Information about the accuracy of self-reported food and fluid intake during competitions is scarce. The objective of this study was to validate a previously developed food and fluid exercise ...questionnaire (FFEQ) against direct observations made during competitions in athletes. Fifty-eight recreational endurance athletes participating in four different running events and one cross duathlon in the Netherlands between 2015 and 2017 were recruited. The FFEQ overestimated the median energy and carbohydrate intake by 27.6 kcal/h (20.6%) and 9.25 g/h (30.8%) (
< 0.001), respectively, compared to direct observation. Reporting bias (i.e., correlation between the difference between methods and average of both methods) increased with a higher energy (
: 0.41,
< 0.01) and carbohydrate intake (
: 0.44,
< 0.01). No statistically significant difference was found between FFEQ-reported fluid intake per hour and observations (median difference: -2.93 mL, -1.1%;
= 0.48) and no fluid reporting bias was identified (
: 0.23,
= 0.08). FFEQ-reported energy (
: 0.74), carbohydrate (r: 0.74), and fluid (r: 0.85) intake was strongly correlated with the observed intake (all
-values < 0.001). In conclusion, the FFEQ accurately estimates the fluid intake on a group level during competitions in recreational athletes. Even though FFEQ overestimates the energy and carbohydrate intake, it is still a useful tool for ranking individuals based on their intake.
We sought to determine if a common polymorphism can influence vulnerability to LDL cholesterol, and thereby influence the clinical benefit derived from therapies that reduce LDL cholesterol.
We ...conducted a meta-analysis of the association between a common Trp719Arg polymorphism in the kinesin-like protein 6 (KIF6) gene and the risk of cardiovascular disease (CVD), and a meta-regression analysis to measure the effect modification of this polymorphism on the association between LDL cholesterol and the risk of CVD. We used this measure of genetic effect modification to predict the expected difference in clinical benefit among KIF6 719Arg allele carriers and non-carriers in response to therapies that reduce LDL cholesterol. We then conducted a meta-analysis of statin trials to compare the expected difference in clinical benefit with the observed difference during treatment with a statin.
In a meta-analysis involving 144,931 participants, the KIF6 719Arg allele was not associated with the relative risk (RR) of CVD (RR: 1.02, 95%CI: 0.98-1.07, p=0.288). Meta-regression analysis involving 88,535 participants, however, showed that the 719Arg allele appears to influence the effect of LDL cholesterol on the risk of CVD. KIF6 carriers experienced a 13% greater reduction in the risk of CVD per mmol/L decrease in LDL cholesterol than non-carriers. We interpreted this difference as the expected difference in clinical benefit among KIF6 carriers and non-carriers in response to therapies that lower LDL cholesterol. The difference in clinical benefit predicted by the increased vulnerability to LDL cholesterol among KIF6 carriers (ratio of RR: 0.87, 95%CI: 0.80-0.94, p = 0.001) agreed very closely with the observed difference among 50,060 KIF6 carriers and non-carriers enrolled in 8 randomized trials of statin therapy (ratio of RR: 0.87, 95%CI: 0.77-0.99, p=0.038).
The KIF6 719Arg allele increases vulnerability to LDL cholesterol and thereby influences the expected clinical benefit of therapies that reduce LDL cholesterol.
Histone deacetylase (HDAC) inhibitors have garnered considerable interest for the treatment of adult and pediatric malignant brain tumors. However, owing to their broad-spectrum nature and inability ...to effectively penetrate the blood-brain barrier, HDAC inhibitors have failed to provide substantial clinical benefit to patients with glioblastoma (GBM) to date. Moreover, global inhibition of HDACs results in widespread toxicity, highlighting the need for selective isoform targeting. Although no isoform-specific HDAC inhibitors are currently available, the second-generation hydroxamic acid-based HDAC inhibitor quisinostat possesses subnanomolar specificity for class I HDAC isoforms, particularly HDAC1 and HDAC2. It has been shown that HDAC1 is the essential HDAC in GBM. This study analyzed the neuropharmacokinetic, pharmacodynamic, and radiation-sensitizing properties of quisinostat in preclinical models of GBM. It was found that quisinostat is a well-tolerated and brain-penetrant molecule that extended survival when administered in combination with radiation in vivo. The pharmacokinetic-pharmacodynamic-efficacy relationship was established by correlating free drug concentrations and evidence of target modulation in the brain with survival benefit. Together, these data provide a strong rationale for clinical development of quisinostat as a radiosensitizer for the treatment of GBM.
Dietary patterns are sensitive to differences across socio-economic strata or cultural habits and may impact programing of diseases in later life. The purpose of this study was to identify distinct ...dietary patterns during pregnancy in the Mid-South using factor analysis. Furthermore, we aimed to analyze the differences in the food groups and in macro- and micronutrients among the different food patterns. The study was a cross-sectional analysis of 1155 pregnant women (mean age 26.5 ± 5.4 years; 62% African American, 35% Caucasian, 3% Other; and pre-pregnancy BMI 27.6 ± 7.5 kg/m(2)). Using food frequency questionnaire data collected from participants in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study between 16 and 28 weeks of gestation, dietary patterns were identified using factor analysis. Three major dietary patterns, namely, Healthy, Processed, and US Southern were identified among pregnant women from the Mid-South. Further analysis of the three main patterns revealed four mixed dietary patterns, i.e., Healthy-Processed, Healthy-US Southern, Processed-US Southern, and overall Mixed. These dietary patterns were different (p < 0.001) from each other in almost all the food items, macro- and micro nutrients and aligned across socioeconomic and racial groups. Our study describes unique dietary patterns in the Mid-South, consumed by a cohort of women enrolled in a prospective study examining the association of maternal nutritional factors during pregnancy that are known to affect brain and cognitive development by age 3.
Background: Monitoring cancer trends allows evaluation of the effectiveness of cancer screening or detection methods and determination of priorities in cancer control programs. Government officials ...and policy makers also use information on cancer trends to allocate resources for cancer research and prevention. Although data from the Surveillance, Epidemiology, and End results (SEER)-affiliated cancer registry are accessible to the public, there is a shortage of published research describing cancer incidence rates for White, Black, and other residents in Georgia. The objective of this research is to provide an overview of how to use SEER data through analysis of the incidence rate for cervical cancer. Methods: Cervical cancer cases (ICD-O-3/WHO 2008 =’Cervix Uteri’, corresponding to C530-C539) were obtained from the SEER18 database. It includes the largest geographic coverage compared to SEER 9 and SEER 13 data. The incidence and incidence rates for cervical cancer were obtained, stratified by year (2000-2012), sex, race/ethnic groups, and region (Georgia and US). Age-adjusted incidence and incidence rates (to the 2000 US standard population) were calculated using SEER*Stat software, which is available, free of charge, on the SEER Web site: http://seer.cancer.gov. Results: Age-adjusted incidences and incidence rates in Georgia and the US from SEER 18 data were created by SEER*Stat. The incidence rates were stratified by age variable (5-year category), sex, race/ethnicity, and other socio-demographic variables. Annual percent changes (APC) and 95% CI were also obtained to characterize trends in cancer rates over time. The trends for age-adjusted incidence rates for regions (Georgia and the US) and race (white, black, others) were compared using APC. Furthermore, age-specific incidence and incidence rates for cervical cancer for Georgia and US for recent five years (2008-2012) were reported. Conclusions: The Surveillance, Epidemiology, and End results (SEER) program provides cancer researchers a convenient and intuitive system for viewing individual cancer records and producing statistics useful in studying the impact of cancer on a population.
Background To date, work-hour restrictions have not been imposed on attending surgeons in the United States. The purpose of this study was to investigate the impact of working an overnight trauma ...shift on outcomes of general surgery operations performed the next day by the post-call attending physician. Study Design Consecutive patients over a 3.5-year period undergoing elective general surgical procedures were reviewed. Procedures were limited to hernia repairs (inguinal and ventral), cholecystectomies, and intestinal operations. Any operations that were performed the day after the attending surgeon had taken an overnight trauma shift were considered post-call (PC) cases; all other cases were considered nonpost-call (NP). Outcomes from the PC operations were compared with those from the NP operations. Results There were 869 patients identified; 132 operations were performed PC and 737 were NP. The majority of operations included hernia repairs (46%), followed by cholecystectomies (35%), and intestinal procedures (19%). Overall, the PC operations did not differ from the NP operations with respect to complication rate (13.7% vs 13.5%, p = 0.93) or readmission within 30 days (5% vs 6%, p = 0.84). Additionally, multivariable logistic regression failed to identify an association between PC operations and the development of adverse outcomes. Follow-up was obtained for an average of 3 months. Conclusions Performance of general surgery operations the day after an overnight in-hospital trauma shift did not affect complication rates or readmission rates. At this time, there is no compelling evidence to mandate work-hour restrictions for attending general surgeons.
Objectives The purpose of this study was to estimate the effect of long-term exposure to lower plasma low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD). ...Background LDL-C is causally related to the risk of CHD. However, the association between long-term exposure to lower LDL-C beginning early in life and the risk of CHD has not been reliably quantified. Methods We conducted a series of meta-analyses to estimate the effect of long-term exposure to lower LDL-C on the risk of CHD mediated by 9 polymorphisms in 6 different genes. We then combined these Mendelian randomization studies in a meta-analysis to obtain a more precise estimate of the effect of long-term exposure to lower LDL-C and compared it with the clinical benefit associated with the same magnitude of LDL-C reduction during treatment with a statin. Results All 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I2 = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10−19 ). Conclusions Prolonged exposure to lower LDL-C beginning early in life is associated with a substantially greater reduction in the risk of CHD than the current practice of lowering LDL-C beginning later in life.
Abstract Purpose The purpose of this study was to study the outcome of patients with injection drug use–associated infective endocarditis (IDU-IE) admitted to an intensive care unit (ICU). Material ...and Methods A retrospective review of medical records of 33 consecutive patients with IDU-IE admitted to ICU was conducted. Results Main indications for admission to ICU were as follows: severe sepsis or septic shock (36%), respiratory failure (33%), and neurologic deterioration (18%). Staphylococcus aureus was found in 94% of patients, and 15% had polymicrobial infection. Fifteen (45%) patients had septic emboli to 1 or more organs, including 12 (36%) to lungs and 7 (21%) to central nervous system. In-hospital mortality was 27%, and in univariate analysis, previous history of endocarditis (odds ratio OR, 11.2; P = .03), respiratory failure (OR, 7; P = .03), neurologic failure (OR, 6.25; P = .03), and high Acute Physiology and Chronic Health Evaluation II (OR, 1.21; P = .016) and Sequential Organ Failure Assessment scores (OR, 1.25; P = .01) increased risk of death. By multivariate logistic regression analysis, previous history of endocarditis and high Acute Physiology and Chronic Health Evaluation II score were independently associated with poor survival. Conclusions Complicated IDU-IE necessitating admission to ICU is associated with high mortality. In addition to consequences of sepsis, septic embolization to central nervous system and lungs contributes to development of organ failure. Increased severity of illness and prior history of endocarditis are associated with poor outcome.
Abstract
Even though the randomized controlled trials (RCTs) are still the preferred approach to evaluate the effects of treatments, single-arm study designs have been traditionally used in Phase II ...oncology clinical trials. The single-arm studies using historical control or external control might be inevitable and even fatal when concurrent controls are impractical or unethical in rare and high-risk diseases. Due to recruiting difficulty, ethical and economic reasons, the single-arm trials can be a good option to test the experimental efficacy with the external control data of historical control rates for early efficacy phase 2 trials in glioblastoma. The FDA guidelines on external control data focus on the use of patient-level data from other clinical trials or real-world data (RWD), and so there is no guidance for summary-level historical control. Furthermore, there exist methodological issues to use historical data like identification of relevant data, amount of discounting (time difference and dissimilarity), prior robustness or operating characteristics. In this study, we propose a synthetic data based predictive scoring method optimally to match the historical control data with the characteristic conditions of the experimental studies. We consider both a binary (PFS on six months) and survival (median PFS) endpoints as surrogates for Phase 2 single-arm trials in newly diagnosed and recurrent glioblastoma patients. We perform meta-analysis to summarize the endpoints and the related socio-demographic, treatment and genetic factors from the summary-level historical data. Then we generate the synthetic patients based on the meta-summarized data. The generalized boosted regression models will be used to identify significant characteristics affecting the survival of GBM patients using the synthetic data. Finally the predictive score-based historical data model will be developed to provide the optimal matching with the characteristics of the experimental studies. This study will be validated using existing patient-level data as well as cross-validation methods.
Purpose To determine whether overcorrection shifts occur after vertical rectus recession on adjustable suture in the absence of thyroid eye disease. Methods The medical records of patients without ...thyroid eye disease who underwent vertical rectus recession surgery from 2001 to 2008 were retrospectively reviewed for shifts in alignment between suture adjustment at postoperative day 1 and 2 months’ follow-up. Superior rectus and inferior rectus recessions were compared. In addition, we compared the use of a nonabsorbable polyester suture to an absorbable polyglactin 910 suture in nonthyroid patients undergoing inferior rectus recessions. Results A total of 59 patients were included (superior rectus, 30; inferior rectus, 29). We found a mean undercorrection shift of 1.1 (range, 17.5Δ undercorrection to 16Δ overcorrection) and 1.0Δ (range, 12Δ undercorrection shift to 6Δ overcorrection shift) for superior and inferior rectus recessions, respectively, between 1 day and 2 months postoperatively. Conclusions There was no trend toward overcorrection following unilateral vertical rectus adjustable suture recessions in patients without thyroid eye disease, suggesting that thyroid myopathy may account for overcorrection shifts seen with this surgery.
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