Associations between Child Opportunity Index and Pediatric Cardiac Surgical Outcomes.

OBJECTIVE: To assess the relationship between the Child Opportunity Index (COI), a comprehensive measurement of social determinants of health, and specific COI domains on patient-specific outcomes following congenital cardiac surgery in the metropolitan region of Atlanta, Georgia. STUDY DESIGN: In this retrospective chart review, we included patients who underwent an index operation for congenital heart disease between 2010 and 2020 in a single pediatric health care system. Patients' addresses were geocoded and mapped to census tracts. Descriptive statistics, univariable analysis, and multivariable regression models were employed to assess associations between variables and outcomes. RESULTS: Of the 7460 index surgeries, 3798 (51%) met eligibility criteria. Presence of an adverse outcome, defined as either mortality or 1 of several other major postoperative morbidities, was significantly associated with COI in the univariable model (P = .008), but not the multivariable regression model (P = .39). Postoperative hospital length of stay was significantly associated with COI (P < .001) in univariable and multivariable regression models. There was no significant association between COI and readmission within 30 days of hospital discharge in univariable (P < .094) and multivariable (P = .49) models. CONCLUSION: COI is associated with postoperative hospital length of stay but not all outcomes in patients after congenital heart surgery. By understanding the role of COI in outcomes related to cardiac surgery, targeted interventions can be developed to improve health equity.

Comparing effectiveness of first-line antiretroviral therapy between peri-urban and rural clinics in KwaZulu-Natal, South Africa.

OBJECTIVES: Viral suppression (VS) is the hallmark of successful antiretroviral therapy (ART) programmes. We sought to compare clinic retention, virological outcomes, drug resistance and mortality between peri-urban and rural settings in South Africa after first-line ART. METHODS: Beginning in July 2014, 1000 (500 peri-urban and 500 rural) ART-naïve patients with HIV were enrolled and managed according to local standard of care. Clinic retention, virological suppression, virological failure (VF), genotypic drug resistance and mortality were assessed. The definition of VS was a viral load ≤1000 copies/ml. Time to event analyses were stratified by site, median age and gender. Kaplan-Meier curves were calculated and graphed with log-rank modelling to compare curves. RESULTS: Based on 2741 patient-years of follow-up, retention and mortality did not differ between sites. Among all 1000 participants, 47%, 84% and 91% had achieved VS by 6, 12 and 24 months, respectively, which was observed earlier in the peri-urban site. At both sites, men aged < 32 years had the highest proportion of VF (15.5%), while women aged > 32 years had the lowest, at 7.1% (p = 0.018). Among 55 genotypes, 42 (76.4%) had at one or more resistance mutations, which did not differ by site. K103N (59%) and M184V (52%) were the most common mutations, followed by V106M and K65R (31% each). Overall, death was infrequent (< 4%). CONCLUSIONS: No significant differences in treatment outcomes between peri-urban and rural clinics were observed. In both settings, young men were especially susceptible to clinic attrition and VF. More effective adherence support for this important demographic group is needed to achieve UNAIDS targets.

Timing of Intubation and Mortality Among Critically Ill Coronavirus Disease 2019 Patients: A Single-Center Cohort Study.

OBJECTIVES: Increasing time to mechanical ventilation and high-flow nasal cannula use may be associated with mortality in coronavirus disease 2019. We examined the impact of time to intubation and use of high-flow nasal cannula on clinical outcomes in patients with coronavirus disease 2019. DESIGN: Retrospective cohort study. SETTING: Six coronavirus disease 2019-specific ICUs across four university-affiliated hospitals in Atlanta, Georgia. PATIENTS: Adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received high-flow nasal cannula or mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 231 patients admitted to the ICU, 109 (47.2%) were treated with high-flow nasal cannula and 97 (42.0%) were intubated without preceding high-flow nasal cannula use. Of those managed with high-flow nasal cannula, 78 (71.6%) ultimately received mechanical ventilation. In total, 175 patients received mechanical ventilation; 44.6% were female, 66.3% were Black, and the median age was 66 years (interquartile range, 56-75 yr). Seventy-six patients (43.4%) were intubated within 8 hours of ICU admission, 57 (32.6%) between 8 and 24 hours of admission, and 42 (24.0%) greater than or equal to 24 hours after admission. Patients intubated within 8 hours were more likely to have diabetes, chronic comorbidities, and higher admission Sequential Organ Failure Assessment scores. Mortality did not differ by time to intubation (≤ 8 hr: 38.2%; 8-24 hr: 31.6%; ≥ 24 hr: 38.1%; p = 0.7), and there was no association between time to intubation and mortality in adjusted analysis. Similarly, there was no difference in initial static compliance, duration of mechanical ventilation, or ICU length of stay by timing of intubation. High-flow nasal cannula use prior to intubation was not associated with mortality. CONCLUSIONS: In this cohort of critically ill patients with coronavirus disease 2019, neither time from ICU admission to intubation nor high-flow nasal cannula use were associated with increased mortality. This study provides evidence that coronavirus disease 2019 respiratory failure can be managed similarly to hypoxic respiratory failure of other etiologies.

Field potential 1/f activity in the subcallosal cingulate region as a candidate signal for monitoring deep brain stimulation for treatment-resistant depression.

Subcallosal cingulate cortex deep brain stimulation (SCC-DBS) is an experimental therapy for treatment-resistant depression (TRD). Refinement and optimization of SCC-DBS will benefit from increased study of SCC electrophysiology in context of ongoing high-frequency SCC-DBS therapy. The study objective was a 7-mo observation of frequency-domain 1/f slope in off-stimulation local field potentials (SCC-LFPs) alongside standardized measurements of depression severity in 4 patients undergoing SCC-DBS. SCC was implanted bilaterally with a combined neurostimulation-LFP recording system. Following a 1-mo off-stimulation postoperative phase with multiple daily recordings, patients received bilateral SCC-DBS therapy (130 Hz, 90 µs) and weekly resting-state SCC-LFP recordings over a 6-mo treatment phase. 1/f slopes for each time point were estimated via linear regression of log-transformed Welch periodograms. General linear mixed-effects models were constructed to estimate pretreatment sources of 1/f slope variance, and 95% bootstrap confidence intervals were constructed to estimate treatment phase 1/f slope association with treatment response (50% decrease in preimplantation symptom severity). Results show the time of recording was a prominent source of pretreatment 1/f slope variance bilaterally, with increased 1/f slope magnitude observed during night hours (2300-0659). Increase in right 1/f slope was observed in the setting of treatment response, with bootstrap analysis supporting this observation in 3 of 4 subjects. We conclude that 1/f slope can be measured longitudinally in a combined SCC-DBS/LFP recording system and likely conforms to known 1/f circadian variability. The preliminary evidence of 1/f slope increase during treatment response suggests a potential utility as a candidate biomarker for ongoing development of adaptive TRD-neuromodulation strategies.NEW & NOTEWORTHY In four patients with treatment-resistant depression undergoing therapeutic deep brain stimulation (DBS), we present the first longitudinal observations of local field potentials (LFP) from the subcallosal cingulate region outside the postoperative period. Specifically, our results demonstrate that frequency-domain 1/f activity is measurable in a combined DBS-LFP recording system and that right hemisphere recordings appear sensitive to mood state, thus suggesting a potential readout suitable for consideration in ongoing efforts to develop adaptive DBS delivery systems.

Associations of inflammation-related proteome with demographic and clinical characteristics of people with HIV in South Africa.

PURPOSE: Elevated levels of inflammation associated with human immunodeficiency virus (HIV) infection are one of the primary causes for the burden of age-related diseases among people with HIV (PWH). Circulating proteins can be used to investigate pathways to inflammation among PWH. EXPERIMENTAL DESIGN: We profiled 73 inflammation-related protein markers and assessed their associations with chronological age, sex, and CD4+ cell count among 87 black South African PWH before antiretroviral therapy (ART). RESULTS: We identified 1, 1, and 14 inflammatory proteins significantly associated with sex, CD4+ cell count, and age respectively. Twelve out of 14 age-associated proteins have been reported to be associated with age in the general population, and 4 have previously shown significant associations with age for PWH. Furthermore, many of the age-associated proteins such as CST5, CCL23, SLAMF1, MMP-1, MCP-1, and CDCP1 have been linked to chronic diseases such as cardiovascular disease and neurocognitive decline in the general population. We also found a synergistic interaction between male and older age accounting for excessive expression of CST5. CONCLUSIONS AND CLINICAL RELEVANCE: We found that advanced age may lead to the elevation of multiple inflammatory proteins among PWH. We also demonstrated the potential utility of proteomics for evaluating and characterizing the inflammatory status of PWH.

Convergence of HIV and non-communicable disease epidemics: geospatial mapping of the unmet health needs in an HIV hyperendemic community in South Africa.

INTRODUCTION: As people living with HIV (PLHIV) are experiencing longer survival, the co-occurrence of HIV and non-communicable diseases has become a public health priority. In response to this emerging challenge, we aimed to characterise the spatial structure of convergence of chronic health conditions in an HIV hyperendemic community in KwaZulu-Natal, South Africa. METHODS: In this cross-sectional study, we used data from a comprehensive population-based disease survey conducted in KwaZulu-Natal, South Africa, which collected data on HIV, diabetes and hypertension. We implemented a novel health needs scale to categorise participants as: diagnosed and well-controlled (Needs Score 1), diagnosed and suboptimally controlled (Score 2), diagnosed but not engaged in care (Score 3) or undiagnosed and uncontrolled (Score 4). Scores 2-4 were indicative of unmet health needs. We explored the geospatial structure of unmet health needs using different spatial clustering methods. RESULTS: The analytical sample comprised 18 041 individuals. We observed a similar spatial structure for HIV among those with combined needs Score 2-3 (diagnosed but uncontrolled) and Score 4 (undiagnosed and uncontrolled), with most PLHIV with unmet needs clustered in the southern urban and peri-urban areas. Conversely, a high prevalence of need Scores 2 and 3 for diabetes and hypertension was mostly distributed in the more rural central and northern part of the surveillance area. A high prevalence of need Score 4 for diabetes and hypertension was mostly distributed in the rural southern part of the surveillance area. Multivariate clustering analysis revealed a significant overlap of all three diseases in individuals with undiagnosed and uncontrolled diseases (unmet needs Score 4) in the southern part of the catchment area. CONCLUSIONS: In an HIV hyperendemic community in South Africa, areas with the highest needs for PLHIV with undiagnosed and uncontrolled disease are also areas with the highest burden of unmet needs for other chronic health conditions, such as diabetes and hypertension. Our study has revealed remarkable differences in the distribution of health needs across the rural to urban continuum even within this relatively small study site. The identification and prioritisation of geographically clustered vulnerable communities with unmet health needs for both HIV and non-communicable diseases provide a basis for policy and implementation strategies to target communities with the highest health needs.

Identifying sex-specific anthropometric measures and thresholds for dysglycemia screening in an HIV-endemic rural South African population.

Valid screening and diagnostic algorithms are needed to achieve 2030 targets proposed by the WHO's Global Diabetes Compact. We explored anthropometric thresholds to optimally screen and refer individuals for diabetes testing in rural South Africa. We evaluated screening thresholds for waist circumference (WC), body mass index (BMI), and waist-hip ratio (WHR) to detect dysglycemia based on a glycated hemoglobin (HbA1C) ≥6.5% among adults in a population-based study in South Africa using weighted, non-parametric ROC regression analyses. We then assessed the diagnostic validity of traditional obesity thresholds, explored optimal thresholds for this population, and fit models stratified by sex, age, and HIV status. The prevalence of dysglycemia in the total study population (n = 17,846) was 7.7%. WC had greater discriminatory capacity than WHR to detect dysglycemia in men (p-value<0.001) and women (p<0.001). WC had greater discriminatory capacity than BMI to detect dysglycemia in women (p<0.001). However, BMI and WC performed similarly for men (p = 0.589). Whereas traditional WC thresholds for women (>81cm) performed well (sensitivity 91%, positive predictive value [PPV] 14.9%), substantially lower thresholds were needed to achieve acceptable sensitivity and PPV among men (traditional >94cm, derived >79.5cm). WC outperforms BMI as an anthropometric screening measure for dysglycemia in rural South Africa. Whereas WC guideline thresholds are appropriate for women, male-derived WC cutoffs performed better at lower thresholds. In this rural South African population, thresholds that maximize specificity and PPV for efficient resource allocation may be preferred.

Convergence of HIV and non-communicable disease epidemics: Geospatial mapping of the unmet health needs in a HIV Hyperendemic South African community.

Background: As people living with HIV (PLHIV) are experiencing longer survival, the co-occurrence of HIV and non-communicable diseases has become a public health priority. In response to this emerging challenge, we aimed to characterize the spatial structure of convergence of chronic health conditions in a HIV hyperendemic community in KwaZulu-Natal, South Africa. Methods: We utilized data from a comprehensive population-based disease survey conducted in KwaZulu-Natal, South Africa, which collected data on HIV, diabetes, and hypertension. We implemented a novel health needs scale to categorize participants as: diagnosed and well-controlled (Needs Score 1), diagnosed and sub-optimally controlled (Score 2), diagnosed but not engaged in care (Score 3), or undiagnosed and uncontrolled (Score 4). Scores 2-4 were indicative of unmet health needs. We explored the geospatial structure of unmet health needs using different spatial clustering methods. Findings: The analytical sample comprised of 18,041 individuals. We observed a similar spatial structure for HIV among those with a combined needs Score 2-3 (diagnosed but uncontrolled) and Score 4 (undiagnosed and uncontrolled), with most PLHIV with unmet needs clustered in the southern peri-urban area, which was relatively densely populated within the surveillance area. Multivariate clustering analysis revealed a significant overlap of all three diseases in individuals with undiagnosed and uncontrolled diseases (unmet needs Score 4) in the southern part of the catchment area. Interpretation: In a HIV hyperendemic community in South Africa, areas with the highest needs for PLHIV with undiagnosed and uncontrolled disease are also areas with the highest burden of unmet needs for other chronic health conditions, such as diabetes and hypertension. The identification and prioritization of geographically clustered vulnerable communities with unmet health needs for both HIV and non-communicable diseases provide a basis for policy and implementation strategies to target communities with the highest health needs. Funding: Research reported in this publication was supported by the Fogarty International Center (R21 TW011687; D43 TW010543), the National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases (K24 HL166024; T32 AI007433) of the National Institutes of Health, and Heart Lung and Blood Institute (K24 HL166024, T32 AI007433). The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the funders.

Geospatial assessment of the convergence of communicable and non-communicable diseases in South Africa.

Introduction: Several low-and middle-income countries are undergoing rapid epidemiological transition with a rising burden of non-communicable diseases (NCDs). South Africa (SA) is a country with one of the largest HIV epidemics worldwide and a growing burden of NCDs where the collision of these epidemics poses a major public health challenge. Methods: Using data from a large nationally representative survey, the South Africa Demographic and Health Survey (SADHS 2016), we conducted a geospatial analysis of several diseases including HIV, tuberculosis (TB), cardiovascular, respiratory, and metabolic diseases to identify areas with a high burden of co-morbidity within the country. We explored the spatial structure of each disease and associations between diseases using different spatial and visual data methodologies. We also assessed the individual level co-occurrence of HIV and the other diseases included in the analysis. Results: The spatial distribution for HIV prevalence showed that this epidemic is most intense in the eastern region of the country, mostly within the Gauteng, Mpumalanga, and Kwazulu-Natal provinces. In contrast, chronic diseases had their highest prevalence rates the southern region of the country, particularly in the Eastern and Western Cape provinces. Individual-level analyses were consistent with the spatial correlations and found no statistically significant associations between HIV infection and the presence of any NCDs. Conclusions: We found no evidence of geospatial overlap between the HIV epidemic and NCDs in SA. These results evidence the complex epidemiological landscape of the country, characterized by geographically distinct areas exhibiting different health burdens. The detailed description of the heterogenous prevalence of HIV and NCDs in SA reported in this study could be a useful tool to inform and direct policies to enhance targeted health service delivery according to the local health needs of each community.

Heart Rate Does Not Reflect the %VO2max in Recreational Runners during the Marathon.

Exercise physiologists and coaches prescribe heart rate zones (between 65 and 80% of maximal heart rate, HRmax) during a marathon because it supposedly represents specific metabolic zones and the percentage of V˙O2max below the lactate threshold. The present study tested the hypothesis that the heart rate does not reflect the oxygen uptake of recreational runners during a marathon and that this dissociation would be more pronounced in the lower performers' group (>4 h). While wearing a portable gas exchange system, ten male endurance runners performed an incremental test on the road to determine V˙O2max, HRmax, and anaerobic threshold. Two weeks later, the same subjects ran a marathon with the same device for measuring the gas exchanges and HR continuously. The %HRmax remained stable after the 5th km (between 88% and 91%, p = 0.27), which was not significantly different from the %HRmax at the ventilatory threshold (89 ± 4% vs. 93 ± 6%, p = 0.12). However, the %V˙O2max and percentage of the speed associated with V˙O2max decreased during the marathon (81 ± 5 to 74 ± 5 %V˙O2max and 72 ± 9 to 58 ± 14 %vV˙O2max, p < 0.0001). Hence, the ratio between %HRmax and %V˙O2max increased significantly between the 5th and the 42nd km (from 1.01 to 1.19, p = < 0.001). In conclusion, pacing during a marathon according to heart rate zones is not recommended. Rather, learning about the relationship between running sensations during training and racing using RPE is optimal.

Crosstalk between Host Genome and Metabolome among People with HIV in South Africa.

Genome-wide association studies (GWAS) of circulating metabolites have revealed the role of genetic regulation on the human metabolome. Most previous investigations focused on European ancestry, and few studies have been conducted among populations of African descent living in Africa, where the infectious disease burden is high (e.g., human immunodeficiency virus (HIV)). It is important to understand the genetic associations of the metabolome in diverse at-risk populations including people with HIV (PWH) living in Africa. After a thorough literature review, the reported significant gene−metabolite associations were tested among 490 PWH in South Africa. Linear regression was used to test associations between the candidate metabolites and genetic variants. GWAS of 154 plasma metabolites were performed to identify novel genetic associations. Among the 29 gene−metabolite associations identified in the literature, we replicated 10 in South Africans with HIV. The UGT1A cluster was associated with plasma levels of biliverdin and bilirubin; SLC16A9 and CPS1 were associated with carnitine and creatine, respectively. We also identified 22 genetic associations with metabolites using a genome-wide significance threshold (p-value < 5 × 10−8). In a GWAS of plasma metabolites in South African PWH, we replicated reported genetic associations across ancestries, and identified novel genetic associations using a metabolomics approach.

The Carbon Footprint of Marathon Runners: Training and Racing.

Marathon running leaves a significant carbon footprint regarding CO2 emissions; for example, 37 percent of New York Marathon participants travel internationally to New York. The aim of this study is to estimate the CO2 footprint of a person training and competing in a marathon; we will also propose methods to minimize the CO2 footprint because of transportation. In addition, we also examine the influence of food practices and hygiene on training and racing a marathon. METHODS: We estimated the annual carbon footprint of one person taking part in a marathon. We considered all training, racing, and travelling (local and international) for one person (we are going to give him the first name of "Henri"), and then compared his CO2 footprint with his colleagues playing tennis and soccer. The excess CO2 footprint whilst running and for shoes, clothing, books, magazines, insurance, travel, hygiene, laundry, and resources for electronics and additional food consumed were calculated. For competitions, we estimated and compared the CO2 emission from transportation to national vs. international marathon (New York). RESULTS: We estimated that our runner emitted 4.3 tons of CO2 equivalent (CO2e), including all greenhouse gases. A transatlantic flight to New York corresponded to 3.5 tons CO2, which is 83% of the annual carbon footprint of an average French citizen which is about 11 tons CO2e/year. This leads to a sudden 40% increase in Henri's annual carbon footprint. CONCLUSIONS: By focusing on the additional carbon footprint from one year of marathon training and racing, and traveling locally versus internationally, this sport still has a potentially significant carbon footprint that runners and race organizers ought to consider. We wanted to answer a growing question of marathon runners who are wondering about the carbon footprint of their sports practice in following with a new environmentalist trend that considers not traveling anymore to participate in marathons and to stay local. However, the representativeness in the selection of calculation objectives is very low. There is no need for statistics since this study is a theoretical simulation of traditional training and competition practices of marathon runners.

Tenofovir diphosphate levels in dried blood spots are associated with virologic failure and resistance to first-line therapy in South Africa: a case-control cohort study.

INTRODUCTION: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), a measure of cumulative antiretroviral therapy (ART) adherence, is associated with viral suppression and predicts future viremia in persons with HIV (PWH). However, its utility to identify those at risk for virologic failure (VF) and drug resistance is unknown. To address this, we aimed to establish the association between this adherence biomarker and VF with drug resistance in a cohort of PWH initiating first-line ART in KwaZulu-Natal, South Africa. METHODS: PWH initiating TFV disoproxil fumarate (TDF)-based ART within a parent prospective cohort were evaluated. Using a nested design, DBS for TFV-DP were collected from cases who developed VF (HIV-1 RNA ≥1000 copies/ml) after ≥5 months on ART versus controls, matched 1:2 by site, age, gender, race and ART duration. Cases were categorized as having VF with or without resistance using genotyping. One-way analysis of variance (ANOVA) was used to compare TFV-DP for controls, cases with VF and resistance, and cases with VF without resistance. Data are presented as mean (standard deviation, SD) or geometric mean [95% confidence interval, 95% CI]. RESULTS AND DISCUSSION: One thousand participants were enrolled in the parent study between 2014 and 2016, of which 288 (29%) had DBS available. Of these, 94 (33%) were cases and 194 (67%) were controls; 59% were women. Mean age of our population was 33 (SD 8) years. Genotyping was available in 50 (53%) of the 94 cases. Geometric mean TFV-DP in DBS from controls was 708 [95% CI; 647-773] fmol/punch, which was higher compared to participants having VF with resistance (n = 36), 386 [95% CI; 241-617] fmol/punch and VF without resistance (n = 14), 61 [95% CI; 22-164] fmol/punch; p<0.001. Genotype could not be obtained in 44 (47%) cases. CONCLUSIONS: TFV-DP in DBS showed a stepwise association with VF and drug resistance in South African PWH. Participants having VF with resistance had mid-range concentrations of TFV-DP, which were higher than those for PWH without resistance. Future research on the clinical utility of TFV-DP concentrations in DBS to predict and prevent the development of VF and drug resistance is needed.

Maximal Time Spent at VO2max from Sprint to the Marathon.

Until recently, it was thought that maximal oxygen uptake (VO2max) was elicited only in middle-distance events and not the sprint or marathon distances. We tested the hypothesis that VO2max can be elicited in both the sprint and marathon distances and that the fraction of time spent at VO2max is not significantly different between distances. METHODS: Seventy-eight well-trained males (mean [SD] age: 32 [13]; weight: 73 [9] kg; height: 1.80 [0.8] m) performed the University of Montreal Track Test using a portable respiratory gas sampling system to measure a baseline VO2max. Each participant ran one or two different distances (100 m, 200 m, 800 m, 1500 m, 3000 m, 10 km or marathon) in which they are specialists. RESULTS: VO2max was elicited and sustained in all distances tested. The time limit (Tlim) at VO2max on a relative scale of the total time (Tlim at VO2max%Ttot) during the sprint, middle-distance, and 1500 m was not significantly different (p > 0.05). The relevant time spent at VO2max was only a factor for performance in the 3000 m group, where the Tlim at VO2max%Ttot was the highest (51.4 [18.3], r = 0.86, p = 0.003). CONCLUSIONS: By focusing on the solicitation of VO2max, we demonstrated that the maintenance of VO2max is possible in the sprint, middle, and marathon distances.

Geospatial variation in caesarean delivery.

Aim: The purpose of this study was to evaluate the variation in caesarean delivery rates across counties in Georgia and to determine whether county-level characteristics were associated with clusters. Design: This was a retrospective, observational study. Methods: Rates of primary and repeat caesarean by maternal county of residence were calculated for 2008 through 2012. Global Moran's I (Spatial Autocorrelation) was used to identify geographic clustering. Characteristics of high and low-rate counties were compared using student's t test and chi-squared test. Results: Spatial analysis of both primary and repeat caesarean rate identified the presence of clusters (Moran's I = 0.375; p < .001). Counties in high-rate clusters had significantly lower access to midwives, more deliveries paid by Medicaid, higher proportion of births for women belonging to racial/ethnic minority groups and were more likely to be rural.

Initial Unilateral Exposure to Deep Brain Stimulation in Treatment-Resistant Depression Patients Alters Spectral Power in the Subcallosal Cingulate.

Background: High-frequency Deep Brain Stimulation (DBS) of the subcallosal cingulate (SCC) region is an emerging strategy for treatment-resistant depression (TRD). This study examined changes in SCC local field potentials (LFPs). The LFPs were recorded from the DBS leads following transient, unilateral stimulation at the neuroimaging-defined optimal electrode contact. The goal was identifying a putative electrophysiological measure of target engagement during implantation. Methods: Fourteen consecutive patients underwent bilateral SCC DBS lead implantation. LFP recordings were collected from all electrodes during randomized testing of stimulation on each DBS contact (eight total). Analyses evaluated changes in spectral power before and after 3 min of unilateral stimulation at the contacts that later facilitated antidepressant response, as a potential biomarker of optimal contact selection in each hemisphere. Results: Lateralized and asymmetric power spectral density changes were detected in the SCC with acute unilateral SCC stimulation at those contacts subsequently selected for chronic, therapeutic stimulation. Left stimulation induced broadband ipsilateral decreases in theta, alpha, beta and gamma bands. Right stimulation effects were restricted to ipsilateral beta and gamma decreases. These asymmetric effects contrasted with identical white matter stimulation maps used in each hemisphere. More variable ipsilateral decreases were seen with stimulation at the adjacent "suboptimal" contacts, but changes were not statistically different from the "optimal" contact in either hemisphere despite obvious differences in impacted white matter bundles. Change in theta power was, however, most robust and specific with left-sided optimal stimulation, which suggested a putative functional biomarker on the left with no such specificity inferred on the right. Conclusion: Hemisphere-specific oscillatory changes can be detected from the DBS lead with acute intraoperative testing at contacts that later engender antidepressant effects. Our approach defined potential target engagement signals for further investigation, particularly left-sided theta decreases following initial exposure to stimulation. More refined models combining tractography, bilateral SCC LFP, and cortical recordings may further improve the precision and specificity of these putative biomarkers. It may also optimize and standardize the lead implantation procedure and provide input signals for next generation closed-loop therapy and/or monitoring technologies for TRD.

Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions.

BACKGROUND: The dissociative anesthetic agent ketamine is increasingly being utilized to treat depression, despite not having FDA (Food and Drug Administration) approval for this indication. There are many questions about the potential risks of this treatment and hence the proper setting and degree of monitoring required to ensure patient safety. There is limited data about the cardiovascular safety of ketamine when administered at subanesthetic doses to treat depression. METHODS: 66 patients in the Department of Psychiatry at Emory University received a total of 684 ketamine infusions between 2014 and 2016. Ketamine was dosed at 0.5 mg/kg body weight and infused over 40 min. Blood pressure was measured every 10 min during the infusions and every 15 min thereafter. RESULTS: Mean age of the patients was 56.7 years, 87.9% had unipolar depression and 36.1% had essential hypertension. No infusions were discontinued due to instability of vital signs, adverse physiological consequences or acute psychotomimetic effects. The biggest increases in blood pressure were measured at 30 min (systolic 3.28 mmHg, diastolic 3.17 mmHg). Hypertensive patients had higher blood pressure peaks during the infusions. Blood pressures returned to baseline during post-infusion monitoring. There was no development of tolerance to the blood pressure elevating effects of ketamine between the first and sixth infusions. LIMITATIONS: This is a single site, retrospective analysis, of patients who were spontaneously seeking clinical care. CONCLUSIONS: The blood pressure changes observed when ketamine is administered over 40 min at 0.5 mg/kg for the treatment of depression are small, well tolerated and clinically insignificant.

Extravasation injury of the upper extremity by intravenous phenytoin.

IMPLICATIONS: Extravasation or IV injury attributable to phenytoin can cause severe soft tissue damage. Anesthesiologists are likely to encounter this problem and should recognize it and the potential complications. With increased awareness, the occurrence may be minimized.

Forearm compartment syndrome from intravenous mannitol extravasation during general anesthesia.

IMPLICATIONS: Complications of IV mannitol administration resulting in compartment syndrome may warrant surgical intervention. Compartment syndrome is difficult to diagnose in the anesthetized patient. Infusing mannitol in an observed IV site permits discontinuation of mannitol before complications ensue. Early recognition and surgical intervention averted potential impairment in our patient.