A combined analysis of five observational studies evaluating the efficacy and tolerability of bimatoprost/timolol fixed combination in patients with primary open-angle glaucoma or ocular hypertension

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a fixed combination of bimatoprost 0.03% and timolol (BTFC) in a clinical setting, in a large sample of patients with primary open-angle glaucoma or ocular hypertension and insufficient intraocular pressure (IOP) lowering on prior therapy. METHODS: Patient data were combined (n = 5556) from five multicenter, observational, non-controlled, open-label studies throughout Europe. Patients were identified from 830 sites in Austria, France, Germany, The Netherlands, and Switzerland. Assessments were made at baseline, 6 weeks (in Austrian, German and Swiss centers), and 12 weeks in all centers. RESULTS: BTFC lowered mean IOP from baseline by 5.4 mmHg over the 12-week duration of the studies (P < 0.0001). At study entry, 92.9% of patients were receiving another ocular hypotensive medication. In patients with no previous treatment (n = 311), BTFC reduced IOP by -9.1 mmHg, corresponding to a reduction from baseline of 36.4% (P < 0.0001). In patients receiving prior therapy of a prostaglandin analog, a beta-blocker, or a fixed combination, BTFC reduced IOP by a further 24.5%, 25.9%, and 21.4%, respectively. The majority of patients (90.3%) reported no adverse events. The most common adverse events were conjunctival hyperemia (3.2%) and eye irritation (2.8%). BTFC was rated as "good" or "very good" by 92.5% of physicians and 88.0% of patients. Most patients (96.3%) were equally or more compliant with BTFC than with their previous treatment. CONCLUSION: In routine clinical practice, BTFC achieved consistent IOP lowering in both previously treated and untreated patients with primary open-angle glaucoma or ocular hypertension. BTFC was associated with significant IOP reductions, good tolerability, and good compliance

Transitions in lifelong learning: public issues, private troubles, liminal identities

The paper seeks to reconceptualise the significance of transitions in adult learning. It combines reflection on existing research with an analysis of original data on adults' experiences of significant educational transitions. The paper starts by considering how lifelong learning and mobilities of various kinds have become absorbed into, and expressed in, the policy mainstream. It then discusses the ways in which researchers are addressing this topic. While researchers are pursuing many lines of inquiry into transitions, and using a wide range of methods (including new statistical techniques), the analysis in this paper is primarily concerned with questions of identity, and particularly the idea of learner identity. I then briefly illustrate the analysis with cases from a research project that is designed to explore aspects of a very specific pair of transitions: movement into, and then through, the higher education system among a group of people who can be defined as non-traditional students. The paper concludes by proposing the idea of a liminal identity, understood as shaped through social and cultural processes which are formed and re-formed in dynamic relationships with others. This perspective has implications for practice as well as for research

Impact of target site distribution for Type I restriction enzymes on the evolution of methicillin-resistant Staphylococcus aureus (MRSA) populations.

A limited number of Methicillin-resistant Staphylococcus aureus (MRSA) clones are responsible for MRSA infections worldwide, and those of different lineages carry unique Type I restriction-modification (RM) variants. We have identified the specific DNA sequence targets for the dominant MRSA lineages CC1, CC5, CC8 and ST239. We experimentally demonstrate that this RM system is sufficient to block horizontal gene transfer between clinically important MRSA, confirming the bioinformatic evidence that each lineage is evolving independently. Target sites are distributed randomly in S. aureus genomes, except in a set of large conjugative plasmids encoding resistance genes that show evidence of spreading between two successful MRSA lineages. This analysis of the identification and distribution of target sites explains evolutionary patterns in a pathogenic bacterium. We show that a lack of specific target sites enables plasmids to evade the Type I RM system thereby contributing to the evolution of increasingly resistant community and hospital MRSA

A laminated polymer film formulation for enteric delivery of live vaccine and probiotic bacteria

Live bacterial cells (LBC) are administered orally as attenuated vaccines, to deliver biopharmaceutical agents, and as probiotics to improve gastrointestinal health. However, LBC present unique formulation challenges and must survive gastrointestinal antimicrobial defenses including gastric acid after administration. We present a simple new formulation concept, termed Polymer Film Laminate (PFL). LBC are ambient dried onto cast acid-resistant enteric polymer films that are then laminated together to produce a solid oral dosage form. LBC of a model live bacterial vaccine and a probiotic were dried directly onto a cast film of enteric polymer. The effectiveness at protecting dried cells in a simulated gastric fluid (pH 2.0) depended on the composition of enteric polymer film used, with a blend of ethylcellulose plus Eudragit L100 55 providing greater protection from acid than Eudragit alone. However, although PFL made from blended polymers films completely released low molecular weight dye into intestinal conditions (pH 7.0), they failed to release LBC. In contrast, PFL made from Eudragit alone successfully protected dried probiotic or vaccine LBC from simulated gastric fluid for 2h, and subsequently released all viable cells within 60min of transfer into simulated intestinal fluid. Release kinetics could be controlled by modifying the lamination method

Exploring real-world symptom impact and improvement in well-being domains for tardive dyskinesia in VMAT2 inhibitor-treated patients via clinician survey and chart review

Introduction: Two vesicular monoamine transporter 2 (VMAT2) inhibitors are approved in the United States (US) for the treatment of tardive dyskinesia (TD). There is a paucity of information on the impact of VMAT2 inhibitor treatment on patient social and physical well-being. The study objective was to elucidate clinician-reported improvement in symptoms and any noticeable changes in social or physical well-being in patients receiving VMAT2 inhibitors. Methods: A web-based survey was offered to physicians, nurse practitioners, and physician assistants based in the US who prescribed valbenazine for TD within the past 24 months. Clinicians reported data from the charts of patients who met the inclusion criteria and were allowed to recall missing information. Results: Respondents included 163 clinicians who reviewed charts of 601 VMAT2-treated patients with TD: 47% had TD symptoms in ≥2 body regions, with the most common being in the head or face and upper extremities. Prior to treatment, 93% of patients showed impairment in ≥1 social domain, and 88% were impaired in ≥1 physical domain. Following treatment, among those with improvement in TD symptoms (n = 540), 80% to 95% showed improvement in social domains, 90% to 95% showed improvement in physical domains, and 73% showed improvement in their primary psychiatric condition. Discussion: In VMAT2-treated patients with TD symptom improvement, clinicians reported concomitant improvement in psychiatric disorder symptoms and in social and physical well-being. Regular assessment of TD impact on these types of domains should occur simultaneously with movement disorder ratings when evaluating the value of VMAT2 inhibitor therapy

Physical tests for shoulder impingements and local lesions of bursa, tendon or labrum that may accompany impingement

BackgroundImpingement is a common cause of shoulder pain. Impingement mechanisms may occur subacromially (under the coraco-acromial arch) or internally (within the shoulder joint), and a number of secondary pathologies may be associated. These include subacromial-subdeltoid bursitis (inflammation of the subacromial portion of the bursa, the subdeltoid portion, or both), tendinopathy or tears affecting the rotator cuff or the long head of biceps tendon, and glenoid labral damage. Accurate diagnosis based on physical tests would facilitate early optimisation of the clinical management approach. Most people with shoulder pain are diagnosed and managed in the primary care setting.ObjectivesTo evaluate the diagnostic accuracy of physical tests for shoulder impingements (subacromial or internal) or local lesions of bursa, rotator cuff or labrum that may accompany impingement, in people whose symptoms and/or history suggest any of these disorders.Search methodsWe searched electronic databases for primary studies in two stages. in the first stage, we searched MEDLINE, EMBASE, CINAHL, AMED and DARE (all from inception to November 2005). in the second stage, we searched MEDLINE, EMBASE and AMED(2005 to 15 February 2010). Searches were delimited to articles written in English.Selection criteriaWe considered for inclusion diagnostic test accuracy studies that directly compared the accuracy of one or more physical index tests for shoulder impingement against a reference test in any clinical setting. We considered diagnostic test accuracy studies with cross-sectional or cohort designs (retrospective or prospective), case-control studies and randomised controlled trials.Data collection and analysisTwo pairs of review authors independently performed study selection, assessed the study quality using QUADAS, and extracted data onto a purpose-designed form, noting patient characteristics (including care setting), study design, index tests and reference standard, and the diagnostic 2 x 2 table. We presented information on sensitivities and specificities with 95% confidence intervals (95% CI) for the index tests. Meta-analysis was not performed.Main resultsWe included 33 studies involving 4002 shoulders in 3852 patients. Although 28 studies were prospective, study quality was still generally poor. Mainly reflecting the use of surgery as a reference test in most studies, all but two studies were judged as not meeting the criteria for having a representative spectrum of patients. However, even these two studies only partly recruited from primary care.The target conditions assessed in the 33 studies were grouped under five main categories: subacromial or internal impingement, rotator cuff tendinopathy or tears, long head of biceps tendinopathy or tears, glenoid labral lesions and multiple undifferentiated target conditions. the majority of studies used arthroscopic surgery as the reference standard. Eight studies utilised reference standards which were potentially applicable to primary care (local anaesthesia, one study; ultrasound, three studies) or the hospital outpatient setting (magnetic resonance imaging, four studies). One study used a variety of reference standards, some applicable to primary care or the hospital outpatient setting. in two of these studies the reference standard used was acceptable for identifying the target condition, but in six it was only partially so. the studies evaluated numerous standard, modified, or combination index tests and 14 novel index tests. There were 170 target condition/index test combinations, but only six instances of any index test being performed and interpreted similarly in two studies. Only two studies of a modified empty can test for full thickness tear of the rotator cuff, and two studies of a modified anterior slide test for type II superior labrum anterior to posterior (SLAP) lesions, were clinically homogenous. Due to the limited number of studies, meta-analyses were considered inappropriate. Sensitivity and specificity estimates from each study are presented on forest plots for the 170 target condition/index test combinations grouped according to target condition.Authors' conclusionsThere is insufficient evidence upon which to base selection of physical tests for shoulder impingements, and local lesions of bursa, tendon or labrum that may accompany impingement, in primary care. the large body of literature revealed extreme diversity in the performance and interpretation of tests, which hinders synthesis of the evidence and/or clinical applicability.University of Teesside, Middlesbrough, UKDepartment of Health, UKUniv Teesside, Hlth & Social Care Inst, Middlesbrough TS1 3BA, Tees Valley, EnglandUniversidade Federal de São Paulo, Dept Orthopaed & Traumatol, São Paulo, BrazilUniv Birmingham, Birmingham, W Midlands, EnglandUniversidade Federal de São Paulo, Dept Orthopaed & Traumatol, São Paulo, BrazilWeb of Scienc

Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

The realtime follow-up of neutrino events is a promising approach to searchfor astrophysical neutrino sources. It has so far provided compelling evidencefor a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 observedin coincidence with the high-energy neutrino IceCube-170922A detected byIceCube. The detection of very-high-energy gamma rays (VHE, $\mathrm{E} >100\,\mathrm{GeV}$) from this source helped establish the coincidence andconstrained the modeling of the blazar emission at the time of the IceCubeevent. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) -FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program oftarget-of-opportunity observations of neutrino alerts sent by IceCube. Thisprogram has two main components. One are the observations of known gamma-raysources around which a cluster of candidate neutrino events has been identifiedby IceCube (Gamma-ray Follow-Up, GFU). Second one is the follow-up of singlehigh-energy neutrino candidate events of potential astrophysical origin such asIceCube-170922A. GFU has been recently upgraded by IceCube in collaborationwith the IACT groups. We present here recent results from the IACT follow-upprograms of IceCube neutrino alerts and a description of the upgraded IceCubeGFU system.<br

ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice

Understanding the burden of illness of excessive daytime sleepiness associated with obstructive sleep apnea: a qualitative study

Background Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS), which may go undiagnosed and can significantly impair a patient's health-related quality of life (HRQOL). This qualitative research examined timing and reasons patients sought medical care for their EDS and OSA symptoms, and the impact of EDS on HRQOL. Methods Focus groups were conducted in 3 US cities with 42 participants currently experiencing EDS with OSA. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. Results Over three-fifths of study participants (n=26, 62%) were currently using a positive airway pressure (PAP) or dental device; one-third (n=14, 33%) had previously used a positive airway pressure (PAP) or dental device, and the remainder had either used another treatment (n=1, 2%) or were treatment naive (n=1, 2%). Twenty-two participants (52%) reported experiencing OSA symptoms for >= 1 year, with an average duration of 11.4 (median 8.0, range 1-37) years before seeking medical attention. Several (n=7, 32%) considered their symptoms to be "normal," rather than signaling a serious medical condition. Thirty participants (71%) discussed their reasons for ultimately seeking medical attention, which included: input from spouse/partner, another family member, or friend (n=20, 67%); their own concern about particular symptoms (n=7, 23%); and/or falling asleep while driving (n=5, 17%). For all 42 participants, HRQOL domains impacted by EDS included: physical health and functioning (n=40, 95%); work productivity (n=38, 90%); daily life functioning (n=39, 93%); cognition (n=38, 90%); social life/relationships (n=37, 88%); and emotions (n=30, 71%). Conclusions Findings suggest that patients may be unaware that their symptoms could indicate OSA requiring evaluation and treatment. Even following diagnosis, EDS associated with OSA can continue to substantially affect HRQOL and daily functioning. Further research is needed to address diagnostic delays and unmet treatment needs for patients with EDS associated with OSA.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]