Advanced practice nurse pharmacogenomics capacity and utilization.

BACKGROUND: Guided by Clinical Pharmacogenomic Implementation Consortium (CPIC) guidelines for >140 medications, pharmacogenomic tests inform medication selection and dosing to optimize efficacy while minimizing toxicities. PURPOSE: This study assessed pharmacogenomic self-reported curricular content, knowledge, skills, attitudes, and usage in advanced practice registered nurses (APRNs) with prescriptive privileges. METHODOLOGY: An online survey was administered assessing pharmacogenomic curricular content, knowledge, skills, attitudes, and usage. RESULTS: Data from 266 APRNs were analyzed. Most graduated with their highest nursing degree ∼10 years ago and reported pharmacogenomic curricular content ( n = 124, 48%). Pharmacogenomic curricular content was associated with pharmacogenomic familiarity ( p = .045) but not with knowledge confidence ( p = .615). Pharmacogenomic usage, defined as ordering a pharmacogenomic test within the past year, was low ( n = 76, 29%) and most ( n = 210, 84%) reported never using CPIC Guidelines. Advanced practice registered nurses ( n = 162) who did not anticipate ordering a pharmacogenomic test in the next year ( n = 77, 48%) indicated that they did not know what test to order. CONCLUSIONS: Deficits were identified in APRN pharmacogenomic knowledge and skills despite academic training. Most reported not ordering pharmacogenomic tests, did not know what test to order, and did not use CPIC guidelines. IMPLICATIONS: Pharmacogenomics is a quality and safety issue. Academic training did not result in practice integration and most reported capacity deficits. Recommendation for overcoming academic deficits include: (1) assessment of pharmacogenomics curricular content and faculty teaching capacity; (2) training addressing identified deficiencies; and (3) Commission of Collegiate Nursing Education policies that include pharmacogenomics in advanced pharmacology. Practicing APRN plans include on-the-job training and/or mandatory training at the time of relicensure.

Design and conduct of a randomized controlled feeding trial in a residential setting with mitigation for COVID-19.

BACKGROUND: Evaluating effects of different macronutrient diets in randomized trials requires well defined infrastructure and rigorous methods to ensure intervention fidelity and adherence. METHODS: This controlled feeding study comprised two phases. During a Run-in phase (14-15 weeks), study participants (18-50 years, BMI, ≥27 kg/m2) consumed a very-low-carbohydrate (VLC) diet, with home delivery of prepared meals, at an energy level to promote 15 ± 3% weight loss. During a Residential phase (13 weeks), participants resided at a conference center. They received a eucaloric VLC diet for three weeks and then were randomized to isocaloric test diets for 10 weeks: VLC (5% energy from carbohydrate, 77% from fat), high-carbohydrate (HC)-Starch (57%, 25%; including 20% energy from refined grains), or HC-Sugar (57%, 25%; including 20% sugar). Outcomes included measures of body composition and energy expenditure, chronic disease risk factors, and variables pertaining to physiological mechanisms. Six cores provided infrastructure for implementing standardized protocols: Recruitment, Diet and Meal Production, Participant Support, Assessments, Regulatory Affairs and Data Management, and Statistics. The first participants were enrolled in May 2018. Participants residing at the conference center at the start of the COVID-19 pandemic completed the study, with each core implementing mitigation plans. RESULTS: Before early shutdown, 77 participants were randomized, and 70 completed the trial (65% of planned completion). Process measures indicated integrity to protocols for weighing menu items, within narrow tolerance limits, and participant adherence, assessed by direct observation and continuous glucose monitoring. CONCLUSION: Available data will inform future research, albeit with less statistical power than originally planned.

A comparison between perceived rurality and established geographic rural status among Indiana residents.

The study assessed the association and concordance of the traditional geography-based Rural-Urban Commuting Area (RUCA) codes to individuals' self-reported rural status per a survey scale. The study included residents from rural and urban Indiana, seen at least once in a statewide health system in the past 12 months. Surveyed self-reported rural status of individuals obtained was measured using 6 items with a 7-point Likert scale. Cronbach's alpha was used to measure the internal consistency between the 6 survey response items, along with exploratory factor analysis to evaluate their construct validity. Perceived rurality was compared with RUCA categorization, which was mapped to residential zip codes. Association and concordance between the 2 measures were calculated using Spearman's rank correlation coefficient and Gwet's Agreement Coefficient (Gwet's AC), respectively. Primary self-reported data were obtained through a cross-sectional, statewide, mail-based survey, administered from January 2018 through February 2018, among a random sample of 7979 individuals aged 18 to 75, stratified by rural status and race. All 970 patients who completed the survey answered questions regarding their perceived rurality. Cronbach's alpha value of 0.907 was obtained indicating high internal consistency among the 6 self-perceived rurality items. Association of RUCA categorization and self-reported geographic status was moderate, ranging from 0.28 to 0.41. Gwet's AC ranged from -0.11 to 0.26, indicating poor to fair agreement between the 2 measures based on the benchmark scale of reliability. Geography-based and self-report methods are complementary in assessing rurality. Individuals living in areas of relatively high population density may still self-identify as rural, or individuals with long commutes may self-identify as urban.

Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations.

BACKGROUND: There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. OBJECTIVES: We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. METHODS: We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. RESULTS: A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. CONCLUSIONS: Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.

Incorrect analysis in "Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study" has resulted in incorrect conclusions of demonstrated effects where no such effects have been demonstrated.

In their 2023 Nutrition and Health paper "Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study", Giacomello et al. investigated the effects of an educational intervention based on the Dietary Guidelines for the Brazilian Population among obese women. The authors concluded that the intervention significantly improved weight loss, quality of life, components of metabolic syndrome, and pain. However, we believe the statistical analysis employed in the study was flawed. The authors used within-group changes to draw conclusions, which is known as a difference in nominal significance error. This error has the potential to inflate Type I error rates substantially. To address this issue, we re-analyzed the data obtained from the authors. We focused on body mass and hip circumference and replicated the incorrectly chosen within-group analyses, which remained significant. However, to properly evaluate the intervention's effectiveness, it is essential to compare the differences between the groups directly. Therefore, we calculated change scores for each participant and used independent samples t-tests and linear mixed models to compare between-group differences. Both methods yielded similar non-significant p-values, indicating that there is no significant effect of treatment on body mass or hip circumference. The original paper's conclusions regarding the effectiveness of the intervention are not supported by the proper statistical analysis. The data should be re-analyzed using appropriate between-group comparisons, and the corrected results should be published, or the incorrect results and original paper should be retracted.

Evaluation of Unintended Consequences of COVID-19 Pandemic Restrictions and Obesity Prevalence Among Youths.

This cohort study examines the association between COVID-19 pandemic restrictions and obesity prevalence among youths aged 2 to 19 years in Monroe County, Indiana.

Comparison of health information exchange data with self-report in measuring cancer screening.

BACKGROUND: Efficient measurement of the receipt of cancer screening has been attempted with electronic health records (EHRs), but EHRs are commonly implemented within a single health care setting. However, health information exchange (HIE) includes EHR data from multiple health care systems and settings, thereby providing a more population-based measurement approach. In this study, we set out to understand the value of statewide HIE data in comparison to survey self-report (SR) to measure population-based cancer screening. METHODS: A statewide survey was conducted among residents in Indiana who had been seen at an ambulatory or inpatient clinical setting in the past year. Measured cancer screening tests included colonoscopy and fecal immunochemical test (FIT) for colorectal cancer, human papilloma virus (HPV) and Pap tests for cervical cancer, and mammogram for breast cancer. For each screening test, the self-reported response for receipt of the screening (yes/no) and 'time since last screening' were compared with the corresponding information from patient HIE to evaluate the concordance between the two measures. RESULTS: Gwet's AC for HIE and self-report of screening receipt ranged from 0.24-0.73, indicating a fair to substantial concordance. For the time since receipt of last screening test, the Gwet's AC ranged from 0.21-0.90, indicating fair to almost perfect concordance. In comparison with SR data, HIE data provided relatively more additional information about laboratory-based tests: FIT (19% HIE alone vs. 4% SR alone) and HPV tests (27% HIE alone vs. 12% SR alone) and less additional information about procedures: colonoscopy (8% HIE alone vs. 23% SR alone), Pap test (13% HIE alone vs. 19% SR alone), or mammography (9% HIE alone vs. 10% SR alone). CONCLUSION: Studies that use a single data source should consider the type of cancer screening test to choose the optimal data collection method. HIE and self-report both provided unique information in measuring cancer screening, and the most robust measurement approach involves collecting screening information from both HIE and patient self-report.

Comment on Qiu et al. Effect of Protein-Rich Breakfast on Subsequent Energy Intake and Subjective Appetite in Children and Adolescents: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2021, 13, 2840.

In reading Qiu et al. [...].

Randomized controlled trial of a novel lifestyle intervention used with or without meal replacements in work sites.

OBJECTIVE: Lifestyle interventions have had limited effectiveness in work sites when evaluated in randomized trials. This study assessed the effectiveness of a novel lifestyle intervention for weight loss (Healthy Weight for Living [HWL]) implemented with or without meal replacements (MR) in work sites. HWL used a new behavioral approach emphasizing reducing hunger and building healthy food preferences, and, unlike traditional lifestyle interventions, it did not require calorie counting. METHODS: Twelve work sites were randomized to an 18-month intervention (n = 8; randomization within work sites to HWL, HWL + MR) or 6-month wait-listed control (n = 4). Participants were employees with overweight or obesity (N = 335; age = 48 [SD 10] years; BMI = 33 [6] kg/m2 ; 83% female). HWL was group-delivered in person or by videoconference. The primary outcome was 6-month weight change; secondary outcomes included weight and cardiometabolic risk factors measured at 6, 12, and 18 months in intervention groups. RESULTS: Mean 6-month weight change was -8.8% (95% CI: -11.2% to -6.4%) for enrollees in HWL and -8.0% (-10.4% to -5.5%) for HWL + MR (p < 0.001 for both groups vs. controls), with no difference between interventions (p = 0.40). Clinically meaningful weight loss (≥5%) was maintained at 18 months in both groups (p < 0.001). CONCLUSIONS: A new lifestyle intervention approach, deliverable by videoconference with or without MR, supported clinically impactful weight loss in employees.

RELATIONSHIP BETWEEN REPRODUCTIVE AND BONE BIOMARKERS AND OSTEOARTHRITIS IN ZOO ASIAN (ELEPHAS MAXIMUS) AND AFRICAN (LOXODONTA AFRICANA) ELEPHANTS.

Osteoarthritis (OA) is common in zoo Asian (Elephas maximus) and African (Loxodonta africana) elephants. This study investigated the relationship between confirmed or suspected OA with ovarian cyclicity, gonadotropins, progestagens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and collagen type I (CTX-I) in zoo elephants. In Asian elephants, odds of having confirmed or suspected OA decreased with cycling (OR = 0.22, P = 0.016; OR = 0.29, P = 0.020, respectively), however, not when adjusted for age (odds ratio [OR] = 0.31, P = 0.112; OR = 0.58, P = 0.369, respectively). In African elephants, none of the models between confirmed OA and cycling status were significant (P > 0.060), while the odds of having suspected OA decreased with cycling (OR = 0.12, P = 0.001), even after adjusting for age (OR = 0.15, P = 0.005). Progestagens (Asian elephants P > 0.096; African elephants P > 0.415), LH (Asian P > 0.129; African P > 0.359), and FSH (Asian P > 0.738; African P > 0.231) did not differ with confirmed or suspected OA status, unadjusted. CTX-I concentrations were not related to OA status (P > 0.655). This study concluded hormonal changes may not have a strong impact on OA, so additional investigation into other serologic biomarkers is warranted.

Re-Analysis and Additional Information Needed to Inform Conclusions. Comment on Halenova et al. Deuterium-Depleted Water as Adjuvant Therapeutic Agent for Treatment of Diet-Induced Obesity in Rats. Molecules 2020, 25, 23.

We were interested to read the report by Halenova et al. [...].

French-fried potato consumption and energy balance: a randomized controlled trial.

BACKGROUND: Epidemiologic observations suggest increased potato consumption correlates with weight gain, adiposity, and diabetes risk, whereas nut consumption is associated with weight control and metabolic health. Randomized controlled trial (RCT) data indicate humans respond to changes in energy intake in single dietary components and compensate for extra energy consumed. OBJECTIVES: We completed an RCT testing whether increased daily potato consumption influences energy balance [specifically, fat mass (FM)] compared with calorie-matched almond consumption. METHODS: A 30-d RCT of 180 adults prescribed calorie-matched (300 kcal/d, n = 60 participants/group) than consumed 1 of the following: 1) almonds (almond group), 2) French fries (potato group), or 3) French fries with herb/spices mix (potato + herb/spices group). Baseline and 30-d FM were measured by DXA (primary outcome), with secondary outcomes including body weight and carbohydrate metabolism markers [glycated hemoglobin (HbA1c), fasting blood glucose and insulin, HOMA-IR)]. A subset of 5 participants/group participated in a postprandial meal-based tolerance test. RESULTS: A total of 180 participants were randomly assigned [gender: 67.8% female; mean ± SD age: 30.4 ± 8.7 y; BMI (in kg/m2): 26.1 ± 4.2; and weight: 75.6 ± 15.4 kg], with 12 dropouts and 3 terminations. No significantly different FM changes were observed between almond and potato consumption [combined ± herb/spices; mean ± SE almond: 230.87 ± 114.01 g; potato: 123.73 ± 86.09 g; P = 0.443], fasting glucose (P = 0.985), insulin (P = 0.082), HOMA-IR (P = 0.080), or HbA1c (P = 0.269). Body weight change was not significantly different in the potato groups combined compared with the almond group (P = 0.116), but was significantly different among the 3 groups (P = 0.014; almond: 0.49 ± 0.20 kg; potato: -0.24 ± 0.20 kg; potato + herb/spices: 0.47 ± 0.21 kg). In meal tests, significantly lower post-prandial glucose and insulin responses to almonds compared with potatoes were observed (P = 0.046, P = 0.006, respectively), with potato + herb/spices having intermediate effects. CONCLUSION: There were no significant differences in FM or in glucoregulatory biomarkers after 30 d of potato consumption compared with almonds. Results do not support a causal relation between increased French fried potato consumption and the negative health outcomes studied. This trial was registered at clinicaltrials.gov as NCT03518515.

Evaluation of the type I error rate when using parametric bootstrap analysis of a cluster randomized controlled trial with binary outcomes and a small number of clusters.

BACKGROUND: Cluster randomized controlled trials (cRCTs) are increasingly used but must be analyzed carefully. We conducted a simulation study to evaluate the validity of a parametric bootstrap (PB) approach with respect to the empirical type I error rate for a cRCT with binary outcomes and a small number of clusters. METHODS: We simulated a case study with a binary (0/1) outcome, four clusters, and 100 subjects per cluster. To compare the validity of the test with respect to error rate, we simulated the same experiment with K=10, 20, and 30 clusters, each with 2,000 simulated datasets. To test the null hypothesis, we used a generalized linear mixed model including a random intercept for clusters and obtained p-values based on likelihood ratio tests (LRTs) using the parametric bootstrap method as implemented in the R package "pbkrtest". RESULTS: The PB test produced error rates of 9.1%, 5.5%, 4.9%, and 5.0% on average across all ICC values for K=4, K=10, K=20, and K=30, respectively. The error rates were higher, ranging from 9.1% to 36.5% for K=4, in the models with singular fits (i.e., ignoring clustering) because the ICC was estimated to be zero. CONCLUSION: Using the parametric bootstrap for cRCTs with a small number of clusters results in inflated error rates and is not valid.

Bifidobacteriumlongum subsp. infantis EVC001 Administration Is Associated with a Significant Reduction in the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants.

OBJECTIVE: To assess the effects of Bifidobacteriumlongum subsp. infantis EVC001 (Binfantis EVC001) administration on the incidence of necrotizing enterocolitis (NEC) in preterm infants in a single level IV neonatal intensive care unit (NICU). STUDY DESIGN: Nonconcurrent retrospective analysis of 2 cohorts of very low birth weight (VLBW) infants not exposed and exposed to Binfantis EVC001 probiotic at Oregon Health & Science University from 2014 to 2020. Outcomes included NEC incidence and NEC-associated mortality, including subgroup analysis of extremely low birth weight (ELBW) infants. Log-binomial regression models were used to compare the incidence and risk of NEC-associated outcomes between the unexposed and exposed cohorts. RESULTS: The cumulative incidence of NEC diagnoses decreased from 11.0% (n = 301) in the no EVC001 (unexposed) cohort to 2.7% (n = 182) in the EVC001 (exposed) cohort (P < .01). The EVC001 cohort had a 73% risk reduction of NEC compared with the no EVC001 cohort (adjusted risk ratio, 0.27; 95% CI, 0.094-0.614; P < .01) resulting in an adjusted number needed to treat of 13 (95% CI, 10.0-23.5) for Binfantis EVC001. NEC-associated mortality decreased from 2.7% in the no EVC001 cohort to 0% in the EVC001 cohort (P = .03). There were similar reductions in NEC incidence and risk for ELBW infants (19.2% vs 5.3% [P < .01]; adjusted risk ratio, 0.28; 95% CI, 0.085-0.698 [P = .02]) and mortality (5.6% vs 0%; P < .05) in the 2 cohorts. CONCLUSIONS: In this observational study of 483 VLBW infants, Binfantis EVC001 administration was associated with significant reductions in the risk of NEC and NEC-related mortality. Binfantis EVC001 supplementation may be considered safe and effective for reducing morbidity and mortality in the NICU.

Randomization, design and analysis for interdependency in aging research: no person or mouse is an island.

Investigators traditionally use randomized designs and corresponding analysis procedures to make causal inferences about the effects of interventions, assuming independence between an individual's outcome and treatment assignment and the outcomes of other individuals in the study. Often, such independence may not hold. We provide examples of interdependency in model organism studies and human trials and group effects in aging research and then discuss methodologic issues and solutions. We group methodologic issues as they pertain to (1) single-stage individually randomized trials; (2) cluster-randomized controlled trials; (3) pseudo-cluster-randomized trials; (4) individually randomized group treatment; and (5) two-stage randomized designs. Although we present possible strategies for design and analysis to improve the rigor, accuracy and reproducibility of the science, we also acknowledge real-world constraints. Consequences of nonadherence, differential attrition or missing data, unintended exposure to multiple treatments and other practical realities can be reduced with careful planning, proper study designs and best practices.