Exploring Biases of the Healthy Eating Index and Alternative Healthy Eating Index When Scoring Low-Carbohydrate and Low-Fat Diets.

BACKGROUND: The Healthy Eating Index 2010 (HEI-2010) and Alternative Healthy Eating Index 2010 (AHEI-2010) are commonly used to measure dietary quality in research settings. Neither index is designed specifically to compare diet quality between low-carbohydrate (LC) and low-fat (LF) diets. It is unknown whether biases exist in making these comparisons. OBJECTIVE: The aim was to determine whether HEI-2010 and AHEI-2010 contain biases when scoring LC and LF diets. DESIGN: Secondary analyses of the Diet Intervention Examining the Factors Interacting With Treatment Success (DIETFITS) weight loss trial were conducted. The trial was conducted in the San Francisco Bay Area of California between January 2013 and May 2016. Three approaches were used to investigate whether biases existed for HEI-2010 and AHEI-2010 when scoring LC and LF diets. PARTICIPANTS/SETTING: DIETFITS participants were assigned to follow healthy LC or healthy LF diets for 12 months (n = 609). MAIN OUTCOMES MEASURES: Mean diet quality index scores for each diet were measured. STATISTICAL ANALYSIS: Approach 1 examined both diet quality indices' scoring criteria. Approach 2 compared scores garnered by exemplary quality LC and LF menus created by registered dietitian nutritionists. Approach 3 used 2-sided t tests to compare the HEI-2010 and AHEI-2010 scores calculated from 24-hour dietary recalls of DIETFITS trial participants (n = 608). RESULTS: Scoring criteria for both HEI-2010 (100 possible points) and AHEI-2010 (110 possible points) were estimated to favor an LF diet by 10 points. Mean scores for exemplary quality LF menus were higher than for LC menus using both HEI-2010 (91.8 vs 76.8) and AHEI-2010 (71.7 vs 64.4, adjusted to 100 possible points). DIETFITS participants assigned to a healthy LF diet scored significantly higher on HEI and AHEI than those assigned to a healthy LC diet at 3, 6, and 12 months (all, P < .001). Mean baseline scores were lower than mean scores at all follow-up time points regardless of diet assignment or diet quality index used. CONCLUSIONS: Commonly used diet quality indices, HEI-2010 and AHEI-2010, showed biases toward LF vs LC diets. However, both indices detected expected changes in diet quality within each diet, with HEI-2010 yielding greater variation in scores. Findings support the use of these indices in measuring diet quality differences within, but not between, LC and LF diets.

Testing for Primary Hyperparathyroidism in 17,491 Patients With Hypercalcemia.

BACKGROUND: Primary hyperparathyroidism (PHPT) is underdiagnosed and associated with many adverse health effects. Historically, many hypercalcemic patients have not received parathyroid hormone (PTH) testing; however, underlying reasons are uncertain. Our goals are to determine the PTH testing rate among hypercalcemic individuals at a large academic health system and to assess for characteristics associated with testing versus not testing for PHPT to inform future strategies for closing testing gaps. METHODS: This retrospective study included adult patients with ≥1 elevated serum calcium result between 2018 and 2022. Based on the presence or absence of a serum PTH result, individuals were classified as "screened" versus "unscreened" for PHPT. Demographic and clinical characteristics of these groups were compared. RESULTS: The sample comprised 17,491 patients: 6567 male (37.5%), 10,924 female (62.5%), mean age 59 y. PTH testing was performed in 6096 (34.9%). Characteristics independently associated with the greatest odds of screening were 5+ elevated calcium results (odds ratio [OR] 5.02, P < 0.0001), chronic kidney disease (OR 3.63, P < 0.0001), maximum calcium >12.0 mg/dL (OR 2.48, P < 0.0001), and osteoporosis (OR 2.42, P < 0.0001). Characteristics associated with lowest odds of screening were age <35 y (OR 0.60, P < 0.0001), death during the study period (OR 0.68, P < 0.0001), age ≥85 y (OR 0.70, P = 0.0007), and depression (OR 0.84; P = 0.0081). CONCLUSIONS: Only 35% of hypercalcemic patients received PTH testing. Although the presence of PHPT-associated morbidity was generally associated with increased rates of screening, hypercalcemic patients with depression were 16% less likely to be tested.

Automated generation of comparator patients in the electronic medical record.

Background: Well-designed randomized trials provide high-quality clinical evidence but are not always feasible or ethical. In their absence, the electronic medical record (EMR) presents a platform to conduct comparative effectiveness research, central to the emerging academic learning health system (aLHS) model. A barrier to realizing this vision is the lack of a process to efficiently generate a reference comparison group for each patient. Objective: To test a multi-step process for the selection of comparators in the EMR. Materials and Methods: We conducted a mixed-methods study within a large aLHS in North Carolina. We (1) created a list of 35 candidate variables; (2) surveyed 270 researchers to assess the importance of candidate variables; and (3) built consensus rankings around survey-identified variables (ie, importance scores >7) across two panels of 7-8 clinical research experts. Prioritized algorithm inputs were collected from the EMR and applied using a greedy matching technique. Feasibility was measured as the percentage of patients with 100 matched comparators and performance was measured via computational time and Euclidean distance. Results: Nine variables were selected: age, sex, race, ethnicity, body mass index, insurance status, smoking status, Charlson Comorbidity Index, and neighborhood percentage in poverty. The final process successfully generated 100 matched comparators for each of 1.8 million candidate patients, executed in less than 100 min for the majority of strata, and had average Euclidean distance 0.043. Conclusion: EMR-derived matching is feasible to implement across a diverse patient population and can provide a reproducible, efficient source of comparator data for observational studies, with additional testing in clinical research applications needed.

Role of continuous pulse oximetry and capnography monitoring in the prevention of postoperative respiratory failure, postoperative opioid-induced respiratory depression and adverse outcomes on hospital wards: A systematic review and meta-analysis.

OBJECTIVE: The current standards of postoperative respiratory monitoring on medical-surgical floors involve spot-pulse oximetry checks every 4-8 h, which can miss the opportunity to detect prolonged hypoxia and acute hypercapnia. Continuous respiratory monitoring can recognize acute respiratory depression episodes; however, the existing evidence is limited. We sought to review the current evidence on the effectiveness of continuous pulse oximetry (CPOX) with and without capnography versus routine monitoring and their effectiveness for detecting postoperative respiratory failure, opioid-induced respiratory depression, and preventing downstream adverse events. METHODS: We performed a systematic literature search on Ovid Medline, Embase, and Cochrane Library databases for articles published between 1990 and April 2023. The study protocol was registered in Prospero (ID: 439467), and PRISMA guidelines were followed. The NIH quality assessment tool was used to assess the quality of the studies. Pooled analysis was conducted using the software R version 4.1.1 and the package meta. The stability of the results was assessed using sensitivity analysis. DESIGN: Systematic Review and Meta-Analysis. SETTING: Postoperative recovery area. PATIENTS: 56,538 patients, ASA class II to IV, non-invasive respiratory monitoring, and post-operative respiratory depression. INTERVENTIONS: Continuous pulse oximetry with or without capnography versus routine monitoring. MEASUREMENTS: Respiratory rate, oxygen saturation, adverse events, and rescue events. RESULTS: 23 studies (17 examined CPOX without capnography and 5 examined CPOX with capnography) were included in this systematic review. CPOX was better at recognizing desaturation (SpO2 < 90%) OR: 11.94 (95% CI: 6.85, 20.82; p < 0.01) compared to standard monitoring. No significant differences were reported for ICU transfer, reintubation, and non-invasive ventilation between the two groups. CONCLUSIONS: Oxygen desaturation was the only outcome better detected with CPOX in postoperative patients in hospital wards. These comparisons were limited by the small number of studies that could be pooled for each outcome and the heterogeneity between the studies.

Association of Lifestyle Intervention With Risk for Cardiovascular Events Differs by Level of Glycated Hemoglobin.

PURPOSE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c). METHODS: Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on CVD risk by baseline HbA1c. RESULTS: Mean baseline HbA1c was 7.3% (SD 1.2) and ranged from 4.4% (quintile 1) to 14.5% (quintile 5). We observed additive and multiplicative heterogeneity of the association between ILI and CVD (all P < .001) by baseline HbA1c. Randomization to ILI was associated with lower CVD risk for HbA1c quintiles 1 [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.53, 0.88] and 2 (HR: 0.80, 95% CI: 0.66, 0.96) and associated with higher CVD risk for HbA1c quintile 5 (HR: 1.27, 95% CI: 1.02, 1.58), compared to DSE. CONCLUSION: Among adults with type 2 diabetes and overweight/obesity, randomization to a lifestyle intervention was differentially associated with CVD risk by baseline HbA1c such that it was associated with lower risk at lower HbA1c levels and higher risk at higher HbA1c levels. There is a critical need to develop and tailor lifestyle interventions to be successful for individuals with type 2 diabetes and high HbA1c.

Association of dietary adherence and dietary quality with weight loss success among those following low-carbohydrate and low-fat diets: a secondary analysis of the DIETFITS randomized clinical trial.

BACKGROUND: Eating a high-quality diet or adhering to a given dietary strategy may influence weight loss. However, these 2 factors have not been examined concurrently for those following macronutrient-limiting diets. OBJECTIVE: To determine whether improvement in dietary quality, change in dietary macronutrient composition, or the combination of these factors is associated with differential weight loss when following a healthy low-carbohydrate (HLC) or healthy low-fat (HLF) diet. DESIGN: Generally healthy adults were randomly assigned to HLC or HLF diets for 12 mo (n = 609) as part of a randomized controlled weight loss study. Participants with complete 24-h dietary recall data at baseline and 12-mo were included in this secondary analysis (total N = 448; N = 224 HLC, N = 224 HLF). Participants were divided into 4 subgroups according to 12-mo change in HEI-2010 score [above median = high quality (HQ) and below median = low quality (LQ)] and 12-mo change in macronutrient intake [below median = high adherence (HA) and above median = low adherence (LA) for net carbohydrate (g) or fat (g) for HLC and HLF, respectively]. Baseline to 12-mo changes in mean BMI were compared for those in HQ/HA, HQ/LA, LQ/HA subgroups with the LQ/LA subgroup within HLC and HLF. RESULTS: For HLC, changes (95 % confidence level [CI]) in mean BMI were -1.15 kg/m2 (-2.04, -0.26) for HQ/HA, -0.30 (-1.22, 0.61) for HQ/LA, and -0.80 (-1.74, 0.14) for LQ/HA compared with the LQ/LA subgroup. For HLF, changes (95% CI) in mean BMI were -1.11kg/m2 (-2.10, -0.11) for HQ/HA, -0.26 (-1.26, 0.75) for HQ/LA, and -0.66 (-1.74, 0.41) for LQ/HA compared with the LQ/LA subgroup. CONCLUSION: Within both HLC and HLF diet arms, 12-mo decrease in BMI was significantly greater in HQ/HA subgroups relative to LQ/LA subgroups. Neither HQ nor HA alone were significantly different than LQ/LA subgroups. Results of this analysis support the combination of dietary adherence and high-quality diets for weight loss. CLINICAL TRIAL REGISTRY: clinicaltrials.gov (Identifier: NCT01826591).

Corrigendum: Weight, insulin resistance, blood lipids, and diet quality changes associated with ketogenic and ultra low-fat dietary patterns: a secondary analysis of the DIETFITS randomized clinical trial.

[This corrects the article DOI: 10.3389/fnut.2023.1220020.].

Uric Acid Is Not Associated With Cardiovascular Health in Youth With Type 1 Diabetes: SEARCH for Diabetes in Youth Study.

CONTEXT: Uric acid's role in cardiovascular health in youth with type 1 diabetes is unknown. OBJECTIVE: Investigate whether higher uric acid is associated with increased blood pressure (BP) and arterial stiffness over time in adolescents and young adults with type 1 diabetes and if overweight/obesity modifies this relationship. METHODS: Longitudinal analysis of data from adolescents and young adults with type 1 diabetes from 2 visits (mean follow up 4.6 years) in the SEARCH for Diabetes in Youth multicenter prospective cohort study from 2007 to 2018. Our exposure was uric acid at the first visit and our outcome measures were the change in BP, pulse wave velocity (PWV), and augmentation index between visits. We used multivariable linear mixed-effects models and assessed for effect modification by overweight/obesity. RESULTS: Of 1744 participants, mean age was 17.6 years, 49.4% were female, 75.9% non-Hispanic White, and 45.4% had a follow-up visit. Mean uric acid was 3.7 mg/dL (SD 1.0). Uric acid was not associated with increased BP, PWV-trunk, or augmentation index over time. Uric acid was marginally associated with PWV-upper extremity (ß = .02 m/s/year, 95% CI 0.002 to 0.04). The magnitude of this association did not differ by overweight/obesity status. CONCLUSION: Among adolescents and young adults with type 1 diabetes, uric acid was not consistently associated with increased BP or arterial stiffness over time. These results support findings from clinical trials in older adults with diabetes showing that lowering uric acid levels does not improve cardiovascular outcomes.

Skin Tone and Gender of High-Fidelity Simulation Manikins in Emergency Medicine Residency Training and their Use in Cultural Humility Training.

INTRODUCTION: It is important for physicians to learn how to provide culturally sensitive care. Cultural humility is defined as a lifelong process with a goal of fixing power imbalances and creating institutional accountability through learning about another's culture as well as performing self-exploration about one's own beliefs, identities, and biases. One way to teach cultural humility in medicine is simulation. However, there are no peer-reviewed published studies that examine whether the skin tone or gender of the high-fidelity simulation manikins (HFSM) used by emergency medicine (EM) residency programs reflects the US population nor whether high-fidelity simulation is used to teach cultural humility. We aimed to address that gap in the literature. Our primary objective was to evaluate what proportion of EM residency programs use HFS to teach cultural humility. Our secondary objective was to evaluate whether the skin tone and gender breakdown of the EM residency program HFSM is representative of the US population. METHODS: We conducted a simple random sample of 80 EM residency programs to characterize HFSM and cultural humility training. Selected programs were emailed a questionnaire. Key outcomes included HFSM skin tone and gender and whether cultural humility was taught via HFSM. We calculated point and interval estimates for the proportion of dark-, medium-, and light-toned skin and the proportion of female and male manikins. Confidence intervals were employed to test the null hypothesis that dark/medium/light skin tone was 20/20/60 and that the female/male ratio was 50/50. Both ratios were extrapolated from the US Census data. RESULTS: Our response rate was 74% (59/80). Fifty-five of 59 EM residency programs that had manikins (0.93, 95% confidence interval [CI] 0.88-0.99) reported data on a total of 348 manikins. Thirty-nine of the 55 programs with manikins reported using HFS to teach cultural humility (0.71, 95% CI 0.60-0.82). Proportions of light-, medium-, and dark-toned manikins were 0.52 (0.43-0.62), 0.38 (0.29-0.47), and 0.10 (0.07-0.14), respectively. Proportions of male and female HFSM were 0.69 (0.64-0.76) and 0.31 (0.24-0.36), respectively. The null hypotheses that skin tone follows a 60/20/20 split and gender follows a 50/50 split were rejected, as not all confidence intervals contained these hypothesized values. CONCLUSION: While most EM residency programs surveyed use high-fidelity simulation to teach cultural humility, the manikins do not reflect either the skin tone or gender of the US population.

Weight, insulin resistance, blood lipids, and diet quality changes associated with ketogenic and ultra low-fat dietary patterns: a secondary analysis of the DIETFITS randomized clinical trial.

Background: The DIETFITS trial reported no significant difference in 12-month weight loss between a healthy low-fat and healthy low-carbohydrate diet. Participants were instructed to restrict fat or carbohydrates to levels consistent with a ketogenic or ultra low-fat diet for 2 months and to subsequently increase intakes until they achieved a comfortable maintenance level. Objective: To compare 3- and 12-month changes in body weight and cardiometabolic risk factors between a subsample of participants who reported 3-month fat or carbohydrates intakes consistent with either a ketogenic-like diet (KLD) or ultra low-fat diet (ULF). Design: 3-month and 12-month weight and risk factor outcomes were compared between KLD (n = 18) and ULF (n = 21) sub-groups of DIETFITS participants (selected from n = 609, healthy overweight/obese, aged 18-50 years). Results: Less than 10% of DIETFITS participants met KLD or ULF criteria at 3-months. Both groups achieved similar weight loss and insulin resistance improvements at 3-months and maintained them at 12- months. Significant differences at 3-months included a transient ~12% increase in LDL cholesterol (LDL-C) for KLD with a concomitant greater reduction in log(TG/HDL), a measure of LDL-C's atherogenic potential. The latter was maintained at 12-months, despite substantial diet recidivism for both groups, whereas LDL-C levels were similar for ULF at baseline and 12-months. KLD participants achieved and maintained the greatest reductions in added sugars and refined grains at 3- months and 12-months, whereas ULF participants reported a 50% increase in refined grains intake from baseline to 12-months. Conclusion: Among the ~10% of study participants that achieved the most extreme restriction of dietary fat vs. carbohydrate after 3 months, weight loss and improvement in insulin sensitivity were substantial and similar between groups. At 12 months, after considerable dietary recidivism, the few significant differences in diet quality and blood lipid parameters tended to favor KLD over ULF.

Association of CT-Derived Skeletal Muscle and Adipose Tissue Metrics with Frailty in Older Adults.

RATIONALE AND OBJECTIVES: Tools are needed for frailty screening of older adults. Opportunistic analysis of body composition could play a role. We aim to determine whether computed tomography (CT)-derived measurements of muscle and adipose tissue are associated with frailty. MATERIALS AND METHODS: Outpatients aged ≥ 55 years consecutively imaged with contrast-enhanced abdominopelvic CT over a 3-month interval were included. Frailty was determined from the electronic health record using a previously validated electronic frailty index (eFI). CT images at the level of the L3 vertebra were automatically segmented to derive muscle metrics (skeletal muscle area [SMA], skeletal muscle density [SMD], intermuscular adipose tissue [IMAT]) and adipose tissue metrics (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT]). Distributions of demographic and CT-derived variables were compared between sexes. Sex-specific associations of muscle and adipose tissue metrics with eFI were characterized by linear regressions adjusted for age, race, ethnicity, duration between imaging and eFI measurements, and imaging parameters. RESULTS: The cohort comprised 886 patients (449 women, 437 men, mean age 67.9 years), of whom 382 (43%) met the criteria for pre-frailty (ie, 0.10 < eFI ≤ 0.21) and 138 (16%) for frailty (eFI > 0.21). In men, 1 standard deviation changes in SMD (ß = -0.01, 95% confidence interval [CI], -0.02 to -0.001, P = .02) and VAT area (ß = 0.008, 95% CI, 0.0005-0.02, P = .04), but not SMA, IMAT, or SAT, were associated with higher frailty. In women, none of the CT-derived muscle or adipose tissue metrics were associated with frailty. CONCLUSION: We observed a positive association between frailty and CT-derived biomarkers of myosteatosis and visceral adiposity in a sex-dependent manner.

Prevalence, Progression, and Modifiable Risk Factors for Diabetic Retinopathy in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To determine the prevalence, progression, and modifiable risk factors associated with the development of diabetic retinopathy (DR) in a population-based cohort of youth-onset diabetes. RESEARCH DESIGN AND METHODS: We conducted a multicenter, population-based prospective cohort study (2002-2019) of youth and young adults with youth-onset type 1 diabetes (n = 2,519) and type 2 diabetes (n = 447). Modifiable factors included baseline and change from baseline to follow-up in BMI z score, waist/height ratio, systolic and diastolic blood pressure z score, and A1C. DR included evidence of mild or moderate nonproliferative DR or proliferative retinopathy. Prevalence estimates were standardized to estimate the burden of DR, and inverse probability weighting for censoring was applied for estimating risk factors for DR at two points of follow-up. RESULTS: DR in youth-onset type 1 and type 2 diabetes is highly prevalent, with 52% of those with type 1 diabetes and 56% of those with type 2 diabetes demonstrating retinal changes at follow-up (mean [SD] 12.5 [2.2] years from diagnosis). Higher baseline A1C, increase in A1C across follow-up, and increase in diastolic and systolic blood pressure were associated with the observation of DR at follow-up for both diabetes types. Increase in A1C across follow-up was associated with retinopathy progression. BMI z score and waist/height ratio were inconsistently associated, with both positive and inverse associations noted. CONCLUSIONS: Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ∼12 years postdiagnosis. Tight glucose and blood pressure management may offer the opportunity to mitigate development and progression of DR in youth-onset diabetes.

Diagnosis of Bacterial Tracheostomy-Associated Respiratory Tract Infections in Pediatric Patients.

OBJECTIVES: To identify demographic and clinical characteristics of children with fever and/or respiratory illness associated with a diagnosis of bacterial tracheostomy-associated respiratory tract infections (bTARTI). Secondary objectives included comparison of diagnostic testing, length of stay (LOS), and readmission rates between children diagnosed with bTARTI and others. METHODS: We performed a retrospective chart review of encounters over 1 year for fever and/or respiratory illness at a single academic children's hospital for children with tracheostomy dependence. Patient characteristics, features of presenting illness, and laboratory and imaging results were collected. Generalized linear mixed models were employed to study associations between patient characteristics, diagnosis of bTARTI, and impact on LOS or readmission rates. RESULTS: Among 145 children with tracheostomies identified, 79 children contributed 208 encounters. bTARTI was diagnosed in 66 (31.7%) encounters. Significant associations with bTARTI diagnosis included chest radiograph consistent with bacterial pneumonia (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.50-2.08), positive tracheal aspirate culture (OR, 1.3; 95% CI, 1.05-1.61), higher white blood cell count (16.4 vs 13.1 × 103/µ; P = .03), change in oxygen requirement (OR, 1.14; 95% CI, 1.00-1.31), telephone encounter (OR, 1.41; 95% CI, 1.09-1.81), and living at home with family (OR, 1.42; 95% CI, 1.06-1.92). LOS for admitted patients with bTARTI was 2.19 times longer (CI, 1.23-3.88). CONCLUSIONS: In our single-center study, we identified several clinical and nonclinical factors associated with a diagnosis of bTARTI. Despite widespread use, few laboratory tests were predictive of a diagnosis of bTARTI. There is need for standardization in diagnosis.

Development and evaluation of a novel dietary bisphenol A (BPA) exposure risk tool.

BACKGROUND: Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) is primarily from the diet through canned foods. Characterizing dietary exposures can be conducted through biomonitoring and dietary surveys; however, these methods can be time-consuming and challenging to implement. METHODS: We developed a novel dietary exposure risk questionnaire to evaluate BPA exposure and compared these results to 24-hr dietary recall data from participants (n = 404) of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study, a dietary clinical trial, to validate questionnaire responses. High BPA exposure foods were identified from the dietary recalls and used to estimate BPA exposure. Linear regression models estimated the association between exposure to BPA and questionnaire responses. A composite risk score was developed to summarize questionnaire responses. RESULTS: In questionnaire data, 65% of participants ate canned food every week. A composite exposure score validated that the dietary exposure risk questionnaire captured increasing BPA exposure. In the linear regression models, utilizing questionnaire responses vs. 24-hr dietary recall data, participants eating canned foods 1-2 times/week (vs. never) consumed 0.78 more servings (p < 0.001) of high BPA exposure foods, and those eating canned foods 3+ times/week (vs. never) consumed 0.89 more servings (p = 0.013) of high BPA exposure foods. Participants eating 3+ packaged items/day (vs. never) consumed 62.65 more total grams of high BPA exposure food (p = 0.036). CONCLUSIONS: Dietary exposure risk questionnaires may provide an efficient alternative approach to 24-hour dietary recalls to quantify dietary BPA exposure with low participant burden. TRIAL REGISTRATION: The trial was prospectively registered at clinicaltrials.gov as NCT01826591 on April 8, 2013.

stratamatch: Prognostic Score Stratification Using a Pilot Design.

In a block-randomized controlled trial, individuals are subdivided by prognostically important baseline characteristics (e.g., age group, sex, or smoking status), prior to randomization. This step reduces the heterogeneity between the treatment groups with respect to the baseline factors most important to determining the outcome, thus enabling more precise estimation of treatment effect. The stratamatch package extends this approach to the observational setting by implementing functions to separate an observational data set into strata and interrogate the quality of different stratification schemes. Once an acceptable stratification is found, treated and control individuals can be matched by propensity score within strata, thereby recapitulating the block-randomized trial design for the observational study. The stratification scheme implemented by stratamatch applies a "pilot design" approach (Aikens, Greaves, and Baiocchi 2019) to estimate a quantity called the prognostic score (Hansen 2008), which is used to divide individuals into strata. The potential benefits of such an approach are twofold. First, stratifying the data enables more computationally efficient matching of large data sets. Second, methodological studies suggest that using a prognostic score to inform the matching process increases the precision of the effect estimate and reduces sensitivity to bias from unmeasured confounding factors (Aikens et al. 2019; Leacy and Stuart 2014; Antonelli, Cefalu, Palmer, and Agniel 2018). A common mistake is to believe reserving more data for the analysis phase of a study is always better. Instead, the stratamatch approach suggests how clever use of data in the design phase of large studies can lead to major benefits in the robustness of the study conclusions.

Association Between Patient-Reported Outcomes and Treatment Failure in Juvenile Idiopathic Arthritis.

OBJECTIVE: Children with juvenile idiopathic arthritis (JIA) frequently exhibit symptoms months before diagnosis. The aims of this study were to assess whether baseline patient-reported outcomes (PROs) are associated with changes in JIA pharmacotherapy treatment and whether symptom duration prior to JIA diagnosis is associated with disease activity scores over time. METHODS: This is a retrospective cohort study of patients with an incident diagnosis of JIA. Patient-reported symptom duration, pain, energy, disease activity, sleep, anxiety, and depression screenings, as well as provider-reported disease activity and joint count, were collected during routine clinical care. Cox proportional hazards evaluated PROs, disease activity scores, and symptom duration with initial medication failure within 9 months of diagnosis. Multivariate mixed effects linear regression evaluated the association of symptom duration with disease activity scores. RESULTS: There were 58 children (66% female, 35% oligoarticular JIA) in the cohort. Nearly half of patients failed initial therapy within 9 months. Unadjusted analysis showed that higher energy (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.69-0.99; P = 0.04) and longer symptom duration (HR: 0.96; 95% CI: 0.93-0.99; P = 0.03) at diagnosis were protective against medication failure. Adjusted analysis showed that symptom duration prior to diagnosis was protective against medication failure (HR: 0.95; 95% CI: 0.92-0.99; P = 0.02); there was no association between medication failure and pain, psychiatric symptoms, or disease activity scores. There was a positive association with longer symptom duration and higher disease activity at 30 and 60 days, but this was not sustained. CONCLUSION: Higher energy levels and longer symptom duration are protective against initial JIA treatment failures. Initial treatments informed by patient-reported data could lead to more successful outcomes by changes in treatment paradigms.

Social Risk Factors Influence Pediatric Emergency Department Utilization and Hospitalizations.

OBJECTIVE: To characterize the association of children's social risk factors with total number of emergency department (ED) visits or hospitalization and time to first subsequent ED or hospitalization. STUDY DESIGN: This was a retrospective cohort study of patients seen at a general pediatric clinic between 2017 and 2021 with documented ≥1 social risk factors screened per visit. Negative binomial or Poisson regression modeled ED utilization and hospitalizations as functions of the total number of risk factors or each unique risk factor. Time-varying Cox models were used to evaluate differences between those who screened positive and those who screened negative, controlling for demographic and clinical covariates. RESULTS: Overall, 4674 patients (mean age, 6.6 years; 49% female; 64% Hispanic; 21% Black) were evaluated across a total of 20 927 visits. Children with risk factors had higher rates of attention-deficit hyperactivity disorder, failure to gain weight, asthma, and prematurity compared with children with no risk (all P < .01). Adjusted models show a positive association between increased total number of factors and ED utilization (incidence rate ratio [IRR], 1.18; 95% CI, 1.12-1.23) and hospitalizations (IRR, 1.36; 95% CI, 1.26-1.47). There were no associations between a positive screen and time to first ED visit (hazard ratio [HR], 0.95; 95% CI, 0.85-1.06; P = .36) or hospitalization (HR, 1.15; 95% CI, 0.84-1.59; P = .40). CONCLUSIONS: Social risk factors were associated with increased ED utilization and hospitalizations at the patient level but were not significantly associated with time to subsequent acute care use. Future research should evaluate the effect of focused interventions on health care utilization, such as those addressing food insecurity and transportation challenges.

Duration of Antibiotic Therapy in Necrotizing Soft Tissue Infections: Shorter is Safe.

Background: Early debridement improves outcome in necrotizing soft tissue infection (NSTI), but there is no consensus on duration of antimicrobial therapy. We recently changed practice to discontinue antibiotic agents early with a goal of 48 hours after adequate source control. We hypothesized that discontinuing antibiotic agents after a short course is safe in the treatment of NSTI. Patients and Methods: This was a prospective study of patients with NSTI comparing short duration of antibiotic agents to a control population after a change in practice. In 2018 we began discontinuing antibiotic agents within 48 hours of source control (absence of cellulitis and no evidence of active infection). Previously, antibiotic duration was at the discretion of the attending surgeon (generally 7-10 days). Patients were excluded from analysis if they were initially debrided at a referring facility, immune compromised, or died prior to source control. Patient characteristics and outcomes were evaluated. The primary outcome was treatment failure requiring antibiotic agents to be restarted with or without further debridement of infected tissue. Secondary outcomes included the duration of antibiotic therapy after source control. Results: We evaluated 151 patients; 119 admitted between January 1, 2011 and January 31, 2018 (PRE) and 32 admitted after January 31, 2018 (POST). Patients were not statistically different regarding characteristics, admission physiologic variables, and comorbidities. The median duration of antibiotic agents after source control in the PRE group was 180.3 hours (interquartile range [IQR], 100.7-318.8) versus 48 hours (IQR, 32.3-100.8) in the POST group (p < 0.01). Patients in each group were treated as described above, and treatment failure occurred in seven (5.9%) PRE patients and two (6.3%) POST (99.3% post hoc power at non-inferiority limit 20%, significance p < 0.05). Thirty-day all-cause mortality was not different between groups (6.7% vs. 6.3%; p = 0.94). Conclusions: Short-duration (48 hours) antibiotic agents after NSTI source control is as safe and effective as a longer course.

Associations between persistent organic pollutants and type 1 diabetes in youth.

BACKGROUND: Diabetes affects millions of people worldwide with a continued increase in incidence occurring within the pediatric population. The potential contribution of persistent organic pollutants (POPs) to diabetes in youth remains poorly known, especially regarding type 1 diabetes (T1D), generally the most prevalent form of diabetes in youth. OBJECTIVES: We investigated the associations between POPs and T1D in youth and studied the impacts of POPs on pancreatic ß-cell function and viability in vitro. METHODS: We used data and plasma samples from the SEARCH for Diabetes in Youth Case Control Study (SEARCH-CC). Participants were categorized as Controls, T1D with normal insulin sensitivity (T1D/IS), and T1D with insulin resistance (T1D/IR). We assessed plasma concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides and estimated the odds of T1D through multivariable logistic regression. In addition, we performed in vitro experiments with the INS-1E pancreatic ß-cells. Cells were treated with PCB-153 or p,p'-DDE at environmentally relevant doses. We measured insulin production and secretion and assessed the mRNA expression of key regulators involved in insulin synthesis (Ins1, Ins2, Pdx1, Mafa, Pcsk1/3, and Pcsk2), glucose sensing (Slc2a2 and Gck), and insulin secretion (Abcc8, Kcnj11, Cacna1d, Cacna1b, Stx1a, Snap25, and Sytl4). Finally, we assessed the effects of PCB-153 and p,p'-DDE on ß-cell viability. RESULTS: Among 442 youths, 112 were controls, 182 were classified with T1D/IS and 148 with T1D/IR. The odds ratios (OR) of T1D/IS versus controls were statistically significant for p,p'-DDE (OR 2.0, 95% confidence interval (CI) 1.0, 3.8 and 2.4, 95% CI 1.2, 5.0 for 2nd and 3rd tertiles, respectively), trans-nonachlor (OR 2.5, 95% CI 1.3, 5.0 and OR 2.3, 95% CI 1.1, 5.1 for 2nd and 3rd tertiles, respectively), and PCB-153 (OR 2.3, 95% CI 1.1, 4.6 for 3rd tertile). However, these associations were not observed in participants with T1D/IR. At an experimental level, treatment with p,p'-DDE or PCB-153, at concentrations ranging from 1 × 10-15 M to 5 × 10-6 M, impaired the ability of pancreatic ß-cells to produce and secrete insulin in response to glucose. These failures were paralleled by impaired Ins1 and Ins2 mRNA expression. In addition, among different targeted genes, PCB-153 significantly reduced Slc2a2 and Gck mRNA expression whereas p,p'-DDE mainly affected Abcc8 and Kcnj11. While treatment with PCB-153 or p,p'-DDE for 2 days did not affect ß-cell viability, longer treatment progressively killed the ß-cells. CONCLUSION: These results support a potential role of POPs in T1D etiology and demonstrate a high sensitivity of pancreatic ß-cells to POPs.

Goals of Care Documentation: Insights from A Pilot Implementation Study.

CONTEXT: The Life Sustaining Treatment Decision Initiative is a national effort by the Veterans Health Administration to ensure goals of care documentation occurs among all patients at high risk of life-threatening events. OBJECTIVES: Examine likelihood to receive goals of care documentation and explore associations between documentation and perceived patient care experience at the individual and site level. METHODS: Retrospective, quality improvement analysis of initiative pilot data from four geographically diverse Veterans Affairs (VA) sites (Fall 2014-Winter 2016) before national roll-out. Goals of care documentation according to gender, marital status, urban/rural status, race/ethnicity, age, serious health condition, and Care Assessment Needs scores. Association between goals of care documentation and perceived patient care experience analyzed based on Bereaved Family Survey outcomes of overall care, communication, and support. RESULTS: Veterans were more likely to have goals of care documentation if widowed, urban residents, and of white race. Patients older than 65-years and those with a higher Care Assessment Needs score were twice as likely as a frail patient to have goals of care documented. One pilot site demonstrated a positive association between documentation and perceived support. Pilot site was a statistically significant predictor of the occurrence of goals of care documentation and Bereaved Family Survey scores. CONCLUSION: Older and seriously ill patients were most likely to have goals of care documented. Association between a documented goals of care conversation and perceived patient care experience were largely unsupported. Site-level largely contributed to understanding the likelihood of documentation and care experience.