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Predictors of low-level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort

HIV Med. 2022 Mar 1. doi: 10.1111/hiv.13265. Online ahead of print.

ABSTRACT

OBJECTIVES: To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART.

METHODS: We included adults aged > 18 years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥ 50 copies/mL at week 48 and pVL ≥ 200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route.

RESULTS: Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA > 5 log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0-48.3] and VF (aOR = 5.4, 95% CI: 1.9-15.1), even in participants treated with INSTIs.

CONCLUSIONS: The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA > 5 log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.

PMID:35234328 | DOI:10.1111/hiv.13265

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Family-centred care change during COVID-19

Nurs Crit Care. 2022 Mar 2. doi: 10.1111/nicc.12766. Online ahead of print.

ABSTRACT

BACKGROUND: Family-centred care (FCC) is an approach to promote family and health care provider partnership. This has been incorporated into neonatal intensive care units (NICUs) worldwide. However, FCC in low resource health settings, such as Thailand, is challenging and further impacted by coronavirus disease 2019 (COVID-19).

AIMS: To evaluate FCC innovations to improve respect, collaboration and support in a Thai NICU.

STUDY DESIGN: A quasi-experimental study was conducted in an NICU in southern Thailand. Pre-implementation was prior to COVID-19, and parental and staff perceptions of FCC were measured via Perceptions of Family Centred Care-Parent (PFCC-P) and -Staff (PFCC-S) survey. The FCC innovations were developed by stakeholders based on the COVID-19 restrictions, pre-survey results, parents’ and clinicians’ interviews and integrative review, then implemented via a flowchart. Post-implementation evaluation was via repeated surveys. Comparisons were made pre-and post-implementation, with Mann-Whitney U-test statistics for parents and Wilcoxon’s Rank Sum for staff.

RESULTS: A total of 185 (85 pre; 100 post) parents and 20 (pre and post; paired group) health care professionals participated. Because of COVID-19, many planned interventions were unfeasible, however, other innovations achieved (e.g., structured telephone updates, information booklet revision). There was an increase in parents’ perception of respect ([median] 2.50-3.50), collaboration (2.33-3.33) and support (2.60-3.60) domains and overall (2.50-3.43; p < .001; 95% CI: 2.93-3.11). Interdisciplinary professionals’ perception of FCC did not significantly change pre-and post-implementation/COVID-19 pandemic for respect (3.00-2.92), collaboration (3.22-3.33), support (3.20-3.20) and overall (3.15-3.20; 95% CI: 3.10-3.25).

CONCLUSION: Despite the challenges of COVID-19 restricting NICU access, the provision of FCC was maintained and even improved.

RELEVANCE TO CLINICAL PRACTICE: Further research is necessary to develop FCC practice innovations associated with communication, across diverse health care systems and resources.

PMID:35234320 | DOI:10.1111/nicc.12766

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Effect of perfusate volume on amikacin concentrations after saphenous intravenous regional limb perfusion in standing, sedated horses

Vet Surg. 2022 Mar 2. doi: 10.1111/vsu.13789. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the influence of perfusate volume on synovial fluid amikacin concentrations in the joints of the hind limb after standing saphenous intravenous regional limb perfusion (IVRLP).

STUDY DESIGN: Randomized crossover design.

ANIMALS: Six adult horses.

METHODS: Saphenous IVRLP was performed in 6 standing horses with 1 g of amikacin diluted with 0.9% NaCl to volumes of 10 ml, 60 ml, and 120 ml. Samples of synovial fluid from the tarsocrural, metatarsophalangeal, and hind limb distal interphalangeal joints were collected at 15 and 30 min after perfusate administration. Concentrations of 40 μg/ml and 160 μg/ml were considered therapeutic for susceptible and resistant pathogens, respectively.

RESULTS: No difference in synovial fluid amikacin concentrations was detected between volumes in any joint (P = .4). All synovial fluid amikacin concentrations were higher at 30 min compared to 15 min (P = .003). All median synovial fluid amikacin concentrations at 30 min were > 40 μg/ml using the 60 ml and 120 ml volumes. Synovial fluid amikacin concentrations >40 μg/ml were only reached in the hind limb distal interphalangeal joint when the 10 ml volume was used. All median synovial fluid amikacin concentrations observed were < 160 μg/ml.

CONCLUSIONS: Target concentrations for pathogens that were considered susceptible were consistently reached with perfusate volumes of 60 ml and 120 ml. However, median synovial fluid amikacin concentrations did not reach target levels for resistant pathogens.

CLINICAL SIGNIFICANCE: Perfusate volumes of 60 ml or 120 ml are recommended to treat infections due to susceptible pathogens in the joints of the distal hind limb. These results justify investigation of saphenous IVRLP with different perfusate volumes using higher doses of amikacin.

PMID:35234300 | DOI:10.1111/vsu.13789

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The Impact of COVID-19 on Adolescent Wellness in Chicago

Child Care Health Dev. 2022 Mar 1. doi: 10.1111/cch.12994. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to understand the impact of the initial COVID-19 pandemic remote schooling period on self-reported wellness among adolescents in Chicago.

METHODS: Students (n=55) completed a 22-item wellness questionnaire before (February 2020) and shortly after the onset of the COVID-19 outbreak (April 2020). Pre/post comparisons (overall and by survey item) were evaluated using two-sided paired t-tests with an alpha level of 0.05. Descriptive statistics were used to evaluate mean scores overall by demographic variables.

RESULTS: Significant differences were found in the following areas: Balance (Pre: 7.3, During: 6.4, p=0.02), Education (Pre: 8.4, During 7.7, p=0.03) and Friends (Pre:8.0, During: 6.3, p=0.001). Overall wellness scores varied by demographic variables, though not significantly.

CONCLUSIONS: Results suggest the onset of the pandemic impacted students’ ability to effectively learn, as well as to maintain balance in their lives and social relationships. Comprehensive support is needed in these areas to promote adolescent wellness.

PMID:35234301 | DOI:10.1111/cch.12994

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COVID-19 in pregnancy-what study designs can we use to assess the risk of congenital anomalies in relation to COVID-19 disease, treatment and vaccination?

Paediatr Perinat Epidemiol. 2022 Mar 2. doi: 10.1111/ppe.12840. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has accelerated pregnancy outcome research, but little attention has been given specifically to the risk of congenital anomalies (CA) and first trimester exposures.

OBJECTIVES: We reviewed the main data sources and study designs used internationally, particularly in Europe, for CA research, and their strengths and limitations for investigating COVID-19 disease, medications and vaccines.

POPULATION: We classify research designs based on four data sources: a) spontaneous adverse event reporting, where study subjects are positive for both exposure and outcome, b) pregnancy exposure registries, where study subjects are positive for exposure, c) congenital anomaly registries, where study subjects are positive for outcome and d) population healthcare data where the entire population of births is included, irrespective of exposure and outcome.

STUDY DESIGN: Each data source allows different study designs, including case series, exposed pregnancy cohorts (with external comparator), ecological studies, case-control studies and population cohort studies (with internal comparator).

METHODS: The quality of data sources for CA studies is reviewed in relation to criteria including diagnostic accuracy of CA data, size of study population, inclusion of terminations of pregnancy for foetal anomaly, inclusion of first trimester COVID-19-related exposures and use of an internal comparator group. Multinational collaboration models are reviewed.

RESULTS: Pregnancy exposure registries have been the main design for COVID-19 pregnancy studies, but lack detail regarding first trimester exposures relevant to CA, or a suitable comparator group. CA registries present opportunities for improving diagnostic accuracy in COVID-19 research, especially when linked to other data sources. Availability of inpatient hospital medication use in population healthcare data is limited. More use of ongoing mother-baby linkage systems would improve research efficiency. Multinational collaboration delivers statistical power.

CONCLUSIONS: Challenges and opportunities exist to improve research on CA in relation to the COVID-19 pandemic and future pandemics.

PMID:35234297 | DOI:10.1111/ppe.12840

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Pharmacotherapy for post traumatic stress disorder (PTSD)

Cochrane Database Syst Rev. 2022 Mar 2;3:CD002795. doi: 10.1002/14651858.CD002795.pub3.

ABSTRACT

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment.

OBJECTIVES: To assess the effects of medication for reducing PTSD symptoms in adults with PTSD.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020.

SELECTION CRITERIA: All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD.

DATA COLLECTION AND ANALYSIS: Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity.

MAIN RESULTS: We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis. For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence. For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events.

AUTHORS’ CONCLUSIONS: The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.

PMID:35234292 | DOI:10.1002/14651858.CD002795.pub3

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Using Social Media to Promote School Nutrition Programs During the COVID-19 Pandemic

J Sch Health. 2022 Mar 2. doi: 10.1111/josh.13151. Online ahead of print.

ABSTRACT

BACKGROUND: Millions of school-aged children receive free or reduced-price lunches through the United States Department of Agriculture’s (USDA) National School Lunch Program; that service was disrupted when public schools closed at the beginning of the coronavirus pandemic. Prior to the pandemic, this program received little attention on school districts’ social media accounts.

METHODS: We collected Twitter data from 70 Ohio public school districts to construct a measure of attention paid toward school nutrition programs from 2008 to 2021. We also collected district-level data to analyze the relationship between district characteristics and mentions of school nutrition programs.

RESULTS: We show that attention to school nutrition programs significantly increased during the pandemic. School districts with a greater student population density and greater geographic area were more likely to tweet about these programs.

CONCLUSIONS: School districts can, and should, use social media to inform residents about school nutrition programs and food security programs more generally. Social media provides a low-cost way to lessen the administrative burden for families trying to access these programs.

PMID:35234278 | DOI:10.1111/josh.13151

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Crystallography-based exploration of non-covalent interactions for the design and synthesis of coumarin for stronger protein binding

Phys Chem Chem Phys. 2022 Mar 2. doi: 10.1039/d2cp00082b. Online ahead of print.

ABSTRACT

Protein molecules are a good target for the inhibition or promotion of biological processes. Different methods like QSAR and molecular docking have been developed to accurately design small binder molecules for target proteins. An alternative model has been developed wherein a statistical method is used to find the propensity of different non-covalent interactions between small molecules and amino acid residues of the protein. The results give hints as to the choice of substituents required at the SM to strongly bind to a protein. In this case, 75 different types of proteins bound with coumarin derivatives have been investigated and the non-covalent interactions observed between the basic coumarin moiety and amino acids have been analyzed. Density functional theory (DFT) calculations were used to identify the electronic features of coumarin to understand the feasibility of the observed non-covalent interactions and to find appropriate groups that can modulate these interactions. The binding affinity towards a protein (β-lactoglobulin (BLG)) and the stability of the protein complex have been investigated through docking and molecular dynamics of 100 ns, respectively. The modeled compounds were synthesized and investigated with regards to their interactions with the model carrier protein. The thermodynamics of the interactions were also investigated and the binding is governed by the Le Chatelier principle.

PMID:35234237 | DOI:10.1039/d2cp00082b

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Lack of an association between SCFD1 rs10139154 polymorphism and amyotrophic lateral sclerosis

Mol Med Rep. 2022 Apr;25(4):146. doi: 10.3892/mmr.2022.12662. Epub 2022 Mar 2.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Through a genome‑wide association study (GWAS), the Sec1 family domain‑containing protein 1 (SCFD1) rs10139154 variant at 14q12 has emerged as a risk factor gene for ALS. Moreover, it has been reported to influence the age at onset (AAO) of patients with ALS. The aim of the present study was to assess the association of the SCFD1 rs10139154 polymorphism with the risk of developing ALS. For this purpose, 155 patients with sporadic ALS and 155 healthy controls were genotyped for the SCFD1 rs10139154. The effect of the SCFD1 rs10139154 polymorphism was then examined on the following parameters: i) The risk of developing ALS; ii) the AAO of ALS; iii) the site of ALS onset (patients with bulbar onset ALS vs. healthy controls; and patients with limb onset ALS vs. healthy controls); and iv) the AAO of ALS onset with subgroup analyses based on the site of onset (bulbar and limb, crude and adjusted for sex). The analysis of all the outcomes was performed assuming five genetic models. Crude and adjusted analyses were applied. The threshold for statistical significance was set at 0.05. The results revealed no association between SCFD1 rs10139154 and any of the examined phenotypes in any of the models examined. On the whole, based on the findings of the present study, SCFD1 rs10139154 does not appear to play a determining role in the risk of developing ALS.

PMID:35234271 | DOI:10.3892/mmr.2022.12662

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Combined clinical and specific positron emission tomography/computed tomography-based radiomic features and machine-learning model in prediction of thymoma risk groups

Nucl Med Commun. 2022 Mar 1. doi: 10.1097/MNM.0000000000001547. Online ahead of print.

ABSTRACT

OBJECTIVES: In this single-center study, we aimed to propose a machine-learning model and assess its ability with clinical data to classify low- and high-risk thymoma on fluorine-18 (18F) fluorodeoxyglucose (FDG) (18F-FDG) PET/computed tomography (CT) images.

METHODS: Twenty-seven patients (14 male, 13 female; mean age: 49.6 ± 10.2 years) who underwent PET/CT to evaluate the suspected anterior mediastinal mass and histopathologically diagnosed with thymoma were included. On 18F-FDG PET/CT images, the anterior mediastinal tumor was segmented. Standardized uptake value (SUV)max, SUVmean, SUVpeak, MTV and total lesion glycolysis of primary mediastinal lesions were calculated. For texture analysis first, second, and higher-order texture features were calculated. Clinical information includes gender, age, myasthenia gravis status; serum levels of lactate dehydrogenase (LDH), alkaline phosphatase, C-reactive protein, hemoglobin, white blood cell, lymphocyte and platelet counts were included in the analysis.

RESULTS: Histopathologic examination was consistent with low risk and high-risk thymoma in 15 cases and 12 cases, respectively. The age and myasthenic syndrome were statistically significant in both groups (P = 0.039 and P = 0.05, respectively). The serum LDH level was also statistically significant in both groups (450.86 ± 487.07 vs. 204.82 ± 59.04; P < 0.001). The highest AUC has been achieved with MLP Classifier (ANN) machine learning method, with a range of 0.830 then the other learning classifiers. Three features were identified to differentiate low- and high-risk thymoma for the machine learning, namely; myasthenia gravis, LDH, SHAPE_Sphericity [only for 3D ROI (nz>1)].

CONCLUSIONS: This small dataset study has proposed a machine-learning model by MLP Classifier (ANN) analysis on 18F-FDG PET/CT images, which can predict low risk and high-risk thymoma. This study also demonstrated that the combination of clinical data and specific PET/CT-based radiomic features with image variables can predict thymoma risk groups. However, these results should be supported by studies with larger dataset.

PMID:35234213 | DOI:10.1097/MNM.0000000000001547