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Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.
We describe a simple model for turbulence in a marginally unstable, forced, stratified shear flow. The model illustrates the essential physics of marginally unstable turbulence, in particular the tendency of the mean flow to fluctuate about the marginally unstable state. Fluctuations are modelled as an oscillatory interaction between the mean shear and the turbulence. The interaction is made quantitative using empirically established properties of stratified turbulence. The model also suggests a practical way to estimate both the mean kinetic energy of the turbulence and its viscous dissipation rate. Solutions compare favourably with observations of fluctuating ‘deep cycle’ turbulence in the equatorial oceans.
Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months’ duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. Results: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). Conclusions: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.
A small eddy viscosity or mass diffusivity that varies with height has been found to have unexpected effects on the Kelvin–Helmholtz (KH) instability of a stably stratified shear layer near the neutral stability boundary. In particular, varying viscosity can increase the growth rate of the instability in contrast to the effect of uniform viscosity. Here, these results are extended to parameter ranges relevant in many geophysical and engineering contexts. We find that linearization of the viscous terms based on the assumption of weak viscosity/diffusivity is valid for non-dimensional values (inverse Reynolds number) up to
. Decreasing the Richardson number far below its critical value
can change, or even reverse, the effects of eddy viscosity and diffusivity. A primary goal is to explain the unexpected destabilization by viscosity. Varying viscosity affects vorticity (and other fluid properties) in a manner identical to advection with an advecting velocity equal to minus the gradient of viscosity. Destabilization occurs when this viscous ‘advection’ reinforces the vorticity distribution of a growing mode.
General Practitioner consultation rates for influenza-like illness (ILI) are monitored through several geographically distinct schemes in the UK, providing early warning to government and health services of community circulation and intensity of activity each winter. Following on from the 2009 pandemic, there has been a harmonization initiative to allow comparison across the distinct existing surveillance schemes each season. The moving epidemic method (MEM), proposed by the European Centre for Disease Prevention and Control for standardizing reporting of ILI rates, was piloted in 2011/12 and 2012/13 along with the previously proposed UK method of empirical percentiles. The MEM resulted in thresholds that were lower than traditional thresholds but more appropriate as indicators of the start of influenza virus circulation. The intensity of the influenza season assessed with the MEM was similar to that reported through the percentile approach. The MEM pre-epidemic threshold has now been adopted for reporting by each country of the UK. Further work will continue to assess intensity of activity and apply standardized methods to other influenza-related data sources.
The effect of non-zero, but small, viscosity and diffusivity on the marginal stability of a stably stratified shear flow is examined by making perturbations around the neutral solution for an inviscid and non-diffusive flow. The results apply to turbulent flows in which horizontal and vertical turbulent transports of momentum and buoyancy are represented by eddy coefficients of viscosity and diffusivity that vary in the vertical ($z$) direction. General expressions are derived for the modified phase speed and the growth rate of small disturbances as a function of wavenumber. To first order in their coefficients, the effect on the phase speed of adding viscosity and diffusivity is zero. Growth rates are found for two mean flows when the horizontal or vertical coefficients of viscosity and diffusivity vary in $z$ in such a way that the rates can be found analytically. The first flow, denoted as a ‘Holmboe flow’, has a velocity and density interface: the mean horizontal velocity and the density are both proportional to $\tanh az$, where $a$ is proportional to the inverse of the interface thickness. The second, ‘Drazin flow’, has a similar velocity variation in $z$ but uniform density gradient. The analytical results compare favourably with numerical calculations. Small horizontal coefficients of viscosity and diffusivity may affect disturbances to the flow in opposite ways. Although the effect of uniform vertical coefficients of viscosity is to decrease the growth rates, and uniform vertical coefficients of diffusivity increase them, cases are found in which, with suitably chosen $z$ dependence, vertical coefficients of viscosity (or diffusivity) may cause a previously neutral disturbance to grow (or to diminish); viscosity may destabilize a stably stratified shear flow. The introduction of viscosity and diffusivity may consequently increase the critical Richardson number to a value exceeding $1/ 4$. While some patterns of behaviour are apparent, no simple rule appears to hold about whether flows that are neutral in the absence of these effects (viscosity or diffusivity) will be stabilized or destabilized when they are added. One such rule, namely our conjecture that viscosity is always stabilizing and that diffusivity is destabilizing, is explicitly refuted.
Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery.
A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement.
Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008).
Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.
Syndromic surveillance is vital for monitoring public health during mass gatherings. The London 2012 Olympic and Paralympic Games represents a major challenge to health protection services and community surveillance. In response to this challenge the Health Protection Agency has developed a new syndromic surveillance system that monitors daily general practitioner out-of-hours and unscheduled care attendances. This new national system will fill a gap identified in the existing general practice-based syndromic surveillance systems by providing surveillance capability of general practice activity during evenings/nights, over weekends and public holidays. The system will complement and supplement the existing tele-health phone line, general practitioner and emergency department syndromic surveillance systems. This new national system will contribute to improving public health reassurance, especially to meet the challenges of the London 2012 Olympic and Paralympic Games.
To evaluate the outcomes of patients with giant pituitary tumours (GPTs) who underwent a purely binasal endoscopic transsphenoidal surgery (BETS) and compare their outcomes with those achieved through craniotomy and microscopic transsphenoidal surgery (MTS).
Seventy-two consecutive patients with GPTs (greater than 10 cm3 in volume) who were treated surgically with BETS, craniotomy, or MTS from October 1994 to July 2009 were reviewed for clinical outcomes, degree of tumor resection, recurrence rates, and surgical complications.
The BETS group had significantly better mean reduction of tumor volume (91%) than the craniotomy (63%, p = 0.001), and the MTS (63%, p = 0.010) groups. Gross total resection rates were also higher for BETS patients than for craniotomy patients (p = 0.010). Improvements in vision and headaches were noted in 96% and 100% of patients in the BETS group, respectively; these rates were similar to those in the craniotomy and MTS groups. Of the four patients with hormone-secreting tumours in the BETS group, three remained in remission. The median length-of-stay (four days) for the BETS group was shorter (p = 0.010), and surgical complications were less frequent (p = 0.037) and less severe compared to the craniotomy group. There were no differences in the recurrence rates: 79% percent of patients in the BETS group, 69% in the craniotomy group, and 79% in the MTS group were recurrence free at last follow-up (p = 0.829).
Treatment of GPT with BETS offers excellent oncologic and clinical outcomes and can frequently obviate the need for craniotomy in these patients.
An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42–66); age-specific adjusted VE was 87% (95% CI 45–97) in <5-year-olds and 84% (95% CI 27–97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI −6 to 51) overall and 72% (95% CI 15–91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42–68) and in 5- to 14-year-olds 75% (95% CI 32–91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.
The Taylor–Goldstein (T–G) equation is extended to include the effects of small-scale turbulence represented by non-uniform vertical and horizontal eddy viscosity and diffusion coefficients. The vertical coefficients of viscosity and diffusion, and , respectively, are assumed to be equal and are expressed in terms of the buoyancy frequency of the flow, , and the dissipation rate of turbulent kinetic energy per unit mass, , quantities that can be measured in the sea. The horizontal eddy coefficients, and , are taken to be proportional to the dimensionally correct form, , found appropriate in the description of horizontal dispersion of a field of passive markers of scale . The extended T–G equation is applied to examine the stability and greatest growth rates in a turbulent shear flow in stratified waters near a sill, that at the entrance to the Clyde Sea in the west of Scotland. Here the main effect of turbulence is a tendency towards stabilizing the flow; the greatest growth rates of small unstable disturbances decrease, and in some cases flows that are unstable in the absence of turbulence are stabilized when its effects are included. It is conjectured that stabilization of a flow by turbulence may lead to a repeating cycle in which a flow with low levels of turbulence becomes unstable, increasing the turbulent dissipation rate and so stabilizing the flow. The collapse of turbulence then leads to a condition in which the flow may again become unstable, the cycle repeating. Two parameters are used to describe the ‘marginality’ of the observed flows. One is based on the proximity of the minimum flow Richardson number to the critical Richardson number, the other on the change in dissipation rate required to stabilize or destabilize an observed flow. The latter is related to the change needed in the flow Reynolds number to achieve zero growth rate. The unstable flows, typical of the Clyde Sea site, are relatively further from neutral stability in Reynolds number than in Richardson number. The effects of turbulence on the hydraulic state of the flow are assessed by examining the speed and propagation direction of long waves in the Clyde Sea. Results are compared to those obtained using the T–G equation without turbulent viscosity or diffusivity. Turbulence may change the state of a flow from subcritical to supercritical.
This article examines the changes in herbicide use in relation to canola production in Western Canada, comparing 1995 and 2006. The commercialization and widespread adoption of herbicide-resistant (HR) canola has changed weed management practices in Western Canada. Before the introduction of HR canola, weeds were controlled by herbicides and tillage as the leading herbicides at that time required tillage to allow for soil incorporation of the herbicide. Much of the tillage associated with HR canola production has been eliminated as 64% of producers are now using zero or minimum tillage as their preferred form of crop and soil management. Additionally, there have been significant changes regarding the use and application of herbicides for weed control in canola. This research shows that when comparing canola production in 1995 and 2006, the environmental impact of herbicides applied to canola decreased 53%, producer exposure to chemicals decreased 56%, and quantity of active ingredient applied decreased 1.3 million kg. The cumulative environmental impact was reduced almost 50% with the use of HR herbicides. If HR canola had not been developed and Canadian canola farmers continued to use previous production technologies, the amount of active ingredient applied to control weeds in 2007 would have been 60% above what was actually applied.
To report a large outbreak of Clostridium difficile infection (CDI; ribotype 027) between June 2007 and August 2008, describe infection control measures, and evaluate the impact of restricting the use of fluoroquinolones in controlling the outbreak.
Outbreak investigation in 3 acute care hospitals of the Northern Health and Social Care Trust in Northern Ireland.
Implementation of a series of CDI control measures that targeted high-risk antibiotic agents (ie, restriction of fluoroquinolones), infection control practices, and environmental hygiene.
A total of 318 cases of CDI were identified during the outbreak, which was the result of the interaction between C. difficile ribotype 027 being introduced into the affected hospitals for the first time and other predisposing risk factors (ranging from host factors to suboptimal compliance with antibiotic guidelines and infection control policies). The 30-day all-cause mortality rate was 24.5%; however, CDI was the attributable cause of death for only 2.5% of the infected patients. Time series analysis showed that restricting the use of fluoroquinolones was associated with a significant reduction in the incidence of CDI (coefficient, —0.054; lag time, 4 months; P = .003).
These findings provide additional evidence to support the value of antimicrobial stewardship as an essential element of multifaceted interventions to control CDI outbreaks. The present CDI outbreak was ended following the implementation of an action plan improving communication, antibiotic stewardship, infection control practices, environmental hygiene, and surveillance.
The assumption that the transmission of social behaviors and political preferences is purely cultural has been challenged repeatedly over the last 40 years by the combined evidence of large studies of adult twins and their relatives, adoption studies, and twins reared apart. Variance components and path modeling analyses using data from extended families quantified the overall genetic influence on political attitudes, but few studies have attempted to localize the parts of the genome which accounted for the heritability estimates found for political preferences. Here, we present the first genome-wide analysis of Conservative-Liberal attitudes from a sample of 13,000 respondents whose DNA was collected in conjunction with a 50-item sociopolitical attitude questionnaire. Several significant linkage peaks were identified and potential candidate genes discussed.
The UK was one of few European countries to document a substantial wave of pandemic (H1N1) 2009 influenza in summer 2009. The First Few Hundred (FF100) project ran from April–June 2009 gathering information on early laboratory-confirmed cases across the UK. In total, 392 confirmed cases were followed up. Children were predominantly affected (median age 15 years, IQR 10–27). Symptoms were mild and similar to seasonal influenza, with the exception of diarrhoea, which was reported by 27%. Eleven per cent of all cases had an underlying medical condition, similar to the general population. The majority (92%) were treated with antiviral drugs with 12% reporting adverse effects, mainly nausea and other gastrointestinal complaints. Duration of illness was significantly shorter when antivirals were given within 48 h of onset (median 5 vs. 9 days, P=0·01). No patients died, although 14 were hospitalized, of whom three required mechanical ventilation. The FF100 identified key clinical and epidemiological characteristics of infection with this novel virus in near real-time.