-
Journal of Visualized Experiments : JoVE Jul 2022This study aimed to develop a repeatable, reliable, high-throughput protocol to monitor bacterial growth in 96-well plates and analyze the maximum growth rate. The...
This study aimed to develop a repeatable, reliable, high-throughput protocol to monitor bacterial growth in 96-well plates and analyze the maximum growth rate. The growth curves and maximum growth rates of two bacterial species were determined. Issues including (i) lid condensation, (ii) pathlength correction, (iii) inoculation size, (iv) sampling time interval, and (v) spatial bias were investigated. The repeatability of the protocol was assessed with three independent technical replications, with a standard deviation of 0.03 between the runs. The maximum growth rates of Bacillus mycoides and Paenibacillus tundrae were determined to be (mean ± SD) 0.99 h ± 0.03 h and 0.85 h ± 0.025 h, respectively. These bacteria are more challenging to monitor optically due to their affinity to clump together. This study demonstrates the critical importance of inoculation size, path length correction, lid warming, sampling time intervals, and well-plate spatial bias to obtain reliable, accurate, and reproducible data on microplate readers. The developed protocol and its verification steps can be expanded to other methods using microplate readers and high-throughput protocols, reducing the researchers' innate errors and material costs.
Topics: Bacteria; Reproducibility of Results
PubMed: 35969072
DOI: 10.3791/63849 -
Nihon Hoshasen Gijutsu Gakkai Zasshi Oct 2022There are problems with dose management in X-ray computed tomography (CT) because the protocol used for any examination is not always in the same scan range. The purpose...
PURPOSE
There are problems with dose management in X-ray computed tomography (CT) because the protocol used for any examination is not always in the same scan range. The purpose of this study was to investigate the usefulness of setting the CT protocol based on the scan range.
METHODS
We evaluated the examination data of patients who underwent plain CT based on a scan range of chest to pelvis and abdomen to pelvis. The previous protocol [Chest-Abdomen Routine] was changed to the current protocols [Chest_Abdomen] and [Chest_Pelvis], and the previous protocol of [Abdomen Routine] was changed to the current protocols [Abdomen] and [Abdomen_Pelvis]. Examination data of height, scan length, volume CT dose index (CTDI), and dose length product (DLP) were obtained from digital imaging and communications in medicine, and radiation dose structured report using Radimetrics. The relationship between patient height and scan range, and CTDI and DLP was indicated in a scatter plot. Standard deviation (SD) of scan length and DLP were compared between current and previous protocols. Outliers were defined as the data exceeding average ±2SD.
RESULTS
The SD of scan length decreased by 77.1% on abdomen to pelvis, and the SD of DLP decreased by 65.2% on abdomen to pelvis. The causes of the outliers were CT scan range, scan parameter, arm position, metal implants, and body thickness of patients.
CONCLUSION
Setting CT protocols based on the scan range reduced SD of scan length and DLP. It was helpful for reducing the number of scan range outliers and analyzing the cause of outliers.
Topics: Humans; Radiation Dosage; Tomography, X-Ray Computed; Pelvis; Thorax; Abdomen
PubMed: 36031372
DOI: 10.6009/jjrt.2022-1131 -
Frontiers in Reproductive Health 2022Prospective cohort studies that enroll participants before conception are crucial for deepening scientific understanding of how the preconception environment influences...
BACKGROUND
Prospective cohort studies that enroll participants before conception are crucial for deepening scientific understanding of how the preconception environment influences reproductive outcomes. While web-based research methods provide efficient and effective strategies to collect questionnaire-based data, few of these studies incorporate biospecimen collection, which can enhance the validity of exposure assessment. There is limited literature on the feasibility and cost-effectiveness of collecting biospecimens in web-based preconception cohort studies.
METHODS
We evaluated the feasibility and cost-effectiveness of in-clinic and mail-based biospecimen collection in Pregnancy Study Online (PRESTO), a North American web-based preconception cohort study. Both members of the couple were eligible to participate if their conception attempt time was ≤3 months at enrollment. We invited study participants from the Boston, MA and Detroit, MI metropolitan areas to attend a study visit and provide urine and blood (hereafter "in-clinic protocol"). We invited all other participants to complete mail-based collection of urine and blood spots (hereafter "mail-based protocol"). We compared overall consent and protocol completion rates, demographic characteristics of those who consented and completed either of the protocols, and costs between mail-based and in-clinic protocols for biospecimen collection. Finally, we described logistical challenges pertaining to reliance on mail-based delivery of time-sensitive biospecimens compared with in-clinic methods.
RESULTS
During January 2022-July 2022, 69% of female participants (134/195) and 42% of male participants (31/74) consented to participate in the mail-based protocol. Consent rates for the in-clinic protocol were 39% for female participants (289/739 during March 2014-July 2022) and 25% for male participants (40/157 during March 2017-July 2022). Participants who consented to participate were generally of higher socioeconomic position than non-participants. Deviations from the protocol occurred more frequently within the mail-based protocol but were easily corrected. The cost per participant enrolled was similar across protocols (mail-based: $276.14 vs. in-clinic: $270.38).
CONCLUSIONS
Our results indicate that mail-based collection of biospecimens may create opportunities to recruit a larger and more geographically diverse participant population at a comparable cost-per-participant enrolled to in-clinic methods.
PubMed: 36699143
DOI: 10.3389/frph.2022.1052231 -
JAMA Network Open Feb 2021The cohort size of phase 1 clinical trials and thus the timing of the interim decisions are typically prespecified in the trial protocol. During trial implementation,...
IMPORTANCE
The cohort size of phase 1 clinical trials and thus the timing of the interim decisions are typically prespecified in the trial protocol. During trial implementation, however, the cohort size often deviates from the planned one, which shifts the schedule of the interims. Despite its pervasiveness in phase 1 trials, the association of cohort size deviation with the operating characteristics of these trials is not clear.
OBJECTIVE
To explore the association between cohort size deviation and the operating characteristics of phase 1 clinical trials.
DESIGN, SETTING, AND PARTICIPANTS
In this cross-sectional simulation study, a review was conducted of 102 phase 1 dose-escalation trials published between January 2017 and May 2018 in 3 peer-reviewed journals (Journal of Clinical Oncology, Clinical Cancer Research, and Cancer). After exclusion of studies that did not report the cohort size, 45 trials remained for analysis. Based on the analysis results, a simulation study was performed to systematically investigate the association of cohort size deviation with the operating characteristics of the trials.
MAIN OUTCOMES AND MEASURES
The prevalence of cohort size deviation and the percentage of correct selection of the maximum tolerated dose.
RESULTS
Of the 45 reviewed trials, 10 (22.2%) adhered strictly to the planned cohort size. The simulation study showed that when cohort size deviation was random, it had little association with the performance of novel model-based and model-assisted designs (mean reduction in the percentage of correct selection of the maximum tolerated dose was 0.87 percentage point for the continual reassessment method and 0.84 percentage point for the bayesian optimal interval design). When the cohort size deviation was informative and made based on the observed data on toxicity (eg, if dose-limiting toxicity was observed, the size of the next or current cohort was reduced or expanded), the variation of the design performance increased. The range of the change in the percentage of correct selection was -3.7 to 1.3 percentage points for the continual reassessment method and -4.5 to 0 percentage points for the bayesian optimal interval design.
CONCLUSIONS AND RELEVANCE
The findings suggest that when novel phase 1 clinical trial designs are used, some cohort size deviation is acceptable and has little association with the performance of the designs. These deviations may be used by expert investigators to properly interpret the data, ensure safety, and leverage flexibility in the protocol.
Topics: Antineoplastic Agents; Bayes Theorem; Clinical Trial Protocols as Topic; Clinical Trials, Phase I as Topic; Computer Simulation; Cross-Sectional Studies; Humans; Maximum Tolerated Dose; Neoplasms; Research Design; Sample Size
PubMed: 33595664
DOI: 10.1001/jamanetworkopen.2020.37563 -
Trials Dec 2023Retention to trials is important to ensure the results of the trial are valid and reliable. The SPIRIT guidelines (18b) require "plans to promote participant retention... (Review)
Review
BACKGROUND
Retention to trials is important to ensure the results of the trial are valid and reliable. The SPIRIT guidelines (18b) require "plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols" be included in trial protocols. It is unknown how often protocols report this retention information. The purpose of our scoping review is to establish if, and how, trial teams report plans for retention during the design stage of the trial.
MATERIALS AND METHODS
A scoping review with searches in key databases (PubMed, Scopus, EMBASE, CINAHL (EBSCO), and Web of Science from 2014 to 2019 inclusive) to identify randomised controlled trial protocols. We produced descriptive statistics on the characteristics of the trial protocols and also on those adhering to SPIRIT item 18b. A narrative synthesis of the retention strategies was also conducted.
RESULTS
Eight-hundred and twenty-four protocols met our inclusion criteria. RCTs (n = 722) and pilot and feasibility trial protocols (n = 102) reported using the SPIRIT guidelines during protocol development 35% and 34.3% of the time respectively. Of these protocols, only 9.5% and 11.4% respectively reported all aspects of SPIRIT item 18b "plans to promote participant retention and to complete follow-up, including list of any outcome data for participants who discontinue or deviate from intervention protocols". Of the RCT protocols, 36.8% included proactive "plans to promote participant retention" regardless of whether they reported using SPIRIT guidelines or not. Most protocols planned "combined strategies" (48.1%). Of these, the joint most commonly reported were "reminders and data collection location and method" and "reminders and monetary incentives". The most popular individual retention strategy was "reminders" (14.7%) followed by "monetary incentives- conditional" (10.2%). Of the pilot and feasibility protocols, 40.2% included proactive "plans to promote participant retention" with the use of "combined strategies" being most frequent (46.3%). The use of "monetary incentives - conditional" (22%) was the most popular individual reported retention strategy.
CONCLUSION
There is a lack of reporting of plans to promote participant retention in trial protocols. Proactive planning of retention strategies during the trial design stage is preferable to the reactive implementation of retention strategies. Prospective retention planning and clear communication in protocols may inform more suitable choice, costing and implementation of retention strategies and improve transparency in trial conduct.
Topics: Humans; Randomized Controlled Trials as Topic; Retention in Care; Research Design
PubMed: 38049833
DOI: 10.1186/s13063-023-07775-2 -
Open Heart Dec 2023Targeted temperature management (TTM) is a recommended therapy for postcardiac arrest patients. Hyperthermia worsened the patient outcome, and overcooling increased the... (Observational Study)
Observational Study
BACKGROUND
Targeted temperature management (TTM) is a recommended therapy for postcardiac arrest patients. Hyperthermia worsened the patient outcome, and overcooling increased the incidence of complications; therefore, a high-quality TTM is required. The target temperature tended to be modified worldwide after the TTM trial in 2013. Our institute modified the target temperature to 35°C in 2017. This study aimed to compare the conventional and modified protocols, assess the relationship between target temperature deviation and patient outcomes, and identify the factors influencing temperature deviation.
METHODS
This single-centre, retrospective, observational study included adult out-of-hospital cardiac arrest patients who underwent TTM between April 2013 and October 2019. We compared the conventional and modified protocol groups to evaluate the difference in the background characteristics and details on TTM. Subsequently, we assessed the relationship of deviation (>±0.5°C, >37°C, or<33°C) rates from the target temperature with mortality and neurological outcomes. We assessed the factors that influenced the deviation from the target temperature.
RESULTS
Temperature deviation was frequently observed in the conventional protocol group (p=0.012), and the modified protocol group required higher doses of neuromuscular blocking agents (NMBAs) during TTM (p=0.016). Other background data, completion of protocol, incidence of complications, mortality and rate of favourable neurological outcomes were not significantly different. The performance rate of TTM was significantly higher in the modified group than in the conventional protocol group (p<0.001). Temperature deviation did not have an impact on the outcomes. Age, sex, body surface area, NMBA doses and type of cooling device were the factors influencing temperature deviation.
CONCLUSIONS
A target temperature of 35°C might be acceptable and easily attainable if shivering of the patients was well controlled using NMBAs. Temperature deviation did not have an impact on outcomes. The identified factors influencing deviation from target temperature might be useful for ensuring a high-quality TTM.
Topics: Adult; Humans; Body Temperature; Hypothermia, Induced; Retrospective Studies; Temperature; Treatment Outcome; Male; Female
PubMed: 38101858
DOI: 10.1136/openhrt-2023-002459 -
Journal of Clinical Pharmacy and... Mar 2022Paediatric intensive care patients are at high risk for prescription errors due to the more complex process of medication prescribing. Clinical decision support systems... (Observational Study)
Observational Study
WHAT IS KNOWN AND OBJECTIVE
Paediatric intensive care patients are at high risk for prescription errors due to the more complex process of medication prescribing. Clinical decision support systems (CDSS) have shown good results in effectively reducing prescription errors. A specific dosing CDSS was developed that can check and suggest normal dose, dose limits and administration frequencies. This study aimed to assess the effect of this CDSS on protocol deviation (as measure of prescription error) types and frequency in a paediatric intensive care unit (PICU).
METHODS
A retrospective observational study was conducted evaluating 9342 prescriptions in a 4-month period before and after the implementation of a CDSS in the PICU of the University Medical Center Utrecht. Medication forms were reviewed to identify protocol deviations (and therefore possible prescription errors). The incidence and nature of deviations from evidence-based protocols that were unintended and needed to be adjusted, were determined.
RESULTS AND DISCUSSION
In the period before the dosing CDSS, we identified 45 protocol deviations in 5034 prescriptions (0.89%), 28 of which could not be justified (0.56%) and 11 needed to be adjusted (0.22%). In the period after the implementation of the CDSS, there were 21 protocol deviations in 4308 prescriptions (0.49%) of which ten without a valid reason (0.23%) of which two were adjusted (0.05%).
WHAT IS NEW AND CONCLUSION
The specific dosing CDSS was able to significantly reduce unintentional prescription dose deviations and the number of prescriptions that needed to be adjusted, in an existing low incidence situation.
Topics: Child; Decision Support Systems, Clinical; Drug Prescriptions; Humans; Incidence; Intensive Care Units, Pediatric; Medication Errors
PubMed: 34734650
DOI: 10.1111/jcpt.13562 -
Journal of the American Dental... Nov 2022Dental health care personnel (DHCP) may be at increased risk of exposure to severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19, as well as...
BACKGROUND
Dental health care personnel (DHCP) may be at increased risk of exposure to severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19, as well as other clinically important pathogens. Proper use of personal protective equipment (PPE) reduces occupational exposure to pathogens. The authors performed an assessment of PPE donning and doffing practices among DHCP, using a fluorescent marker as a surrogate for pathogen transmission.
METHODS
Participants donned PPE (that is, disposable gown, gloves, face mask, and eye protection) and the fluorescent marker was applied to their palms and abdomen. DHCP then doffed PPE according to their usual practices. The donning and doffing processes were video recorded, areas of fluorescence were noted, and protocol deviations were assessed. Statistical analyses included frequency, type, and descriptions of protocol deviations and factors associated with fluorescence.
RESULTS
Seventy DHCP were enrolled. The donning and doffing steps with the highest frequency of protocol deviations were hand hygiene (66% of donning and 78% of doffing observations involved a deviation) and disposable gown use (63% of donning and 60% of doffing observations involved a deviation). Fluorescence was detected on 69% of DHCP after doffing, most frequently on hands. An increasing number of protocol deviations was significantly associated with increased risk of fluorescence. DHCP with a gown doffing deviation, excluding doffing out of order, were more likely to have fluorescence detected.
CONCLUSIONS
DHCP self-contamination was common with both donning and doffing PPE.
PRACTICAL IMPLICATIONS
Proper use of PPE is an important component of occupational health.
Topics: Humans; Personal Protective Equipment; COVID-19; Health Personnel; SARS-CoV-2; Delivery of Health Care
PubMed: 36175202
DOI: 10.1016/j.adaj.2022.08.004 -
Clinical Trials (London, England) Feb 2019Intention-to-treat comparisons of randomized trials provide asymptotically consistent estimators of the effect of treatment assignment, without regard to compliance....
BACKGROUND
Intention-to-treat comparisons of randomized trials provide asymptotically consistent estimators of the effect of treatment assignment, without regard to compliance. However, decision makers often wish to know the effect of a per-protocol comparison. Moreover, decision makers may also wish to know the effect of treatment assignment or treatment protocol in a user-specified target population other than the sample in which the trial was fielded. Here, we aimed to generalize results from the ACTG A5095 trial to the US recently HIV-diagnosed target population.
METHODS
We first replicated the published conventional intention-to-treat estimate (2-year risk difference and hazard ratio) comparing a four-drug antiretroviral regimen to a three-drug regimen in the A5095 trial. We then estimated the intention-to-treat effect that accounted for informative dropout and the per-protocol effect that additionally accounted for protocol deviations by constructing inverse probability weights. Furthermore, we employed inverse odds of sampling weights to generalize both intention-to-treat and per-protocol effects to a target population comprising US individuals with HIV diagnosed during 2008-2014.
RESULTS
Of 761 subjects in the analysis, 82 dropouts (36 in the three-drug arm and 46 in the four-drug arm) and 59 protocol deviations (25 in the three-drug arm and 34 in the four-drug arm) occurred during the first 2 years of follow-up. A total of 169 subjects incurred virologic failure or death. The 2-year risks were similar both in the trial and in the US HIV-diagnosed target population for estimates from the conventional intention-to-treat, dropout-weighted intention-to-treat, and per-protocol analyses. In the US target population, the 2-year conventional intention-to-treat risk difference (unit: %) for virologic failure or death comparing the four-drug arm to the three-drug arm was -0.4 (95% confidence interval: -6.2, 5.1), while the hazard ratio was 0.97 (95% confidence interval: 0.70, 1.34); the 2-year risk difference was -0.9 (95% confidence interval: -6.9, 5.3) for the dropout-weighted intention-to-treat comparison (hazard ratio = 0.95, 95% confidence interval: 0.68, 1.32) and -0.7 (95% confidence interval: -6.7, 5.5) for the per-protocol comparison (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34).
CONCLUSION
No benefit of four-drug antiretroviral regimen over three-drug regimen was found from the conventional intention-to-treat, dropout-weighted intention-to-treat or per-protocol estimates in the trial sample or target population.
Topics: Adult; Anti-Retroviral Agents; Clinical Protocols; Female; HIV Infections; Humans; Intention to Treat Analysis; Male; Middle Aged; Sustained Virologic Response; Viral Load
PubMed: 30326736
DOI: 10.1177/1740774518806311 -
European Journal of Dental Education :... Aug 2022This study measured the duration, deviation and operator's perception of implant placement by fully guided (FG), pilot-guided (PG) and freehand (FH) protocols by...
INTRODUCTION
This study measured the duration, deviation and operator's perception of implant placement by fully guided (FG), pilot-guided (PG) and freehand (FH) protocols by postgraduate students with minimal implant experience.
MATERIALS AND METHODS
Twenty postgraduate students participated in the study. Half of them placed single anterior (S-Ant) and single posterior (S-Post) implants, and the other half placed anterior (B-Ant) and posterior (B-Post) implants in a wide edentulous area. The PG placement involved surgical guides that only controlled pilot drilling, whilst the FG placement controlled all the drilling steps and implant placement. The duration of implant placement and the operator's perception (ease of drilling, ease of implant placement and operator's preference) were measured. The deviations of placed implants were quantified by measuring the trueness and angulation deviations in relation to the planned implants.
RESULTS
The PG placement was the quickest for inserting implants, followed by FG and FH placements, respectively (p < .05). The location of the implant had influenced the duration of implant placement only for the PG placement. In relation to ease of drilling, ease of implant placement and operator's preference, there was no significant difference amongst the different placement protocols or implant locations. The FG placement was associated with least deviations, followed by PG and FH placements, respectively (p < .05).
CONCLUSIONS
In the hands of postgraduate students with minimal implant experience, FG and PG placements reduced the implant placement duration in comparison with FH placement. The FG placement was consistently more accurate followed by PG placement.
Topics: Computers; Cone-Beam Computed Tomography; Dental Implants; Education, Dental; Humans; Imaging, Three-Dimensional; Perception; Surgery, Computer-Assisted
PubMed: 34797018
DOI: 10.1111/eje.12724