Clinical and cost-effectiveness of remote-delivered, online lifestyle therapy versus psychotherapy for reducing depression: results from the CALM non-inferiority, randomised trial.

Background: We conducted the first non-inferiority, randomised controlled trial to determine whether lifestyle therapy is non-inferior to psychotherapy with respect to mental health outcomes and costs when delivered via online videoconferencing. Methods: An individually randomised, group treatment design with computer-generated block randomisation was used. Between May 2021-April 2022, 182 adults with a Distress Questionnaire-5 score = ≥8 (indicative depression) were recruited from a tertiary mental health service in regional Victoria, Australia and surrounds. Participants were assigned to six 90-min sessions over 8-weeks using group-based, online videoconferencing comprising: (1) lifestyle therapy (targeting nutrition, physical activity) with a dietitian and exercise physiologist (n = 91) or (2) psychotherapy (Cognitive Behavioural Therapy) with psychologists (n = 91). The primary outcome was Patient Health Questionnaire-9 (PHQ-9) depression at 8-weeks (non-inferiority margin ≤2) using Generalised Estimating Equations (GEE). Cost-minimisation analysis estimated the mean difference in total costs from health sector and societal perspectives. Outcomes were assessed by blinded research assistants using Computer Assisted Telephone Interviews. Results are presented per-protocol (PP) and Intention to Treat (ITT) using beta coefficients with 95% Confidence Intervals (CIs). Findings: The sample was 80% women (mean: 45-years [SD:13.4], mean PHQ-9:10.5 [SD:5.7]. An average 4.2 of 6 sessions were completed, with complete data for n = 132. Over 8-weeks, depression reduced in both arms (PP: Lifestyle (n = 70) mean difference:-3.97, 95% CIs:-5.10, -2.84; and Psychotherapy (n = 62): mean difference:-3.74, 95% CIs:-5.12, -2.37; ITT: Lifestyle (n = 91) mean difference:-4.42, 95% CIs: -4.59, -4.25; Psychotherapy (n = 91) mean difference:-3.82, 95% CIs:-4.05, -3.69) with evidence of non-inferiority (PP GEE ß:-0.59; 95% CIs:-1.87, 0.70, n = 132; ITT GEE ß:-0.49, 95% CIs:-1.73, 0.75, n = 182). Three serious adverse events were recorded. While lifestyle therapy was delivered at lower cost, there were no differences in total costs (health sector adjusted mean difference: PP AUD$156 [95% CIs -$182, $611, ITT AUD$190 [95% CIs -$155, $651] ]; societal adjusted mean difference: PP AUD$350 [95% CIs:-$222, $1152] ITT AUD$ 408 [95% CIs -$139, $1157]. Interpretation: Remote-delivered lifestyle therapy was non-inferior to psychotherapy with respect to clinical and cost outcomes. If replicated in a fully powered RCT, this approach could increase access to allied health professionals who, with adequate training and guidelines, can deliver mental healthcare at comparable cost to psychologists. Funding: This trial was funded by the Australian Medical Research Future Fund (GA133346) under its Covid-19 Mental Health Research Grant Scheme.

Evaluating the effectiveness of a multi-component lifestyle therapy program versus psychological therapy for managing mood disorders (HARMON-E): protocol of a randomised non-inferiority trial.

BACKGROUND: Mood disorders, including unipolar and bipolar depression, contribute significantly to the global burden of disease. Psychological therapy is considered a gold standard non-pharmacological treatment for managing these conditions; however, a growing body of evidence also supports the use of lifestyle therapies for these conditions. Despite some clinical guidelines endorsing the application of lifestyle therapies as a first-line treatment for individuals with mood disorders, there is limited evidence that this recommendation has been widely adopted into routine practice. A key obstacle is the insufficient evidence on whether lifestyle therapies match the clinical and cost effectiveness of psychological therapy, particularly for treating those with moderate to severe symptoms. The HARMON-E Trial seeks to address this gap by conducting a non-inferiority trial evaluating whether a multi-component lifestyle therapy program is non-inferior to psychological therapy on clinical and cost-effectiveness outcomes over 8-weeks for adults with major depressive disorder and bipolar affective disorder. METHODS: This trial uses an individually randomised group treatment design with computer generated block randomisation (1:1). Three hundred and seventy-eight adults with clinical depression or bipolar affective disorder, a recent major depressive episode, and moderate-to-severe depressive symptoms are randomised to receive either lifestyle therapy or psychological therapy (adjunctive to any existing treatments, including pharmacotherapies). Both therapy programs are delivered remotely, via a secure online video conferencing platform. The programs comprise an individual session and six subsequent group-based sessions over 8-weeks. All program aspects (e.g. session duration, time of day, and communications between participants and facilitators) are matched except for the content and program facilitators. Lifestyle therapy is provided by a dietitian and exercise physiologist focusing on four pillars of lifestyle (diet, physical activity, sleep, and substance use), and the psychological therapy program is provided by two psychologists using a cognitive behavioural therapy approach. Data collection occurs at baseline, 8-weeks, 16-weeks, and 6 months with research assistants blinded to allocation. The primary outcome is depressive symptoms at 8 weeks, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) (minimal clinically important difference = 1.6). A pre-specified within-trial economic evaluation will also be conducted. DISCUSSION: Should lifestyle therapy be found to be as clinically and cost effective as psychological therapy for managing mood disorders, this approach has potential to be considered as an adjunctive treatment for those with moderate to severe depressive symptoms. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12622001026718, registered 22nd July 2022. PROTOCOL VERSION:  4.14, 26/06/2024.

Estimating optimal therapeutic drug levels of anti-tuberculosis medications based on treatment safety and effectiveness.

Background: Therapeutic drug ranges (TDR) for standard anti-tuberculosis (TB) treatment have been determined based on expected drug levels at least 2 hours after taking the dose. In this study we constructed TDR for TB drug levels based on minimizing drug toxicity and maximizing treatment effectiveness. Methods: Participants were followed prospectively in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil observational cohort study. We focused on participants with culture-confirmed drug-susceptible pulmonary TB who underwent standard TB therapy. TDR were estimated for each TB drug separately: isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA). TDR were defined as drug concentrations that were both safe and effective: safety was defined as the probability of having an ADR of at most 5%, while effectiveness was defined as a probability of at least 95% of not having either TB treatment failure or recurrence. Results: There were 765 plasma samples from 448 patients; 110 (24.6%) were people with HIV, 9 (2.0%) had a grade 3 or higher ADR, and 15 (3.3%) had treatment failure/recurrence. Higher drug concentrations of INH, RIF and EMB were associated with increased odds of having ADR. High concentrations of INH suggested protection against treatment failure/recurrence. Estimated therapeutic drug range for INH (2.3-8.2 µg/ml) and for RIF (0.5-7.5 µg/ml) differed from the currently recommended drug ranges (3-5 µg/ml and 8-24 µg/ml, respectively). Estimates for PZA and EMB were similar to the currently recommended values. Conclusions: Our estimated upper end TDR were higher for INH and lower for RIF compared to currently recommended ranges.

Understanding the relationship between childhood abuse and affective symptoms in bipolar disorder: New insights from a network analysis.

The impact of childhood abuse on the presentation of bipolar disorder could be further elucidated by comparing the networks of affective symptoms among individuals with and with no history of childhood abuse. Data from 476 participants in the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study were used to fit several regularised Gaussian Graphical Models. Differences in the presentation of depressive and manic symptoms were uncovered: only among participants with a history of childhood abuse, inadequacy and pessimism were central symptoms in the network of depressive symptoms, while racing thoughts was an important symptom in the network of manic symptoms. Following network theory, focusing treatments at the symptom-level and on central symptoms - like inadequacy, pessimism, and racing thoughts - could be an effective approach for managing affective symptoms among the sizeable proportion of people with bipolar disorder who have experienced childhood abuse. This study contributes a thorough investigation of the networks of affective symptoms among participants with and with no history of childhood abuse, albeit limited by the use of a binary, self-report measure of childhood abuse, thereby emphasising the importance of assessing for childhood abuse and taking needed steps towards identifying novel targets for treating bipolar disorder.

Conduit Ischemia After Esophagectomy: A Spectrum of Clinical Manifestations, Prevention, and Management.

This article outlines the anatomic and physiologic basis for gastric conduit ischemia and the range of its possible manifestations, from superficial mucosal ischemia to gross conduit necrosis. Methods by which these complications are suspected and ultimately diagnosed are discussed, focusing on clinical and laboratory signs as the harbingers and the use of imaging and endoscopy for confirmation. From there, management options are detailed based on the Esophagectomy Complications Consensus Group classification of esophageal leak and gastric necrosis. Finally, the short- and long-term implications of these complications are reviewed.

Blue Ribbon Committee II: Reports of the Subcommittees on the Optimization of Surgical Education and Training in the United States WORK-LIFE INTEGRATION, RESILIENCE, AND WELLNESS.

OBJECTIVE: Define recommendations for work-life integration and wellness and provide a pathway for supporting, teaching, and strengthening the skills needed to live as an authentic, empathic, compassionate, emotionally intelligent surgeon who provides the best care to patients. SUMMARY BACKGROUND DATA: Burnout is common during surgical residency. It is important to assess how we are addressing the human needs in surgical trainees. We report the recommendations of the work-life integration, wellness, and resilience subcommittee of the Blue Ribbon Committee II. METHODS: We met monthly via a virtual format and established the needs of the surgical trainee according to Maslow's Triangle. Barriers to meeting needs were identified, classified (local, state, national, etc.), and assigned to "easy" or "hard to address." Recommendations were developed for each Maslow's Triangle level and organized into 1-2- and 3-5-year goals. The Blue Ribbon Committee II (BRCII) narrowed these down to 6 recommendations that were included in a Delphi Analysis with 80% consensus needed to be included in the BRCII paper. RESULTS: Six recommendations were developed by the BRCII and four met consensus. Final recommendations addressed resident wages, a culture of belonging, workplace safety, and reporting mistreatment. CONCLUSION: Creating a culture of belonging by focusing on program culture through accountability, safety, and collaboration can lead surgical training programs to train highly successful surgeons.

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.

Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin-18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). STUDY DESIGN: Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 h of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined. RESULTS: In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p = 0.024.) A multivariate model including IL-18 at 24 HOL and 5-min Apgar performed best, with an AUC of 0.84 (SE = 0.07, p = 0.02). CONCLUSIONS: Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.

The Xpert® MTB/RIF cycle threshold value predicts M. tuberculosis transmission to close contacts in a Brazilian prospective multicenter cohort.

BACKGROUND: The Xpert® MTB/RIF rapid molecular test provides a quantitative measure of Mycobacterium tuberculosis (Mtb) DNA in the form of cycle threshold (Ct) values. This information can be translated into mycobacterial load and used as a potential risk measure of bacterial spread for tuberculosis cases, which can impact infection control. However, the role of Ct values in assessing Mtb transmission to close contacts has not yet been demonstrated. METHODS: A prospective study was performed to investigate the association between Xpert® MTB/RIF Ct values and Mtb transmission to close contacts of patients with culture-confirmed pulmonary TB in a multi-center Brazilian cohort. We evaluated clinical and laboratory data, such as age, sex, race, smoking habits, drug use, alcohol use, chest radiograph, Xpert® MTB/RIF results among pulmonary tuberculosis cases, and QuantiFERON(QFT)-Plus results at baseline and after six months for close contacts who had a negative result at baseline. RESULTS: A total of 1,055 close contacts of 382 pulmonary tuberculosis cases were included in the study. The median Ct values from pulmonary tuberculosis cases of QFT-Plus positive (at baseline or six months) close contacts were lower compared with those who were QFT-Plus negative. An adjusted logistic regression demonstrated that reduced Ct values from the index cases were independently associated with QFT-Plus conversion from negative to positive (OR: 1.61, 95% CI: 1.12-2.32) after adjusting for clinical characteristics. CONCLUSION: Close contacts of pulmonary TB index cases exhibiting low Xpert MTB/RIF Ct values displayed higher rates of TB infection, reflecting Mtb transmission.

Flexible approaches to eCOA administration in clinical trials: The site perspective.

The Critical Path Institute convened the Support Flexible Approaches to PRO Data Collection project as part of the eCOA: Getting Better Together Initiative which was instigated to identify and address common challenges and drive positive change with eCOA implementation in clinical trials. The project aimed to identify clinical trial stakeholders' concerns related to electronic PRO (ePRO) implementation and propose areas of improvement via simplification and flexibility. One workstream focused on patient-/site-centric approaches for simplification and surveyed representatives of clinical sites and site monitors for their perspectives. A semi-structured questionnaire was developed and distributed via snowball sampling to site professionals and clinical research associates (CRAs) that had ePRO experience who had been identified via representative groups or sponsor-led site networks. Responses were received from various site roles across a range of global regions; the largest contribution was from the United States. Topics raised included helpdesk capabilities, technical concerns, device types, and user interfaces among others and are discussed further in this paper. The feedback derived from the questionnaire provided the basis for concrete ideas that sponsors should consider incorporating into protocol design for participant visits, technology use, devices, and methods of back-up data collection.

Isoniazid Monoresistance and Antituberculosis Treatment Outcome in Persons With Pulmonary Tuberculosis in Brazil.

Background: The high burden of drug-resistant tuberculosis (TB) is a problem to achieve the goals of the End TB Strategy by 2035. Whether isoniazid monoresistance (Hr) affects anti-TB treatment (ATT) outcomes remains unknown in high-burden countries. Methods: We evaluated determinants of ATT outcome among pulmonary TB cases reported to the National Notifiable Disease Information System (SINAN) between June 2015 and June 2019, according to drug sensitivity testing (DST) results. Binomial logistic regression models were employed to evaluate whether Hr was associated with an unfavorable ATT outcome: death or failure, compared to cure or treatment completion. Results: Among 60 804 TB cases reported in SINAN, 21 197 (34.9%) were included in the study. In this database, the frequency of unfavorable outcomes was significantly higher in those with Hr in contrast to isoniazid-sensitive persons with pulmonary TB (9.1% vs 3.05%; P < .001). Using a binomial logistic regression model, Hr was independently associated with unfavorable outcomes (odds ratio, 3.34 [95% confidence interval, 2.06-5.40]; P < .001). Conclusions: Hr detected prior to ATT was predictive of unfavorable outcomes at the national level in Brazil. Our data reinforce the need for high-TB-burden countries to prioritize DST to detect Hr. Effective treatment regimens for Hr-TB are needed to improve outcomes.

Misclassification of Loss to Care Among Persons With Human Immunodeficiency Virus: Improved Capture of Silent Transfers Through Surveillance Linkage Using Statewide Mandatorily Reported Laboratory Measures.

Human Immunodeficiency Virus (HIV)-positive individuals lost to follow-up from particular clinics may not be lost to care (LTC). After linking Vanderbilt's Comprehensive Care Clinic cohort to Tennessee's statewide HIV surveillance database, LTC decreased from 48.4% to 35.0% at 10 years. Routine surveillance linkage by domestic HIV clinics would improve LTC and retention measure accuracy.

Piloting Safety and Stabilization: A Multi-component Trauma Intervention to Improve HIV Viral Suppression, Retention in Care, and Post-traumatic Stress Disorder in a Southern United States HIV Service Organization.

In this observational study, we assessed the extent to which a community-created pilot intervention, providing trauma-informed care for persons with HIV (PWH), affected HIV care retention and viral suppression among PWH attending an HIV Services Organization in the Southern US. PWH with trauma exposure and/or trauma symptoms (N = 166) were offered a screening and referral to treatment (SBIRT) session. Per self-selection, 30 opted-out, 29 received SBIRT-Only, 25 received SBIRT-only but reported receiving other behavioral health care elsewhere, and 82 participated in the Safety and Stabilization (S&S) Intervention. Estimates from multivariable logistic regression analyses indicated S&S Intervention participants had increased retention in HIV care (adjusted odds ratio [aOR] 5.46, 95% CI 1.70-17.50) and viral suppression (aOR 17.74, 95% CI 1.83-172), compared to opt-out participants. Some evidence suggested that PTSD symptoms decreased for intervention participants. A randomized controlled trial is needed to confirm findings.

Potential Adjuncts to Therapeutic Hypothermia to Mitigate Multiorgan Injury in Perinatal Hypoxia-Ischemia.

Over the last 2 decades, therapeutic hypothermia has become the standard of care to reduce morbidity and mortality in neonates affected by moderate-to-severe hypoxic-ischemic encephalopathy (HIE). There is a significant interest in improving the neurologic outcomes of neonatal HIE, ranging from adjunctive therapy to therapeutic hypothermia. Importantly, the pathophysiologic mechanisms underlying HIE also affect multiple other organs, contributing to high morbidity and mortality in this patient population. This review focuses on the adjunct therapies currently under investigation to mitigate the impact of hypoxic-ischemic injury on the brain, kidneys, liver, heart, and gastrointestinal system.

Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management.

Populations with common physical diseases - such as cardiovascular diseases, cancer and neurodegenerative disorders - experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug-drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic-pituitary-adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio-environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases.

Pharmacogenetics of tuberculosis treatment toxicity and effectiveness in a large Brazilian cohort.

Background: Genetic polymorphisms have been associated with risk of anti-tuberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil. Methods: Participants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil. We included persons with culture-confirmed drug-susceptible pulmonary tuberculosis who started treatment between 2015-2019, and who were evaluable for pharmacogenetics. Treatment included 2 months of isoniazid, rifampin or rifabutin, pyrazinamide, and ethambutol, then 4 months of isoniazid and rifampin or rifabutin, with 24 month follow-up. Analyses included 43 polymorphisms in 20 genes related to anti-tuberculosis drug hepatotoxicity or pharmacokinetics. Whole exome sequencing was done in a case-control toxicity subset. Results: Among 903 participants in multivariable genetic association analyses, NAT2 slow acetylator status was associated with increased risk of treatment-related grade 2 or greater adverse events, including hepatotoxicity. Treatment failure/recurrence was more likely among NAT2 rapid acetylators, but not statistically significant at the 5% level. A GSTM1 polymorphism (rs412543) was associated with increased risk of treatment-related adverse events, including hepatotoxicity. SLCO1B1 polymorphisms were associated with increased risk of treatment- related hepatoxicity and treatment failure/recurrence. Polymorphisms in NR1/2 were associated with decreased risk of adverse events and increased risk of failure/recurrence. In whole exome sequencing, hepatotoxicity was associated with a polymorphism in VTI1A , and the genes METTL17 and PRSS57 , but none achieved genome-wide significance. Conclusions: In a clinical cohort representing three regions of Brazil, NAT2 acetylator status was associated with risk for treatment-related adverse events. Additional significant polymorphisms merit investigation in larger study populations.

Anemia and anti-tuberculosis treatment outcome in persons with pulmonary tuberculosis: A multi-center prospective cohort study.

BACKGROUND: Tuberculosis (TB) remains a major plague of humanity. People with TB (PWTB) are commonly anemic. Here, we assessed whether the severity of anemia in PWTB prior to anti-TB treatment (ATT) was a risk factor for an unfavorable outcome. METHODS: Patients ≥ 18 years old with culture-confirmed drug-susceptible pulmonary TB enrolled between 2015 and 2019 in a multi-center Brazilian cohort were followed for up to 24 months and classified according to anemia severity (mild, moderate, and severe), based on hemoglobin levels. A multinomial logistic regression model was employed to assess whether anemia was associated with unfavorable outcome (death, failure, loss to follow-up, regimen modification or relapse), compared to treatment success (cure or treatment completion). RESULTS: Among 786 participants who met inclusion criteria, 441 (56 %) were anemic at baseline. Patients with moderate/severe anemia were more HIV-seropositive, as well as more symptomatic and had higher frequencies of unfavorable outcomes compared to the other groups. Moderate/severe anemia (adjusted OR [aOR]: 7.80, 95 %CI:1.34-45.4, p = 0.022) was associated with death independent of sex, age, BMI, HIV and glycemic status. CONCLUSION: Moderate/severe anemia prior to ATT was a significant risk factor for death. Such patients should be closely monitored given the high risk of unfavorable ATT outcomes.

Neonatal acute kidney injury during indomethacin therapy: does it predict ductal closure?

BACKGROUND: Preterm newborns are at risk for patent ductus arteriosus, and non-steroidal anti-inflammatory drugs are often used to facilitate patent ductus arteriosus closure. Acute kidney injury is common in critically ill neonates and may be caused by non-steroidal anti-inflammatory drugs. We sought to describe the incidence of acute kidney injury among preterm infants receiving indomethacin and determine whether acute kidney injury during indomethacin therapy is associated with subsequent patent ductus arteriosus closure. METHODS: Retrospective cohort including neonates < 33 weeks gestational age, admitted to two level IIIb neonatal intensive care units between November 2016 and November 2019, who received indomethacin in the first 2 weeks of life. Acute kidney injury in the 7-day period after treatment was defined by neonatal modified Kidney Disease Improving Global Outcomes (KDIGO) criteria. Patent ductus arteriosus closure was defined clinically and/or via echocardiogram. Clinical characteristics were extracted from medical records. Association between acute kidney injury during treatment and successful closure of patent ductus arteriosus was evaluated using chi-square tests and logistic regression. RESULTS: One hundred fifty preterm infants were included; acute kidney injury occurred in 8% (all KDIGO Stage 1). Patent ductus arteriosus closed in 52.9% of the non-acute kidney injury group and 66.7% of the acute kidney injury group (p = 0.55). Serum creatinine was checked a mean of 3.1 times in the acute kidney injury group and 2.2 times in the non-acute kidney injury group. There was no difference in survival. CONCLUSION: We found no association between acute kidney injury during indomethacin therapy and patent ductus arteriosus closure. Paucity of serum creatinine values likely underdiagnosed acute kidney injury. Surveillance of kidney function during indomethacin therapy using more sensitive renal biomarkers may better identify infants who develop acute kidney injury in the context of non-steroidal anti-inflammatory drug use.

Day Case Local Anaesthetic Thoracoscopy: Experience from 2 District General Hospitals in the United Kingdom.

BACKGROUND: Local anaesthetic thoracoscopy (LAT) can be a vital procedure for diagnosis of unexplained pleural effusions. Traditionally, poudrage for pleurodesis and insertion of a large bore drain necessitated admission. There has been a shift towards performing LAT as a day case procedure with indwelling pleural catheter (IPC) insertion. This was advocated during the COVID pandemic by the British Thoracic Society (BTS). To determine the feasibility of such pathways, continuous evaluations are required. METHODS: All day case LAT procedures with IPC insertion, performed in theatre, were identified at two large district general hospitals (Northumbria HealthCare in the North East of England and Victoria Hospital, NHS Fife, in Scotland). Rapid pleurodesis with talc was not performed due to local staffing problems. All patients had their LAT in theatre under conscious sedation with a rigid scope. Demographics, clinical, radiological and histopathological characteristics and outcomes were collected. RESULTS: 79 patients underwent day case LAT. The lung did not deflate, meaning biopsies were not enabled, in four of the patients. The mean age was 72 years (standard deviation 13). Fifty-five patients were male and twenty-four were female. The main diagnoses were lung cancers, mesotheliomas and fibrinous pleuritis with an overall diagnostic sensitivity of 93%. Other diagnoses were breast, tonsillar, unknown primary cancers and lymphomas. Seventy-three IPCs were simultaneously placed and, due to normal macroscopic appearances in two patients, two large bore drains were placed and removed within one hour of LAT termination. Sixty-six (88%) patients were discharged on the same day. Seven patients required admission: one for treatment of surgical emphysema, four because they lived alone, one for pain control and one for control of a cardiac arrythmia. Within 30 days, there were five IPC site infections with two resultant empyemas (9%), with no associated mortality. Two patients developed pneumonia requiring admission and one patient required admission for pain management. The median number of days for which the IPCs remained in situ was 78.5 days (IQR 95). The median length of stay (LoS) was 0 days (IQR 0). No patients required further interventions for pleural fluid management. CONCLUSIONS: Day case LAT with IPC insertion is feasible with this current set up, with a median stay of 0 days, and should be widely adopted. The health economics of preventing admission are considerable, as our previous analysis showed a median length of stay of 3.96 days, although we are not comparing matched cohorts.

Sex and Race Disparities in Mortality and Years of Potential Life Lost Among People With HIV: A 21-Year Observational Cohort Study.

Background: Since the availability of antiretroviral therapy, mortality rates among people with HIV (PWH) have decreased; however, this does not quantify premature deaths among PWH, and disparities persist. Methods: We examined all-cause and premature mortality among PWH receiving care at the Vanderbilt Comprehensive Care Clinic from January 1998 to December 2018. Mortality rates were compared by demographic and clinical factors, and adjusted incidence rate ratios (aIRRs) were calculated using multivariable Poisson regression. For individuals who died, age-adjusted years of potential life lost (aYPLL) per total person-years living with HIV were calculated from US sex-specific life tables, and sex and race differences were examined using multivariable linear regression. Results: Among 6531 individuals (51% non-Hispanic [NH] White race, 40% NH Black race, 21% cis-gender women, 78% cis-gender men) included, 956 (14.6%) died. In adjusted analysis, PWH alive in the most recent calendar era (2014-2018) had decreased risk of mortality compared with those in the earliest calendar era (1998-2003; aIRR, 0.22; 95% CI, 0.17-0.29), and women had increased risk of death compared with men (aIRR, 1.31; 95% CI, 1.12-1.54). Of those who died, Black women had the highest aYPLL (aIRR, 592.5; 95% CI, 588.4-596.6), followed by Black men (aIRR, 470.7; 95% CI, 468.4-472.9), White women (aIRR, 411.5; 95% CI, 405.6-417.4), then White men (aIRR, 308.6; 95% CI, 308.0-309.2). In adjusted models, higher YPLL remained associated with NH Black race and cis-gender women, regardless of HIV risk factor. Conclusions: Despite marked improvement over time, sex disparities in mortality as well as sex and race disparities in YPLL remained among PWH in this cohort.