Accurate long-term prediction of death for patients with cirrhosis.

BACKGROUND AND AIMS: Cirrhosis is a major cause of death and is associated with extensive health care use. Patients with cirrhosis have complex treatment choices due to risks of morbidity and mortality. To optimally counsel and treat patients with cirrhosis requires tools to predict their longer-term liver-related survival. We sought to develop and validate a risk score to predict longer-term survival of patients with cirrhosis. APPROACH AND RESULTS: We conducted a retrospective cohort study of adults with cirrhosis with no major life-limiting comorbidities. Adults with cirrhosis within the Veterans Health Administration were used for model training and internal validation, and external validation used the OneFlorida Clinical Research Consortium. We used four model-building approaches including variables predictive of cirrhosis-related mortality, focused on discrimination at key time points (1, 3, 5, and 10 years). Among 30,263 patients with cirrhosis ≤75 years old without major life-limiting comorbidities and complete laboratory data during the baseline period, the boosted survival tree models had the highest discrimination, with 1-year, 3-year, 5-year, and 10-year survival rates of 0.77, 0.81, 0.84, and 0.88, respectively. The 1-year, 3-year, and 5-year discrimination was nearly identical in external validation. Secondary analyses with imputation of missing data and subgroups by etiology of liver disease had similar results to the primary model. CONCLUSIONS: We developed and validated (internally and externally) a risk score to predict longer-term survival of patients with cirrhosis. This score would transform management of patients with cirrhosis in terms of referral to specialty care and treatment decision-making for non-liver-related care.

Association Between Child Access Prevention and State Firearm Laws With Pediatric Firearm-Related Deaths.

INTRODUCTION: We aim to study the association between state child access prevention (CAP) and overall firearm laws with pediatric firearm-related mortality. METHODS: The Centers for Disease Control and Prevention Web-based Injury Statistics Query and Reporting System was queried for pediatric (aged < 18 y) all-intent (accidental, suicide, and homicide) firearm-related crude death rates (CDRs) among the 50 states from 1999 to 2019. States were into three groups: Always CAP (throughout the 20-year period), Never CAP, and New CAP (enacted CAP during study period). We used the Giffords Law Center Annual Gun Law Scorecard (A, B, C, D, F) to group states into strict (A, B) and lenient (C, D, F) firearm laws. A scatter plot was constructed to display state CDR based on CAP laws by year. The top 10 states by CDR per year were tabulated based on CAP law status. Wilcoxon rank-sum was used to compare CDR between strict and lenient scorecard states in 2019. RESULTS: There were 12 Always CAP, 21 Never CAP, and 17 New CAP states from 1999 to 2019. No states changed from CAP laws to no CAP laws. Never CAP and New CAP states dominated the high outliers in CDR compared to Always CAP. The top 10 states with the highest CDR per year were most commonly Never CAP. Strict firearm laws states had lower median CDR in 2019 than lenient states (0.79 [0-1.67] versus 2.59 [1.66-3.53], P = 0.007). CONCLUSIONS: Stricter overall gun laws are associated with three-fold lower all-intent pediatric firearm-related deaths. For 2 decades, the 10 states with the highest CDR were almost universally those without CAP laws. Our findings support the RAND Gun Policy in America initiative's claims on the importance of CAP laws in reducing suicide, unintentional deaths, and violent crime among children, but more research is needed.

A Syndemic Approach to Explore Factors Associated with Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most common genital infection in women and is associated with an increased risk of sexually transmitted infections and HIV. This study uses a syndemic approach to evaluate factors associated with BV. Non-pregnant, HIV-negative, sexually active, cis-gender women aged 18-45 years living in Miami, Florida were recruited from Nov.2018- Jun.2021. Participants completed a sociodemographic and behavioral questionnaire along with gynecological examinations. BV was diagnosed by Amsel criteria and confirmed by a Nugent score ≥ 4. A syndemic score was calculated as the sum of factors associated with BV. The association between syndemic score and BV was assessed using logistic regression. Of 166 women included, 60.2% had BV. Race, ethnicity, education, vaginal sex, recent cannabis use, and reasons for intravaginal practices were included in the syndemic score. Higher odds of BV were found in women with a score of ≥ 3 compared to women with a score of 0/1. A higher syndemic score was associated with increased odds of having BV. Multilevel interventions to decrease BV are needed to decrease women's risk of acquiring HIV.

RESUMEN: La vaginosis bacteriana (VB) es la infección genital más común en mujeres y está asociada con un mayor riesgo de enfermedades de transmisión sexual (ETS) y de VIH. Este estudio utilizó un enfoque sindémico para evaluar factores asociados con VB. Entre noviembre del 2018 y junio del 2021, se reclutaron mujeres cisgénero de entre 18­45 años, que no estuvieran embarazadas, que fueran VIH negativas y sexualmente activas, y que vivieran en Miami, Florida. Las participantes completaron un cuestionario sociodemográfico y de comportamiento junto con un examen ginecológico. Se diagnosticó VB empleando los criterios de Amsel y se confirmó empleando el criterio de Nugent con una puntuación ≥ 4. La puntuación sindémica fue calculada como la suma de factores asociados con VB utilizando. La asociación entre la puntuación sindémica con VB se evaluó mediate una regresión logística. De 166 mujeres incluidas, 60.2% fueron diagnosticadas con VB. Los factores incluidos en la puntuación sindémica fueron la raza, etnia, educación, sexo vaginal, consumo reciente de cannabis, y el uso de prácticas intravaginales. Se encontraron mayores probabilidades de VB en mujeres con una puntuación ≥ 3 en comparación con aquellas con una puntuación de 0/1. Una puntuación sindémica alta se asoció con una mayor probabilidad de tener VB. Son necesarias intervenciones multinivel para disminuir la VB y disminuir el riesgo de que las mujeres contraigan ETS y VIH.

Opiate vs non-opiate prescription medication for pain control after endoscopic sinus surgery for chronic rhinosinusitis.

PURPOSE: Research indicates that most providers give opiates after endoscopic sinonasal surgery. The effectiveness of non-opiate medications after sinonasal surgery is poorly understood and most studies do not assess medication failure. This study compares oral opiate, oral opiate and topical steroid, and oral non-opiate pain control. Patient call-backs are used as a proxy for pain medication failure. MATERIALS AND METHODS: This study compares three medication regiments after sinonasal surgery for 180 adults with chronic rhinosinusitis. Patients were instructed to take acetaminophen for mild pain. For moderate/severe pain, patients used: 1) oxycodone-acetaminophen, 2) oxycodone-acetaminophen + budesonide nasal rinses, or 3) meloxicam + acetaminophen. Patients were instructed to call clinic if pain was not controlled. Descriptive statistics compared cohorts. Chi-square tests compared call-backs between cohorts. Logistic regression adjusted for baseline differences in covariates, comorbidities, and operative sites. RESULTS: Cohorts had similar age, sex distribution, disease features, and extent of surgery. The meloxicam cohort had less subjects with pain disorders. The oxycodone cohort had less subjects with diabetes, septoplasty, and turbinate reduction. After adjusting for baseline differences and using oxycodone as the reference group (n = 50), the odds of calling clinic for poorly controlled pain was 0.18 (95% Confidence Interval (CI): 0.05-0.6) in the meloxicam cohort (n = 45) and 0.19 (95% CI:0.07-0.5) in the oxycodone + budesonide rinses cohort (n = 85). CONCLUSION: In this study, both meloxicam and oxycodone + budesonide rinses were more effective at controlling pain after sinonasal surgery than oxycodone alone.

Predicting survival after liver transplantation in patients with hepatocellular carcinoma using the LiTES-HCC score.

BACKGROUND & AIMS: Liver transplant priority in the US and Europe follows the 'sickest-first' principle. However, for patients with hepatocellular carcinoma (HCC), priority is based on binary tumor criteria to expedite transplant for patients with 'acceptable' post-transplant outcomes. Newer risk scores developed to overcome limitations of these binary criteria are insufficient to be used for waitlist priority as they focus solely on HCC-related pre-transplant variables. We sought to develop a risk score to predict post-transplant survival for patients using HCC- and non-HCC-related variables. METHODS: We performed a retrospective cohort study using national registry data on adult deceased-donor liver transplant (DDLT) recipients with HCC from 2/27/02-12/31/18. We fit Cox regression models focused on 5- and 10-year survival to estimate beta coefficients for a risk score using manual variable selection. We then calculated absolute predicted survival time and compared it to available risk scores. RESULTS: Among 6,502 adult DDLT recipients with HCC, 11 variables were selected in the final model. The AUCs at 5- and 10-years were: 0.62, 95% CI 0.57-0.67 and 0.65, 95% CI 0.58-0.72, which was not statistically significantly different to the Metroticket and HALT-HCC scores. The LiTES-HCC score was able to discriminate patients based on post-transplant survival among those meeting Milan and UCSF criteria. CONCLUSION: We developed and validated a risk score to predict post-transplant survival for patients with HCC. By including HCC- and non-HCC-related variables (e.g., age, chronic kidney disease), this score could allow transplant professionals to prioritize patients with HCC in terms of predicted survival. In the future, this score could be integrated into survival benefit-based models to lead to meaningful improvements in life-years at the population level. LAY SUMMARY: We created a risk score to predict how long patients with liver cancer will live if they get a liver transplant. In the future, this could be used to decide which waitlisted patients should get the next transplant.

Development and Validation of a Model to Predict Long-Term Survival After Liver Transplantation.

Patients are prioritized for liver transplantation (LT) under an "urgency-based" system using the Model for End-Stage Liver Disease score. This system focuses solely on waitlist mortality, without considerations of posttransplant morbidity, mortality, and health care use. We sought to develop and internally validate a continuous posttransplant risk score during 5-year and 10-year time horizons. This retrospective cohort study used national registry data of adult deceased donor LT (DDLT) recipients with ≥90 days of pretransplant waiting time from February 27, 2002 to December 31, 2018. We fit Cox regression models at 5 and 10 years to estimate beta coefficients for a risk score using manual variable selection and calculated the absolute predicted survival time. Among 21,103 adult DDLT recipients, 11 variables were selected for the final model. The area under the curves at 5 and 10 years were 0.63 (95% confidence interval [CI], 0.60-0.66) and 0.67 (95% CI, 0.64-0.70), respectively. The group with the highest ("best") scores had 5-year and 10-year survivals of 89.4% and 85.4%, respectively, compared with 45.9% and 22.2% for those with the lowest ("worst") scores. Our score was significantly better at predicting long-term survival compared with the existing scores. We developed and validated a risk score using nearly 17 years of data to prioritize patients with end-stage liver disease based on projected posttransplant survival. This score can serve as the building block by which the transplant field can change the entire approach to prioritizing patients to an approach that is based on considerations of maximizing benefits (ie, survival benefit-based allocation) rather than simply waitlist mortality.

The Disaggregated Repeated Measures Design: A Novel Approach to Assess Sexual Risk Behaviors.

Although numerous studies have examined sexual and substance use behaviors that put people at risk for sexually transmitted infections including HIV, most focus on an overall measure of aggregate risk or a few simple and particular subtypes of sexual acts assessed in separate analyses. In this article, we introduce a more sensitive approach to assess how the relative characteristics of sex acts may determine the level of risk in which an individual chooses to engage. Project AWARE, a randomized clinical trial conducted among 5012 patients in nine STD clinics across the U.S., is used to illustrate the approach. Our study was guided by two aims: (1) describe a new approach to examine the count of sexual acts using a disaggregated repeated measures design and (2) show how this new approach can be used to evaluate interactions among different categories of sexual risk behaviors and other predictors of interest (such as gender/sexual orientation). Profiles of different subtypes of sexual acts in the past 6 months were assessed. Potential interactions of the characteristics associated with each subtype which resulted in up to 48 distinct subtypes of sexual risk behaviors-sex with a primary/non-primary partner; partner's HIV status; vaginal/anal sex; condom use; and substance use before or during sex act-can be examined. Specifically, we chose condom use and primary and non-primary status of partner as an application in this paper to illustrate our method. There were significantly more condomless sex acts (M = 23, SE = 0.9) and sex acts with primary partners (M = 27.1, SE = 0.9) compared to sex acts with condoms (M = 10.9, SE = 0.4, IRR = 2.10, 95% CI 1.91-2.32, p < .001) and sex acts with non-primary partner (M = 10.9, SE = 0.5, IRR = 2.5, 95% CI 2.33-2.78, p < .001). In addition, there were significant differences for the count of sexual risk behaviors among women who have sex with men (WSM), men who have sex with women (MSW) and men who have sex with men (MSM) for sex acts with and without condom use, primary and non-primary partner, and their interaction (ps = .03, < .0001, and .001, respectively). This approach extends our understanding of how people make choices among sexual behaviors and may be useful in future research on disaggregated characteristics of sex acts.

Conditional uncertainty: Misinterpretations of "significant" p values.

Misapplication of p values can lead to very misleading conclusions. The frequent insignificance of a "significant" p value 1 provides examples illustrating situations where p values are misused in interpretation and describes alternatives to p values to consider. The concern about p values, and their potential shortcomings and misinterpretations, has been widely discussed and has received a lot of debate from the statistical community. While we agree with much of the content presented in the article, the issue fundamentally represents a misinterpretation of conditional probability, misapplication of measures regarding diagnostic accuracy, and consequently violations of assumptions inherent in experimental design and the validity of many approaches to statistical analysis and inference. One way this can be remedied is through team science, and collaboration between clinical and biostatistical scientists in research.

Rapid improvement in organ procurement organization performance: Potential for change and impact of new leadership.

Recently proposed rulemaking from Centers for Medicare and Medicaid Services would change how organ procurement organizations (OPOs) are evaluated. The proposals include using national inpatient death data to define a standardized denominator to calculate comparable donation rates among OPOs. Based on these objective metrics, OPOs not performing at a prespecified threshold will be required to rapidly improve performance to avoid decertification. We sought to determine whether rapid OPO improvement was possible based on objective donation metrics, and whether leadership change was associated with rapid improvement. We evaluated United Network for Organ Sharing and Centers for Disease Control and Prevention (CDC) data from 2011 to 2018, and measured donation rates using CDC data on inpatient deaths from causes consistent with donation, based on the location of deaths. During the two 4-year cycles, we found that an OPO's ranking relative to other OPOs was fairly static, with more than 90% of the OPOs at risk of flagging at the end of each 4-year cycle (2014, 2018) being in the bottom 75% of OPOs in the preceding 3 years. In multivariable logistic regression models, leadership changes were only statistically significantly associated with an improvement in OPO rankings during the 2011-2014 cycle. These data demonstrate that rapid improvements in OPO performance are uncommon, and while leadership changes increase the odds of rapid improvement, they do not guarantee improvement.

Electronic Decision support for Improvement of Contemporary Therapy for Stroke Prevention.

BACKGROUND: Despite ample clinical trial data demonstrating that oral anticoagulation (OAC) treatment is highly effective in reducing stroke for patients with atrial fibrillation (AF), OAC treatment remains underutilized in current clinical practice. Targeting hospitalist and emergency department providers with electronic decision support represents a potential quality improvement opportunity in the use of OAC medication in AF patients. METHODS: We conducted a 3-center study in which 2 sites utilized an electronic alert (EA) embedded in the electronic health record and 1 site provided usual care. The EA calculated the CHA2DS2-VASc score for clinicians. Patients were tracked following discharge from either the emergency department or hospital. We hypothesized that the EA would increase the rate of OAC use by 15% compared to usual care, with a study sample size of 360 patients. Study exclusions included severe heart valve disease, advanced renal disease, and severe dementia. The primary endpoint was OAC use at the time of hospital discharge or 30 days after hospital discharge (whichever was the last observation recorded). RESULTS: Among 309 patients included for analysis (mean age 70.2 years), the median CHA2DS2-VASc score was 3.5. The frequency of OAC use at follow-up at the usual care hospital was 55.9% (95% confidence interval 47.4-67.9). At the 2 EA sites, the rate of OAC use at the last observation point was 43.9% (P = .06). Aspirin use at follow-up was similar at the usual care site and the EA sites (53.8% versus 46.3%). The rate of OAC use in patients greater than 75 years was 60.0% in the usual care site and 48.4% (P = .09) at the EA sites. CONCLUSIONS: The EA in our study was not sufficient to ameliorate therapeutic inertia in the use of OAC for stroke prevention in AF.

Predicting COVID-19 cases using SARS-CoV-2 RNA in air, surface swab and wastewater samples.

Genomic footprints of pathogens shed by infected individuals can be traced in environmental samples, which can serve as a noninvasive method of infectious disease surveillance. The research evaluates the efficacy of environmental monitoring of SARS-CoV-2 RNA in air, surface swabs and wastewater to predict COVID-19 cases. Using a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory housing roughly 500 students from March to May 2021 at the University of Miami, Coral Gables, FL. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 concentration in environmental samples was quantified using Volcano 2nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and COVID-19 cases. SARS-CoV-2 was detected in air, surface swab and wastewater samples on 52 (63.4 %), 40 (50.0 %) and 57 (68.6 %) days, respectively. On 19 (24 %) of 78 days SARS-CoV-2 was detected in all three sample types. COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100 %), 9 (81.8 %) and 8 (72.7 %) days in air, surface swab and wastewater samples, respectively. SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases and a 3-day lead indicator for a potential outbreak at the dormitory building scale. Proactive environmental surveillance of SARS-CoV-2 or other pathogens in multiple environmental media has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks within communities.

Frontal lobe position after single-layer cadaveric dermal matrix repair of large anterior skull base defects.

Objective: Endoscopic repair of large anterior skull base (ASB) defects has excellent results when using multilayered repairs with a nasoseptal flap. However, in extensive intranasal tumors, a nasoseptal flap may not always be available. One alternative option is a flexible single-layer ASB repair. Initial studies indicate low cerebrospinal fluid leak rates with a single-layer repair. However, the level of frontal lobe support, particularly the propensity for a significant inferior displacement of the frontal lobe, is not known. The goal of this study is to determine the frontal lobe position after single-layer acellular dermal allograft repair in large ASB defects. Study Design: Retrospective cohort study. Setting: Tertiary care medical center. Subjects and Methods: This cohort study compares the frontal lobe position in adults who underwent endoscopic endonasal ASB tumor resection and single-layer cadaveric dermal matrix repair (ASB cohort) with control subjects without intracranial abnormalities (control cohort). The ASB cohort includes subjects with an ASB defect of ≥5 cm anterior/posterior and ≥1.5 cm wide and who had imaging at least 2 months after surgery. The frontal lobe position is measured on sagittal CT/MRI using a reference line from the base of the sella to the nasion. A value of zero indicates that the inferior-most aspect of the frontal lobe is at the level of the nasion-sellar line. A positive value indicates that the frontal lobe is inferior to the nasion-sellar line. The ASB cohort frontal lobe position is compared with the control cohort using the Mann-Whitney U test. A priori we set an absolute difference of 5 mm as a clinically significant difference. Results: The ASB cohort includes 47 subjects who are 57% male with an average age of 60 years (range: 31-89 years). The most common ASB pathology is esthesioneuroblastoma (n = 21) and 81% of the ASB cohort had postoperative radiation. The control cohort includes 20 subjects who are 60% male, with a mean age of 45 years (range: 19-74 years). The majority of controls underwent imaging for head trauma (n = 13). The ASB mean frontal lobe position is -0.2 mm superior to the nasion-sellar line (range: -9.2 to 10.4 mm), while the control's mean frontal lobe position is 1.1 mm inferior to the nasion-sellar line. This difference is not statistically significant (P = 0.13) and does not reach our a priori definition of clinical significance. The frontal lobe position of ASB subjects who had radiation is closer to the nasion-sellar line as compared with those who did not undergo radiation. Conclusions: Single-layer acellular dermal graft repair maintains frontal lobe support and position in large ASB defects.

Increasing Rates of Pancreatic and Hepatocellular Cancers Parallel Increasing Obesity Rates.

OBJECTIVES: Gastrointestinal (GI) cancers are now the second leading cause of cancer death in the United States, and six are convincingly associated with obesity. We interrogate the association of a state's obesity prevalence with cancer incidence. METHODS: We use data from US Cancer Statistics for each of the 6 cancers of interest from 2011 to 2018. Age-adjusted incidences were calculated, and the Behavioral Risk Factor Surveillance System was used to identify prevalence of obesity in each state. A generalized estimating equation model was used to relate the rate of cancer with the rate of obesity. RESULTS: Increased state-level prevalence of obesity was significantly associated with increasing state-level incidence of pancreatic and hepatocellular cancers. The rate of colorectal cancer was not associated with increasing obesity in 2011-2014 but from 2015 to 2018 was inversely associated with increasing rates of obesity. State-level prevalence of obesity was not associated with esophageal, gastric, or gallbladder cancers. CONCLUSIONS: Weight management interventions may reduce risk of pancreatic and hepatocellular cancers.

Complex And Simple Appendicitis: REstrictive or Liberal postoperative Antibiotic eXposure (CASA RELAX) using Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR): study protocol for a randomized controlled trial.

Objectives: After appendectomy for simple or complicated appendicitis, the optimal duration of postoperative antibiotics (postop abx) is unclear and great practice variability exists. We propose to compare restrictive versus liberal postop abx using a hierarchical composite endpoint which includes patient-centered outcomes and accounts for duration of antibiotic exposure. Methods/Design: Participants with simple or complicated appendicitis undergoing appendectomy are randomly assigned to either restricted or liberal strategy. Eligible subjects declining randomization will be recruited to enroll in an observation only cohort. The primary endpoint is an ordinal scale of mutually exclusive clinical outcomes with within-category rankings determined by duration of antibiotic exposure. Subjects in both randomized and observation only cohorts will be analyzed as intention-to-treat, per-protocol, and as-treated. Exploratory Bayesian analyses will be performed. Conclusion: The complex and simple appendicitis: restrictive or liberal postoperative antibiotic exposure multicenter randomized controlled trial will enroll surgical appendectomy patients and seeks to analyze if a strategy of restricted (compared with liberal) postoperative antibiotics results in similar clinical outcomes with the benefit of reduced antibiotic exposure. Trial registration number: NCT05002829.

Using machine learning to understand microgeographic determinants of the Zika vector, Aedes aegypti.

There are limited data on why the 2016 Zika outbreak in Miami-Dade County, Florida was confined to certain neighborhoods. In this research, Aedes aegypti, the primary vector of Zika virus, are studied to examine neighborhood-level differences in their population dynamics and underlying processes. Weekly mosquito data were acquired from the Miami-Dade County Mosquito Control Division from 2016 to 2020 from 172 traps deployed around Miami-Dade County. Using random forest, a machine learning method, predictive models of spatiotemporal dynamics of Ae. aegypti in response to meteorological conditions and neighborhood-specific socio-demographic and physical characteristics, such as land-use and land-cover type and income level, were created. The study area was divided into two groups: areas affected by local transmission of Zika during the 2016 outbreak and unaffected areas. Ae. aegypti populations in areas affected by Zika were more strongly influenced by 14- and 21-day lagged weather conditions. In the unaffected areas, mosquito populations were more strongly influenced by land-use and day-of-collection weather conditions. There are neighborhood-scale differences in Ae. aegypti population dynamics. These differences in turn influence vector-borne disease diffusion in a region. These results have implications for vector control experts to lead neighborhood-specific vector control strategies and for epidemiologists to guide vector-borne disease risk preparations, especially for containing the spread of vector-borne disease in response to ongoing climate change.

A small cluster randomised clinical trial to improve health outcomes among Argentine patients disengaged from HIV care.

Background: Patients disengaged from HIV care, e.g., missed medication pick-ups, not attending physician visits, account for ≥70% of new HIV infections. Re-engaging and sustaining engagement is essential to controlling the HIV pandemic. This study tested a physician-delivered evidence-based intervention, Motivational Interviewing (MI), to improve health outcomes, adherence to antiretroviral therapy (ART), HIV virologic suppression, CD4+ count, retention in HIV care, and self-efficacy among patients disengaged from care in Argentina. Methods: Regional clinics (n = 6) were randomised to condition, MI Intervention or Enhanced Standard of Care (ESOC), and recruited N = 360 patients disengaged from HIV care. ART adherence, HIV RNA viral load, CD4+ count retention, and self-efficacy were assessed at baseline, 6, 12, 18, and 24-months. Indirect effects from condition to main outcomes were examined using patient-provider relationship as a mediator. The study was a cluster-randomised clinical trial entitled Conexiones y Opciones Positivas en la Argentina 2 (COPA2) and was registered at clinicaltrials.gov, NCT02846350. Findings: Participants were an average age of 39·15 (SD = 10·96), 51% were women; intervention participants were older (p = ·019), and more ESOC participants were women (60% vs. 42%, p = 0·001). Using mixed models, the intervention had no effect on ART adherence over time by condition on HIV RNA viral load, CD4+ count retention, or self-efficacy. However, analysing mediated paths, there was an indirect effect of condition on ART adherence (B = 0·188, p = 0·009), HIV viral load (B = -0·095, P = 0·027), and self-efficacy (B = 0·063, P = 0·001), suggesting the intervention was associated with improved patient-provider relationships, which was in turn associated with increased ART adherence, lower HIV viral load, and higher self-efficacy. Interpretation: These findings suggest that physician-delivered MI may enhance the patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. However, these findings are preliminary due to the small number of clusters randomised, and replication is warranted. Funding: National Institutes of Health.

Early hypermetabolism is uncommon in trauma intensive care unit patients.

BACKGROUND: Classic experiments demonstrating hypermetabolism after major trauma were performed in a different era of critical care. We aim to describe the modern posttraumatic metabolic response in the trauma intensive care unit (TICU). METHODS: This prospective observational study enrolled TICU mechanically ventilated adults (aged ≥18) from 3/2018-2/2019. Multiple, daily resting energy expenditure (REE) measurements were recorded. Basal energy expenditure (BEE) was calculated by the Harris-Benedict equation. Hypometabolism was defined as average daily REE < 0.85*BEE and hypermetabolism defined as average daily REE > 1.15*BEE. Demographics, interventions, and clinical outcomes were abstracted. Descriptive statistics and multivariable logistical regression models evaluating demographics with the outcome variable of hypermetabolism for the first 3 days ("sustained hypermetabolism") were performed, along with group-based trajectory modeling (GBTM). RESULTS: Fifty-five patients were analyzed: median age was 38 (28-56) years; 38 (69%) were male; body mass index (kg/m2 ) was 28 (26-32); and Injury Severity Score was 27 (19-34), with (38 [71%] blunt, 8 [15%] penetrating, 7 [13%] burn) injury mechanism. Overall, 19 (35%) had hypermetabolism on day 1 ("immediate hypermetabolism"), and 11 (21%) had sustained hypermetabolism for the first 3 days. Logistic regression analysis identified penetrating mechanism (adjusted odds ratio [AOR], 16.4; 95% CI, 1.9-199.6; p = .015), burn mechanism (AOR, 11.1; 95% CI, 1.3-116.8; p =.029), and maximum temperature (AOR, 4.2; 95% CI, 1.3-20.3; p= .041) as independent predictors of sustained hypermetabolism. GBTM identified 4 nutrition phenotypes, with 2 hyperconsumptive phenotypes associated with increased risk of malnutrition at discharge. CONCLUSION: Only a minority of injured patients is hypermetabolic in the first week after injury. Elevated temperature, penetrating mechanism, and burn mechanism are independently associated with sustained hypermetabolism. Hyperconsumptive phenotype patients are more likely to develop malnutrition during hospitalization.

Infection with SARS-CoV-2 is associated with menstrual irregularities among women of reproductive age.

BACKGROUND: Biological and psychological mechanisms may be responsible for menstrual irregularities occurring among women during the COVID-19 pandemic. STUDY DESIGN: From January 2019 to September 2021, women (18- to 45-years-old and not using hormonal contraception) were recruited in Miami-Dade County, Florida. Cross-sectional, self-report surveys collected data on menstrual irregularities, COVID-19 vaccination, stress, depression, and loneliness. A EUA approved rapid test assay using whole blood measured SARS-CoV-2 IgG antibodies. Chi-square and Fisher's exact tests described menstrual irregularities among women recruited before versus after the start of the COVID-19 pandemic and with detectable versus undetectable SARS-CoV-2 IgG antibodies. A logistic regression examined the relationship between the presence of SARS-CoV-2 IgG antibodies and menstrual irregularities controlling for age, stress, depression, and loneliness. RESULTS: Among 182 women enrolled, 73 were enrolled after pandemic onset, and 36 provided vaccination data. Having detectable SARS-CoV-2 IgG antibodies was associated with a higher percentage of menstrual irregularities among unvaccinated women (0% vs. 39%, p = .026) and among all women regardless of vaccination status (31% vs. 5%; p = .005). Adjusting for age and psychological variables, the odds of menstrual irregularities were 7.03 times (95% CI [1.39, 35.60]; p = .019) higher among women with detectable antibodies compared to women without detectable antibodies. Neither enrollment date, age, nor psychological factors were associated to menstrual irregularities. CONCLUSIONS: Biological mechanisms related to SARS-CoV-2 infection may be responsible for irregular menstruation and should be further examined to mitigate the impact of the COVID-19 pandemic on women's health.

Combining Pentoxifylline With Vedolizumab for Crohn's Disease: Results of a Randomised, Placebo-controlled Pilot Study.

BACKGROUND AND AIMS: The efficacy of current biologics may be limited by targeting only one pathway. Pentoxifylline [PTX] interferes with tumour necrosis factor [TNF] gene expression. We performed a randomised, placebo-controlled pilot study to determine if PTX plus vedolizumab [VDZ] in patients with Crohn's disease [CD] is safe and improves response compared with VDZ monotherapy. METHODS: Thirty adult patients with active CD were randomised to VDZ/PTX or VDZ/placebo and followed for 24 weeks. Endoscopic activity and inflammatory cytokines were measured at baseline and Week 24. Descriptive statistics were used to determine estimates of effect. RESULTS: Demographics were similar but baseline disease activity was higher in the VDZ/PTX group. There was no difference in clinical remission at Week 14 (60.0% vs 66.67%, odds ratio [OR] 0.76, 95% confidence interval [CI] 0.16, 3.51) or steroid-free clinical remission at Week 24 in patients receiving VDZ/PTX. Improved clinical response was noted in the VDZ/PTX group at Weeks 6, 14, and 24 [Week 6: 20% vs 6.67%, Week 14: 26.67% vs 6.67%, Week 24: 40% vs 20%]. The rate of endoscopic remission was similar between the groups [40% vs 33.33%], with a greater mean decrease in Simple Endoscopic Score-CD [SES-CD] and C-reactive protein [CRP] with VDZ/PTX [SES-CD -3.17 vs -0.15, CRP -5.56 vs 0.46]. An increase in serum TNF-α concentration was observed with VDZ/placebo group; PTX mitigated this effect. No serious adverse events occurred. CONCLUSIONS: VDZ/PTX did not provide benefit over VDZ monotherapy in clinical or endoscopic remission but appeared to improve clinical response and was safe. These data should inform a fully powered study.