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Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, spinal cord injury, or multiple sclerosis. These syndromes are much less common than peripheral etiologies, with less known regarding optimal treatment. The objective of this study was to determine the long-term clinical effectiveness of the management of central relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified from a prospective observational cohort from seven Canadian tertiary centers. Data regarding patient -characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome was the composite of reduced average pain intensity and pain interference. Secondary outcomes included assessments of function, mood, and quality-of-life. Results: At 12-month follow-up, 13.5% (95%CI,5.6-25.8) of patients achieved ≥30% reduction in pain, whereas 38.5% (95%CI,25.3-53.0) achieved a ≥1 point reduction in pain interference; 9.6% (95%CI,3.2-21.0) of patients achieving both these measures. Patients with peripheral neuropathic pain were more likely to achieve this primary outcome at 12-months (25.3% of patients; 95%CI,21.4-29.5) (p=.012). Conclusions: Patients with central neuropathic pain were less likely to achieve a meaningful improvement in pain and function compared to patients with peripheral neuropathic pain at 12-month follow-up.
Background: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent–offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. Methods: We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime ‘ever’ smoking measure was obtained from twins and relatives in the ‘Virginia 30,000’ sample and the ‘Australian 25,000’. Results: Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent–offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. Conclusions: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI.
There are no available medications for the management of alcohol dependence for patients with alcoholic liver disease (ALD).
To conduct a multisite, double blind, placebo-controlled, randomised clinical trial of baclofen in the treatment of alcohol dependence, with or without liver disease (trial registration: ClinicalTrials.gov, NCT01711125).
Patients (n = 104) were randomised to placebo, baclofen 30 mg/day or 75 mg/day for 12 weeks. Primary outcomes included survival time to lapse (any drinking), relapse (≥5 drinks per day in men and ≥4 in women), and the composite outcome of drinks per drinking day, number of heavy drinking days, and percentage days abstinent.
There was a significant effect of baclofen (composite groups) on time to lapse (χ2 = 6.44, P<0.05, Cohen's d = 0.56) and relapse (χ2 = 4.62, P<0.05, d = 0.52). A significant treatment effect of baclofen was observed for percentage days abstinent (placebo 43%, baclofen 30 mg 69%, baclofen 75 mg 65%; P<0.05). There was one serious adverse event (overdose) directly related to medication (75 mg).
Baclofen may be an effective treatment option for patients with ALD. However, given the profile of adverse events, the role for this medication might be best limited to specialist services.
Evidence is emerging regarding the influence of meteorological factors on seasonal respiratory syncytial virus outbreaks. Data however, are limited for subtropical regions, especially in the southern hemisphere. We examined whether meteorological data (daily minimum and maximum temperatures, rainfall, relative humidity, dew point, daily global solar exposure) and tourist numbers were associated with the incidence of RSV in children aged <5 years for the Gold Coast region of South-East Queensland, Australia (latitude 28.0°S). RSV cases between 1 July 2007 and 30 June 2016 were identified from the Pathology Queensland Gold Coast Laboratory database. Time-series methods were used to identify seasonal patterns. RSV activity peaked in mid-to-late autumn (April–May), tapering in winter (June–August). While most meteorological variables measured were associated with RSV incidence, rainfall (ρ = 0.40, 95% confidence interval (CI) 0.32–0.48) and humidity (ρ = 0.38, 95% CI 0.29–0.46) 8 weeks earlier had the nearest temporal relationship. Tourist numbers were not correlated with RSV activity. Identifying meteorological conditions associated with seasonal RSV epidemics can improve understanding of virus transmission and assist planning for their impact upon the health sector, including timing of passive RSV immunoprophylaxis for high-risk infants and future public health interventions, such as maternal immunisation with RSV vaccines.
The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use.
A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype.
Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency.
There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology.
Skin care practices for radiotherapy patients are complicated by dosimetric concerns. This study measures the effect on skin dose of various topical agents and dressings.
Materials and methods
Superficial doses were measured under 17 topical agents and dressings and three clinical materials for reference. Dose was measured using a MOSFET detector under a 1 mm polymethyl methacrylate slab, with 6 MV photon beams at 100 cm source to surface distance.
Relative skin dose under reference materials was 128% (thermoplastic mask), 158% (5 mm bolus) and 171% (10 mm bolus). Under a realistic application of topical agent (0·5 mm), relative skin doses were 106–111%. All dry dressings yielded relative dose of ≤111%; two wet dressings yielded higher relative doses (133 and 141%).
Under clinically relevant conditions, no cream, gel or dry dressing increased the skin dose beyond that seen with a thermoplastic mask. Dressings soaked with water produced less skin dose than 5 mm bolus. This may be unacceptable if wet dressings are in place for the majority of the treatment course. Our results suggest that skin care practices should not be limited by dosimetric concerns when using a 6 MV photon beam.
A number of sophisticated modelling approaches are available to investigate potential associations between antimicrobial use (AMU) and resistance (AMR) in animal health settings. All have their advantages and disadvantages, making it unclear as to which model is most appropriate. We used advanced regression modelling to investigate AMU-AMR associations in faecal non-type-specific Escherichia coli (NTSEC) isolates recovered from 275 pens of feedlot cattle. Ten modelling strategies were employed to investigate AMU associations with resistance to chloramphenicol, ampicillin, sulfisoxazole, tetracycline and streptomycin. Goodness-of-fit statistics did not show a consistent advantage for any one model type. Three AMU-AMR associations were significant in all models. Recent parenteral tetracycline use increased the odds of finding tetracycline-resistant NTSEC [odds ratios (OR) 1·1–3·2]; recent parenteral sulfonamide use increased the odds of finding sulfisoxazole-resistant NTSEC (OR 1·4–2·5); and recent parenteral macrolide use decreased the odds of recovering ampicillin-resistant NTSEC (OR 0·03–0·2). Other results varied markedly depending on the modelling approach, emphasizing the importance of exploring and reporting multiple modelling methods based on a balanced consideration of important factors such as study design, mathematical appropriateness, research question and target audience.
Jupiter-sized brown dwarfs are found in the solar neighborhood with effective temperature Teff as low as 250 K . Iron, silicates, chlorides and sulfides condense in the atmospheres of the Teff ≈ 2000 K L-type and Teff ≈ 1000 K T-type dwarfs . At the T-/Y-type boundary, Teff ≈ 500 K and atmospheres are clear . The next species to condense are H2O at Teff ≈ 350 K and NH3 at Teff ≈ 200 K .
Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of duration ≤3 months. Limited data are available on the long-term outcomes of this chronic disease. This study aims 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, 43 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) guidelines including Brief Pain Inventory (BPI). Results: At 12-month follow-up, 37.2% of 43 patients achieved pain reduction of ≥30%, 51.2% achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, BPI), and 30.2% (95% CI: 17.2% to 46.1%) had achieved both these measures. Symptom management included at least 2 medication classes in 55.3%, and 3 medications classes (opioids, antidepressants, anticonvulsants) in 25.5%. Conclusions: A sizable minority of patients being managed for PDN in a tertiary care setting achieve meaningful improvement. Polypharmacy, including analgesic antidepressants, anticonvulsants and opioids, is often necessary to attain symptom management.
Childhood cardiovascular risk factors affect vascular function long before overt cardiovascular disease. Twin studies provide a unique opportunity to examine the influence of shared genetic and environmental influences on childhood cardiovascular function. We examined the relationship between birth parameters, markers of adiposity, insulin resistance, lipid profile and blood pressure and carotid–femoral pulse wave velocity (PWV), a validated non-invasive measure of arterial stiffness in a healthy cohort of school-aged twin children.
PWV was performed on a population-based birth cohort of 147 twin pairs aged 7–11 years. Fasting blood samples, blood pressure and adiposity measures were collected concurrently. Mixed linear regression models were used to account for twin clustering, within- and between-twin pair associations.
There were positive associations between both markers of higher adiposity, insulin resistance, elevated triglycerides and PWV, which remained significant after accounting for twin birth-set clustering. There was a positive association between both diastolic and mean arterial blood pressure and PWV in within-pair analysis in dizygotic, but not monozygotic twins, indicating genetic differences evident in dizygotic not monozygotic twins may affect these associations.
Increased blood pressure, triglycerides and other metabolic markers are associated with increased PWV in school-aged twins. These results support both the genetic and environmental contribution to higher PWV, as a marker of arterial stiffness, and reiterate the importance of preventing metabolic syndrome from childhood.
Determine whether daily bathing with chlorhexidine-based soap decreased methicillin-resistant Staphylococcus aureus (MRSA) transmission and intensive care unit (ICU)-acquired S. aureus infection among ICU patients.
Prospective pre-post-intervention study with control unit.
A 1,250-bed tertiary care teaching hospital.
Medical and surgical ICU patients.
Active surveillance for MRSA colonization was performed in both ICUs. In June 2005, a chlorhexidine bathing protocol was implemented in the surgical ICU. Changes in S. aureus transmission and infection rate before and after implementation were analyzed using time-series methodology.
The intervention unit had a 20.68% decrease in MRSA acquisition after institution of the bathing protocol (12.64 cases per 1,000 patient-days at risk before the intervention vs 10.03 cases per 1,000 patient-days at risk after the intervention; β, −2.62 [95% confidence interval (CI), −5.19 to −0.04]; P = .046). There was no significant change in MRSA acquisition in the control ICU during the study period (10.97 cases per 1,000 patient-days at risk before June 2005 vs 11.33 cases per 1,000 patient-days at risk after June 2005; β, −11.10 [95% CI, −37.40 to 15.19]; P = .40). There was a 20.77% decrease in all S. aureus (including MRSA) acquisition in the intervention ICU from 2002 through 2007 (19.73 cases per 1,000 patient-days at risk before the intervention to 15.63 cases per 1,000 patient-days at risk after the intervention [95% CI, −7.25 to −0.95]; P = .012)]. The incidence of ICU-acquired MRSA infections decreased by 41.37% in the intervention ICU (1.96 infections per 1,000 patient-days at risk before the intervention vs 1.15 infections per 1,000 patient-days at risk after the intervention; P = .001).
Institution of daily chlorhexidine bathing in an ICU resulted in a decrease in the transmission of S. aureus, including MRSA. These data support the use of routine daily chlorhexidine baths to decrease rates of S. aureus transmission and infection.
We report a missed case of otosyphilis presenting as otic capsule lucencies on temporal bone computed tomography.
A 58-year-old woman presented with a 15-year history of bilateral, mixed hearing loss together with otic capsule lucencies, subsequently confirmed as otosyphilis. A literature review of otosyphilis was undertaken based on a PubMed search of studies published between 1988 and 2012, using the key words ‘otosyphilis’, ‘otodystrophy’, ‘otic capsule lucencies’ and ‘luetic osteitis’.
Results and conclusion:
Although rare, otosyphilis is important to recognise as it is one of the few treatable causes of deafness when diagnosed early. The differentiating computed tomography features of luetic osteitis (otosyphilis) of the temporal bone have only rarely been described. We emphasise how these imaging features can be used to distinguish the rare but treatable condition of luetic osteitis from other, more common conditions with similar imaging findings.
The study objective was to use Bayesian latent class analysis to evaluate the accuracy of susceptibility test results obtained from disk diffusion and broth microdilution using bacteria recovered from beef feedlot cattle. Isolates of Escherichia coli and Mannheimia haemolytica were tested for susceptibility to ampicillin, ceftiofur, streptomycin, sulfisoxazole, tetracycline, and trimethoprim-sulfamethoxazole. Results showed that neither testing method was always or even generally superior to the other. Specificity (ability to correctly classify non-resistant isolates) was extremely high for both testing methods, but sensitivity (ability to correctly classify resistant isolates) was lower, variable in the drugs evaluated, and variable between the two bacterial species. Predictive values estimated using Bayesian Markov chain Monte Carlo models showed that the ability to predict true susceptibility status was equivalent for test results obtained with the two testing methods for some drugs, but for others there were marked differences between results obtained from disk diffusion and broth microdilution tests.
This paper investigates the impact of institutions on the dollarization of the domestic banking system using a unique policy experiment: the process of accession of countries to the European Union (EU). Using a dynamic factor model, we decompose fluctuations in financial dollarization for 24 transition economies into a common factor, an EU factor, a non-EU factor, and country-specific factors. The EU factor, which proxies for improvements in institutions under the set criteria for eventual membership, reveals the importance of institutions for the extent of financial dollarization over time. The results also indicate the asymmetric impact of improved institutions on the domestic bank's balance sheets by inducing higher loan dollarization and lower deposit dollarization. The relative importance of the EU factor to the financial dollarization of a country is associated to the degree of comovement of its business cycle with that of the EU.
Patient teaching in radiation therapy may include restrictions on applying skin products owing to concerns that the presence of such materials may increase skin dose. These restrictions may create unnecessarily complicated and conflicting self-care instructions.
To determine what thickness of skin product is necessary to produce a clinically meaningful dose increase to the skin, and provide recommendations for evidence-based patient instructions.
Dosimetric measurements and Monte Carlo simulations were used to calculate skin dose under 0–1·5 mm thicknesses of two common classes of skin product for a variety of treatment geometries. The thickness of product required to produce a clinically significant dose increase to the skin was determined.
The thickness of product required to create a clinically meaningful dose increase was >0·7 mm for 10 × 10 cm2 fields and >1·5 mm for 1 × 1 cm2 fields. A typical application of product would be only 0·3 mm.
It seems unrealistic to anticipate patients using sufficiently large quantities of skin product to be of clinical concern. We therefore recommend that there are no dosimetric reasons to restrict the use of these types of skin products during radiation therapy for common treatment scenarios.