Obesity in adolescent men increases the risk of venous thromboembolism in adult life.

BACKGROUND: As the population of obese and severely obese young adults grows, it is becoming increasingly important to recognize the long-term risks associated with adolescent obesity. OBJECTIVES: This study aimed to determine the association between body mass index (BMI) in young men at enlistment for military service and later risk of venous thromboembolism (VTE). METHODS: Nationwide register-based prospective cohort study of men enlisting 1969 to 2005, followed through the Swedish National Patient and Cause of Death registries. We identified 1 639 838 men (mean age, 18.3 years) free of prior venous thromboembolism, of whom 29 342 were obese (BMI 30 to <35 kg m-2 ) and 7236 severely obese (BMI ≥ 35 kg m-2 ). The participants were followed until a first registered diagnosis of VTE. RESULTS: During a median follow-up of 28 years (interquartile interval, 20 to 36 years), 11 395 cases of deep vein thrombosis and 7270 cases of pulmonary embolism were recorded. Compared with men with a BMI of 18.5 to <20 kg m-2 , men with higher BMI in young adulthood showed an incrementally increasing risk of VTE that was moderately but significantly increased already at normal BMI levels. Adolescent obese men with a BMI of 30 to 35 kg m-2 had an adjusted hazard ratio of 2.93 (95% confidence interval, 2.65 to 3.24) for VTE. Severely obese men with a BMI of ≥35 kg m-2 had a hazard ratio of 4.95 (95% confidence interval, 4.16 to 5.90). CONCLUSIONS: Men who were obese or severely obese in young adulthood had a marked increase in risk of VTE.

Single bead investigation of a clinical drug delivery system - A novel release mechanism.

Microgels, such as polymeric hydrogels, are currently used as drug delivery devices (DDSs) for chemotherapeutics and/or unstable drugs. The clinical DDS DC bead® was studied with respect to loading and release, measured as relative bead-volume, of six amphiphilic molecules in a micropipette-assisted microscopy method. Theoretical models for loading and release was used to increase the mechanistic understanding of the DDS. It was shown that equilibrium loading was independent of amphiphile concentration. The loading model showed that the rate-determining step was diffusion of the molecule from the bulk to the bead surface ('film control'). Calculations with the developed and applied release model on the release kinetics were consistent with the observations, as the amphiphiles distribute unevenly in the bead. The rate determining step of the release was the diffusion of the amphiphile molecule through the developed amphiphile-free depletion layer. The release rate is determined by the diffusivity and the tendency for aggregation of the amphiphile where a weak tendency for aggregation (i.e. a large cacb) lead to faster release. Salt was necessary for the release to happen, but at physiological concentrations the entry of salt was not rate-determining. This study provides valuable insights into the loading to and release from the DDS. Also, a novel release mechanism of the clinically used DDS is suggested.

Pain-relieving effectiveness, quality of life and tolerability of repeated capsaicin 8% patch treatment of peripheral neuropathic pain in Scandinavian clinical practice.

CONTEXT: Clinical trials have demonstrated the efficacy and safety of the capsaicin 8% patch in patients with peripheral neuropathic pain (PNP); however, few studies have assessed this treatment in a clinical practice. OBJECTIVE: To determine whether treatment and re-treatment with the capsaicin 8% patch reduce PNP intensity in clinical practice. METHODS: Three non-interventional, observational studies were concurrently conducted in Denmark, Norway and Sweden. Patients with probable or definite PNP received one or two treatments with the capsaicin 8% patch according to usual clinical practice. All analyses were performed on combined data. RESULTS: Overall, 382 and 181 patients received treatment and re-treatment, respectively, with the capsaicin 8% patch. At the group level, a significant reduction in mean level of 'usual pain' intensity (Numerical Pain Rating Scale) over the last 24 h' score was observed from baseline to Weeks 2 through 8 [-1.05 (95% confidence interval: -1.27, 0.82); p < 0.001] with 28% and 31% of patients reporting a ≥30% reduction in pain after first treatment and re-treatment, respectively. Improvements in health-related quality of life (EQ-5D-3L index) and overall health status (Patient Global Impression of Change) were observed early (Week 1) and throughout the treatment periods. Most application site reactions subsided within a week after treatment. Following treatment and re-treatment, 57% and 71% of patients, respectively, were willing to undergo further treatment with the capsaicin 8% patch. CONCLUSION: In Scandinavian clinical practice, capsaicin 8% patch treatment was associated with significant reductions in pain intensity and was well tolerated with over half of patients willing to undergo re-treatment.

A shorter system delay for haemorrhagic stroke than ischaemic stroke among patients who use emergency medical service.

OBJECTIVES: We compare various aspects in the early chain of care among patients with haemorrhagic stroke and ischaemic stroke. MATERIALS & METHODS: The Emergency Medical Services (EMS) and nine emergency hospitals, each with a stroke unit, were included. All patients hospitalised with a first and a final diagnosis of stroke between 15 December 2010 and 15 April 2011 were included. The primary endpoint was the system delay (from call to the EMS until diagnosis). Secondary endpoints were: (i) use of the EMS, (ii) delay from symptom onset until call to the EMS; (iii) priority at the dispatch centre; (iv) priority by the EMS; and (v) suspicion of stroke by the EMS nurse and physician on admission to hospital. RESULTS: Of 1336 patients, 172 (13%) had a haemorrhagic stroke. The delay from call to the EMS until diagnosis was significantly shorter in haemorrhagic stroke. The patient's decision time was significantly shorter in haemorrhagic stroke. The priority level at the dispatch centre did not differ between the two groups, whereas the EMS nurse gave a significantly higher priority to patients with haemorrhage. There was no significant difference between groups with regard to the suspicion of stroke either by the EMS nurse or by the physician on admission to hospital. CONCLUSIONS: Patients with a haemorrhagic stroke differed from other stroke patients with a more frequent and rapid activation of EMS.

EAN guidelines on central neurostimulation therapy in chronic pain conditions.

BACKGROUND AND PURPOSE: Our aim was to update previous European Federation of Neurological Societies guidelines on neurostimulation for neuropathic pain, expanding the search to new techniques and to chronic pain conditions other than neuropathic pain, and assessing the evidence with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. METHODS: A systematic review and meta-analysis of trials published between 2006 and December 2014 was conducted. Pain conditions included neuropathic pain, fibromyalgia, complex regional pain syndrome (CRPS) type I and post-surgical chronic back and leg pain (CBLP). Spinal cord stimulation (SCS), deep brain stimulation (DBS), epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS) and transcranial direct electrical stimulation (tDCS) of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) were assessed. The GRADE system was used to assess quality of evidence and propose recommendations. RESULTS: The following recommendations were reached: 'weak' for SCS added to conventional medical management in diabetic painful neuropathy, CBLP and CRPS, for SCS versus reoperation in CBLP, for MCS in neuropathic pain, for rTMS of M1 in neuropathic pain and fibromyalgia and for tDCS of M1 in neuropathic pain; 'inconclusive' for DBS in neuropathic pain, rTMS and tDCS of the DLPFC, and for motor cortex tDCS in fibromyalgia and spinal cord injury pain. CONCLUSIONS: Given the poor to moderate quality of evidence identified by this review, future large-scale multicentre studies of non-invasive and invasive neurostimulation are encouraged. The collection of higher quality evidence of the predictive factors for the efficacy of these techniques, such as the duration, quality and severity of pain, is also recommended.

Surfactant-induced core/shell phase equilibrium in hydrogels.

The formation of core/shell structures in hydrogels upon interaction with surfactants is a well-known phenomenon, but whether they are equilibrium states or not is still under debate. This paper presents an equilibrium theory of phase coexistence in hydrogels meant to answer the question of the stability of core/shell separation. The theory suggests that core/shell separation caused by surfactants can indeed be thermodynamically stable if the amount of added surfactant is not too large, but that the exact phase behaviour is governed by both the volume and concentration of the added surfactant solution.

Recommendations on practice of conditioned pain modulation (CPM) testing.

Protocols for testing conditioned pain modulation (CPM) vary between different labs/clinics. In order to promote research and clinical application of this tool, we summarize the recommendations of interested researchers consensus meeting regarding the practice of CPM and report of its results.

Incidence of Type 2 diabetes among occupational classes in Sweden: a 35-year follow-up cohort study in middle-aged men.

AIMS: To assess if low occupational class was an independent predictor of Type 2 diabetes in men in Sweden over a 35-year follow-up, after adjustment for both conventional risk factors and psychological stress. METHODS: A random population-based sample of 6874 men aged 47-56 years without a history of diabetes was divided into five occupational classes and the men were followed from 1970 to 2008. Diabetes cases were identified through the Swedish inpatient and death registers. Subdistribution hazard ratios (SHRs) and 95% CIs from competing risk regressions, cumulative incidence and conditional probabilities were calculated, after accounting for the risk of death attributed to other causes. RESULTS: A total of 907 (13%) men with diabetes were identified over 35 years with a median follow-up of 27.9 years. The cumulative incidence of diabetes, when taking into account death as a competing event, was 11% in high officials, 12% in intermediate non-manual employees, 14% in assistant non-manual employees, 14% in skilled workers, and 16% in unskilled and semi-skilled workers. Men with unskilled and semi-skilled manual occupations had a significantly higher risk of diabetes than high officials (reference) after adjustment for age, BMI, hypertension, smoking and physical activity (SHR 1.39, 95% CI 1.08-1.78). Additional adjustment for self-reported psychological stress did not attenuate the results. CONCLUSIONS: A low occupational class suggests a greater risk of Type 2 diabetes, independently of conventional risk factors and psychological stress.

The influence of intensity and duration of a painful conditioning stimulation on conditioned pain modulation in volunteers.

BACKGROUND AND METHOD: The aim was to investigate influence from variations in intensity of a painful conditioning stimulation (CS) on early (0-6 min) and prolonged (6-12 min) conditioned pain modulation (CPM) in volunteers during concurrent exposure to test stimuli (TS). CS was applied to either forearm using painful heat with an intensity of 2/10 and 5/10, respectively, rated on a 0-10 numerical pain rating scale. At a second session, CS with an intensity of 7/10 was applied to the arm using a tourniquet. Threshold and suprathreshold painful heat and pressure as well as painful repeated monofilament pricking (RMP) were assessed as TS. RESULTS: Regardless of TS, there was no significant difference in the magnitude of CPM within the same stimulus modality during the various intensities and phases of the CS. Significant modulation of heat pain thresholds (HPTs) was found during the early phase at 5/10 and 7/10, but not at 2/10. Only at 5/10 the prolonged CS resulted in a significant additional increase in HPT. During the early CS phase, CPM of suprathreshold heat pain was found at 2/10 and 5/10. The prolonged CS resulted in a significant additional temperature increase at 5/10. Only during the early phase significant CPM of pressure pain thresholds were found for all three pain intensities in conjunction with a significant CPM of suprathreshold pressure pain at 5/10. There was no CPM of RMP. CONCLUSION: The CS intensity and the duration of CPM modulated pain sensitivity differentially across TS modalities.

Life cycle assessment of energy self-sufficiency systems based on agricultural residues for organic arable farms.

The agricultural industry today consumes large amounts of fossil fuels. This study used consequential life cycle assessment (LCA) to analyse two potential energy self-sufficient systems for organic arable farms, based on agricultural residues. The analysis focused on energy balance, resource use and greenhouse gas (GHG) emissions. A scenario based on straw was found to require straw harvest from 25% of the farm area; 45% of the total energy produced from the straw was required for energy carrier production and GHG emissions were reduced by 9% compared with a fossil fuel-based reference scenario. In a scenario based on anaerobic digestion of ley, the corresponding figures were 13%, 24% and 35%. The final result was sensitive to assumptions regarding, e.g., soil carbon content and handling of by-products.

Factors associated with reaching 90 years of age: a study of men born in 1913 in Gothenburg, Sweden.

OBJECTIVES: Increasing numbers of people reach old age. We wanted to identify variables of importance for reaching 90 years old and determine how the predictive ability of these variables might change over time. SETTING AND SUBJECTS: All men in the city of Gothenburg born in 1913 on dates divisible by 3, which is on the 3rd, 6th, 9th etc., were included in the study. Thus, 973 men were invited, and 855 were examined in 1963 at age 50. Further examinations were made at age 54, 60 and 67. Anthropometric data, lifestyle and parental factors, blood pressure, lung function, X-ray of heart and lungs and maximum work performance were recorded. The area under the receiver operating characteristic curve was used to analyse the predictive capacity of a variable. RESULTS: A total of 111 men (13%) reached 90 years of age, men who reached 90 years were more likely at age 50 to be nonsmokers, consume less coffee, have higher socio-economic status and have low serum cholesterol levels than those who did not reach this age; however, at age 50 or 62, parents' survival was of no prognostic importance. Variables of greatest importance at higher ages were low blood pressure and measures related to good cardiorespiratory function. In multivariable analysis, including all examinations, being a nonsmoker, consuming small amounts of coffee, having high housing costs at age 50, good maximum working capacity and low serum cholesterol were related to a better chance of survival to age 90. CONCLUSIONS: Low levels of cardiovascular risk factors, high socio-economic status and good functional capacity, irrespective of parents' survival, characterize men destined to reach the age of 90.

EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision.

BACKGROUND AND OBJECTIVES: This second European Federation of Neurological Societies Task Force aimed at updating the existing evidence about the pharmacological treatment of neuropathic pain since 2005. METHODS: Studies were identified using the Cochrane Database and Medline. Trials were classified according to the aetiological condition. All class I and II randomized controlled trials (RCTs) were assessed; lower class studies were considered only in conditions that had no top-level studies. Treatments administered using repeated or single administrations were considered, provided they are feasible in an outpatient setting. RESULTS: Most large RCTs included patients with diabetic polyneuropathies and post-herpetic neuralgia, while an increasing number of smaller studies explored other conditions. Drugs generally have similar efficacy in various conditions, except in trigeminal neuralgia, chronic radiculopathy and HIV neuropathy, with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions). Combination therapy appears useful for TCA-gabapentin and gabapentin-opioids (level A). CONCLUSIONS: There are still too few large-scale comparative studies. For future trials, we recommend to assess comorbidities, quality of life, symptoms and signs with standardized tools and attempt to better define responder profiles to specific drug treatments.

Obesity and trends in cardiovascular risk factors over 40 years in Swedish men aged 50.

OBJECTIVE: To study trends over 40 years in cardiovascular risk factors in normal weight, overweight and obese men, all aged 50 when examined. Design. Cross-sectional studies of five successive cohorts of men aged 50. SETTING: City of Göteborg, Sweden. SUBJECTS: Random population samples of altogether 3251 urban Swedish men born in 1913, 1923, 1933, 1943 and 1953. MAIN OUTCOME MEASURES: Anthropometry, cardiovascular risk factors, rates of nonsmoking, normotension and serum cholesterol <5 mmol L(-1) over four decades. RESULTS: Over 40 years, there was a net increase in body mass index (BMI) from 24.8 (SD = 3.2) to 26.4 (3.7) kg m(-2) (P < 0.0001), with an increase in the prevalence of obesity (BMI >or= 30 kg m(-2)) from 6.0% in 1963 to 13.8% in 2003. Favourable trends with respect to smoking, blood pressure and serum cholesterol were observed similarly amongst normal weight, overweight and obese men. In 1963, 24% of obese men were normotensive compared to 45% in 2003, and 6% had serum cholesterol <5 mmol L(-1) compared to 34% in 2003. Compared with obese men in 1963, men who were obese in 2003 had an odds ratio (OR) of 3.39 being a nonsmoker [95% confidence interval (CI): 1.56 to 7.36], 2.67 of being normotensive (1.23 to 5.83) and having serum cholesterol <5 mmol L(-1) of 8.30 (2.37 to 29.0). However, optimal risk factor status - no smoking, normotension and total serum cholesterol <5 mmol L(-1)- was still present in less than one in six men in 2003, similar across BMI categories. CONCLUSIONS: Obese Swedish men who are now in their fifties have much lower levels of other risk factors compared with obese men 40 years ago. This could contribute to explain why coronary heart disease death rates still are falling despite increasing rates of obesity.

Secular changes in cardiovascular risk factors and attack rate of myocardial infarction among men aged 50 in Gothenburg, Sweden. Accurate prediction using risk models.

AIMS: Coronary risk factor changes were related to attack rate of acute myocardial infarction (AMI). METHODS AND RESULTS: Cross-sectional population samples of 50-year-old men were examined every 10th year from 1963 to 2003. Attack rates of AMI were recorded from 1975 to 2004. Prevalence of smoking decreased from 56% in 1963 to 22% in 2003. Leisure time physical activity decreased (n.s.), while psychological stress remained the same. Diabetes prevalence increased from 3.6% to 6.6%. Body mass index (BMI) increased from 24.8 to 26.4 kg m(-2). Blood pressures decreased from 138.2/90.6 to 134.7/84.9 mmHg (P = 0.00001). Serum total cholesterol decreased from 6.42 to 5.50 mmol L(-1) (P = 0.0001), but serum triglycerides increased from 1.26 to 1.71 mmol L(-1) (P = 0.0001). The multivariable risk according to total cholesterol, blood pressure and smoking for AMI decreased from the set value 1.0 in 1963 to 0.418. From 1975-1979 to 2000-2004 attack rates for AMI for the age groups 35-44, 45-54 and 55-64 declined to 45%, 46% and 45%, respectively. The 28-day case fatality declined from 30%, 38% and 46% to 12%, 16% and 20%. CONCLUSION: The more than 50% decline in attack rate of AMI during 30 years was comparable with the decline in risk factors.

Psychosocial factors and venous thromboembolism: a long-term follow-up study of Swedish men.

BACKGROUND: The link between psychosocial factors and coronary heart disease is well established, but although effects on coagulation and fibrinolysis variables may be implicated, no population-based study has sought to determine whether venous thromboembolism is similarly related to psychosocial factors. OBJECTIVE: To determine whether venous thromboembolism (deep vein thrombosis or pulmonary embolism) is related to psychosocial factors. PATIENTS/METHODS: A stress questionnaire was filled in by 6958 men at baseline from 1970 to 1973, participants in a cardiovascular intervention trial. Their occupation was used to determine socio-economic status. RESULTS: After a maximum follow-up of 28.8 years, 358 cases of deep vein thrombosis and/or pulmonary embolism were identified through the Swedish hospital discharge and cause-specific death registries. In comparison with men who, at baseline, had no or moderate stress, men with persistent stress had increased risk of pulmonary embolism [hazard ratio (HR)=1.80, 95% CI: 1.21-2.67]. After multivariable adjustment, the HR decreased slightly to 1.66 (95% CI: 1.12-2.48). When compared with manual workers, men with white-collar jobs at intermediate or high level and professionals showed an inverse relationship between occupational class and pulmonary embolism (multiple-adjusted HR=0.57, 95% CI: 0.39-0.83). Deep vein thrombosis was not significantly related to either stress or occupational class. CONCLUSION: Both persistent stress and low occupational class were independently related to future pulmonary embolism. The mechanisms are unknown, but effects on coagulation and fibrinolytic factors are likely.

Neuropathic pain: redefinition and a grading system for clinical and research purposes.

Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.