Crevasse refreezing and signatures of retreat observed at Kamb Ice Stream grounding zone.

Ice streams flowing into Ross Ice Shelf are presently responsible for around 10% of the mass flux from West Antarctica, with the noteworthy exception of Kamb Ice Stream, which stagnated in the late 1800s. The subsequent reduction in ice supply led to grounding-line retreat at the coastal margin where Kamb transitions into the floating Ross Ice Shelf. Grounding-line migration is linked to broader changes in ice-sheet mass balance and sea level, but our understanding of related ice, ocean and seafloor interactions is limited by the difficulty in accessing these remote regions. Here we report in situ observations from an underwater vehicle deployed at Kamb that show how fine-scale variability in ice and ocean structure combine to influence a diversity of ice-ocean interactions. We found a stratified water column within a tenth of a degree of freezing at the ice base and mapped basal crevasses with supercooled water and active marine ice formation. At the seafloor, we interpret parallel ridges as crevasse impressions left as the ice lifted off during grounding-line retreat. These observations from a recently ungrounded sub-shelf environment illuminate both the geomorphological signatures of past grounding-line retreat and the fine-scale sensitivity of ongoing ice-ocean interactions to ice topography.

Heterogeneous melting near the Thwaites Glacier grounding line.

Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment1-3. Because it is grounded below sea level4,5, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean6,7. Recent ice-flow acceleration2,8 and retreat of the ice front8-10 and GL11,12 indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice-ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming.

The associations between anthropometric measurements and left ventricular structure and function: the Echo-SOL Study.

OBJECTIVE: The objective of this study is to determine associations between anthropometry and echocardiographic measures of cardiac structure and function in Hispanic/Latinos. METHODS: A total of 1,824 participants from ECHO-SOL were included. We evaluated associations between echocardiographic measures of left ventricular structure and function and anthropometric measures using multivariable-adjusted linear and logistic regression models adjusting for traditional cardiovascular risk factors. RESULTS: The mean age was 56 ± 0.17 years, 57% were women. The mean body mass index (BMI) was 30 ± 9.4 kg m-2, waist circumference (WC) was 100 ± 18 cm, and waist-to-hip ratio (WHR) was 0.93 ± 0.15. Adjusted analysis showed that 5-unit increment in BMI and 5-cm increase in WC was associated with 3.4 ± 0.6 and 1.05 ± 0.05 g m-2.7 (p < 0.05 for both) higher left ventricular (LV) mass index, respectively. Similarly, 0.1-unit increment in WHR was associated with 2.0 ± 0.16 g m-2.7 higher LV mass index (p < 0.01). WHR was associated with 0.22 ± 0.08% decrease in ejection fraction (p < 0.05). Concomitantly, 5-unit increment in BMI and WC was associated with increased odds of abnormal LV geometry (odds ratio 1.40 and 1.16, p = 0.03 and <0.01, respectively); 0.1-unit increment in WHR was associated with increased odds of abnormal LV geometry (odds ratio 1.51, p < 0.01). CONCLUSIONS: Among Hispanic/Latinos, higher anthropometric measures were associated with adverse cardiac structure and function.

16S rRNA gene sequencing on a benchtop sequencer: accuracy for identification of clinically important bacteria.

AIMS: Test the choice of 16S rRNA gene amplicon and data analysis method on the accuracy of identification of clinically important bacteria utilizing a benchtop sequencer. METHODS AND RESULTS: Nine 16S rRNA amplicons were tested on an Ion Torrent PGM to identify 41 strains of clinical importance. The V1-V2 region identified 40 of 41 isolates to the species level. Three data analysis methods were tested, finding that the Ribosomal Database Project's SequenceMatch outperformed BLAST and the Ion Reporter Metagenomics analysis pipeline. Lastly, 16S rRNA gene sequencing mixtures of four species through a six log range of dilution showed species were identifiable even when present as 0·1% of the mixture. CONCLUSIONS: Sequencing the V1-V2 16S rRNA gene region, made possible by the increased read length Ion Torrent PGM sequencer's 400 base pair chemistry, may be a better choice over other commonly used regions for identifying clinically important bacteria. In addition, the SequenceMatch algorithm, freely available from the Ribosomal Database Project, is a good choice for matching filtered reads to organisms. Lastly, 16S rRNA gene sequencing's sensitivity to the presence of a bacterial species at 0·1% of a mixture suggests it has sufficient sensitivity for samples in which important bacteria may be rare. SIGNIFICANCE AND IMPACT OF THE STUDY: We have validated 16S rRNA gene sequencing on a benchtop sequencer including simple mixtures of organisms; however, our results highlight deficits for clinical application in place of current identification methods.

James Parkinson's Chimera: syndrome or disease?

It is 200 years since James Parkinson published An Essay on the Shaking Palsy. While his monograph continues to be acclaimed for its precedence and clarity of description, what is often overlooked is the originality of Parkinson's ideas. Here we show that he appreciated the weakness of the systematic 18th century nosologies, which presupposed that medical species, the building blocks of these Linnaean taxonomic schemes, were as distinct as plant and animal species; and that Parkinson made a conceptual leap about combinations of clinical phenomena in recurring patterns, now recognised to be one of the germs of neurological thinking about syndromes. The Essay's written style underpins another aspect of significance to contemporary neurological practice - an inherent intellectual humility. In this commemorative year we locate the continuing importance of the related notions of syndrome and disease in successive frameworks of knowledge about the shaking palsy. Syndrome and disease are interpreted as dual character concepts, one clinically-based and the other restricted to pathophysiological causation. They both remain fundamental to understanding Parkinson's syndrome-disease today.

Depressive symptoms linked to 1-h plasma glucose concentrations during the oral glucose tolerance test in men and women with the metabolic syndrome.

AIMS: The addition of the 1-h plasma glucose concentration measure from an oral glucose tolerance test to prediction models of future Type 2 diabetes has shown to significantly strengthen their predictive power. The present study examined the relationship between severity of depressive symptoms and hyperglycaemia, focusing on the 1-h glucose concentration vs. fasting and 2-h glucose measures from the oral glucose tolerance test. METHODS: Participants included 140 adults with the metabolic syndrome and without diabetes who completed a baseline psychobiological assessment and a 2-h oral glucose tolerance test, with measurements taken every 30 min. Depressive symptoms were assessed using the Beck Depression Inventory. RESULTS: Multivariate linear regression revealed that higher levels of depressive symptoms were associated with higher levels of 1-h plasma glucose concentrations after adjusting for age, gender, ethnicity, BMI, antidepressant use and high-sensitivity C-reactive protein. Results were maintained after controlling for fasting glucose as well as for indices of insulin resistance and secretion. Neither fasting nor 2-h plasma glucose concentrations were significantly associated with depressive symptoms. CONCLUSIONS: Elevated depressive symptoms in persons with the metabolic syndrome were associated with greater glycaemic excursion 1-h following a glucose load that was not accounted for by differences in insulin secretory function or insulin sensitivity. Consistent with previous findings, this study highlights the value of the 1-h plasma glucose measurement from the oral glucose tolerance test in the relation between depressive symptoms and glucose metabolism as an indicator of metabolic abnormalities not visible when focusing on fasting and 2-h post-oral glucose tolerance test measurements alone.

House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review.

BACKGROUND: To assess the benefits and harms of measures designed to reduce house dust mite (HDM) exposure in the management of house dust mite-sensitive allergic rhinitis. METHODS: Systematic review of randomized controlled trials was made, in which HDM control measures have been evaluated in comparison with placebo or other HDM avoidance measures, in patients with clinically proven allergic rhinitis. RESULTS: Nine trials involving 501 participants satisfied the inclusion criteria. These trials have investigated the effectiveness of bedroom environmental control programmes involving the use of HDM impermeable bedding covers (n = 4), acaricides (n = 2), high-efficiency particulate air filters (n = 2) and, using a factorial design, acaricide and HDM impermeable bedding covers in isolation and combination (n = 1). Seven of the nine trials reported that, when compared with control, the interventions studied resulted in significant reductions in HDM load. Of the interventions studied to date, acaricides appear to be the most promising, although the findings from these studies need to be interpreted with care because of their methodological limitations. House dust mite impermeable bedding as an isolated intervention is unlikely to offer benefit. CONCLUSIONS: Trials have tended to be small and of poor methodological quality, making it difficult to offer any definitive recommendations. Interventions that achieve substantial reductions in HDM load may offer some benefit in reducing rhinitis symptoms. Isolated use of HDM impermeable bedding is unlikely to prove effective.

MR imaging in multiple sclerosis: review and recommendations for current practice.

MR imaging is widely used for the diagnosis and monitoring of patients with MS. Applications and protocols for MR imaging continue to evolve, prompting a need for continual reassessments of the optimal use of this technique in clinical practice. This article provides updated recommendations on the use of MR imaging in MS, based on a review of the trial evidence and personal experiences shared at a recent expert meeting of radiologists and neurologists.

Important sources of variability in clinical studies of neutralizing antibodies against interferon beta.

Interferon (IFN) beta treatment of relapsing-remitting multiple sclerosis (RRMS) stimulates production of neutralizing antibodies (NAbs) in some patients. However, clinical data supporting the hypothesis that NAbs to IFN beta adversely affect patient outcomes are not consistent across multiple studies or different forms of IFN beta. Only the PRISMS trial has produced data showing a negative impact of NAbs to IFN beta-1a (Rebif) across multiple study endpoints. No such data are available for IFN beta-1b (Betaseron) despite completion of a large registry study. Biological factors affecting the development of NAbs to IFN beta include protein structure, product formulation, administration frequency and/or dosing, and patients' immunological responses. Technical factors affecting interpretation of clinical trial data on NAbs include inadequate randomization; differences in the methods used to measure NAbs and in definitions of NAb positivity; selection of NAb-positive patient subpopulations according to titer and duration of NAb response; lack of power to detect differences in patient subgroups; and different trial durations. Given the complexity of NAb studies, it is not possible to generalize from current data regarding the potential impact of NAbs on the clinical efficacy of all IFN beta therapies. Differences between IFN beta products and their specific trials should be considered when evaluating the evidence on this topic.

Neutralizing antibodies to interferon beta-1b are not associated with disease worsening in multiple sclerosis.

The clinical impact of neutralizing antibodies (NAbs) on interferon beta (IFNbeta) efficacy was studied in three large patient cohorts comprising 6698 multiple sclerosis (MS) patients receiving IFNbeta-1b across North America, Europe, and Australia. In North America and Europe, NAb testing was generally undertaken because of a poor clinical response; in Australia, it was mandatory for every patient. Of the 6697 patients tested, 28.9% had at least one NAb titre > or = 20 neutralizing units (NU)/ml, 14.4% had NAb titres > or = 100 NU/ml and 7.7% had NAb titres > or = 400 NU/ml. The NAb-positive rate of 37.0% in Australia was significantly greater than those in North America (21.3%) and Europe (27.6%), and this was observed at every NAb titre level. Our results suggest that NAbs are not responsible for poor clinical responses and that NAb status is of little clinical value. These findings will need to be confirmed in a large independent study.

Neutralizing antibodies to interferon beta: assessment of their clinical and radiographic impact: an evidence report: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

The clinical and radiologic impact of developing neutralizing antibodies (NAbs) to interferon beta (IFNbeta) while on this therapy for multiple sclerosis (MS) is assessed. On the basis of Class II and III evidence, it is concluded that treatment of patients with MS with IFNbeta (Avonex, Betaseron, or Rebif) is associated with the production of NAbs (Level A). NAbs in the serum are probably associated with a reduction in the radiographic and clinical effectiveness of IFNbeta treatment (Level B). In addition, the rate of NAb production is probably less with IFNbeta-1a treatment than with IFNbeta-1b treatment, although the magnitude and persistence of this difference is difficult to determine (Level B). Finally, it is probable that there is a difference in seroprevalence due to variability in the dose of IFNbeta injected or in the frequency or route of its administration (Level B). Regardless of the explanation, it seems clear that IFNbeta-1a (as it is currently formulated for IM injection) is less immunogenic than the current IFNbeta preparations (either IFNbeta-1a or IFNbeta-1b) given multiple times per week subcutaneously (Level A). However, because NAbs disappear in some patients even with continued IFNbeta treatment (especially in patients with low titers), the persistence of this difference is difficult to determine (Level B). Although the finding of sustained high-titer NAbs (>100 to 200 NU/mL) is associated with a reduction in the therapeutic effects of IFNbeta on radiographic and clinical measures of MS disease activity, there is insufficient information on the utilization of NAb testing to provide specific recommendations regarding when to test, which test to use, how many tests are necessary, or which cutoff titer to apply (Level U).

House dust mite avoidance measures for perennial allergic rhinitis.

BACKGROUND: In developed countries, it is estimated that approximately 30% of the general population suffer from one or more allergic disorders, of which allergic rhinitis is the most common. Perennial rhinitis is most often due to allergy to the house dust mite. In such patients, house dust mite avoidance is logical, but there is considerable uncertainty regarding the efficacy and effectiveness of interventions designed to reduce dust mite exposure. OBJECTIVES: To assess the benefit (and harm) of measures designed to reduce house dust mite exposure in the management of house dust mite sensitive allergic rhinitis. SEARCH STRATEGY: Our search included the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials Register (CENTRAL) (The Cochrane Library, Issue 2, 2005), MEDLINE (1951 to 2005) and EMBASE (1974 to 2005). No restrictions on the language of publication were employed. The bibliography of each paper and other published reviews were checked for further references. The date of the last search was May 2005. SELECTION CRITERIA: Randomised controlled trials (with or without blinding), in which house dust mite control measures have been evaluated in comparison with placebo or other dust mite avoidance measures, in patients with clinician diagnosed allergic rhinitis and confirmed allergy to dust mite. DATA COLLECTION AND ANALYSIS: Two authors independently checked titles and abstracts identified by the searches and full text copies of all papers of potential relevance were considered. Trials were graded for methodological quality using the Cochrane approach. Data extraction was performed in a standardised manner. Meta-analysis was neither possible nor appropriate, because of the heterogeneity of the patient groups studied; a narrative overview of the results is therefore presented. MAIN RESULTS: Seven trials satisfied the inclusion criteria. Of these, only two studies investigating the effectiveness of mite impermeable bedding covers were of good quality; the remaining five studies were small and of poor quality. Two trials investigated the efficacy of acaricides, another two trials investigated the role of high-efficiency particulate air filters; the remaining three trials investigated the efficacy of bedroom environmental control programmes involving use of house dust mite impermeable bedding covers. Six of the seven trials showed that the interventions result in significant reductions in house dust mite load when compared with control. Of the house dust mite interventions studied to date, acaricides appear to be the most promising type of intervention, although the findings from the two studies which employed these interventions need to be interpreted with care because of their methodological limitations. Use of house dust mite impermeable bedding as an isolated intervention is unlikely to offer clinical benefit. No serious adverse effects were reported from any of the interventions. AUTHORS' CONCLUSIONS: Trials to date have on the whole been small and of poor methodological quality, making it difficult to offer any definitive recommendations on the role, if any, of house dust mite avoidance measures in the management of house dust mite sensitive perennial allergic rhinitis. The results of these studies suggest that use of acaricides and extensive bedroom based environmental control programmes may be of some benefit in reducing rhinitis symptoms and, if considered appropriate, these should be the interventions of choice. Isolated use of house dust mite impermeable bedding is unlikely to prove effective.

Allergen injection immunotherapy for seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis is the most common of the allergic diseases. Despite improved understanding of the pathophysiology of allergic rhinitis and advances in its pharmacological treatment, its prevalence has increased worldwide. For patients whose symptoms remain uncontrolled despite medical treatment, allergen injection immunotherapy is advised. An allergen-based treatment may reduce symptoms, the need for medication and modify the natural course of this disease. OBJECTIVES: To evaluate the efficacy and safety of subcutaneous specific allergen immunotherapy, compared with placebo, for reducing symptoms and medication requirements in seasonal allergic rhinitis patients. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), Pre-MEDLINE, KOREAMED, INDMED, LILACS, PAKMEDINET, Scisearch, mRCT and the National Research Register. The date of the last search was February 2006. SELECTION CRITERIA: All studies identified by the searches were assessed to identify randomised controlled trials involving participants with symptoms of seasonal allergic rhinitis and proven allergen sensitivity, treated with subcutaneous allergen specific immunotherapy or corresponding placebo. DATA COLLECTION AND ANALYSIS: Two independent authors identified all studies reporting double-blind, placebo controlled randomised trials of specific immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Two authors independently performed quality assessment of studies. Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.2.8. Analysis was performed using the Standardised Mean Difference (SMD) method and a random-effects model; P values < 0.05 were considered statistically significant. The primary outcome measures were symptom scores, medication use, quality of life and adverse events. MAIN RESULTS: We retrieved 1111 publications of which 51 satisfied our inclusion criteria. In total there were 2871 participants (1645 active, 1226 placebo), each receiving on average 18 injections. Duration of immunotherapy varied from three days to three years. Symptom score data from 15 trials were suitable for meta-analysis and showed an overall reduction in the immunotherapy group (SMD -0.73 (95% CI -0.97 to -0.50, P < 0.00001)). Medication score data from 13 trials showed an overall reduction in the immunotherapy group (SMD of -0.57 (95% CI -0.82 to -0.33, p<0.00001)). Clinical interpretation of the effect size is difficult. Adrenaline was given in 0.13% (19 of 14085 injections) of those on active treatment and in 0.01% (1 of 8278 injections) of the placebo group for treatment of adverse events. There were no fatalities. AUTHORS' CONCLUSIONS: This review has shown that specific allergen injection immunotherapy in suitably selected patients with seasonal allergic rhinitis results in a significant reduction in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events.

Antibiotics versus placebo for acute bacterial conjunctivitis.

BACKGROUND: There are concerns about whether antibiotic therapy confers significant clinical benefit in the treatment of acute bacterial conjunctivitis. OBJECTIVES: The aim of this review was to assess the benefit and harm of antibiotic therapy in the management of acute bacterial conjunctivitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register), MEDLINE, EMBASE, SIGLE, NRR, PubMed and the reference lists of identified trial reports. We used the Science Citation Index to look for articles that cited the relevant studies, and we contacted investigators and pharmaceutical companies for information about additional trials. SELECTION CRITERIA: We included double masked randomised controlled trials in which any form of antibiotic treatment had been compared with placebo in the management of acute bacterial conjunctivitis. This included topical, systemic and combination (for example, antibiotics and steroids) antibiotic treatments. DATA COLLECTION AND ANALYSIS: One author extracted data and the accuracy was checked by a second author. MAIN RESULTS: This review includes five trials which randomised a total of 1034 participants. One further trial is currently 'awaiting assessment'. This has been published in abstract form and has yet to be fully reported. Three of the trials have been conducted on a selected specialist care patient population and the two more recent trials have been conducted in a community care setting. The trials were heterogeneous in terms of their inclusion and exclusion criteria, the nature of the intervention, and the outcome measures assessed. Meta-analyses of data on clinical and microbiological remission rates reveal that topical antibiotics are of benefit in improving early (days 2 to 5) clinical (RR 1.24, 95% CI 1.05 to 1.45) and microbiological (RR 1.77, 95% CI 1.23 to 2.54) remission rates; later (days 6 to 10) data reveal that these early advantages in clinical (RR 1.11, 95% CI 1.02 to 1.21) and microbiological cure rates are reduced (RR 1.56, 95% CI 1.17 to 2.09), but persist. Most cases however resolve spontaneously with clinical remission being achieved in 65% (95% CI 59 to 70) by days 2 to 5 in those receiving placebo. No serious outcomes were reported in either the active or placebo arms of these trials, indicating that important sight-threatening complications are an infrequent occurrence. AUTHORS' CONCLUSIONS: Acute bacterial conjunctivitis is frequently a self-limiting condition, but the use of antibiotics is associated with significantly improved rates of clinical and microbiological remission.

Interventions in primary care to reduce medication related adverse events and hospital admissions: systematic review and meta-analysis.

OBJECTIVE: To identify and evaluate studies of interventions in primary care aimed at reducing medication related adverse events that result in morbidity, hospital admission, and/or mortality. METHODS: Fourteen electronic databases were systematically searched for published and unpublished data. Bibliographies of retrieved papers were searched and experts and first authors contacted in an attempt to locate additional studies. There were no restrictions on language of publication. All interventions applied in primary care settings which aimed to improve patient safety by reducing adverse events resulting from medication overuse or misuse were considered. Randomised controlled trials, controlled trials, controlled before and after studies, and interrupted time series studies were eligible for inclusion. Study quality assessment and data extraction were undertaken using the Cochrane Effective Practice and Organisation of Care data collection checklist and template. Meta-analysis was performed using a random effects model. RESULTS: 159 studies were initially identified, of which 38 satisfied our inclusion criteria. These were categorised as follows: 17 pharmacist-led interventions (of which 15 reported hospital admissions as an outcome); eight interventions led by other primary healthcare professionals that reported preventable drug related morbidity as an outcome; and 13 complex interventions that included a component of medication review aimed at reducing falls in the elderly (the outcome being falls). Meta-analysis found that pharmacist-led interventions are effective at reducing hospital admissions (OR 0.64 (95% CI 0.43 to 0.96)), but restricting analysis to the randomised controlled trials failed to demonstrate significant benefit (OR 0.92 (95% CI 0.81 to 1.05)). Pooling the results of studies in the other categories did not demonstrate any significant effect. CONCLUSIONS: There is relatively weak evidence to indicate that pharmacist-led medication reviews are effective in reducing hospital admissions. There is currently no evidence for the effectiveness of other interventions which aim at reducing admissions or preventable drug related morbidity. More randomised controlled trials of primary care based pharmacist-led interventions are needed to decide whether or not this intervention is effective in reducing hospital admissions.

Comparative tolerance of IFN beta-1a regimens in patients with relapsing multiple sclerosis. The EVIDENCE study.

The EVIDENCE study was a direct comparative study of two dose regimens of interferon (IFN) beta-1a used in the treatment of relapsing-remitting multiple sclerosis (RRMS): 30 mcg intramuscularly once weekly (qw; n=338) and 44 mcg subcutaneously three times weekly (tiw; n=339). The study continued for an average of 64 weeks. The safety population consisted of all patients receiving at least one dose of study drug. Clinical assessments occurred every 4 weeks for 24 weeks and then every 12 weeks. Blood tests for safety were taken at baseline and at weeks 4 and 12, and every 12 weeks thereafter. Overall adverse events were more common with the 44 mcg tiw regimen (p=0.007), and were due predominantly to differences in injection-site reactions. The majority of adverse events were rated mild by investigators. Hepatic and haematological adverse events and asymptomatic laboratory abnormalities were more common with 44 mcg tiw (p<0.001),with no difference seen for severe events. Flu-like symptoms were more common with 30 mcg qw (p=0.031), were more severe and persisted for longer. Serious adverse events were comparable for both groups, as were drug discontinuations. In conclusion, although adverse events were more common with high-dose, high-frequency IFN therapy, differences were primarily for mild events and did not affect treatment adherence. Based on superior clinical and magnetic resonance imaging outcomes over an average of 64 weeks, coupled with modest safety differences, the risk-benefit ratio for IFN therapy in RRMS favours the 44 mcg tiw regimen over this period of time.

Education for people with progressive neurological conditions can have negative effects: evidence from a randomized controlled trial.

OBJECTIVES: To test the effects of a home-based educational intervention in reducing the incidence and the risk of falls and pressure sores in adults with progressive neurological conditions. DESIGN: Randomized controlled trial with 12 months follow-up. SETTING: Participants' homes in the City of Nottingham. PARTICIPANTS: One hundred and fourteen people with progressive neurological conditions recruited from general practices in Nottingham, including 53 with Parkinson's disease and 45 with multiple sclerosis. INTERVENTIONS: In the education group (EG), baseline data were reviewed by an expert panel which advised on actions most likely to promote each individual's physical, social and psychological well-being. An occupational therapist (OT) then visited EG participants to provide education and information and to discuss a personalized 12-month health action plan. The comparison group (CoG) received standardized printed information delivered to their home. MAIN MEASURES: Numbers of participants reporting falls and skin sores at two-monthly phone calls during the follow-up period of 12 months. RESULTS: The EG reported significantly more falls during the follow-up period and at 12 months (adjusted odds ratio 2.83 (95% CI 1.07-7.47), p=0.036) and significantly more skin sores (adjusted odds ratio 12.74 (95% CI 1.14-142.6), p =0.039) than the CoG. There was no difference between CoG and EG in the Nottingham Extended Activities of Daily Living score, but EG patients showed a significant rise in this score over the study period of 1.62 (95% CI 0.69-2.55, p=0.002). CONCLUSIONS: Our findings provide evidence that education for people with progressive neurological conditions can have negative effects.