Objective To investigate the impact of industry funding on reporting of subgroup analyses in randomised controlled trials.Design Systematic review.Data sources Medline.Study selection Randomised controlled trials published in 118 core clinical journals (defined by the National Library of Medicine) in 2007. 1140 study reports in a 1:1 ratio by high (five general medicine journals with largest number of total citations in 2007) versus lower impact journals, were randomly sampled. Two reviewers, independently and in duplicate, used standardised, piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a randomised controlled trial reported subgroup analyses. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of subgroup analyses.Results 469 randomised controlled trials were included, of which 207 (44%) reported subgroup analyses. High impact journals (adjusted odds ratio 2.64, 95% confidence interval 1.62 to 4.33), non-surgical (versus surgical) trials (2.10, 1.26 to 3.50), and larger sample size (3.38, 1.64 to 6.99) were associated with more frequent reporting of subgroup analyses. The strength of association between trial funding and reporting of subgroups differed in trials with and without statistically significant primary outcomes (interaction P=0.02). In trials without statistically significant results for the primary outcome, industry funded trials were more likely to report subgroup analyses (2.29, 1.30 to 4.72) than non-industry funded trials. This was not true for trials with a statistically significant primary outcome (0.79, 0.46 to 1.36). Industry funded trials were associated with less frequent prespecification of subgroup hypotheses (31.3% v 38.0%, adjusted odds ratio 0.49, 0.26 to 0.94), and less use of the interaction test for analyses of subgroup effects (41.4% v 49.1%, 0.52, 0.28 to 0.97) than non-industry funded trials.Conclusion Industry funded randomised controlled trials, in the absence of statistically significant primary outcomes, are more likely to report subgroup analyses than non-industry funded trials. Industry funded trials less frequently prespecify subgroup hypotheses and less frequently test for interaction than non-industry funded trials. Subgroup analyses from industry funded trials with negative results for the primary outcome should be viewed with caution.
There is variability in some techniques and approaches used by hepatobiliary surgeons. Future research focusing on areas of uncertainty including techniques of blood conservation and post-operative analgesia are needed.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal-glial interactions. Previous studies have suggested that WM damage may occur prior to the death of motor neurons, and thus may be considered an early indicator for the diagnosis and prognosis of ALS. However, the exact molecular mechanisms underlying early-onset WM damage in ALS have yet to be elucidated. The present review explored the detailed anatomy of WM and identified several pathological mechanisms that may be implicated in WM damage in ALS. In addition, it associated the pathophysiological alterations of WM, which may contribute to motor neuron death in ALS, with similar mechanisms of WM damage that are involved in multiple sclerosis (MS). Furthermore, the early detection of WM damage in ALS, using neuroimaging techniques, may lead to earlier therapeutic intervention, using immunomodulatory treatment strategies similar to those used in relapsing-remitting MS, aimed at delaying WM damage in ALS. Early therapeutic approaches may have the potential to delay motor neuron damage and thus prolong the survival of patients with ALS. The therapeutic interventions that are currently available for ALS are only marginally effective. However, early intervention with immunomodulatory drugs may slow the progression of WM damage in the early stages of ALS, thus delaying motor neuron death and increasing the life expectancy of patients with ALS.
Background: Discordant practice patterns may be a consequence of evidence-practice gaps or deficiencies in knowledge translation. We examined the current strategies used by hepato-pancreatico-biliary (HPB) surgeons in Canada for the perioperative management of pancreaticoduodenectomy (PD). Methods:We generated a web-based survey that focused on the perioperative measures surrounding PD. The survey was distributed to all members of the Canadian Hepato-Pancreatico-Biliary Association. Results:The survey was distributed to 74 surgeons and received a response rate of 50%. Many similarities in surgical techniques were reported; for example, most surgeons (86.5%) reconstruct the pancreas with pancreaticojejunostomy rather than pancreaticogastrostomy. In contrast, variable techniques regarding the use of peritoneal drainage tubes, anastomotic stents, octreotide and other intraoperative modalities were reported. Most surgeons (75.7%) reported that their patients frequently required preoperative biliary drainage, yet there was minimal agreement with the designated criteria. There was variability in postoperative care, including the use of epidural analgesia and timing of postoperative oral nutrition. Conclusion:We identified heterogeneity among Canadian HPB surgeons, suggesting a number of evidence-practice gaps within specific domains of pancreatic resections. Focused research in these areas may facilitate technical agreement and improve patient outcomes following PD.Contexte : La discordance entre les modes de pratique pourrait être due à des lacunes au plan des pratiques fondées sur des preuves ou à une déficience du transfert des connaissances. Nous avons étudié les stratégies actuellement utilisées par les chirurgiens hépato-pancréato-biliaires (HPB) au Canada pour la prise en charge périopératoire de la pancréatoduodénectomie (PD). Méthodes :Nous avons préparé un questionnaire électronique sur les mesures péri-opératoires entourant la PD. Le questionnaire a été distribué à tous les membres de l'Association hépato-pancréato-biliaire canadienne.Résultats : Le questionnaire a été distribué à 74 chirurgiens et a généré un taux de réponse de 50 %. De nombreuses similitudes dans les techniques chirurgicales ont été signalées : par exemple, la majorité des chirurgiens (86,5 %) reconstruisent le pancréas par pancréatojéjunostomie plutôt que par pancréatogastrostomie. En revanche, on a observé une variabilité dans les techniques d'utilisation des drains péritonéaux, des endoprothèses anastomotiques, des octréotides et autres modalités peropératoires. La majorité des chirurgiens (75,7 %) ont signalé que leurs patients avaient souvent besoin de drains biliaires préopératoires et pourtant, les critères désignés ne semblaient pas faire l'unanimité. On a aussi noté des différences dans les soins postopératoires, y compris en ce qui concerne le recours à l'analgésie péridurale et le moment de la reprise de l'alimentation orale après la chirurgie. Conclusion :Nous avons observé une hétérogénéité dans la pratique des chirurgiens HP...
Patient factors indicative of socioeconomic status are relevant predictors of functional outcome after distal radius fractures. There is currently limited evidence in this area of research, and further examination should be considered to improve outcomes from a patient and system standpoint.
Receipt of RBCT is associated independently with perioperative MM and prolonged hospitalization after partial hepatectomy. These findings further the rationale supporting the need for a strategy of blood management to decrease the use of RBCT after hepatectomy.
Citrullination of arginine residues is a post-translational modification (PTM) found on myelin basic protein (MBP), which neutralizes MBPs positive charge, and is implicated in myelin damage and multiple sclerosis (MS). Here we identify lysine acetylation as another neutralizing PTM to MBP that may be involved in myelin damage. We quantify changes in lysine and arginine PTMs on MBP derived from mice induced with an experimental autoimmune encephalomyelitis (EAE) model of MS using liquid chromatography tandem mass spectrometry. The changes in PTMs are correlated to changes in neurological disability scoring (NDS), as a marker of myelin damage. We found that lysine acetylation increased by 2-fold on MBP during peak NDS post-EAE induction. We also found that mono- and dimethyl-lysine, as well as asymmetric dimethyl-arginine residues on MBP were elevated at peak EAE disability. These findings suggest that the acetylation and methylation of lysine on MBP are PTMs associated with the neurological disability produced by EAE. Since histone deacetylase (HDAC) inhibitors have been previously shown to improve neurological disability, we also show that treatment with trichostatin A (a HDAC inhibitor) improves the NDS of EAE mice but does not change MBP acetylation.
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