Clinical and radiographic phenotypes of patients with multifocal subcortical versus cortical cerebral infarcts.

BACKGROUND AND PURPOSE: Infarct topology is a key determinant in classification of a stroke as potentially embolic, with cortical and multifocal lesions being presumed embolic. Whether isolated subcortical multifocal infarcts are likely embolic has not been well studied. METHODS: A prospective, single-center cohort study of consecutive patients with acute multifocal strokes confirmed on diffusion-weighting imaging (DWI) was queried, and patients compared according to the presence of isolated subcortical infarct topology versus cortical ± subcortical topology. Descriptive statistics and multivariable logistic regression were used to determine independent predictors of cryptogenic, subcortical infarcts. RESULTS: Of 1739 patients screened, 743 had complete diagnostic testing with DWI evidence of acute infarction, 183 (24.6%) of whom had a multifocal stroke pattern. Isolated subcortical involvement was disproportionate among patients with ESUS (64.9%) when compared to patients with cardioembolic (24.3%) or large vessel disease (10.8%, p<0.01). Following multivariable adjustment, independent predictors of isolated subcortical multifocal infarction were milder strokes (OR 0.94, 95%CI 0.89-0.98) and higher grade Fazekas score (OR 2.32, 95%CI 1.02-5.29), while cardioembolism (OR 0.30, 95%CI 0.08-1.13) and large vessel disease (OR 0.27, 95%CI 0.08-0.91) remained inversely associated (as compared to ESUS). CONCLUSIONS: These data suggest that multifocal subcortical infarctions are less likely to have an associated proximal embolic source than multifocal infarctions with cortical involvement. The strong association with chronic microvascular disease suggests this topology is more consistent with acute-on-chronic microvascular injury rather than an occult embolic source.

Nonmonotonic Classical Magnetoconductivity of a Two-Dimensional Electron Gas in a Disordered Array of Obstacles.

Magnetotransport measurements in combination with molecular dynamics simulations on two-dimensional disordered Lorentz gases in the classical regime are reported. In quantitative agreement between experiment and simulation, the magnetoconductivity displays a pronounced peak as a function of the perpendicular magnetic field B which cannot be explained by existing kinetic theories. This peak is linked to the onset of a directed motion of the electrons along the contour of the disordered obstacle matrix when the cyclotron radius becomes smaller than the size of the obstacles. This directed motion leads to transient superdiffusive motion and strong scaling corrections in the vicinity of the insulator-to-conductor transitions of the Lorentz gas.

Performance of the 2015 ACR-EULAR classification criteria for gout in a primary care population presenting with monoarthritis.

Objective: To test the performance of the 2015 ACR-EULAR gout classification criteria against presence of SF MSU crystals in a primary healthcare population. Methods: The criteria were applied to an existing dataset of consecutive patients with monoarthritis presenting to Dutch family physicians; all patients underwent microscopic SF analysis by design. The data had been prospectively collected to develop a diagnostic decision rule for gout in 2010. Diagnostic performance was assessed by calculating area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and constructing calibration plots for the full version of the criteria (including SF analysis results of all patients) and the clinical-only version (not including SF analysis results). Performance of both versions was compared with the 2010 diagnostic rule. Results: Of 381 patients enrolled into the study, 216 (57%) were MSU crystal-positive. The full and clinical-only versions of the criteria had satisfactory area under the receiver operating characteristic curve (0.96 and 0.87, respectively), high specificity (0.98 and 0.84), high PPV (0.98 and 0.84), but lower sensitivity (0.68 and 0.68) and NPV (0.70 and 0.67). Specificity and PPV of both versions were higher compared with 0.71 and 0.89 of the 2010 diagnostic decision rule. The decison rule had the highest sensitivity and NPV (0.99 and 0.97). Conclusion: This study presents the first external validation of the 2015 ACR-EULAR gout classification criteria in a primary healthcare setting. The criteria perform well in this setting in patients presenting with monoarthritis for the purpose of enrolling into gout clinical trials.

Performance of classification criteria for gout in early and established disease.

OBJECTIVES: To compare the sensitivity and specificity of different classification criteria for gout in early and established disease. METHODS: This was a cross-sectional study of consecutive rheumatology clinic patients with joint swelling in which gout was defined by presence or absence of monosodium urate crystals as observed by a certified examiner at presentation. Early disease was defined as patient-reported onset of symptoms of 2 years or less. RESULTS: Data from 983 patients were collected and gout was present in 509 (52%). Early disease was present in 144 gout cases and 228 non-cases. Sensitivity across criteria was better in established disease (95.3% vs 84.1%, p<0.001) and specificity was better in early disease (79.9% vs 52.5%, p<0.001). The overall best performing clinical criteria were the Rome criteria with sensitivity/specificity in early and established disease of 60.3%/84.4% and 86.4%/63.6%. Criteria not requiring synovial fluid analysis had sensitivity and specificity of less than 80% in early and established disease. CONCLUSIONS: Existing classification criteria for gout have sensitivity of over 80% in early and established disease but currently available criteria that do not require synovial fluid analysis have inadequate specificity especially later in the disease. Classification criteria for gout with better specificity are required, although the findings should be cautiously applied to non-rheumatology clinic populations.

Low resting heart rates are associated with new-onset atrial fibrillation in patients with vascular disease: results of the ONTARGET/TRANSCEND studies.

BACKGROUND: Elevated systolic blood pressure (SBP) and high resting heart rate (HR) are associated with cardiovascular end-points. Although the association between atrial fibrillation (AF) and SBP is well established, the relation between AF and HR remains unclear. METHODS: In patients from the ONTARGET and TRANSCEND studies with high cardiovascular disease risk (n = 27 064), new-onset AF was evaluated in relation to mean SBP, visit-to-visit variation in SBP (SBP-CV; i.e. SD/mean × 100%), mean HR and visit-to-visit variation in HR (HR-CV). RESULTS: Low mean HR (P < 0.0001) and high SBP (P = 0.0021) were associated with incident AF. High SBP-CV (P = 0.031) and HR-CV (P < 0.0001) were also associated with incident AF. After adjustment for confounders, SBP and SBP-CV were no longer significantly associated with AF. The detrimental effect of low HR was particularly evident in subjects who were not receiving treatment with beta-blockers (P = 0.014 for interaction between beta-blocker use and mean HR). In addition to low HR, high HR-CV and high SBP had additive effects on incident AF. CONCLUSIONS: Low mean HR (<60 beats min(-1) ) is independently associated with incident AF, and low HR-CV and high SBP further increase the incidence of new-onset AF in patients at high risk of cardiovascular disease.

Resting heart rate is associated with renal disease outcomes in patients with vascular disease: results of the ONTARGET and TRANSCEND studies.

BACKGROUND: Resting heart rate (RHR) is associated with cardiovascular disease outcomes in high-risk patients. It is not known whether RHR is predictive of renal outcomes such as albuminuria, end-stage renal disease (ESRD) or doubling of creatinine. We evaluated whether RHR could predict renal endpoints in patients at a high risk of cardiovascular disease. We also tested the effects of RHR at different levels of systolic blood pressure (SBP). METHODS: We analysed data from 28 757 patients in the ONTARGET and TRANSCEND trials. RHR and SBP were available for a mean of 4.9 ± 0.4 visits (range 3-5) within the first 2 years of the studies. Albuminuria was determined at baseline, at 2 years and at study end. RESULTS: Mean RHR was predictive of incident micro-albuminuria [hazard ratio (HR) for RHR ≥80 vs. <60 beats min(-1) 1.49, 95% confidence interval (CI) 1.29-1.71, P < 0.0001], incident macro-albuminuria (HR 1.84, 95% CI 1.39-2.42, P < 0.0001), doubling of creatinine (HR 1.47, 95% CI 1.00-2.17, P = 0.050) and ESRD (HR 1.78, 95% CI 1.00-3.16, P = 0.050), and the combined renal end-point (HR 1.51, 95% CI 1.32-1.74, P < 0.0001). Associations were robust at SBPs from <120 to ≥150 mmHg, with the lowest risk at a SBP of 130-140 mmHg. CONCLUSION: Resting heart rate is a potent predictor of these renal outcomes, as well as their combination, in patients with cardiovascular disease. RHR at all SBP levels should be considered as a possible renal disease risk predictor and should be investigated as a treatment target with RHR-reducing agents.

Imaging modalities for the classification of gout: systematic literature review and meta-analysis.

BACKGROUND: Although there has been major progress in gout imaging, no gout classification criteria currently include advanced imaging techniques. OBJECTIVE: To examine the usefulness of imaging modalities in the classification of gout when compared to monosodium urate (MSU) crystal confirmation as the gold standard, in order to inform development of new gout classification criteria. METHODS: We systematically reviewed the published literature concerning the diagnostic performance of plain film radiography, MRI, ultrasound (US), conventional CT and dual energy CT (DECT). Only studies with MSU crystal confirmation as the gold standard were included. When more than one study examined the same imaging feature, the data were pooled and summary test characteristics were calculated. RESULTS: 11 studies (9 manuscripts and 2 meeting abstracts) satisfied the inclusion criteria. All were set in secondary care, with mean gout disease duration of at least 7 years. Three features were examined in more than one study: the double contour sign (DCS) on US, tophus on US, and MSU crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus, were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively. CONCLUSIONS: US and DECT show promise for gout classification but the few studies to date have mostly been in patients with longstanding, established disease. The contribution of imaging over clinical features for gout classification criteria requires further examination.

2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSIONS: The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

Platelets can enhance vascular permeability.

Platelets survey blood vessels, searching for endothelial damage and preventing loss of vascular integrity. However, there are circumstances where vascular permeability increases, suggesting that platelets sometimes fail to fulfill their expected function. Human inflammatory arthritis is associated with tissue edema attributed to enhanced permeability of the synovial microvasculature. Murine studies have suggested that such vascular leak facilitates entry of autoantibodies and may thereby promote joint inflammation. Whereas platelets typically help to promote microvascular integrity, we examined the role of platelets in synovial vascular permeability in murine experimental arthritis. Using an in vivo model of autoimmune arthritis, we confirmed the presence of endothelial gaps in inflamed synovium. Surprisingly, permeability in the inflamed joints was abrogated if the platelets were absent. This effect was mediated by platelet serotonin accumulated via the serotonin transporter and could be antagonized using serotonin-specific reuptake inhibitor antidepressants. As opposed to the conventional role of platelets to microvascular leakage, this demonstration that platelets are capable of amplifying and maintaining permeability adds to the rapidly growing list of unexpected functions for platelets.

Endovascular repair of acute uncomplicated aortic type B dissection promotes aortic remodelling: 1 year results of the ADSORB trial.

OBJECTIVES: Uncomplicated acute type B aortic dissection (AD) treated conservatively has a 10% 30-day mortality and up to 25% need intervention within 4 years. In complicated AD, stent grafts have been encouraging. The aim of the present prospective randomised trial was to compare best medical treatment (BMT) with BMT and Gore TAG stent graft in patients with uncomplicated AD. The primary endpoint was a combination of incomplete/no false lumen thrombosis, aortic dilatation, or aortic rupture at 1 year. METHODS: The AD history had to be less than 14 days, and exclusion criteria were rupture, impending rupture, malperfusion. Of the 61 patients randomised, 80% were DeBakey type IIIB. RESULTS: Thirty-one patients were randomised to the BMT group and 30 to the BMT+TAG group. Mean age was 63 years for both groups. The left subclavian artery was completely covered in 47% and in part in 17% of the cases. During the first 30 days, no deaths occurred in either group, but there were three crossovers from the BMT to the BMT+TAG group, all due to progression of disease within 1 week. There were two withdrawals from the BMT+TAG group. At the 1-year follow up there had been another two failures in the BMT group: one malperfusion and one aneurysm formation (p = .056 for all). One death occurred in the BMT+TAG group. For the overall endpoint BMT+TAG was significantly different from BMT only (p < .001). Incomplete false lumen thrombosis, was found in 13 (43%) of the TAG+BMT group and 30 (97%) of the BMT group (p < .001). The false lumen reduced in size in the BMT+TAG group (p < .001) whereas in the BMT group it increased. The true lumen increased in the BMT+TAG (p < .001) whereas in the BMT group it remained unchanged. The overall transverse diameter was the same at the beginning and after 1 year in the BMT group (42.1 mm), but in the BMT+TAG it decreased (38.8 mm; p = .062). CONCLUSIONS: Uncomplicated AD can be safely treated with the Gore TAG device. Remodelling with thrombosis of the false lumen and reduction of its diameter is induced by the stent graft, but long term results are needed.

Discontinuation of antiviral prophylaxis correlates with high prevalence of hepatitis B virus (HBV) reactivation in rheumatoid arthritis patients with HBV carrier state: a real-world clinical practice.

BACKGROUND: To investigate the risk of hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with HBV carrier state during treatment of disease-modifying antirheumatic drugs (DMARDs) and the use of antiviral prophylaxis in real-world clinical practice. METHODS: Consecutive RA patients with HBV carrier state were included. Clinical data including liver evaluation, HBV infection evaluation and the use of antiviral prophylaxis were recorded. RESULTS: Fifty-three RA patients with HBV carrier state were screened and 36 patients were qualified for analysis. Thirty-six percentage of patients developed HBV reactivation and 17% developed HBV hepatitis together with reactivation, one of which developed decompensate cirrhosis. Only 50% of patients accepted lamivudine although all patients were recommended antiviral prophylaxis with entecavir or tenofovir and only 31% continued during DMARDs therapy. Seventy-one percentage of patients who discontinued antiviral prophylaxis developed HBV reactivation 3 ~ 21 months after discontinuation. Logistic regression analyses showed discontinuation of antiviral prophylaxis (OR: 66, p = 0.027), leflunomide (OR: 64, p = 0.011) and past history of hepatitis (OR: 56, p = 0.013) were risk factors of HBV reactivation. Past history of hepatitis (OR: 10, p = 0.021) was also risk factor of HBV hepatitis together with reactivation. CONCLUSION: Our results suggest poor patient acceptance and discontinuation of antiviral prophylaxis should not be ignored for Chinese RA patients with HBV carrier state in real-world clinical practice. Discontinuation of antiviral prophylaxis, past history of hepatitis and LEF might increase risk of HBV reactivation for RA patients with HBV carrier state during DMARDs therapy.

Randomized double-blind crossover study of the efficacy of a tart cherry juice blend in treatment of osteoarthritis (OA) of the knee.

OBJECTIVE: To assess the efficacy of tart cherry juice in treating pain and other features of knee osteoarthritis (OA). METHODS: 58 non-diabetic patients with Kellgren grade 2-3 OA were randomized to begin treatment with cherry juice or placebo. Two 8 oz bottles of tart cherry juice or placebo were consumed daily for 6 weeks with a 1 week washout period before switching treatments (crossover design). Western Ontario McMaster Osteoarthritis Index (WOMAC) scores and walking times were recorded prior to and after each treatment period. Additionally, plasma urate, creatinine and high sensitivity C-reactive protein (hsCRP) were recorded at baseline, after the first treatment period and after the second treatment period. Acetaminophen was allowed as a rescue drug and self reported after each treatment period. Treatment effect was examined with repeated measures analysis of variance (ANOVA) using an intention-to-treat (ITT) analysis. RESULTS: There were five withdrawals during the cherry juice treatment (four adverse events (AEs)) and seven withdrawals during the placebo treatment (three AEs). WOMAC scores decreased significantly (P < 0.01) after the cherry juice treatment but not after the placebo treatment (P = 0.46); differences between treatments were not significant (P = 0.16). hsCRP declined during the cherry juice treatment vs placebo (P < 0.01). The decline in hsCRP was associated with WOMAC improvement (P < 0.01). Walking time, acetaminophen use, plasma urate and creatinine were unaffected by treatments. CONCLUSIONS: Tart cherry juice provided symptom relief for patients with mild to moderate knee OA, but this effect was not significantly greater than placebo. Tart cherry juice lowered hsCRP levels and this effect was associated with improved WOMAC scores.

New classification criteria for gout: a framework for progress.

The definitive classification or diagnosis of gout normally relies upon the identification of MSU crystals in SF or from tophi. Where microscopic examination of SF is not available or is impractical, the best approach may differ depending upon the context. For many types of research, clinical classification criteria are necessary. The increasing prevalence of gout, advances in therapeutics and the development of international research collaborations to understand the impact, mechanisms and optimal treatment of this condition emphasize the need for accurate and uniform classification criteria for gout. Five clinical classification criteria for gout currently exist. However, none of the currently available criteria has been adequately validated. An international project is currently under way to develop new validated gout classification criteria. These criteria will be an essential step forward to advance the research agenda in the modern era of gout management.

Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of IL-1 inhibitor rilonacept (IL-1 Trap) for gout flare (GF) prevention during initiation of uric acid-lowering therapy (ULT) with allopurinol in a multiregional phase 3 clinical trial. METHODS: Hyperuricaemic adults (n = 248) from South Africa, Germany and Asia with gout and two or more GFs within the past year were initiated on allopurinol and randomized 1:1:1 to once-weekly s.c. treatment with placebo (PBO), rilonacept 80 mg (R80) or rilonacept 160 mg (R160) for 16 weeks. The primary endpoint was the number of GFs per patient through week 16. RESULTS: The population was predominantly male and racially diverse (white, 53.2%; Asian, 33.1%; black, 13.7%). Across treatments, most patients completed the study (87.8-92.9%). At 16 weeks the mean number of GFs per patient was reduced by 71.3% with R80 (0.35) and by 72.6% with R160 (0.34) relative to PBO (1.23; both P < 0.0001). The proportion of patients without GFs was higher with R80 (74.4%) and R160 (79.5%) than with PBO (43.9%; both P ≤ 0.0001), and the proportions of patients on rilonacept with multiple GFs were significantly lower (P < 0.001). Overall, the incidence of adverse events (AEs) was similar between PBO (61.0%) and rilonacept (65.1%). Injection site reactions, generally mild, were the most frequent AE with rilonacept (1.2% PBO, 12.2% R80 and 17.9% R160); none of these injection site reactions led to withdrawal. There were no study drug-related serious AEs or deaths. CONCLUSION: Rilonacept significantly reduced the occurrence of GFs associated with initiation of ULT, with >70% of patients having no flares, and demonstrated an acceptable safety and tolerability profile. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00958438.

Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy. METHODS: In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained. RESULTS: Baseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept- and placebo-treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept-treated patients (98%) compared with placebo-treated patients (79%) completed the primary 12-week evaluation period (P = 0.015). CONCLUSION: The current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate-lowering therapy, with a favorable safety profile.

Developing a provisional definition of flare in patients with established gout.

OBJECTIVE: Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. METHODS: Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. RESULTS: The mean ± SD age of the study participants was 56.2 ± 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient-reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (0-10 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). CONCLUSION: We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials.

The structure of affective symptomatology in older adults with osteoarthritis.

OBJECTIVE: To examine the structure of symptoms of affective disorder among older adults with a chronic health problem (osteoarthritis) and to explore cross-sectional and longitudinal associations of obtained affective symptom clusters with key health outcomes (pain, functional disability, perceived health). METHODS: One-year longitudinal study of older adults with diagnosed osteoarthritis of the knee. Symptoms of DSM depression and anxiety were assessed in a research diagnostic interview by using a DSM-IV symptom checklist; self-reports captured demographic characteristics, objective health, pain, disability, and perceived health. Confirmatory factor analysis tested comparability of affective symptom structure in this sample to findings of previous research; ordinary least squares regression examined cross-sectional and longitudinal associations of affective symptoms with health outcomes, controlling for demographics and objective health. RESULTS: The current sample displayed an affective symptom structure comparable with that observed in previous research, with symptoms clustering into depressed mood (DM), somatic symptoms (SS), and psychic anxiety (PA) factors. DM was cross-sectionally associated with pain and disability and marginally with perceived health; SS predicted current pain and perceived health. Only DM predicted 1 year change in disability and perceived health (but not pain). CONCLUSIONS: This research confirms the role of SS of distress in fueling disability and perceived ill health among older adults who are chronically ill. However, it is DM that drives changes in perceived health and functional ability.

Early combination therapy with telmisartan plus amlodipine for rapid achievement of blood pressure goals.

BACKGROUND: Rapid and sustained blood pressure (BP) goal attainment is important to reduce cardiovascular risk. Initial use of combination therapy may improve BP goal attainment. METHODS: The Boehringer Ingelheim trial database was searched for randomised, double-blind studies comparing telmisartan/amlodipine combination therapy with monotherapy. Eight studies were identified. Eight separate analyses were used to compare combination therapy with respective monotherapies at the earliest available time points (weeks 1, 2 and/or 4). RESULTS: In patients initiated on combination therapy, greater systolic BP (SBP)/diastolic BP (DBP) reductions were seen with combination therapy (p < 0.0001); BP (< 140/90 mmHg), SBP (< 140 mmHg) and DBP (< 90 mmHg) goal attainment rates were significantly higher with combination therapy at all time points. In patients uncontrolled by monotherapy, greater SBP/DBP reductions were seen with combination therapy (p < 0.05 in all but one measure), and all goal attainment rates were significantly higher with combination therapy, except in one measure. CONCLUSION: Many people can achieve their BP targets when taking a combination of telmisartan and amlodipine after failing to do so with monotherapy. Furthermore, BP targets can be achieved more rapidly using a combination of telmisartan and amlodipine as initial therapy than with either monotherapy.

Integrating acupuncture with exercise-based physical therapy for knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Knee osteoarthritis is a chronic disease associated with significant morbidity and economic cost. The efficacy of acupuncture in addition to traditional physical therapy has received little study. OBJECTIVE: The objective of this study was to compare the efficacy and safety of integrating a standardized true acupuncture protocol versus nonpenetrating acupuncture into exercise-based physical therapy (EPT). METHODS: This was a randomized, double-blind, controlled trial at 3 physical therapy centers in Philadelphia, PA. We studied 214 patients (66% African Americans) with at least 6 months of chronic knee pain and x-ray-confirmed Kellgren scores of 2 or 3. Patients received 12 sessions of acupuncture directly following EPT over 6 to 12 weeks. Acupuncture was performed at the same 9 points dictated by the traditional Chinese "Bi" syndrome approach to knee pain, using either standard needles or Streitberger non-skin-puncturing needles. The primary outcome was the proportion of patients with at least a 36% improvement in Western Ontario and McMaster Universities Osteoarthritis Index score at 12 weeks. RESULTS: Both treatment groups showed improvement from combined therapy with no difference between true (31.6%) and nonpenetrating acupuncture (30.3%) in Western Ontario and McMaster Universities Osteoarthritis Index response rate (P = 0.5) or report of minor adverse events. A multivariable logistic regression prediction model identified an association between a positive expectation of relief from acupuncture and reported improvement. No differences were noted by race, sex, or age. CONCLUSIONS: Puncturing acupuncture needles did not perform any better than nonpuncturing needles integrated with EPT. Whether EPT, acupuncture, or other factors accounted for any improvement noted in both groups could not be determined in this study. Expectation for relief was a predictor of reported benefit.

Current status of endovascular stroke treatment.

The management of acute ischemic stroke is rapidly developing.Although acute ischemic stroke is a major cause of adult disability and death, the number of patients requiring emergency endovascular intervention remains unknown, but is a fraction of the overall stroke population. Public health initiatives endeavor to raise public awareness about acute stroke to improve triage for emergency treatment, and the medical community is working to develop stroke services at community and academic medical centers throughout the United States. There is an Accreditation Council for Graduate Medical Education­approved pathway for training in endovascular surgical neuroradiology, the specialty designed to train physicians specifically to treat cerebrovascular diseases. Primary and comprehensive stroke center designations have been defined, yet questions remain about the best delivery model. Telemedicine is available to help community medical centers cope with the complexity of stroke triage and treatment. Should comprehensive care be provided at every community center, or should patients with complex medical needs be triaged to major stroke centers with high-level surgical,intensive care, and endovascular capabilities? Although the answers to these and other questions about stroke care delivery remain unanswered owing to the paucity of empirical data, we are convinced that stroke care regionalization is crucial for delivery of high-quality comprehensive ischemic stroke treatment. A stroke team available 24 hours per day, 7 days per week requires specialty skills in stroke neurology, endovascular surgical neuroradiology, neurosurgery, neurointensive care, anesthesiology, nursing, and technical support for optimal success. Several physician groups with divergent training backgrounds (i.e., interventional neuroradiology, neurosurgery,neurology, peripheral interventional radiology, and cardiology) lay claim to the treatment of stroke patients,particularly the endovascular or interventional methods. Few would challenge neurologists over the responsibility for emergency evaluation and triage of stroke victims for intra intravenous fibrinolysis, even though emergency physicians are most commonly the first to evaluate these patients. There are many unanswered questions about the role of imaging in defining best treatment. Perfusion imaging with CT or MRI appears to have relevance even though its role remains undefined and is the subject of ongoing research. Meanwhile, investigators are exploring new, and perhaps more specific,imaging methods with cerebral metabolic rate of oxygen and cellular acid-base imbalance. There are currently 6 ongoing trials of stroke intervention, many with proprietary technologies and private funding, competing for the same patient population as multicenter trials funded by the NIH. At the same time, much of the interventional stroke treatment currently occurs outside of trials in the community and academic settings without the collection of much-needed data. Market forces will certainly shape future stroke therapy, but it is unclear whether the current combination of private and public funding for these endeavors is the best method of development.