Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. PURPOSE/HYPOTHESIS: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. STUDY TYPE: Cohort. SUBJECTS: Four community-dwelling adults with obesity. FIELD STRENGTH/SEQUENCE: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. ASSESSMENT: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. STATISTICAL TESTS: Linear regression in MATLAB, ICC analyses using SAS 9.4, one-sided 95% confidence intervals for the ICC. RESULTS: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. CONCLUSIONS: We demonstrated harmonization of PDFF, MRS, and MRE-based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Medical and psychosocial outcomes of state-funded population genomic screening.

As the uptake of population screening expands, assessment of medical and psychosocial outcomes is needed. Through the Alabama Genomic Health Initiative (AGHI), a state-funded genomic research program, individuals received screening for pathogenic or likely pathogenic variants in 59 actionable genes via genotyping. Of the 3874 eligible participants that received screening results, 858 (22%) responded to an outcomes survey. The most commonly reported motivation for seeking testing through AGHI was contribution to genetic research (64%). Participants with positive results reported a higher median number of planned actions (median = 5) due to AGHI results as compared to negative results (median = 3). Interviews were conducted with survey participants with positive screening results. As determined by certified genetic counselors, 50% of interviewees took appropriate medical action based on their result. There were no negative or harmful actions taken. These findings indicate population genomic screening of an unselected adult population is feasible, is not harmful, and may have positive outcomes on participants now and in the future; however, further research is needed in order to assess clinical utility.

Associations between pain catastrophizing and resting-state functional brain connectivity: Ethnic/race group differences in persons with chronic knee pain.

Chronic pain is a significant public health problem, and the prevalence and societal impact continues to worsen annually. Multiple cognitive and emotional factors are known to modulate pain, including pain catastrophizing, which contributes to pain facilitation and is associated with altered resting-state functional connectivity in pain-related cortical and subcortical circuitry. Pain and catastrophizing levels are reported to be higher in non-Hispanic black (NHB) compared with non-Hispanic White (NHW) individuals. The current study, a substudy of a larger ongoing observational cohort investigation, investigated the pathways by which ethnicity/race influences the relationship between pain catastrophizing, clinical pain, and resting-state functional connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), insula, and primary somatosensory cortex (S1). Participants included 136 (66 NHBs and 70 NHWs) community-dwelling adults with knee osteoarthritis. Participants completed the Coping Strategies Questionnaire-Revised Pain Catastrophizing subscale and Western Ontario and McMaster Universities Osteoarthritis Index. Magnetic resonance imaging data were obtained, and resting-state functional connectivity was analyzed. Relative to NHW, the NHB participants were younger, reported lower income, were less likely to be married, and self-reported greater clinical pain and pain catastrophizing (ps < 0.05). Ethnicity/race moderated the mediation effects of catastrophizing on the relationship between clinical pain and resting-state functional connectivity between the ACC, dlPFC, insula, and S1. These results indicate the NHB and NHW groups demonstrated different relationships between pain, catastrophizing, and functional connectivity. These results provide evidence for a potentially important role of ethnicity/race in the interrelationships among pain, catastrophizing, and resting-state functional connectivity.

Perioperative Mobile Telehealth Program for Post-Prostatectomy Incontinence: A Randomized Clinical Trial.

PURPOSE: Perioperative pelvic floor muscle training can hasten recovery of bladder control and reduce severity of urinary incontinence following radical prostatectomy. Nevertheless, most men undergoing prostatectomy do not receive this training. The purpose of this trial was to test the effectiveness of interactive mobile telehealth (mHealth) to deliver an evidence-based perioperative behavioral training program for post-prostatectomy incontinence. MATERIALS AND METHODS: This was a 3-site, 2-arm, randomized trial (2014-2019). Men with prostate cancer scheduled to undergo radical prostatectomy were randomized to a perioperative behavioral program (education, pelvic floor muscle training, progressive exercises, bladder control techniques) or a general prostate cancer education control condition, both delivered by mHealth for 1-4 weeks preoperatively and 8 weeks postoperatively. The primary outcome was time to continence following surgery measured by the ICIQ (International Consultation on Incontinence Questionnaire) Short-Form. Secondary outcomes measured at 6, 9 and 12 months included Urinary Incontinence Subscale of Expanded Prostate Cancer Index Composite; pad use; International Prostate Symptom Score QoL Question and Global Perception of Improvement. RESULTS: A total of 245 men (ages 42-78 years; mean=61.7) were randomized. Survival analysis using the Kaplan-Meier estimate showed no statistically significant between-group differences in time to continence. Analyses at 6 months indicated no statistically significant between-group differences in ICIQ scores (mean=7.1 vs 7.0, p=0.7) or other secondary outcomes. CONCLUSIONS: mHealth delivery of a perioperative program to reduce post-prostatectomy incontinence was not more effective than an mHealth education program. More research is needed to assess whether perioperative mHealth programs can be a helpful addition to standard prostate cancer care.

COVID-19 Vaccine Knowledge, Attitudes, and Practices in Alabama: The Case for Primary Health Care Providers.

OBJECTIVE: To examine knowledge, attitudes, and practices about COVID-19 in Alabama, with a primary focus on vaccination perception and utilization. DESIGN: We used a COVID-19 Knowledge, Attitudes, and Practices survey and recruited adult Alabama residents in April-May 2021. PARTICIPANTS: Initial surveys from 1324 Alabamian participants were considered for analysis; after careful review of incomplete responses, 953 were ultimately included for analysis. MAIN OUTCOME MEASURE: Vaccine behavior and hesitancy comprise a self-reported response contained in the survey instrument. Three primary vaccine groups were used to assess differences in demographic characteristics, health status, perception of susceptibility and severity of COVID-19, sources of information, and trust about COVID-19. RESULTS: Of the 953 survey participants included for analysis, 951 had self-identified vaccine status in which 153 (16.1%) reported to have received the vaccine at the time of the survey, 375 (39.4%) were very likely or somewhat likely to get an approved COVID-19 vaccine if it was offered, and 423 (44.5%) were somewhat unlikely or very unlikely to get an approved COVID-19 vaccine. Health care providers were the most trusted sources of information, regardless of vaccine status. For participants unlikely to receive a vaccine, social media and local news sources were consistently more trusted and utilized than those who were vaccinated or were likely to be. CONCLUSIONS: The perceptions among unvaccinated participants are actionable and provide teachable opportunities to decrease vaccine apprehension.

Comparison of Two Methods for Implementing Comfort Care Order Sets in the Inpatient Setting: a Cluster Randomized Trial.

BACKGROUND: There is an ongoing need for interventions to improve quality of end-of-life care for patients in inpatient settings. OBJECTIVE: To compare two methods for implementing a Comfort Care Education Intervention for Palliative Care Consultation Teams (PCCT) in Veterans Affairs Medical Centers (VAMCs). DESIGN: Cluster randomized implementation trial conducted March 2015-April 2019. PCCTs were assigned to a traditional implementation approach using a teleconference or to an in-person, train-the-champion workshop to prepare PCCTs to be clinical champions at their home sites. PARTICIPANTS: One hundred thirty-two providers from PCCTs at 47 VAMCs. INTERVENTIONS: Both training modalities involved review of educational materials, instruction on using an electronic Comfort Care Order Set, and coaching to deliver the intervention to other providers. MAIN MEASUREMENTS: Several processes of care were identified a priori as quality endpoints for end-of-life care (last 7 days) and abstracted from medical records of veterans who died within 9 months before or after implementation (n = 6,491). The primary endpoint was the presence of an active order for opioid medication at time of death. Secondary endpoints were orders/administration of antipsychotics, benzodiazepines, and scopolamine, do-not-resuscitate orders, advance directives, locations of death, palliative care consultations, nasogastric tubes, intravenous lines, physical restraints, pastoral care visits, and family presence at/near time of death. Generalized estimating equations were conducted adjusting for potential covariates. KEY RESULTS: Eighty-eight providers from 23 VAMCs received teleconference training; 44 providers from 23 VAMCs received in-person workshop training. Analyses found no significant differences between intervention groups in any process-of-care endpoints (primary endpoint AOR (CI) = 1.18 (0.74, 1.89). Furthermore, pre-post changes were not significant for any endpoints (primary endpoint AOR (CI) = 1.16 (0.92, 1.46). Analyses may have been limited by high baseline values on key endpoints with little room for improvement. CONCLUSION: Findings suggest the clinical effectiveness of palliative care educational intervention was not dependent on which of the two implementation methods was used. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02383173.

Knee pain trajectories over 18 months in non-Hispanic Black and non-Hispanic White adults with or at risk for knee osteoarthritis.

BACKGROUND: Pain is the hallmark symptom of knee osteoarthritis (OA), and varies widely across individuals. Previous research has demonstrated both fluctuating and stable pain trajectories in knee OA using various time periods. Changes in pain assessed quarterly (i.e. 3-month intervals) in knee OA are relatively unknown. The current study aimed to investigate temporal variations in pain over a one and a half year period (18 months) based on quarterly characteristic pain assessments, and to examine differences in pain patterns by sociodemographic and baseline pain characteristics. METHODS: The sample included a prospective cohort of 188 participants (mean age 58 years; 63% female; 52% non-Hispanic Black) with or at risk for knee OA from an ongoing multisite investigation of ethnic/race group differences. Knee pain intensity was self-reported at baseline and quarterly over an18-month period. Baseline pain assessment also included frequency, duration, and total number of pain sites. Group-based trajectory modeling was used to identify distinct pain trajectories. Multinomial logistic regression was used to examine associations between sociodemographic characteristics, risk factors, and pain trajectory groups. RESULTS: Pain trajectories were relatively stable among a sample of adults with knee pain. Four distinct pain trajectories emerged in the overall sample, with the largest proportion of participants (35.1%) classified in the moderate-high pain group. There were significant relationships between age, education, income, ethnicity/race and trajectory group; with younger, less educated, lower income, and non-Hispanic Black participants had a greater representation in the highest pain trajectory group. CONCLUSIONS: Pain remained stable across a one and a half-year period in adults with or at risk for knee osteoarthritis, based on quarterly assessments. Certain sociodemographic variables (e.g. ethnicity/race, education, income, age) may contribute to an increased risk of experiencing greater pain.

Neuropathic-Like Pain Symptoms in a Community-Dwelling Sample with or at Risk for Knee Osteoarthritis.

OBJECTIVE: To characterize neuropathic-like pain among individuals with or at risk for knee osteoarthritis. SUBJECTS: One hundred eighty-four individuals who self-identified as non-Hispanic black or non-Hispanic white and presented with unilateral or bilateral knee pain. DESIGN: Neuropathic-like pain was assessed using the painDETECT, and those with high vs low neuropathic-like pain were compared on clinical pain, psychological symptoms, physical function, and quantitative sensory testing. Analyses were unadjusted, partially and fully adjusted for relevant covariates. RESULTS: Thirty-two (17.4%) participants reported experiencing neuropathic-like pain features above the painDETECT clinical cut-score. The neuropathic-like pain group reported significantly greater pain severity on all measures of clinical pain and higher levels of psychological symptoms when fully adjusted for covariates, but no differences emerged for disability and lower extremity function. The neuropathic-like pain group also reported greater overall heat pain ratings during the heat pain threshold and increased temporal summation of heat pain in the fully adjusted model. Additionally, those with neuropathic-like pain symptoms reported greater painful after-sensations following heat pain temporal summation in all analyses. No significant group differences in pressure pain threshold emerged at any of the testing sites. In contrast, temporal summation of mechanical pain was significantly greater at both the index knee and the ipsilateral hand for the neuropathic-like pain group in all analyses. CONCLUSIONS: Participants with or at risk for knee osteoarthritis who reported high neuropathic-like pain experienced significantly greater clinical pain and increased heat and mechanical temporal summation at the index knee and other body sites tested, suggesting central sensitization.

Comparison of 3 risk factor-based screening tools for the identification of prediabetes.

OBJECTIVE: To compare risk factor-based screening tools for identifying prediabetes. METHODS: Participants in an employer-based wellness program were tested for glycosylated hemoglobin (A1C) at a regularly scheduled appointment, and prediabetes risk factor information was collected. The likelihood of having prediabetes and the need for laboratory testing were determined based on 3 risk factor-based screening tools: the Prediabetes Screening Test (PST), Prediabetes Risk Test (PRT), and 2016 American Diabetes Association guidelines (ADA2016). The results from the screening tools were compared with those of the A1C test. The predictive ability of the PST, PRT, and ADA2016 were compared using logistic regression. Results were validated with data from a secondary population. RESULTS: Of the 3 risk factor-based tools examined, the PRT demonstrated the best combination of sensitivity and specificity for identifying prediabetes. From July 2016 to March 2017, 740 beneficiaries of an employer-sponsored wellness program had their A1C tested and provided risk factor information. The population prevalence of prediabetes was 9.3%. Analysis of a second independent population with a prediabetes prevalence of more than 50% of confirmed PRT's superiority despite differences in the calculated sensitivity and specificity for each population. CONCLUSION: Because PRT predicts prediabetes better than PST or ADA2016, it should be used preferentially.

Description of a pharmacist-led diabetes prevention service within an employer-based wellness program.

OBJECTIVES: To describe a pharmacist-led diabetes prevention service piloted within an employer-based wellness program. PRACTICE DESCRIPTION: A pharmacist-led ambulatory care clinic within a school of pharmacy that provides wellness services to university employees. PRACTICE INNOVATION: Implementation of a diabetes prevention service using opportunistic A1C screening within a biometric screening program. Patients with a prediabetes-level A1C from July 2016 to March 2019 were invited to participate in the National Diabetes Prevention Program (NDPP). EVALUATION: Comparison of baseline characteristics of participants with normal and elevated A1C. Evaluation of participation in the NDPP and changes in clinical values at the subsequent biometric screening appointment for individuals with a prediabetes-level AlC. RESULTS: A1C testing of 740 individuals identified 69 participants (9.3%) with a prediabetes-level A1C and 7 (1.0%) with a diabetes-level A1C. Compared with those with a normal A1C (< 5.7%), participants with an elevated A1C were more likely to be older, nonwhite, obese, and physically inactive, to have a sibling with diabetes, higher random blood sugar (RBS), lower high-density lipoprotein (HDL), and more likely to have hypertension. Twelve patients participated in the NDPP, although most attended only 1 session. Attenders had a significantly lower baseline weight and body mass index (BMI). There were no significant differences in the changes in A1C, BMI, weight, RBS, or HDL between attenders and nonattenders approximately 1 year later. CONCLUSION: This pilot demonstrated that opportunistic A1C testing could be incorporated into an ambulatory care clinic within a pharmacist-led employer-based wellness program. Uptake and retention of the NDPP were poor. Barriers to NDPP participation need to be investigated and addressed to improve service impact.

Identification of Key Bacteria Involved in the Induction of Incident Bacterial Vaginosis: A Prospective Study.

Background: The sequence of events preceding incident bacterial vaginosis (iBV) is unclear. Methods: African American women who have sex with women, who had no Amsel criteria and Nugent scores of 0-3, were followed for 90 days to detect iBV (defined as a Nugent score of 7-10 on at least 2-3 consecutive days), using self-collected vaginal swab specimens. For women with iBV (cases) and women maintaining normal vaginal flora (healthy women), 16S ribosomal RNA gene sequencing targeting V4 was performed. Longitudinal vaginal microbiome data were analyzed. Results: Of 204 women screened, 42 enrolled; of these, 45% developed iBV. Sequencing was performed on 448 specimens from 14 cases and 8 healthy women. Among healthy women, Lactobacillus crispatus dominated the vaginal microbiota in 75%. In contrast, prior to iBV, the vaginal microbiota in 79% of cases was dominated by Lactobacillus iners and/or Lactobacillus jensenii/Lactobacillus gasseri. The mean relative abundance of Prevotella bivia, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera type I became significantly higher in cases 4 days before (P. bivia), 3 days before (G. vaginalis), and on the day of (A. vaginae and Megasphaera type I) iBV onset. The mean relative abundance of Sneathia sanguinegens, Finegoldia magna, BV-associated bacteria 1-3, and L. iners was not significantly different between groups before onset of iBV. Conclusion: G. vaginalis, P. bivia, A. vaginae, and Megasphaera type I may play significant roles in iBV.

A quantitative appraisal of African Americans' decisions to become registered organ donors at the driver's license office.

African American (AA) organ donation registration rates fall short of national objectives. The goal of the present study was to utilize data acquired from a quantitative telephone survey to provide information for a future Department of Motorized Vehicles (DMV) intervention to increase AA organ donor registration at the DMV. AAs (n = 20 177) that had visited an Alabama DMV office within a 3-month period were recruited via direct mailing to participate in a quantitative phone survey. Data from 155 respondents that participated in the survey were analyzed. Of those respondents deciding to become a registered organ donor (ROD; n = 122), one-third made that decision at the time of visiting the DMV. Of those who chose not to become a ROD (n = 33), one-third made the decision during the DMV visit. Almost 85% of all participants wanted to learn more about organ donation while waiting at the DMV, preferably via TV messaging (digital signage), with the messaging delivered from organ donors, transplant recipients, and healthcare experts. Altruism, accurate organ donation information, and encouragement from family and friends were the most important educational topics to support AAs becoming a ROD. These data provide a platform to inform future interventions designed to increase AAs becoming a ROD at the DMV.

A SEER Database Analysis of the Survival Advantage of Transarterial Chemoembolization for Hepatocellular Carcinoma: An Underutilized Therapy.

PURPOSE: To measure transarterial chemoembolization utilization and survival benefit among patients with hepatocellular carcinoma (HCC) in the Surveillance, Epidemiology, and End Results (SEER) patient population. MATERIALS AND METHODS: A retrospective study identified 37,832 patients with HCC diagnosed between 1991 and 2011. Survival was estimated by Kaplan-Meier method and compared by log-rank test. Propensity-score matching was used to address an imbalance of covariates. RESULTS: More than 75% of patients with HCC did not receive any HCC-directed treatment. Transarterial chemoembolization was the most common initial therapy (15.9%). Factors associated with the use of chemoembolization included younger age, more HCC risk factors, more comorbidities, higher socioeconomic status, intrahepatic tumor, unifocal tumor, vascular invasion, and smaller tumor size (all P < .001). Median survival was improved in patients treated with chemoembolization compared with those not treated with chemoembolization (20.1 vs 4.3 mo; P < .0001). Similar findings were demonstrated in propensity-scoring analysis (14.5 vs 4.2 mo; P < .0001) and immortal time bias sensitivity analysis (9.5 vs 3.6 mo; P < .0001). There was a significantly improved survival hazard ratio (HR) in patients treated with chemoembolization (HR, 0.42; 95% confidence interval, 0.39-0.45). CONCLUSIONS: Patients with HCC treated with transarterial chemoembolization experienced a significant survival advantage compared with those not treated with transarterial chemoembolization. More than 75% of SEER/Medicare patients diagnosed with HCC received no identifiable oncologic treatment. There is a significant public health need to increase awareness of efficacious HCC treatments such as transarterial chemoembolization.

Psychometric evaluation of an online and paper accidental bowel leakage questionnaire: The ICIQ-B questionnaire.

AIMS: To evaluate the psychometric properties of an online versus paper US-English version of the International Consultation on Incontinence Questionnaire-Bowel (ICIQ-B). METHODS: The ICIQ-B includes 17 items under 3 domains: bowel pattern (5 items), bowel control (7 items), and quality of life (5 items). We recruited community-dwelling adults seeking treatment for ≥monthly bowel leakage from specialty clinics within a VA medical center and university affiliate. An online versus paper version was evaluated at baseline, 2 weeks later, and 3 months after nonsurgical treatments per usual care. We assessed test-retest reliability (Pearson correlations) at 2 weeks, internal consistency (Cronbach's alpha), and convergent validity (Pearson correlations). Sensitivity to change was the difference between the baseline and post-treatment (3-month) scores. RESULTS: Mean age was 58.0 ± 11.9; 36% Veterans, 52% women. At baseline, 2 weeks, and 3 months, we found no differences in the online vs paper scores for the bowel control and quality of life domains. The ICIQ-B demonstrated fair internal consistency for the bowel pattern domain (Cronbach's α = 0.36-0.54). Internal consistency on the bowel pattern domain was better with the paper version than the online version at 2 weeks (P < 0.05) and 3 months (P < 0.01) with no difference at baseline. All other domains had good internal consistency (Cronbach's α > 0.80), good retest reliability (r ≥ 0.70, P < 0.001), domain-specific convergent validity for stool consistency (P < 0.05), incontinence severity (P ≤ 0.002), and quality of life impact (P < 0.05). After nonsurgical treatments, we found a reasonable response to change (P ≤ 0.05). CONCLUSIONS: Online and paper versions had robust psychometric data for use among U.S. men and women, including Veterans. Neurourol. Urodynam. 36:166-170, 2017. © 2015 Wiley Periodicals, Inc.

Factors Perceived to Influence the Decision for African Americans to Become Registered Organ Donors at the Department of Motorized Vehicles.

BACKGROUND: African Americans (AA) are a third as likely as Caucasians to become registered organ donors at the Department of Motorized Vehicles (DMV). The Department of Health and Human Services has set the goal that at least 50% of adults in each state are registered donors. AIMS: The purpose of this study was to explore the personal, behavioral and environmental factors associated with AA donor registration decision-making at the DMV. METHODS: Guided by the Social Cognitive Theory, 13 focus groups (n = 100 participants) were conducted with AAs within 3 months of visiting a DMV and making a decision regarding whether to become or to not become a registered donor. The data were analyzed using inductive thematic and qualitative content analyses. RESULTS: Study participants expressed a desire to learn more information while waiting in line at the DMV. Knowing a family member or friend in need of an organ transplant, and the desire to make one's own decision were two salient factors associated with the decision to become a registered organ donor. Several aspects of the DMV environment (e.g., noisy, overcrowded, lacking privacy) were cited as deterrents to becoming a registered donor. DISCUSSION: This study highlights the personal, behavioral and environmental factors associated with AA organ donor registration decision-making at the DMV. CONCLUSION: The DMV is a setting where many adults make a decision about organ donation. Policies that create an environment in the DMV to support informed decision-making (e.g., privacy, informed clerks, available educational materials, etc.) are indicated.

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease.

BACKGROUND: Subsets of myeloid-derived regulatory cells (MDRCs), which are phenotypically similar to the myeloid-derived suppressor cells found in patients with cancer, have recently been appreciated as critical regulators of airway inflammation in mouse models of asthma. OBJECTIVE: We test the hypothesis that subsets of airway MDRCs contribute differentially to the inflammatory milieu in human asthma and chronic obstructive pulmonary disease (COPD). METHODS: We used bronchoalveolar lavage to identify and characterize human airway MDRCs from 10 healthy subjects, 9 patients with mild asthma, and 8 patients with COPD, none of whom were treated with inhaled or systemic corticosteroids. We defined subsets of airway MDRCs using flow cytometry, the molecular mediators they produce, and their abilities to regulate proliferation of polyclonally activated autologous T lymphocytes. RESULTS: We found substantial differences in the functional potential of MDRC subsets in healthy subjects, patients with asthma, and patients with COPD, with these differences regulated by the nitrosative and oxidative free radicals and cytokines they produced. Nitric oxide-producing MDRCs suppressed and superoxide-producing MDRCs enhanced proliferation of polyclonally activated autologous CD4 T cells. HLA-DR(+)CD11b(+)CD11c(+)CD163(-) superoxide-producing MDRCs, which stimulated proliferation of autologous T cells, comprised a high fraction of MDRCs in the airways of patients with mild asthma or COPD but not those of healthy control subjects. CD11b(+)CD14(+)CD16(-)HLA-DR(-) nitric oxide-producing MDRCs, which suppressed T-cell proliferation, were present in high numbers in airways of patients with mild asthma but not patients with COPD or healthy control subjects. CONCLUSION: Subsets of airway MDRCs conclusively discriminate patients with mild asthma, patients with COPD, and healthy subjects from each other. The distinctive activities of these MDRCs in patients with asthma or COPD might provide novel targets for new therapeutics for these common disorders. [Corrected]

Vertical Sculpted Pillar Reduction Mammaplasty in 317 Patients: Technique, Complications, and BREAST-Q Outcomes.

BACKGROUND: The senior author (JCG) has described the vertical sculpted pillar breast reduction. OBJECTIVES: This manuscript aimed to compare this technique's safety profile to other established techniques via complication rate reporting. Few studies have utilized the BREAST-Q for long-term outcomes reporting in bilateral reduction mammaplasty patients. BREAST-Q outcome comparisons, between cosmetic and insurance-based breast reduction cohorts, have not been previously reported. METHODS: A retrospective chart review was performed on patients who underwent reduction mammaplasty using the vertical sculpted pillar technique. The BREAST-Q postoperative reduction mammaplasty module was administered. Complication rates and outcomes data were compared among patient cohorts distinguished by pedicle, scar pattern, and payor population. Statistically significant differences were set at P < .05. RESULTS: Compared to the superior pedicle, use of the superomedial pedicle statistically increased rates of postoperative fat necrosis in this series. Complication rates did not differ among scar patterns, but use of a J, L-shaped, or short-T scar decreased the need for secondary/revisional surgery. Cosmetic and insurance-based outcomes did not differ in any domain of the postoperative reduction mammaplasty BREAST-Q module. CONCLUSIONS: Complications data for the vertical sculpted pillar reduction mammaplasty were comparable to published results for other techniques. Complication rates are unaffected by scar pattern. Superomedial pedicle selection and larger insurance-based reductions may predispose to statistically significant increases in fat necrosis compared to use of the superior pedicle. Payor source neither affects the majority of complication rates, nor BREAST-Q satisfaction and quality of life domains. This information can be used to improve management of expectations during the preoperative consultation process. LEVEL OF EVIDENCE: 4 Therapeutic.

Simple regression for correcting ΔCt bias in RT-qPCR low-density array data normalization.

BACKGROUND: Reverse transcription quantitative PCR (RT-qPCR) is considered the gold standard for quantifying relative gene expression. Normalization of RT-qPCR data is commonly achieved by subtracting the Ct values of the internal reference genes from the Ct values of the target genes to obtain ΔCt. ΔCt values are then used to derive ΔΔCt when compared to a control group or to conduct further statistical analysis. RESULTS: We examined two rheumatoid arthritis RT-qPCR low density array datasets and found that this normalization method introduces substantial bias due to differences in PCR amplification efficiency among genes. This bias results in undesirable correlations between target genes and reference genes, which affect the estimation of fold changes and the tests for differentially expressed genes. Similar biases were also found in multiple public mRNA and miRNA RT-qPCR array datasets we analysed. We propose to regress the Ct values of the target genes onto those of the reference genes to obtain regression coefficients, which are then used to adjust the reference gene Ct values before calculating ΔCt. CONCLUSIONS: The per-gene regression method effectively removes the ΔCt bias. This method can be applied to both low density RT-qPCR arrays and individual RT-qPCR assays.

Small sample performance of bias-corrected sandwich estimators for cluster-randomized trials with binary outcomes.

The sandwich estimator in generalized estimating equations (GEE) approach underestimates the true variance in small samples and consequently results in inflated type I error rates in hypothesis testing. This fact limits the application of the GEE in cluster-randomized trials (CRTs) with few clusters. Under various CRT scenarios with correlated binary outcomes, we evaluate the small sample properties of the GEE Wald tests using bias-corrected sandwich estimators. Our results suggest that the GEE Wald z-test should be avoided in the analyses of CRTs with few clusters even when bias-corrected sandwich estimators are used. With t-distribution approximation, the Kauermann and Carroll (KC)-correction can keep the test size to nominal levels even when the number of clusters is as low as 10 and is robust to the moderate variation of the cluster sizes. However, in cases with large variations in cluster sizes, the Fay and Graubard (FG)-correction should be used instead. Furthermore, we derive a formula to calculate the power and minimum total number of clusters one needs using the t-test and KC-correction for the CRTs with binary outcomes. The power levels as predicted by the proposed formula agree well with the empirical powers from the simulations. The proposed methods are illustrated using real CRT data. We conclude that with appropriate control of type I error rates under small sample sizes, we recommend the use of GEE approach in CRTs with binary outcomes because of fewer assumptions and robustness to the misspecification of the covariance structure.

Loperamide Versus Psyllium Fiber for Treatment of Fecal Incontinence: The Fecal Incontinence Prescription (Rx) Management (FIRM) Randomized Clinical Trial.

BACKGROUND: Fecal incontinence is a devastating condition with few US Food and Drug Administration-approved pharmacologic treatment options. Loperamide and psyllium, both first-line treatments, have different mechanisms of action without any comparative data. OBJECTIVE: The purpose of this study was to examine the effectiveness and tolerability of loperamide compared with psyllium for reducing fecal incontinence. We hypothesized that psyllium fiber supplementation would be more effective than loperamide for reducing fecal incontinence episodes and have fewer adverse effects. DESIGN: We conducted a randomized, double-blind, placebo-controlled crossover trial comparing loperamide (followed by psyllium) with psyllium (followed by loperamide). SETTINGS: Our sites included outpatient clinics within a Veterans Affairs medical center and university affiliate. PATIENTS: Participants included community-dwelling adults (n = 80) with at least 1 fecal incontinent episode on a 7-day bowel diary. INTERVENTION: Participants received either daily loperamide (plus placebo psyllium powder) or psyllium powder (plus loperamide placebo) for 4 weeks. After a 2-week washout, participants crossed over to 4 weeks of alternate treatment. MAIN OUTCOME MEASURES: The primary outcome was the number of fecal incontinence episodes from 7-day bowel diaries. Secondary outcomes included symptom severity, quality of life, and tolerability. RESULTS: Mean age was 60.7 ± 10.1 years; 68% were men. After determining nonsignificant carryover effects, combined analyses showed no differences between the loperamide and psyllium groups for reducing fecal incontinent episodes, symptom severity, or quality of life. Within each group, both loperamide and psyllium reduced fecal incontinent episodes and improved symptom severity and quality of life. Constipation occurred in 29% of participants for loperamide vs 10% for psyllium. LIMITATIONS: Limitations include the washout period length and dropout rate after crossing over to the second intervention. CONCLUSIONS: Both loperamide and psyllium improve fecal incontinence. Loperamide was associated with more adverse effects, especially constipation.