Purpose Perioperative intravenous ketamine may be a useful addition in pain management regimens. Previous systematic reviews have included all methods of ketamine administration, and heterogeneity between studies has been substantial. This study addresses this issue by narrowing the inclusion criteria, using a random effects model, and performing subgroup analysis to determine the specific types of patients, surgery, and clinical indications which may benefit from perioperative ketamine administration. Source We included published studies from 1966 to 2010 which were randomized, double-blinded, and placebocontrolled using intravenous ketamine (bolus or infusion) to decrease postoperative pain. Studies using any form of regional anesthesia were excluded. No limitation was placed on the ketamine dose, patient age, or language of publication. Principal findings Ninety-one comparisons in seventy studies involving 4,701 patients met the inclusion criteria (2,652 in ketamine groups and 2,049 in placebo groups). Forty-seven of these studies were appropriate for evaluation in the core meta-analysis, and the remaining 23 studies were used to corroborate the results. A reduction in total opioid consumption and an increase in the time to first analgesic were observed across all studies (P \ 0.001). The greatest efficacy was found for thoracic, upper abdominal, and major orthopedic surgical subgroups. Despite using less opioid, 25 out of 32 treatment groups (78%) experienced less pain than the placebo groups at some point postoperatively when ketamine was efficacious. This finding implies an improved quality of pain control in addition to decreased opioid consumption. Hallucinations and nightmares were more common with ketamine but sedation was not. When ketamine was efficacious for pain, postoperative nausea and vomiting was less frequent in the ketamine group. The dose-dependent role of ketamine analgesia could not be determined. Conclusion Intravenous ketamine is an effective adjunct for postoperative analgesia. Particular benefit was observed in painful procedures, including upper abdominal, thoracic, and major orthopedic surgeries. The analgesic effect of ketamine was independent of the type of intraoperative opioid administered, timing of ketamine administration, and ketamine dose. RésuméObjectif La ke´tamine intraveineuse pe´riope´ratoire peut constituer un ajout utile a`l'arsenal the´rapeutique de prise en charge de la douleur. Les revues me´thodiques pre´ce´dentes ont examine´toutes les me´thodes d'administration de la ke´tamine, et l'he´te´roge´ne´ite´entre les e´tudes est conside´rable. Cette e´tude aborde la question en limitant les crite`res d'inclusion, en utilisant un mode`le a`effets ale´atoires et en re´alisant une analyse de sous-groupe afin de de´terminer les types spe´cifiques de patients et de chirurgie ainsi que les indications cliniques qui pourraient be´ne´ficier de l'administration pe´riope´ratoire de ke´tamine.
We report a meta-analysis of a series of studies in which 24-hour ambulatory pH monitoring was performed in 1) normal subjects, 2) the normal control subjects in studies of laryngopharyngeal reflux (LPR), and 3) the patients with LPR in these controlled studies. The statistical analysis utilized the fixed-effects model by Mantel-Haenszel and the random-effects mixed model. There were 16 studies from the past 12 years that fulfilled the inclusion criteria. They involved 793 subjects (264 normal and 529 with LPR). The numbers of positive pharyngeal reflux events for normal subjects and for patients with LPR differed with a p value of <.0001. There was also a significant difference in the mean percentage of acid exposure times between normal subjects and patients with LPR (p = .003). We conclude that the upper probe gives accurate and consistent information in normal subjects and patients with LPR. The numbers of reflux events and acid exposure times are most important in distinguishing normal subjects from patients with LPR. The technology and methodology of probe testing is quite reliable and is consistent on a worldwide basis.
Different clones, protocol conditions, instruments, and scoring/readout methods may pose challenges in introducing different PD-L1 assays for immunotherapy. The diagnostic accuracy of using different PD-L1 assays interchangeably for various purposes is unknown. The primary objective of this meta-analysis was to address PD-L1 assay interchangeability based on assay diagnostic accuracy for established clinical uses/purposes. A systematic search of the MEDLINE database using PubMed platform was conducted using “PD-L1” as a search term for 01/01/2015 to 31/08/2018, with limitations “English” and “human”. 2,515 abstracts were reviewed to select for original contributions only. 57 studies on comparison of two or more PD-L1 assays were fully reviewed. 22 publications were selected for meta-analysis. Additional data were requested from authors of 20/22 studies in order to enable the meta-analysis. Modified GRADE and QUADAS-2 criteria were used for grading published evidence and designing data abstraction templates for extraction by reviewers. PRISMA was used to guide reporting of systematic review and meta-analysis and STARD 2015 for reporting diagnostic accuracy study. CLSI EP12-A2 was used to guide test comparisons. Data were pooled using random-effects model. The main outcome measure was diagnostic accuracy of various PD-L1 assays. The 22 included studies provided 376 2×2 contingency tables for analyses. Results of our study suggest that, when the testing laboratory is not able to use an Food and Drug Administration-approved companion diagnostic(s) for PD-L1 assessment for its specific clinical purpose(s), it is better to develop a properly validated laboratory developed test for the same purpose(s) as the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic, than to replace the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic with a another PD-L1 Food and Drug Administration-approved companion diagnostic that was developed for a different purpose.
The initial scores indicate high self-direction. The drop in scores one year after admission, and the lack of change with increased training, show that the current educational interventions may require reexamination and alteration to ones that promote SDL. Comparison with schools using a different curricular approach may bring to light the impact of curriculum on SDL.
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