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The Insulin Resistance Intervention after Stroke (IRIS) trial recently found that pioglitazone reduced risk for stroke and myocardial infarction in patients with insulin resistance but without diabetes who had had a recent ischemic stroke or transient ischemic attack (TIA). This report provides detailed results on the metabolic effects of pioglitazone and the trial's prespecified secondary aim of diabetes prevention.A total of 3,876 patients with recent ischemic stroke or TIA, no history of diabetes, fasting plasma glucose (FPG)126 mg/dL, and insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) score3.0 were randomly assigned to pioglitazone or placebo. Surveillance for diabetes onset during the trial was accomplished by periodic interviews and annual FPG testing.At baseline, the mean FPG, HbA1c, insulin, and HOMA-IR were 98.2 mg/dL (5.46 mmol/L), 5.8% (40 mmol/mol), 22.4 μIU/mL, and 5.4, respectively. After 1 year, mean HOMA-IR and FPG decreased to 4.1 and 95.1 mg/dL (5.28 mmol/L) in the pioglitazone group and rose to 5.7 and 99.7 mg/dL (5.54 mmol/L), in the placebo group (all P0.0001). Over a median follow-up of 4.8 years, diabetes developed in 73 (3.8%) participants assigned to pioglitazone compared with 149 (7.7%) assigned to placebo (hazard ratio [HR] 0.48 [95% CI 0.33-0.69]; P0.0001). This effect was predominately driven by those with initial impaired fasting glucose (FPG100 mg/dL [5.6 mmol/L]; HR 0.41 [95% CI 0.30-0.57]) or elevated HbA1c (5.7% [39 mmol/mol]; HR 0.46 [0.34-0.62]).Among patients with insulin resistance but without diabetes who had had a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events. Pioglitazone is the first medication shown to prevent both progression to diabetes and major cardiovascular events as prespecified outcomes in a single trial.

Background: New approaches are needed to treat patients with stroke. Among acute ischemic stroke patients, our primary objectives were to describe the prevalence of sleep apnea and demonstrate the feasibility of providing auto-titrating continuous positive airway pressure (auto-CPAP). A secondary objective was to examine the effect of auto-CPAP on stroke severity. Methods: Stroke patients randomized to the intervention group received 2 nights of auto-CPAP, but only those with evidence of sleep apnea received auto-CPAP for the remainder of the 30-day period. Intervention patients received polysomnography 30 days post-stroke. Control patients received polysomnography at baseline and after 30 days. Acceptable auto-CPAP adherence was defined as ≥ 4 h/night for ≥ 75% nights. Change in stroke severity was assessed comparing the NIH Stroke Scale (NIHSS) at baseline versus at 30 days. Results: The 2 groups (intervention N = 31, control N = 24) had similar baseline stroke severity (both median NIHSS, 3.0). Among patients with complete polysomnography data, the majority had sleep apnea: baseline, 13/15 (86.7%) control patients; 30 days, 24/35 (68.6%) control and inter- vention patients. Intervention patients had greater improvements in NIHSS (−3.0) than control patients (−1.0); P = 0.03. Among patients with sleep apnea, greater improvement was observed with increasing auto-CPAP use: −1.0 for control patients not using auto-CPAP; −2.5 for intervention patients with some auto-CPAP use; and −3.0 for intervention patients with acceptable auto-CPAP adherence. Conclusions: The majority of acute stroke patients had sleep apnea. Auto-CPAP was well tolerated, appears to improve neurological recovery from stroke, and may represent a new therapeutic approach for selected patients with acute cerebral infarction.

223 Background: We have engaged 10 patient partners in the development and implementation of S1415CD, a five-year pragmatic clinical trial currently in year 3 assessing the effectiveness of a guideline-based colony stimulating factor standing order intervention (NCT02728596). Patient partners serve as part of a 21-person External Stakeholder Advisory Group (ESAG), which also includes providers, payers and guidelines experts. This abstract explores the influence of patient partners on the design, tools and implementation of S1415CD Methods: Patient partners advise the study team on protocol development, patient-facing materials and implementation challenges over four teleconferences each year, annual in-person meetings and targeted email communication. All patient partner input from 2014-2017 was tracked, collected and reviewed for impact on the trial. Results: Input from patient partners led to the refinement of the study’s patient-reported outcome (PRO) survey questions, the creation of a highly utilized patient brochure, and the formation of talking points for clinic staff to help explain the study. Patient partners in conjunction with high performing sites helped develop strategies for sites with lower patient accrual to optimize the approach and consent of study participants. Conclusions: The sustained engagement of patient partners in S1415CD ensured patient-centeredness in trial design and guided the development of PRO surveys and relevant, high quality patient-facing materials. Drawing on experiential knowledge and insights from their roles as caregivers and advocates, patient partners provided valuable feedback that influenced patient approach and engagement in the study. Embedding patient partners in the research continuum has catalyzed critical discussions and problem solving among the patient partners and study team, which has led to patient-centered solutions to study challenges. Clinical trial information: NCT02728596.

Background and Purpose— Transient ischemic attack (TIA) patients are at risk of recurrent vascular events. The primary objectives were to evaluate among TIA patients the prevalence of sleep apnea and among patients with sleep apnea auto-titrating continuous positive airway pressure (auto-CPAP) adherence. The secondary objective was to describe among TIA patients with sleep apnea the recurrent vascular event rate by auto-CPAP use category. Methods— All intervention patients received auto-CPAP for 2 nights, but only intervention patients with evidence of sleep apnea received auto-CPAP for the remainder of the 90-day period. Intervention patients received polysomnography at 90 days after TIA. Control patients received polysomnography at baseline and at 90 days. Acceptable auto-CPAP adherence was defined as ≥4 hours per night for ≥75% of nights. Vascular events included recurrent TIA, stroke, hospitalization for congestive heart failure, myocardial infarction, or death. Results— We enrolled 70 acute TIA patients: 45 intervention and 25 control. The majority of patients had sleep apnea: 57% at baseline and 59% at 90 days. Among the 30 intervention patients with airflow obstruction, 12 (40%) had acceptable auto-CPAP adherence, 18 (60%) had some use, and none had no use. Three intervention patients (12%) had recurrent events compared with 1 (2%; P =0.13) control patient. The vascular event rate was highest among sleep apnea patients with no CPAP use: none, 16%; some, 5%; acceptable adherence 0% ( P =0.08). Conclusions— Sleep apnea is common among acute TIA patients. It appears feasible to provide auto-CPAP in the acute TIA period. Larger studies should evaluate whether a strategy of diagnosing and treating sleep apnea can reduce recurrent vascular events after TIA.

Importance There is growing recognition that patients may respond differently to therapy and that the average treatment effect from a clinical trial may not apply equally to all candidates for a therapy. Objective To determine whether, among patients with an ischemic stroke or transient ischemic attack and insulin resistance, those at higher risk for future stroke or myocardial infarction (MI) derive more benefit from the insulin-sensitizing drug pioglitazone hydrochloride compared with patients at lower risk. Design, Setting, and Participants A secondary analysis was conducted of the Insulin Resistance Intervention After Stroke trial, a double-blind, placebo-controlled trial of pioglitazone for secondary prevention. Patients were enrolled from 179 research sites in 7 countries from February 7, 2005, to January 15, 2013, and were followed up for a mean of 4.1 years through the study’s end on July 28, 2015. Eligible participants had a qualifying ischemic stroke or transient ischemic attack within 180 days of entry and insulin resistance without type 1 or type 2 diabetes. Interventions Pioglitazone or matching placebo. Main Outcomes and Measures A Cox proportional hazards regression model was created using baseline features to stratify patients above or below the median risk for stroke or MI within 5 years. Within each stratum, the efficacy of pioglitazone for preventing stroke or MI was calculated. Safety outcomes were death, heart failure, weight gain, and bone fracture. Results Among 3876 participants (1338 women and 2538 men; mean [SD] age, 63 [11] years), the 5-year risk for stroke or MI was 6.0% in the pioglitazone group among patients at lower baseline risk compared with 7.9% in the placebo group (absolute risk difference, –1.9% [95% CI, –4.4% to 0.6%]). Among patients at higher risk, the risk was 14.7% in the pioglitazone group vs 19.6% for placebo (absolute risk difference, –4.9% [95% CI, –8.6% to 1.2%]). Hazard ratios were similar for patients below or above the median risk (0.77 vs 0.75; P = .92). Pioglitazone increased weight less among patients at higher risk but increased the risk for fracture more. Conclusions and Relevance After an ischemic stroke or transient ischemic attack, patients at higher risk for stroke or MI derive a greater absolute benefit from pioglitazone compared with patients at lower risk. However, the risk for fracture is also higher. Trial Registration clinicaltrials.gov Identifier:NCT00091949

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Keloid scars are pathological scars, which develop as a result of exaggerated dermal tissue proliferation following cutaneous injury and often cause physical, psychological and cosmetic problems. Various theories regarding keloidogenesis exist, however the precise pathophysiological events remain unclear. Many different treatment modalities have been implicated in their management, but currently there is no entirely satisfactory method for treating all keloid lesions. We review a number of different chemotherapeutic agents which have been proposed for the treatment of keloid and hypertrophic scars while giving insight into some of the novel chemotherapeutic drugs which are currently being investigated. Non-randomized trials evaluating the influence of different chemotherapeutic agents, such as 5-fluorouracil (5-FU); mitomycin C; bleomycin and steroid injection, either alone or in combination with other chemotherapeutic agents or alternative treatment modalities, for the treatment of keloids were identified using a predefined PubMed search strategy. Twenty seven papers were identified. Scar improvement ≥50% was found in the majority of cases treated with 5-FU, with similar results found for mitomycin C, bleomycin and steroid injection. Combined intralesional 5-FU and steroid injection produced statistically significant improvements when compared to monotherapy. Monotherapy recurrence rates ranged from 0-47% for 5-FU, 0-15% for bleomycin and 0-50% for steroid injection. However, combined therapy in the form of surgical excision and adjuvant 5-FU or steroid injections demonstrated lower recurrence rates; 19% and 6% respectively. Currently, most of the literature supports the use of combination therapy (usually surgery and adjuvant chemotherapy) as the mainstay treatment of keloids, however further investigation is necessary to determine success rates over longer time frames. Furthermore, there is the potential for novel therapies, but further investigation is required to elucidate their true efficacy.

Introduction. “See and treat” one-stop clinics (OSCs) are an advocated NHS initiative to modernise care, reducing cancer treatment waiting times. Little studied in plastic surgery, the existing evidence suggests that though they improve care, they are rarely implemented. We present our experience setting up a plastic surgery OSC for minor skin surgery and survey their use across the UK. Methods. The OSC was evaluated by 18-week wait target compliance, measures of departmental capacity, and patient satisfaction. Data was obtained from 32 of the 47 UK plastic surgery departments to investigate the prevalence of OSCs for minor skin cancer surgery. Results. The OSC improved 18-week waiting times, from a noncompliant mean of 80% to a compliant 95% average. Department capacity increased 15%. 95% of patients were highly satisfied with and preferred the OSC to a conventional service. Only 25% of UK plastic surgery units run OSCs, offering varying reasons for not doing so, 42% having not considered their use. Conclusions. OSCs are underutilised within UK plastic surgery, where a significant proportion of units have not even considered their benefit. This is despite associated improvements in waiting times, department capacity, and levels of high patient satisfaction. We offer our considerations and local experience instituting an OSC service.

Skin cancer has been shown to present asymmetrically, prevalent on the left side of the body, more so in subtypes of cutaneous melanoma such as lentigo maligna. Biases have been linked to cumulative UV light exposure and automobile driving patterns. Though left-right ratios have previously correlated with the side men or women tend to position themselves or countries drive on, more recent trends indicate a consistent left-sided bias. To clarify reasons for changing trends, a review of the evidence base and LM’s laterality in a UK cohort (99 cases 2000–2011) was conducted for the first time. The strong correlation of left-sided excess, found in both genders (ratios 1.381–1.5,P<0.05 X20.841), is congruent with more recent findings. Though evidence indicates that driving position is no longer a risk factor for LM, due most likely to improved car window UV protection, it remains the most commonly attributed cause. Understanding phenomena such as UV lights “scatter effect” or that cumulative exposure may not be a significant risk factor helps rationalize older conclusions that would otherwise appear contradictory. The reasons for left-sided excess remain unclear but may be due to factors requiring further research such as the body’s anatomical/embryological asymmetry.

We prospectively examined the effect of arundic acid (AA; ONO-2506) on S-100beta, an astrocyte-derived protein, in a phase I acute stroke study. Subjects with acute ischemic stroke were randomized to daily infusion of AA or placebo for 7 days. Serum S-100beta levels were assayed pre-infusion on Days 1-7 and post-infusion on Days 1, 3, and 7, and correlated with National Institutes of Health Stroke Scale (NIHSS). Samples were obtained from 86 subjects (46 AA, 40 placebo). Increase in S-100beta protein level from baseline was less in the AA cohort than in the placebo cohort at 7 (p=0.0471; t-test) and 12 (p=0.0095)-hours post-infusion on Day 3. Baseline NIHSS correlated with maximal S-100beta levels between Days 1 and 3 in the AA (r=0.51; p=0.0003) and placebo (r=0.41; p=0.0084) cohorts and in the pooled aggregate (n=86; r=0.46; p

Arundic acid (AA; ONO-2506), a novel modulator of astrocyte activation, may improve neuronal survival after stroke. We conducted a multicenter, dose-escalating, randomized, double-blind Phase I trial of AA in acute ischemic stroke. Subjects were randomized to treatment with AA or placebo in sequential dose tiers of 2-12 mg/kg/h (10-16 patients/group) within 24 h of stroke onset. Study drug was infused for 1 h daily over 7 days, and follow-up terminated at 40 days. Neurological and functional outcomes were evaluated through Day 40 as exploratory endpoints. A total of 92 subjects were enrolled with no dose-related pattern of serious adverse events (AEs). Premature terminations caused by AEs occurred in four (8.2%) patients treated with AA and five (11.6%) treated with placebo. Two subjects treated with AA (4.1%) and four given placebo (9.3%) died. Exploratory efficacy analysis showed a trend toward improvement in the change from baseline National Institutes of Health Stroke Scale (NIHSS) in the 8 mg/kg/h AA group on Days 3 (p=0.023 vs. placebo), 7 (p=0.002), 10 (p=0.003), and 40 (p=0.018). A dose of 8 mg/kg/h AA produced a favorable trend in reduction of NIHSS that should be confirmed in a future clinical trial.

Depression is a frequent complication of stroke, but few nurse researchers have studied poststroke depression (PSD). We reviewed all published research (January 1980-March 2005) that examined the incidence of and risk factors for depression among stroke survivors during the first 3 months after stroke. Many of the 49 studies reviewed were complicated by methodological limitations, including differing definitions of stroke and depression, the use of screening instruments to diagnose depression, selection bias, assessment at different time intervals poststroke, exclusion of patients with physical or cognitive impairments, and failure to control for associated variables. The incidence of PSD ranged from 5% to 63%. A history of depression, increased stroke severity, and poststroke cognitive or physical impairment were found to be risk factors for PSD.

Background Variations in transcranial Doppler (TCD) examination performance techniques and interpretive paradigms between individual laboratories are a common challenge in the practice of TCD. Demand for rapid access to patient ultrasound examination data and report for use in intensive care settings has necessitated a more flexible approach to data management. Both of these issues may benefit from a computerized approach. Methods We describe the application of a World Wide Web-based database system for use in an ultrasound laboratory. Results. Databasing information while generating a TCD report is efficient. Web accessibility allows rapid and flexible communication of time-sensitive report information and interpretation for more expeditious clinical decision making. Conclusions Web-based applications can extend the reach and efficiency of traditionally structured medical laboratories.

The paper reviews the evidence from qualitative research into old age poverty and finds it is a significant problem in development countries. Old age poverty is multidimensional in that, in addition to low income, it reflects poor access to services and employment, as well as gender differentials extending into old age. The limitations of policy on ageing and poverty arise from underestimating the contribution of older people to the development process. Copyright © 2002 John Wiley & Sons, Ltd.

Objective: To determine whether early environmental factors, such as cesarean delivery, breastfeeding, and exposure to smoking or herpes viruses, are associated with neuromyelitis optica (NMO) risk in children. Methods: This is a case-control study of pediatric NMO, multiple sclerosis (MS), and healthy subjects. Early-life exposures were obtained by standardized questionnaire. Epstein-Barr virus, cytomegalovirus, and herpes simplex virus 1 antibody responses were determined by ELISA. Multivariate logistic regression models were used to adjust for age at sampling, sex, race, and ethnicity. Results: Early-life exposures were obtained from 36 pediatric subjects with NMO, 491 with MS, and 224 healthy controls. Daycare (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.14, 0.78; p p = 0.05) were associated with lower odds of having NMO compared with healthy subjects. Cesarean delivery tended to be associated with 2-fold-higher odds of NMO compared with having MS/clinically isolated syndrome (OR 1.98, 95% CI 0.88, 4.59; p = 0.12) or with being healthy (OR 1.95, 95% CI 0.81, 4.71; p = 0.14). Sera and DNA were available for 31 subjects with NMO, 189 with MS, and 94 healthy controls. Epstein-Barr virus, herpes simplex virus 1, cytomegalovirus exposure, and being HLA-DRB1*15 positive were not associated with odds of having NMO compared with healthy subjects. Conclusions: Exposure to other young children may be an early protective factor against the development of NMO, as previously reported for MS, consistent with the hypothesis that infections contribute to disease risk modification. Unlike MS, pediatric NMO does not appear to be associated with exposures to common herpes viruses.

Background.DSM-5revisions have been criticized in the popular press for overpathologizing normative eating patterns—particularly among individuals with obesity. To evaluate the evidence for this and otherDSM-5critiques, we compared the point prevalence and interrater reliability ofDSM-IVversusDSM-5eating disorders (EDs) among adults seeking weight-loss treatment.Method.Clinicians (n=2) assignedDSM-IVandDSM-5ED diagnoses to 100 participants via routine clinical interview. Research assessors (n=3) independently conferred ED diagnoses via Structured Clinical Interview forDSM-IVand aDSM-5checklist.Results. Research assessors diagnosed a similar proportion of participants with EDs underDSM-IV(29%) versusDSM-5(32%).DSM-5research diagnoses included binge eating disorder (9%), bulimia nervosa (2%), subthreshold binge eating disorder (5%), subthreshold bulimia nervosa (2%), purging disorder (1%), night eating syndrome (6%), and other (7%). Interrater reliability between clinicians and research assessors was “substantial” for bothDSM-IV(κ= 0.64, 84% agreement) andDSM-5(κ= 0.63, 83% agreement).Conclusion.DSM-5ED criteria can be reliably applied in an obesity treatment setting and appear to yield an overall ED point prevalence comparable toDSM-IV.

Context Pioglitazone reduces cardiovascular risk in nondiabetic patients after an ischemic stroke or transient ischemic attack (TIA) but is associated with increased risk for bone fracture. Objective To characterize fractures associated with pioglitazone by location, mechanism, severity, timing, and sex. Design, setting, and patients Patients were 3876 nondiabetic participants in the Insulin Resistance Intervention after Stroke trial randomized to pioglitazone or placebo and followed for a median of 4.8 years. Fractures were identified through quarterly interviews. Results At 5 years, the increment in fracture risk between pioglitazone and placebo groups was 4.9% [13.6% vs 8.8%; hazard ratio (HR), 1.53; 95% confidence interval (CI), 1.24 to 1.89). In each group, ∼80% of fractures were low energy (i.e., resulted from fall) and 45% were serious (i.e., required surgery or hospitalization). For serious fractures most likely to be related to pioglitazone (low energy, nonpathological), the risk increment was 1.6% (4.7% vs 3.1%; HR, 1.47; 95% CI, 1.03 to 2.09). Increased risk for any fracture was observed in men (9.4% vs 5.2%; HR, 1.83; 95% CI, 1.36 to 2.48) and women (14.9% vs 11.6%; HR, 1.32; 95% CI, 0.98 to 1.78; interaction P = 0.13). Conclusions Fractures affected 8.8% of placebo-treated patients within 5 years after an ischemic stroke or TIA. Pioglitazone increased the absolute fracture risk by 1.6% to 4.9% and the relative risk by 47% to 60%, depending on fracture classification. Our analysis suggests that treatments to improve bone health and prevent falls may help optimize the risk/benefit ratio for pioglitazone.

The pre-malignant skin lesion lentigo maligna (LM) presents a particular challenge. Pathologists demonstrate poor diagnostic concordance and often struggle to assess whether excision margins are truly negative. This can lead to equivocal histology reports and a lack of clear guidance with which surgeons may rationalise their surgical management plans. Based upon the biological principle that tumour burden increases the chance of recurrence, we propose a shift in diagnostic paradigm, using melanocyte count (MC) at an excision margin to predict LM recurrence.This retrospective study reviewed all cases of LM from a regional UK melanoma centre (1996-2011), to include 167 excisions, from 99 patients. Pathology slides were assessed for MC (blinded) at the most affected margin. Seven secondary markers of neoplasia were additionally evaluated. Logistic regression analysis was used to model the relationship between MC and recurrence.MC is a strong predictor of LM recurrence (p 0.0001). A regression curve predicts risk for individual MCs, which may also be divided into three risk strata; low (0-11% [MC 0-20]), intermediate (15-89% [MC 21-30]), and high risk (92-100% [MC ≥ 31]). MC misclassified 0.6% of cases in the low and high risk groups compared with 21% for pathologists, who were also equivocal for 18% of excisions. MC's inter-rater concordance was high (0.9). The secondary factors were all independently associated with recurrence, but failed to improve predictive ability supplementary to MC.MC confidently predicts LM recurrence and is more accurate and reliable, whilst also reducing the uncertainty of current pathology assessment. Risk estimates for any given MC can be easily charted using the regression curve graph, where confidence interval and risk group boundaries demonstrate the degree of certainty associated with any given prediction. This change in approach is congruent with tumour behaviour. A recurrence 'tipping point' corresponds to the sharp risk increase across the intermediate group's narrow band of MC.

This paper examines the growing problem of violence against older persons, particularly older women, in developing countries in general and in African countries in particular. An attempt is made to set out the nature and scale of the problem, and to examine some consequences of violence for older persons, based on local experience of HelpAge International (HAI) partners. Finally, selected innovative interventions designed and implemented by HAI partners to address the problem are described.

Background —Time is of the essence for effective intervention in acute ischemic stroke. Efforts including stroke teams that are “on call” around-the-clock are emerging to reduce the time from emergency room arrival to evaluation and treatment. Summary of Comment —Based on the results of the NINDS rt-PA Stroke Trial, which demonstrated both clinical effectiveness in reducing neurological deficits and disability and cost savings to health care systems, many community hospitals and managed-care organizations are exploring methods to enhance and expedite acute stroke care in their local communities. Only a small fraction of acute stroke victims is currently treated with thrombolytics ( Conclusions —Computer-based technology can now be used to integrate electronic medical information, clinical assessment tools, neuroradiology, laboratory data, and clinical pathways to bring state-of-the-art expert stroke care to underserved areas.

We report a case of Hashimoto's encephalopathy with prominent unsteadiness of gait. Nerve conduction studies and electromyographic findings were consistent with a sensory ganglionopathy. Symptoms and clinical findings resolved with high-dose corticosteroid therapy and paralleled the levels of anti-microsomal antibodies. Sensory ganglionopathy seems to be another aspect of the broad clinical syndrome labeled Hashimoto's encephalopathy.

This paper offers a rare examination of older people’s mobility in a developing country context. It presents findings from a recent mixed-methods study of the transport and mobility constraints faced by older people in 10 settlements in Kibaha district Tanzania and is concerned, in particular, with the interconnections between transport, health and livelihoods. The study demonstrates the diverse ways in which older people’s health, livelihoods and access to transport are interconnected, the growing importance of motorcycle–taxi services for rural connectivity, and how the relationality between older people and younger generations contributes to the shaping of mobility patterns.

N-acryloylmorpholine (NAM) was photo-polymerized to produce the homopolymer poly(N-acryloylmorpholine) (PNAM). PNAM behaves as a physical hydrogel in aqueous solvents, doubling its dry weight over a 2 h period before undergoing dissolution following a second order exponential decay profile. In vitro cellular experiments using mouse myoblasts showed that PNAM acts as an effective spatial cell barrier for 38 h, with slow migration of cells into the PNAM area occurring between 45 and 73 h after cell seeding. At 80 h myoblasts fully occupied the area initially blocked by PNAM. Immunofluorescent staining of myoblasts adjacent to PNAM showed normal cytoskeletal structure and well developed focal adhesions indicating limited PNAM toxicity. This study shows that PNAM is an easy to synthesize physical hydrogel that acts as a temporal and spatial barrier to cell adhesion.

Purpose To develop an evidence-based guideline on central venous catheter (CVC) care for patients with cancer that addresses catheter type, insertion site, and placement as well as prophylaxis and management of both catheter-related infection and thrombosis. Methods A systematic search of MEDLINE and the Cochrane Library (1980 to July 2012) identified relevant articles published in English. Results The overall quality of the randomized controlled trial evidence was rated as good. There is consistency among meta-analyses and guidelines compiled by other groups as well. Recommendations There is insufficient evidence to recommend one CVC type or insertion site; femoral catheterization should be avoided. CVC should be placed by well-trained providers, and the use of a CVC clinical care bundle is recommended. The use of antimicrobial/antiseptic-impregnated and/or heparin-impregnated CVCs is recommended to decrease the risk of catheter-related infections for short-term CVCs, particularly in high-risk groups; more research is needed. The prophylactic use of systemic antibiotics is not recommended before insertion. Data are not sufficient to recommend for or against routine use of antibiotic flush/lock therapy; more research is needed. Before starting antibiotic therapy, cultures should be obtained. Some life-threatening infections require immediate catheter removal, but most can be treated with antimicrobial therapy while the CVC remains in place. Routine flushing with saline is recommended. Prophylactic use of warfarin or low–molecular weight heparin is not recommended, although a tissue plasminogen activator (t-PA) is recommended to restore patency to occluded catheters. CVC removal is recommended when the catheter is no longer needed or if there is a radiologically confirmed thrombosis that worsens despite anticoagulation therapy.

Ageing populations, already a well-established phenomenon in the countries of the North, are also a growing issue in the South. This demographic transition is, however, occurring in the South without the rising affluence which accompanied industrialisation in the North. This article examines a variety of dimensions of the problem in the South, including older people's socio-economic and health situations, and their roles in family and community. It questions whether changes in the status of older people are due to modernising forces, or to structural inequalities (differences in wealth and social position) which exist in all societies, but are particularly prevalent in the poorer countries of the South.

Jose Biller, Jose M. Ferro, eds 334 pages. Shrewsbury, UK: tfm Publishing Ltd, 2011. $99.00. ISBN: 978-1-903378-76-2 Evidence-based medicine is the mantra of modern-day practice, the bedrock of today's clinical care. We feel justified, and to a certain degree protected, when we build our daily patient care decisions with randomized clinical trial data as the substratum for our house of informed management. When our patient happens to stray from this foundation slightly by not meeting the criteria of the original studies, we generalize with a mild degree of reticence. When the issue ventures out into unsupported territory, we rely on the joists of our own clinical judgment and experience, our understanding of the pathophysiology, and the expert opinion and guidelines put together by our professional organizations. Perhaps we, collectively, rest uneasy as we venture out into those areas. When examining the current state of our medical architecture, we might find it at once impressive in its scope but perhaps lacking in solidity. Today's practitioner of stroke medicine is constantly presented with patients and situations that challenge one's level and depth of understanding of the literature. The diagnosis and management of acute stroke involves a series of difficult decisions that must be rapidly executed. Some rest on solid experimental and theoretical ground, others do not. Guidelines for Food and Drug Administration–approved intravenous tissue-type plasminogen activator within 3 hours of stroke onset are straightforward, but many patients fall outside the recommendations. How does one calculate the risk-benefit ratio? How should these decisions be made? How should one manage blood pressure and …

Multiple sclerosis (MS) can present with many clinical pictures, but only rarely as a lacunar syndrome. The following case presentation is of multiple sclerosis with initial presentation as ataxic hemiparesis (AH), indistinguishable from the vascular syndrome. This case serves to illustrate that even classic lacunar syndromes can actually be the initial manifestation of multiple sclerosis and that other etiologies besides ischemic stroke need to remain in the differential diagnosis until a definitive has been concluded.

Background: Elderly patients with acute ischemic stroke often do worse than younger counterparts independent of thrombolytic therapy. Further, tissue-type plasminogen activator, (t-PA) is frequently withheld from the very old. This may be the result of comorbid conditions prohibiting its use or possibly the fear of causing more harm than good. We present a case of a 100-year-old woman who was treated with t-PA for acute ischemic stroke with rapid resolution of symptoms. Case Description: A 100-year-old woman presented to the emergency department with slurred speech, right hemiparesis and right hemisensory loss. Computed tomography revealed neither hemorrhage nor early ischemic changes. Intravenous t-PA was administered at 0.9 mg/kg 3 min prior to the 3-hour limit. She improved rapidly (NIHSS from 12 on admission to 4 at 1 month) and was discharged to the care of her family after 4 hospital days. Conclusion: Intravenous thrombolysis may be beneficial in the very elderly and should be considered in any eligible elderly patients with acute ischemic stroke, with a risk/benefit analysis individualized to each case.

Background Clinical trials of stroke therapy have been hampered by slow rates of enrolment. Purpose Our purpose is to validate a previously developed model for accelerating enrolment in clinical trials by replicating it at new locations. The model employs coordinators who travel from a host institution to enrol participants from a network of participating hospitals. Active surveillance assures identification of all eligible patients. Methods Among 70 U.S. investigators participating in National Institutes of Health-funded trial of stroke prevention, five investigators were invited to develop local identification and outreach networks (LIONs). Each LION comprised a LION coordinating centre servicing multiple hospitals. Hospitals provided names of patients with stroke or transient ischaemic attack to researchers at the LION coordinating centre who initiated contact; patients were offered home visits for consent and randomization. Outcomes were feasibility, enrolment, data quality, and cost. Results Five LIONs varied in size from two to eight hospitals. All 24 hospitals we approached agreed to participate. The average monthly rate of enrolment at the research sites increased from 1.4 participants to 3.5 after expanding from a single institution model to the LION format (mean change = 2.1, range 0.9–3.7). Monthly performance improved over time. Data quality was similar for LIONs and non-LION sites, except for drug adherence which was lower at LIONs. The average cost to randomize and follow one participant during the study interval was 2.4 times the cost under the per-patient, cost-reimbursement strategy at non-LION sites. The cost ratio declined from 3.4 in year one to 1.8 in year two. Limitations The LION strategy requires unprecedented collaboration and trust among institutions. Applicability beyond stroke requires confirmation. Conclusion LIONs are a practical, reproducible method to increase enrolment in trial research. Twelve months were required for the average site to reach its potential. The per-participant cost at LIONs was higher than conventional sites but declined over time.

Anemia is a known predictor of in-hospital mortality among patients with such vascular conditions as acute myocardial infarction, congestive heart failure, and chronic kidney disease. The role of anemia in patients with acute ischemic stroke is less well understood. We sought to examine the association between anemia at hospital admission and the combined outcome of in-hospital mortality and discharge to hospice in patients with acute ischemic stroke. We evaluated data from a retrospective cohort of consecutive ischemic stroke patients presenting within 48 hours of symptom onset at 5 hospitals between 1998 and 2003. Anemia was defined as an admission hematocrit value of

Background: Because common viruses are encountered during childhood, pediatric multiple sclerosis (MS) offers a unique opportunity to investigate the influence of these viruses on disease susceptibility and the interactions between seroprevalence and select HLA genotypes. We studied seroprevalence for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) type 1 and HLA-DRB1 * 1501/1503 status as predictors of pediatric MS. Methods: This was a retrospective analysis of prospectively collected demographic, clinical, and biologic data in subjects up to 18 years of age with early MS, control subjects seen at the same regional referral pediatric MS clinics, and additional healthy pediatric control subjects. Results: Patients with early pediatric MS (n = 189) and pediatric control subjects (n = 66) were tested. Epstein-Barr nuclear antigen-1 seropositivity was associated with an increased odds of MS (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.52–9.38, p = 0.004) in analyses adjusted for age, sex, race, ethnicity, and HLA-DRB1 * 1501/1503 status. In multivariate analyses including EBV status, a remote infection with CMV (OR 0.27, 95% CI 0.11–0.67, p = 0.004) was associated with a lower risk of developing MS. Although a remote infection with HSV-1 was not associated with an increased odds of MS, a strong interaction was found between HSV-1 status and HLA-DRB1 in predicting MS ( p DRB1 * 15 allele (OR 4.11, 95% CI 1.17–14.37, p = 0.03), whereas the effect was reversed in those who were DRB1 * 15 -positive (OR 0.07, 95% CI 0.02–0.32, p = 0.001). Conclusions: These findings suggest that some infections with common viruses may in fact lower MS susceptibility. If this is confirmed, the pathways for risk modification remain to be elucidated.

The paper explores the relationship between old age and chronic poverty in the developing world, and the implications of this for achieving global targets for poverty reduction.For the majority of the world's older people, the meaning of old age is not a chronological definition but the changing roles accompanying physical change and reduced capacity to contribute or maintain a livelihood. As a result of trends towards lower fertility and mortality, populations are aging. Whilst this demographic transition is global, the growth in numbers and proportions of older people is most rapid in the so-called "developing" countries. In the absence of policies, infrastructure, services and information increasing numbers of people in the south are aging in poverty.Available evidence reviewed in this paper highlights three key features of chronic poverty in old age: it is strongly associated with reduced framework of capacity, it is a condition from which few if any can be expected to escape, and it is both caused by and perpetuates chronic intergenerational poverty. Opportunities to employ physical strength, often the most critical asset of poor people, are reduced in old age. Widespread institutional and social exclusion on the basis of age and gender represent formidable barriers for the poorest older people in their efforts to achieve income and social security, and crucially their health. The differential impacts of age on women and men is only beginning to be understood.Factors indicating high risk of chronic poverty for older women include their greater longevity and likelihood of widowhood, inequitable inheritance laws, and low access to education and health services, while risk factors for men in some communities include abrupt loss of status and low levels of support from children.A review of the actions of government, civil society and international agencies to address old age poverty indicates that aging is still distant from the overall social development agendas at all levels. Current poverty reduction measures and proposals have not sufficiently acknowledged the intergenerational dimension of poverty, nor has attention been paid to older people's own survival strategies. The paper argues that these are critical elements of any credible poverty reduction programme.

Falls are a serious medical complication following stroke. The objectives of this study were to (1) confirm the prevalence of falls among patients with stroke during acute hospitalization, (2) identify factors associated with falls during the acute stay, and (3) examine whether in-hospital falls were associated with loss of function after stroke (new dependence at discharge). We completed a secondary analysis of data from a retrospective cohort study of patients with ischemic stroke who were hospitalized at one of four hospitals. We used logistic regression to identify factors associated with inpatient falls and examine the association between falls and loss of function. Among 1,269 patients with stroke, 65 (5%) fell during the acute hospitalization period. We found two characteristics independently associated with falls: greater stroke severity (National Institutes of Health Stroke Scale [NIHSS] ≥8, adjusted odds ratio [OR] = 3.63, 95% confidence interval [CI]: 1.46-9.00) and history of anxiety (adjusted OR = 4.90, 95% CI: 1.70-13.90). Falls were independently associated with a loss of function (adjusted OR = 9.85, 95% CI: 1.22-79.75) even after adjusting for age, stroke severity, gait abnormalities, and past stroke. Stroke severity (NIHSS >8) may be clinically useful during the acute inpatient setting in identifying those at greatest risk of falling. Given the association between falls and poor patient outcomes, rehabilitation interventions should be implemented to prevent falls poststroke.

L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n = 106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondisease-related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype genotype relationship. Hum Mutat 31:380-390, 2010. (C) 2010 Wiley-Liss, Inc.

Background: Transcranial Doppler (TCD) ultrasound is a procedure commonly used to screen individuals with the major hemoglobin S diseases, Hb SS and Hb S-beta 0 , for significant stenoses in the circle of Willis. Flow velocities above 200 cm/s have been shown to identify patients at elevated risk for cerebral infarction. Among TCD’s limitations is the inability to insonate the distal extracranial, petrous, and cavernous internal carotid artery (ICA) through the standard transtemporal approach. Methods: We extended the submandibular approach to include infra-siphon portions of the ICA. Results: Using the extended submandibular approach to evaluate these portions of the ICA, we identified stenotic lesions in 4 patients with Hb SS disease out of a population of 131 children with Hb SS. Three of the 4 patients had no history of overt stroke or stroke-like symptoms. Neuroimaging confirmed the stenotic lesions, and also revealed watershed infarction as well as discrete areas of silent infarction. All 4 children had neuropsychological impairment. Conclusions: The submandibular approach, when added to a standard transcranial Doppler examination, may increase the sensitivity of this technique to identify important potential sources of cerebral infarction.

The rationale was to develop recommendations on the use of 18F-FDG PET in breast, colorectal, esophageal, head and neck, lung, pancreatic, and thyroid cancer; lymphoma, melanoma, and sarcoma; and unknown primary tumor. Outcomes of interest included the use of 18F-FDG PET for diagnosing, staging, and detecting the recurrence or progression of cancer. Methods: A search was performed to identify all published randomized controlled trials and systematic reviews in the literature. An additional search was performed to identify relevant unpublished systematic reviews. These publications comprised both retrospective and prospective studies of varied methodologic quality. The anticipated consequences of false-positive and false-negative tests when evaluating clinical usefulness, and the impact of 18F-FDG PET on the management of cancer patients, were also reviewed. Results and Conclusion:18F-FDG PET should be used as an imaging tool additional to conventional radiologic methods such as CT or MRI; any positive finding that could lead to a clinically significant change in patient management should be confirmed by subsequent histopathologic examination because of the risk of false-positive results. 18F-FDG PET should be used in the appropriate clinical setting for the diagnosis of head and neck, lung, or pancreatic cancer and for unknown primary tumor. PET is also indicated for staging of breast, colon, esophageal, head and neck, and lung cancer and of lymphoma and melanoma. In addition, 18F-FDG PET should be used to detect recurrence of breast, colorectal, head and neck, or thyroid cancer and of lymphoma.

Anti-Hu antibodies (anti-neuronal nuclear antibodies, type 1) are associated with paraneoplastic encephalomyelitis in adults, especially those with small cell lung cancer. Anti-Hu antibodies are extremely rare in children, but they have been observed in neuroblastoma with or without opsoclonus-myoclonus syndrome or in limbic encephalitis without associated malignancy.1 However, anti-Hu antibodies are not typically associated with clinical features of Rasmussen encephalitis (RE). Acknowledgment: The authors thank Sean J. Pittock, MD, for his assistance in the interpretation of serum and CSF anti-Hu antibody titers and for explaining the methodologic processes involved in the Mayo Clinic Paraneoplastic Antibody Panel.

A 32-year-old man with mental retardation and uncontrolled complex partial epilepsy receiving carbamazepine (CBZ) and divalproex sodium (VPA), developed frequent episodes of forced upward gaze after increase in the daily VPA dosage. CBZ dosage was decreased, with prompt resolution of symptoms. The upward gaze problem recurred several months later. CBZ dosage was decreased further with subsequent resolution of symptoms. Therefore, the oculogyric crisis (OGC) appeared to be induced by CBZ.

Ear reconstruction with full-thickness skin grafts can be a challenging task for plastic surgeons. It is often necessary to remove the underlying cartilage with the skin lesion and the resultant defect may be deeply concave. We present a short clinical report to describe an improved technique that we find useful in reducing the diameter and depth of anterior pinna contour defects, in improving graft take, and in reducing the size of the donor-site scar.

In an increasingly globalized world, many issues once seen as exclusive either to ‘developed’ or ‘developing’ countries are becoming the shared experience of both. One such issue is that of the demographic transition of the late 20th century, the major feature of which has been accelerating population ageing in all countries, rich and poor. Awareness of this transition is growing, albeit at varying rates. In countries whose populations already include significant numbers of older people, questions affecting old age are already high on policy agendas. In countries yet to experience the full force of demographic changes these questions still have a lower priority. However, some common themes between North and South are already beginning to emerge strongly. These concerns include the potentially rising costs of social welfare that are seen to be associated with older populations. The capacity of public provision to support such costs is being questioned. Consequently there is increasing emphasis on identifying what are seen as ‘cost-effective’ measures, such as enhancing the caring capacity of families and communities, asserting the responsibility of individuals to make provision for their own old age, and drawing on collective support for older people from ‘civil society’ institutions, including non-governmental organizations (NGO). In such a context this article examines the roles of NGO particularly in the newly-ageing countries of the South. It seeks to illustrate some of the ways in which NGO are responding to the demographic transition and to policy change relating to ageing societies, by moving beyond narrowly defined service delivery roles, to become advocates for policy change.