Harvest plots are used to graphically display evidence from complex and diverse studies or results. Overviews of reviews bring together evidence from two or more systematic reviews. Our objective was ...to determine the feasibility of using harvest plots to depict complex results of overviews of reviews.
We conducted a survey of 279 members of Cochrane Child Health to determine their preferences for graphical display of data, and their understanding of data presented in the form of harvest plots. Preferences were rated on a scale of 0-100 (100 most preferred) and tabulated using descriptive statistics. Knowledge and accuracy were assessed by tabulating the number of correctly answered questions for harvest plots and traditional data summary tables; t-tests were used to compare responses between formats.
53 individuals from 7 countries completed the survey (19%): 60% were females; the majority had an MD (38%), PhD (47%), or equivalent. Respondents had published a median of 3 systematic reviews (inter-quartile range 1 to 8). There were few differences between harvest plots and tables in terms of being: well-suited to summarize and display results from meta-analysis (52 vs. 56); easy to understand (53 vs. 51); and, intuitive (49 vs. 44). Harvest plots were considered more aesthetically pleasing (56 vs. 44, p = 0.03). 40% felt the harvest plots could be used in conjunction with tables to display results from meta-analyses; additionally, 45% felt the harvest plots could be used with some improvement. There was no statistically significant difference in percentage of knowledge questions answered correctly for harvest plots compared with tables. When considering both types of data display, 21% of knowledge questions were answered incorrectly.
Neither harvest plots nor standard summary tables were ranked highly in terms of being easy to understand or intuitive, reflecting that neither format is ideal to summarize the results of meta-analyses in overviews of reviews. Responses to knowledge questions showed some misinterpretation of results of meta-analyses. Reviewers should ensure that messages are clearly articulated and summarized in the text to avoid misinterpretation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVETo identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure ...cessation.
METHODSThis was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation.
RESULTSWe included 289 patients (55.7% male) with a median age of 4.3 (1.3–9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio OR 2, 95% confidence interval CI 1.18–3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05–1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23–3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24–3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57–0.95).
CONCLUSIONBZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation.
CLASSIFICATION OF EVIDENCEThis study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.
The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus ...(RSE) in children.
An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus rESE) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with
< 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE.
We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes IQR 5-45; rESE 18 minutes IQR 6-44,
= 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes;
= 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70,
= 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53,
= 0.0012) was associated with decreased odds of RSE.
Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner.
This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.
Cochrane Child Health maintains a register of child-relevant Cochrane systematic reviews (SRs) to provide a comprehensive source of high-quality evidence. However, a large number of SRs are published ...outside of The Cochrane Collaboration (Cochrane), impacting the comprehensiveness of the Cochrane Database of Systematic Reviews (CDSR). We surveyed authors who published child-relevant SRs with Cochrane and elsewhere in the medical literature to (1) understand their experiences in preparing and publishing SRs and (2) identify factors influencing choice of publication venue.
We identified SRs published in the CDSR for the most recent complete year prior to our study (2013; n = 145). We searched the medical literature and randomly selected the same number of SRs published the same year. We developed an internet-based survey and contacted the corresponding author of each review via email. Data were analyzed descriptively. Qualitative analysis elicited common themes from open-ended questions.
Seventy-six (26 %) responded: 41 % Cochrane, 42 % non-Cochrane, and 17 % published in both venues. Among respondents who published their SR in both venues (n = 13), 46 % found it easier to publish in a non-Cochrane journal, 15 % easier with Cochrane, and 31 % similar. Main reasons for conducting SRs with Cochrane (n = 44) were Cochrane's positive reputation (82 %) and good impact factor (66 %). Among respondents who published their SR in a non-Cochrane journal (n = 32), most frequent reasons for not conducting their SR with Cochrane were time required to follow Cochrane processes (25 %), lack of knowledge about how to conduct an SR with Cochrane (19 %), administrative processes (16 %), and perception that non-Cochrane journals yielded more interest (16 %). Among respondents who published their SR in a non-Cochrane journal (n = 32), 78 % did not register their review and 22 % did not prepare a protocol.
Key reasons for publishing in Cochrane are its positive reputation and impact factor. Reasons for publishing in non-Cochrane sources include lack of familiarity or challenges with the Cochrane processes and desire to publish in a source more directly relevant to the topic of interest. End users looking for evidence in the form of SRs need to be aware that there is a vast number of SRs published across the medical literature. Efforts to optimize the identification of SRs in non-Cochrane sources (e.g., through effective labeling or protocol/review registration) and their content will help end users find the necessary synthesized evidence to support clinical practice.
ObjectivesWe evaluated 300 paediatric trials to determine: the consent and recruitment strategies used, who trial information was targeted to, how incentives were used and if they achieved their ...recruitment targets.MethodsFor this cross-sectional evaluation, we searched the Cochrane Central Register of Controlled Trials for paediatric trials published in 2012 and randomly selected 300 that reported on outcomes for participants aged ≤21 years. We collected data on consent and recruitment procedures for each trial and undertook descriptive analyses in SPSS statistics V.23.ResultsAll but one trial (99.7%) used a standard recruitment strategy. Most (92%) trials reported that consent was obtained but only 13% reported who obtained consent. Two-thirds (65%) of trials included school-aged participants, and of these 68% reported obtaining assent. Half (50%) of the trials reported who the trial information was targeted to. Most trials (75%) of school-aged participants targeted information towards children or children and their parents. Fourteen per cent of trials reported using incentives, half (50%) of which were in the form of compensation. Only 48% of trials reported sufficient data to determine if their recruitment targets were achieved. Of these, 70% achieved their targets.ConclusionsNotable reporting shortcomings included: how families were recruited into the trial, who obtained consent and/or assent and how, who trial information was directed to, whether incentives were used and sufficient data to determine if the recruitment target was achieved. Forthcoming paediatric-specific reporting standards may improve reporting in this priority area. Our data provide a baseline for ongoing monitoring of the state of the research.
Genomic analysis of “microphenotypes” in epilepsy Stanley, Kate; Hostyk, Joseph; Tran, Linh ...
American journal of medical genetics. Part A,
January 2022, 2022-01-00, 20220101, Letnik:
188, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as “all focal epilepsy” and “all genetic generalized epilepsy”. In ...addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or “microphenotype” may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome‐wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau–Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A).
ObjectivesFor 300 paediatric trials, we evaluated the reporting of: a data monitoring committee (DMC); interim analyses, stopping rules and early stopping; and adverse events and harm-related ...endpoints.MethodsFor this cross-sectional evaluation, we randomly selected 300 paediatric trials published in 2012 from the Cochrane Central Register of Controlled Trials. We collected data on the reporting of a DMC; interim analyses, stopping rules and early stopping; and adverse events and harm-related endpoints. We reported the findings descriptively and stratified by trial characteristics.ResultsEighty-five (28%) of the trials investigated drugs, and 18% (n=55/300) reported a DMC. The reporting of a DMC was more common among multicentre than single centre trials (n=41/132, 31% vs n=14/139, 10%, p<0.001) and industry-sponsored trials compared with those sponsored by other sources (n=16/50, 32% vs n=39/250, 16%, p=0.009). Trials that reported a DMC enrolled more participants than those that did not (median range): 224 (10–60480) vs 91 (10–9528) (p<0.001). Only 25% of these trials reported interim analyses, and 42% reported stopping rules. Less than half (n=143/300, 48%) of trials reported on adverse events, and 72% (n=215/300) reported on harm-related endpoints. Trials that reported a DMC compared with those that did not were more likely to report adverse events (n=43/55, 78% vs 100/245, 41%, p<0.001) and harm-related endpoints (n=52/55, 95% vs. 163/245, 67%, p<0.001). Only 32% of drug trials reported a DMC; 18% and 19% did not report on adverse events or harm-related endpoints, respectively.ConclusionsThe reporting of a DMC was infrequent, even among drug trials. Few trials reported stopping rules or interim analyses. Reporting of adverse events and harm-related endpoints was suboptimal.
Optimization of a pyrrolidine-based template using structure-based design and physicochemical considerations has provided a development candidate 20b (3082) with submicromolar potency in the HCV ...replicon and good pharmacokinetic properties.
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