Enhancing a Somatic Maturity Prediction Model Moore, Sarah A; McKay, Heather A; Macdonald, Heather ...
Medicine and science in sports and exercise,
2015-August, Letnik:
47, Številka:
8
Journal Article
Recenzirano
Assessing biological maturity in studies of children is challenging. Sex-specific regression equations developed using anthropometric measures are widely used to predict somatic maturity. However, ...prediction accuracy was not established in external samples. Thus, we aimed to evaluate the fit of these equations, assess for overfitting (adjusting as necessary), and calibrate using external samples.
We evaluated potential overfitting using the original Pediatric Bone Mineral Accrual Study (PBMAS; 79 boys and 72 girls; 7.5-17.5 yr). We assessed change in R and standard error of the estimate (SEE) with the addition of predictor variables. We determined the effect of within-subject correlation using cluster-robust variance and fivefold random splitting followed by forward-stepwise regression. We used dominant predictors from these splits to assess predictive abilities of various models. We calibrated using participants from the Healthy Bones Study III (HBS-III; 42 boys and 39 girls; 8.9-18.9 yr) and Harpenden Growth Study (HGS; 38 boys and 32 girls; 6.5-19.1 yr).
Change in R and SEE was negligible when later predictors were added during step-by-step refitting of the original equations, suggesting overfitting. After redevelopment, new models included age × sitting height for boys (R, 0.91; SEE, 0.51) and age × height for girls (R, 0.90; SEE, 0.52). These models calibrated well in external samples; HBS boys: b0, 0.04 (0.05); b1, 0.98 (0.03); RMSE, 0.89; HBS girls: b0, 0.35 (0.04); b1, 1.01 (0.02); RMSE, 0.65; HGS boys: b0, -0.20 (0.02); b1, 1.02 (0.01); RMSE, 0.85; HGS girls: b0, -0.02 (0.03); b1, 0.97 (0.02); RMSE, 0.70; where b0 equals calibration intercept (standard error (SE)) and b1 equals calibration slope (SE), and RMSE equals root mean squared error (of prediction). We subsequently developed an age × height alternate for boys, allowing for predictions without sitting height.
Our equations provided good fits in external samples and provide an alternative to commonly used models. Original prediction equations were simplified with no meaningful increase in estimation error.
In patients at risk of hypoxic ischemic brain injury following cardiac arrest, we sought to: 1) characterize brain oxygenation and determine the prevalence of brain hypoxia, 2) characterize ...autoregulation using the pressure reactivity index and identify the optimal mean arterial pressure, and 3) assess the relationship between optimal mean arterial pressure and brain tissue oxygenation.
Prospective interventional study.
Quaternary ICU.
Adult patients with return of spontaneous circulation greater than 10 minutes and a postresuscitation Glasgow Coma Scale score under 9 within 72 hours of cardiac arrest.
All patients underwent multimodal neuromonitoring which included: 1) brain tissue oxygenation, 2) intracranial pressure, 3) jugular venous continuous oximetry, 4) regional saturation of oxygen using near-infrared spectroscopy, and 5) pressure reactivity index-based determination of optimal mean arterial pressure, lower and upper limit of autoregulation. We additionally collected mean arterial pressure, end-tidal CO2, and temperature. All data were captured at 300 Hz using ICM+ (Cambridge Enterprise, Cambridge, United Kingdom) brain monitoring software.
Ten patients (7 males) were included with a median age 47 (range 20-71) and return to spontaneous circulation 22 minutes (12-36 min). The median duration of monitoring was 47 hours (15-88 hr), and median duration from cardiac arrest to inclusion was 15 hours (6-44 hr). The mean brain tissue oxygenation was 23 mm Hg (SD 8 mm Hg), and the mean percentage of time with a brain tissue oxygenation below 20 mm Hg was 38% (6-100%). The mean pressure reactivity index was 0.23 (0.27), and the percentage of time with a pressure reactivity index greater than 0.3 was 50% (12-91%). The mean optimal mean arterial pressure, lower and upper of autoregulation were 89 mm Hg (11), 82 mm Hg (8), and 96 mm Hg (9), respectively. There was marked between-patient variability in the relationship between mean arterial pressure and indices of brain oxygenation. As the patients' actual mean arterial pressure approached optimal mean arterial pressure, brain tissue oxygenation increased (p < 0.001). This positive relationship did not persist when the actual mean arterial pressure was above optimal mean arterial pressure.
Episodes of brain hypoxia in hypoxic ischemic brain injury are frequent, and perfusion within proximity of optimal mean arterial pressure is associated with increased brain tissue oxygenation. Pressure reactivity index can yield optimal mean arterial pressure, lower and upper limit of autoregulation in patients following cardiac arrest.
Objective: Fear-avoidance and endurance behavior are well-established maladaptive coping styles in several chronic health conditions. There is also emerging evidence that both fear-avoidance and ...endurance coping are associated with poor outcome from mild traumatic brain injury (mTBI). The current study sought to characterize the early trajectories of avoidance and endurance behavior and confirm their association with disability outcomes. Method: Adults with mTBI (N = 88) completed measures of avoidance, endurance, and postconcussive symptoms at clinic intake (M = 40.2 days since injury). Avoidance and endurance measures were readministered 1 month later (N = 79), and a measure of perceived functional disability (World Health Organization Disability Assessment Schedule 2.0) was completed 3 months after clinic intake (N = 69). Results: Avoidance and endurance coping were weakly positively correlated with each other at intake (r = .28) and at 1 month postintake (r = .28). Change scores on these two measures over time were not significantly correlated (r = .04). Avoidance coping tended to decrease over time (95% CI 0.6, 2.5; p = .002), whereas changes in endurance coping were variable. In generalized linear modeling, higher avoidance and endurance at clinic intake and increasing (or less rapidly decreasing) levels of these coping styles over 1 month was associated with greater perceived disability ratings at 3 months, even after controlling for postconcussion symptom severity at intake. Conclusion: These findings suggest that avoidance and endurance behavior are distinct coping styles with unique trajectories during the subacute recovery period. The results also support the need for psychologically informed early interventions that target specific profiles of maladaptive coping to mitigate risk for poor outcomes post-mTBI.
Impact and Implications
The present study replicated the previous finding that avoidance and endurance coping were risk factors for chronic disability after mild traumatic brain injury. We also showed here that changes in avoidance and endurance coping over the subacute recovery period contributed unique prognostic value. Maladaptive coping after mild traumatic brain injury may be an important target for early intervention, and tailoring treatment to avoidance versus endurance coping might optimize outcomes.
Repeat exposures to culprit medications are a common cause of preventable adverse drug events. Health information technologies have the potential to reduce repeat adverse drug events by improving ...information continuity. However, they rarely interoperate to ensure providers can view adverse drug events documented in other systems. We designed ActionADE to enable rapid documentation of adverse drug events and communication of standardized information across health sectors by integrating with legacy systems. We will leverage ActionADE's implementation to conduct two parallel, randomized trials: patients with adverse drug reactions in the main trial and those diagnosed with non-adherence in a secondary trial. Primary objective of the main trial is to evaluate the effects of providing information continuity about adverse drug reactions on culprit medication re-dispensations over 12 months. Primary objective of the secondary trial is to evaluate the effect of providing information continuity on adherence over 12 months.
We will conduct two parallel group, triple-blind randomized controlled trials in participating hospitals in British Columbia, Canada. We will enroll adults presenting to hospital with an adverse drug event to prescribed outpatient medication. Clinicians will document the adverse drug event in ActionADE. The software will use an algorithm to determine patient eligibility and allocate eligible patients to experimental or control. In the experimental arm, ActionADE will transmit information to PharmaNet, where adverse drug event information will be displayed in community pharmacies when re-dispensations are attempted. In the control arm, ActionADE will retain information in the local record. We will enroll 3600 adults with an adverse drug reaction into the main trial. The main trial's primary outcome is re-dispensation of a culprit or same-class medication within 12 months; the secondary trial's primary outcome will be adherence to culprit medication. Secondary outcomes include health services utilization and mortality.
These studies have the potential to guide policy decisions and investments needed to drive health information technology integrations to prevent repeat adverse drug events. We present an example of how a health information technology implementation can be leveraged to conduct pragmatic randomized controlled trials.
ClinicalTrials.gov NCT04568668 , NCT04574648 . Registered on 1 October 2020.
We studied the effect of botulinum toxin type A (BTX-A) injections to the scalene muscles on pain in subjects with thoracic outlet syndrome (TOS) in this double-blind, randomized, parallel group ...trial with follow-up at 6 weeks, 3 months, and 6 months. Thirty-eight patients referred to physiatrists for management of TOS with BTX-A injection were included. One subject was lost to follow-up and all other subjects completed the trial. A 75-unit dose of BTX-A reconstituted with 0.75 cc of normal saline was injected to the anterior scalene (37.5 units) and middle scalene (37.5 units) muscles using electromyographic guidance. The primary outcome measure was pain as measured on a horizontal visual analog scale (VAS) 6 weeks-post-injection. Secondary outcomes were paresthesias measured on a VAS and function measured with the Disabilities of the Arm, Shoulder and Hand (DASH) and Short-form 36 (SF-36) questionnaires. For the primary outcome measure of VAS scores for pain at 6 weeks, the difference in the means adjusted for baseline VAS scores between placebo and BTX-A was 5.03 mm in favor of BTX-A (95% confidence interval -15.7 to 5.7, P=.36). Changes in secondary outcome measures were also not statistically significant. We conclude that BTX-A injections to the scalene muscles did not result in clinically or statistically significant improvements in pain, paresthesias, or function in this population of subjects with TOS.
Hip fractures can have a significant impact on the lives of older people and their families. We conducted a pragmatic randomized controlled trial of post-discharge comprehensive geriatric care (CGC) ...for community-dwelling older adults after a surgically repaired hip fracture. The objective of this study was to conduct a secondary analysis to compare changes in health status and perceived capability from baseline to 12 months after randomization with: the EuroQol 5-Dimension (EQ-5D-5L) (1) utility score and (2) visual analog scale (VAS); and (3) well-being as measured by participants' perceptions of their ability (or capability) toward completing life activities using the ICEpop Capability Measure for Older People (ICECAP-O).
We tested the effect of usual care (control) versus usual care and an outpatient CGC clinic (intervention) on mobility after hip fracture in community-dwelling older adults (65 years+). In this secondary analysis, we report the following outcomes: EQ-5D-5L utility score and VAS collected monthly via telephone and ICECAP-O collected in person three times at baseline, 6 months, and 12 months. Data were analyzed using area under the curve and regression adjusted for baseline values for utility scores and capability, and constrained longitudinal data analysis for VAS.
We enrolled 53 older adults, including 34 women and 19 men, with mean (SD) age of 80 (8) years. There were no statistical or clinically meaningful differences between groups (control group - intervention group values) for all variables: utility score = -0.028 (95% CI: -0.071, 0.014; p = 0.18); VAS: -0.03 (95% CI: -0.39 to 0.33; p = 0.86); and capability = -0.021 (95% CI: -0.090, 0.046; p = 0.54).
There were no differences in outcomes between groups over 12 months, but values remained constant, contrary to a potential decline for this age group, especially after a major life event like a hip fracture.
North America is in the midst of an unabated opioid overdose epidemic due to the increasing non-medical use of fentanyl and ultra-potent opioids. Naloxone is an effective antidote to opioid toxicity, ...yet its optimal dosing in the context of fentanyl and ultra-potent opioid overdoses remains unknown. This review aims to determine the relationship between the first empiric dose of naloxone and reversal of toxicity, adverse events, and the total cumulative dose required among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Secondary objectives include evaluating the relationship between the cumulative naloxone dose and toxicity reversal and adverse events, among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids.
To identify studies, we will search MEDLINE, Embase, CENTRAL, DARE, CDAG, CINAHL, Science Citation Index, multiple trial registries, and the gray literature. Included studies will evaluate patients with suspected or confirmed opioid toxicity from undifferentiated opioids and ultra-potent opioids, who received an empiric and possibly additional doses of naloxone. The main outcomes of interest are the relationship between naloxone dose and toxicity reversal and adverse events. We will include controlled and non-controlled interventional studies, observational studies, case reports/series, and reports from poison control centers. We will extract data and assess study quality in duplicate with discrepancies resolved by consensus or a third party. We will use the Downs and Black and Cochrane risk of bias tools for observational and randomized controlled studies. If we find sufficient variation in dose, we will fit a random effects one-stage model to estimate a dose-response relationship. We will conduct multiple subgroup analyses, including by type of opioid used and by suspected high and low prevalence of ultra-potent opioid use based on geographic location and time of the original studies.
Our review will include the most up-to-date available data including ultra-potent opioids to inform the current response to the opioid epidemic, addressing the limitations of recent reviews. We anticipate limitations relating to study heterogeneity. We will disseminate study results widely to update overdose treatment guidelines and naloxone dosing in Take Home Naloxone programs.
Purpose
In drug safety and effectiveness studies based on secondary data, the choice of an appropriate exposure measure for a given outcome can be challenging. Different measures of exposure can ...yield different estimates of treatment effect and safety. There is a knowledge gap with respect to developing and refining measures of drug exposure, to ensure that the exposure measure addresses the study question and is suitable for statistical analysis.
Methods
We present a transparent, step‐by‐step approach to the development of drug exposure measures involving secondary data. This approach would be of interest to students and investigators with initial training in pharmacoepidemiology. We illustrate the approach using a study about Parkinson's disease.
Results
We described the exposure specifications according to the study question. Next, we refined the exposure measure by linking it to knowledge about four major concepts in drug safety and effectiveness studies: drug use patterns, duration, timing, and dose. We then used this knowledge to guide the ultimate choice of exposure measure: time‐varying, cumulative 6‐month exposure to tamsulosin (a drug used to treat prostate hyperplasia).
Conclusions
The proposed approach links exposure specifications to four major concepts in drug safety and effectiveness studies. Formulating subject‐matter knowledge about these major concepts provides an avenue to develop the rationale and specifications for the exposure measure.
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