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A questionnaire which provides desirable reliability and validity has been previously developed to assess the disease awareness of diagnosed chronic kidney disease (CKD) patients. However, conventional paper questionnaires often have disadvantages, including recall bias. To substantially improve this, we therefore aimed to explore the feasibility of developing a smartphone-based electronic version (e-version) based upon its original paper version and subsequently tested its validity, reliability, and applicability. A pilot study was conducted at Guangdong Provincial Hospital of Chinese Medicine in Guangzhou, China, during August 2019. The e-version had identical content to the paper version and was adapted in terms of layout and assisted functions via the Wechat-incorporated Wen-Juan-Xing platform. Eligible patients with diagnosed CKD were invited to participate and were assigned the e-version. Randomly selected respondents received a test-retest of the same e-version 2 weeks after their first completion. In some instances, psychometric properties, including validity and reliability of the e-version, were examined. In others, its clinical application was also tested, which included comparisons among the clinical profiles of patients who had/had not responded to the questionnaire as well as patients with above or below average questionnaire scores. Of the 225 patients screened, 217 were enrolled to participate, with a response rate of 52.5%. Desirable reliability (Cronbachα = 0.962, ICC for total scores = 0.948), while good convergent validity (Cronbachα = 0.962) and low discriminant validity (one extracted component), of the e-version were detected. Performing inter-group comparisons highlighted statistical differences in terms of higher education level (z = −2.436, P = 0.015) and earlier CKD stages (z = −1.978, P = 0.048), with these patients often preferring to respond. No significant differences were detected in the clinical profiles between respondents who obtained an above or below average questionnaire score. The e-version is reliable but was not shown to be a valid approach. Audiences with higher education levels and less advanced disease condition may prefer to respond to the e-version. Adaptation of this e-questionnaire, from its original paper version, may not be a direct transition and meticulous modifications may be required during the transition process. Chinese Clinical Trial Registry (ChiCTR1900024633). [ABSTRACT FROM AUTHOR]

Patient engagement is currently considered the cornerstone of a revolution in healthcare for its positive impact on health outcomes, health behaviors and healthcare costs. Patient engagement is focused on personalized care to consumers through providing knowledge, skills and confidence. Mobile health (mHealth) applications are an innovative means to facilitate patient engagement. Nevertheless, the extent to which the current mHealth applications are designed to engage patients in managing their chronic diseases is unclear. This paper aims to identify the Persuasive System Design (PSD) features present in current mHealth applications that increased the engagement of patients with chronic diseases. This review also aims to identify patient engagement-related outcomes of these features. This paper conducted a systematic literature review and meta-analysis to find relevant studies published from all years up to 2020 through six databases: PubMed, Scopus, Web of Science, Cinahl plus with full text, MEDLINE with full text, and Cochrane Library (Central register of controlled trials). The database search returned 4939 articles; after applying the inclusion and exclusion criteria, the number of included articles for the final review was 13. A qualitative content analysis was performed to identify PSD model features and their patient engagement-related outcomes. The quality assessment has been done through the Cochrane Risk of Bias tool for RCTs. The systematic literature review and meta-analysis identified eleven PSD features that can increase patient engagement through using mHealth applications. The identified PSD features have been shown to have various patient engagement-related outcomes. Behavior Change Techniques (BCTs) were combined with the identified PSD features. This paper identified persuasive features of mHealth application design that influence the engagement of patients with chronic diseases toward changing their behavior. The impact of these features is also analyzed in this review. The results show that an mHealth technology-mediated patient engagement model is needed. [ABSTRACT FROM AUTHOR]

This paper examines the role of nurseries in the Green Revolution. Nurseries were sets of seeds assembled to test particular traits and sent to breeders around the world to trial. Focusing on wheat nurseries of the 1960s and 70s, I highlight the materials that were central to their distribution, as well as the breeders who planted them. Through this analysis, I trouble the common narrative of the Green Revolution as emerging from centers of international agricultural science, showing the networks of expertise, seed transfer, field trials, and data collection that underpinned this process of agricultural transformation. [ABSTRACT FROM AUTHOR]

In the era of social media, journalism is no longer the preserve of journalists. In specialised fields, such as law, the public in general and lawyers and legal academics specifically are able to "push in" and report and comment publicly on legal matters including trials, commissions, acts of law passed in parliament and other legal processes. These contributions, as this paper explores, are reshaping the contours and content of public discussions of legal matters and of legal journalism in South Africa. This paper suggests that recent theorising of journalism role theory can help understand not just the motivations of these legal interlopers in the journalism space but also how they are shaping a new informational ecosystem in which legal issues, including human rights, administrative and criminal law, and other topics, are brought into the public domain. The paper explores what some South African lawyers understand about the roles they are playing in digital public spaces and how they perceive their contributions and their relationship to the journalism profession and to journalists within that profession. The paper suggests that these lawyers' practices challenge our understanding about how digital media informational ecosystems work and explores how this is impacting journalism in South Africa. [ABSTRACT FROM AUTHOR]

Introduction: Registering study protocols in a trial registry is important for methodologic transparency and reducing selective reporting bias. The objective of this investigation was to determine whether published studies of intimate partner violence (IPV) that had been registered matched the registration record on key study design elements. Methods: We systematically searched three trial registries to identify registered IPV studies and the published literature for the associated publication. Two authors independently determined for each study whether key study elements in the registry matched those in the published paper. Results: We included 66 studies published between 2006 and 2017. Nearly half (29/66, 44%) were registered after study completion. Many (26/66, 39%) had discrepancies regarding the primary outcome, and nearly two-thirds (42/66, 64%) had discrepancies in secondary outcomes. Discrepancies in study design were less frequent (13/66, 20%). However, large changes in sample size (26/66, 39%) and discrepancies in funding source (28/66, 42%) were frequently observed. Conclusions: Trial registries are important tools for research transparency and identifying and preventing outcome switching and selective outcome reporting bias. Published IPV studies often differ from their records in trial registries. Researchers should pay close attention to the accuracy of trial registry records. [ABSTRACT FROM AUTHOR]

In clinical research, longitudinal trials are frequently conducted to evaluate the treatment effect by comparing trends in repeated measurements among different intervention groups. For such longitudinal trials, many researchers have developed the sample size estimation methods for comparison between two groups measurements. In contrast, relatively less attention has been paid to trials with K-group (K ≥ 3) comparison. Jung and Ahn (2004) and Lou et al. (2017) derived the sample size formulas for comparing trends among K groups using the generalized estimating equations approach for repeated continuous and count outcomes, respectively. However, to the best of our knowledge, there has been no development in sample size calculation for binary outcomes in multi-arms trials. In this paper, we present a sample size formula for comparing trends in K-group repeated binary measurements that accommodates various missing patterns and correlation structures. Simulation results show that the proposed method performs well under a wide range of design parameter settings. We illustrate the proposed method through an example. [ABSTRACT FROM AUTHOR]

This paper outlines a range of factors associated with extradition and transnational online intellectual property offending by examining the Australian case of Hew Griffiths. In documenting key legal issues from available domestic and international verdicts examining this case, we show how broad legislative drafting in Australia works alongside the decision to initiate conspiracy charges to favour extradition. We also examine how Australian legal requirements that remove the presumption of bail for transnational fugitives limit the prospect of mounting a fair defence against extradition and during a foreign trial, and the limited direct impact of determinations by the United Nations Human Rights Committee on these national processes. We critically discuss the implications of these rulings in the Griffiths case in light of the evolving role of extradition law in a digital age and their implications on theories of criminal jurisdiction founded on the principle of extraterritoriality. [ABSTRACT FROM AUTHOR]

Single-arm trials with binary endpoint are firmly established in e.g., early clinical oncology. Here, two-stage designs are often employed to allow early termination of the trial in the case of an unexpectedly large or small response rate to the new treatment. Various designs have been proposed over the last few years which usually require strong assumptions about the true response rate during planning. Often, these designs are not robust to deviations from the planning assumptions. In this paper, we define a Bayesian framework for scoring two-stage designs under uncertainty and investigate the characteristics of designs optimizing a commonly employed performance score of Liu et al. The resulting optimal designs are compared with an alternative, utility-based approach incorporating expected power and sample size. We provide insights in the underlying implicit assumptions of using expected power for scoring adaptive designs and relate the global score function to the practice of sample size recalculation based on conditional power. An in-depth comparison of the features of the different performance scores and their respective optimizing designs provides the guidance for practitioners who face the problem of choosing between the various options. A software implementation of the proposed methods is publicly available online. [ABSTRACT FROM AUTHOR]

Background During the past two decades, the number and complexity of clinical trials have risen dramatically increasing the difficulty of choosing sites for inspection. FDA's resources are limited and so sites should be chosen with care. Purpose To determine if data mining techniques and/or unsupervised statistical monitoring can assist with the process of identifying potential clinical sites for inspection. Methods Five summary-level clinical site datasets from four new drug applications (NDA) and one biologics license application (BLA), where the FDA had performed or had planned site inspections, were used. The number of sites inspected and the results of the inspections were blinded to the researchers. Five supervised learning models from the previous two years (2016–2017) of an on-going research project were used to predict site inspections results, i.e., No Action Indicated (NAI), Voluntary Action Indicated (VAI), or Official Action Indicated (OAI). Statistical Monitoring Applied to Research Trials (SMARTTM) software for unsupervised statistical monitoring software developed by CluePoints (Mont-Saint-Guibert, Belgium) was utilized to identify atypical centers (via a p-value approach) within a study.Finally, Clinical Investigator Site Selection Tool (CISST), developed by the Center for Drug Evaluation and Research (CDER), was used to calculate the total risk of each site thereby providing a framework for site selection. The agreement between the predictions of these methods was compared. The overall accuracy and sensitivity of the methods were graphically compared. Results Spearman's rank order correlation was used to examine the agreement between the SMARTTM analysis (CluePoints' software) and the CISST analysis. The average aggregated correlation between the p-values (SMARTTM) and total risk scores (CISST) for all five studies was 0.21, and range from −0.41 to 0.50. The Random Forest models for 2016 and 2017 showed the highest aggregated mean agreement (65.1%) amongst outcomes (NAI, VAI, OAI) for the three available studies. While there does not appear to be a single most accurate approach, the performance of methods under certain circumstances is discussed later in this paper. Limitations Classifier models based on data mining techniques require historical data (i.e., training data) to develop the model. There is a possibility that sites in the five-summary level datasets were included in the training datasets for the models from the previous year's research which could result in spurious confirmation of predictive ability. Additionally, the CISST was utilized in three of the five site selection processes, possibly biasing the data. Conclusion The agreement between methods was lower than expected and no single method emerged as the most accurate. [ABSTRACT FROM AUTHOR]

Anterior segment optical coherence tomography (AS-OCT) has become one of the cornerstones of non-contact imaging modalities for assessing such structures as the cornea, anterior chamber angle, aqueous outflow pathway, sclera, and ocular surface structures. As such, it has a broad range of clinical applications, which have been independently reported in the literature. This paper aims to present a review of extant literature on the utility of AS-OCT and its efficacy in clinical applications, and to evaluate the quality of available evidence. The following databases were searched from inception to 24 June 2018: Medline via Ovid, Cochrane Central Register of Controlled Trials, PubMed, World Health Organization International Clinical Trials Registry Platform, EMBASE, and CINAHL. Bibliographies of identified papers were hand searched. Inclusion criteria: articles describing or assessing the use of OCT for visualising the AS. The authors excluded studies without an identified primary outcome variable. One author independently selected studies, extracted data, and assessed for risk of bias using PRISMA guidelines. This review included 82 studies, of which there were 11 cohort studies, 37 case series, 10 case studies, 21 comparative observational studies, and three non-systematic review articles. Primary outcome variables included anterior chamber angle, angle opening distance, angle recess area, trabecular iris angle, trabecula-iris space area, corneal thickness, tear meniscus height, tear meniscus area, tear meniscus volume, and the morphology of AS structures, including the ocular surface, blebs, flaps, and graft sites. This review attempts to encompass the breadth and depth of evidence for AS-OCT in the arena of diagnostics, therapeutics, and prognostics. At the same time, it brings to light the dearth of high-level evidence on this topic, suggesting the important role of randomised controlled trials and meta-analyses for the future validation of this technology. [ABSTRACT FROM AUTHOR]

Objective: The objective of this systematic review was to explore the effectiveness of various systemic corticosteroid (SCS) regimens to mitigate relapse in children with asthma discharged from an acute care setting. Data Sources: Medline, EMBASE, Global Health, International Pharmaceutical Abstracts, EMB ALL, CINAHL, SCOPUS, Proquest Dissertations and Theses Global, and LILACS were searched using controlled vocabulary and key words. Additional citations were searched via clinical trial registries, Google Scholar, bibliographies, a SCOPUS forward search of a sentinel paper, and hand searching conference abstracts. Study Selection: No limitations based on language, publication status, or year of publication were applied. Two independent reviewers searched to identify randomized controlled trials comparing the effectiveness of SCS regimens to prevent relapse in children following treatment for acute asthma. Results: Fifteen studies were included. In 3 studies comparing SCS to placebo, asthma relapse was significantly reduced (RR = 0.10; 95% CI: 0.01, 0.77; I2 = 0%). A network analysis identified a significant reduction in relapse in children treated with intramuscular corticosteroids (OR = 0.038; 95% CrI: 0.001, 0.397), short-course oral prednisone (OR = 0.054; 95% CrI: 0.002, 0.451), and oral dexamethasone (OR = 0.071; 95% CrI: 0.002, 0.733) compared to placebo. Conclusion: This review found evidence that SCS reduces relapse in children following treatment for acute asthma, albeit based on a limited number of studies. Additional studies are required to assess the differential effect of SCS doses and treatment duration to prevent relapse in children following discharge for acute asthma. [ABSTRACT FROM AUTHOR]

During evaluation of the integrity of 172 clinical trial publications, we identified 138 unique trial registration documents linked to 157 publications. Eighty-eight (64%) registrations were retrospective. Discrepancies in key trial characteristics – ethics oversight, study timeline, study location, participant number and sample size – between 68 registration documents and their linked publications were reported to journals, publishers and a national regulatory body. Subsequently, revisions to 119/138 registration documents were lodged at the registry website, a median (IQR) of 44 (32–56) months after initial registration. Revisions were made to 56 of the 68 registration documents included in the report: there was a median of 8 (IQR 6–9) changes per document. 79–93% of revised documents contained ≥1 alteration to the primary outcome(s), the secondary outcome(s), and the participant inclusion/exclusion criteria. Changes in each of study location, study timeline, participant age, sample size, and randomization method were made in ≥33% of revised documents. Eight months after journals, publishers and the regulatory body were apprised of the revisions, none of the affected publications has been corrected with an , expression of concern, or retraction. These results call into question whether regulators and publishers regard trial registration documents as helpful in ensuring publication integrity. [ABSTRACT FROM AUTHOR]

Background: Pharmacist-led medication reviews are considered a valuable measure to address risks of polypharmacy. The software Medinspector® is used in community pharmacies to assist the performance of this complex service by structuring the medication review process and supporting pharmacists in their decision-making with targeted clinical knowledge. Key feature is a computerized risk assessment of both the initial and adjusted medication regimen of a patient in multiple domains, thus aiming to support the identification and solving of drug-related problems. This study will examine the effects of medication reviews performed with the clinical decision support system in daily routine practice on medication-related and patient-reported outcomes in elderly patients with polypharmacy. Methods: A prospective, before–after observational study is conducted in German community pharmacies aiming to include 148 patients aged 65 or older, who chronically use five or more active pharmaceutical substances with systemic effects and utilize the software-supported medication review service. The study is based on routine documentation within the software over the course of the medication review, including a patient's baseline medication, the medication proposed by pharmacists, and the final medication regimen. A software-implemented questionnaire comprising self-developed and literature-derived instruments is used to collect patient-reported outcome data at baseline and follow-up. Primary outcome is the appropriateness of medication measured with an adapted version of the Medication Appropriateness Index (MAI). Secondary medication-related outcomes are medication underuse, exposition towards anticholinergic/sedative drugs, number of drugs in long-term use and the implementation of pharmacist-proposed medication adjustments by the physicians. Secondary patient-reported outcomes are symptom burden, medication-related quality of life, adherence, fulfillment of medication review-related goals, and perception of the service. Discussion: With the recently introduced remuneration of community pharmacist-led MR in Germany, the demand for digital tools supporting the MR process is assumed to rise. The OPtiMed-study is expected to create evidence on the effects of a novel tool on patient care in a vulnerable patient population. Trial registration German Clinical Trials Register, DRKS00027410. Registered 22 December 2021, https://www.drks.de/drks%5fweb/navigate.do?navigationId=trial.HTML&TRIAL%5fID=DRKS00027410. Also available on the WHO meta-registry: https://trialsearch.who.int/?TrialID=DRKS00027410 [ABSTRACT FROM AUTHOR]

There are many studies showing a positive relationship between depression level and cognitive distortions in the literature. The study was carried out to determine the effects of cognitive behavioral therapy–based psychoeducation on cognitive distortions, negative automatic thoughts and dysfunctional attitudes of patients diagnosed with depression. This study was designed as a two-group pre-posttest study. The study sample composed of a total of 60 patients (30 patients in the treatment group and 30 patients in the control group) who met the eligibility criteria. The data have been collected by using The Personal Information Form, Automatic Thoughts Questionnaire, The Dysfunctional Attitude Scale and Interpersonal Cognitive Distortions Scale. Psychoeducation was provided in the form of individual training once a week in total of eight sessions. For the pretest, assumption and schemas that make people predispose to depression, dysfunctional attitudes and cognitive distortions in interpersonal relationships were seen frequently to be above average in all patients. It was determined that patients in the treatment group used significantly less dysfunctional attitudes and to had lower negative automatic thoughts and interpersonal cognitive distortions compared with patients in the control group in posttest (p < 0.05). Consequently, cognitive behavioral therapy–based psychoeducation has become considerably effective in decreasing the use of negative automatic thoughts, interpersonal cognitive distortions and dysfunctional attitudes in patients with depression. cognitive behavioral therapy–based psychoeducation should be thought of as a treatment component due to its effectiveness in nursing care of depressed patients. [ABSTRACT FROM AUTHOR]

Patients with haematologic malignancies are at high risk of developing invasive fungal infections (IFIs). Current guidelines recommend the use of azoles for IFI prophylaxis; however, in many clinical situations, antifungal prophylaxis is used off-label. We conducted a systematic literature review to provide haematologists with the available evidence on the effectiveness and safety of isavuconazole in IFI prophylaxis in interventional and real-world, observational studies. Embase, MEDLINE and Cochrane Library databases, and relevant conference proceedings and clinical trial registries, were searched for studies on the effectiveness and safety of isavuconazole prophylaxis in adults at high risk of IFIs. Studies were assessed for inclusion and risk of bias. Nine studies were eligible for inclusion in the review, eight of which were in haematologic populations (patients undergoing haematopoietic stem cell transplantation or with acute myeloid leukaemia or myelodysplastic syndromes; n = 5) or included haematologic populations (n = 3). Evidence from these studies suggests isavuconazole is effective for IFI prophylaxis in the haematologic setting. However, the studies frequently lacked safety data, most were based on small patient populations from single centres and risk of bias could not be assessed for five studies. These findings provide evidence for isavuconazole as an alternative azole for prophylaxis in high-risk populations. Limitations include lack of applicability of risk of bias assessment tools, level of filtering applied in the search strategy and focus on English-language publications. Isavuconazole may be an effective azole for IFI prophylaxis in high-risk haematologic populations, although further studies are needed. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a heterogeneous condition characterized by increased morbidity and mortality. This systematic review and meta-analysis of 19 studies was conducted to evaluate the role of copeptin in diagnosis and outcome prediction in HF patients. A systematic literature search for clinical trials reporting copeptin levels in HF patients was performed using EMBASE, PubMed, Cochrane Register of Controlled Trials, and Google Scholar. Articles from databases published by 2 January 2022, that met the selection criteria were retrieved and reviewed. The random effects model was used for analyses. Pooled analysis found higher mean copeptin levels in HF vs. non-HF populations (43.6 ± 46.4 vs. 21.4 ± 21.4; MD= 20.48; 95% CI: 9.22 to 31.74; p < 0.001). Pooled analysis of copeptin concentrations stratified by ejection fraction showed higher concentrations in HFrEF vs. HFpEF (17.4 ± 7.1 vs. 10.1 ± 5.5; MD= −4.69; 95% CI: −7.58 to −1.81; p = 0.001). Copeptin level was higher in patients with mortality/acute HF-related hospitalization vs. stable patients (31.3 ± 23.7 vs. 20.4 ± 12.8; MD= −13.06; 95% CI: −25.28 to −0.84; p = 0.04). Higher copeptin concentrations were associated with mortality and observed in all follow-up periods (p < 0.05). The present meta-analysis showed that elevated copeptin plasma concentrations observed in HF patients are associated with an increased risk of all-cause mortality, thus copeptin may serve as predictor of outcome in HF. [ABSTRACT FROM AUTHOR]

The article offers information on the concerns related to the Mototab supplement, which was use for the treatment of neuron disease, and sponsored by Oslo Health Solutions. It mentions that ALSUntangled does not know any of their patients that taken the mototab, and there was no clinical trial taken that will prove its effectiveness and safety. It also says that many people have ordered the said supplements on their website, but they never received them as well as the refund.

Objectives: As the role and importance of patient-reported outcomes (PROs) increase, the validity and reliability of PRO measures come under greater scientific and regulatory scrutiny. One key issue is selecting the 'most appropriate' recall period for capturing PROs in clinical trials. This paper draws on survey research, health-specific literature, and results from clinical trials to summarize factors that can influence recall and provide guidance on selecting an optimal recall period. Methods: We conducted a systematic review of six databases and additional literature drawn from bibliographies of the selected articles. Results: Six major factors can influence recall; these can be classified into two broad areas: characteristics of the recalled phenomenon (recency, attributes, complexity) and context or meaning of the recalled phenomenon (salience, patient experience, mood). Results of different recall periods for three classes of PROs are presented: health behaviors, symptoms, and health-related quality of life. We present findings on the effect of alternative recall periods for three commonly used PROs. Finally, we propose a heuristic model to link the concept under investigation with an optimal recall period. Conclusions: No single recall period is best for all measures or all phenomena. The recall period must correspond to the characteristics of the phenomenon of interest and the purpose of the assessment. Recall period is an issue of internal validity. An incorrect recall period introduces measurement error that may reduce the chances of detecting a treatment effect. Researchers should consider recall period as seriously as they do other measurement properties. [ABSTRACT FROM AUTHOR]

Over the past 30-years, the U.S. Dietary Guidelines for Americans have included recommendations around dairy consumption, largely based on meeting recommendations for calcium intake with the intended purpose of osteoporosis prevention. Although dairy products provide more bone-beneficial nutrients (e.g., calcium, magnesium, potassium, zinc, phosphorus, and protein) per unit of energy than any other food group, the relevance of dairy products for long-term bone health and fracture prevention has resurged as some observational studies have suggested consumption to be associated with a greater risk of fractures. Given this controversy, we sought to synthesize the evidence on dairy consumption and bone health across the lifespan. We searched the PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases for English-language publications through June 2, 2020. Case-controlled, cross-sectional, prospective cohort or nestled case-control (or case cohort), and clinical trials reporting the effect of dairy products on bone mineral density, bone mineral content, and/or fractures were included in the systematic review. Two reviewers independently performed data extractions. Data from 91 publications, including 30 RCTs, 28 prospective cohorts, 23 cross-sectional studies, and 10 case-control studies were included in the systematic review. We assigned a "D" grade or "insufficient evidence" for the effect of dairy in infants and toddlers (0- to <36-months), children (3- to <10-years), and young adults (19- to <50-years). A "C" grade or "limited evidence" was assigned for the effect of dairy in adolescents (10- to <19-years). A "B" grade or "moderate" evidence was assigned for the effect of dairy in middle aged to older adults (≥50-years). Research on bone mass in adults between the ages of 20- to 50-years and individuals from other ethnic groups apart from Chinese females and Caucasians is greatly needed. Daily intake of low or nonfat dairy products as part of a healthy habitual dietary pattern may be associated with improved BMD of the total body and at some sites and associated with fewer fractures in older adults. [ABSTRACT FROM AUTHOR]

A Data Monitoring Committee (DMC) evaluates patient safety in a clinical trial of an investigational intervention through periodic review of adverse events (AEs) and clinical safety assessments. Our aim was to construct DMC report displays to enhance the DMC safety review through use of graphics and clear identification and adjustment for missing data caused by early discontinuations and ongoing study participation. Suggested displays include a study snapshot graph, enhanced adverse event incidence tables including the incidence density and plotted incidence proportions, line graphs in place of by-patient listings, and trend plots in place of tables for continuous assessments. [ABSTRACT FROM AUTHOR]

Blue-blocking glasses, also known as amber glasses, are plastic glasses that primarily block blue light. Blue-blocking glasses have been studied as a sleep intervention for insomnia, delayed sleep-phase disorder, shift work, jet lag, and nonpathologic sleep improvement. Blue-blocking glasses have also been studied as a treatment for bipolar disorder, major depression, and postpartum depression. Blue-blocking glasses improve sleep by inducing dim-light melatonin onset by reducing activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) which are most sensitive to blue light and are a major input for circadian regulation; their mechanism for mood regulation is unclear but may be similar to that of dark therapy for bipolar disorder where patients are kept in darkness for an extended period every night. A systematic search of the scientific literature identified a total of 29 experimental publications involving evening wear of blue-blocking glasses for sleep or mood disorders. These consisted of 16 randomized controlled trials (RCTs) published in journals with a total of 453 patients, 5 uncontrolled trials, 1 case series, 1 case study, and 6 abstracts from conference proceedings. Only 1 case study and 1 RCT were for acutely manic patients but both found substantial decreases in manic symptoms with the use of blue-blocking glasses; these give preliminary clinical evidence of efficacy that makes blue-blocking glasses a high-yield intervention to study for bipolar disorder. Findings in the 3 publications for major depression and postpartum depression were heterogeneous and conflicting as to their efficacy. Out of the 24 publications focusing on sleep, there was substantial evidence for blue-blocking glasses being a successful intervention for reducing sleep onset latency in patients with sleep disorders, jet lag, or variable shift work schedules. Given the well-established biological mechanism and clinical research showing that blue-blocking glasses are effective for inducing sleep, they are a viable intervention to recommend to patients with insomnia or a delayed sleep phase. [ABSTRACT FROM AUTHOR]

Systematically review the medical literature for the impact of beta-blockers on mortality and functional capacity in patients who suffered severe traumatic brain injury. The search included MEDLINE, EMBASE, and Ovid Evidence-Based Medicine, clinical trial registries, and bibliographies. All articles that reported outcome in TBI patients treated with beta-blockers. Publication year, number of patients, outcome and follow-up. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences. 12 studies were included, which involved retrospectively and prospectively collected data on 14,057 patients. The treatment with beta-blockers was associated with a reduction in mortality in patients who were treated with beta-blockers compared to the control group (OR 0.40, 95% CI 0.30–0.54p = <0.00001), with acceptable heterogeneity between studies (I2 = 65% p = 0.00008). Beta-blocker therapy decreases the risk of negative neurological and functional outcomes (OR 0.59, 95% CI 0.38–0.92 p = <0.00001), a very high statistical heterogeneity between the included studies (I2 = 80% p = 0.00004), being able to influence the results. An increase in favorable neurological and functional outcomes is shown (OR 1.19, 95% CI 1.07–1.31 p = 0.001) with acceptable heterogeneity (I2 = 52% p = 0.08) The beta-blockers therapy is associated with significantly improves outcome in patients with TBI. Treatment with beta-blockers in patients with TBI is a promising frontier in neurotrauma. CI: confidence interval; BB: Beta-Blockers; OR = odds ratio; TBI: Traumatic Brain Injury SD: Standard deviation; SNS: Sympathetic nervous system [ABSTRACT FROM AUTHOR]

Background: Single-agent cyclophosphamide can deplete regulatory T-cells (Treg). We aimed to determine optimal dosing and scheduling of oral cyclophosphamide, alongside pemetrexed-based chemotherapy, to deplete Treg in mesothelioma or non-small-cell lung cancer patients. Methods: 31 Patients received pemetrexed ± cisplatin or carboplatin on day 1 of a 21-day cycle (maximum 6 cycles). From cycle two, patients received cyclophosphamide, 50 mg/day, with intrapatient escalation to maximum 100/150 mg/day alternately. Immunological changes were examined by flow cytometry. Primary endpoint was Treg proportion of CD4+ T-cells, with doses tailored to target Treg nadir <4%. Results: Reduction in Treg proportion was observed on day 8 of all cycles, and was not augmented by cyclophosphamide. Few patients achieved the <4% Treg target. Treg proliferation reached nadir one week after chemotherapy, and peaked on day 1 of the subsequent cycle. Efficacy parameters were similar to chemotherapy alone. Seventeen percent of patients ceased cyclophosphamide due to toxicity. Conclusions: Specific Treg depletion to the degree seen with single-agent cyclophosphamide was not observed during pemetrexed-based chemotherapy. This study highlights the poor evidence basis for use of cyclophosphamide as an immunotherapeutic in combination with chemotherapy, and the importance of detailed flow cytometry studies. Trial registration: Clinical trial registration: identifier is ACTRN12609000260224. [ABSTRACT FROM AUTHOR]

To investigate the continuation rate with a reduced lubiprostone dose (12 mcg twice daily, BD) after the onset of adverse events (AEs) in patients with chronic constipation (CC). In this exploratory, open-label, multicenter study, patients with CC received lubiprostone 24 mcg BD and the dose was reduced to 12 mcg BD in subjects experiencing AEs. The primary objective was the continuation rate after dose reduction due to nausea/vomiting. Secondary objectives included the continuation rate after dose reduction due to diarrhea/any AE and efficacy, including changes in number of weekly bowel movements and Bristol Stool Form Scale. Of the 146 patients included in the study, 42 (28.8%) received lubiprostone 12 mcg BD (dose-reduced group) due to any AE. Thirty-six (85.7%) subjects in the dose-reduced group continued treatment and completed the study. 22/27 (81.5%) and 17/19 (89.5%) patients in whom the dose was reduced due to nausea/vomiting or diarrhea, respectively, continued treatment. There was no clinically relevant difference in efficacy after dose reduction. These results suggest that treatment withdrawal due to AEs associated with lubiprostone 24 mcg BD could be minimized in patients with CC after dose reduction to 12 mcg BD, thus resulting in improved long-term outcomes. Japan Registry of Clinical Trials () [ABSTRACT FROM AUTHOR]

Background: The RESORT trial showed no longer relapse free survival (RFS) with sorafenib following radical metastasectomy in metastatic renal cell carcinoma. We present the updated 42-month follow-up data. Methods: The phase II RESORT trial randomized patients to sorafenib or observation within 12 weeks from surgery. RFS was the primary endpoint. Results: We analyzed 68 patients (32 in sorafenib and 36 in the observation arm), randomized between November 2012 and November 2017. Eighty-one percent in the sorafenib arm and 80% in the observation arm had one metastasis. At a median follow-up of 42 months (interquartile range 31–58), in the observation arm the median RFS was 35 months, RFS probability was 57% (95% CI 42–76%) at 24 and 44% (95% CI 30–65%) at 48 months. In the sorafenib arm, median RFS was 21 months, RFS probability was 50% (95% CI 34–71%) at 24 and 32% (95% CI 18–57%) at 48 months (p = 0.342;HR 1.35;95% CI 0.72–2.54). Forty-seven percent and 37.5% of the patients in the two arms, respectively, are disease free. The site of relapses was independent of the previous metastasectomy site. Expert commentary: Sorafenib after metastasectomy did not improve RFS, but surgery in selected patients should be considered in order to potentially improve survival. Clinical trial registration: www.clinicaltrials.gov identifier is NCT0144480 [ABSTRACT FROM AUTHOR]

Objective: The research has shown an association with sensorimotor integration and symptomology of Autism Spectrum Conditions (ASC). Specific areas of the brain that are involved in sensorimotor integration, such as the cerebellum and basal ganglia, are pathologically different in individuals with ASC in comparison to typically developing (TD) peers. These brain regions contain GABAergic inhibitory neurons that release an inhibitory neurotransmitter, γ-Aminobutyric acid (GABA). Brain GABA levels are decreased in ASC. This study explored the effect of introducing a non-invasive GABA substitute, in the form of GABA Oolong tea, on sensorimotor skills, ASC profiles, anxieties and sleep of children with ASC. Methods: Nine children took part: (5 male, 4 female). Each child participated in three tea conditions: high GABA, high L-Theanine (a compound that increases GABA), placebo with low GABA. A double-blind, repeated measures design was employed. Measures were taken after each tea condition. Sensory and ASC profiles were scored using parental questionnaires. Motor skills were assessed using a gold standard coordination assessment. Sleep was monitored using an actiwatch and anxiety measured through cortisol assays. Subjective views were sought from parents on 'best' tea. Results: The results showed significant improvement in manual dexterity and some large individual improvements in balance, sensory responsivity, DSM-5 criteria and cortisol levels with GABA tea. Improvements were also seen in the L-Theanine condition although they were more sporadic. Conclusions: These results suggest that sensorimotor abilities, anxiety levels and DSM-5 symptomology of children with ASC can benefit from the administration of GABA in the form of Oolong tea. [ABSTRACT FROM AUTHOR]

A small body of research investigates recruitment and retention of bereaved people in experimental and intervention research. The present study compares the effectiveness of different recruitment strategies implemented by a grief laboratory at a large state university in order to optimize recruitment efforts. The most effective method is letters sent to bereaved community members identified through online newspaper obituaries. Despite a small overall response rate, the large population from which to sample provides continuous accrual every month. Other methods include electronic/print media, community institution referrals, word of mouth and community outreach. Best practices for recruitment and retention are recommended. [ABSTRACT FROM AUTHOR]

Independence has been top of the agenda of accrediting bodies worldwide for many years and has just recently been aligned in a consensus document [[1]] adopted by major accrediting bodies. Thus, the only way to preserve decision autonomy is to provide physicians with the available problem-related information (evidence), but leave the ultimate decision entirely to the treating physician without interference from third parties. Available from: https://academy4cpdaccreditation.files.wordpress.com/2018/11/consensus-statement-for-independence-and-funding-of-cme cpd final sept-en1.pdf 2 Gehle HA, Herrmann H. Criteria to assess independence of continuing medical education (CME)- Independence through competence and transparency. [Extracted from the article]

To determine the efficacy of paracetamol and tramadol analgesia via patient controlled pump and intermittent administration using the Short-Form McGill Pain Questionnaire after L4/L5 discectomy in neurosurgical patients. Fourteen months prospective quantitative study with 200 neurosurgical patients' participation who underwent elective discectomy of the L4/L5 intervertebral disc extrusion. The study was conducted due to a patient-controlled analgesia pump and intermittent analgesia application. Pain was assessed using the Short-Form McGill Pain Questionnaire in the Croatian language during the zero, first, and second postoperative day. Perception of pain was reduced in patient controlled analgesia pump groups after the second measurement during the first postoperative day [95% CI: −3.89, −0.76], regardless of administered analgesic (p< 0.001). After the final measurement, at 7 PM on the second postoperative day, the differences were not significant (p= 0.070). This study results are registered and allocated in the Australian New Zealand Clinical Trials Registry (ANZCTR). Analgesia administration via patient-controlled pump contributes to the alleviation of postoperative pain after L4/L5 disc extrusion surgery regardless of administered analgesic. [ABSTRACT FROM AUTHOR]

Background: We assessed the safety and immunogenicity of 2 + 1 infant regimens initiated with the 13-valent pneumococcal conjugate vaccine (PCV13) and completed with the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV). Methods: This partially blinded study randomized 6–12-week-old infants to receive two-dose priming and a booster (at ages 2, 4, 12–15 months) with: PCV13 at priming and PHiD-CV at boosting (PPS); PCV13 then PHiD-CV at priming and PHiD-CV at boosting (PSS); or PHiD-CV at priming and boosting (SSS control). All analyses were descriptive, i.e., no statistical significance tests were done. Results: The total vaccinated cohort at priming comprised 294 infants. Grade 3 adverse events were reported after 8.7% (PPS), 11.4% (PSS), and 16.9% (SSS) of primary doses (primary objective). No serious adverse events were considered vaccination-related. For most PHiD-CV serotypes, observed percentages of children reaching antibody concentrations ≥0.2 µg/mL and opsonophagocytic activity (OPA) titers above cutoffs were similar across groups 1 month post-priming and post-booster. Observed geometric mean antibody concentrations and OPA titers were lower for some PHiD-CV serotypes with the mixed regimens than with PHiD-CV only, especially for PSS. However, no tests of statistical significance were performed. Conclusions: Immunogenicity of the two mixed PCV13/PHiD-CV regimens seemed mostly similar to that of a PHiD-CV-only series, although observed antibody GMCs and OPA GMTs for some PHiD-CV serotypes were lower. No safety concerns were raised. The clinical relevance of the observed differences is unknown. Clinical trial registration: ClinicalTrials.gov: NCT01641133 Focus on the patient What is the context? Infant immunization programs worldwide include the pneumococcal conjugate vaccines Synflorix and Prevnar 13 to help combat pneumococcal diseases. Countries or regions choose whether to use Synflorix or Prevnar 13 and may decide to switch from one vaccine to the other. This can result in infants receiving a mixed vaccination regimen. Limited information is available about such mixed regimens. What is new? We assessed the immunogenicity of three infant vaccination regimens: 1) priming with two doses of Prevnar 13 and boosting with Synflorix; 2) priming with one dose of Prevnar 13 followed by one dose of Synflorix and boosting with Synflorix; 3) priming and boosting with Synflorix. The study showed that: Switching from Prevnar 13 to Synflorix at any time during the vaccination regimen did not seem to affect safety. When switching from Prevnar 13 to Synflorix at the time of boosting, immunogenicity was mostly similar to that of the Synflorix- only regimen. Switching vaccines during priming resulted in a trend toward lower immune responses for some vaccine components. What is the impact? This piece of evidence can be considered by doctors and health authorities when evaluating the possibility of switching pneumococcal vaccines in an immunization program or individual immunization regimen. Further effectiveness studies from countries or regions switching from Prevnar 13 to Synflorix (or vice versa) may shed more light on the feasibility of switching between these vaccines. [ABSTRACT FROM AUTHOR]

Approximately one-third of all ischemic strokes and the ensuing health and economic burden can be attributed to the presence of atrial fibrillation (AF). The global prevalence of AF continues to rise, thus making it by far the most common diagnosed cardiac arrhythmia. Percutaneous left atrial appendage (LAA) occlusion or obliteration has been developed to protect from the occurrence of stroke in patients with nonvalvular AF. We address the characteristics and techniques for implantation as well as some clinical registries and randomized trials of the various catheter-based devices for the occlusion of the LAA that are either currently available or in the clinical evaluation stage. Over less than 2 decades, LAA occlusion progressed from being a concept applied in a few specialized centers to a globally recognized procedure implemented in numerous hospitals as part of daily interventional practice. The respective devices are to date safer and easier to deploy than initially. Periprocedural and postprocedural complications will continue to decrease as already evident from prospective randomized trials and registries. Although current indications focus on patients with nonvalvular AF and contraindications for oral anticoagulation, it is all but certain that the future will bring a widening in the spectrum of indications, applicability, and usage of these devices. [ABSTRACT FROM AUTHOR]

Objectives: Circulating cytokines have been associated with depression, but their detection has limitations, which may be overcome by direct detection of intracellular cytokines (ICCs) after lipopolysaccharide (LPS) stimulation in vitro. This study compared circulating versus LPS-induced inflammatory markers as correlates of subthreshold depressive symptoms. Methods: Secondary data analysis of a cross-sectional insomnia study in healthy community-dwelling older adults was conducted. In 117 participants (≥55 years), plasma tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP) and in vitro LPS-induced monocyte production of IL-6 and TNF-α were assayed. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). Multivariate linear regression was conducted to test the associations between inflammatory markers and subthreshold depressive symptoms in the entire sample as well as in subgroups stratified into higher and lower inflammation levels. Results: LPS-induced TNF-α (adjusted β = 0.28, p =.04), IL-6 (0.29, p =.03) and TNF-α + IL-6 (0.43, p =.001) significantly positively correlated with subthreshold depressive symptoms only in higher inflammation subgroups. No circulating biomarkers positively correlated in any subgroups. In the entire sample, no biomarkers were significantly associated with subthreshold depressive symptoms. Conclusions: LPS-induced cytokines may be more sensitive correlates of subthreshold depressive symptoms than circulating cytokines, particularly in older adults with higher systemic inflammation. Clinical Trials Registry: ClinicalTrials.gov NCT00280020. [ABSTRACT FROM AUTHOR]

Background: It has been hypothesized that Irvingia gabonensis can promote weight loss by increasing fatty acid breakdown and inhibiting fatty acid synthesis.Objective: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Irvingia gabonensis seed extract supplementation on weight-related health outcomes.Methods: Literature searches were conducted in 4 databases from January 2018 to identify randomized controlled trials (RCTs) investigating the effects of Irvingia gabonensis seed extract supplementation on anthropometric measures and cardiovascular biomarkers. Two investigators independently performed abstract screenings, full-text screenings, data extraction, and risk of bias (ROB) assessments. Random effects meta-analyses were performed when 3 or more RCTs reported the same outcome.Results: Five RCTs met the eligibility criteria for this systematic review. Four of the 5 RCTs were rated as having a high ROB, and only one RCT was rated as having a low ROB. Random-effects meta-analysis of the 5 RCTs showed that a significant decrease in body weight, body fat, and waist circumference was observed in relation to Irvingia gabonensis seed extract supplementation. However, the only one low-ROB trial did not have significantly different outcomes. Meta-analysis also showed beneficial effects of Irvingia gabonensis seed extract supplementation on total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Only the low-ROB trial showed a trend of increasing HDL-cholesterol levels (net percent change = 11.61%; 95% confidence interval (CI: -6.12%, 29.34%) and decreasing triglyceride levels (net percent change = -29%; 95% CI: -76%, 19%). The reported adverse events were minor in these 5 RCTs.Conclusions: Overall efficacy of Irvingia gabonensis seed extract supplementation on weight loss seems positive but is limited due to poor methodological quality and the insufficient reporting of the clinical trials. Further high quality RCTs are needed to determine the effectiveness of Irvingia gabonensis seed extract supplement on the weight-related health outcomes. [ABSTRACT FROM AUTHOR]

The extraction of digital evidence from storage media is a growing concern in digital forensics, due to the time and space complexity in acquiring, preserving and analysing digital evidence. Microsoft Windows Registry is an example of a potential source of digital evidence that contains a database of evidential information about both the system and users. However, due to the vastness of the Registry, it is difficult to manually sift through this database to extract potential evidence. Furthermore, manually sifting provides room for human error, which could invalidate the entire forensic investigation. This time-consuming and error-prone process can cause several delays in processing and presenting criminal cases during litigation. The need for an automated extraction and analysis process of digital evidence is therefore inherently needed. The aim of this research is to develop an automated forensically sound process for Windows Registry investigation. This entails setting up strict and reliable measures for an investigator to follow whilst minimizing human interaction through automation. To achieve this, an acquisition and analysis tool was developed. A comparative analysis of the developed tool to existing tools showed increased performance with respect to time and forensic soundness. [ABSTRACT FROM AUTHOR]

Patients receiving adjuvant or neo-adjuvant treatment Patients in this group received their treatment and were managed through one-day or a more extended hospitalization, if required. Patients living far from the oncological center We entrusted these patients to the oncological center nearest their home offering a detailed clinical report to our colleagues and all our support for any queries regarding patients. Patients requiring intravenous treatment To further reduce the risk of infection between patients receiving intravenous treatments other measures were applied. [Extracted from the article]

Background: This study examined the effects of whey protein supplementation, compared with an isocaloric carbohydrate beverage and water, consumed immediately following an intense swimming trial on bone turnover in adolescent swimmers. Methods: Fifty-eight (31 female, 27 male) swimmers (14.1 ± 0.4 years) were stratified into three groups matched for age, sex and body mass. The protein and carbohydrate groups consumed two isocaloric post-exercise beverages each containing 0.3 g.kg− 1 of whey protein (with ~ 6 mg of calcium) or maltodextrin while the control group consumed water. Participants provided a morning, fasted, resting blood sample, then performed an intense swimming trial consisting of a maximal 200 m swim followed by a high intensity interval swimming protocol (5x100m, 5x50m and 5x25m; 1:1 work-to-rest ratio). Following swimming, they consumed their first respective post-exercise beverage, and 2 h later, they performed a second maximal swim immediately followed by the second beverage. Approximately 3 h after the second beverage, two post-consumption blood samples were collected at 8 h and 24 h from baseline. Procollagen type 1 intact N-terminal propeptide (PINP) and carboxy-terminal collagen crosslinks (CTXI) were measured in serum. The multiples of medians of PINP and CTXI were also used to calculate bone turnover rate and balance. Results: No significant changes were observed in PINP. CTXI increased (+ 11%) at 8 h in all groups, but then significantly decreased (− 22%) at 24 h in the protein group only. The protein group also had a significantly higher calculated rate of bone turnover at 8 h and 24 h compared to baseline, which was not observed in the other groups. Conclusions: These results shed light on the potential importance of protein consumed shortly after intense swimming in promoting positive bone turnover responses up to 24 h following exercise in adolescent athletes. Clinical trial registration: ClinicalTrials.gov PRS; NCT04114045. Registered 1 October 2019 - Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective: Although extensively studied in children, the safety and tolerability of ketone supplementation in adults is unclear, particularly in the acute brain injury population. The purpose of this study was to examine the feasibility and safety of inducing ketosis using an enteric ketogenic formulation and determine its impact on intracranial and cerebral perfusion pressures and metabolic parameters. Methods: Prospective interventional Phase II trial of ventilated critically ill patients with acute brain injury administered a ketogenic feed over a 6 day period. Results: 20 patients were recruited, 5 females and 15 males, 3 with stroke, 2 with subarachnoid haemorrhage and 15 with traumatic brain injury. Feeds were well tolerated with 19 patients completing study. There was a significant increase in both plasma beta-hydroxybutyrate and acetoacetate from 0.24± 0.31 mmol/l and 0.19 ± 0.16 mmol/l to 0.61 ± 0.53 mmol/l (p =0.0005) and 0.52 ± 0.40 mmol/l (p<0.0001) respectively over the 6 day period. Total daily Ketocal® caloric intake was positively correlated with plasma beta-hydroxybutyrate concentrations (p=0.0011). There was no significant correlation between the cerebral hypertension and cerebral hypoperfusion indices and plasma ketone concentrations. In 95% of patients there were no clinically significant changes in acid/base status over the 6 days with pH remaining within normal range. Conclusion: In patients with acute brain injury, an enterally administered ketogenic formulation increased plasma ketone concentrations, was well tolerated, did not impact on cerebral hemodynamics and can be safely administered. Clinical trial registered at the Australian New Zealand Clinical Trials Registry (ACTRN12616000332426) Abbreviations: BHB: betahydroxybutyrate; AcAc: acetoacetate; ABI: acute brain injury; TBI: traumatic brain injury; CSF: cerebrospinal fluid; SAH: subarachnoid injury; CVA: cerebrovascular accidents; ICP: intracranial pressure; CPP: cerebral perfusion pressure; ICU: intensive care unit; EVD: external ventricular device; CHI: cerebral hypoperfusion index; IHI: intracranial hypertension index; GCS: Glasgow Coma Scale [ABSTRACT FROM AUTHOR]

Our main objective was to demonstrate that, in smoker patients hospitalised for Chronic Obstructive Pulmonary Disease (COPD) exacerbation, early initiation of varenicline during 12 weeks, combined with an intensive counselling, is associated with a higher continuous abstainers rate (CAR) at one year as compared to intensive counselling alone. In this multicenter, prospective, double-blind, randomised study, 81 smoking COPD patients hospitalised for an acute exacerbation for at least 24 h were allocated to receive either varenicline (n = 42) or placebo (n = 39) for 12 weeks, in association with an intensive counselling in the 2 groups, and followed up for 40 weeks. The primary outcome was CAR at week 52. Secondary outcomes included CAR at week 12 and 26, partial abstinence rate (PAR) at week 12, 26 and 52, nicotinic substitute consumption and adverse events. At week 52, CAR was not different in placebo and varenicline groups (25.6%). At week 12, CAR was significantly higher in the varenicline group (50%) as compared to placebo group (27%) (p = 0.041). Nicotine consumption was significantly higher at week 52 in the placebo group (55.3%) as compared to the varenicline group (24.4%) (p = 0.005). There was no significant difference in PAR at week 12, 26 and 52; the frequency of adverse events was similar between the two groups. Among active smoker COPD patients with exacerbation, 12-week varenicline associated with intensive counselling for smoking cessation increased the rate of continuous abstainers as compared to placebo. However, benefit was not maintained after varenicline discontinuation. Clinical Trials Registration: URL: . Unique identifier: NCT01694732 [ABSTRACT FROM AUTHOR]

Introduction: Many patients with advanced Parkinson's disease (PD) have inadequate control of motor symptoms despite optimized treatment. Predictable and unpredictable OFF periods severely interfere with the quality of life. A drug that easily and rapidly reverts the OFF state is still needed. Subcutaneous apomorphine, the only approved drug for this indication, although efficacious, is not widely used probably due to its potential side effects and complicated administration. Levodopa is the most efficacious drug for the treatment of PD motor symptoms. However, issues related to the oral route and intestinal absorption in later disease stages render this route lengthy and inefficacious. Areas covered: Literature on the development of an inhaled formulation of levodopa has been reviewed. Significant advances in the field of pulmonary delivery systems and in dry powders have enabled the development of a new formulation of levodopa that can be inhaled and adequate blood levels rapidly achieved, bypassing intestinal absorption. Several clinical trials have reported efficacy, safety, and tolerability data. Some pulmonary-related adverse events have been reported but are mostly mild. Expert opinion: This new way of administering levodopa is likely to be very welcome and may fill a gap for OFF rescue treatments, at least for some patients. [ABSTRACT FROM AUTHOR]

Introduction: STOPP (Screening Tool of Older Persons' Prescriptions) and START (Screening Tool to Alert to Right Treatment) are explicit criteria that facilitate medication review in multi-morbid older people in most clinical settings. This review examines the clinical trial evidence pertaining to STOPP/START criteria as an intervention. Areas covered: The literature was searched for registered clinical trials that used STOPP/START criteria as an intervention. In single-center trials, applying STOPP/START criteria improved medication appropriateness, reduced polypharmacy, reduced adverse drug reactions (ADRs), led to fewer falls, and lower medication costs. Two large-scale multi-center trials (SENATOR and OPERAM) examined the impact of computer-generated STOPP/START criteria on incident ADRs (SENATOR) and drug-related hospitalizations (OPERAM) in multi-morbid older people. Results of these trials will be publicized in 2020. Expert opinion: Applying STOPP/START criteria improves clinical outcomes in multi-morbid older people. Electronic deployment of STOPP/START criteria is a substantial technical challenge; however, recent clinical trials of software prototypes demonstrate feasibility. Even with well-functioning software for the application of STOPP/START criteria, the need remains for face-to-face interaction between attending clinicians and appropriately trained personnel (likely pharmacists) to explain and qualify specific STOPP/START recommendations in individual multi-morbid older patients. Such interaction is essential for the implementation of relevant STOPP/START recommendations. [ABSTRACT FROM AUTHOR]

Objective: While widely used in the treatment of cardiac conditions, only limited data characterize out-of-hospital nitroglycerin (NTG) use. We sought to determine the safety of out-of-hospital sublingual NTG administered for suspected ST-segment elevation myocardial infarction (STEMI) and its effect on the patient's pain score. Methods: We prospectively identified adult patients with suspected STEMI transported by paramedics to three percutaneous Coronary Intervention PCI-capable hospitals in a large urban-suburban emergency medical services (EMS) system. We compared patients who received field NTG to those who did not. The primary outcome was the change in systolic blood pressure (SBP) between initial EMS measurement and emergency department (ED) triage vital signs. Secondary outcomes included the frequency of hypotension (SBP < 100 mmHg) and bradycardia (HR < 60) on ED arrival, drop in SBP ≥ 30 mmHg, out-of-hospital cardiac arrest (OHCA), and the change in pain score compared to an a priori threshold of −1.39. Results: Among 940 EMS transports for suspected STEMI, we excluded 160 for initial SBP < 100 mmHg, leaving 780 subjects for the analysis. Median age was 67 with 61% male. NTG was administered to 340 (44%) patients. The median change in SBP was −10 mmHg (IQR −27, 2) and −3 mmHg (IQR −20, 9) in patients treated with and without NTG, respectively. The median difference in the decrease in SBP was 6 mmHg (95% CI 3, 9 mmHg). The frequencies of ED hypotension and bradycardia, the drop in SBP ≥ 30 mmHg, and the OHCA did not differ between groups. For patients with an initial pain score > 0, the average change in pain score for patients treated with NTG was −2.6 (95% CI −3.0, −2.2), while patients who did not receive NTG had a change in pain score of −1.4 (95% CI −1.8, −1.0). Conclusion: In this cohort, field NTG did not result in a clinically significant decrease in blood pressure when compared with patients who did not receive NTG. However, NTG did cause a clinically significant reduction in pain. [ABSTRACT FROM AUTHOR]

Aim: We investigated the outcomes of transcatheter (TAVR) and surgical aortic valve replacement (SAVR) in Finland during the last decade. Methods: The nationwide FinnValve registry included data from 6463 patients who underwent TAVR or SAVR with a bioprosthesis for aortic stenosis from 2008 to 2017. Results: The annual number of treated patients increased three-fold during the study period. Thirty-day mortality declined from 4.8% to 1.2% for TAVR (p =.011) and from 4.1% to 1.8% for SAVR (p =.048). Two-year survival improved from 71.4% to 83.9% for TAVR (p <.001) and from 87.2% to 91.6% for SAVR (p =.006). During the study period, a significant reduction in moderate-to-severe paravalvular regurgitation was observed among TAVR patients and a reduction of the rate of acute kidney injury was observed among both SAVR and TAVR patients. Similarly, the rate of red blood cell transfusion and severe bleeding decreased significantly among SAVR and TAVR patients. Hospital stay declined from 10.4 ± 8.4 to 3.7 ± 3.4 days after TAVR (p <.001) and from 9.0 ± 5.9 to 7.8 ± 5.1 days after SAVR (p <.001). Conclusions: In Finland, the introduction of TAVR has led to an increase in the invasive treatment of severe aortic stenosis, which was accompanied by improved early outcomes after both SAVR and TAVR. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT03385915 This study demonstrated that the introduction of transcatheter aortic valve replacement has led to its widespread use as an invasive treatment for severe aortic stenosis. Early and 2-year survival after transcatheter and surgical aortic valve replacement has improved during past decade. Transcatheter aortic valve replacement has fulfilled its previously unmet clinical needs and has surpassed surgical aortic valve replacement as the most common invasive treatment for aortic stenosis. [ABSTRACT FROM AUTHOR]

Prospective memory (the ability to remember to do things) has clear implications for everyday functioning, including employment, in people with severe mental illnesses (SMI). This study aimed to evaluate prospective memory performance and its relationship to real-world functional variables in an employment-seeking sample of people with SMI (Clinical Trial registration number NCT00895258). 153 individuals with DSM-IV diagnosis of depression (n = 58), bipolar disorder (n = 37), or schizophrenia (n = 58) who were receiving outpatient psychiatric care at a university clinic enrolled in a trial of supported employment and completed a baseline assessment. Prospective memory was measured with the Memory for Intentions Test (MIST); real-world functional status included work history variables, clinical history variables, baseline functional capacity (UCSD Performance-based Skills Assessment-Brief), and work outcomes (weeks worked and wages earned during two years of supported employment). Participants with schizophrenia performed worse on the MIST than did those with affective disorders. Independent of diagnosis, education, and estimated intellectual functioning, prospective memory significantly predicted variance in measures of disability and illness burden (disability benefits, hospitalization history, current functional capacity), and work outcomes over two years of supported employment (weeks worked). Worse prospective memory appears to be associated with greater illness burden and functional disability in SMI. Mental health clinicians and employment specialists may counsel clients to use compensatory prospective memory strategies to improve work performance and decrease functional disability associated with SMI. [ABSTRACT FROM AUTHOR]

Cachexia not only has a dramatically harmful impact on a patient's life, but also a poor response to therapeutic agents. The purpose of the present review is to provide updated information concerning the pharmacokinetic aspects of drugs used to treat cardiopulmonary cachexia in patients with no signs of hepatic or renal pathology. A systematic search of PubMed, the Cochrane Central Register of Control Trials, Science Direct, and Clinical Trials Registry (ClinicalTrials.gov), encompassing the period between 2000 and 2017, was conducted in accordance to PRISMA guidelines. Seven studies were identified. Collectively, these studies included a total of 196 individuals (19 healthy subjects and 177 diseased patients). This data review found no differences in bisoprolol and prothionamide absorption in cachectic patients with chronic heart failure and tuberculosis, but higher absorption of oflaxocin in the same set of patients was observed. The distribution of bisoprolol, prothionmaide, ceftazidime, and cefipirome was reduced in cardiopulmonary cachexia patients. Hepatic clearance of rifampin was equivalent in cachectic and non-cachectic patients that had normal hepatic function. Similarly in cardiopulmonary cachexia patients, renal clearance of ceftazidime was reduced by 19% but no significant differences in bisorpolol and prothionamide clearance were observed. In the case of cefipirome, both renal clearance and creatinine clearance were higher in cachectic patients with cystic fibrosis. From the limited evidence available, the main drug pharmacokinetic changes seen in cardiopulmonary cachexia patients were a reduction in the volume of distribution and impairment of clearance. [ABSTRACT FROM AUTHOR]

Background: Exhaustive exercise causes muscle damage accompanied by oxidative stress and inflammation leading to muscle fatigue and muscle soreness. Lemon verbena leaves, commonly used as tea and refreshing beverage, demonstrated antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of a proprietary lemon verbena extract (Recoverben®) on muscle strength and recovery after exhaustive exercise in comparison to a placebo product. Methods: The study was performed as a randomized, placebo-controlled, double-blind study with parallel design. Forty-four healthy males and females, which were 22–50 years old and active in sports, were randomized to 400 mg lemon verbena extract once daily or placebo. The 15 days intervention was divided into 10 days supplementation prior to the exhaustive exercise day (intensive jump-protocol), one day during the test and four days after. Muscle strength (MVC), muscle damage (CK), oxidative stress (GPx), inflammation (IL6) and volunteer-reported muscle soreness intensity were assessed pre and post exercise. Results: Participants in the lemon verbena group benefited from less muscle damage as well as faster and full recovery. Compared to placebo, lemon verbena extract receiving participants had significantly less exercise-related loss of muscle strength (p = 0.0311) over all timepoints, improved glutathione peroxidase activity by trend (p = 0.0681) and less movement induced pain (p = 0.0788) by trend. Creatine kinase and IL-6 didn't show significant discrimmination between groups. Conclusion: Lemon verbena extract (Recoverben®) has been shown to be a safe and well-tolerated natural sports ingredient, by reducing muscle damage after exhaustive exercise. Trial registration: The trial was registered in the clinical trials registry (clinical trial.gov NCT02923102). Registered 28 September 2016 [ABSTRACT FROM AUTHOR]

Objective. Methods currently used to triage patients from mass casualty events have a sparse evidence basis. The objective of this project was to assess gaps of the widely used Simple Triage and Rapid Transport (START) algorithm using a large database when it is used to triage low-acuity patients. Subsequently, we developed and tested evidenced-based improvements to START. Methods. Using the National Trauma Database (NTDB), a large set of trauma victims were assigned START triage levels, which were then compared to recorded patient mortality outcomes using area under the receiver-operator curve (AUC). Subjects assigned to the 'Minor/Green' level who nevertheless died prior to hospital discharge were considered mistriaged. Recursive partitioning identified factors associated with of these mistriaged patients. These factors were then used to develop candidate START models of improved triage, whose overall performance was then re-evaluated using data from the NTDB. This process of evaluating performance, identifying errors, and further adjusting candidate models was repeated iteratively. Results. The study included 322,162 subjects assigned to 'Minor/Green' of which 2,046 died before hospital discharge. Age was the primary predictor of under-triage by START. Candidate models which re-assigned patients from the 'Minor/Green' triage level to the 'Delayed/Yellow' triage level based on age (either for patients >60 or >75), reduced mortality in the 'Minor/Green' group from 0.6% to 0.1% and 0.3%, respectively. These candidate START models also showed net improvement in the AUC for predicting mortality overall and in select subgroups. Conclusion. In this research model using trauma registry data, most START under-triage errors occurred in elderly patients. Overall START accuracy was improved by placing elderly but otherwise minimally injured-mass casualty victims into a higher risk triage level. Alternatively, such patients would be candidates for closer monitoring at the scene or expedited transport ahead of other, younger 'Minor/Green' victims. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 1 continues to be the leading cause of infectious corneal blindness. Clinical trials for vaccines against genital HSV infection have been ongoing for more than three decades. Despite this, no approved vaccine exists, and no formal clinical trials have evaluated the impact of HSV vaccines on eye health. We review here the current state of development for an efficacious herpes simplex virus type 1 vaccine and call for involvement of ophthalmologists and vision researchers. [ABSTRACT FROM AUTHOR]

Objective: To assess the characteristics of current clinical trials investigating the treatment of concussion. Background: Recent systematic literature reviews have concluded that there is minimal evidence to support any specific treatment for concussion, including the principles of return-to-activity protocols such as type or duration of rest. Design/methods: Clinical trial data was extracted from Clinicaltrials.gov and seven additional World Health Organization primary registries. The trial databases were accessed up until 3 October 2013. This study used search terms of 'concussion' or 'mild traumatic brain injury' (mTBI) and filtered for interventional trials. Trials that were terminated, already published or not interventional trials of concussion/mTBI were excluded. Results: Of the 142 concussion/mTBI interventional clinical trials identified, 71 met inclusion criteria. Trials had a median estimated enrolment of 60 participants. There was a wide-range of treatments studied, including cognitive/behavioural therapies (28.2%), medications (28.2%), devices (11.3%), dietary supplements (8.5%), return-to-activity/rest (1.4%) and others (22.4%). Heterogeneity among trials for concussion identification/diagnosis and primary outcomes utilized was evident. Symptom-based questionnaires (39.4%) and neuropsychological tests (28.2%) were the most common outcome measures. Conclusions: Diverse, potentially promising therapeutics are currently being studied for the treatment of concussion. However, several deficiencies were identified including a paucity of trials addressing return-to-activity principles. Also, small sample size and trial heterogeneity may threaten scientific evaluation and subsequent clinical application. [ABSTRACT FROM AUTHOR]

Background: UK guidelines recommend that patients with schizophrenia are offered access to social activities, however, the impact of such interventions have not been examined in a large randomized trial. Aims: To investigate the effect of an activity group intervention on mental health and global functioning 12 months after randomization compared to standard care alone. Methods: Secondary analysis of data from the MATISSE study. Primary outcomes were global functioning, assessed using the Global Assessment of Functioning (GAF), and mental health symptoms measured using the Positive and Negative Syndrome Scale (PANSS). Results: About 140 participants were randomized to activity groups and 137 to standard care alone. Follow-up data were collected from 242 (87%) participants. Mental health improved significantly among those offered activity groups (change in PANSS score = −6.0, 95% CI −2.3 to −9.8) but global functioning did not (change in GAF score = 0.8, 95% CI −1.7 to 3.3). No significant differences were found between treatment arms. Conclusions: Offering activity groups to patients with schizophrenia was not associated with any additional clinical benefits. There was poor uptake and attendance at activity groups. Interventions that aim to improve negative symptoms may be useful in enabling engagement in psychosocial interventions. [ABSTRACT FROM AUTHOR]