studied in acute appendicitis. This study aimed to determine CFP in acute appendicitis and compare diagnostic accuracy with standard serological biomarkers. METHODS: A prospective cohort study was carried out between June 2015 and February 2016 at University Hospital Limerick. The CFP was determined by dual-staining peripheral venous samples for CD45 and collagen I using fluorescence-activated cell sorting, and correlated with histopathological diagnoses. The accuracy of CFP in determining histological acute appendicitis was characterized and compared with the white cell count, C-reactive protein concentration, neutrophil count, lymphocyte count and neutrophil : lymphocyte ratio. RESULTS: Of 95 adults recruited, 15 were healthy individuals and 80 had suspected appendicitis at presentation. Forty-six of these 80 patients had an appendicectomy, of whom 34 had histologically confirmed appendicitis. The CFP was statistically higher in patients with pathologically proven acute appendicitis than in healthy controls (median 6·1 (i.q.r. 1·6-11·6) versus 2·3 (0·9-3·4) per cent respectively; P = 0·008). The diagnostic accuracy of CFP, as determined using the area under the receiver operating characteristic (ROC) curve, was similar to that of standard biomarkers. In multinomial regression analysis, only raised CFP was retained as an independent prognostic determinant of acute appendicitis (odds ratio 1·57, 95 per cent c.i. 1·05 to 2·33; P = 0·027). CONCLUSION: The CFP is increased in histologically confirmed acute appendicitis and is as accurate as standard serological biomarkers in terms of diagnosis.

Lysophosphatidylcholine acyltransferase 2 (LPCAT2) co-localises with TLR4 and regulates macrophage inflammatory gene expression in response to LPS.

Despite extensive investigations, an effective treatment for sepsis remains elusive and a better understanding of the inflammatory response to infection is required to identify potential new targets for therapy. In this study we have used RNAi technology to show, for the first time, that the inducible lysophosphatidylcholine acyltransferase 2 (LPCAT2) plays a key role in macrophage inflammatory gene expression in response to stimulation with bacterial ligands. Using siRNA- or shRNA-mediated knockdown, we demonstrate that, in contrast to the constitutive LPCAT1, LPCAT2 is required for macrophage cytokine gene expression and release in response to TLR4 and TLR2 ligand stimulation but not for TLR-independent stimuli. In addition, cells transfected to overexpress LPCAT2 exhibited increased expression of inflammatory genes in response to LPS and other bacterial ligands. Furthermore, we have used immunoprecipitation and Western blotting to show that in response to LPS, LPCAT2, but not LPCAT1, rapidly associates with TLR4 and translocates to membrane lipid raft domains. Our data thus suggest a novel mechanism for the regulation of inflammatory gene expression in response to bacterial stimuli and highlight LPCAT2 as a potential therapeutic target for development of anti-inflammatory and anti-sepsis therapies.

Social isolation and loneliness of UK veterans: a Delphi study.

BACKGROUND: Evidence increasingly acknowledges the impact of social isolation and loneliness on the lives of military veterans and the wider Armed Forces Community. AIMS: The study gathered expert consensus to (i) understand if veterans are considered 'unique' in their experiences of social isolation and loneliness; (ii) examine perceived factors leading to social isolation and loneliness of veterans; (iii) identify ways to tackle veterans' social isolation and loneliness. METHODS: This study adopted a three-phase Delphi method. Phase 1 utilized a qualitative approach and Phase 2 and Phase 3 utilized a mixed-methods approach. RESULTS: Several outcomes were identified across the three phases. Transition out of the military was viewed as a period to build emotional resilience and raise awareness of relevant services. It was also concluded that veterans would benefit from integrating into services within the wider community, and that social prescribing services could be a vehicle to link veterans to relevant services. Furthermore, access to, and the content of, programmes was also of importance. CONCLUSIONS: These findings illustrate various important interventional aspects to consider when funding and implementing programmes focussed on tackling social isolation and loneliness.

Changes in long term peripheral nerve biophysical properties in childhood cancer survivors following neurotoxic chemotherapy.

OBJECTIVE: In the context of increasing numbers of childhood cancer survivors (CCS), this study aimed to enhance understanding of the biophysical basis for long term chemotherapy induced peripheral neuropathy from different chemotherapy agents in CCS. METHODS: Detailed cross-sectional neurophysiological examination, using median nerve axonal excitability studies, alongside clinical assessments, in 103 long term CCS (10.5 ± 0.6 years post-treatment). RESULTS: Cisplatin treated CCS (n = 16) demonstrated multiple sensory axonal excitability changes including increased threshold (P < 0.05), alterations in depolarising and hyperpolarising threshold electrotonus (P < 0.05) and reduction in resting and minimum IV slope (P < 0.01). Vincristine treated CCS (n = 73) were comparable to controls, except for prolonged distal motor latency (P = 0.001). No differences were seen in the non-neurotoxic chemotherapy group (n = 14). Abnormalities were more evident in the cisplatin subgroup with greater clinical neuropathy manifestations. CONCLUSION: Persistent long term changes in axonal biophysical properties vary with different chemotherapy agents, most evident after cisplatin exposure. Longitudinal studies of nerve function during chemotherapy treatment are required to further evaluate these differences and their mechanistic basis. SIGNIFICANCE: This study provides a unique biophysical perspective for persistent cisplatin related neurotoxicity in children, previously under recognised.

Sonographic assessment of nerve blood flow in diabetic neuropathy.

AIMS: To undertake sonographic assessment of nerve blood flow in people with Type 2 diabetes and correlate the findings with neuropathy severity scores and electrophysiological measurements. METHODS: Median and tibial nerve ultrasound scans were undertaken in 75 people with diabetes and 30 aged-matched controls without diabetes, using a high-resolution linear probe at non-entrapment sites. Nerve blood flow was quantified using power Doppler techniques to obtain the vessel score and the maximum perfusion intensity. Neuropathy severity was assessed using a total neuropathy score. RESULTS: Diabetic nerves had higher rates of nerve blood flow detection (28%) compared to the control group (P < 0.0001). Significant correlations were found between nerve blood flow measurements and nerve size (P <0.001), reported sensory symptoms (P < 0.05) and neuropathy severity scores (P < 0.001). The cohort with diabetes had significantly larger median (8.5 ± 0.3 mm2 vs 7.2 ± 0.1 mm2 ; P < 0.05) and tibial nerves (18.0 ± 0.9 mm2 vs 12.8 ± 0.5 mm2 ; P < 0.05) compared with controls. CONCLUSION: Peripheral nerve hypervascularity is detectable by ultrasonography in moderate to severe diabetic neuropathy with prominent sensory dysfunction.

Respiratory function and cognitive profile in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder with 30%-50% of patients exhibiting cognitive impairment. The pathophysiological mechanisms of cognitive dysfunction are probably multifactorial although hypoventilation secondary to respiratory dysfunction may contribute to cognitive decline. The current study aimed to identify the relationship between respiratory function in ALS patients and the presence and degree of cognitive impairment. METHODS: Amyotrophic lateral sclerosis patients were prospectively recruited from a multidisciplinary ALS clinic. Baseline clinical assessments including respiratory function as assessed by spirometry were recorded with forced vital capacity (FVC) ≤ 75% considered to be reduced respiratory function. Cognitive testing was performed utilizing the Addenbrooke's Cognitive Examination (ACE) and the Mini-Mental State Examination (MMSE). RESULTS: From a cohort of 100 ALS patients, 48% were categorized as having impaired respiratory function (FVC = 58.24% ± 2.15%) whilst 52% had normal function (88.65% ± 1.27%). Compared to the group with normal respiratory function (ACE 90.68 ± 0.89, MMSE 28.22 ± 0.21), patients with respiratory dysfunction had significantly reduced cognitive function (ACE 86.83 ± 1.5, P = 0.025; MMSE 26.29 ± 0.45, P = 0.029). Furthermore, subscores demonstrated significant differences between the groups with respect to domains in memory (P = 0.003) and attention (P = 0.05) with a trend observed in fluency (P = 0.082). There was a significant correlation between patient baseline FVC and ACE scores as well as between FVC and memory and fluency subscores (P < 0.01). CONCLUSION: Amyotrophic lateral sclerosis patients with respiratory compromise were more likely to develop reduced cognitive function. In addition to improving physical function, it remains plausible that non-invasive ventilation may alter the progression of cognitive impairment in ALS patients and potentially improve overall quality of life and carer burden.

Top research priorities in healthcare-associated infection in the UK.

BACKGROUND: There is a mismatch between research questions which are considered to be important by patients, carers and healthcare professionals and the research performed in many fields of medicine. No relevant studies which have assessed research priorities in healthcare-associated infection (HCAI) that have involved patients' and carers' opinions were identified in the literature. AIM: The Healthcare-Associated Infections Priority Setting Partnership was established to identify the top research priorities in the prevention, diagnosis and treatment of HCAI in the UK, considering the opinions of all these groups. METHODS: The methods broadly followed the principles of the James Lind Alliance (JLA) priority setting activity. FINDINGS: In total, 259 unique valid research questions were identified from 221 valid responses to a consultation of patients, carers and healthcare professionals after seeking their opinions for research priorities. The steering committee of the priority setting partnership rationalized these to 50 unique questions. A literature review established that for these questions there were no recent high-quality systematic reviews, high-quality systematic reviews which concluded that further studies were necessary, or the steering committee considered that further research was required despite the conclusions of recent systematic reviews. An interim survey ranked the 50 questions, and the 10 main research priorities were identified from the top 32 questions by consensus at a final priority setting workshop of patients, carers and healthcare professionals using group discussions. CONCLUSIONS: A priority setting process using JLA methods and principles involving patients, carers and healthcare professionals was used to identify the top 10 priority areas for research related to HCAI. Basic, translational, clinical and public health research would be required to address these uncertainties.