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1.
Sci Rep ; 11(1): 4282, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608577

RESUMO

Two large-scale Florida manatee (Trichechus manatus latirostris) mortality episodes were reported on separate coasts of Florida in 2013. The east coast mortality episode was associated with an unknown etiology in the Indian River Lagoon (IRL). The west coast mortality episode was attributed to a persistent Karenia brevis algal bloom or 'red tide' centered in Southwest Florida. Manatees from the IRL also had signs of cold stress. To investigate these two mortality episodes, two proteomic experiments were performed, using two-dimensional difference in gel electrophoresis (2D-DIGE) and isobaric tags for relative and absolute quantification (iTRAQ) LC-MS/MS. Manatees from the IRL displayed increased levels of several proteins in their serum samples compared to controls, including kininogen-1 isoform 1, alpha-1-microglobulin/bikunen precursor, histidine-rich glycoprotein, properdin, and complement C4-A isoform 1. In the red tide group, the following proteins were increased: ceruloplasmin, pyruvate kinase isozymes M1/M2 isoform 3, angiotensinogen, complement C4-A isoform 1, and complement C3. These proteins are associated with acute-phase response, amyloid formation and accumulation, copper and iron homeostasis, the complement cascade pathway, and other important cellular functions. The increased level of complement C4 protein observed in the red tide group was confirmed through the use of Western Blot.

3.
J Clin Epidemiol ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561528

RESUMO

OBJECTIVE: To evaluate the power of responder analyses in a randomized controlled trial. STUDY DESIGN AND SETTING: Simulations were based on the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST), which compared sertraline to placebo for the treatment of depression in kidney disease. Baseline disease severity, placebo response, effect size, and the proportion of responders were varied across 72 scenarios. Power was assessed using a t-test for change scores, and the chi-square test for dichotomized outcomes of the minimal important difference (MID), improvement and remission in 10000 datasets with a fixed sample size of 193. RESULTS: The t-test had >80% power except for scenarios with the lowest sertraline effect size. The chi-square test using the MID had <7% power in all scenarios while improvement and remission of achieved >80% power only at higher effect sizes and/or when the proportion of responders was highest at 0.5. The chi-square test for improvement had marginal power increases compared to the t-test (4/72 scenarios = 5.6%) and that for remission did not outperform the t-test in any scenario. CONCLUSIONS: The t-test outperforms the chi-square test for dichotomized outcomes regardless of baseline disease severity, placebo response, effect size and the proportion of responders to the intervention.

4.
Nat Commun ; 12(1): 985, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579957

RESUMO

Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 84 pediatric tMN cases (tMDS: n = 28, tAML: n = 56). Our data show that Ras/MAPK pathway mutations, alterations in RUNX1 or TP53, and KMT2A rearrangements are frequent somatic drivers, and we identify cases with aberrant MECOM expression secondary to enhancer hijacking. Unlike adults with tMN, we find no evidence of pre-existing minor tMN clones (including those with TP53 mutations), but rather the majority of cases are unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms.

5.
Am J Kidney Dis ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33418015

RESUMO

Only a handful of interventions are known to prevent the progression of chronic kidney disease (CKD) and the need for kidney replacement therapy. This exclusive list previously only featured angiotensin converting enzyme inhibitors and angiotensin receptor blockers but recently was expanded to include sodium glucose cotransporter 2 (SGLT2) inhibitors. These medications also reduce the risk of cardiovascular (CV) events in patients with kidney disease. Despite current, effective treatments, many patients will continue to suffer from kidney failure and an excess of CV events and the need for additional therapies remains.

6.
Biomaterials ; 269: 120651, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33476892

RESUMO

This study addresses a crucial gap in the literature by characterising the relationship between urethral tissue mechanics, composition and gross structure. We then utilise these data to develop a biomimetic urethral scaffold with physical properties that more accurately mimic the native tissue than existing gold standard scaffolds; small intestinal submucosa (SIS) and urinary bladder matrix (UBM). Nine human urethra samples were mechanically characterised using pressure-diameter and uniaxial extension testing. The composition and gross structure of the tissue was determined using immunohistological staining. A pressure stiffening response is observed during the application of intraluminal pressure. The elastic and viscous tissue responses to extension are free of regional or directional variance. The elastin and collagen content of the tissue correlates significantly with tissue mechanics. Building on these data, a biomimetic urethral scaffold was fabricated from collagen and elastin in a ratio that mimics the composition of the native tissue. The resultant scaffold is comprised of a dense inner layer and a porous outer layer that structurally mimic the submucosa and corpus spongiosum layers of the native tissue, respectively. The porous outer layer facilitated more uniform cell infiltration relative to SIS and UBM when implanted subcutaneously (p < 0.05). The mechanical properties of the biomimetic scaffold better mimic the native tissue compared to SIS and UBM. The tissue characterisation data presented herein paves the way for the development of biomimetic urethral grafts, and the novel scaffold we develop demonstrates positive findings that warrant further in vivo evaluation.

7.
BMJ ; 372: m4573, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441402

RESUMO

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Mortalidade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Humanos , Hipoglicemiantes/efeitos adversos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
8.
Clin Chem ; 67(1): 308-316, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33418576

RESUMO

BACKGROUND: The effect of hemodialysis on cardiac biomarkers is unclear. We sought to evaluate the degree and causes of intradialytic variability of high sensitivity troponin I (hs-TnI), galectin-3 (gal-3), and heart-type fatty acid binding protein (hFABP). METHODS: hs-TnI, gal-3, and hFABP were prospectively measured pre-dialysis and post-dialysis for 1 week every month for 6 months in 178 prevalent adult hemodialysis patients at a single center in Hamilton, Canada. The degree of change from pre-dialysis to post-dialysis for each cardiac biomarker was estimated with multilevel linear regression models. RESULTS: The median change in the concentration of hs-TnI during hemodialysis was -1 ng/L (interquartile range [IQR] -1 to 2 ng/L) while gal-3 and hFABP changed by -36.3 ng/mL (IQR -27.7 to -46.8 ng/mL) and -19.41 ng/mL (IQR -13.61 to -26.87 ng/mL), respectively. The median (IQR) percentage intradialytic changes for hs-TnI, gal-3, and hFABP were 2.6% (-4.4% to 12.5%), -59.8% (-54.7% to -64.8%) and -35.3% (-28.4% to -42.1%), respectively. Ultrafiltration was associated with an increase in concentration of hs-TnI, gal-3, and hFABP (mean 0.99 ng/L, 1.05 ng/mL, and 1.9 ng/mL per L ultrafiltration, respectively, P < 0.001). Both gal-3 and hFABP concentrations decreased in association with the volume of blood processed (P < 0.001) and with hemodialysis treatment time (P = 0.02 and P = 0.04) while hs-TnI concentration decreased only in association with hemodialysis treatment time (P < 0.001). CONCLUSIONS: Ultrafiltration volume and hemodialysis treatment time influenced hs-TnI, gal-3, and hFABP concentrations during hemodialysis and should be considered when interpreting their measurement.

9.
Emerg Infect Dis ; 27(1): 297-300, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33350933

RESUMO

We report a human case of ocular filariasis, caused by a species of Breinlia nematode, from Queensland, Australia. Morphological and molecular evidence indicated that the nematode Breinlia (Johnstonema) annulipapillata, or a closely related taxon, likely transmitted from a macropodid marsupial host was involved, which might represent an accidental finding or an emerging zoonosis.

10.
Can J Kidney Health Dis ; 7: 2054358120968959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294203

RESUMO

Background: Restless legs syndrome (RLS) affects approximately 30% of patients with end-stage kidney disease and is associated with impaired sleep and health-related quality of life. Medications used to treat RLS in patients receiving dialysis may have an increased risk of adverse events with dose titration, and residual RLS symptoms are common despite the use of effective treatments. Randomized controlled trials of monotherapy and combination pharmacologic therapy for RLS in hemodialysis are needed. Objective: To perform a randomized, crossover, placebo-controlled blinded trial of pharmacologic therapy for RLS in hemodialysis. Design/setting: The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) trial is a randomized, crossover, placebo-controlled blinded trial of fixed low-dose pharmacologic therapy in patients receiving hemodialysis in 10 centers across Canada. It uses patient partners in its design, conduct, and reporting. Participants: Adults receiving thrice-weekly hemodialysis for at least 3 months with RLS of at least mild symptoms defined International Restless Legs Syndrome Study Group Rating Scale (IRLS) of 10 or more will enter a double placebo run-in period to exclude nonadherent participants and those unable to tolerate double placebo. Seventy-two participants who completed the run-in period will be randomized to 1 of 8 treatment sequences based on modeling with 4 treatment periods. Methods: Each treatment period lasts 4 weeks and consists of ropinirole 0.5 mg daily and gabapentin 100 mg daily, both together or neither with a double dummy placebo control for each treatment. The primary outcome is the difference in change scores of the IRLS between study treatments. Secondary outcomes are the differences in change scores of the Restless Legs Syndrome-6 Scale, patient global impression, 5-level EQ-5D version, and safety outcomes. Results: This randomized, crossover, placebo-controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination of ropinirole and gabapentin in patients receiving hemodialysis with RLS. Limitations: Patients with chronic kidney disease not on dialysis, kidney transplant recipients and those receiving peritoneal dialysis or home hemodialysis are not included. The intervention's long term safety and efficacy including the risk of augmentation is not captured. Conclusion: This randomized crossover placebo controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination ropinirole and gabapentin in patients receiving hemodialysis with RLS. Trial Registration: ClinicalTrials.gov (NCT03806530).

11.
BMJ Open ; 10(12): e041425, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33371036

RESUMO

INTRODUCTION: The transition from child to adult health services is a challenging and complex process for young people with cerebral palsy (CP). Poorly managed transition is associated with deterioration in health, increased hospitalisations and reduced quality of life. While international research identifies key practices that can improve the experience and outcomes of transition, there is a paucity of data in the Irish context. This research study aims to gain an insight into the experience of transition for young people with CP in Ireland. METHODS AND ANALYSIS: A convergent parallel mixed-methods design will be used to collect, analyse and interpret quantitative and qualitative data. Participants will be young people aged 16-22 years with CP, their parent(s)/carer(s) and service providers. Quantitative and qualitative data will be collected through questionnaires and interviews, respectively. Quantitative data will be reported using descriptive statistics. Where sufficient data are collected, we will examine associations between the experience of transition practices and sociodemographic and CP-related factors, respectively, using appropriate regression models. Associations between service provider characteristics and provision of key transition practices may also be explored using appropriate regression models. Qualitative data will be analysed using the Framework Method. A coding matrix based on key transitional practices identified from the literature will be used to identify convergence and divergence across study components at the integration stage. ETHICS AND DISSEMINATION: The study has been approved by the RCSI University of Medicine and Health Sciences Research Ethics Committee (REC201911010). Results will be presented to non-academic stakeholders through a variety of knowledge translation activities. Results will be published in open access, peer-reviewed journals and presented at national and international scientific conferences.

12.
Viruses ; 12(11)2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187179

RESUMO

Highly pathogenic avian influenza (HPAI) virus, subtype H5N1, constitutes one of the world's most important health and economic concerns given the catastrophic impact of epizootics on the poultry industry, the high mortality attending spillover in humans, and its potential as a source subtype for a future pandemic. Nevertheless, we still lack an adequate understanding of HPAI H5N1 epidemiology and infection ecology. The nature of the wild waterfowl-poultry interface, and the sharing of diverse wetland habitat among these birds, currently underscore important knowledge gaps. India has emerged as a global hotspot for HPAI H5N1, while also providing critical wintering habitat for many species of migratory waterfowl and year-round habitat for several resident waterfowl species. The current study sought to examine the extent to which the wild waterfowl-poultry interface, varied wetland habitat, and climate influence HPAI H5N1 epizootics in poultry in India. Using World Organisation for Animal Health reported outbreaks, this study showed that the wild waterfowl-poultry interface and lacustrine, riparian, and coastal marsh wetland systems were strongly associated with landscape suitability, and these relationships varied by scale. Although increasing poultry density was associated with increasing risk, this was only the case in the absence of wild waterfowl habitat, and only at a local scale. In landscapes increasingly shared between wild waterfowl and poultry, suitability was greater among lower density poultry, again at a local scale only. These findings provide further insight into the occurrence of HPAI H5N1 in India and suggest important landscape targets for blocking the waterfowl-poultry interface to interrupt virus transmission and prevent future outbreaks.

13.
Epidemics ; 33: 100416, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33161184

RESUMO

The rainforests of the Western Ghats exhibit some of the highest biodiversity on the planet, and yet are undergoing rapid land use change due to the expansion of agriculture and other industries. As the landscape of the region is transformed, more people are coming into conflict with wildlife and becoming exposed to pathogens that previously circulated beyond the boundaries of human incursion. Despite an ecological knowledge imperative, this emerging landscape is ill-defined with respect to the ecology of zoonotic viruses and their mammalian wildlife hosts. Without a better understanding of the underlying infection ecology, the epidemiology of viral spillover will remain elusive and unsuited to the task of predicting and preventing outbreaks. The current investigation explored the association between mammalian zoonotic virus richness and species-level landscape, life-history, and dietary traits to describe an initial ecological profile of zoonotic virus hosts in the Western Ghats. Social group composition and dietary forage were both non-linearly associated with greater zoonotic viral richness among these species, whereby species active in smaller social groups, albeit in higher population densities, and exhibiting a tendency toward a generalist diet hosted more zoonotic viruses. While these findings provide no definitive ecological demarcation of zoonotic virus hosts or their contribution to viral maintenance or amplification, it is expected that this preliminary profile can help to develop targeted wildlife pathogen surveillance programs and to expand the current approach to epidemiological modelling of emerging zoonoses in the region, which typically do not account for the macroecological parameters of infection transmission.

14.
ACS Appl Mater Interfaces ; 12(47): 53115-53124, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33200602

RESUMO

A nanohybrid architecture composed of single-wall carbon nanotube films and graphene heterostructures (SWCNT/graphene) was developed as a three-dimensional (3D) electrode. Atomic layer deposition (ALD) was used for conformal coating of catalytic Pt nanoparticles on the 3D ALD-Pt@SWCNT/graphene nanohybrid architecture for further enhancement of H2 sensing, taking advantage of the large sensing area and conformally coated nanostructures of the catalytic Pt. Remarkably, the H2 response was found to be improved by 50% in the SWCNT/graphene nanohybrid, indicating that graphene provides a more efficient charge transport. The ALD-Pt further enhances the H2 responsivity of the 3D ALD-Pt @SWCNT/graphene nanohybrids. By coating 10 cycles of ALD-Pt on the SWCNT/graphene nanohybrid, the H2 response (2.77%) is approximately twice that (1.4%) of its counterpart without the ALD-Pt. By further optimizing the 3D ALD-Pt@SWCNT/graphene nanohybrids with respect to the ALD-Pt cycle numbers and SWCNT film thickness, a H2 responsivity as high as 7.5% was achieved on the SWCNT/graphene nanohybrid sample with a 560 nm thick SWCNT film and 50 cycles of ALD-Pt.

15.
Eval Health Prof ; : 163278720975833, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33251854

RESUMO

We previously developed a workplace-based tool for assessing point of care ultrasound (POCUS) skills and used a modified Delphi technique to identify critical items (those that learners must successfully complete to be considered competent). We performed a standard setting procedure to determine cut scores for the full tool and a focused critical item tool. This study compared ratings by 24 experts on the two checklists versus a global entrustability rating. All experts assessed three videos showing an actor performing a POCUS exam on a patient. The performances were designed to show a range of competences and one included potentially critical errors. Interrater reliability for the critical item tool was higher than for the full tool (intraclass correlation coefficient = 0.84 [95% confidence interval [CI] 0.42-0.99] vs. 0.78 [95% CI 0.25-0.99]). Agreement with global ratings of competence was higher for the critical item tool (κ = 0.71 [95% CI 0.55-0.88] vs 0.48 [95% CI 0.30-0.67]). Although sensitivity was higher for the full tool (85.4% [95% CI 72.2-93.9%] vs. 81.3% [95% CI 67.5-91.1%]), specificity was higher for the critical item tool (70.8% [95% CI 48.9-87.4%] vs. 29.2% [95% CI 12.6-51.1%]). We recommend the use of critical item checklists for the assessment of POCUS competence.

16.
One Health ; : 100177, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33052311

RESUMO

The health and economic impacts of infectious disease pandemics are catastrophic as most recently manifested by coronavirus disease 2019 (COVID-19). The emerging infections that lead to substantive epidemics or pandemics are typically zoonoses that cross species boundaries at vulnerable points of animal-human interface. The sharing of space between wildlife and humans, and their domesticated animals, has dramatically increased in recent decades and is a key driver of pathogen spillover. Increasing animal-human interface has also occurred in concert with both increasing globalisation and failing health systems, resulting in a trifecta with dire implications for human and animal health. Nevertheless, to date we lack a geographical description of this trifecta that can be applied strategically to pandemic prevention. This investigation provides the first geographical quantification of the intersection of animal-human interfaces, poor human health system performance and global connectivity via the network of air travel. In so doing, this work provides a systematic, data-driven approach to classifying spillover hazard based on the distribution of animal-human interfaces while simultaneously identifying globally connected cities that are adjacent to these interfaces and which may facilitate global pathogen dissemination. We present this geography of high-impact spillover as a tool for developing targeted surveillance systems and improved health infrastructure in vulnerable areas that may present conduits for future pandemics.

17.
Sensors (Basel) ; 20(19)2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33028042

RESUMO

The rapid technological advancements of Industry 4.0 have opened up new vectors for novel industrial processes that require advanced sensing solutions for their realization. Motion capture (MoCap) sensors, such as visual cameras and inertial measurement units (IMUs), are frequently adopted in industrial settings to support solutions in robotics, additive manufacturing, teleworking and human safety. This review synthesizes and evaluates studies investigating the use of MoCap technologies in industry-related research. A search was performed in the Embase, Scopus, Web of Science and Google Scholar. Only studies in English, from 2015 onwards, on primary and secondary industrial applications were considered. The quality of the articles was appraised with the AXIS tool. Studies were categorized based on type of used sensors, beneficiary industry sector, and type of application. Study characteristics, key methods and findings were also summarized. In total, 1682 records were identified, and 59 were included in this review. Twenty-one and 38 studies were assessed as being prone to medium and low risks of bias, respectively. Camera-based sensors and IMUs were used in 40% and 70% of the studies, respectively. Construction (30.5%), robotics (15.3%) and automotive (10.2%) were the most researched industry sectors, whilst health and safety (64.4%) and the improvement of industrial processes or products (17%) were the most targeted applications. Inertial sensors were the first choice for industrial MoCap applications. Camera-based MoCap systems performed better in robotic applications, but camera obstructions caused by workers and machinery was the most challenging issue. Advancements in machine learning algorithms have been shown to increase the capabilities of MoCap systems in applications such as activity and fatigue detection as well as tool condition monitoring and object recognition.

18.
J Clin Epidemiol ; 128: 148-156, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33002638

RESUMO

OBJECTIVE: To systematically review the epidemiology of prerandomized run-in periods in randomized controlled trials (RCTs) of chronic diseases. STUDY DESIGN AND SETTING: Meta-epidemiologic study of all RCTs from the four highest impact medical journals from 2011 to 2016. Eligible trials included parallel RCTs that evaluated pharmacologic therapies in adults with chronic diseases with a minimum follow-up of 24 weeks. RESULTS: Of 262 eligible manuscripts, 48 (18.3%), representing 42 unique RCTs, included run-in periods. Run-in periods were most common in cardiovascular disease and diabetes trials. Of the 42 RCTs, in 22 patients received the experimental therapy, 15 placebo, 4 both (either sequentially or in combination), and one did not report the run-in period drug. The median run-in period duration was 28 days (Q1: Q3 14: 66 days). Reasons for including a run-in period included ensuring eligibility criteria were met (18, 42.9%), excluding participants with nonadherence (18, 42.9%) and intolerances to therapy (15, 35.7%), and to standardize therapy prior to randomization (8, 19.0%). The median run-in completion rate was 77.4% (Q1: Q3 62.2:87.8%). CONCLUSIONS: Run-in periods are uncommon in RCTs of chronic drug treatments and when used, their reporting is heterogeneous. Further research to improve the design, use, and reporting of run-in periods is necessary.

19.
Biomed Opt Express ; 11(7): 3996-4007, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33014581

RESUMO

Tissue fibrosis is a progressive and destructive disease process that can occur in many different organs including the liver, kidney, skin, and lungs. Fibrosis is typically initiated by inflammation as a result of chronic insults such as infection, chemicals and autoimmune diseases. Current approaches to examine organ fibrosis are limited to radiological and histological analyses. Infrared spectroscopic imaging offers a potential alternative approach to gain insight into biochemical changes associated with fibrosis progression. In this study, we demonstrate that IR imaging of a mouse model of pulmonary fibrosis can identify biochemical changes observed with fibrosis progression and the beginning of resolution using K-means analysis, spectral ratios and multivariate data analysis. This study demonstrates that IR imaging may be a useful approach to understand the biochemical events associated with fibrosis initiation, progression and resolution for both the clinical setting and for assessing novel anti-fibrotic drugs in a model system.

20.
BMJ Open ; 10(8): e035892, 2020 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-32868352

RESUMO

INTRODUCTION: Cerebral palsy (CP) is a neurodisability that primarily results in motor impairments and activity limitations, but is often associated with epilepsy and disturbances of sensation, perception, cognition, behaviour and speech. Most children with CP survive well into adulthood. Adults with CP experience increased risk of age-related chronic conditions such as arthritis, stroke, cardiorespiratory and mental health conditions in addition to the ongoing disabilities experienced from childhood. Therefore, adults with CP often require extensive health services. However, health service use among adults with CP has not been well documented. This mixed method review aims to identify, appraise and synthesise quantitative and qualitative literature examining health service use among adults with CP. METHODS AND ANALYSIS: The mixed method systematic review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology. A systematic search of MEDLINE (Ovid), CINAHL, Embase, PsycINFO and Cochrane Library from inception to March 2020 will be conducted. Quantitative observational studies, qualitative studies and mixed method studies examining health service use among adults with CP (≥18 years) will be included. Outcomes of interest are the proportion of adults using health services frequency of use and experiences of health services from the perspectives of adults with CP, caregivers and health service providers. Two reviewers will independently screen titles, abstracts and full-texts, extract data and assess the quality of included studies using JBI instruments. Where possible a pooled analysis and aggregation of findings will be performed for quantitative and qualitative data, respectively, and Grading of Recommendations Assessment, Development and Evaluation (GRADE)/GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) employed. Quantitative and qualitative findings will be integrated using a triangulation approach at the synthesis stage. A narrative synthesis will be carried out where this is not possible. ETHICS AND DISSEMINATION: Ethical approval is not required for this review. The findings will be disseminated through a peer-reviewed journal and conferences. PROSPERO REGISTRATION NUMBER: CRD42020155 380.

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