Bedside Ultrasound in the Emergency Department Enables Rapid Diagnosis of PUJ Obstruction Syndrome.

Presentation A 27-year-old male presented to the Emergency Department with acute severe left flank pain following ingestion of 5 pints of beer. Approximately 20 bouts of similar episodes over the past year, in the setting of alcohol ingestion. Despite attending GP, no diagnosis reached yet. Diagnosis "Pelvo-ureteric junction (PUJ) obstruction Syndrome". Bedside ultrasound in the Emergency Department during the acute pain crisis: massive hydronephrosis left kidney. Finding confirmed on CT scan. Subsequent 99m-Tec renogram showed markedly decreased renal function on the left. Treatment Interval Pyeloplasty two months later. Conclusion Delayed recognition is the norm for PUJ obstruction syndrome, as CT/MRI/US studies often do not display hydronephrosis if the patient is asymptomatic. We could not find any reports in the literature of diagnosing PUJ obstruction syndrome using bedside ultrasound in the Emergency Department. We advise acquiring rapid bedside ultrasound imaging in suspected cases of PUJ obstruction syndrome, enabling earlier diagnosis.

Transparency and sustainability in global commodity supply chains.

Over the last few decades rapid advances in processes to collect, monitor, disclose, and disseminate information have contributed towards the development of entirely new modes of sustainability governance for global commodity supply chains. However, there has been very little critical appraisal of the contribution made by different transparency initiatives to sustainability and the ways in which they can (and cannot) influence new governance arrangements. Here we seek to strengthen the theoretical underpinning of research and action on supply chain transparency by addressing four questions: (1) What is meant by supply chain transparency? (2) What is the relevance of supply chain transparency to supply chain sustainability governance? (3) What is the current status of supply chain transparency, and what are the strengths and weaknesses of existing initiatives? and (4) What propositions can be advanced for how transparency can have a positive transformative effect on the governance interventions that seek to strengthen sustainability outcomes? We use examples from agricultural supply chains and the zero-deforestation agenda as a focus of our analysis but draw insights that are relevant to the transparency and sustainability of supply chains in general. We propose a typology to distinguish among types of supply chain information that are needed to support improvements in sustainability governance, and illustrate a number of major shortfalls and systematic biases in existing information systems. We also propose a set of ten propositions that, taken together, serve to expose some of the potential pitfalls and undesirable outcomes that may result from (inevitably) limited or poorly designed transparency systems, whilst offering guidance on some of the ways in which greater transparency can make a more effective, lasting and positive contribution to sustainability.

Differences in statin associated neuroprotection corresponds with either decreased production of IL-1ß or TNF-α in an in vitro model of neuroinflammation-induced neurodegeneration.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been associated with conflicting effects within the central nervous system (CNS), with underlying mechanisms remaining unclear. Although differences between individual statins' CNS effects have been reported clinically, few studies to date have compared multiple statins' neuroprotective effects. This study aimed to compare six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin; 0-100 µM) using an in vitro model of lipopolysaccharide (LPS)-induced neuroinflammation and subsequent neurodegeneration. To achieve this, HAPI microglia were treated with LPS (0.1 µg/mL; 24 h), resulting in increased reactive oxygen species (ROS), nitric oxide, and IL-1ß, TNF-α and PGE2 release. Conditioned media ("HAPI-CM") was then transferred to SH-SY5Y neuroblastoma cells, and effects on cellular viability, mitochondrial membrane permeability, apoptosis, autophagy and ROS production assessed. Of the statins investigated, only atorvastatin, pravastatin and rosuvastatin protected SH-SY5Y cells from LPS-induced decreases in cellular viability; this appeared mediated through reduced caspase 3/7 activation and was associated with decreased IL-1ß (atorvastatin, pravastatin) and/or TNF-α (atorvastatin, pravastatin, rosuvastatin). Only pravastatin conferred protection at all tested concentrations. ROS production and autophagic vacuole formation was decreased by all statins, suggesting these two mechanisms are unlikely to be sole mediators of neuroprotection seen with selected statins. Ultimately, our model suggests that despite all statins reducing microglial inflammation, subsequent effects on neuronal viability and cell death signalling pathways varies between statins. Our findings highlight the need to consider individual statins as inducing discrete pharmacological effects within the CNS in future in vitro/in vivo studies and in clinical practice.

Development and validation of Spasticity Index-Amyotrophic Lateral Sclerosis.

OBJECTIVES: Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS. METHODS: Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life. RESULTS: A total of 465 patients (mean age 64.7 years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale-the Spasticity Index for ALS (SI-ALS)-which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life. CONCLUSIONS: The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS.

A Review of the Parenteral Nutrition Supply Service in an Irish Neonatal Unit

Background Neonatal Intensive Care (NICU) patients have individual nutritional requirements often requiring Patient Specific Parenteral Nutrition (PSPN). From October 2015, the national PSPN compounding service availability changed from 7 days per week service to 5 days per week (i.e. no weekend and limited bank holiday ordering available). The aim of this study was to examine the introduction of a 5 day only PSPN supply on neonatal patient parenteral nutrition availability in a tertiary NICU. Methods We performed a prospective assessment of the provision of a 5 day rather than 7 day ordering of PSPN over a one month period (June 2017). Results Fifteen neonatal patients received a cumulative 89 days of PN during June 2017. 10 (66%) patients received PSPN during this time period. There was same day availability of PSPN in 62 of 89 days of PN (69%). Conclusion Thorough education and training will help prescribers to make appropriate PSPN ordering decisions. Improvements to available stock bags may reduce the amount of PSPN that is required but a 7 day PSPN ordering service would improve efficient provision of clinically indicated PSPN to premature infants in NICU in Ireland.

Multiple births by a captive swellshark Cephaloscyllium ventriosum via facultative parthenogenesis.

Using a novel set of 12 microsatellites, a captive, adult female swellshark Cephaloscyllium ventriosum that produced five pups via parthenogenesis is described; naturally occurring parthenogenesis has been observed in every vertebrate class with the exception of mammals. As demonstrated in this study, a captive environment is ideal for long-term monitoring of animals under controlled conditions, and easily allows the detection of particular facets of their biology.

Creatine kinase enzyme level correlates positively with serum creatinine and lean body mass, and is a prognostic factor for survival in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition for which there is no single diagnostic test or biomarker. The level of the creatine kinase (CK) enzyme in serum may be mild to moderately elevated in some patients with ALS, the precise cause of which and its behaviour with disease progression is unknown. The aim of this study was to examine the usefulness of monitoring CK serially during the ALS disease trajectory and to determine whether CK levels mirror disease progression. METHODS: This was a prospective observational cohort study, using the clinical database of the olesoxime (TRO19622) investigational medicinal product trial. RESULTS: The baseline CK was raised in 52% of the trial participants with the mean CK ± SD being 257 ± 239 U/l. The mean CK was significantly higher in male participants than in female participants (P < 0.001) and amongst participants with limb onset ALS compared to participants with bulbar onset ALS (P < 0.001). There was no significant difference in the CK levels between upper limb and lower limb onset disease (P = 0.746). The CK level co-related positively with serum creatinine and estimated lean body mass but there was no relationship between CK and muscle scores and limb function. A higher CKlog was associated with significantly better survival, even when adjusted for prognostic co-variants (P = 0.013). CONCLUSIONS: The serum CK level seems to be an independent prognostic factor for survival in ALS. The cellular mechanism of CK enzyme suggests that it may be upregulated to provide energy in the face of metabolic stress in ALS.

Equipping for risk: Lessons learnt from the UK shale-gas experience on assessing environmental risks for the future geoenergy use of the deep subsurface.

findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 ± 1.4 t CH4). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term.

Lack of unique neuropathology in amyotrophic lateral sclerosis associated with p.K54E angiogenin (ANG) mutation.

AIMS: Five to 10% of cases of amyotrophic lateral sclerosis are familial, with the most common genetic causes being mutations in the C9ORF72, SOD1, TARDBP and FUS genes. Mutations in the angiogenin gene, ANG, have been identified in both familial and sporadic patients in several populations within Europe and North America. The aim of this study was to establish the incidence of ANG mutations in a large cohort of 517 patients from Northern England and establish the neuropathology associated with these cases. METHODS: The single exon ANG gene was amplified, sequenced and analysed for mutations. Pathological examination of brain, spinal cord and skeletal muscle included conventional histology and immunohistochemistry. RESULTS: Mutation screening identified a single sporadic amyotrophic lateral sclerosis case with a p.K54E mutation, which is absent from 278 neurologically normal control samples. The clinical presentation was of limb onset amyotrophic lateral sclerosis, with rapid disease progression and no evidence of cognitive impairment. Neuropathological examination established the presence of characteristic ubiquitinated and TDP-43-positive neuronal and glial inclusions, but no abnormality in the distribution of angiogenin protein. DISCUSSION: There is only one previous report describing the neuropathology in a single case with a p.K17I ANG mutation which highlighted the presence of eosinophilic neuronal intranuclear inclusions in the hippocampus. The absence of this feature in the present case indicates that patients with ANG mutations do not always have pathological changes distinguishable from those of sporadic amyotrophic lateral sclerosis.

Neuro-ophthalmological Complications of Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) can lead to prominent nerve hypertrophy, which can mimic other forms of neuropathy radiologically. Neuro-ophthalmological complications can also occur in CIDP, either at presentation or chronically in the disorder. This can also cause diagnostic difficulties. We report three cases of neuro-ophthalmological complications of CIDP: two cases of papilloedema and one case of proptosis. In all three cases cranial nerve hypertrophy was present. CIDP should be considered in neuro-ophthalmological presentations associated with cranial/spinal nerve root hypertrophy.

Supratherapeutic dabigatran: a cause of life-threatening haemorrhage.

In this case report, we present a rare case of life-threatening gastrointestinal haemorrhage associated with deranged coagulation due to supratherapeutic levels of dabigatran. Dabigatran is a potent, synthetic, reversible non-peptide thrombin inhibitor which is increasingly used for stroke prevention in patients with non-valvular atrial fibrillation. It is generally accepted that dabigatran dosing does not require titration or the monitoring of plasma levels due to its predictable pharmacokinetics and pharmacodynamics. However, this case report challenges this viewpoint while identifying an important knowledge gap in relation to the effect of altered gastrointestinal motility on the absorption of direct oral anticoagulants. Furthermore, it demonstrates the successful use of high-dose idarucizumab in a critical care setting. Idarucizumab is a monoclonal antibody fragment that binds specifically to dabigatran and its metabolites, thereby reversing the anticoagulant effect.

Development of 'gastrostomy tube - is it for me?', a web-based patient decision aid for people living with motor neurone disease considering having a gastrostomy tube placed.

Objective: To develop and pilot a web-based patient decision aid (PDA) to support people living with motor neurone disease (plwMND) considering having a gastrostomy tube placed. Methods: In Phase 1, content and design were informed by semi-structured interviews, literature reviews and a prioritization survey. In Phase 2, the prototype PDA was tested with users and developed iteratively with feedback from surveys and 'think-aloud' interviews. Phase 1 and 2 participants were plwMND, carers and healthcare professionals (HCPs). In Phase 3, the PDA was evaluated by plwMND using validated questionnaires and HCPs provided feedback in focus groups. Results: Sixteen plwMND, 16 carers and 25 HCPs took part in Phases 1 and 2. Interviews and the literature review informed a prioritization survey with 82 content items. Seventy-seven per cent (63/82) of the content of the PDA was retained. A prototype PDA, which conforms to international standards, was produced and improved during Phase 2. In Phase 3, 17 plwMND completed questionnaires after using the PDA. Most plwMND (94%) found the PDA completely acceptable and would recommend it to others in their position, 88% had no decisional conflict, 82% were well prepared and 100% were satisfied with their decision-making. Seventeen HCPs provided positive feedback and suggestions for use in clinical practice. Conclusion: Gastrostomy Tube: Is it for me? was co-produced with stakeholders and found to be acceptable, practical and useful. Freely available from the MND Association website, the PDA is a valuable tool to support the shared decision-making process for gastrostomy tube placement.

Prevalence of depression in amyotrophic lateral sclerosis/motor neuron disease: multi-attribute ascertainment and trajectories over 30 months.

Objective: Evidence is equivocal about the prevalence of depression in amyotrophic lateral sclerosis (ALS). This study uses a multi-attribute ascertainment of the prevalence of depression and examines this prevalence over time. Methods: Patients with ALS were recruited into the Trajectories of Outcome in Neurological Conditions (TONiC-ALS) study. Caseness was identified by the Modified-Hospital Anxiety and Depression Scale (M-HADS). In addition, participants provided data on co-morbidities and medication use. A combination of the three was used to derive the estimate for the prevalence of depression, treated or untreated. Longitudinal data were analyzed by trajectory analysis of interval level M-HADS-Depression data. Results: Among 1120 participants, the mean age was 65.0 years (SD 10.7), 60.4% male, and the median duration since diagnosis was 9 months (IQR 4-24). Caseness of probable depression at baseline, defined by M-HADS-Depression, was 6.45% (95%CI: 5.1-8.0). Taken together with antidepressant medication and co-morbidity data, the prevalence of depression was 23.1% (95%CI: 20.7-25.6). Of those with depression, 17.8% were untreated. Trajectory analysis identified three groups, one of which contained the most cases; the level of depression for each group remained almost constant over time. Conclusion: Depression affects almost a quarter of those with ALS, largely confined to a single trajectory group. Prevalence estimates based on screening for current depressive symptoms substantially under-estimate the population experiencing depression. Future prevalence studies should differentiate data based on current symptoms from those including treated patients. Both have their place in assessing depression and the response by the health care system, including medication, depending upon the hypothesis under test.

Patterns of blood product use among patients with myelodysplastic syndrome.

BACKGROUND AND OBJECTIVES: Most patients with myelodysplastic syndrome (MDS) require blood product support to manage the severe anaemias, which frequently accompany MDS. Our objective was to show the feasibility of linking the Surveillance, Epidemiology and End Results (SEER) database with records from Puget Sound Blood Center (PSBC) to characterize blood product use over time in successive cohorts of patients with MDS. MATERIALS AND METHODS: We identified patients with MDS in the SEER registry. The cohort was then linked to PSBC records to discern blood product use. RESULTS: Included in the analysis were 783 patients with MDS entered in the SEER database from 2001 to 2007 for whom data were also available in the PSBC database. Among patients with MDS who received transfusions, 97% received packed red blood cells; 52% received platelets. The proportion of patients with MDS receiving blood products declined from 2001 to 2007. CONCLUSION: These data show a recent decline in blood product use for patients with MDS. Future studies are needed to further evaluate the reasons for this finding, specifically exploring the impact of newer medications on blood product use in patients with MDS.

A comparison of approaches for association studies of polymorphisms and colorectal cancer risk.

AIM: Meta-analyses have been used to evaluate associations between polymorphisms and colorectal cancer risk, but the quality of individual studies used to inform them may vary substantially. Our aim was to apply well-established quality-control criteria to individual association studies and then compare the results of meta-analyses that included or excluded studies that did not meet these criteria. METHOD: We used meta-analyses of studies reporting a relationship between polymorphisms and colorectal cancer published between 1996 and 2008. Polymorphism-cancer associations were derived in separate meta-analyses including only those meeting the quality-control criteria. RESULTS: Relative ORs varied substantially between the open and restricted group meta-analyses for all variants except MTHFR 677 CT. However, the associations were modest and the direction of relative risk did not change after applying criteria. Publication bias was detected for all associations, except the restricted set of studies for GSTP1 GG. CONCLUSION: We observed variation in calculated relative risk and changes in tests for publication bias that were dependent on the inclusion criteria used for association studies of polymorphisms and colorectal cancer. Standardizing study inclusion criteria may reduce the variation in findings for meta-analyses of gene-association studies of common diseases such as colorectal cancer.

Patients' hopes and expectations of a specialist chronic fatigue syndrome/ME service: a qualitative study.

BACKGROUND: The 2007 National Institute for Health and Clinical Excellence guidelines on Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) recommend early management of the condition. Investment by the Department of Health has expanded the number of specialist U.K. CFS/ME services but there has been little research on what patients hope or expect from referral. METHODS: A qualitative study exploring hopes and expectations of patients newly referred to a CFS/ME Service in the South of England. Interviews with 20 patients were analysed using the constant comparative method. RESULTS: Participants hoped referral to a specialist service would clarify diagnosis, give guidance and support, assist in understanding the complexity of the illness and provide hope for the future. While many participants valued the support of their GP, all viewed referral as offering a level of specialist expertise beyond that available in primary care. Many participants expressed high levels of uncertainty about the nature of CFS/ME. While participants hoped that the service would be able to provide information and guidance, many expressed the view that more information earlier in their illness would make the waiting period less stressful and make it possible for them to do more to help themselves. CONCLUSIONS: GP referral to a specialist service appeared to be highly valued by the participants in this study. The levels of uncertainty expressed by many patients about the nature of CFS/ME raises the issue of the role of information on CFS/ME during the early stages of the illness and suggests a need for more reassurance and positive advice during the waiting period.

Dysfunctional metacognitions in anorexia nervosa.

OBJECTIVE: The aim was to compare women with anorexia nervosa (AN) and without AN in terms of dysfunctional metacognitions. METHOD: 167 Australian women with AN (N=74; mean age 24.3 yrs) and without AN (N=93; mean age 27.3 yrs) completed the Metacognitions Questionnaire-30. RESULTS: Multivariate analyses revealed that relative to controls, AN patients had higher scores on metacognitive dysfunction: they exhibited low confidence in their cognitive competence, reported obsessively monitoring and striving to control their thoughts, and held negative beliefs about the danger of worrying. Furthermore, this was not due to starvation effects. However, patients did not exhibit significantly more positive beliefs about worry than controls once body mass index had been controlled. CONCLUSION: Metacognitive dysfunction may play a key role in the maintenance of AN; therefore, metacognitive therapy may be usefully applied to its treatment.

Measuring coping in people with amyotrophic lateral sclerosis using the Coping Index-ALS: A patient derived, Rasch compliant scale.

OBJECTIVE: The progressively disabling and terminal nature of ALS/MND imposes major coping demands on patients. We wished to improve the psychometric properties of our previously published MND-Coping Scale, so that parametric analyses were valid, and to make it simpler for patients to complete and clinicians to score. METHODS: After a new qualitative analysis of 26 patients with ALS/MND, the draft Coping Index-ALS (CI-ALS) was administered to 465 additional patients, alongside COPE-60, General Perceived Self Efficacy scale, and WHOQOL-BREF. Validity of the CI-ALS was assessed using the Rasch model. External validity was checked against comparator measures. RESULTS: Thirteen centres contributed 465 patients, mean age 64.9 years (SD 10.8), mean disease duration 28.4 months (SD 37.5). The CI-ALS-Self and CI-ALS-Others both satisfied Rasch model expectations and showed invariance across age, gender, marital status and type of onset. Expected correlations were observed with comparator scales. A nomogram is available to convert the raw scores to interval level measures suitable for parametric analysis. CONCLUSIONS: Coping abilities in ALS/MND can now be measured using a simple 21 item self-report measure, offering two subscales with a focus of 'coping by self ' and 'coping with others'. This allows clinicians to identify individuals with poor coping and facilitates research on interventions that may improve coping skills.

Is non-invasive testing for sexually transmitted infections an efficient and acceptable alternative for patients? A randomised controlled trial.

OBJECTIVES: A randomised controlled trial was conducted to assess and quantify the efficacy and acceptability of non-invasive testing (NIT) for sexually transmitted infections (STI) in asymptomatic patients within a genitourinary medicine clinic. METHODS: Patients were randomly assigned to either standard of care (SOC-STI testing with genital examination) or NIT. The length of time patients spent in the clinic was recorded and patients were asked to complete a satisfaction survey. RESULTS: 391 participants were randomly assigned. The length of time male and female patients spent in the clinic was significantly shorter with NIT (men 26 min; women 23 min) compared with SOC (men 41 min; women 45 min, p<0.0001), but most of this decrease was due to reduced patient waiting time within the clinic, rather than less time spent with medical or nursing staff. Those randomly assigned to NIT were significantly more likely to state they were in clinic for less time than expected (p<0.01) and report that the tests were less uncomfortable than expected (p≤0.04). For both men and women, more patients in the SOC group declined testing for syphilis (14%) and HIV (20%) compared with NIT (7% and 13%, respectively), but this was only significantly different between treatments for female patients (p≤0.02). CONCLUSIONS: NIT for STI in asymptomatic patients can reduce the time patients spend in the clinic when combined with appropriate patient care pathways, and is an acceptable alternative to physician-taken genital swabs.