Introducing extended consultations for patients with severe mental illness in general practice: Results from the SOFIA feasibility study.

BACKGROUND: People with a severe mental illness (SMI) have shorter life expectancy and poorer quality of life compared to the general population. Most years lost are due to cardiovascular disease, respiratory disease, and various types of cancer. We co-designed an intervention to mitigate this health problem with key stakeholders in the area, which centred on an extended consultations for people with SMI in general practice. This study aimed to1) investigate general practitioners' (GPs) experience of the feasibility of introducing extended consultations for patients with SMI, 2) assess the clinical content of extended consultations and how these were experienced by patients, and 3) investigate the feasibility of identification, eligibility screening, and recruitment of patients with SMI. METHODS: The study was a one-armed feasibility study. We planned that seven general practices in northern Denmark would introduce extended consultations with their patients with SMI for 6 months. Patients with SMI were identified using practice medical records and screened for eligibility by the patients' GP. Data were collected using case report forms filled out by practice personnel and via qualitative methods, including observations of consultations, individual semi-structured interviews, a focus group with GPs, and informal conversations with patients and general practice staff. RESULTS: Five general practices employing seven GPs participated in the study, which was terminated 3 ½ month ahead of schedule due to the COVID-19 pandemic. General practices attempted to contact 57 patients with SMI. Of these, 38 patients (67%) attended an extended consultation, which led to changes in the somatic health care plan for 82% of patients. Conduct of the extended consultations varied between GPs and diverged from the intended conduct. Nonetheless, GPs found the extended consultations feasible and, in most cases, beneficial for the patient group. In interviews, most patients recounted the extended consultation as beneficial. DISCUSSION: Our findings suggest that it is feasible to introduce extended consultations for patients with SMI in general practice, which were also found to be well-suited for eliciting patients' values and preferences. Larger studies with a longer follow-up period could help to assess the long-term effects and the best implementation strategies of these consultations.

General practitioners' stay-at-work practices in patients with musculoskeletal disorders: using Intervention Mapping to develop a training program.

OBJECTIVES: To describe current stay-at-work practices among Danish general practitioners (GPs) in relation to patients with musculoskeletal disorders, to identify potential avenues for improvement, and to suggest a training program for the GPs. DESIGN AND SETTING: We followed the principles of Intervention Mapping. Data were collected by means of literature searches, focus group interviews with GPs, and interaction with stakeholder representatives from the Danish labour market. RESULTS: GPs' current stay-at-work practices were influenced by systemic, organisational, and legislative factors, and by personal determinants, including knowledge and skills relating to stay-at-work principles and musculoskeletal disorders, recognition of the patient's risk of long-term work disability, their role as a GP, and expectations of interactions with other stay-at-work stakeholders. GPs described themselves as important partners and responsible for the diagnostic and holistic assessments of the patient but placed themselves on the side line relying on the patient or workplace stakeholders to act. Their practices are influenced both by patients, employers, and by other stakeholders. We propose a training course for GPs that incorporate both concrete tools and behaviour change techniques. CONCLUSIONS: We have identified varied perspectives on the roles and responsibilities of GPs, as well as legislative and organisational barriers, and proposed a training program. Not all barriers identified can be addressed by a training course, and some questions are left unanswered, among others - who are best suited to help patients staying at work?

Musculoskeletal disorders are highly prevalent and one of the most common causes for visiting a GP.In many countries, GPs are important in facilitating that patients stay at work, when they are experiencing musculoskeletal pain and disability.In our research, GPs place themselves on the side line as coaches relying on the patient or workplace to act.Barriers such as role identity, systemic and organisational issues prevent GPs from being more involved in stay-at-work practices.GPs' with knowledge about stay-at-work practices may empower patients to better self-management.

Large-scale changes in marine and terrestrial environments drive the population dynamics of long-tailed ducks breeding in Siberia.

Migratory animals experience very different environmental conditions at different times of the year, i.e., at the breeding grounds, during migration, and in winter. The long-tailed duck Clangula hyemalis breeds in the Arctic regions of the northern hemisphere and migrates to temperate climate zones, where it winters in marine environments. The breeding success of the long-tailed duck is affected by the abundances of predators and their main prey species, lemmings Lemmus sibiricus and Dicrostonyx torquatus, whose population fluctuation is subject to climate change. In the winter quarters, long-tailed ducks mainly eat the blue mussel Mytilus edulis. We examined how North-west Siberian lemming dynamics, assumed as a proxy for predation pressure, affect long-tailed duck breeding success and how nutrient availability in the Baltic Sea influences long-tailed duck population size via mussel biomass and quality. Evidence suggests that the long-tailed duck population dynamics was predator-driven on the breeding grounds and resource-driven on the wintering grounds. Nutrients from fertilizer runoff from farmland stimulate mussel stocks and quality, supporting high long-tailed duck population sizes. The applied hierarchical analysis combining several trophic levels can be used for evaluating large-scale environmental factors that affect the population dynamics and abundance of migrants from one environment to another.

The SOFIA pilot trial: a cluster-randomized trial of coordinated, co-produced care to reduce mortality and improve quality of life in people with severe mental illness in the general practice setting.

BACKGROUND: People with severe mental illness (SMI) have an increased risk of premature mortality, predominantly due to somatic health conditions. Evidence indicates that primary and tertiary prevention and improved treatment of somatic conditions in patients with SMI could reduce this excess mortality. This paper reports a protocol designed to evaluate the feasibility of a coordinated co-produced care program (SOFIA model, a Danish acronym for Severe Mental Illness and Physical Health in General Practice) in the general practice setting to reduce mortality and improve quality of life in patients with severe mental illness. METHODS: The SOFIA pilot trial is designed as a cluster randomized controlled trial targeting general practices in two regions in Denmark. We aim to include 12 practices, each of which is instructed to recruit up to 15 community-dwelling patients aged 18 and older with SMI. Practices will be randomized by a computer in a ratio of 2:1 to deliver a coordinated care program or usual care during a 6-month study period. A randomized algorithm is used to perform randomization. The coordinated care program includes educational training of general practitioners and their clinical staff educational training of general practitioners and their clinical staff, which covers clinical and diagnostic management and focus on patient-centered care of this patient group, after which general practitioners will provide a prolonged consultation focusing on individual needs and preferences of the patient with SMI and a follow-up plan if indicated. The outcomes will be parameters of the feasibility of the intervention and trial methods and will be assessed quantitatively and qualitatively. Assessments of the outcome parameters will be administered at baseline, throughout, and at end of the study period. DISCUSSION: If necessary the intervention will be revised based on results from this study. If delivery of the intervention, either in its current form or after revision, is considered feasible, a future, definitive trial to determine the effectiveness of the intervention in reducing mortality and improving quality of life in patients with SMI can take place. Successful implementation of the intervention would imply preliminary promise for addressing health inequities in patients with SMI. TRIAL REGISTRATION: The trial was registered in Clinical Trials as of November 5, 2020, with registration number NCT04618250 . Protocol version: January 22, 2021; original version.

Effects of climate variation on bird escape distances modulate community responses to global change.

Climate and land use are rapidly changing environmental conditions. Behavioral responses to such global perturbations can be used to incorporate interspecific interactions into predictive models of population responses to global change. Flight initiation distance (FID) reflects antipredator behaviour defined as the distance at which an individual takes flight when approached by a human, under standardized conditions. This behavioural trait results from a balance between disturbance, predation risk, food availability and physiological needs, and it is related to geographical range and population trends in European birds. Using 32,145 records of flight initiation distances for 229 bird species during 2006-2019 in 24 European localities, we show that FIDs decreased with increasing temperature and precipitation, as expected if foraging success decreased under warm and humid conditions. Trends were further altered by latitude, urbanisation and body mass, as expected if climate effects on FIDs were mediated by food abundance and need, differing according to position in food webs, supporting foraging models. This provides evidence for a role of behavioural responses within food webs on how bird populations and communities are affected by global change.

On-site generated peroxy acetic acid (PAA) technology reduces Salmonella and Campylobacter on chicken wings.

Peroxyacetic acid (PAA) is a widely used antimicrobial during poultry processing that requires to be shipped in a concentrated solution, stored under hazardous conditions and diluted for use. On-site PAA generation using nonhazardous ingredients can help eliminate transportation and storage issues at the processing plant and reduce the risk of occupational hazards. The objective of the proposed research was to 1) evaluate the efficacy of on-site generated PAA in reducing Salmonella and Campylobacter populations compared to the commercially available PAA stock solutions and 2) to perform color measurements to evaluate any deviations between treatments. PAA solutions at 50 and 100 ppm were used for treating the chicken wings. Fresh chicken wings (0.45 kg) were inoculated with a cocktail of nalidixic acid resistant Salmonella Typhimurium (STNR) and gentamicin resistant Campylobacter coli (CCGR) and immersed in PAA solutions (50 and 100 ppm) adjusted to pH 8.5 and 10.0 or 10.5, for either 10 s or 60 min. Treated chicken wings were rinsed for 1 min in chilled BPW (100 mL), serially diluted and plated on APC Petrifilm for Salmonella, spread plated on Campy-cefex agar supplemented with gentamicin (200 ppm) for Campylobacter enumeration. Immersion of chicken wings in 100 ppm PAA for 60 min irrespective of pH levels and PAA solutions resulted in greater microbial reductions (P < 0.05) of Salmonella by 1.68 and 1.42 log CFU/mL for SaniDate, 1.82 and 1.83 log CFU/mL for OxyFusion (on-site generated). For the same treatments, Campylobacter reductions of 1.59 and 1.36 log CFU/mL for SaniDate, 1.63 and 1.71 log CFU/mL for OxyFusion were achieved. The antimicrobial efficiency of PAA was not affected by pH and type of PAA solution. No significant differences (P > 0.05) in color were observed between treatments and controls. On-site generated PAA provides poultry processors an effective, safer, and less hazardous alternative to commercially available PAA solutions, ensuring poultry workers' health and safety.

Specialized Outpatient Clinic vs Stroke Unit for TIA and Minor Stroke: A Cohort Study.

Objective: To evaluate the effects of an outpatient clinic set-up for minor stroke/TIA using subsequent admission of patients at 'high risk' of re-stroke.Methods: A cohort study of all patients with suspected minor stroke/TIA seen in an outpatient clinic at Aarhus University Hospital, Denmark, between September 2013 and August 2014. Stroke patients were compared to historic (same hospital) and contemporary (another comparable hospital) matched, hospitalized controls on the non-prioritized outcomes: Length-of-stay, re-admissions, care quality (10 process-performance measures) and mortality. TIA patients were compared to contemporary matched, hospitalized controls.Following complete diagnostic work-up, patients with stroke/TIA were classified into 'low'/high risk' of re-stroke ≤7 days. RESULTS: We analyzed 1,076 consecutive patients of whom 253 (23.5%) were subsequently admitted to the stroke ward. Stroke/TIA was diagnosed in 215/171 patients, respectively. Fifty-six percent (121/215) of the stroke patients were subsequently admitted to the stroke ward. Comparison with the historic stroke cohort (n=191) showed a shorter acute hospital stay for the strokes (median 1 vs 3 days); adjusted length-of-stay ratio 0.49 (95% CI 0.33-0.71). Furthermore, 30-day readmission rate was 3.2% vs 11.6%; adjusted hazard ratio 0.23 (0.09-0.59); and care quality was higher with a risk ratio of 1.30 (1.15-1.47). The comparison of stroke and TIAs to contemporary controls showed similar results. Only one patient in the 'low risk' category and not admitted experienced stroke within 7 days (0.6%). CONCLUSIONS: An outpatient clinic set-up for patients with minor stroke/TIA yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a neurovascular specialist driven outpatient clinic for minor stroke/TIA patients with the ability of subsequent admission is safe and yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units.

Impact of pH on efficacy of peroxy acetic acid against Salmonella, Campylobacter, and Escherichia coli on chicken wings.

Peroxy acetic acid (PAA) is widely used as an antimicrobial in poultry processing, specifically in the chiller. While the natural pH of PAA at the concentrations used is between 4.5 and 6.0, poultry processors adjust the pH to ≥8.0 to maintain product yield. The objective of this study was to evaluate 1) efficacy of PAA at different concentrations, pH, and contact times against Salmonella, Campylobacter, and Escherichia coli and 2) use of E. coli as a surrogate for Salmonella and Campylobacter to conduct validations studies for poultry processing. Fresh chicken wings (0.45 Kg) were inoculated with a cocktail of nalidixic acid-resistant Salmonella Typhimurium, rifampicin-resistant E. coli (5-strain cocktail), and gentamicin-resistant Campylobacter coli. Inoculated chicken wings were immersed in PAA solutions of 50, 250, and 500 ppm adjusted to pH 8.2 and 10.0 as well as nonadjusted PAA solutions for 10 s and 60 min. Treated chicken wings were rinsed in chilled buffered peptone water, serially diluted, and plated on Petrifilm APC for enumerating Salmonella and E. coli populations and spread plated on Campy Cefex Agar containing gentamicin (200 ppm) to enumerate Campylobacter. Immersion of chicken wings in 500 ppm of PAA (non-pH-adjusted) for 60 min resulted in greater microbial reductions (P ≤ 0.05) of Salmonella, Campylobacter, and E. coli populations of 2.56, 1.90, and 2.53 log CFU/mL, respectively. Higher concentrations and longer exposure times resulted in greater reductions (P ≤ 0.05) of Salmonella, E. coli, and Campylobacter populations, and increasing pH of PAA solution did not affect (P > 0.05) its efficacy. A high correlation (r = 0.93) was observed between E. coli (surrogate) and Salmonella populations suggesting that E. coli can be used as a surrogate for Salmonella for conducting validation studies for antimicrobial efficacy testing in poultry processing.

Oncologic outcomes of patients with incidental prostate cancer who underwent RARC: a comparison between nerve sparing and non-nerve sparing approach.

BACKGROUND: Incidental Prostate cancer (iPCa) is a relatively common finding during histopathological evaluation of radical cystectomy (RC) specimens. To reduce the high impact of RC on erectile function, several sexual-preserving techniques have been proposed. The aim of this study was to evaluate and compare the oncologic outcomes of patients with iPCa who underwent nerve spring and no-nerve sparing robot-assisted radical cystectomy (RARC). METHODS: The clinicopathologic data of male patients who underwent RARC at our institution between 2006 and 2016 were retrospectively analysed. Patients with iPCa at definitive pathological examinations were stratified in two groups, according to the preservation of the neurovascular bundles (nerve sparing vs no nerve sparing). Significant PCa was defined as any Gleason score ≥ 3 + 4. Biochemical recurrence (BR) was defined as a sustained PSA level > 0.2 ng/mL on two or more consecutive appraisals. BR rate was assessed only in patients with incidental prostate cancer and at least 2 years of follow-up. Differences in categorical and continuous variables were analysed using the chi-squared test and the Mann-Withney U test, respectively. Biochemical recurrence curves were generated using the Kaplan-Meier method and compared with the Log-rank test. RESULTS: Overall, 343 male patients underwent RARC for bladder cancer within the study period. Nerve-sparing surgery was performed in 143 patients (41%), of these 110 had at least 2 years of follow up after surgery. Patients who underwent nerve-sparing surgery were significantly younger (p < 0.001). Clinically significant PCa was found in 24% of patients. No significant differences regarding preoperative PSA value (p = 0.3), PCa pathological stage (p = 0.5), Gleason score (p = 0.3) and positive surgical margin rates (p = 0.3) were found between the two groups. After a median follow-up of 51 months only one patient, in the no-nerve-sparing group had developed a biochemical recurrence (p = 0.4). CONCLUSIONS: In our series most of the iPca detected in RC specimens can be considered as insignificant with a low rate of BR (0.9%). Nerve-sparing RARC is a safe procedure which did not affect oncological outcomes of patients with iPCa.

Occupational exposure and the risk of new-onset chronic rhinosinusitis â€" a prospective study 2013-2018.

BACKGROUND: The aetiology behind chronic rhinosinusitis (CRS) is still poorly understood. The aim of this study was to investigate the association between the onset of CRS and several common occupational exposures over time. METHODOLOGY: An adult random population from Telemark, Norway, comprising 7,952 subjects, who answered a comprehensive respiratory questionnaire including questions on CRS and occupational exposure first in 2013 and again in 2018. RESULTS: New-onset CRS during the five-year follow-up was independently associated with occupational exposure to hair-care products, cleaning agents among women, super glue, strong acids, cooking fumes and wood dust. CONCLUSION: In this random population cohort from Norway, exposure to several common occupational agents, such as hair-care products, super glue and wood dust, was associated with the onset of CRS. It is important that physicians who see patients with CRS inquire about workplace exposure.

[Sleep-disordered Breathing]. / Atemstörungen im Schlaf.

Sleep disordered breathing disorders in children are of a high clinical relevance. They do not only affect a large proportion of the children's lives in terms of time but they impact on the thriving, cardiovascular function and cognitive development. Different developmental factors have to be considered in the interpretation of sleep studies in children. Adeno-tonsillar hypertrophy is the most frequent reason for paediatric sleep disordered breathing, however the spectrum of aetiologies is very large. Syndromic cranio facial malformations and metabolic disorders are often associated with a very high risk of relevant sleep disordered breathing. Correct and child-oriented diagnostics are essential to enable adequate therapy.

A comparison of trauma scoring systems for injuries presenting to a district-level urban public hospital in Western Cape.

BACKGROUND: Trauma is a major public health issue and has an extensive burden on the health system in South Africa. Many trauma scoring systems have been developed to estimate trauma severity and predict mortality. The prediction of mortality between different trauma scoring systems have not been compared at district-level health facilities in South Africa. The objective was to compare four trauma scoring systems (injury severity score (ISS), revised trauma score (RTS), Kampala trauma score (KTS), trauma and injury severity score (TRISS)) in predicting mortality in trauma-related patients presenting to a district-level hospital in Cape Town. METHODS: A retrospective analysis of all trauma patients managed in the resuscitation unit of Khayelitsha Hospital during a six-month period. Logistic regression was done, and empirical cut-off points used to maximise sensitivity and specificity on receiver operating characteristic curves. The outcome was all-cause in-hospital mortality. RESULTS: In total, 868 participants were analysed after 50 were excluded due to missing data. The mean (± SD) age was 28 ± 11 years, 726 (83.6%) were males, and penetrating injuries (n = 492, 56.6%) dominated. The mortality rate was 5.2% (n = 45). TRISS was the best mortality predictor (c-statistic 0.93, sensitivity 90%, specificity 87%). All scoring systems had overlapping confidence intervals. CONCLUSION: TRISS, ISS, RTS and KTS performed equivocally in predicting mortality in trauma-related patients managed at a district-level facility. The appropriate scoring system should be the simplest one which can be practically implemented and will likely differ between facilities.

The Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala.

BACKGROUND: A Diagnostic Laboratory Hub (DLH) was set up in Guatemala to provide opportunistic infection (OI) diagnosis for people with HIV (PWH). METHODS: Patients newly presenting for HIV, PWH not receiving antiretrovirals (ARVs) for >90 days but returned to care (Return/Restart), and PWH on ARVs with symptoms of OIs (ARV treatment) were prospectively included. Screening for tuberculosis, nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcosis was done. Samples were couriered to the DLH, and results were transmitted electronically. Demographic, diagnostic results, disease burden, treatment, and follow-up to 180 days were analyzed. RESULTS: In 2017, 1953 patients were included, 923 new HIV infections (an estimated 44% of all new HIV infections in Guatemala), 701 on ARV treatment, and 315 Return/Restart. Three hundred seventeen (16.2%) had an OI: 35.9% tuberculosis, 31.2% histoplasmosis, 18.6% cryptococcosis, 4.4% NTM, and 9.8% coinfections. Histoplasmosis was the most frequent AIDS-defining illness; 51.2% of new patients had <200 CD4 cells/mm3 with a 29.4% OI incidence; 14.3% of OIs in new HIV infections occurred with CD4 counts of 200-350 cells/mm3. OIs were the main risk factor for premature death for new HIV infections. At 180 days, patients with OIs and advanced HIV had 73-fold greater risk of death than those without advanced disease who were OI-free. CONCLUSIONS: The DLH OI screening approach provides adequate diagnostic services and obtains relevant data. We propose a CD4 screening threshold of <350 cells/mm3. Mortality remains high, and improved interventions are required, including expansion of the DLH and access to antifungal drugs, especially liposomal amphotericin B and flucytosine.

Pre-operative femoral nerve block for hip fracture-A systematic review with meta-analysis.

BACKGROUND: Pre-operative pain management of hip fracture patients is complex. Femoral nerve block (FNB) is used for hip fractures to reduce pain and demand for systematic analgesia. The objective of the study was to systematically investigate the efficacy of single-shot FNB for hip fracture patients. METHODS: Five databases were searched from inception until 8 May 2019. We included randomized controlled trials (RCT's) assessing pain relief in patients with hip fractures. Intervention was pre-operative FNB compared to any systemic analgesic (eg opioids, non-steroidal anti-inflammatory drugs or paracetamol). Primary outcomes assessed were pre-operative pain and use of rescue analgesics. Secondary outcome was cognitive impairment. We present a bias assessment, a meta-analysis and a grading of certainty of evidence. RESULTS: We included five trials (n = 254), where participants received FNB 30 minutes or more prior to surgery; all were judged as having high risk of bias. All studies found significantly decreased pain scores at least once in the intervention group compared to the control group. Meta-analysis on the primary outcome of pain showed significance. Mean difference was -2.13 point (in cm) (CI:-3.53,-0.72) on visual analogue scale in the intervention group, but is judged low on certainty. CONCLUSIONS: The quantity of evidence supporting pre-operative single-shot FNB for hip fractures is very low, and the certainty of evidence supporting pre-operative single-shot FNB for hip fractures is low. No studies using ultrasound guided technique were identified. Data on non-ultrasound guided FNB's suggest a decreased pain score compared to the use of systemic analgesia.

Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder.

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.

Short echo-time Magnetic Resonance Spectroscopy in ALS, simultaneous quantification of glutamate and GABA at 3 T.

Cortical hyperexcitability has been found in early Amyotrophic Lateral Sclerosis (ALS) and is hypothesized to be a key factor in pathogenesis. The current pilot study aimed to investigate cortical inhibitory/excitatory balance in ALS using short-echo Magnetic Resonance Spectroscopy (MRS). Patients suffering from ALS were scanned on a 3 T Trio Siemens MR scanner using Spin Echo Full Intensity Acquired Localized (SPECIAL) Magnetic Resonance Spectroscopy in primary motor cortex and the occipital lobe. Data was compared to a group of healthy subjects. Nine patients completed the scan. MRS data was of an excellent quality allowing for quantification of a range of metabolites of interest in ALS. In motor cortex, patients had Glutamate/GABA and GABA/Cr- ratios comparable to healthy subjects. However, Glutamate/Cr (p = 0.002) and the neuronal marker N-acetyl-aspartate (NAA/Cr) (p = 0.034) were low, possibly due to grey-matter atrophy, whereas Glutathione/Cr (p = 0.04) was elevated. In patients, NAA levels correlated significantly with both hand strength (p = 0.027) and disease severity (p = 0.016). In summary SPECIAL MRS at 3 T allows of reliable quantification of a range of metabolites of interest in ALS, including both excitatory and inhibitory neurotransmitters. The method is a promising new technique as a biomarker for future studies on ALS pathophysiology and monitoring of disease progression.

Construction of a hybrid clamped cell for high-pressure neutron-diffraction experiments with a large diamond window.

A hybrid pressure cell was fabricated from commercially available copper-beryllium and custom-made Ni-Cr-Al Russian alloy, tailored for usage as a reaction vessel supplying a volume of about 400 mm3. In order to directly (in situ) monitor pressure and chemical reactions within the chamber, a large diamond window suitable for spectroscopic sample analysis was implemented. The performance of the hybrid cell was validated from high-pressure neutron-diffraction measurements on carbon dioxide.

Butyrylcholinesterase deficiency and its clinical importance in anaesthesia: a systematic review.

Butyrylcholinesterase deficiency prolongs the effects of the drugs it degrades; succinylcholine and mivacurium. Existing literature on butyrylcholinesterase deficiency is dominated by genetic and biochemical studies. We searched MEDLINE, Embase, Web of Science and Biosis to systematically review the causes and clinical consequences of butyrylcholinesterase deficiency. We considered outcomes clinically relevant if neuromuscular blockade, induced by succinylcholine or mivacurium, was assessed using clinical criteria or neuromuscular monitoring. We included 66 studies: 25 randomised controlled trials; 13 clinically controlled trials; 26 prospective observational studies; 1 retrospective study; and 1 qualitative study. Data heterogeneity precluded quantitative synthesis. Studies described genetic, physiological, acquired or pharmacologically induced causes of butyrylcholinesterase deficiency. The prolongation of neuromuscular blockade by butyrylcholinesterase deficiency was most pronounced with homozygosity of a genetic variant, but other more common factors included increasing age, pregnancy, severe liver disease, burn injuries and drug interactions.