bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse perinatal outcomes associated with antiretroviral therapy regimens: systematic review and network meta-analysis
Authors: Tshivuila-Matala Chrystelle O.O. , Honeyman Susan , Nesbitt Charlotte , Kirtley Shona , Kennedy Stephen H. , Hemelaar Joris 
Published: July 2020

Objective:
Assess adverse perinatal outcomes associated with antenatal antiretroviral therapy (ART) regimens.

Design:
Systematic review and network meta-analysis of randomized controlled trials (RCTS).

Methods:
We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, EMBASE, and the Cochrane Central Register of Controlled Trials and four clinical trial databases from 1 January 1980 to 28 April 2018. We included RCTs of antenatal ART regimens in HIV-positive pregnant women, which assessed preterm birth (PTB), spontaneous preterm birth (sPTB), very preterm birth (VPTB), low birthweight (LBW), very low birthweight (VLBW), small-for-gestational-age (SGA), neonatal death (NND), and mother-to-child-transmission. We used random-effects network meta-analysis models to calculate relative risks for treatment comparisons and the hierarchy of treatments.

Results:
Of 83 260 citations identified, 10 manuscripts were included, assessing 6285 women. Compared with zidovudine (ZDV) monotherapy, we found a higher risk of LBW after exposure to zidovudine/lamivudine/efavirenz (ZDV/3TC/EFV; relative risk 1.61; 95% CI 1.03–2.51), tenofovir disoproxil fumarate/emtricitabine/ritonavir-boosted lopinavir (TDF/FTC/LPV/r; 1.64; 1.18–2.29), or zidovudine/lamivudine/ritonavir-boosted lopinavir (ZDV/3TC/LPV/r; 1.87; 1.58–2.20). TDF/FTC/LPV/r carried an increased risk of VLBW, compared with ZDV monotherapy (5.40; 1.08–27.08). ZDV/3TC/LPV/r posed a higher risk of PTB than ZDV monotherapy (1.43; 1.08–1.91) and a higher risk of sPTB than zidovudine/lamivudine/abacavir (ZDV/3TC/ABC) (1.81; 1.21–2.71). LPV/r-containing regimens also carried the highest risks of VPTB, SGA and NND, although the limited data showed no significant differences.

Conclusion:
Of the ART regimens assessed in RCTs in pregnancy, LPV/r-containing regimens were associated with the highest risks of adverse perinatal outcomes.
Internalized HIV stigma predicts subsequent viremia in US HIV patients through depressive symptoms and antiretroviral therapy adherence
Authors: Christopoulos Katerina A. , Neilands Torsten B. , Dilworth Samantha , Lisha Nadra , Sauceda John , Mugavero Michael J. , Crane Heidi M. , Fredericksen Rob J. , Mathews William C. , Moore Richard D. , Mayer Kenneth H. , Napravnik Sonia , Johnson Mallory O. 
Published: July 2020

Objective:
We sought to examine the prospective association between internalized HIV stigma and unsuppressed viral load and to investigate whether this relationship was sequentially mediated by depressive symptoms and antiretroviral therapy (ART) adherence.

Design:
Longitudinal study in a multisite observational clinical cohort.

Methods:
The Center for AIDS Research Network of Integrated Clinical Systems patient-reported outcomes survey measures internalized HIV stigma yearly using a four-item assessment (response scale 1 = strongly disagree to 5 = strongly agree). We obtained patient-reported outcome, lab, and appointment data from six center for AIDS research network of integrated clinical systems sites. We used multivariable logistic regression to examine the association between mean stigma and subsequent viremia. We then used Bayesian sequential mediation to fit a longitudinal sequential path model spanning four time points to test if depressive symptoms at T1 and ART adherence at T2 mediated the effect of stigma at T0 on viral load at T3, adjusting for baseline covariates.

Results:
Between February 2016 and November 2018, 6859 patients underwent stigma assessment and were 81% cis-men, 38% Black, 16% Latinx, 32% heterosexual-identified, and 49% at least 50 years of age. Mean stigma level was 2.00 (SD 1.08). Stigma was significantly associated with subsequent viremia (adjusted odds ratio = 1.16, 95% confidence interval: 1.05–1.28, P = 0.004), as were younger age and Black race. The chained indirect effect from stigma to unsuppressed viral load through depressive symptoms and then adherence was significant (standardized β = 0.002; SD = 0.001).

Conclusion:
Internalized HIV stigma positively predicts subsequent viremia through depressive symptoms and ART adherence. Addressing the link between stigma and depressive symptoms could help improve viral suppression.
Dual antiretroviral therapies are effective and safe regimens in the central nervous system of neurologically symptomatic people living with HIV
Authors: Trunfio Mattia , Rugge Walter , Mighetto Lorenzo , Vai Daniela , Atzori Cristiana , Nigra Marco , Domini Simone , Borgogno Enrica , Guastamacchia Giulia , Bonora Stefano , Di Perri Giovanni , Calcagno Andrea 
Published: July 2020

Objective:
Aim of this study was to compare cerebrospinal fluid (CSF) virological control, biomarkers and neurocognition of neurologically symptomatic patients on dual antiretroviral therapies (dual therapy) vs. 2 nucleoside reverse transcriptase inhibitors-based three-drug regimens (triple therapy).

Design:
Retrospective monocentric cross-sectional study.

Methods:
We analysed data from people living with HIV undergoing lumbar puncture for clinical/research reasons with plasma HIV-RNA less than 200 copies/ml and neurological/neurocognitive symptoms without significant contributing comorbidities. We measured CSF HIV-RNA, inflammation, blood–brain barrier integrity, neuronal damage and astrocytosis biomarkers (five biomarkers by ELISA and five indices by immunoturbidimetry) and recorded the neurocognitive performance (14 tests). CSF escape was defined as any case of CSF HIV-RNA 0.5 Log10 higher than viraemia or any case of detectable CSF HIV-RNA coupled with undetectable viraemia.

Results:
A total of 78 patients on triple therapy and 19 on dual therapy were included. Overall, 75.3% male, median age 51 years (46–58), current CD4+ count 545 cells/μl (349–735), time on current regimens 18 months (8–29), but length of plasma suppression 32 months (14–94). The two groups did not differ in terms of HIV-associated neurological diagnoses, demographic and viro-immunological features. Undetectable CSF HIV-RNA (73.7% in dual therapy vs. 78.2% in triple therapy, p.67) and CSF escape (21.1% in dual therapy vs. 19.2% in triple therapy, p.86) did not differ. No difference was observed in depression, anxiety, neurocognition (in 63 participants) nor in any tested biomarker.

Conclusion:
In people living with HIV with neurological/neurocognitive symptoms, peripherally effective dual therapy can show CSF virosuppression, inflammation, neuronal and astrocyte integrity and neurocognition comparable to triple therapy.
High nonnucleoside reverse transcriptase inhibitor resistance levels in HIV-1-infected Zambian mother–infant pairs
Authors: Bennett Sydney J. , Chunda-Liyoka Catherine , Poppe Lisa K. , Meinders Katie , Chileshe Chisanga , West John T. , Wood Charles 
Published: July 2020

Objective(s):
To elucidate relationships in antiretroviral resistance between HIV-1-infected mother–infant pairs by defining the resistance profiles in the mothers and infants and quantifying drug resistance prevalence in the pairs post-Option B+ implementation.

Design:
Collection of dried blood spots from mother–infant pairs during routine HIV-1 screens in Lusaka, Zambia from 2015 to 2018.

Methods:
DNA was extracted from the dried blood spots, the HIV-1 pol region was amplified, and the purified proviral DNA was sequenced using Sanger sequencing. Drug resistance mutations (DRM) were identified in sequenced DNA using the Stanford HIVdb (https://hivdb.stanford.edu/).

Results:
DRM were detected in 45% (44/97) of samples, and these samples were found to harbor resistance to at least two antiretrovirals. The prevalence of nonnucleoside reverse transcriptase inhibitor resistance was significantly higher than that of other antiretroviral classes. DRM were detected disproportionately in infants (67%; 33/49) compared with mothers (23%; 11/48), but the magnitude of resistance did not differ when resistance was detected. The disparity in drug resistance profiles was reinforced in pairwise comparison of resistance profiles in mother–infant pairs.

Conclusion:
While Option B+ is effective in reducing mother-to-child transmission, in cases where this regimen fails, high-level nonnucleoside reverse transcriptase inhibitor resistance is frequently detected in infants. This underscores the importance of pretreatment drug resistance screening in both mothers and infants and emphasizes the necessary change to protease inhibitor-based and integrase inhibitor-based regimens for treatment of HIV-1-infected infants and mothers.
Syndemic burden and systemic inflammation, HIV health status, and blood pressure among women with unsuppressed HIV viral loads among women living with HIV
Authors: Jones Deborah L. , Rodriguez Violeta J. , Alcaide Maria Luisa , Carrico Adam , Fischl Margaret A. , Chichetto Natalie E. , Rodriguez Carlos J. , Welsch Michael A. , Farah-Abraham Rachael , Adimora Adaora A. , D'Souza Gypsyamber , Cohen Mardge H. , Shitole Sanyog , Merenstein Daniel , Lazar Jason 
Published: July 2020

Introduction:Smoking, low education, obesity, and depressive symptoms are all associated with HIV health status, increased blood pressure, and inflammation, and constitute a syndemic burden that may contribute to poor health outcomes. The current study examined syndemic burden and health outcomes among women living with HIV.Methods:Women were participants enrolled in the Women's Interagency HIV Study. Outcomes included blood pressure, HIV health status (HIV-1 RNA viral load and CD4+T-cell counts), and IL-6. Syndemic burden was defined as a count variable of low education, obesity, cigarette use, and depressive symptoms.Results:Women (N = 131) were an average of 60.54 years of age (SD = 8.86), and 49% were non-Hispanic Black. In multivariable analyses, syndemic burden was not significantly associated with SBP (P = 0.342) or DBP (P = 0.763), IL-6 (P = 0.168), or CD4+cell count (P = 0.846). However, syndemic burden was associated with increased viral load (age adjusted β = 0.35,P < 0.001). Comparing women with high versus low syndemic burden, also controlling for women's age, women with high syndemic burden had higher DBP and HIV viral load.Discussion:Syndemic burden appeared to play an important role in HIV health status and could potentially increase the risk of HIV transmission. High syndemic burden, defined as at least two syndemic conditions, had the greatest effects of HIV viral load and DBP. Targeted interventions to address syndemic burden may help improve health outcomes in women living with HIV as well as reduce the risk of hypertension and HIV transmission.
Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV
Authors: Medina Narda , Alastruey-Izquierdo Ana , Mercado Danicela , Bonilla Oscar , Pérez Juan C. , Aguirre Luis , Samayoa Blanca , Arathoon Eduardo , Denning David W. , Rodriguez-Tudela Juan Luis 
Published: July 2020

Objectives:
We evaluated the comparative performance of different assays used in a Diagnostic Laboratory Hub that linked 13 HIV healthcare facilities for the diagnosis of tuberculosis (TB), histoplasmosis, and cryptococcosis, and describing its functions in Guatemala compared with other National Reference Laboratories.

Methods:
The following diagnostic techniques were analyzed in 24 months (2017–2018) in a cohort of patients with HIV: smear microscopy, mycobacterial and fungal cultures, isolator blood culture, PCR assays, and antigen detection tests.

Results:
A total of 4245 patients were included, 716 (16.2%) had an opportunistic infection: 249 (34.7%) TB, 40 (5.6%) nontuberculous mycobacteria, 227 (31.7%) histoplasmosis, 138 (19.3%) cryptococcosis, and 62 (8.6%) had multiple opportunistic infections. Two hundred sixty-three [92.6%; 95% confidence interval (CI), 89–95.1] of TB cases were diagnosed by PCR. Urine antigen assay detected 94% (95% CI, 89–96) of the disseminated histoplasmosis cases. A lateral flow assay to detect cryptococcal antigen diagnosed 97% (95% CI, 93.3–98.7%) of the cryptococcal cases. In 85 patients (51.5%) with a cerobrospinal fluid sample, cryptococcal meningitis was diagnosed in 55 (64.7%), of which 18 (32.7%) were only detected by cryptococcal antigen.

Conclusion:
Validated commercial antigen tests, as used in this program, should be the new gold standard for histoplasmosis and cryptococcosis diagnosis. In their absence, 35% of disseminated histoplasmosis and 32.7% of cryptococcal meningitis cases would have been missed. Patients with multiple opportunistic infections were frequently diagnosed and strategies should be designed to screen patients irrespective of their clinical presentation. In low resource settings, Diagnostic Laboratory Hubs can deliver quality diagnostics services in record time at affordable prices.
Echocardiographic Findings Among Virally Suppressed HIV-Infected Aging Asians Compared with HIV-Negative Individuals
Authors: Chattranukulchai Pairoj , Thimaporn Weerayut , Siwamogsatham Sarawut , Satitthunmmanid Sudarat , Sitticharoenchai Patita , Apornpong Tanakorn , Sangarlangkarn Aroonsiri , Kerr Stephen J. , Ruxrungtham Kiat , Boonyaratavej Smonporn , Avihingsanon Anchalee ,   on behalf of HIV-NAT 006/207 study team
Published: July 2020

Objectives:Prevalence of cardiovascular disease increases with age. Little is known about the prevalence and risk factors for echocardiographic abnormalities among older people living with HIV (PLHIV) from Asia.Design:A cross-sectional study was conducted among PLHIV aged >50 years (N = 298) on antiretroviral treatment (ART) and HIV-negative controls (N = 100) frequency matched by sex and age in Thailand.Methods:All participants underwent standard 2-dimensional transthoracic echocardiography performed by trained cardiologists who were blinded to the participant's care and HIV status. Logistic regression was used to examine the association between cardiac abnormalities and risk factors.Results:The median age was 54.7 years (60.8% men) with 37.2% having hypertension and 16.6% having diabetes mellitus. PLHIV was on ART for a median of 16.2 years with current CD4 cell counts of 616 cells per cubic millimeter. Echocardiogram abnormalities did not differ among PLHIV (55%) and the controls (60%). The major abnormalities in PLHIV were following: left ventricular (LV) hypertrophy: 37% men and 42.2% women, LV systolic dysfunction (0.7%), diastolic dysfunction (24.2%), and pulmonary hypertension (3.9%). From the multivariate analyses in PLHIV, being aged >60 years was independently associated with diastolic dysfunction, whereas female sex and left atrial volume index of >34 mL/m2were associated with pulmonary hypertension (P< 0.05). None of the ART was significantly associated with any major echocardiographic abnormalities.Conclusions:In this long-term, well-suppressed, older, Asian PLHIV cohort, the prevalence of asymptomatic LV systolic dysfunction and pulmonary hypertension were relatively low, whereas the diastolic dysfunction and LV hypertrophy were common. Echocardiographic findings did not differ between PLHIV and HIV-uninfected controls.
Evaluation of 3 Cognitive Load Measures During Repeated Simulation Exercises for Novice Anesthesiology Residents
Authors: Toy Serkan , Miller Christina R. , Daly Guris Rodrigo J. , Duarte Shirley S. , Koessel Sophia , Schiavi Adam 
Published: July 2020

Introduction
Maintaining an appropriate level of cognitive load during simulations is crucial to optimize learning. We evaluated 3 subjective measures of cognitive load in a simulated operating room (OR) context across multiple scenarios of varying complexity.

Methods
This observational study of 25 first-year anesthesiology residents took place during a 5-day simulation “Boot Camp.” Each day, participants completed 2 different high-fidelity scenarios in a fully equipped simulated OR. After each simulation, participants completed 3 cognitive load measures: the Paas scale, NASA Task Load Index (TLX), and Cognitive Load Component (CLC) questionnaire. Two-way repeated-measures and mixed-design analyses of variance, with the cognitive load measures and scenarios as independent factors, were used to determine the effect of using different measures to report cognitive load.

Results
Cognitive load scores reported by all measures correlated significantly with one another (P < 0.01): TLX and Paas (r = 0.65); Paas and CLC (r = 0.63); and TLX and CLC (r = 0.61). The CLC subscale scores (intrinsic, extraneous, germane) also correlated significantly with composite TLX and Paas scores (P < 0.01). Scenarios and measures displayed significant interaction: F(10, 210) = 3.01, P = 0.001. Participants reported highest overall cognitive load using the Paas scale.

Conclusions
All cognitive load measures were sensitive to scenario variability and showed similar fluctuation patterns across the 10 scenarios. The findings suggest that cognitive load measures can help create benchmarks based on learner perceptions of cognitive burden for different simulation scenarios.
Affective traits, states, and breathlessness
Authors: von Leupoldt Andreas , Denutte Ysys 
Published: July 2020

Purpose of review
Breathlessness is a prevalent and aversive symptom in various conditions and closely related to affect. Here, we review recent literature from the previous 18 months examining the interactions between affective traits and states with breathlessness.

Recent findings
Available studies used various qualitative, quantitative, and experimental research designs in diverse samples of patients with breathlessness and in healthy individuals. Most studies clearly demonstrated that nonspecific forms of negative affective personality traits such as anxiety and depression, disease or symptom-specific forms such as fear-of-dyspnea and fear-of-physical activity as well as short-lasting negative affective states such as experimentally induced fear were associated with greater breathlessness. Moreover, breathlessness was shown to evoke negative affect, whereas positive affect reduced breathlessness. Different treatment approaches demonstrated concurrent beneficial effects on both negative affect and breathlessness and several potential mechanisms underlying these interactions were suggested.

Summary
Negative affect is common in diverse patient groups suffering from breathlessness and is related to increased burden because of breathlessness. Future research is required to improve our understanding of the mechanisms underlying these associations together with increased clinical efforts for improved detection and treatment of negative affect in breathless patients.
Staging of Dementia Severity With the Hong Kong Version of the Montreal Cognitive Assessment (HK-MoCA)’s
Authors: Pan Ian Ming Yeung , Lau Mei Suen , Mak Shun Chi , Hariman Keith Wilfred , Hon Simon King Him , Ching Wing Ka , Cheng Koi Man , Chan Cheong Fai 
Published: July 2020

Background:
The Hong Kong version of Montreal Cognitive Assessment (HK-MoCA) has been used to screen for dementia, but it has not been validated to delineate the stages of Alzheimer disease (AD). This study aimed to determine the cut-off score ranges for mild, moderate, and severe AD.

Methods:
The HK-MoCA score was matched against the Clinical Dementia Rating on 155 patients with AD. Investigators performing the HK-MoCA and Clinical Dementia Rating were blinded to each other. Receiver-operating characteristic analysis was used to determine the cut-off scores between different stages of AD (mild, moderate, and severe stage). A secondary analysis with adjustments for age and education received were also performed.

Result:
The cut-off score in HK-MoCA was ≤4 for those with severe AD (sensitivity 84.4%, specificity 91.9%, area under curve=0.92, P<0.001) and 5 to 9 for those with moderate AD (sensitivity 86.3%, specificity of 93.3%, area under curve=0.953, P<0.001). With adjustments for age and education, the cut-off score for moderate AD was adjusted to 5 to 8, whereas the cut-off score for severe AD remained unchanged.

Conclusions:
The severity of AD could be delineated using the HK-MoCA for the Cantonese-speaking population in Hong Kong, and the effect of education on the cut-off score needs further investigation.
Nonepileptic Electroencephalographic Correlates of Episodic Increases in Intracranial Pressure
Authors: Sheikh Zubeda B. , Maciel Carolina B. , Dhakar Monica B. , Hirsch Lawrence J. , Gilmore Emily J. 
Published: July 2020

Purpose:
Continuous EEG can potentially be used as real-time brain telemetry for the early detection of neurologic decline. Scant literature on EEG changes related to elevated intracranial pressure (ICP) limits its use in this context.

Methods:
Retrospective, observational case series of patients in whom we noted EEG changes correlating with a clinical concern for elevated ICP, measured or unmeasured.

Results:
We noted EEG changes of varying severity and duration correlating with either measured or unmeasured clinical concern for elevated ICP. In two patients with recurrent transient unresponsiveness (presumed from plateau waves), generalized rhythmic delta activity and attenuation of fast activity occurred 30 minutes before a clinical change. Elevated ICP in two patients, one related to progressive mass effect from infarctions, and the other to dialysis, correlated with generalized slowing and attenuation of fast activity up to 24 hours before clinical deterioration, leading to diffuse suppression. Two patients with intraventricular hemorrhage had cyclic patterns at ∼1 per minute and ∼6 per minute (similar frequency to described frequency of Lundberg B and C waves, respectively).

Conclusions:
Cyclic patterns and varying degrees of slowing and attenuation often preceded clinical deterioration associated with intracranial hypertension. Future systematic studies of EEG changes in this setting will facilitate early and noninvasive detection of elevated ICP.