Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure.

BACKGROUND: The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals. OBJECTIVES: The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF. METHODS: In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee. RESULTS: For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period. CONCLUSIONS: Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229).

Hormonal Contraception and Risk of Cardiometabolic Disease in Women with HIV.

Objective: We sought to determine the association of hormonal contraception (HC) and cardiometabolic outcomes among women with human immunodeficiency virus (HIV). Methods: We included women with HIV aged 18-45 years in clinical care in the Southeastern United States between 1998 and 2018. Oral and injectable HC use was captured from medication records. Our outcomes included incident cardiovascular/thrombotic disease (CVD) (atherosclerosis, hypertension, cerebrovascular disease, thrombosis, and heart failure) and incident metabolic disorders (diabetes, dyslipidemia, obesity, and non-alcoholic steatohepatitis). We excluded women with prevalent conditions. We used multivariable marginal structural models to examine time-varying current and cumulative HC use and cardiometabolic outcomes in separate analyses, adjusting for age, race, smoking, time-varying comorbidities, CD4 cell count, HIV RNA, and antiretroviral use. Women with HC exposure were compared with women without HC exposure. Results: Among the 710 women included, 201 women (28%) used HC. CVD analyses included 603 women without prevalent CVD and 93 incident events; metabolic analyses included 365 women without prevalent metabolic disease and 150 incident events. Current and cumulative oral HC use was associated with increased odds of CVD, though this was not statistically significant (adjusted odds ratio [aOR] = 2.08, [95% confidence interval (CI): 0.80-5.43] and aOR = 1.24 [95% CI: 0.96-1.60] per year of use, respectively). Oral HC was not associated with risk of incident metabolic disorders. Depot medroxyprogesterone acetate (DMPA) was not associated with risk of incident CVD. Current and cumulative DMPA use was significantly associated with decreased odds of incident metabolic disorders (aOR = 0.48 [95% CI: 0.23, 1.00] and aOR = 0.65 [95% CI: 0.42-1.00] per year of use, respectively). Conclusion: Our results suggest that cardiovascular risk should be considered when selecting contraception for women with HIV.

Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Fixed lateral unicompartmental knee replacement is a reliable treatment for lateral compartment osteoarthritis after mobile-bearing medial unicompartmental replacement.

PURPOSE: Lateral osteoarthritis following medial unicompartmental knee replacement (UKR) is usually treated with total knee replacement, however, lateral UKR is a less invasive option that preserves a well-functioning medial UKR. This study aimed to determine the 5-year outcome of the cemented Fixed Lateral Oxford UKR (FLO) when used for the treatment of severe lateral disease after medial Oxford unicompartmental knee replacement. METHODS: Forty-four knees with lateral bone-on-bone osteoarthritis (n = 43) and avascular necrosis (n = 1) treated with the FLO following medial Oxford UKR were followed up prospectively. The Oxford Knee Score (OKS) and Tegner Activity Score (TAS) were collected pre- and post-operatively. Life-table analysis was used to determine survival rates. RESULTS: The mean patient age at the time of FLO surgery was 74.4 years with a mean time of 12.1 years between the primary medial UKR and the conversion to a bi-UKR with a FLO. Mean follow-up of the FLO was 3.5 years. After FLO no intra-operative or medical complications, re-admissions, or mortality occurred. There was one reoperation in which a bearing was exchanged for a medial bearing dislocation. There were no revisions of the FLO, so the FLO survival rate at 5 years was 100% (24 at risk). The mean pre-operative OKS was 22, which significantly (p < 0.0001) improved to a mean of 42, 42, and 40 at 1, 2, and 5 years, respectively. The median TAS had a non-significant improvement from 2.5 (Range 0-8) pre-operatively to 2 (Range 1-6) at 5 years postoperatively. CONCLUSION: The FLO is a reliable treatment for lateral osteoarthritis following medial UKR. At 5 years there was a 100% survival of the FLO with a mean OKS of 40. LEVEL OF EVIDENCE: IV, Prospective Case Series.

Less pain reported 5 years after cementless compared to cemented unicompartmental knee replacement: an analysis of pain, neuropathy, and co-morbidity scores.

PURPOSE: To compare patient-reported pain scores and assess the influence of neuropathy and co-morbidity, on knee pain following cemented and cementless medial unicompartmental knee replacement (UKR) 5 years after surgery. METHOD: In this longitudinal study, 262 cemented and 262 cementless Oxford UKR performed for the same indications and with the same techniques were recruited. Patients were reviewed at five years, evaluating patient-reported pain and association with clinical outcomes. Intermittent and Constant Osteoarthritis Pain (ICOAP), PainDETECT (PD), Charnley score, Oxford Knee Score (OKS) and American Knee Society Score (AKSS) were compared. RESULTS: In both cohorts, intermittent pain was more common than constant pain (47% vs 21%). Cementless knees reported significantly less pain than cemented (ICOAP-Total 5/100 vs 11/100, p < 0.0001). A greater proportion of cementless knees experienced no pain at all (ICOAP = 0/100, 61% vs 43%, p < 0.0001) and 75% fewer experienced severe or extreme pain. Pain sub-scores in PD, OKS and AKSS follow this trend. Pain was unlikely to be neuropathic (PD positive: 5.26%), but patients reporting high levels of 'strongest' pain were three times more likely to be neuropathic. Patients with co-morbidities (Charnley C) experienced greater pain than those without (Charnley A+B) across all knee-specific scores, despite scores being knee specific. CONCLUSION: Both cemented and cementless UKR in this study had substantially less pain than that reported in literature following TKR. Cementless UKR had significantly less pain than cemented UKR in all scores. Two-thirds of patients with a cementless UKR had no pain at all at 5 years, and pain experienced was most likely to be mild and intermittent with no patients in severe or extreme pain. Patients with cementless UKR that had higher levels of pain were more likely to have co-morbidity or evidence or neuropathic pain. It is unclear why cementless UKR have less pain than cemented; further study is necessary.

Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. CLINICAL TRIAL REGISTRATION: NCT04481919.

'Will I wear purple?'-a school arts-based research project in the UK to disseminate findings from a qualitative evidence synthesis about living to an extreme age.

BACKGROUND: a change in attitude towards ageing is needed. Arts-based research (ABR) refers to the use of any creative art in research. ABR can provide an environment to reflect on challenging social issues and has the potential to make lasting impressions. OBJECTIVE: we aimed to explore the use of ABR to disseminate findings from a qualitative evidence synthesis exploring what it means to live well beyond the age of 80. DESIGN: ABR using art as a stimulus for recorded discussions and written annotations. SETTING: a mixed catchment state secondary school in the UK. SUBJECTS: fifty-four secondary school pupils aged 14-15. The majority identified as female (ratio 5:1). METHODS: school pupils created artwork to represent themes about ageing drawn from a qualitative evidence synthesis. The artwork was a stimulus for recorded discussions. We used thematic analysis to develop themes about children's response to ageing. RESULTS: we developed six themes. Pupils found comfort in recognising that old age can be lived well; they began to see themselves in the older person; they explored the ambiguous nature of memory; they highlighted the dangers of disconnection; they affirmed a need to restore connection with elders and they recognised the need to cherish time and live meaningfully. CONCLUSIONS: this project encouraged pupils to think about what it means to grow old. ABR has the potential to contribute to a more positive relationship with older people and towards ageing. Research stakeholders should not undervalue the potential power of shifts in perspective for powering social change.

Early post-operative physiotherapy rehabilitation after primary unilateral unicompartmental knee replacement: a systematic review.

BACKGROUND: Unicompartmental Knee Replacement (UKR) is an established treatment for end stage arthritis affecting one compartment of the knee. UKR lends itself to rapid recovery and early discharge. The content, type, timing and dose of early post-operative physiotherapy treatment has yet to be reviewed. OBJECTIVE: To review the content of early physiotherapy in the first eight weeks following unilateral UKR. DATA SOURCES: A literature search of Medline, CINAHL, AMED and PubMed and the Physiotherapy Evidence Database (PEDRo) plus citation searching. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) and observational studies reporting a physiotherapy intervention for UKR involving a form of post-operative exercise/education/advice delivered within the first eight weeks of surgery and commencing as an in-patient. Two reviewers independently performed screening, data extraction and risk of bias assessment. DATA SYNTHESIS: Narrative syntheses were undertaken due to the heterogeneity of the primary outcomes. RESULTS: Eleven studies were included (n = 1293 participants), three RCTs and eight observational studies. The dose and content of post-operative physiotherapy was highly variable with a move in recent years to rapid recovery and same day discharge with more self-directed rehabilitation. No studies had a low risk of bias. LIMITATIONS: Small sample sizes and high heterogeneity limit our findings CONCLUSIONS: This review highlights the range of post-operative physiotherapy provision following UKR with a recent move to minimal physiotherapy input. Further research is required to identify those patients who may need additional physiotherapy above that now routinely provided, along with the most effective timing, type, and dosage of the intervention. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021243238. CONTRIBUTION OF THE PAPER.

Cognitive Outcomes in the Pragmatic Investigation of optimaL Oxygen Targets (CO-PILOT) trial: protocol and statistical analysis plan.

INTRODUCTION: Long-term cognitive impairment is one of the most common complications of critical illness among survivors who receive mechanical ventilation. Recommended oxygen targets during mechanical ventilation vary among international guidelines. Different oxygen targets during mechanical ventilation have the potential to alter long-term cognitive function due to cerebral hypoxemia or hyperoxemia. Whether higher, intermediate or lower SpO2 targets are associated with better cognitive function at 12-month follow-up is unknown. METHODS AND ANALYSIS: The Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial is an ongoing pragmatic, cluster-randomised, cluster-crossover trial comparing the effect of a higher SpO2 target (target 98%, goal range 96%-100%), an intermediate SpO2 target (target 94%, goal range 92%-96%) and a lower SpO2 target (target 90%, goal range 88%-92%) on clinical outcomes in mechanically ventilated patients admitted to the medical intensive care unit at a single centre in the USA. For this ancillary study of long-term Cognitive Outcomes (CO-PILOT), survivors of critical illness who are in the PILOT trial and who do not meet exclusion criteria for CO-PILOT are approached for consent. The anticipated number of patients for whom assessment of long-term cognition will be performed in CO-PILOT is 612 patients over 36 months of enrolment. Cognitive, functional and quality of life assessments are assessed via telephone interview at approximately 12 months after enrolment in PILOT. The primary outcome of CO-PILOT is the telephone version of the Montreal Cognitive Assessment. A subset of patients will also complete a comprehensive neuropsychological telephone battery to better characterise the cognitive domains affected. ETHICS AND DISSEMINATION: The CO-PILOT ancillary study was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

High Rates of Viral Suppression and Care Retention Among Youth Born Outside of the United States with Perinatally Acquired HIV.

BACKGROUND: Youth born outside of the US with perinatally acquired HIV infection (YBoUS-PHIV) account for most children living with HIV in the US, but there are few data characterizing their care outcomes. METHODS: We conducted a retrospective study of YBoUS-PHIV receiving care across 3 HIV clinics in the Southeastern US between October 2018 and 2019. Primary outcomes were retention in care and viral suppression defined as (1) proportion of suppressed viral loads (VLs) and (2) having all VLs suppressed (definition 1 presented in the abstract). Primary predictors were age, adoption and disclosure status (full, partial and none/unknown). Multivariable logistic regression and χ 2 tests were used to test for associations with care outcomes. Analysis of disclosure status was restricted to youth greater than or equal to 12 years. RESULTS: The cohort included 111 YBoUS-PHIV. Median age was 14 years (interquartile range, 12-18), 59% were female, and 79% were international adoptees. Overall, 84% of patients were retained in care, and 88% were virally suppressed at each VL measurement. Adopted youth were more likely to be virally suppressed than nonadopted youth [odds ratio (OR), 7.08; P < 0.01] although the association was not statistically significant in adjusted analysis (adjusted OR, 4.26; P = 0.07). Neither age nor adoption status was significantly associated with retention. Among 89 patients greater than or equal to 12 years, 74% were fully disclosed of their HIV status, 12% were partially disclosed, and 13% had not started the disclosure process. There was no significant difference in retention or viral suppression by disclosure status. CONCLUSIONS: YBoUS-PHIV achieved high rates of retention and viral suppression. Adopted youth may be more likely to achieve viral suppression which may reflect the need for tailored interventions for nonadopted youth.

Non-targeted hepatitis C virus screening in acute care healthcare settings in the Southern Appalachian region.

Objectives: The objective of this study was to evaluate the performance of non-targeted hepatitis C virus (HCV) screening in emergency departments (EDs) and other healthcare settings in terms of patients identified with HCV infection and linked to HCV care. Methods: In the Southern Appalachian region of the United States, we developed non-targeted HCV screening and linkage-to-care programs in 10 institutions at different healthcare settings, including EDs, outpatient clinics, and inpatient units. Serum samples were tested for HCV antibodies, and if positive, reflexed to HCV ribonucleic acid (RNA) testing as a confirmatory test for active infection. Patients with positive RNA tests were contacted to link them to HCV care. Results: Between 2017 and 2019, among 195,152 patients screened for HCV infection, 16,529 (8.5%) were positive by antibody testing, 10,139 (5.2% of screened patients and 61.3% of patients positive by antibody test) were positive by RNA testing, and 5778 (3.0% of screened patients and 57.0% of patients positive by RNA test) were successfully linked to HCV care. Among 83,645 patients screened in EDs, 9060 (10.8%) were positive by HCV antibody, and 5243 (6.3%) were positive by RNA test. Among patients positive by RNA testing, linkage to care was lower for patients screened in the ED (44.1%) compared with outpatient clinics (67.6%) (P < 0.01) and inpatient units (50.9%) (P < 0.01). Conclusions: Non-targeted HCV screening in acute care settings can identify large numbers of people with HCV infection. To optimize the utility of these screening programs, future work is needed to develop best practices that consistently link these patients to HCV care.

Electronic Patient Portal Access, Retention in Care, and Viral Suppression Among People Living With HIV in Southeastern United States: Observational Study.

BACKGROUND: Approximately 1.1 million people living with HIV live in the United States, and the incidence is highest in Southeastern United States. Electronic patient portal prevalence is increasing and can improve engagement in primary medical care. Retention in care and viral suppression-measures of engagement in HIV care-are associated with decreased HIV transmission, morbidity, and mortality. OBJECTIVE: We aimed to determine if patient portal access among people living with HIV was associated with retention and viral suppression. METHODS: We conducted an observational cohort study among people living with HIV in care at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee) from 2011-2016. Individual access was defined as patient portal account registration at any point in the year prior. Retention was defined as ≥2 kept appointments or HIV lab measurements ≥3 months apart within a 12-month period. Viral suppression was defined as the last viral load in the calendar year <200 copies/mL. We calculated adjusted prevalence ratios (aPRs) and 95% CIs using modified Poisson regression with generalized estimating equations to estimate the association of portal access with retention and viral suppression. RESULTS: We included 4237 people living with HIV contributing 16,951 person-years of follow-up (median 5, IQR 3-5 person-years). The median age was 43 (IQR 33-50) years. Of the 4237 people living with HIV, 78.1% (n=4237) were male, 40.8% (n=1727) were Black non-Hispanic, and 56.5% (n=2395) had access. Access was independently associated with retention (aPR 1.13, 95% CI 1.10-1.17) and viral suppression (aPR 1.18, 95% CI 1.14-1.22). CONCLUSIONS: In this population, patient portal access was associated with retention and viral suppression. Future prospective studies should assess the impact of increasing portal access among people living with HIV on these HIV outcomes.

Delirium and its association with short-term outcomes in younger and older patients with acute heart failure.

Younger patients (18 to 65 years old) are often excluded from delirium outcome studies. We sought to determine if delirium was associated with short-term adverse outcomes in a diverse cohort of younger and older patients with acute heart failure (AHF). We conducted a multi-center prospective cohort study that included adult emergency department patients with confirmed AHF. Delirium was ascertained using the Brief Confusion Assessment Method (bCAM). The primary outcome was a composite outcome of 30-day all-cause death, 30-day all-cause rehospitalization, and prolonged index hospital length of stay. Multivariable logistic regression was performed, adjusting for demographics, cognitive impairment without delirium, and HF risk factors. Older age (≥ 65 years old)*delirium interaction was also incorporated into the model. Odds ratios (OR) with their 95% confidence intervals (95%CI) were reported. A total of 1044 patients with AHF were enrolled; 617 AHF patients were < 65 years old and 427 AHF patients were ≥ 65 years old, and 47 (7.6%) and 40 (9.4%) patients were delirious at enrollment, respectively. Delirium was significantly associated with the composite outcome (adjusted OR = 1.64, 95%CI: 1.02 to 2.64). The older age*delirium interaction p-value was 0.47. In conclusion, delirium was common in both younger and older patients with AHF and was associated with poorer short-term outcomes in both cohorts. Younger patients with acute heart failure should be included in future delirium outcome studies.

Seamens' Sign: a novel electrocardiogram prediction tool for left ventricular hypertrophy.

Introduction: Patients with left ventricular hypertrophy (LVH) diagnosed by electrocardiogram (ECG) have increased mortality and higher risk for life-threatening cardiovascular disease. ECGs offer an opportunity to identify patients with increased risk for potential risk-modifying therapy. We developed a novel, quick, easy to use ECG screening criterion (Seamens' Sign) for LVH. This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads. Methods: This study was a retrospective chart review of 2,184 patient records of patients who had an ECG performed in the emergency department and a transthoracic echocardiogram performed within 90 days. The primary outcome was whether Seamens' Sign was noninferior in confirming LVH compared to other common diagnostic criteria. Test characteristics were calculated for each of the LVH criteria. Inter-rater agreement was assessed on a random sample using Cohen's Kappa. Results: Median age was 63, 52% of patients were male and there was a 35% prevalence of LVH by transthoracic echocardiogram (TTE). Nine percent were positive for LVH on ECG based on Seamens' Sign. Seamens' Sign had a specificity of 0.92. Tests assessing noninferiority indicated Seamens' Sign was non-inferior to all criteria (p < 0.001) except for Cornell criterion for women (p = 0.98). Seamens' Sign had 90% (0.81-1.00) inter-rater agreement, the highest of all criteria in this study. Conclusion: When compared to both the Sokolow-Lyon criteria and the Cornell criterion for men, Seamens' Sign is noninferior in ruling in LVH on ECG. Additionally, Seamens' Sign has higher inter-rater agreement compared to both Sokolow-Lyon criteria as well as the Cornell criteria for men and women, perhaps related to its ease of use.

Weight gain post-ART in HIV+ Latinos/as differs in the USA, Haiti, and Latin America.

Background: An obesity epidemic has been documented among adult Latinos/as in Latin America and the United States (US); however, little is known about obesity among Latinos/as with HIV (PWH). Moreover, Latinos/as PWH in the US may have different weight trajectories than those in Latin America due to the cultural and environmental contexts. We assessed weight and body mass index (BMI) trajectories among PWH initiating antiretroviral therapy (ART) across 5 countries in Latin America and the Caribbean and the US. Methods: ART-naÿve PWH ≥18 years old, enrolled in Brazil, Honduras, Mexico, Peru, and Haiti (sites within CCA-SAnet) and the US (NA-ACCORD) starting ART between 2000 and 2017, with at least one weight measured after ART initiation were included. Participants were classified according to site/ethnicity as: Latinos/as in US, non-Latinos/as in US, Haitians, and Latinos/as in Latin America. Generalized least squares models were used to assess trends in weight and BMI. Models estimating probabilities of becoming overweight/obese (BMI ≥25 kg/m2) and of becoming obese (BMI ≥30 kg/m2) post ART initiation for males and females were fit using generalized estimating equations with a logit link and an independence working correlation structure. Findings: Among 59,207 PWH, 9% were Latinos/as from Latin America, 9% Latinos/as from the US, 68% non-Latinos/as from the US and 14% were Haitian. At ART initiation, 29% were overweight and 14% were obese. Post-ART weight and BMI increases were steeper for Latinos/as in Latin America compared with other sites/ethnicities; however, BMI at 3-years post ART remained lower compared to Latinos/as and non-Latinos/as in the US. Among females, at 3-years post ART initiation the greatest adjusted probability of obesity was found among non-Latinas in the US (15·2%) and lowest among Latinas in Latin America (8.6%). Among males, while starting with a lower BMI, Latinos in Latin America had the greatest adjusted probability of becoming overweight or obese 3-years post-ART initiation. Interpretation: In the Americas, PWH gain substantial weight after ART initiation. Despite environmental and cultural differences, PWH in Latin America, Haiti and Latinos and non-Latinos in the US share similar BMI trajectories on ART and high probabilities of becoming overweight and obese over time. Multicohort studies are needed to better understand the burden of other metabolic syndrome components in PWH across different countries.

Troponin is unrelated to outcomes in heart failure patients discharged from the emergency department.

Background: Prior data has demonstrated increased mortality in hospitalized patients with acute heart failure (AHF) and troponin elevation. No data has specifically examined the prognostic significance of troponin elevation in patients with AHF discharged after emergency department (ED) management. Objective: Evaluate the relationship between troponin elevation and outcomes in patients with AHF who are treated and released from the ED. Methods: This was a secondary analysis of the Get with the Guidelines to Reduce Disparities in AHF Patients Discharged from the ED (GUIDED-HF) trial, a randomized, controlled trial of ED patients with AHF who were discharged. Patients with elevated conventional troponin not due to acute coronary syndrome (ACS) were included. Our primary outcome was a composite endpoint: time to 30-day cardiovascular death and/or heart failure-related events. Results: Of the 491 subjects included in the GUIDED-HF trial, 418 had troponin measured during the ED evaluation and 66 (16%) had troponin values above the 99th percentile. Median age was 63 years (interquartile range, 54-70), 62% (n = 261) were male, 63% (n = 265) were Black, and 16% (n = 67) experienced our primary outcome. There were no differences in our primary outcome between those with and without troponin elevation (12/66, 18.1% vs 55/352, 15.6%; P = 0.60). This effect was maintained regardless of assignment to usual care or the intervention arm. In multivariable regression analysis, there was no association between our primary outcome and elevated troponin (hazard ratio, 1.00; 95% confidence interval,  0.49-2.01, P = 0.994). Conclusion: If confirmed in a larger cohort, these findings may facilitate safe ED discharge for a group of patients with AHF without ACS when an elevated troponin is the primary reason for admission.

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy.

BACKGROUND: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described. METHODS: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation. RESULTS: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20). CONCLUSIONS: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

CD4/CD8 Ratio and Cancer Risk Among Adults With HIV.

BACKGROUND: Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada. METHODS: We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness. RESULTS: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P < .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. CONCLUSIONS: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.

Individual, community, and structural factors associated with linkage to HIV care among people diagnosed with HIV in Tennessee.

OBJECTIVE: We assessed trends and identified individual- and county-level factors associated with individual linkage to HIV care in Tennessee (TN). METHODS: TN residents diagnosed with HIV from 2012-2016 were included in the analysis (n = 3,751). Individuals were assigned county-level factors based on county of residence at the time of diagnosis. Linkage was defined by the first CD4 or HIV RNA test date after HIV diagnosis. We used modified Poisson regression to estimate probability of 30-day linkage to care at the individual-level and the contribution of individual and county-level factors to this outcome. RESULTS: Both MSM (aRR 1.23, 95%CI 0.98-1.55) and women who reported heterosexual sex risk factors (aRR 1.39, 95%CI 1.18-1.65) were more likely to link to care within 30-days than heterosexual males. Non-Hispanic Black individuals had poorer linkage than White individuals (aRR 0.77, 95%CI 0.71-0.83). County-level mentally unhealthy days were negatively associated with linkage (aRR 0.63, 95%CI: 0.40-0.99). CONCLUSIONS: Racial disparities in linkage to care persist at both individual and county levels, even when adjusting for county-level social determinants of health. These findings suggest a need for structural interventions to address both structural racism and mental health needs to improve linkage to care and minimize racial disparities in HIV outcomes.

Early results of fixed-bearing unicompartmental knee replacement designed for the lateral compartment.

BACKGROUND: Isolated lateral compartment knee arthritis is less prevalent than medial. While the reported results of medial unicompartmental knee replacement (UKR) have been good and comparable to total knee replacement, the results of lateral UKR have been mixed. We present the short-term results and survivorship of a fixed-bearing UKR designed specifically for the lateral compartment. METHODS: We report the result of 130 primary fixed-bearing lateral Oxford (FLO) UKRs (123 patients) performed between 2015 and 2019 with a minimum follow-up of 1 year. The indications for lateral UKR were: isolated lateral osteoarthritis (n = 122), post-trauma (n = 5) and osteonecrosis (n = 3). The mean age was 69.1 (± 11.6), mean BMI 28.4 (± 4.9), 66.9% female, 60% right-sided, and mean follow-up 3 (range 1-4.8 years, standard deviation ± 1) years. The primary outcome measure was the Oxford knee score (OKS). Survival analysis was performed with "revision for any reason", "reoperation", and "implant failure" as the endpoints. RESULTS: Six patients died from unrelated reasons. None of the implants failed. One required the addition of a medial UKR for medial arthritis. There were no other reoperations. At 4 years, the survival for implant failure was 100% and for both revision and all reoperations was 99.5% (95% CI 96.7-99.9%). At the last review, at a mean of 3 years, the mean Oxford knee score was 41. CONCLUSION: The good survivorship and outcome scores suggest that UKR designed for the lateral compartment is an excellent alternative to total knee replacement in selected patients with isolated lateral tibiofemoral arthritis at short-term follow-up.