Combining Inserts With Warning Labels on Cigarette Packs to Promote Smoking Cessation: A 2-Week Randomized Trial.

BACKGROUND: Cigarette pack inserts with messages on cessation benefits and advice are a promising labeling policy that may help promote smoking cessation. PURPOSE: To assess insert effects, with and without accompanying pictorial health warning labels(HWLs), on hypothesized psychosocial and behavioral outcomes. METHODS: We conducted a 2 × 2 between-subject randomized trial (inserts with efficacy messages vs. no inserts; large pictorial HWLs vs. small text HWLs), with 367 adults who smoked at least 10 cigarettes a day. Participants received a 14-day supply of their preferred cigarettes with packs modified to reflect their experimental condition. Over 2 weeks, we surveyed participants approximately 4-5 times a day during their smoking sessions, querying feelings about smoking, level of worry about harms from smoking, self-efficacy to cut down on cigarettes, self-efficacy to quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported their perceived susceptibility to smoking harms and, for the last 24 hr, their frequency of thinking about smoking harms and cessation benefits, conversations about smoking cessation or harms, and foregoing or stubbing out cigarettes before they finished smoking. Mixed-effects ordinal and logistic models were estimated to evaluate differences between groups. RESULTS: Participants whose packs included inserts were more likely than those whose packs did not include inserts to report foregoing or stubbing out of cigarettes (OR = 2.39, 95% CI = 1.36, 4.20). Otherwise, no statistically significant associations were found between labeling conditions and outcomes. CONCLUSIONS: This study provides some evidence, albeit limited, that pack inserts with efficacy messages can promote behaviors that predict smoking cessation attempts.

Cigarette pack inserts (small leaflets inside packs) with messages about quitting benefits and tips to quit may promote smoking cessation. We randomly assigned 367 adult smokers to one of four groups: control group with small health warning labels (HWLs) on the side of packs; inserts with cessation messages and small HWLs; large picture HWLs showing health effects from smoking; inserts and large picture HWLs. Participants received a 14-day supply of their preferred cigarettes in packs that reflected their assigned group. Over 2 weeks, we surveyed participants 4­5 times a day during times when they smoked, asking their feelings about smoking and smoking-related harms, confidence to reduce cigarettes and quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported on the prior 24 hr: how often they thought about smoking harms and cessation benefits; conversations about smoking cessation or harms; and foregoing or stubbing out cigarettes before they finished smoking. People whose packs had inserts (with or without picture HWLs) were more likely than those whose packs did not include inserts (control group or picture HWLs only) to report foregoing or stubbing out of cigarettes. This study provides some evidence that inserts with cessation messages may promote smoking cessation.

Differential responses to cigarette package labeling alternatives among adults who smoke: Results from a randomized trial.

INTRODUCTION: Little experimental research has evaluated whether the effects of cigarette package inserts with efficacy messages and/or pictorial health warning labels (PHWLs) differ across key subgroups of adults who smoke. METHODS: Adults who reported currently smoking (n=367) were randomly assigned to one of four groups: small text-only health warning labels (HWLs) on pack sides (control); inserts with efficacy messages and small HWLs (inserts-only); PHWLs showing harms of smoking (PHWLs-only); both (inserts+PHWLs). Participants received a 14-day supply of cigarettes labeled to reflect their group. Every evening over two weeks, participants reported forgoing and stubbing out cigarettes before they finished smoking over the prior 24 hours, combined into a binary indicator of either behavior (e.g., forgoing/stubbing). Separate mixed-effects logistic models were estimated to evaluate moderation of labeling group contrasts (i.e., PHWLs vs not; inserts vs. not; inserts-only vs. inserts+PHWLs; PHWLs-only vs. inserts+PHWLs) by baseline covariates (self-efficacy to quit, intention to quit, education, health literacy, time discounting), predicting day-level forgoing/stubbing. RESULTS: Education moderated PHWL effects, with PHWLs predicting more forgoing/stubbing only among those with low education (OR=4.68, p<0.001). Time discounting moderated insert effects, with inserts promoting fogoing/stubbing only among those with low time discounting (i.e., lower impulsivity; OR=4.35, p<0.001). CONCLUSIONS: Inserts with efficacy messages appear effective mostly among people with low time discounting, whereas PHWLs appear most effective amongst those with low education, suggesting their potential to address education-related disparities. Labeling strategies appeared equally effective across subgroups defined by self-efficacy to quit, quit intention, and health literacy. Combining inserts with PHWLs did not appear to mitigate moderation effects. IMPLICATIONS: This randomized trial with adults who smoke suggests that cigarette packs with inserts describing cessation benefits and tips can promote cessation-related behaviors (i.e., forgoing or stubbing out cigarettes) among those with low time discounting (i.e., low impulsivity). Alternative interventions may be needed for people with high time discounting, as found in cessation trials. Pictorial health warning labels (PHWLs) appear most effective among those with low education, potentially addressing education-related disparities. No differential effects were found for those with different levels of self-efficacy to quit, quit intentions, or health literacy. Combining inserts and PHWLs may not be more effective than either alone.

Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration.

Alu retroelements propagate via retrotransposition by hijacking long interspersed nuclear element-1 (L1) reverse transcriptase (RT) and endonuclease activities. Reverse transcription of Alu RNA into complementary DNA (cDNA) is presumed to occur exclusively in the nucleus at the genomic integration site. Whether Alu cDNA is synthesized independently of genomic integration is unknown. Alu RNA promotes retinal pigmented epithelium (RPE) death in geographic atrophy, an untreatable type of age-related macular degeneration. We report that Alu RNA-induced RPE degeneration is mediated via cytoplasmic L1-reverse-transcribed Alu cDNA independently of retrotransposition. Alu RNA did not induce cDNA production or RPE degeneration in L1-inhibited animals or human cells. Alu reverse transcription can be initiated in the cytoplasm via self-priming of Alu RNA. In four health insurance databases, use of nucleoside RT inhibitors was associated with reduced risk of developing atrophic macular degeneration (pooled adjusted hazard ratio, 0.616; 95% confidence interval, 0.493-0.770), thus identifying inhibitors of this Alu replication cycle shunt as potential therapies for a major cause of blindness.

Functional Multivariable Logistic Regression With an Application to HIV Viral Suppression Prediction.

Motivated by improving the prediction of the human immunodeficiency virus (HIV) suppression status using electronic health records (EHR) data, we propose a functional multivariable logistic regression model, which accounts for the longitudinal binary process and continuous process simultaneously. Specifically, the longitudinal measurements for either binary or continuous variables are modeled by functional principal components analysis, and their corresponding functional principal component scores are used to build a logistic regression model for prediction. The longitudinal binary data are linked to underlying Gaussian processes. The estimation is done using penalized spline for the longitudinal continuous and binary data. Group-lasso is used to select longitudinal processes, and the multivariate functional principal components analysis is proposed to revise functional principal component scores with the correlation. The method is evaluated via comprehensive simulation studies and then applied to predict viral suppression using EHR data for people living with HIV in South Carolina.

Effect of body mass index on acute postoperative complications following Total Ankle Arthroplasty (TAA).

BACKGROUND: Total ankle arthroplasty (TAA) is an effective treatment for various ankle pathologies, but some concern remains for the high associated complication and failure rates relative to major joint arthroplasty of the hip and knee. Patient body mass index (BMI) is a modifiable and potentially important preoperative variable when evaluating postoperative complications. The purpose of this study is to evaluate the effect of BMI, age and sex on the acute postoperative complication rate after TAA. METHODS: We retrospectively reviewed adult patients who underwent TAA between 2006 and 2021 from the NSQIP database. Using overweight patients as the reference BMI group, we utilized log-binomial models to estimate risk ratios on outcomes while adjusting for sex and age to investigate whether there were significant adjusted differences in complication rates among the BMI groups. RESULTS: We found that, relative to overweight patients, there were no statistically significant differences in the risk of acute complications for underweight (BMI < 18.5) (P = .118), healthy weight (18.5≤BMI < 25) (P = .544), obese (30≤BMI < 40) (P = .930), or morbidly obese (BMI < 40) (P = .602) patients who underwent TAA. There were also no statistically significant differences in the risk of acute complications based on age category (P = .482,.824) or sex (P = .440) for TAA. Additionally, there were no significant differences between the BMI groups for either major complications (P = .980) or minor complications (P = .168). CONCLUSION: Ultimately, we found that BMI, age, and sex did not lead to statistically significant differences in the risk of complications within 30 days postoperatively for TAA, even when stratified by major vs minor complications. LEVEL OF EVIDENCE: Level III.

Periodontal Disease Treatment After Stroke or Transient Ischemic Attack: The PREMIERS Study, a Randomized Clinical Trial.

BACKGROUND: Patients with stroke/transient ischemic attack and periodontal disease (PD) are at increased risk for cardiovascular events. PD treatments that can improve stroke risk factors were tested if they might assist patients with cerebrovascular disease. METHODS: In this multicenter phase II trial, patients with stroke/transient ischemic attack and moderately severe PD were randomly assigned to intensive or standard PD treatment arms. The primary outcome measure was a composite of death, myocardial infarction, and recurrent stroke, as well as adverse events. Secondary outcome included changes in stroke risk factors. RESULTS: A total of 1209 patients with stroke/transient ischemic attack were screened, of whom 481 met the PD eligibility criteria; 280 patients were randomized to intensive arm (n=140) and standard arm (n=140). In 12-month period, primary outcome occurred in 11 (8%) in the intensive arm and 17 (12%) in the standard arm. The intensive arm was nonsuperior to the standard arm (hazard ratio, 0.65 [95% CI, 0.30-1.38]) with similar rates of adverse events (sepsis 2.1% versus 0.7%; dental bleeding 1.4% versus 0%; and infective endocarditis 0.7% versus 0%). Secondary-outcome improvements were noted in both arms with diastolic blood pressure and high-density lipoprotein cholesterol (P<0.05). CONCLUSIONS: In patients with recent stroke/transient ischemic attack and PD, intensive PD treatment was not superior to standard PD treatment in prevention of stroke/myocardial infarction/death. Fewer events were noted in the intensive arm and the 2 arms were comparable in the safety outcomes. Secondary-outcome measures showed a trend toward improvement, with significant changes noted in diastolic blood pressure and high-density lipoprotein in both the treatment arms.

Real-world clinical outcomes among US Veterans with oral factor xa inhibitor-related major bleeding treated with andexanet alfa or 4-factor prothrombin complex concentrate.

Oral factor Xa (FXa) inhibitors significantly reduce incidence of stroke and thromboembolic events in patients with atrial fibrillation or venous thromboembolism. Due to various factors and the lack of a randomized controlled trial comparing andexanet alfa to usual care, non-specific replacement agents including 4 F-PCC are still used off-label for FXa inhibitor bleed management. Clinical and mortality data were extracted from the inpatient medical data and Veteran Affairs (VA) vital status files over the time of March 2014 through December 2020. Propensity score-weighted models were used for this retrospective cohort study using data from the Veterans Affairs Informatics and Computing Infrastructure (VINCI). The study included 255 patients (85-andexanet alfa and 170-4 F-PCC) exposed to an oral factor Xa inhibitor and hospitalized with an acute major, gastrointestinal (GI), intracranial (ICH) or other bleed. In-hospital mortality was significantly lower in the andexanet alfa cohort compared to the 4 F-PCC cohort (10.6% vs. 25.3%, p = 0.01). Propensity score-weighted Cox models reveal a 69% lower hazard of in-hospital mortality for those treated with andexanet alfa (HR 0.31, 95% CI 0.14-0.71) compared to those treated with 4 F-PCC. Additionally, those treated with andexanet alfa had a lower 30-day mortality rate and lower 30-day hazard of mortality in the weighted Cox model (20.0% vs. 32.4%, p = 0.039; HR 0.54, 95% CI 0.30-0.98) compared to those treated with 4 F-PCC. Among 255 US veterans with major bleeding in the presence of an oral factor Xa inhibitor, treatment with andexanet alfa was associated with lower in-hospital and 30-day mortality than treatment with 4 F-PCC.

A mixed-method study of perceptions of cigarette pack inserts among adult smokers from New York and South Carolina exposed as part of a randomized controlled trial.

While many countries require prominent pictorial health warning labels (PHWLs) on the outside of cigarette packs to communicate the harms of smoking, there is evidence that cigarette pack inserts that contain efficacy messages may enhance the effectiveness of PHWLs. The US Food and Drug Administration (FDA) has regulatory authority to communicate with smokers through inserts. While current labeling regulations do not require inclusion of inserts, the FDA could implement them in the future. This study assesses US smokers' perceptions of cigarette package inserts at the conclusion of a two-week randomized trial on cigarette labeling where half of participants were exposed to insert messages (two response-efficacy messages and two self-efficacy messages) in their packs. Participants (n = 359) completed a 30- to 60-min interview with both quantitative and qualitative assessments, including measures of recall and perceived message effectiveness (PME) for specific inserts. Correlates of recall and PME were estimated using mixed-effects regression models. Qualitative responses to PME items were analyzed using thematic analysis. Response-efficacy messages had higher PME and recall than self-efficacy messages. People had diverse responses to the inserts, including that they were positive, thought-provoking, and helpful. Reactions to and perceptions of the inserts indicate potential benefits of integrating efficacy messages into labeling policies.

Leukotriene receptor antagonism with montelukast as a possible therapeutic for venous thromboembolism prophylaxis: An observational study.

BACKGROUND: Arachidonic acid (AA), which is metabolized via the cyclooxygenase (COX) and the lipoxygenase (LOX) pathways, was found to be associated with venous thromboembolism (VTE). Metabolites of the LOX pathway include cysteinyl (Cys) Leukotrienes (LT), potent proinflammatory mediators, which have also been implicated in cardiovascular disease. OBJECTIVE: The purpose of this study was to examine if cysteinyl leukotriene receptor blockade by montelukast, lowers the risk of VTE. METHODS: We conducted a retrospective cohort study examining VTE risk among COPD patients from the United States Department of Veterans Affairs. We use propensity score matching and Cox survival models to estimate the hazard ratio comparing montelukast exposure to non-exposure. Montelukast exposure was associated with a 15.9% reduction in risk of VTE compared to those unexposed (HR= 0.841; 95% CI= (0.758-0.934)). CONCLUSION: The results of this study demonstrate that targeting LTs might be beneficial for VTE prophylaxis using the clinically available LT inhibitor, montelukast. Importantly, further research on LTs is warranted to fully understand and validate this relationship.

Melatonin use and the risk of 30-day mortality among US veterans with sepsis: A retrospective study.

Prior research suggests melatonin has beneficial effects that could improve survival among sepsis patients. This exploratory analysis sought to compare 30-day survival among melatonin treated and untreated patients with sepsis. A retrospective cohort study was conducted among patients with a primary inpatient admission diagnosis for sepsis utilizing the International Classification of Diseases, versions 9 and 10, Clinical Modification (ICD-9-CM and ICD-10-CM) diagnosis codes between 2000 and 2021. Propensity score weighting was utilized, accounting for demographic, clinical, and laboratory factors. Weighted Cox models were estimated for 30-day in-hospital and 30-day overall survival. A total of 9386 patients were included in the study with 593 exposed to melatonin within the first day of hospitalization. Propensity score weighted Cox models reveal melatonin was associated with a 37.9% decreased risk of 30-day in-hospital mortality (HR = 0.621; 95% CI = [0.415-0.931]) and a 33.5% decreased risk of 30-day overall mortality (HR = 0.665; 95% CI = [0.493-0.897]). Factors associated with higher risk of both in-hospital and overall mortality include male sex, white race, age, higher Charlson comorbidity burden, sodium and potassium levels, intensive care unit stay, invasive ventilation, and vasopressor use. Higher serum albumin levels are associated with lower mortality risks. Among patients diagnosed with sepsis, exposure to melatonin was associated with a lower in-hospital and 30-day mortality. Additional research is warranted to fully understand the role of melatonin in sepsis.

Messaging about very low nicotine cigarettes (VLNCs) to influence policy attitudes, harm perceptions and smoking motivations: a discrete choice experiment.

BACKGROUND: To reduce smoking and the harms it causes, countries, including the USA, are considering policies to reduce nicotine in combustible tobacco to minimally addictive levels. Effective messages about very low nicotine cigarettes (VLNCs) and this policy are crucial in combating misperceptions threatening the policy's effectiveness. DATA AND METHODS: A discrete choice experiment assessed messages about VLNCs. Participants were 590 adults who smoked exclusively, 379 adults who both smoked and used e-cigarettes, 443 adults who formerly smoked and 351 young adults who never smoked (total n=1763). Seven message attributes were varied systematically (source, harm, chemicals, nicotine, satisfaction, addictiveness and quitting efficacy). Outcomes were selection of messages that generated the most positive attitude towards reduced nicotine policy, the greatest perceived harmfulness of VLNCs, and most strongly motivated quitting and initiating behaviour for VLNCs. RESULTS: Information about specific harms and chemicals of VLNCs had the largest effects on selection of messages as eliciting more negative attitudes towards VLNCs policy, increasing perceived VLNC harmfulness, increasing motivation to quit VLNCs and decreasing motivation to try VLNCs. Messages with information about quitting efficacy were selected as more motivating to quit among those who smoke, but also more motivating to try VLNCs among those who do not smoke. CONCLUSION: Harm and chemical information can be prioritised to ensure VLNCs are not misperceived as less harmful than regular cigarettes. Messages about increased quitting efficacy and reduced addictiveness associated with VLNCs may backfire if presented to those who do not smoke.

Association Between the Use of Antibiotics, Antivirals, and Hospitalizations Among Patients With Laboratory-confirmed Influenza.

BACKGROUND: Clinicians may prescribe antibiotics to influenza patients at high risk for bacterial complications. We explored the association between antibiotics, antivirals, and hospitalization among people with influenza. METHODS: A retrospective cohort study of patients with confirmed influenza with encounters during January 2011-January 2019 was conducted using data from the Veterans Affairs Informatics and Computing Infrastructure (VINCI). We compared inpatient hospitalizations (all-cause and respiratory) within 30 days of influenza diagnosis between 4 patient cohorts: (1) no treatment (n = 4228); (2) antibiotic only (n = 671); (3) antiviral only (n = 6492); and (4) antibiotic plus antiviral (n = 1415). We estimated relative risk for hospitalization using Poisson generalized linear model and robust standard errors. RESULTS: Among 12 806 influenza cases, most were white men (mean age, 57-60 years). Those with antivirals only, antibiotic plus antiviral, and antibiotics only all had a statistically significant lower risk of all-cause and respiratory hospitalization compared to those without treatment. Comparing the antibiotic plus antiviral cohort to those who were prescribed an antiviral alone, there was a 47% lower risk for respiratory hospitalization (relative risk, 0.53 [95% confidence interval, .31-.94]), and no other statistical differences were detected. CONCLUSIONS: Those prescribed an antiviral, antibiotic, or both had a lower risk of hospitalization within 30 days compared to those without therapy. Furthermore, intervention with both an antibiotic and antiviral had a lower risk of respiratory hospitalization within 30 days compared to those with an antiviral alone. Importantly, the absolute magnitude of decreased risk with antibiotic plus antiviral therapy is small and must be interpreted within the context of the overall risk of antibiotic usage.

Effect of initial treatment on health-related quality of life in patients with newly diagnosed multiple myeloma without immediate stem cell transplant intent: results from the Connect® MM Registry.

Although new multiple myeloma (MM) therapies are effective in alleviating some disease-associated symptoms (e.g. bone pain, fatigue, functional decline), they can result in additional toxicities, further impacting health-related quality of life (HRQoL). Here, we compared HRQoL and safety of lenalidomide-bortezomib-dexamethasone [RVd (n = 445)], bortezomib-melphalan-prednisone [VMP (n = 77)] and Vd or VMP (n = 588) in patients with newly diagnosed MM (NDMM) from the Connect® MM Registry, a large, USA, multicentre, prospective observational cohort study. Functional Assessment of Cancer Therapy-Multiple Myeloma subscale, EuroQol-5D overall score and Bone Pain Inventory HRQoL scores were significantly improved with RVd versus Vd/VMP. Serious adverse event rates were similar in all groups. Treatment with RVd maintained HRQoL in this real-world, largely community-based population of patients with NDMM.

3D Printing of Supramolecular Polymer Hydrogels with Hierarchical Structure.

Liquid crystalline hydrogels are an attractive class of soft materials to direct charge transport, mechanical actuation, and cell migration. When such systems contain supramolecular polymers, it is possible in principle to easily shear align nanoscale structures and create bulk anisotropic properties. However, reproducibly fabricating and patterning aligned supramolecular domains in 3D hydrogels remains a challenge using conventional fabrication techniques. Here, a method is reported for 3D printing of ionically crosslinked liquid crystalline hydrogels from aqueous supramolecular polymer inks. Using a combination of experimental techniques and molecular dynamics simulations, it is found that pH and salt concentration govern intermolecular interactions among the self-assembled structures where lower charge densities on the supramolecular polymers and higher charge screening from the electrolyte result in higher viscosity inks. Enhanced hierarchical interactions among assemblies in high viscosity inks increase the printability and ultimately lead to greater nanoscale alignment in extruded macroscopic filaments when using small nozzle diameters and fast print speeds. The use of this approach is demonstrated to create materials with anisotropic ionic and electronic charge transport as well as scaffolds that trigger the macroscopic alignment of cells due to the synergy of supramolecular self-assembly and additive manufacturing.

Leukotriene inhibition and the risk of lung cancer among U.S. veterans with asthma.

Leukotriene inhibition, in vitro and in vivo, is found to suppress tumor growth across a variety of cancer cells. A mouse model of lung cancer revealed that the leukotriene inhibitor montelukast induced lung cancer cell death. Based on the preclinical data we hypothesize that exposure to a leukotriene inhibitor is associated with a lower risk of lung cancer. We conducted a national retrospective cohort study among U.S. Veterans with asthma to explore the relationship between leukotriene inhibition and incident lung cancer. We utilize a variety of statistical techniques, including cox proportional hazards models, propensity score matching and falsification testing to examine the association. A total of 558,466 patients met study criteria consisting of 23,730 patients with leukotriene exposure and 534,736 patients with no leukotriene medication use. Leukotriene inhibitor exposure reduced the risk of lung cancer by 17% (HR = 0.830; 95% CI = (0.757-0.911)) in the unmatched and 22.2% in the matched analysis (HR = 0.778 95% CI = (0.688-0.88)). Falsification testing with appendicitis and rotator cuff injury end points, suggest no evidence of selection bias. However, because treatment was not randomized, residual confounding cannot be ruled out. The pre-clinical data on leukotriene inhibition and lung cancer combined with our database analysis provide intriguing evidence warranting further research into the relationship between leukotrienes and lung cancer.

A 'novel' multi-component approach to promote physical activity among older cancer survivors: a pilot randomized controlled trial.

BACKGROUND: Physical activity (PA) provides many benefits for recovery from cancer treatments. Many older (65+ years) cancer survivors which comprise the majority of the cancer survivor population, do not meet recommended PA guidelines. This study explored the feasibility and acceptability of using audiobooks as part of a 12-week multi-component intervention to increase steps/day, light and moderate-to-vigorous intensity PA among older survivors. METHODS: Twenty older cancer survivors (95% female, mean age = 71.55 years, 90% White, 85% overweight/obese, 75% breast cancer survivors, mean 1.96 years since treatment completion) were randomized into one of the two study groups (Audiobook Group, n = 12, Comparison Group, n = 8). Both study groups were provided a tailored step goal program over the 12-week intervention; weekly step increases were based on a percent increase from baseline. Participant self-monitored their steps using a Fitbit Charge 2. In addition, the Audiobook group were encouraged to listen to audiobooks (downloaded onto a smartphone device via an app available at no cost from the local library) during PA to add enjoyment and increase PA. Regression analyses on steps/day, light and moderate-to-vigorous PA/week and sedentary time/week as assessed by the Actigraph were conducted, after adjusting for Actigraph wear time. Data from the post-intervention questionnaire were summarized. RESULTS: Overall, majority of participants (89%) stated they were very satisfied with their participation and 100% reported that they were able to maintain their activity upon study completion. Retention rates were high. At post-intervention, there were significant differences favoring the Audiobook group for steps/day and moderate-to-vigorous PA/week. No significant group differences were found for minutes of light intensity PA/week and sedentary time/week. CONCLUSION: Piloting the implementation of a sustainable, innovative intervention among older survivors to increase their PA has significance for this group of survivors.

Predicting Infection in Very Preterm Infants: A Study Protocol.

BACKGROUND: Neonatal sepsis causes morbidity and mortality in preterm infants. Clinicians need a predictive tool for the onset of neonatal infection to expedite treatment and prevent morbidity. Abnormal thermal gradients, a central-peripheral temperature difference (CPtd) of >2°C or <0°C, and elevated heart rate characteristic (HRC) scores are associated with infection. OBJECTIVE: This article presents the protocol for the Predictive Analysis Using Temperature and Heart Rate Study. METHODS: This observational trial will enroll 440 very preterm infants to measure abdominal temperature and foot temperature every minute and HRC scores hourly for 28 days to compare infection data. Time with abnormal thermal gradients (Model 1) and elevated HRC scores (Model 2) will be compared to the onset of infections. For data analysis, CPtd (abdominal temperature - foot temperature) will be investigated as two derived variables, high CPtd (number/percentage of minutes with CPtd of >2°C) and low CPtd (number/percentage of minutes with CPtd of <0°C). In the infant-level model, the outcome yi will be an indicator of whether the infant was diagnosed with an infection in the first 28 days of life, and the high CPtd and low CPtd variables will be the average over the entire observation period, logit(yi) = ß0 + xiß1 + ziγ. For the day-level model, the outcome yit will be an indicator of whether the ith infant was diagnosed with an infection on the tth day from t = 4 through t = 28 or the day that infection is diagnosed (25 possible repeated measures), logit(yit) = ß0 + xitß1 + zitγ. It will be determined whether a model with only high CPtd or only low CPtd is superior in predicting infection. Also, the correlation of abnormal HRC scores with high CPtd and low CPtd values will be assessed. DISCUSSION: Study results will inform the design of an interventional study using temperatures and/or heart rate as a predictive tool to alert clinicians of cardiac and autonomic instability present with infection.

Statin Exposure and Risk of Prosthetic Joint Infection After Total Knee or Hip Arthroplasty Among U.S. Veterans.

BACKGROUND: Statins have a variety of pleiotropic effects that could be beneficial for patients undertaking total knee or hip arthroplasty. In vitro and in vivo models suggest the beneficial effects of statins through bone formation and modulating proinflammatory cytokines triggered by implant debris. However, statins also exhibit antimicrobial action and may reduce the risk of revision surgery via reducing the risk of infection. We sought to explore the relationship between statin use and prosthetic joint infection (PJI) after total knee or hip arthroplasty. METHODS: We use a retrospective cohort of patients undergoing total knee or hip arthroplasty performed within the Department of Veterans Affairs. To minimize selection bias between the statin exposed and unexposed patients, we used 1:1 ratio propensity score matching. We fit adjusted Cox proportional hazards models to quantify the risk of PJI between the cohorts within 1 year, 3 years, and all follow-up time. RESULTS: With a study period beginning from January 2000, a total of 60,241 patients were included. The unmatched Cox models reveal, over the entire follow-up time, a statistically significant lower risk of infection for the statin exposed patients (hazard ratio = 0.869; 95% confidence interval = [0.79-0.956]). The matched Cox model results reveal a statistically significant lower risk of PJI, only in the overall model, for the statin exposed cohort compared with the unexposed cohort (hazard ratio = 0.895, 95% confidence interval = [0.807-0.993]). CONCLUSION: Our analysis finds some support for the beneficial effects of statins for preventing PJI among patients undergoing total knee or hip arthroplasty.

Association between race and treatment patterns and survival outcomes in multiple myeloma: A Connect MM Registry analysis.

BACKGROUND: Studies have reported racial disparities in access to and use of multiple myeloma (MM) treatments between African American (AA) and White patients. Although AA patients demonstrate longer disease-specific survival, this has not uniformly translated into improved survival over time. The association between race and treatment patterns and survival outcomes was analyzed using data from the Connect MM Registry. METHODS: The Connect MM Registry is a large US, multicenter, prospective observational cohort study of patients with newly diagnosed MM. Patients who received first-line (1L) stem cell transplantation (SCT) or who did not receive SCT (non-SCT or non-stem cell transplantation [NSCT]) were grouped by raceEffects of race and transplantation status on the use of triplet treatment were estimated using logistic regression. RESULTS: Treatment patterns in 1L (types and duration of induction, posttransplantation maintenance) were similar between AA and White patients. SCT rates in 1L (32% vs 36%) and triplet treatment use (AA: 44% for NSCT patients and 72% for SCT patients; and White: 48% for NSCT patients and 72% for SCT patients) during first induction were similar. No significant effect of race or transplantation status on 1L triplet treatment use was observed. Race was not found to be associated with survival outcomes among patients who underwent NSCT; however, AA patients who received SCT had significantly longer overall survival compared with White patients who underwent SCT (not reached vs 88.2 months; hazard ratio, 0.56; 95% CI, 0.35-0.89 [P = .0141]). CONCLUSIONS: AA and White patients were found to have similar treatment patterns in the Connect MM Registry, suggesting that both groups had equal access to health care. In this real-world setting, AA patients received standard-of-care treatment, which might have contributed to better MM-specific survival compared with White patients.

Joint modeling of eQTLs and parent-of-origin effects using an orthogonal framework with RNA-seq data.

Extensive studies have been conducted on the analysis of genome function, especially on the expression quantitative trait loci (eQTL). These studies offered promising results for characterization of the functional sequencing variation and understanding of the basic processes of gene regulation. Parent of origin effect (POE) is an important epigenetic phenomenon describing that the expression of certain genes depends on their allelic parent-of-origin and it is known to play important roles in human complex diseases. However, traditional eQTL mapping approaches do not allow for the detection of imprinting, or they focus on modeling the additive genetic effect thereby ignoring the estimation of the dominance genetic effect. In this study, we proposed a statistical framework to test the additive and dominance genetic effects of the candidate eQTLs along with detection of the POE with a functional model and an orthogonal model for RNA-seq data. We demonstrated the desirable power and preserved Type I errors of the methods in most scenarios, especially the orthogonal model with un-biased estimation of the genetic effects and over-dispersion of the RNA-seq data. The application to a HapMap project trio dataset validated existing imprinting genes and discovered two novel imprinting genes with potential dominance genetic effect and RB1 and IGF1R genes. This study provides new insights into the next generation statistical modeling of eQTL mapping for better understanding of the genetic architecture underlying the mechanisms of gene expression regulation.