Nevin Manimala

Turk J Anaesthesiol Reanim. 2022 Apr;50(2):135-141. doi: 10.5152/TJAR.2021.1356.

ABSTRACT

OBJECTIVE: Arterial pulse-derived cardiac output monitors are routinely employed to guide hemodynamic management during liver transplant surgery. In this study, we sought to assess the reliability by evaluating the agreement of the cardiac output measured by the FloTrac Vigileo versus pulmonary artery catheter (continuous cardiac output) at specified times during liver transplant.

METHODS: Liver transplant database with cardiac output values measured by FloTrac Vigileo and continuous cardiac output was analyzed retrospectively at a tertiary care hospital. Data were compared at T0: baseline, T1: 1 hour in dissection phase, T2: anhepatic phase, T3: portosystemic shunt, T4: reperfusion, T5: 1 hour after reperfusion, and T6: skin closure. Statistical analysis was done using Bland-Altman analysis and percentage error (<30%) to assess the agreement between cardiac output measured by 2 techniques, Lin’s concordance correlation coefficient for quantifying the agreement and 4-quadrant plots to compare the trends of cardiac output.

RESULTS: Bland-Altman analysis showed mean cardiac output ± standard deviation L min-1 (95% CI) at T0: 0.2 ± 2.09 (-3.9 to 4.3), T1: 0.53 ± 3.0 (-5.4 to 6.4), T2: 0.47 ± 2.1(-3.7 to 4.6), T3: 0.31 ± 1.9 (-3.4 to 4.0), T4: 0.44 ± 2.15 (-3.8 to 4.7), T 5:0.69 ± 1.9. (-2.9 to 4.3), and at T6: 0.43 ± 2.25 (-4.0 to 4.8). Percentage error was 44%-72% and concordance correlation coefficient was poor (<0.65) at all points.

CONCLUSIONS: There is poor agreement between the cardiac output measured by FloTrac and pulmonary artery catheter among liver transplant recipients. The need for superior hemodynamic monitoring is mandated in liver transplant.

PMID:35544253 | DOI:10.5152/TJAR.2021.1356

J Nutr. 2022 May 11:nxac076. doi: 10.1093/jn/nxac076. Online ahead of print.

ABSTRACT

BACKGROUND: Structural racism and economic marginalization shape dietary patterns in complex ways. Most research examining race and income inequities discount their interactions in shaping dietary intakes. An intersectional approach is needed to identify interconnected sources of social inequities and to more precisely locate dietary inequities.

OBJECTIVES: We examined whether racial identity and perceived income adequacy independently and jointly shape dietary quality, defined using the Healthy Eating Index (HEI) 2015, among a large sample of adults in Canada.

METHODS: Cross-sectional data from 2540 adults (≥18 years of age) in Canada who participated in the 2019 International Food Policy Study were analyzed. Multivariable linear regression models were executed to test the independent associations and interactions between racial identity and perceived income adequacy with HEI-2015 scores. Models were constructed to examine HEI-2015 total and component scores, adjusting for age, gender, and education.

RESULTS: Perceived income adequacy, but not racial identity, was independently associated with HEI-2015 total scores. The interaction between racial identity and perceived income adequacy was significantly associated with HEI-2015 scores. Compared to the reference group (individuals identifying as White and reporting income adequacy), those identifying as Black and reporting income adequacy were associated with lower HEI-2015 scores (β, -7.30; 95% CI, -13.07 to -1.54) and those identifying as Black and reporting income inadequacy were associated with lower HEI-2015 scores (β, -6.37; 95% CI, -12.13 to -0.60). Individuals who identified as indigenous and reported neither income adequacy nor inadequacy had lower HEI-2015 scores (β, -8.50; 95% CI, -13.82 to -3.18) compared to the reference group.

CONCLUSIONS: Findings suggest that racial identity and perceived income adequacy jointly shape dietary quality. Inequities in dietary quality may be missed when intersecting racial identities and socioeconomic positions are not explicitly investigated. To support healthier dietary patterns, strategies must reduce socioeconomic barriers that impose dietary constraints on some racialized groups.

PMID:35544238 | DOI:10.1093/jn/nxac076

CBE Life Sci Educ. 2022 Jun;21(2):ar25. doi: 10.1187/cbe.21-09-0237.

ABSTRACT

Community colleges have an opportunity to promote achievement of more science, technology, engineering, and mathematics (STEM) students and meet larger goals of scientific advancement and educational equity. Understanding community college students’ needs and backgrounds is key to increasing students’ success in STEM fields and realizing this potential. The objective of this paper is to use data from the U.S. Department of Education’s National Center for Education Statistics and other sources to characterize community college students and their academic achievement and to offer equity-based approaches to increase success, particularly in STEM. Here, I document that community college students, who constitute approximately one-third of U.S. undergraduates, are a unique population with greater proportions of underrepresented STEM minorities, parents, and students requiring developmental education. They are also more likely to be older, working, part-time, low-income, and first-generation students and more likely to differ demographically from faculty. I also found lower rates of academic achievement among community college students, including lower rates of retention and STEM degree attainment with evidence of even lower achievement for STEM underrepresented groups. The data point to the need for equity-based strategies to address achievement disparities for STEM community college students, including increasing community college faculty diversity and sensitivity to diverse students’ needs and experiences; adopting inclusive, active-learning pedagogies; and reforming developmental education.

PMID:35544203 | DOI:10.1187/cbe.21-09-0237

JAMA Psychiatry. 2022 May 11. doi: 10.1001/jamapsychiatry.2022.1017. Online ahead of print.

ABSTRACT

IMPORTANCE: Psychiatric and cognitive phenotypes have been associated with a range of specific, rare copy number variants (CNVs). Moreover, IQ is strongly associated with CNV risk scores that model the predicted risk of CNVs across the genome. But the utility of CNV risk scores for psychiatric phenotypes has been sparsely examined.

OBJECTIVE: To determine how CNV risk scores, common genetic variation indexed by polygenic scores (PGSs), and environmental factors combine to associate with cognition and psychopathology in a community sample.

DESIGN, SETTING, AND PARTICIPANTS: The Philadelphia Neurodevelopmental Cohort is a community-based study examining genetics, psychopathology, neurocognition, and neuroimaging. Participants were recruited through the Children’s Hospital of Philadelphia pediatric network. Participants with stable health and fluency in English underwent genotypic and phenotypic characterization from November 5, 2009, through December 30, 2011. Data were analyzed from January 1 through July 30, 2021.

EXPOSURES: The study examined (1) CNV risk scores derived from models of burden, predicted intolerance, and gene dosage sensitivity; (2) PGSs from genomewide association studies related to developmental outcomes; and (3) environmental factors, including trauma exposure and neighborhood socioeconomic status.

MAIN OUTCOMES AND MEASURES: The study examined (1) neurocognition, with the Penn Computerized Neurocognitive Battery; (2) psychopathology, with structured interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children; and (3) brain volume, with magnetic resonance imaging.

RESULTS: Participants included 9498 youths aged 8 to 21 years; 4906 (51.7%) were female, and the mean (SD) age was 14.2 (3.7) years. After quality control, 18 185 total CNVs greater than 50 kilobases (10 517 deletions and 7668 duplications) were identified in 7101 unrelated participants genotyped on Illumina arrays. In these participants, elevated CNV risk scores were associated with lower overall accuracy on cognitive tests (standardized β = 0.12; 95% CI, 0.10-0.14; P = 7.41 × 10-26); lower accuracy across a range of cognitive subdomains; increased overall psychopathology; increased psychosis-spectrum symptoms; and higher deviation from a normative developmental model of brain volume. Statistical models of developmental outcomes were significantly improved when CNV risk scores were combined with PGSs and environmental factors.

CONCLUSIONS AND RELEVANCE: In this study, elevated CNV risk scores were associated with lower cognitive ability, higher psychopathology including psychosis-spectrum symptoms, and greater deviations from normative magnetic resonance imaging models of brain development. Together, these results represent a step toward synthesizing rare genetic, common genetic, and environmental factors to understand clinically relevant outcomes in youth.

PMID:35544191 | DOI:10.1001/jamapsychiatry.2022.1017

Lancet Microbe. 2021 Apr;2(4):e141-e150. doi: 10.1016/S2666-5247(21)00009-4. Epub 2021 Mar 2.

ABSTRACT

BACKGROUND: The epidemiology and severity of non-falciparum malaria in endemic settings has garnered little attention. We aimed to characterise the prevalence, interaction, clinical risk factors, and temporal trends of non-falciparum Plasmodium species among symptomatic individuals presenting at health-care facilities in endemic settings of Kenya.

METHODS: We diagnosed and analysed infecting malaria species (Plasmodium falciparum, Plasmodium ovale curtisi, Plasmodium ovale wallikeri, and Plasmodium malariae) via PCR in clinical samples collected between March 1, 2008, and Dec 31, 2016, from six hospitals located in different regions of Kenya. We recruited patients aged 6 months or older who presented at outpatient departments with symptoms of malaria or tested positive for uncomplicated malaria by malaria rapid diagnostic test. Descriptive statistics were used to describe the prevalence and distribution of Plasmodium species. A statistical model was designed and used for estimating the frequency of Plasmodium species and assessing interspecies interactions. Mixed-effect linear regression models with random slopes for each location were used to test for change in prevalence over time.

FINDINGS: Samples from 2027 symptomatic participants presenting at care facilities were successfully analysed for all Plasmodium species. 1469 (72·5%) of the samples were P falciparum single-species infections, 523 (25·8%) were mixed infections, and only 35 (1·7%) were single non-falciparum species infections. 452 (22·3%) were mixed infections containing P ovale spp. A likelihood-based model calculation of the population frequency of each species estimated a significant within-host interference between P falciparum and P ovale curtisi. Mixed-effect logistic regression models identified a significant increase in P ovale wallikeri (2·1% per year; p=0·043) and P ovale curtisi (0·7% per year; p=0·0002) species over time, with a reciprocal decrease in P falciparum single-species infections (2·5% per year; p=0·0065). The frequency of P malariae infections did not significantly change over time. Risk of P falciparum infections presenting with fever was lower if co-infected with P malariae (adjusted odds ratio 0·43, 95% CI 0·25-0·74; p=0·0023).

INTERPRETATION: Our results show a prevalence of non-falciparum species infections of 27·5% among symptomatic individuals presenting at care facilities, which is higher than expected from previous cross-sectional surveys. The proportion of infections with P ovale wallikeri and P ovale curtisi was observed to significantly increase over the period of study, which could be due to attenuated responsiveness of these species to malaria drug treatment. The increase in frequency of P ovale spp could threaten the malaria control efforts in Kenya and pose increased risk of malaria to travellers.

FUNDING: Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance Section.

PMID:35544189 | DOI:10.1016/S2666-5247(21)00009-4

JAMA Netw Open. 2022 May 2;5(5):e2211620. doi: 10.1001/jamanetworkopen.2022.11620.

NO ABSTRACT

PMID:35544143 | DOI:10.1001/jamanetworkopen.2022.11620

JAMA Netw Open. 2022 May 2;5(5):e2211634. doi: 10.1001/jamanetworkopen.2022.11634.

ABSTRACT

IMPORTANCE: Stimulant medication use is common among individuals receiving buprenorphine for opioid use disorder (OUD). Associations between prescription stimulant use and treatment outcomes in this population have been understudied.

OBJECTIVES: To investigate whether use of prescription stimulants was associated with (1) drug-related poisoning and (2) buprenorphine treatment retention.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, recurrent-event cohort study with a case-crossover design used a secondary analysis of administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Primary analyses were conducted from March 1 through August 31, 2021. Individuals aged 12 to 64 years with an OUD diagnosis and prescribed buprenorphine who experienced at least 1 drug-related poisoning were included in the analysis. Unit of observation was the person-day.

EXPOSURES: Days of active stimulant prescriptions.

MAIN OUTCOMES AND MEASURES: Primary outcomes were drug-related poisoning and buprenorphine treatment retention. Drug-related poisonings were defined using International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes; treatment retention was defined by continuous treatment claims until a 45-day gap was observed.

RESULTS: There were 13 778 567 person-days of observation time among 22 946 individuals (mean [SD] age, 32.8 [11.8] years; 50.3% men) who experienced a drug-related poisoning. Stimulant treatment days were associated with 19% increased odds of drug-related poisoning (odds ratio [OR], 1.19 [95% CI, 1.06-1.34]) compared with nontreatment days; buprenorphine treatment days were associated with 38% decreased odds of poisoning (OR, 0.62 [95% CI, 0.59-0.65]). There were no significant interaction effects between use of stimulants and buprenorphine. Stimulant treatment days were associated with decreased odds of attrition from buprenorphine treatment (OR, 0.64 [95% CI, 0.59-0.70]), indicating that stimulants were associated with 36% longer mean exposure to buprenorphine and its concomitant protection.

CONCLUSIONS AND RELEVANCE: Among persons with OUD, use of prescription stimulants was associated with a modest increase in per-day risk of drug-related poisoning, but this risk was offset by the association between stimulant use and improved retention to buprenorphine treatment, which is associated with protection against overdose.

PMID:35544135 | DOI:10.1001/jamanetworkopen.2022.11634

Lancet Microbe. 2022 May;3(5):e336-e347. doi: 10.1016/S2666-5247(21)00356-6. Epub 2022 Mar 23.

ABSTRACT

BACKGROUND: Tafenoquine was recently approved as a prophylaxis and radical cure for Plasmodium vivax infection, but its Plasmodium falciparum transmission-blocking efficacy is unclear. We aimed to establish the efficacy and safety of three single low doses of tafenoquine in combination with dihydroartemisinin-piperaquine for reducing gametocyte density and transmission to mosquitoes.

METHODS: In this four-arm, single-blind, phase 2, randomised controlled trial, participants were recruited at the Clinical Research Unit of the Malaria Research and Training Centre of the University of Bamako in Mali. Eligible participants were aged 12-50 years, with asymptomatic P falciparum microscopy-detected gametocyte carriage, had a bodyweight of 80 kg or less, and had no clinical signs of malaria defined by fever. Participants were randomly assigned (1:1:1:1) to standard treatment with dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus a single dose of tafenoquine (in solution) at a final dosage of 0·42 mg/kg, 0·83 mg/kg, or 1·66 mg/kg. Randomisation was done with a computer-generated randomisation list and concealed with sealed, opaque envelopes. Dihydroartemisinin-piperaquine was administered as oral tablets over 3 days (day 0, 1, and 2), as per manufacturer instructions. A single dose of tafenoquine was administered as oral solution on day 0 in parallel with the first dose of dihydroartemisinin-piperaquine. Tafenoquine dosing was based on bodyweight to standardise efficacy and risk variance. The primary endpoint, assessed in the per-protocol population, was median percentage change in mosquito infection rate 7 days after treatment compared with baseline. Safety endpoints included frequency and incidence of adverse events. The final follow-up visit was on Dec 23, 2021; the trial is registered with ClinicalTrials.gov, NCT04609098.

FINDINGS: From Oct 29 to Nov 25, 2020, 1091 individuals were screened for eligibility, 80 of whom were enrolled and randomly assigned (20 per treatment group). Before treatment, 53 (66%) individuals were infectious to mosquitoes, infecting median 12·50% of mosquitoes (IQR 3·64-35·00). Within-group reduction in mosquito infection rate on day 7 was 79·95% (IQR 57·15-100; p=0·0005 for difference from baseline) following dihydroartemisinin-piperaquine only, 100% (98·36-100; p=0·0005) following dihydroartemisinin-piperaquine plus tafenoquine 0·42 mg/kg, 100% (100-100; p=0·0001) following dihydroartemisinin-piperaquine plus tafenoquine 0·83 mg/kg, and 100% (100-100; p=0·0001) following dihydroartemisinin-piperaquine plus tafenoquine 1·66 mg/kg. 55 (69%) of 80 participants had a total of 94 adverse events over the course of the trial; 86 (92%) adverse events were categorised as mild, seven (7%) as moderate, and one (1%) as severe. The most common treatment-related adverse event was mild or moderate headache, which occurred in 15 (19%) participants (dihydroartemisinin-piperaquine n=2; dihydroartemisinin-piperaquine plus tafenoquine 0·42 mg/kg n=6; dihydroartemisinin-piperaquine plus tafenoquine 0·83 mg/kg n=3; and dihydroartemisinin-piperaquine plus tafenoquine 1·66 mg/kg n=4). No serious adverse events occurred. No significant differences in the incidence of all adverse events (p=0·73) or treatment-related adverse events (p=0·62) were observed between treatment groups.

INTERPRETATION: Tafenoquine was well tolerated at all doses and accelerated P falciparum gametocyte clearance. All tafenoquine doses showed improved transmission reduction at day 7 compared with dihydroartemisinin-piperaquine alone. These data support the case for further research on tafenoquine as a transmission-blocking supplement to standard antimalarials.

FUNDING: Bill & Melinda Gates Foundation.

TRANSLATIONS: For the French, Portuguese, Spanish and Swahili translations of the abstract see Supplementary Materials section.

PMID:35544095 | DOI:10.1016/S2666-5247(21)00356-6

Nephrol Dial Transplant. 2022 May 11:gfac174. doi: 10.1093/ndt/gfac174. Online ahead of print.

ABSTRACT

BACKGROUND: In the general population, the seroconversion rate after primary vaccination with two doses of an anti-SARS-CoV-2 mRNA vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here, we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients.

METHODS: A systematic literature research was performed in Pubmed, Web of Science, and the Cochrane library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated.

RESULTS: Eight studies that described the development of antibodies against receptor-binding domain (RBD) and/or spike protein were eligible for meta-analysis. Two of these studies also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 (44.3%; 95% confidence interval (CI): [34.1%-54.7%]) as compared to such patients vaccinated with two doses of mRNA-1273 (58.4%; 95% CI: [47.2%-69.2%]). The relative seroconversion rate amounted 0.795 (95% CI: [0.732-0.864]).

CONCLUSIONS: This systematic review and meta-analysis indicates that, in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared to BNT162b2.

PMID:35544087 | DOI:10.1093/ndt/gfac174

Lancet Microbe. 2022 Apr;3(4):e294-e302. doi: 10.1016/S2666-5247(21)00327-X. Epub 2022 Mar 11.

ABSTRACT

BACKGROUND: Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients.

METHODS: We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection.

FINDINGS: Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24-0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19-0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37-14·21, p<0·0001) or dominance (3·97, 1·20-13·08, p=0·024) of Staphylococcus aureus was linked with lower survival. Moreover, dominance of Enterobacteriaceae was associated with higher risk of death (2·26, 1·03-4·93, p=0·041).

INTERPRETATION: Pleural infection is a predominantly polymicrobial infection, explaining the requirement for broad spectrum antibiotic cover in most individuals. High mortality infection associated with S aureus and Enterobacteriaceae favours more aggressive, with a narrower spectrum, antibiotic strategies.

FUNDING: UK Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, Wellcome Trust, Oxfordshire Health Services Research Committee, Chinese Academy of Medical Sciences, and John Fell Fund.

PMID:35544066 | DOI:10.1016/S2666-5247(21)00327-X