Cerebrospinal fluid opening pressure: The effect of body mass index and body composition.

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is strongly related to obesity. The relationship between intracranial pressure, body mass index (BMI), percentage body fat and distribution of body fat in non-IIH patients remains less clear. The aim of this study was to examine the relationship between intracranial pressure and body type in non-IIH patients. PATIENTS AND METHODS: Lumbar puncture manometry was used to measure cerebrospinal fluid opening pressure (CSFOP). BMI, in addition to neck, waist and hip circumferences were calculated. Air displacement plethysmography (BODPOD) was used to assess body composition. RESULTS: Data was collected from 100 subjects. 11 subjects with conditions known to cause raised intracranial pressure were excluded from analysis. According to Pearson correlation factors displaying a significant relationship with CSFOP included: BMI (R = 0.635, p < 0.0001); waist circumference (R = 0.498, p < 0.0001), hip circumference (R = 0.513, p < 0.0001) and percentage body fat (R = 0.435, p < 0.001). Multivariate analysis indicated that BMI was the only independent factor which predicted CSFOP. Sub-analysis according to gender indicated that BMI was predictive in females and percentage body fat was predictive in males. We did not identify any differences in BMI, percentage body fat or distribution of body fat in 7 IIH patients and 7 wt-matched non-IIH patients. CONCLUSION: BMI and percentage body fat both positively correlated with CSFOP, but BMI was more predictive in women and percentage body fat was more predictive in men. We did not find a relationship between distribution of body fat and CSFOP.

Lighten UP! A Community-Based Group Intervention to Promote Eudaimonic Well-Being in Older Adults: A Multi-Site Replication with 6 Month Follow-Up.

Objectives: Eudaimonic well-being (EWB), increasingly recognized as a critical component of health, typically declines in later life, and there are no existing programs to sustain or increase EWB in older adults. Lighten UP! is an 8-week program to promote EWB through facilitated group sessions in community settings and at-home practice. Building on earlier pilot research, the current study assessed the effect of the Lighten UP! Program using a longitudinal, multi-site design. Methods: Men and women (N = 169) aged 60 and over were recruited from three Wisconsin communities. EWB, life satisfaction, depression, and diverse aspects of health were assessed before and after the program and at 6-month follow up. Results: Participants reported significantly increased EWB; these changes were maintained 6 months later. The specific EWB domains of self-acceptance, positive relations, and personal growth showed the most robust gains. Participants also showed significant and sustained declines in depressive symptoms, anxiety, and hostility. Conclusions: Lighten UP! Program confirmed its positive effects for enhancing EWB in older adults living in multiple community settings. Clinical Implications: Programs that sustain or enhance EWB in older adults can be expected to yield improvements in diverse aspects of mental and physical health.

Evaluation of a novel cricothyroidotomy introducer in a simulated obese porcine model: a randomised crossover comparison with scalpel cricothyroidotomy.

The Difficult Airway Society 2015 guidelines for management of unanticipated difficulties in tracheal intubation in adults have generated much discussion regarding Plan D: emergency front-of-neck access with a scalpel-bougie cricothyroidotomy technique. There is concern that this technique may not provide an adequate pathway for the bougie and subsequently the tracheal tube, especially in obese patients with deeper airway structures. This could lead to the formation of a false passage, trauma and failure. A novel cricothyroidotomy introducer, 8 mm wide and 170 mm long, with a sharp leading edge and guiding channel to pass a bougie into the trachea, has been designed to complement the scalpel cricothyroidotomy technique. A comparison study of the use of this novel introducer with the scalpel technique in a simulated obese porcine laryngeal model demonstrated shorter insertion times (median (IQR [range]) 85 (65-123 [48-224]) s vs. 84 (72-184 [46-377]) s, p = 0.030). All 26 (100%) participants successfully performed cricothyroidotomy in the introducer group, whereas only 24 (92%) participants were successful in the scalpel group. The introducer group required fewer attempts to access the trachea compared with the scalpel group (p = 0.046). False passages occurred eight (31%) times in the introducer group compared with 17 (65%) times in the scalpel group (p = 0.022). There were no statistical differences in tracheal trauma (p = 0.490), ease of use (p = 0.220) and device preference (p = 0.240). This novel cricothyroidotomy introducer has shown promising results in securing the airway in an emergency front-of-neck access situation. With robust training, this introducer could potentially be complementary to the scalpel-bougie cricothyroidotomy technique.

Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets.

The application of toxicogenomics as a predictive tool for chemical risk assessment has been under evaluation by the toxicology community for more than a decade. However, it predominately remains a tool for investigative research rather than for regulatory risk assessment. In this study, we assessed whether the current generation of microarray technology in combination with an in vitro experimental design was capable of generating robust, reproducible data of sufficient quality to show promise as a tool for regulatory risk assessment. To this end, we designed a prospective collaborative study to determine the level of inter- and intra-laboratory reproducibility between three independent laboratories. All test centres (TCs) adopted the same protocols for all aspects of the toxicogenomic experiment including cell culture, chemical exposure, RNA extraction, microarray data generation and analysis. As a case study, the genotoxic carcinogen benzo[a]pyrene (B[a]P) and the human hepatoma cell line HepG2 were used to generate three comparable toxicogenomic data sets. High levels of technical reproducibility were demonstrated using a widely employed gene expression microarray platform. While differences at the global transcriptome level were observed between the TCs, a common subset of B[a]P responsive genes (n=400 gene probes) was identified at all TCs which included many genes previously reported in the literature as B[a]P responsive. These data show promise that the current generation of microarray technology, in combination with a standard in vitro experimental design, can produce robust data that can be generated reproducibly in independent laboratories. Future work will need to determine whether such reproducible in vitro model(s) can be predictive for a range of toxic chemicals with different mechanisms of action and thus be considered as part of future testing regimes for regulatory risk assessment.

Applicability of three alternative instruments for food authenticity analysis: GMO identification.

Ensuring foods are correctly labelled for ingredients derived from genetically modified organisms (GMOs) is an issue facing manufacturers, retailers, and enforcement agencies. DNA approaches for the determination of food authenticitys often use the polymerase chain reaction (PCR), and PCR products can be detected using capillary or gel electrophoresis. This study examines the fitness for purpose of the application of three laboratory electrophoresis instruments (Agilent Bioanalyzer 2100, Lab901 TapeStation, and Shimadzu MCE-202 MultiNA) for the detection of GMOs using PCR based on a previously validated protocol. Whilst minor differences in the performance characteristics of bias and precision were observed, all three instruments demonstrated their applicability in using this protocol for screening of GMO ingredients.

A Multiple Indicators Multiple Causes (MIMIC) model of Behavioural and Psychological Symptoms in Dementia (BPSD).

INTRODUCTION: Although there is evidence for distinct behavioural sub-phenotypes in Alzheimer's disease (AD), their inter-relationships and the effect of clinical variables on their expression have been little investigated. METHODS: We have analysed a sample of 1850 probable AD patients from the UK and Greece with 10 item Neuropsychiatric Inventory (NPI) data. We applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of MMSE, disease duration, gender, age and age of onset on the structure of a four-factor model consisting of "psychosis", "moods", "agitation" and "behavioural dyscontrol". RESULTS: Specific clinical variables predicted the expression of individual factors. When the inter-relationship of factors is modelled, some previously significant associations are lost. For example, lower MMSE scores predict psychosis, agitation and behavioural dyscontrol factors, but psychosis and mood predict the agitation factor. Taking these associations into account MMSE scores did not predict agitation. CONCLUSIONS: The complexity of the inter-relations between symptoms, factors and clinical variables is efficiently captured by this MIMIC model.

Diabetic retinopathy and socioeconomic deprivation in Gloucestershire.

OBJECTIVES: To investigate socioeconomic variations in diabetes prevalence, uptake of screening for diabetic retinopathy, and prevalence of diabetic retinopathy. METHODS: The County of Gloucestershire formed the setting of the study. A cross-sectional study of people with diabetes was done on a countywide retinopathy-screening database. Diabetes prevalence with odds ratios, uptake of screening, prevalence of any retinopathy and prevalence of sight-threatening retinopathy at screening were compared for different area deprivation quintiles. Logistic regression was used to adjust for confounding. RESULTS: With each increasing quintile of deprivation, diabetes prevalence increased (odds ratio 0.84), the probability of having been screened for diabetic retinopathy decreased (odds ratio 1.11), and the prevalence of sight-threatening diabetic retinopathy among screened patients increased (odds ratio of 0.98), while the prevalence of non-sight-threatening diabetic retinopathy remained unchanged with each increasing quintile of deprivation. CONCLUSION: Sight-threatening diabetic retinopathy was associated with socioeconomic deprivation, but non-sight-threatening diabetic retinopathy was not. Uptake of screening was inversely related to socioeconomic deprivation.

Randomised trial of flush saphenofemoral ligation for primary great saphenous varicose veins.

OBJECTIVES: The aim of this study was to assess different techniques of saphenofemoral ligation in the treatment of primary varicose veins. METHODS: One hundred and eighty-two patients (210 legs) with primary saphenofemoral junction incompetence were randomised to standard saphenofemoral ligation (transfixion with an absorbable suture) (SSL) or flush saphenofemoral ligation (oversewing with 4/0 polypropylene) (FSL). All legs underwent additional great saphenous vein stripping and multiple phlebectomies. Patients underwent assessment preoperatively, and at 6 weeks, 1 year and 2 years postoperatively with clinical examination, duplex imaging and completion of the Aberdeen Varicose Vein Symptom Severity Score (AVVSSS). RESULTS: A total of 148 patients (172 legs) attended follow-up at 2 years postoperatively. Recurrent varicose veins were visible in 30 legs (33 per cent) in the SSL group and 26 legs (32 per cent) in the FSL group (P=0.90). Neovascularisation was present in 20 groins (22 per cent) in the SSL group and 15 groins (19 per cent) in the FSL group (P=0.57). Nine cases of neovascularisation in the SSL group and five in the FSL group directly resulted in clinical recurrence (P=0.37). CONCLUSIONS: Flush ligation of the saphenofemoral junction confers no advantage over standard ligation with respect to clinical recurrence and neovascularisation. REGISTRATION NUMBER: ISRCTN20235689 (http://www.controlled-trials.com).

Visual acuity measurement and ocular co-morbidity in diabetic retinopathy screening.

AIMS: To evaluate the relationship between best corrected visual acuity (BCVA), age, type of diabetes, sight-threatening diabetic retinopathy (STDR) and ocular co-morbidity. METHODS: 1549 randomly selected people with diabetes mellitus (DM) from a countywide digital photographic screening programme had standardised logarithm of minimum angle of resolution (logMAR) BCVA measurement, followed by slit-lamp biomicroscopy examination by an experienced ophthalmologist. RESULTS: Subnormal vision (logMAR > or =0.3, Snellen < or =6/12) and blindness (logMAR >1.3, Snellen <3/60) in the better-seeing eye were found in 9.0% and 0.45%. The sensitivity, specificity and positive and negative predictive values of using subnormal vision to screen for STDR in an individual eye were 33.4%, 85.9%, 18.6% and 93.0%, respectively. Important contributory causes of moderate visual loss (logMAR 0.50 to 0.98, Snellen 6/18 or worse but better than 6/60) and of Acuity Blindness (logMAR > or =1.0, Snellen 6/60 or worse) in an individual eye were lenticular opacity (including capsular opacification) 49%, macular degeneration (including myopic degeneration) 29%, diabetic maculopathy 15%, other media causes (including corneal opacity) 13% and amblyopia 10%. CONCLUSION: The majority of visual loss in a population with diabetes is due to causes other than diabetic retinopathy. BCVA alone is not a reliable criterion in predicting STDR.

The nature of local recurrence after colorectal cancer resection.

OBJECTIVE: Local recurrence (LR) after rectal cancer resection has long been regarded as a particular problem, its incidence having been high. This study aims to determine the reasons why. METHOD: A prospective record was kept of all 887 cases of colorectal adenocarcinoma referred to one surgeon between 1989 and 2000. Of these, 802 underwent major resection. They were followed up for 5 years or until death. RESULTS: There was no significant difference between LR rates throughout the colorectum (P = 0.74). LR was significantly related to tumour grade (P < 0.001) and to tumour stage (P < 0.001), but not to the need to resect involved adjacent structures (P = 0.08), nor, after restorative rectal resection, to the distal margin of clearance (P = 0.97). A difference became apparent between recurrence resulting from tumour left in or implanted into the operation field and tumour resulting from pre-excision metastasis, here called, respectively, technique-related (TLR) and pre-excision metastatic (MLR) local recurrence. MLR was significantly related to tumour stage (P < 0.001), while TLR was not. Some TLR can be curatively excised. CONCLUSION: Rectal LR is no more common than colonic LR. There may be practical merit in discriminating between TLR and MLR.

Platelet beta-secretase activity is increased in Alzheimer's disease.

beta-Secretase activity is the rate-limiting step in Abeta peptide production from amyloid precursor protein. Abeta is a major component of Alzheimer's disease (AD) cortical amyloid plaques. beta-Secretase activity is elevated in post mortem brain tissue in AD. The current study investigated whether beta-secretase activity was also elevated in peripheral blood platelets. We developed a novel fluorimetric beta-secretase activity assay to investigate platelets isolated from individuals with AD (n=86), and age-matched controls (n=115). Platelet membrane beta-secretase activity (expressed as initial rate) varied over fourfold between individuals, raising important questions about in vivo regulation of this proteolytic activity. Nonetheless, we identified a significant 17% increase in platelet membrane beta-secretase activity in individuals with AD compared to controls (p=0.0003, unpaired t-test). Platelet membrane beta-secretase activity did not correlate with mini-mental state examination (MMSE) score in the AD group (mean MMSE=17.7, range 1-23), indicating that the increase did not occur as a secondary result of the disease process, and may even have preceded symptom onset.

Comparison of different methods of risk stratification in urgent and emergency surgery.

BACKGROUND: The aim was to compare a number of risk scoring systems prospectively in a cohort of patients who underwent non-elective surgery. METHODS: This was a cohort study of 2349 consecutive patients who had urgent or emergency surgery in a district general hospital in the UK. All patients were scored prospectively using the Revised Goldman Cardiac Risk Index (RGCRI), Portsmouth modification of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM), Surgical Risk Score (SRS) and Biochemistry and Haematology Outcome Models (BHOM). Actual 30-day and 1-year survival rates were compared with the predicted outcomes using receiver-operator characteristic (ROC) curves and Hosmer-Lemeshow analysis. RESULTS: Some 141 patients (6.0 per cent) died within 30 days of operation. This increased to 254 (10.8 per cent) by 1 year. The area under the ROC curve for death within 30 days was 0.90 for P-POSSUM, 0.85 for SRS, 0.84 for BHOM and 0.73 for RGCRI. Only the first three risk scores were able to discriminate accurately within the groups (area under ROC curve over 0.8), with no significant variation between expected and observed mortality rates confirmed by Hosmer-Lemeshow analysis. Similar results were found for the ability of each score to predict outcome at 1 year. CONCLUSION: P-POSSUM, SRS and BHOM scoring systems were all able to predict outcome after emergency and urgent surgery, but the SRS had the advantage of ease of calculation. BHOM requires only the most commonly available blood test data and the computer holding these data can easily perform the calculation.

Endoscopic endonasal laser versus endonasal surgical dacryocystorhinostomy for epiphora due to nasolacrimal duct obstruction: prospective, randomised, controlled trial.

BACKGROUND: Rhinostomy patency is a problem in all forms of dacryocystorhinostomy. Laser-assisted procedures are potentially fast and result in excellent haemostasis. However, they may induce more fibroblastic activity, resulting in excessive scarring and stenosis of the rhinostomy, compared with non-laser dissection. OBJECTIVES: The objective of this study was to compare subjective outcomes following dacryocystorhinostomy conducted with endoscopic endonasal laser and with endonasal surgical techniques. STUDY DESIGN: Prospective, randomised, controlled trial comparing potassium titanyl phosphate endonasal laser dissection with endonasal surgical techniques, for dacryocystorhinostomy to treat epiphora due to primary, acquired nasolacrimal duct obstruction. PARTICIPANTS: One hundred and twenty-six adult patients with chronic epiphora due to primary, acquired nasolacrimal sac or duct obstruction. INTERVENTIONS: INTERVENTIONS comprised endonasal dacryocystorhinostomy, performed using potassium titanyl phosphate laser or surgical dissection, in order to open the lacrimal sac into the nasal cavity. OUTCOME MEASURES: These were: symptom score and symptom relief of epiphora (at three and 12 months post-procedure); duration and ease of procedure; and duration of hospital stay. RESULTS: Sixty patients underwent endonasal laser dacryocystorhinostomy and 66 underwent endonasal surgical dacryocystorhinostomy. Symptomatic success was 82 per cent at three months and 68 per cent at 12 months in the laser group, and 76 per cent at three months and 74 per cent at 12 months in the surgical group. A two-point reduction in the symptom score was associated with symptomatic success at three and 12 months. Eight patients randomised to the laser group required additional instrumentation in order to remove thick bone over the lacrimal sac. CONCLUSIONS: At three months, endonasal laser dacryocystorhinostomy had better results than endonasal surgical dacryocystorhinostomy. However, at 12 months, the surgical procedure had better results than the laser procedure. There was no statistically significant difference between the two groups at three or 12 months with regard to symptomatic outcome. The ease of procedure (on a scale of zero to 10) was 4.5 for the laser procedure and 4.1 for the surgical procedure. The average times for the procedures were 25 minutes in the laser group and 20 minutes in the surgical group. No statistical difference was found when comparing: symptom score improvement for local anaesthetic vs general anaesthetic; ages over and under 70 years; laterality; or operating surgeon. Change in the symptom score was a useful indicator of symptomatic success.

Interaction between the ADAM12 and SH3MD1 genes may confer susceptibility to late-onset Alzheimer's disease.

The neuropathology of Alzheimer's disease (AD) is characterized by intracellular neurofibrillary tangles and the extracellular deposition of beta-amyloid (Abeta) in senile plaques. Abeta has been shown to mediate neurodegenerative and inflammatory changes associated with amyloid plaques, although the pathological mechanism of Abeta remains largely unknown. Recent evidence suggests that the FISH adapter protein binds to, and potentially regulates, ADAM12 (a disintegrin and metalloprotease 12) to mediate a neurotoxic effect of Abeta. The ADAM12 gene lies on chromosome 10q26.3, and the gene encoding FISH, SH3MD1, lies within a region of linkage to late-onset AD (LOAD) on 10q25.1. This study investigates whether there is a relationship between variation in ADAM12 and SH3MD1 and susceptibility to LOAD in a sample of 1,051 AD cases and 1,269 matched controls. We observe significant interactions between variants in the two genes that may influence susceptibility to LOAD. The most significant statistical interaction is between rs3740473, a synonymous single nucleotide polymorphism (SNP) in SH3MD1 and rs11244787, an intronic SNP in ADAM12 (effect size = 2.1 for interaction term, P = 0.006).

The effects of commonly prescribed drugs in patients with Alzheimer's disease on the rate of deterioration.

BACKGROUND: Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progression of their disease, both positively and negatively. AIM: To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer's disease. METHODS: Patients with the diagnosis of probable Alzheimer's disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period. RESULTS: Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin-angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively). CONCLUSION: Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin-angiotensin system and statins in reducing progression in clinical trials.

Proteome-based plasma biomarkers for Alzheimer's disease.

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.

'Losing my touch': decline in self-reported confidence in performing practical procedures in consultant oncologists.

This study aimed to compare the confidence of oncology consultants and specialist registrars (SpRs) in the performance of practical procedures, to contrast this with confidence in other areas of practice and to determine at what grade they felt most confident. Questionnaires were sent to all 57 oncology consultants and SpRs in the South-West region. Respondents scored confidence on a five-point Likert scale. The response rate was 70%. SpRs were significantly more confident in cardiopulmonary resuscitation (p = 0.003) and central line insertion (p = 0.006). Consultants were significantly more confident in developing management plans (p = 0.001) and performing committee work (p = 0.002). Only 6% of consultants felt most confident performing practical procedures as a consultant, and were less confident about these than other tasks (p = 0.001). Some 86% of SpRs considered they were more confident performing practical procedures as senior house officers (SHOs). In conclusion, self-reported confidence in performing practical procedures declines during career progression in oncology. This raises questions about the teaching and supervision of these procedures. If there is a greater emphasis on a consultant-provided service, their educational needs will need to be recognized and retraining or outsourcing of these procedures to other specialties may be necessary.

Lessons learned from a randomised controlled study of perioperative beta blockade in high risk patients undergoing emergency surgery.

BACKGROUND: Perioperative beta blockade has been shown to reduce mortality after major elective surgery. The aim of this study was to determine whether it could reduce the rate of death and morbidity from cardiac complications in high risk patients undergoing emergency surgery. METHODS: Over a one-year interval all patients undergoing major non-elective orthopaedic or general surgery were screened to identify those at high risk of cardiac complications. Consenting, high risk patients were randomly allocated atenolol or placebo for seven days, commencing at anaesthetic induction. Deaths and cardiac complications within 30 days were recorded. RESULTS: Some 2351 patients had an emergency operation; 145 were at high risk and eligible for the study. Of 89 patients approached, 57 initially consented. Only 38 patients, however, completed the study protocol, 19 were withdrawn. Of those who completed the study, 5/20 patients in the placebo group and 3/18 in the treatment group died before hospital discharge (p=0.520). Four others in the placebo group and two in the atenolol group had post-operative non-fatal cardiac events (positive troponin T), p=0.311. CONCLUSIONS: This study of emergency surgery proved more difficult than similar trials in elective surgery. The final study groups were small and there were no significant differences in outcomes. A much larger study is required for a definitive answer.