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BACKGROUND: Acute respiratory illness (ARI) is one of the most common reasons children receive antibiotic treatment. Measurement of C-reaction protein (CRP) has been shown to reduce unnecessary antibiotic use among children with ARI in a range of clinical settings. In many resource-constrained contexts, patients seek care outside the formal health sector, often from lay community health workers (CHWs). This study's objective was to determine the impact of CRP measurement on antibiotic use among children presenting with febrile ARI to CHW in Uganda. METHODS AND FINDINGS: We conducted a cross-sectional, stepped wedge cluster randomized trial in 15 villages in Bugoye subcounty comparing a clinical algorithm that included CRP measurement by CHW to guide antibiotic treatment (STAR Sick Child Job Aid [SCJA]; intervention condition) with the Integrated Community Care Management (iCCM) SCJA currently in use by CHW in the region (control condition). Villages were stratified into 3 strata by altitude, distance to the clinic, and size; in each stratum, the 5 villages were randomly assigned to one of 5 treatment sequences. Children aged 2 months to 5 years presenting to CHW with fever and cough were eligible. CHW conducted follow-up assessments 7 days after the initial visit. Our primary outcome was the proportion of children who were given or prescribed an antibiotic at the initial visit. Our secondary outcomes were (1) persistent fever on day 7; (2) development of prespecified danger signs; (3) unexpected visits to the CHW; (4) hospitalizations; (5) deaths; (6) lack of perceived improvement per the child's caregiver on day 7; and (7) clinical failure, a composite outcome of persistence of fever on day 7, development of danger signs, hospitalization, or death. The 65 participating CHW enrolled 1,280 children, 1,220 (95.3%) of whom had sufficient data. Approximately 48% (587/1,220) and 52% (633/1,220) were enrolled during control (iCCM SCJA) and intervention periods (STAR SCJA), respectively. The observed percentage of children who were given or prescribed antibiotics at the initial visit was 91.8% (539/587) in the control periods as compared to 70.8% (448/633) during the intervention periods (adjusted prevalence difference -24.6%, 95% CI: -36.1%, -13.1%). The odds of antibiotic prescription by the CHW were over 80% lower in the intervention as compared to the control periods (OR 0.18, 95% CI: 0.06 to 0.49). The frequency of clinical failure (iCCM SCJA 3.9% (23/585) v. STAR SCJA 1.8% (11/630); OR 0.41, 95% CI: 0.09, 1.83) and lack of perceived improvement by the caregiver (iCCM SCJA 2.1% (12/584) v. STAR SCJA 3.5% (22/627); OR 1.49, 95% CI: 0.37, 6.52) was similar. There were no unexpected visits or deaths in either group within the follow-up period. CONCLUSIONS: Incorporating CRP measurement into iCCM algorithms for evaluation of children with febrile ARI by CHW in rural Uganda decreased antibiotic use. There is evidence that this decrease was not associated with worse clinical outcomes, although the number of adverse events was low. These findings support expanded access to simple, point-of-care diagnostics to improve antibiotic stewardship in rural, resource-constrained settings where individuals with limited medical training provide a substantial proportion of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05294510. The study was reviewed and approved by the University of North Carolina Institutional Review Board (#18-2803), Mbarara University of Science and Technology Research Ethics Committee (14/03-19), and Uganda National Council on Science and Technology (HS 2631).
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BACKGROUND: Although evidence-based treatments for depression in low-resource settings are established, implementation strategies to scale up these treatments remain poorly defined. We aimed to compare two implementation strategies in achieving high-quality integration of depression care into chronic medical care and improving mental health outcomes in patients with hypertension and diabetes. METHODS: We conducted a parallel, cluster-randomised, controlled, implementation trial in ten health facilities across Malawi. Facilities were randomised (1:1) by covariate-constrained randomisation to either an internal champion alone (ie, basic strategy group) or an internal champion plus external supervision with audit and feedback (ie, enhanced strategy group). Champions integrated a three-element, evidence-based intervention into clinical care: universal depression screening; peer-delivered psychosocial counselling; and algorithm-guided, non-specialist antidepressant management. External supervision involved structured facility visits by Ministry officials and clinical experts to assess quality of care and provide supportive feedback approximately every 4 months. Eligible participants were adults (aged 18-65 years) seeking hypertension and diabetes care with signs of depression (Patient Health Questionnaire-9 score ≥5). Primary implementation outcomes were depression screening fidelity, treatment initiation fidelity, and follow-up treatment fidelity over the first 3 months of treatment, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03711786, and is complete. FINDINGS: Five (50%) facilities were randomised to the basic strategy and five (50%) to the enhanced strategy. Between Oct 1, 2019, and Nov 30, 2021, in the basic group, 587 patients were assessed for eligibility, of whom 301 were enrolled; in the enhanced group, 539 patients were assessed, of whom 288 were enrolled. All clinics integrated the evidence-based intervention and were included in the analyses. Of 60 774 screening-eligible visits, screening fidelity was moderate (58% in the enhanced group vs 53% in the basic group; probability difference 5% [95% CI -38% to 47%]; p=0·84) and treatment initiation fidelity was high (99% vs 98%; 0% [-3% to 3%]; p=0·89) in both groups. However, treatment follow-up fidelity was substantially higher in the enhanced group than in the basic group (82% vs 20%; 62% [36% to 89%]; p=0·0020). Depression remission was higher in the enhanced group than in the basic group (55% vs 36%; 19% [3% to 34%]; p=0·045). Serious adverse events were nine deaths (five in the basic group and four in the enhanced group) and 26 hospitalisations (20 in the basic group and six in the enhanced group); none were treatment-related. INTERPRETATION: The enhanced implementation strategy led to an increase in fidelity in providers' follow-up treatment actions and in rates of depression remission, consistent with the literature that follow-up decisions are crucial to improving depression outcomes in integrated care models. These findings suggest that external supervision combined with an internal champion could offer an important advance in integrating depression treatment into general medical care in low-resource settings. FUNDING: The National Institute of Mental Health.
Subject(s)
Diabetes Mellitus , Hypertension , Adult , Humans , Depression/diagnosis , Depression/therapy , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , Hypertension/diagnosis , Hypertension/therapy , Malawi , Treatment OutcomeABSTRACT
OBJECTIVES: Describe (1) patient or caregiver perceptions of physical function in 30 days after skilled nursing facility (SNF) discharge indicated by Life-Space Assessment (LSA) scores, and (2) patient and caregiver factors associated with LSA scores. DESIGN: Secondary analysis of baseline and outcomes data from the cluster randomized trial of the Connect-Home transitional care intervention. SETTING AND PARTICIPANTS: Six SNFs in North Carolina. Patient and caregiver dyads with LSA scores (N = 245). METHODS: SNF patients or their caregivers serving as proxy reported the life-space of the SNF patient using the LSA tool, a measure of environmental and social factors that influence physical mobility. Simple scores for highest life-space attained depending on equipment and/or caregiver support range from 0 to 5, with higher scores indicating greater mobility. Multiple linear regression models for simple LSA scores and Composite Life-Space (0-120), adjusted for treatment, time via a COVID pandemic indicator, and treatment × COVID effect as fixed effects, were used to estimate the association of patient and caregiver variables and life-space. RESULTS: Patients had a mean age of 76.3 years, 62.6% were female, and 74.7% were white. Caregivers were commonly female (73.9%) and adult children of the patient (46.5%). The mean Composite Life-Space score was 22.6 (16.09). The mean Assisted Life-Space score (range: 0-5) was 1.6 (1.47), and 76.3% of patients could not move beyond their bedroom, house, and yard without assistance of another person. Higher Composite Life-Space scores were associated with lower levels of cognitive impairment and shorter SNF length of stay. CONCLUSIONS AND IMPLICATIONS: SNF patients and their caregivers reported very low LSA scores in 30 days after SNF care. Findings indicate the need for care redesign to promote recovery of physical function of older adults after SNF discharge, such as optimizing SNF rehabilitative therapy and adding postdischarge rehabilitative supports at home.
Subject(s)
COVID-19 , Patient Discharge , Skilled Nursing Facilities , Humans , Female , Male , Aged , North Carolina , Aged, 80 and over , COVID-19/epidemiology , Caregivers/psychology , SARS-CoV-2 , Activities of Daily LivingABSTRACT
Stepped wedge trials are increasingly adopted because practical constraints necessitate staggered roll-out. While a complete design requires clusters to collect data in all periods, resource and patient-centered considerations may call for an incomplete stepped wedge design to minimize data collection burden. To study incomplete designs, we expand the metric of information content to discrete outcomes. We operate under a marginal model with general link and variance functions, and derive information content expressions when data elements (cells, sequences, periods) are omitted. We show that the centrosymmetric patterns of information content can hold for discrete outcomes with the variance-stabilizing link function. We perform numerical studies under the canonical link function, and find that while the patterns of information content for cells are approximately centrosymmetric for all examined underlying secular trends, the patterns of information content for sequences or periods are more sensitive to the secular trend, and may be far from centrosymmetric.
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OBJECTIVE: To investigate the association of demographic and socio-economic characteristics with self-reported oral health (SROH) among older adults who participated in the Health and Retirement Study (HRS) in 2008, 2018, or both, and to describe temporal changes. METHODS: Data were from the University of Michigan's Health and Retirement Study (HRS), a nationally representative longitudinal survey of Americans aged 51 and older. Responses from participants who completed the Core HRS survey and Dental Module (DM) in 2008 (n = 1310), 2018 (n = 1330), and the "common group" at both timepoints (n = 559) were analysed. Using the common group, the outcome measure was 2018 self-rated oral health (Favourable vs Unfavourable). Potential explanatory variables included 2008 self-rated oral health (SROH), sociodemographic, and dental utilisation-related factors. Survey logistic regression analysis was used to identify factors that were associated with unfavourable 2018 SROH in 2018. RESULTS: Unfavourable SROH prevalence was 28.5% and 31.6% in 2008 and 2018, respectively. Among the common, longitudinal group, the unfavourable prevalence remained the same, 26.1% at both timepoints. A positive association was seen between 2018 unfavourable SROH and baseline variables of 2008 unfavourable SROH, male gender, less education, and lower levels of wealth. CONCLUSIONS: Over a quarter of participants reported unfavourable SROH. There was little change in SROH during this period. Sociodemographic factors influence the SROH of the older population. Policies and programs to promote and protect the oral health of older adults should be designed and implemented to reduce social inequalities and improve the SROH of disadvantaged older adults.
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OBJECTIVE: This study investigated whether non-esterified erythrocyte omega-6 PUFAs were associated with subjective assessment of sleep quality and duration, and risk for obstructive sleep apnea. METHODS: In this secondary analysis of the cross-sectional OPPERA-II study, 538 adults completed the Pittsburgh Sleep Quality Index (PSQI), reported their usual hours of sleep, and answered STOP screening questions for obstructive sleep apnea. Circulating non-esterified erythrocyte concentrations of omega-6 PUFA linoleic acid and arachidonic acid were quantified by liquid chromatography tandem mass spectroscopy. Sleep outcomes were dichotomized as poor (PSQI ≤5) vs good (PSQI ≥6) sleep quality, insufficient or excessive (≤6 or >9 h) vs good (7-9 h) sleep duration, and high (≥2 affirmative responses) vs low (<2 affirmative responses) risk for obstructive sleep apnea. Non-esterified omega-6 PUFAs and the continuous covariates of body mass index, Short Form (SF) 12 Health Survey Physical and Mental Component scores and resting measures of systolic and diastolic blood pressure were standardized for multivariable analysis. Categorical covariates were study site, age, sex, and race/ethnicity. Multivariable-adjusted logistic regression first estimated odds ratios (OR) and 95% confidence limits (CL) for sleep outcomes using linoleic acid as the main exposure. Analysis was then repeated using arachidonic acid as the main exposure. RESULTS: In the multivariable-adjusted model, each standard deviation increase in non-esterified erythrocyte linoleic acid was associated with higher odds of poor sleep quality (OR=1.2, 95% CL: 1.1, 1.5), insufficient or excessive sleep (OR= 1.3, 95% CL: 1.1, 1.6) and high-risk for obstructive sleep apnea (OR=1.3, 95% CL: 1.1, 1.6). Likewise, for each standard deviation increase in non-esterified erythrocyte arachidonic acid, odds increased of poor sleep quality (OR=1.2, 95% CL: 1.1, 1.5), and insufficient or excessive sleep (OR=1.2, 95% CL: 1.1, 1.5). Odds of being high risk for obstructive sleep apnea increased with greater circulating arachidonic acid, but the association did not reach statistical significance (OR=1.1, 95% CL: 0.9, 1.4). CONCLUSION: Non-esterified erythrocyte linoleic acid and arachidonic acid were associated with poor sleep quality and insufficient or excessive sleep duration. Linoleic acid, but not arachidonic acid, was also associated with high risk for obstructive sleep apnea.
Subject(s)
Linoleic Acid , Sleep Apnea, Obstructive , Adult , Humans , Arachidonic Acid , Cross-Sectional Studies , Sleep , Fatty Acids, Omega-6 , ErythrocytesABSTRACT
BACKGROUND AND OBJECTIVES: Marginal models with generalized estimating equations (GEE) are usually recommended for analyzing correlated ordinal outcomes which are commonly seen in a longitudinal study or clustered randomized trial (CRT). Within-cluster association is often of interest in longitudinal studies or CRTs, and can be estimated with paired estimating equations. However, the estimators for within-cluster association parameters and variances may be subject to finite-sample biases when the number of clusters is small. The objective of this article is to introduce a newly developed R package ORTH.Ord for analyzing correlated ordinal outcomes using GEE models with finite-sample bias corrections. METHODS: The R package ORTH.Ord implements a modified version of alternating logistic regressions with estimation based on orthogonalized residuals (ORTH), which use paired estimating equations to jointly estimate parameters in marginal mean and association models. The within-cluster association between ordinal responses is modeled by global pairwise odds ratios (POR). The R package also provides a finite-sample bias correction to POR parameter estimates based on matrix multiplicative adjusted orthogonalized residuals (MMORTH) for correcting estimating equations, and bias-corrected sandwich estimators with different options for covariance estimation. RESULTS: A simulation study shows that MMORTH provides less biased global POR estimates and coverage of their 95% confidence intervals closer to the nominal level than uncorrected ORTH. An analysis of patient-reported outcomes from an orthognathic surgery clinical trial illustrates features of ORTH.Ord. CONCLUSIONS: This article provides an overview of the ORTH method with bias-correction on both estimating equations and sandwich estimators for analyzing correlated ordinal data, describes the features of the ORTH.Ord R package, evaluates the performance of the package using a simulation study, and finally illustrates its application in an analysis of a clinical trial.
Subject(s)
Models, Statistical , Humans , Logistic Models , Longitudinal Studies , Cluster Analysis , Computer Simulation , BiasABSTRACT
The zero-inflated negative binomial distribution has been widely used for count data analyses in various biomedical settings due to its capacity of modeling excess zeros and overdispersion. When there are correlated count variables, a bivariate model is essential for understanding their full distributional features. Examples include measuring correlation of two genes in sparse single-cell RNA sequencing data and modeling dental caries count indices on two different tooth surface types. For these purposes, we develop a richly parametrized bivariate zero-inflated negative binomial model that has a simple latent variable framework and eight free parameters with intuitive interpretations. In the scRNA-seq data example, the correlation is estimated after adjusting for the effects of dropout events represented by excess zeros. In the dental caries data, we analyze how the treatment with Xylitol lozenges affects the marginal mean and other patterns of response manifested in the two dental caries traits. An R package "bzinb" is available on Comprehensive R Archive Network.
Subject(s)
Dental Caries , Humans , Models, Statistical , Binomial Distribution , Data Analysis , Poisson DistributionABSTRACT
BACKGROUND: Using a user-centered design approach, we conducted a two-site pilot study to evaluate a decision aid (DA) website, the Hypospadias Hub, for parents of hypospadias patients. OBJECTIVES: The objectives were to assess the Hub's acceptability, remote usability, and feasibility of study procedures, and to evaluate its preliminary efficacy. METHODS: From June 2021-February 2022, we recruited English-speaking parents (≥18 years old) of hypospadias patients (≤5 years) and delivered the Hub electronically ≤2 months before their hypospadias consultation. We collected website analytic data using an ad tracker plug-in. We inquired about treatment preference, hypospadias knowledge, and decisional conflict (Decisional Conflict Scale) at baseline, after viewing the Hub (pre-consultation), and post-consultation. We administered the Decision Aid Acceptability Questionnaire (DAAQ) and the Preparation for Decision-Making Scale (PrepDM) which assessed how well the Hub prepared parents for decision-making with the urologist. Post-consultation, we assessed participants' perception of involvement in decision-making with the Shared Decision-making Questionnaire (SDM-Q-9) and the Decision Regret Scale (DRS). A bivariate analysis compared participants' baseline and pre/post-consultation hypospadias knowledge, decisional conflict, and treatment preference. Using a thematic analysis, we analyzed our semi-structured interviews to uncover how the Hub impacted the consultation and what influenced participants' decisions. RESULTS: Of 148 parents contacted, 134 were eligible and 65/134 (48.5%) enrolled: mean age 29.2, 96.9% female, 76.6% White (Extended Summary Figure). Pre/post-viewing the Hub, there was a statistically significant increase in hypospadias knowledge (54.3 vs. 75.6, p < 0.001) and decrease in decisional conflict (36.0 vs. 21.9, p < 0.001). Most participants (83.3%) thought Hub's length and amount of information (70.4%) was "about right", and 93.0% found most or everything was clear. Pre/post-consultation, there was a statistically significant decrease in decisional conflict (21.9 vs. 8.8, p < 0.001). PrepDM's mean score was 82.6/100 (SD = 14.1); SDM-Q-9's mean score was 82.5/100 (SD = 16.7). DCS's mean score was 25.0/100 (SD = 47.03). Each participant spent an average of 25.75 min reviewing the Hub. Based on thematic analysis, the Hub helped participants feel prepared for the consultation. DISCUSSION: Participants engaged extensively with the Hub and demonstrated improved hypospadias knowledge and decision quality. They felt prepared for the consultation and perceived a high degree of involvement in decision-making. CONCLUSION: As the first pilot test of a pediatric urology DA, the Hub was acceptable and study procedures were feasible. We plan to conduct a randomized controlled trial of the Hub versus usual care to test its efficacy to improve the quality of shared decision-making and reduce long-term decisional regret.
Subject(s)
Decision Making , Hypospadias , Child , Male , Humans , Female , Adolescent , Pilot Projects , Hypospadias/surgery , Parents , Decision Making, SharedABSTRACT
BACKGROUND: Skilled nursing facility (SNF) patients and their caregivers who transition to home experience complications and frequently return to acute care. We tested the efficacy of the Connect-Home transitional care intervention on patient and caregiver preparedness for care at home, and other patient and caregiver-reported outcomes. METHODS: We used a stepped wedge, cluster-randomized trial design to test the intervention against standard discharge planning (control). The setting was six SNFs and six home health offices in one agency. Participants were 327 dyads of patients discharged from SNF to home and their caregivers; 11.1% of dyads in the control condition and 81.2% in the intervention condition were enrolled after onset of COVID-19. Patients were 63.9% female and mean age was 76.5 years. Caregivers were 73.7% female and mean age was 59.5 years. The Connect-Home intervention includes tools, training, and technical assistance to deliver transitional care in SNFs and patients' homes. Primary outcomes measured at 7 days included patient and caregiver measures of preparedness for care at home, the Care Transitions Measure-15 (patient) and the Preparedness for Caregiving Scale (caregiver). Secondary outcomes measured at 30 and 60 days included the McGill Quality of Life Questionnaire, Life Space Assessment, Zarit Caregiver Burden Scale, Distress Thermometer, and self-reported number of patient days in the ED or hospital in 30 and 60 days following SNF discharge. RESULTS: The intervention was not associated with improvement in patient or caregiver outcomes in the planned analyses. Post-hoc analyses that distinguished between pre- and post-pandemic effects suggest the intervention may be associated with increased patient preparedness for discharge and decreased number of acute care days. CONCLUSIONS: Connect-Home transitional care did not improve outcomes in the planned statistical analysis. Post-hoc findings accounting for COVID-19 impact suggest SNF transitional care has potential to increase patient preparedness and decrease return to acute care.
Subject(s)
COVID-19 , Home Care Services , Transitional Care , Humans , Female , Aged , Male , Skilled Nursing Facilities , Quality of LifeABSTRACT
BACKGROUND AND OBJECTIVES: Generalized estimating equations (GEE) are used to analyze correlated outcomes in marginal regression models with population-averaged interpretations of exposure effects. Limitations of popular software for GEE include: (i) user choice is restricted to a small set of within-cluster pairwise correlation (intra-class correlation; ICC) structures; and (ii) inference on ICC parameters is usually not possible because the precision of their estimates is not quantified. This is important because ICC values inform the design of cluster randomized trials. Beyond the standard GEE implementation, use of paired estimating equations (Prentice 1988) provides: (i) flexible specification of models for pairwise correlations and (ii) standard errors for ICC estimates. However, most GEEs give biased estimates of standard errors and correlations when the number of clusters is small (roughly, ≤40). Consequently, there is a need for software to provide GEE analysis with finite-sample bias-corrections. METHODS: The SAS macro GEEMAEE implements paired estimating equations to simultaneously estimate parameters in marginal mean and ICC models. It provides bias-corrected standard errors and uses matrix-adjusted estimating equations (MAEE) for bias-corrected estimation of correlations. Several built-in correlation matrix options, rarely found in software, are offered for multi-period, cluster randomized trials and similarly structured longitudinal observational data structures. Additional options include user-specified correlation structures and deletion diagnostics, namely Cooks' Distance and DBETA statistics that estimate the influence of observations, cluster-periods (when applicable) and clusters. RESULTS: GEEMAEE is illustrated for a binary and a count outcome in two stepped wedge cluster randomized trials and a binary outcome in a longitudinal study of disease surveillance. Use of MAEE resulted in larger values of correlation estimates compared to uncorrected estimating equations. Use of bias-corrected variance estimators resulted in (appropriately) larger values of standard errors compared to the usual sandwich estimators. Deletion diagnostics identified the clusters and cluster-periods having the most influence. CONCLUSIONS: The SAS macro GEEMAEE provides regression analysis for clustered or longitudinal responses, and is particularly useful when the number of clusters is small. Flexible specification and bias-corrected estimation of pairwise correlation parameters and standard errors are key features of the software to provide valid inference in real-world settings.
Subject(s)
Models, Statistical , Computer Simulation , Longitudinal Studies , Cluster Analysis , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVES: Clinical measures of periodontal disease such as attachment loss (CAL) and probing depth (PD) vary considerably between and within individuals with periodontitis and are known to be influenced by person-level factors (e.g. age and race/ethnicity) as well as intraoral characteristics (e.g. tooth type and location). This study sought to characterize site-level disease patterns and correlations using both person-level and intraoral factors through a model-based approach. METHODS: This study used full-mouth, six sites per tooth, periodontal examination data collected from 2301 Hispanic/Latino adults aged 60-74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The presence of site-level CAL ≥3 mm and PD ≥4 mm was estimated using generalized estimating equations (GEE), explicitly modelling pairwise periodontal site correlations, while adjusting for number of teeth, sex and Hispanic/Latino background. Subsequently tooth- and tooth-site patterns of intraoral CAL ≥3 mm and PD ≥4 mm were estimated and visualized in the HCHS/SOL population. RESULTS: The findings showed that posterior sites had the highest odds of CAL ≥3 mm and PD ≥4 mm. Sites located in the interproximal space had higher odds of PD ≥4 mm but lower odds of CAL ≥3 mm than non-interproximal sites. Mexicans had the lowest odds of CAL ≥3 mm among all Hispanic/Latino backgrounds. While Mexicans had lower odds of PD ≥4 mm than Central Americans and Cubans, they had higher odds than Dominicans and Puerto Ricans. Site-level proportions and pairwise correlations of PD ≥4 mm were generally smaller than those of CAL ≥3 mm. CONCLUSIONS: The patterns of site-level probabilities of clinical measures of periodontal disease can be defined based on tooth, site and individual-level characteristics. Intraoral correlation patterns, while complex, are quantifiable. The risk factors for site-level CAL ≥3 mm may differ from those of PD ≥4 mm. Likewise, participant risk factors for site-level clinical measures of periodontal disease are distinct from those that affect individual-level periodontitis prevalence. Future epidemiological investigations should consider model-based approaches when examining site-level disease probabilities to identify intra-oral patterns of periodontal disease and make inferences about the larger population.
Subject(s)
Hispanic or Latino , Periodontal Diseases , Periodontitis , Aged , Humans , Hispanic or Latino/ethnology , Hispanic or Latino/statistics & numerical data , Periodontal Diseases/epidemiology , Periodontal Diseases/etiology , Periodontitis/complications , Periodontitis/epidemiology , Public Health , Middle Aged , North Carolina/epidemiologyABSTRACT
The overdiagnosis of urinary tract infections (UTIs) in nursing home residents is a significant public health threat. Using a discrete choice experiment and a diagnostic guideline, we examined which patient-level information was associated with the overdiagnosis of UTIs and found that urinalysis results and lower urinary tract status were most associated.
Subject(s)
Homes for the Aged , Urinary Tract Infections , Humans , Aged , Overdiagnosis , Urinary Tract Infections/diagnosis , Urinary Tract Infections/epidemiology , Urinary Tract Infections/drug therapy , Nursing Homes , Anti-Bacterial Agents/therapeutic useABSTRACT
Pain intensity is well-known to be influenced by a wide range of biobehavioral variables. Nutritional factors, however, have not been generally considered for their potential importance. This cross-sectional study examined associations between erythrocyte omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and pain intensity in 605 adults. Pain intensity was computed on a 0 to 100 numeric rating scale from questions about 5 chronic pain conditions: orofacial pain, headache, low back pain, irritable bowel syndrome, and bodily pain. For each pain condition, multiple linear regression tested the hypothesis that a higher ratio of n-6 arachidonic acid to the sum of n-3 eicosapentaenoic acid and docosahexaenoic acid (AA/(EPA+DHA) was associated with greater pain intensity. In covariate-adjusted analysis, orofacial pain intensity increased 5.7 points (95% CI: 1.4, 9.9) per unit increase in n-6/n-3 PUFA ratio. Likewise, a 1 unit increase in n-6/n-3 PUFA ratio was associated with significant increases in pain intensity (range 5-8 points) of headache pain, low back pain, and bodily pain, but not abdominal pain. Separate multiple linear regression models investigated the independent strength of association of individual PUFAs to the intensity of each pain condition. Overall, n-3 docosahexaenoic acid was most strongly, and inversely, associated with pain intensity. PERSPECTIVE: A higher ratio of n-6/n-3 long-chain polyunsaturated fatty acids was associated greater pain intensity for orofacial pain, headache, low back pain, and bodily pain, but not abdominal pain. The n-6/n-3 PUFA ratio was more consistently associated with pain intensity than any individual constituent of the long-chain PUFA ratio.
Subject(s)
Chronic Pain , Fatty Acids, Omega-3 , Low Back Pain , Adult , Humans , Docosahexaenoic Acids , Cross-Sectional Studies , Pain Measurement , Fatty Acids, Unsaturated , Headache , Facial PainABSTRACT
Stepped wedge designs have uni-directional crossovers at randomly assigned time points (steps) where clusters switch from control to intervention condition. Incomplete stepped wedge designs are increasingly used in cluster randomized trials of health care interventions and have periods without data collection due to logistical, resource and patient-centered considerations. The development of sample size formulae for stepped wedge trials has primarily focused on complete designs and continuous responses. Addressing this gap, a general, fast, non-simulation based power procedure is proposed for generalized estimating equations analysis of complete and incomplete stepped wedge designs and its predicted power is compared to simulated power for binary and continuous responses. An extensive set of simulations for six and twelve clusters is based upon the Connect-Home trial with an incomplete stepped wedge design. Results show that empirical test size is well controlled using a t-test with bias-corrected sandwich variance estimator for as few as six clusters. Analytical power agrees well with a simulated power in scenarios with twelve clusters. For six clusters, analytical power is similar to simulated power with estimation using the correctly specified model-based variance estimator. To explore the impact of study design choice on power, the proposed fast GEE power method is applied to the Connect-Home trial design, four alternative incomplete stepped wedge designs and one complete design.
Subject(s)
Research Design , Humans , Cluster Analysis , Randomized Controlled Trials as Topic , Sample Size , BiasABSTRACT
OBJECTIVES: This paper illustrates survival models for analysis of trials of substance use treatment programs. It uses public release data from a study of extended-release naltrexone (XR-NTX), relative to buprenorphine-naloxone (BUP-NX). METHODS: We used publicly available data from the X:BOT trial (n = 570), which compared XR-NTX to BUP-NX on 2 efficacy outcomes (opioid relapse, use of nonprescribed opioids; positive opioid urine test) and 1 safety outcome (overdose). Intention-to-treat (ITT) and per-protocol approaches were implemented using survival models that included treatment-by-time interactions. RESULTS: Consistent with the original trial findings, 72% of XR-NTX and 94% of BUP-NX subjects initiated treatment; the ITT hazard ratio for XR-NTX relative to BUP-NX was 1.40 (95% confidence interval: 1.13, 1.73; P < 0.01) for opioid relapse and 1.31 (1.07, 1.60; P = 0.01) for positive urine test. Using treatment-by-time interactions, we examined the time-dependent effect of XR-NTX and found an elevated ITT overdose hazard ratio of 2.4 (1.1, 5.3; P = 0.03) overall and 3.8 (1.2, 11.6; P = 0.02) during the study treatment phase. This result (28 overdoses overall; 17 overdoses during the study treatment phase) contrasts with the previous analysis, which reported minimal differences in overdose between XR-NTX and BUP-NX. CONCLUSIONS: An advantage of using time-dependent Cox models is its ability to isolate effects during specific periods. In general, our survival analyses concur with the conclusions of Lee et al (2018) for the efficacy outcomes, which demonstrated superiority of BUP-NX. In contrast to the original report, our analysis indicates a greater risk of overdose for XR-NTX, predominantly during the study treatment phase. Further investigation of this finding is a pressing research priority.
Subject(s)
Drug Overdose , Opioid-Related Disorders , Analgesics, Opioid/therapeutic use , Buprenorphine, Naloxone Drug Combination/therapeutic use , Delayed-Action Preparations/therapeutic use , Drug Overdose/drug therapy , Humans , Injections, Intramuscular , Naltrexone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapy , Recurrence , Survival AnalysisABSTRACT
OBJECTIVE: Polyunsaturated fatty acids (PUFAs) play a role in pain regulation. This study sought to determine whether free PUFAs found in red blood cells also play a role in nociceptive processing. We examined associations between circulating PUFAs and nociceptive thresholds to noxious mechanical stimuli. We also determined whether nociceptive thresholds were associated with nociplastic pain conditions. METHODS: This cross-sectional study used stored red bloods cells and data from 605 adult participants in the OPPERA-2 study of chronic overlapping pain conditions. In OPPERA-2 adults completed quantitative sensory testing in which pressure algometry measured deep muscular tissue sensitivity at six anatomical sites. Standardized protocols classified adults for presence or absence of five nociplastic pain conditions: temporomandibular disorder, headache, low back pain, irritable bowel syndrome and fibromyalgia. Liquid chromatography tandem mass spectroscopy quantified erythrocyte PUFAs. We conducted three sets of analyses. First, a multivariable linear regression model assessed the association between n-6/n-3 PUFA ratio and the number of overlapping nociplastic pain conditions. Second, a series of 36 multivariable linear regression models assessed covariate-adjusted associations between PUFAs and nociceptive thresholds at each of six anatomical sites. Third, a series of 30 multivariable linear regression models assessed covariate-adjusted associations between nociceptive thresholds at six anatomical sites and each of five pain conditions. RESULTS: In multiple linear regression, each unit increase in n-6/n-3 PUFA ratio was associated with more pain conditions (ß = 0.30, 95% confidence limits: 0.07, 0.53, p = 0.012). Omega-6 linoleic acid and arachidonic acid were negatively associated with lower nociceptive thresholds at three and at five, respectively, anatomical sites. In contrast, omega-3 alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and the n-6/n-3 PUFA ratio were not associated with nociceptive thresholds at any site. Pain cases had significantly lower nociceptive thresholds than non-case controls at all anatomical sites. CONCLUSION: A higher n-6/n-3 PUFA ratio was associated with more pain conditions. Omega-6 PUFAs may promote a generalized upregulation of nociceptive processing.
Subject(s)
Fatty Acids, Omega-3 , Fatty Acids, Omega-6 , Adult , Cross-Sectional Studies , Fatty Acids, Unsaturated , Humans , Pain ThresholdABSTRACT
BACKGROUND: Assisted living (AL) is the largest residential long-term care provider in the United States, including for persons with Alzheimer's disease and related dementias. Despite recognizing the challenge of infection control for persons with dementia, this study of 119 AL communities is the first to describe dementia-relevant COVID-19 infection control across different types of AL communities, and to discuss implications for the future. METHODS: From a parent study sampling frame of 244 AL communities across seven states, 119 administrators provided data about COVID-19 infection control practices and resident behaviors. Data were collected from July 2020 through September 2021. Communities were differentiated based on the presence of beds/units dedicated for persons living with dementia, as being either dementia-specific, mixed, or integrated. Data obtained from administrators related to feasibility of implementing seven infection control practices, and the extent to which residents themselves practiced infection prevention. Analyses compared practices across the three community types. RESULTS: Less than half of administrators found it feasible to close indoor common areas, all community types reported a challenge organizing group activities for safe distancing, and more than half of residents with dementia did not wear a face covering or maintain physical distance from other residents when indicated. Dementia-specific AL communities were generally the most challenged with infection control during COVID-19. CONCLUSION: All AL community types experienced infection control challenges, more so in dementia-specific communities (which generally provide care to persons with more advanced dementia and have fewer private beds). Results indicate a need to bolster infection prevention capacity when caring for this especially vulnerable population, and have implications for care in nursing homes as well.
Subject(s)
Assisted Living Facilities , COVID-19 , Dementia , COVID-19/epidemiology , Dementia/epidemiology , Humans , Infection Control , Nursing Homes , United States/epidemiologyABSTRACT
Recent years have seen a surge of interest in stepped-wedge cluster randomized trials (SW-CRTs). SW-CRTs include several design variations and methodology is rapidly developing. Accordingly, a variety of power and sample size calculation software for SW-CRTs has been developed. However, each calculator may support only a selected set of design features and may not be appropriate for all scenarios. Currently, there is no resource to assist researchers in selecting the most appropriate calculator for planning their trials. In this paper, we review and classify 18 existing calculators that can be implemented in major platforms, such as R, SAS, Stata, Microsoft Excel, PASS and nQuery. After reviewing the main sample size considerations for SW-CRTs, we summarize the features supported by the available calculators, including the types of designs, outcomes, correlation structures and treatment effects; whether incomplete designs, cluster-size variation or secular trends are accommodated; and the analytical approach used. We then discuss in more detail four main calculators and identify their strengths and limitations. We illustrate how to use these four calculators to compute power for two real SW-CRTs with a continuous and binary outcome and compare the results. We show that the choice of calculator can make a substantial difference in the calculated power and explain these differences. Finally, we make recommendations for implementing sample size or power calculations using the available calculators. An R Shiny app is available for users to select the calculator that meets their requirements (https://douyang.shinyapps.io/swcrtcalculator/).