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1.
Dev Psychol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976428

ABSTRACT

Children with a history of behaviorally inhibited (BI) temperament face a heightened risk for anxiety disorders and often use control strategies that are less planful. Although these relations have been observed concurrently in early childhood, middle childhood, and adolescence, few studies leverage longitudinal data to examine long-term prospective relations between cognitive control and anxiety. Using longitudinal data from 149 adolescents (55% female; from predominantly White middle-class families), we assessed temperament in toddlerhood and cognitive control and anxiety at 4, 12, 15, and 18 years of age. At age 4, separate measures of task switching and inhibitory control were obtained via the Dimensional Change Card Sort and Stroop tasks, respectively. At 12, 15, and 18 years of age, planful control was assessed with the AX-Continuous Performance Test, and anxiety symptoms were assessed via self-report. Growth curve models revealed that children with greater inhibitory control at age 4, regardless of BI status, experienced a sharper increase in anxiety symptoms across adolescence. Children with heightened BI during early childhood displayed lower levels of planful control at age 12, but experienced a more rapid improvement in these skills across adolescence. Children with greater task switching ability at age 4 displayed higher levels of planful control at age 12, but experienced a smaller increase in these skills across adolescence. Finally, children's growth rate for anxiety was unrelated to their growth rate for planful control. These findings reveal that early-life temperament, cognitive control, and anxiety remain interconnected across development, from toddlerhood to at least late adolescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

2.
Cureus ; 16(1): e51515, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38304642

ABSTRACT

In 2016, we implemented a non-targeted Emergency Department (ED)-based HIV screening program at our academic medical center following revised CDC guidelines utilizing the Abbott Alinity 4th generation HIV-1/2 antigen (Ag)/antibody (Ab) immunoassay (Abbott Laboratories, Abbott Park, IL). Following the CDC algorithm, after reactive fourth-generation testing, HIV-1/2 Ab testing is conducted. Patients undergoing acute seroconversion (acutes) may express p24 Ag but have a negative confirmatory Ab test. Acutes have the same laboratory signature during the ED encounter as those that are false positive (False +), and the two patient groups are denoted as "equivocals" until viral load testing specifies a definitive HIV status. Among False + patients (Ab/Ag positive, Ab negative, viral load undetectable), there have been limited studies on those also demonstrating a reduction in CD4+ count, an uncommon phenomenon known as "idiopathic CD4 lymphocytopenia." We review a patient with a reactive fourth-generation HIV Ab/p24 Ag test on two separate occasions. Despite lymphopenia with a reduced CD4 count, his symptoms resolved, and an RNA PCR test did not detect any presence of HIV (False +). This patient was unique as False + patient with p24 Ag reactive, as well as a coincidental low CD4 count in the absence of HIV infection. A low CD4 count is often a sign of significant HIV infection.

3.
J Antimicrob Chemother ; 79(4): 859-867, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38380946

ABSTRACT

BACKGROUND: In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12 years of age, at high risk for progression to severe COVID-19. OBJECTIVES: To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system. METHODS: We conducted a cohort study using electronic health records among outpatients with a positive SARS-CoV-2 PCR test between January and August 2022. We evaluated the association of nirmatrelvir/ritonavir therapy with time to hospitalization by estimating adjusted HRs and assessed the impact of nirmatrelvir/ritonavir on predicted COVID-19 hospitalizations using machine-learning methods. RESULTS: Among 44 671 patients, 4948 (11%) received nirmatrelvir/ritonavir, and 201 (0.4%) were hospitalized within 28 days of COVID-19 diagnosis. Nirmatrelvir/ritonavir recipients were more likely to be older, white, vaccinated, have comorbidities and reside in areas with higher average socioeconomic status. The 28 day cumulative incidence of hospitalization was 0.06% (95% CI: 0.02%-0.17%) among nirmatrelvir/ritonavir recipients and 0.52% (95% CI: 0.46%-0.60%) among non-recipients. For nirmatrelvir/ritonavir versus no therapy, the age-adjusted HR was 0.08 (95% CI: 0.03-0.26); the fully adjusted HR was 0.16 (95% CI: 0.05-0.50). In the machine-learning model, the primary features reducing predicted hospitalization risk were nirmatrelvir/ritonavir, younger age, vaccination, female gender and residence in a higher socioeconomic status area. CONCLUSIONS: COVID-19 hospitalization risk was reduced by 84% among nirmatrelvir/ritonavir recipients in a large, diverse healthcare system during the Omicron wave. These results suggest that nirmatrelvir/ritonavir remained highly effective in a setting substantially different than the original clinical trials.


Subject(s)
COVID-19 , Lactams , Leucine , Nitriles , Outpatients , Proline , Humans , Female , COVID-19/epidemiology , North Carolina , COVID-19 Testing , Cohort Studies , Ritonavir/therapeutic use , SARS-CoV-2 , COVID-19 Drug Treatment , Hospitalization , Antiviral Agents/therapeutic use
4.
Res Child Adolesc Psychopathol ; 52(4): 621-634, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37975959

ABSTRACT

Temperament, parenting, and executive functioning (EF) are individual and contextual factors that have been identified to play a role in the development of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Specifically, exuberant temperament in toddlerhood has been associated with both adaptive and maladaptive outcomes, including ADHD symptoms. Therefore, it is important to understand factors that predict which exuberant children experience increased ADHD symptoms and the specific mechanisms through which early exuberant temperament impacts later ADHD symptoms. Using a multi-method, prospective longitudinal design, this study examined a moderated mediation model wherein the interactive effects of observed exuberance and parenting at age 3 predicted the development of parent-reported ADHD symptoms from childhood through adolescence (age 5, 7, 9, 12, and 15) via child EF (i.e., inhibitory control) at age 4. Parent-child dyads (n = 291) from a longitudinal study on child temperament were included. A piecewise model of ADHD symptom growth demonstrated stability in ADHD symptoms from age 5-9 and a decrease from age 9-15. Results support a moderated mediation model wherein an increase in ADHD symptoms throughout childhood was predicted from early childhood exuberant temperament by way of EF, but only for children whose parents displayed less directive parenting. Findings suggest identifiable early markers of risk, including temperament, parenting, and EF- pointing to possible targets for early intervention/prevention.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Humans , Child, Preschool , Adolescent , Child , Parenting , Temperament , Longitudinal Studies , Prospective Studies
5.
J Heart Lung Transplant ; 43(3): 453-460, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37866470

ABSTRACT

BACKGROUND: Heart failure results in significant morbidity and mortality for young children with hypoplastic left heart syndrome (HLHS) following the Norwood procedure. The trajectory in later childhood is not well described. METHODS: We studied the outcome into adolescence of participants enrolled in the Single Ventricle Reconstruction trial who underwent the Fontan procedure or survived to 6 years without having undergone Fontan procedure. The primary outcome was heart failure events, defined as heart transplant listing or death attributable to heart failure. Symptomatic heart failure for participants surviving 10 or more years was also assessed utilizing the Pediatric Quality of Life Inventory (PedsQL). RESULTS: Of the 345 participants who underwent a Fontan operation or survived to 6 years without Fontan, 25 (7.2%) had a heart failure event before the age of 12 years. Among these, 21 were listed for heart transplant, and 4 died from heart failure. Nineteen participants underwent heart transplant, all of whom survived to age 12 years. Factors associated with a heart failure event included longer Norwood hospital length of stay, aortic atresia, and no Fontan operation by age 6 years. Assessment of heart failure symptoms at 12 years of age revealed that 24 (12.2%) of 196 PedsQL respondents "often" or "almost always" had difficulty walking more than one block. CONCLUSIONS: Heart failure events occur in over 5% of children with palliated HLHS between preschool age and adolescence. Outcomes for children listed for transplant are excellent. However, a substantial portion of palliated HLHS children have significant symptoms of heart failure at 12 years of age.


Subject(s)
Heart Failure , Hypoplastic Left Heart Syndrome , Norwood Procedures , Adolescent , Child , Child, Preschool , Humans , Heart Failure/surgery , Hypoplastic Left Heart Syndrome/surgery , Hypoplastic Left Heart Syndrome/diagnosis , Palliative Care/methods , Quality of Life , Clinical Trials as Topic
6.
Dev Sci ; 27(1): e13427, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37345685

ABSTRACT

Behavioral inhibition (BI) is a temperamental style characterized by cautious and fearful behaviors in novel situations. The present multi-method, longitudinal study examined whether young children's observed and parent-reported BI in social versus non-social contexts predicts different long-term psychosocial outcomes. Participants (N = 279) were drawn from a longitudinal study of socioemotional development. BI in social contexts ("social BI") was measured via children's observed wariness toward unfamiliar adults and peers at 24 and 36 months and parents' reports of children's social fear/shyness at 24, 36, and 48 months. BI in non-social contexts ("non-social BI") was measured via children's observed fearful responses to masks and novel toys, and parents' reports of children's distress to non-social novelty at 9 months and non-social fear at 48 months. At 15 years, anxiety was assessed via adolescent- and parent-reports, and global internalizing and externalizing problems were assessed via parent-reports. Confirmatory factor analysis showed that a two-factor model fit the BI data significantly better than a single-factor model, providing evidence for the dissociation of BI in social versus non-social contexts. Social BI was uniquely associated with adolescent social anxiety, whereas non-social BI was specifically associated with adolescent separation anxiety. Neither social BI nor non-social BI predicted global internalizing and externalizing problems, providing evidence for the specific relations between BI and anxiety problems. Together, these results suggest that young children's inhibited responses in social versus non-social situations predict different subtypes of anxiety problems in adolescence, highlighting the multifaceted nature of BI and the divergent trajectories of different anxiety problems.


Subject(s)
Anxiety , Temperament , Child , Adult , Adolescent , Humans , Child, Preschool , Longitudinal Studies , Temperament/physiology , Anxiety/psychology , Anxiety Disorders/psychology , Fear/psychology
7.
Hum Nat ; 34(4): 569-587, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37964105

ABSTRACT

It has been theorized that the contagion of behaviors may be related to social cognitive abilities, but empirical findings are inconsistent. We recorded young adults' behavioral expression of contagious yawning and contagious smiling to video stimuli and employed a multi-method assessment of sociocognitive abilities including self-reported internal experience of emotional contagion, self-reported trait empathy, accuracy on a theory of mind task, and observed helping behavior. Results revealed that contagious yawners reported increases in tiredness from pre- to post-video stimuli exposure, providing support for the internal experience of emotional contagion, and were more likely to provide help to the experimenter relative to non-contagious yawners. Contagious smilers showed stably high levels of self-reported happiness from pre- to post-video exposure, were more likely to provide help to the experimenter, and had increased accuracy on a theory of mind task relative to non-contagious smilers. There were no differences in self-reported trait empathy for contagious versus non-contagious yawners or smilers. Contagious yawning may be related to some basic (i.e., emotional contagion) and advanced (i.e., helping behavior) sociocognitive processes, whereas contagious smiling is related to some advanced sociocognitive processes (i.e., theory of mind and helping behavior).


Subject(s)
Smiling , Yawning , Young Adult , Humans , Emotions , Empathy , Cognition , Imitative Behavior , Social Behavior
8.
Infect Control Hosp Epidemiol ; 44(12): 2068-2070, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37385945

ABSTRACT

We examined the association between multidrug resistance and socioeconomic status (SES), analyzing microbiological and ZIP-code-level socioeconomic data. Using generalized linear models, we determined that multidrug resistance is significantly and persistently more prevalent in samples taken from patients residing in low-income ZIP codes versus high-income ZIP codes in North Carolina.


Subject(s)
Income , Socioeconomic Disparities in Health , Humans , Prevalence , Poverty , Drug Resistance, Multiple , Socioeconomic Factors
9.
Front Neurol ; 14: 1146094, 2023.
Article in English | MEDLINE | ID: mdl-37325225

ABSTRACT

Background: There is evidence that ambulatory people with incomplete spinal cord injury (iSCI) have an impaired ability to control lateral motion of their whole-body center of mass (COM) during walking. This impairment is believed to contribute to functional deficits in gait and balance, however that relationship is unclear. Thus, this cross-sectional study examines the relationship between the ability to control lateral COM motion during walking and functional measures of gait and balance in people with iSCI. Methods: We assessed the ability to control lateral COM motion during walking and conducted clinical gait and balance outcome measures on 20 ambulatory adults with chronic iSCI (C1-T10 injury, American Spinal Injury Association Impairment Scale C or D). To assess their ability to control lateral COM motion, participants performed three treadmill walking trials. During each trial, real-time lateral COM position and a target lane were projected on the treadmill. Participants were instructed to keep their lateral COM position within the lane. If successful, an automated control algorithm progressively reduced the lane width, making the task more challenging. If unsuccessful, the lane width increased. The adaptive lane width was designed to challenge each participant's maximum capacity to control lateral COM motion during walking. To quantify control of lateral COM motion, we calculated lateral COM excursion during each gait cycle and then identified the minimum lateral COM excursion occurring during five consecutive gait cycles. Our clinical outcome measures were Berg Balance Scale (BBS), Timed Up and Go test (TUG), 10-Meter Walk Test (10MWT) and Functional Gait Assessment (FGA). We used a Spearman correlation analysis (ρ) to examine the relationship between minimum lateral COM excursion and clinical measures. Results: Minimum lateral COM excursion had significant moderate correlations with BBS (ρ = -0.54, p = 0.014), TUG (ρ = 0.59, p = 0.007), FGA (ρ = -0.59, p = 0.007), 10MWT-preferred (ρ = -0.59, p = 0.006) and 10MWT-fast (ρ = -0.68, p = 0.001). Conclusion: Control of lateral COM motion during walking is associated with a wide range of clinical gait and balance measures in people with iSCI. This finding suggests the ability to control lateral COM motion during walking could be a contributing factor to gait and balance in people with iSCI.

10.
Soc Dev ; 32(2): 618-632, 2023 May.
Article in English | MEDLINE | ID: mdl-37234510

ABSTRACT

Extant research has produced conflicting findings regarding the link between social fearfulness and prosocial behavior, with some studies reporting negative relations and others reporting null effects. Furthermore, these studies have focused predominantly on toddlerhood, and few have examined prosociality between peers. The present study investigated whether the link between social anxiety and a prosocial behavior (i.e., providing encouragement) varied depending on interpersonal and situational factors (i.e., one's familiarity with a peer, the level of support sought by a peer, respectively). We tested this question using a multimethod approach, which included an ecologically valid stress inducing task and dyadic design with a sample of 9- to 10-year-olds (N = 447). Results revealed that social anxiety was related negatively to providing encouragement among familiar and unfamiliar dyads. In familiar dyads, however, this main effect was qualified by an interaction with the level of support sought by one's peer. Compared to those low in social anxiety, children high in social anxiety provided relatively less encouragement in response to higher levels of support seeking from their peers. The findings are considered in relation to theorizing regarding the effect of overarousal on children's prosocial behavior.

11.
Dev Psychobiol ; 65(4): e22388, 2023 05.
Article in English | MEDLINE | ID: mdl-37073588

ABSTRACT

Previous work has shown that children's shyness is related to personal anxiety during social stress, but we know little about how shyness is related to anxiety during a peer's social stress. Children (Mage  = 10.22 years, SD = 0.81, N = 62) were paired with an unfamiliar peer and engaged in a speech task while electrocardiography was recorded. We modeled changes in children's heart rate, a physiological correlate of anxiety, while they observed their peer prepare and deliver a speech. Results revealed that the observing child's shyness related to increases in their heart rate during their peer's preparation period, but modulation of this arousal was sensitive to the presenting peer's anxious behavior while delivering their speech. Specifically, if the presenting child displayed high levels of anxious behavior, the observing child's shyness was related to further increases in heart rate, but if the presenting child displayed low levels of anxious behavior, the observing child's shyness was related to decreases in heart rate from the preparation period. Shy children may experience physiological arousal to a peer's social stress but can regulate this arousal based on social cues from the peer, which may be due to heightened social threat detection and/or empathic anxiety.


Subject(s)
Anxiety , Shyness , Humans , Child , Empathy , Heart Rate/physiology , Arousal
12.
PLoS One ; 18(2): e0280163, 2023.
Article in English | MEDLINE | ID: mdl-36749770

ABSTRACT

Congenital heart defects are the most common type of birth defects in humans and frequently involve heart valve dysfunction. The current treatment for unrepairable heart valves involves valve replacement with an implant, Ross pulmonary autotransplantation, or conventional orthotopic heart transplantation. Although these treatments are appropriate for older children and adults, they do not result in the same efficacy and durability in infants and young children for several reasons. Heart valve implants do not grow with the. Ross pulmonary autotransplants have a high mortality rate in neonates and are not feasible if the pulmonary valve is dysfunctional or absent. Furthermore, orthotopic heart transplants invariably fail from ventricular dysfunction over time. Therefore, the treatment of irreparable heart valves in infants and young children remains an unsolved problem. The objective of this single-arm, prospective study is to offer an alternative solution based on a new type of transplant, which we call "partial heart transplantation." Partial heart transplantation differs from conventional orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. Similar to Ross pulmonary autotransplants and conventional orthotopic heart transplants, partial heart transplants contain live cells that should allow it to grow with the recipient child. Therefore, partial heart transplants will require immunosuppression. The risks from immunosuppression can be managed, as seen in conventional orthotopic heart transplant recipients. Stopping immunosuppression will simply turn the growing partial heart transplant into a non-growing homovital homograft. Once this homograft deteriorates, it can be replaced with a durable adult-sized mechanical implant. The protocol for our single-arm trial is described. The ClinicalTrials.gov trial registration number is NCT05372757.


Subject(s)
Heart Transplantation , Heart Valve Prosthesis Implantation , Pulmonary Valve , Adolescent , Adult , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Aortic Valve/surgery , Heart Valves/surgery , Prospective Studies , Pulmonary Valve/transplantation , Transplantation, Homologous , Treatment Outcome
13.
Res Child Adolesc Psychopathol ; 51(6): 805-817, 2023 06.
Article in English | MEDLINE | ID: mdl-36708411

ABSTRACT

Social connections are critical for mental and physical health; however, the developmental pathways to children's social connectedness outcomes are not well understood. This study examined the pathways from children's inhibitory control at 4 years to two social connectedness outcomes - loneliness and friendship quality at age 10 - through behavioral problems at age 7. As part of a longitudinal study (N = 291, 54% girls), children's inhibitory control was assessed via a Go/No-Go task when children were 4 years old. Mothers reported on children's behavioral problems at ages 4 and 7 years. Children reported on their friendship quality and loneliness at ages 7 and 10 years. Greater inhibitory control at 4 years predicted lower behavioral problems at 7 years, which in turn predicted better friendship quality and lower loneliness at 10 years. Indirect effects from inhibitory control at 4 years to loneliness and friendship quality at 10 years via behavioral problems at 7 years were significant. Findings suggest that inhibitory control in early childhood may play a key role for the development of social connectedness in middle childhood via its impact on children's behavioral problems.


Subject(s)
Interpersonal Relations , Loneliness , Female , Humans , Child , Child, Preschool , Male , Longitudinal Studies , Mothers , Friends
14.
Emotion ; 23(4): 949-960, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36048036

ABSTRACT

The way children express and respond to emotions when they first meet is crucial to friendship initiation. But for highly shy children, these exchanges are particularly challenging. Existing research is based on individual and total frequency measures of emotion that do not reflect the transactional and dynamic nature of emotions in real-life peer interactions. We examined how shyness and dyadic similarity in shyness influence children's moment-to-moment dyadic emotion sequences with a new peer. Thirty age- and gender-matched dyads (Mage = 10.13 years, 75.8% White) were observed during an unstructured "getting to know you" task. Children's shyness was assessed through parent- and child-report. Using grid-sequence analysis (Brinberg et al., 2017) we identified three dyadic emotion clusters: Flexible and Shared Positive Affect (60%), Flexible and Shared Neutral Affect (35%), and Stable and Shared Negative Affect (17%). Children in the Stable and Shared Negative Affect cluster were rated higher in shyness relative to children in the Flexible and Shared Positive Affect cluster. Further, children more similar in shyness to their dyadic partner displayed more stable negative and neutral affect expressions than children who differed in shyness from their partner. Together, these findings suggest that shyness is related to less positive and less flexible emotion expressions when meeting a new peer, holding critical implications for friendship initiation among children varying in shyness. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Emotions , Shyness , Humans , Child , Peer Group , Friends , Child Behavior/psychology
15.
J Child Psychol Psychiatry ; 64(4): 537-561, 2023 04.
Article in English | MEDLINE | ID: mdl-36123776

ABSTRACT

Behavioral Inhibition is a temperament identified in the first years of life that enhances the risk for development of anxiety during late childhood and adolescence. Amongst children characterized with this temperament, only around 40 percent go on to develop anxiety disorders, meaning that more than half of these children do not. Over the past 20 years, research has documented within-child and socio-contextual factors that support differing developmental pathways. This review provides a historical perspective on the research documenting the origins of this temperament, its biological correlates, and the factors that enhance or mitigate risk for development of anxiety. We review as well, research findings from two longitudinal cohorts that have identified moderators of behavioral inhibition in understanding pathways to anxiety. Research on these moderators has led us to develop the Detection and Dual Control (DDC) framework to understand differing developmental trajectories among behaviorally inhibited children. In this review, we use this framework to explain why and how specific cognitive and socio-contextual factors influence differential pathways to anxiety versus resilience.


Subject(s)
Anxiety Disorders , Anxiety , Child , Adolescent , Humans , Anxiety/psychology , Anxiety Disorders/psychology , Temperament/physiology , Inhibition, Psychological
16.
Pediatr Transplant ; 26(8): e14392, 2022 12.
Article in English | MEDLINE | ID: mdl-36377326

ABSTRACT

This manuscript outlines a clinical approach to vasoplegia incorporating the current state of knowledge regarding vasoplegia in pediatric patients immediately post-transplant and to identify modifiable factors both pre- and post-transplant that may reduce post-operative morbidity, end-organ dysfunction, and mortality. Centers participating in the Pediatric Heart Transplant Society (PHTS) were asked to provide their internal protocols and rationale for vasoplegia management, and applicable adult and pediatric data were reviewed. The authors synthesized the above protocols and literature into the following description of clinical approaches to vasoplegia highlighting areas of both broad consensus and of significant practice variation.


Subject(s)
Heart Transplantation , Vasoplegia , Humans , Child , Adult , Vasoplegia/etiology , Retrospective Studies , Risk Factors
17.
Pediatr Transplant ; 26(8): e14398, 2022 12.
Article in English | MEDLINE | ID: mdl-36377325

ABSTRACT

OBJECTIVE: This document is designed to outline the definition, pathogenesis, diagnostic modalities and therapeutic measures to treat antibody-mediated rejection in children postheart transplant METHODS: Literature review was conducted by a Pediatric Heart Transplant Society (PHTS) working group to identify existing pediatric and adult studies on antibody-mediated rejection (AMR). In addition, the centers participating in PHTS were asked to submit their approach to diagnosis and management of pediatric AMR. This document synthesizes information gathered from both these sources to highlight a practical approach to diagnosing and managing a child with AMR postheart transplant. This document may not represent the practice at all centers in the PHTS and serves as a starting point to understand an approach to this clinical scenario.


Subject(s)
Heart Transplantation , Transplants , Humans , Child , Adult , Graft Rejection/diagnosis , Graft Rejection/pathology , Antibodies
18.
Open Forum Infect Dis ; 9(10): ofac487, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36225740

ABSTRACT

Background: Medically vulnerable individuals are at increased risk of acquiring multidrug-resistant Enterobacterales (MDR-E) infections. People with HIV (PWH) experience a greater burden of comorbidities and may be more susceptible to MDR-E due to HIV-specific factors. Methods: We performed an observational study of PWH participating in an HIV clinical cohort and engaged in care at a tertiary care center in the Southeastern United States from 2000 to 2018. We evaluated demographic and clinical predictors of MDR-E by estimating prevalence ratios (PRs) and employing machine learning classification algorithms. In addition, we created a predictive model to estimate risk of MDR-E among PWH using a machine learning approach. Results: Among 4734 study participants, MDR-E was isolated from 1.6% (95% CI, 1.2%-2.1%). In unadjusted analyses, MDR-E was strongly associated with nadir CD4 cell count ≤200 cells/mm3 (PR, 4.0; 95% CI, 2.3-7.4), history of an AIDS-defining clinical condition (PR, 3.7; 95% CI, 2.3-6.2), and hospital admission in the prior 12 months (PR, 5.0; 95% CI, 3.2-7.9). With all variables included in machine learning algorithms, the most important clinical predictors of MDR-E were hospitalization, history of renal disease, history of an AIDS-defining clinical condition, CD4 cell count nadir ≤200 cells/mm3, and current CD4 cell count 201-500 cells/mm3. Female gender was the most important demographic predictor. Conclusions: PWH are at risk for MDR-E infection due to HIV-specific factors, in addition to established risk factors. Early HIV diagnosis, linkage to care, and antiretroviral therapy to prevent immunosuppression, comorbidities, and coinfections protect against antimicrobial-resistant bacterial infections.

19.
mBio ; 13(5): e0175122, 2022 10 26.
Article in English | MEDLINE | ID: mdl-36135380

ABSTRACT

COVID-19 convalescent plasma (CCP) was an early and widely adopted putative therapy for severe COVID-19. Results from randomized control trials and observational studies have failed to demonstrate a clear therapeutic role for CCP for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Underlying these inconclusive findings is a broad heterogeneity in the concentrations of neutralizing antibodies (nAbs) between different CCP donors. We conducted this study to evaluate the effectiveness and safety of nAb titer-defined CCP in adults admitted to an academic referral hospital. Patients positive by a SARS-CoV-2 nucleic acid amplification test and with symptoms for <10 days were eligible. Participants received either CCP with nAb titers of >1:640 (high-titer group) or ≥1:160 to 1:640 (standard-titer group) in addition to standard of care treatments. The primary clinical outcome was time to hospital discharge, with mortality and respiratory support evaluated as secondary outcomes. Adverse events were contrasted by CCP titer. Between 28 August and 4 December 2020, 316 participants were screened, and 55 received CCP, with 14 and 41 receiving high- versus standard-titer CCP, respectively. Time to hospital discharge was shorter among participants receiving high- versus standard-titer CCP, accounting for death as a competing event (hazard ratio, 1.94; 95% confidence interval [CI], 1.05 to 3.58; Gray's P = 0.02). Severe adverse events (SAEs) (≥grade 3) occurred in 4 (29%) and 23 (56%) of participants receiving the high versus standard titer, respectively, by day 28 (risk ratio, 0.51; 95% CI, 0.21 to 1.22; Fisher's P = 0.12). There were no observed treatment-related AEs. (This study has been registered at ClinicalTrials.gov under registration no. NCT04524507). IMPORTANCE In this study, in a high-risk population of patients admitted for COVID-19, we found an earlier time to hospital discharge among participants receiving CCP with nAb titers of >1:640 compared with participants receiving CCP with a lower nAb titer and no CCP-related AEs. The significance of our research is in identifying a dose response of CCP and clinical outcomes based on nAb titer. Although limited by a small study size, these findings support further study of high-nAb-titer CCP defined as >1:640 in the treatment of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Immunization, Passive/methods
20.
JAC Antimicrob Resist ; 4(4): dlac082, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35935279

ABSTRACT

Background: People with HIV (PWH) may be at increased risk for MDR Enterobacterales (MDR-E) infection or colonization, relative to individuals without HIV, due to a greater burden of comorbidities as well as HIV-related intestinal inflammation and microbiota alterations. Objectives: To characterize antibiotic susceptibility of enteric Enterobacterales and risk factors for antimicrobial-resistant bacterial infections in a sample of PWH attending routine clinic visits. Methods: Participants provided self-administered rectal swabs and completed questionnaires regarding healthcare, travel and occupational exposures for the prior 12 months. Rectal samples were processed to identify Enterobacterales species, and susceptibility testing was performed. Results: Among 82 participants, 110 Enterobacterales isolates were obtained. Non-susceptibility was common for penicillins, sulphonamides and first-generation cephalosporins. MDR-E was present in 20% of participants. HIV-related characteristics, including current or nadir CD4 cell count, viral suppression, or AIDS-defining clinical conditions, were not associated with MDR-E. Conclusions: MDR-E colonization is common in this population of PWH. Further research evaluating risk factors for MDR-E in PWH may inform infection prevention approaches to better protect at-risk populations from these difficult-to-treat infections.

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