Nevin Manimala

J Speech Lang Hear Res. 2024 Aug 15:1-19. doi: 10.1044/2024_JSLHR-24-00030. Online ahead of print.

ABSTRACT

PURPOSE: Individuals with aphasia identify discourse-level communication (i.e., language in use) as a high priority for treatment. The central premise of most aphasia treatments is that restoring language at the phoneme, word, and/or sentence level will generalize to discourse. However, treatment-related changes in discourse-level communication are modest, are poorly understood, and vary greatly among individuals with aphasia. In response, this study consisted of a multilevel discourse analysis of archival, monologic discourse outcomes across two high-intensity Semantic Feature Analysis (SFA) clinical trials. Aim 1 evaluated changes in theoretically motivated discourse outcomes representing lexical-semantic processing, lexical diversity, grammatical complexity, and discourse informativeness. Aim 2 explored the potential moderating role of nonlanguage cognitive factors (semantic memory, divided attention, and executive function) on discourse outcomes.

METHOD: This study was a retrospective analysis of archival monologic discourse outcomes after intensive SFA for n = 60 (Aim 1) and a subset n = 44 (Aim 2). Outcome measures included lexical-semantic processing (% semantic errors), lexical diversity (moving average type-token ratio), grammatical complexity (mean utterance length), and discourse informativeness (% correct information units). Bayesian generalized mixed-effects models were used to examine changes across four study time points: enrollment, entry, exit, and 1-month follow-up.

RESULTS: The present study found no evidence for meaningful or statistically reliable improvements in monologue discourse performance after SFA when measured using standard, general-topic discourse stimuli. There was weak and inconsistent evidence that nonlanguage cognitive factors may play a role in moderating treatment response.

CONCLUSIONS: These findings indicate a clear need to pair theoretically informed treatments designed to facilitate generalization to discourse with intentional measurement paradigms designed to capture it. Furthermore, there is a clear need to examine how established treatments, restorative or compensatory, can better facilitate generalization to discourse-level communication. These priorities are critical for meaningfully improving everyday communication and reducing the profound communication and psychosocial consequences of aphasia.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26524081.

PMID:39146383 | DOI:10.1044/2024_JSLHR-24-00030

PLoS Comput Biol. 2024 Aug 15;20(8):e1012358. doi: 10.1371/journal.pcbi.1012358. Online ahead of print.

ABSTRACT

Reducing spillover of zoonotic pathogens is an appealing approach to preventing human disease and minimizing the risk of future epidemics and pandemics. Although the immediate human health benefit of reducing spillover is clear, over time, spillover reduction could lead to counterintuitive negative consequences for human health. Here, we use mathematical models and computer simulations to explore the conditions under which unanticipated consequences of spillover reduction can occur in systems where the severity of disease increases with age at infection. Our results demonstrate that, because the average age at infection increases as spillover is reduced, programs that reduce spillover can actually increase population-level disease burden if the clinical severity of infection increases sufficiently rapidly with age. If, however, immunity wanes over time and reinfection is possible, our results reveal that negative health impacts of spillover reduction become substantially less likely. When our model is parameterized using published data on Lassa virus in West Africa, it predicts that negative health outcomes are possible, but likely to be restricted to a small subset of populations where spillover is unusually intense. Together, our results suggest that adverse consequences of spillover reduction programs are unlikely but that the public health gains observed immediately after spillover reduction may fade over time as the age structure of immunity gradually re-equilibrates to a reduced force of infection.

PMID:39146377 | DOI:10.1371/journal.pcbi.1012358

PLoS Genet. 2024 Aug 15;20(8):e1011372. doi: 10.1371/journal.pgen.1011372. Online ahead of print.

ABSTRACT

Genome-wide association studies (GWAS) implicate broad genomic loci containing clusters of highly correlated genetic variants. Finemapping techniques can select and prioritize variants within each GWAS locus which are more likely to have a functional influence on the trait. Here, we present a novel method, Finemap-MiXeR, for finemapping causal variants from GWAS summary statistics, controlling for correlation among variants due to linkage disequilibrium. Our method is based on a variational Bayesian approach and direct optimization of the Evidence Lower Bound (ELBO) of the likelihood function derived from the MiXeR model. After obtaining the analytical expression for ELBO’s gradient, we apply Adaptive Moment Estimation (ADAM) algorithm for optimization, allowing us to obtain the posterior causal probability of each variant. Using these posterior causal probabilities, we validated Finemap-MiXeR across a wide range of scenarios using both synthetic data, and real data on height from the UK Biobank. Comparison of Finemap-MiXeR with two existing methods, FINEMAP and SuSiE RSS, demonstrated similar or improved accuracy. Furthermore, our method is computationally efficient in several aspects. For example, unlike many other methods in the literature, its computational complexity does not increase with the number of true causal variants in a locus and it does not require any matrix inversion operation. The mathematical framework of Finemap-MiXeR is flexible and may also be applied to other problems including cross-trait and cross-ancestry finemapping.

PMID:39146375 | DOI:10.1371/journal.pgen.1011372

PLoS One. 2024 Aug 15;19(8):e0308615. doi: 10.1371/journal.pone.0308615. eCollection 2024.

ABSTRACT

Staphylococcus aureus infection and colonization in patients may be transmitted to healthcare providers and the environment and subsequently cause healthcare-associated infections in other patients. Pathogenic S. aureus strains produce virulence factors, such as Panton-Valentine Leukocidin (PVL), that contribute to the severity of infections and aid in their spread. The emergence of antimicrobial resistance (AMR) is additional concern with respect to S. aureus infection. In this study, the virulence genes and antibiotic resistance profiles of S. aureus were characterized from patients’ clinical isolates, healthcare workers’ (HCWs’) nasal colonization screenings, and the environment at a tertiary healthcare hospital in Addis Ababa, Ethiopia. A total of 365 samples were collected from September 2021 to September 2022: 73 patients’ clinical specimens, 202 colonization screenings from HCWs, and 90 hospital environment’s swabs. Fifty-one (25.2%) HCW and 10/90 (11.1%) environment S. aureus isolates were identified. Among the 134 isolates, 10 (7.5%) were methicillin-resistant S. aureus (MRSA). Three (4.1%), five (9.8%), and two (20.0%) of the MRSA isolates were identified from the patients, HCWs, and the environment, respectively. Overall, 118 (88.1%) were ampicillin and penicillin resistant; 70 (52.2%) were trimethoprim sulfamethoxazole resistant; and 28 (20.9%) were erythromycin resistant. S. aureus isolates from patients were more resistant to antibiotics than isolates from HCWs or the hospital environment (p<0.05). A total of 92/134 (68.6%) isolates possessed the lukfF-PV gene, which was identified in 62 (85.0%), 26 (51.0%), and 4 (40.0%) of the patient, HCWs, and the environment, respectively. The proportion of lukfF-PV gene containing S. aureus isolated from patient samples was statistically significant. Four (40.0%) of the MRSA isolates also had the lukfF-PV gene. The identification of highly AMR and virulence factors from patients, HCWs and the environment is concerning. Further studies are needed to identify potential transmission links and improve infection prevention and control.

PMID:39146363 | DOI:10.1371/journal.pone.0308615

Clin Orthop Relat Res. 2024 Aug 14. doi: 10.1097/CORR.0000000000003193. Online ahead of print.

ABSTRACT

BACKGROUND: There is continuing debate about the ideal philosophy for component alignment in TKA. However, there are limited long-term functional and radiographic data on randomized comparisons of kinematic alignment versus mechanical alignment.

QUESTIONS/PURPOSES: We present the 10-year follow-up findings of a single-center, multisurgeon randomized controlled trial (RCT) comparing these two alignment philosophies in terms of the following questions: (1) Is there a difference in PROM scores? (2) Is there a difference in survivorship free from revision or reoperation for any cause? (3) Is there a difference in survivorship free from radiographic loosening?

METHODS: Ninety-nine patients undergoing primary TKA for osteoarthritis were randomized to either the mechanical alignment (n = 50) or kinematic alignment (n = 49) group. Eligibility for the study was patients undergoing unilateral TKA for osteoarthritis who were suitable for a cruciate-retaining TKA and could undergo MRI. Patients who had previous osteotomy, coronal alignment > 15° from neutral, a fixed flexion deformity > 15°, or instability whereby constrained components were being considered were excluded. Computer navigation was used in the mechanical alignment group, and patient-specific cutting blocks were used in the kinematic alignment group. At 10 years, 86% (43) of the patients in the mechanical alignment group and 80% (39) in the kinematic alignment group were available for follow-up performed as a per-protocol analysis. The PROMs that we assessed included the Knee Society Score, Oxford Knee Score, WOMAC, Forgotten Joint Score, and EuroQol 5-Dimension score. Kaplan-Meier analysis was used to assess survivorship free from reoperation (any reason) and revision (change or addition of any component). A single blinded observer assessed radiographs for signs of aseptic loosening (as defined by the presence of progressive radiolucent lines in two or more zones), which was reported as survivorship free from loosening.

RESULTS: At 10 years, there was no difference in any PROM score measured between the groups. Ten-year survivorship free from revision (components removed or added) likewise did not differ between the groups (96% [95% CI 91% to 99%] for the mechanical alignment group and 91% [95% CI 83% to 99%] for the kinematic alignment group; p = 0.38). There were two revisions in the mechanical alignment group (periprosthetic fracture, deep infection) and four in the kinematic alignment group (two secondary patella resurfacings, two deep infections). There was no statistically significant difference in reoperations for any cause between the two groups. There was no difference with regard to survivorship free from loosening on radiographic review (χ2 = 1.3; p = 0.52) (progressive radiolucent lines seen at 10 years were 0% for mechanical alignment and 3% for kinematic alignment).

CONCLUSION: Like the 2-year and 5-year outcomes previously reported, 10-year follow-up for this RCT demonstrated no functional or radiographic difference in outcomes between mechanical alignment and kinematic alignment TKA. Anticipated functional benefits of kinematic alignment were not demonstrated, and revision-free survivorship at 10 years did not differ between the two groups. Given the unknown long-term impact of kinematic alignment with regard to implant position (especially tibial component varus), we must conclude that mechanical alignment remains the reference standard for TKA. We could not demonstrate any advantage to kinematic alignment at 10-year follow-up.

LEVEL OF EVIDENCE: Level I, therapeutic study.

PMID:39145997 | DOI:10.1097/CORR.0000000000003193

JAMA Netw Open. 2024 Aug 1;7(8):e2427331. doi: 10.1001/jamanetworkopen.2024.27331.

NO ABSTRACT

PMID:39145983 | DOI:10.1001/jamanetworkopen.2024.27331

JAMA Netw Open. 2024 Aug 1;7(8):e2427350. doi: 10.1001/jamanetworkopen.2024.27350.

NO ABSTRACT

PMID:39145982 | DOI:10.1001/jamanetworkopen.2024.27350

JAMA Netw Open. 2024 Aug 1;7(8):e2428027. doi: 10.1001/jamanetworkopen.2024.28027.

NO ABSTRACT

PMID:39145981 | DOI:10.1001/jamanetworkopen.2024.28027

JAMA Netw Open. 2024 Aug 1;7(8):e2427786. doi: 10.1001/jamanetworkopen.2024.27786.

ABSTRACT

IMPORTANCE: Patients with trauma exhibit a complex balance of coagulopathy manifested by both bleeding and thrombosis. Antithrombin III is a plasma protein that functions as an important regulator of coagulation. Previous studies have found a high incidence of antithrombin III deficiency among patients with trauma.

OBJECTIVE: To assess whether changes in antithrombin III activity are associated with thrombohemorrhagic complications among patients with trauma.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted from December 2, 2015, to March 24, 2017, at a level I trauma center. A total of 292 patients with trauma were followed up from their arrival through 6 days from admission. Data, including quantification of antithrombin III activity, were collected for these patients. Thromboprophylaxis strategy; hemorrhage, deep vein thrombosis (DVT), and pulmonary embolism screenings; and follow-up evaluations were conducted per institutional protocols. Data analyses were performed from September 28, 2023, to June 4, 2024.

MAIN OUTCOMES AND MEASURES: The primary study outcome measurements were associations between antithrombin III levels and outcomes among patients with trauma, including ventilator-free days, hospital-free days, intensive care unit (ICU)-free days, hemorrhage, venous thromboembolic events, and mortality.

RESULTS: The 292 patients had a mean (SD) age of 54.4 (19.0) years and included 211 men (72.2%). Patients with an antithrombin III deficiency had fewer mean (SD) ventilator-free days (27.8 [5.1] vs 29.6 [1.4]; P = .0003), hospital-free days (20.3 [8.2] vs 24.0 [5.7]; P = 1.37 × 10-6), and ICU-free days (25.7 [4.9] vs 27.7 [2.3]; P = 9.38 × 10-6) compared with patients without a deficiency. Antithrombin III deficiency was also associated with greater rates of progressive intracranial hemorrhage (21.1% [28 of 133] vs 6.3% [10 of 159]; P = .0003) and thrombocytopenia (24.8% [33 of 133] vs 5.0% [8 of 159]; P = 1.94 × 10-6). Although antithrombin III deficiency was not significantly associated with DVT, patients who developed a DVT had a more precipitous decrease in antithrombin III levels that were significantly lower than patients who did not develop a DVT.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased mortality, as well as fewer ventilator-free, hospital-free, and ICU-free days. Although this was an associative study, these data suggest that antithrombin III levels may be useful in the risk assessment of patients with trauma.

PMID:39145978 | DOI:10.1001/jamanetworkopen.2024.27786

JAMA Netw Open. 2024 Aug 1;7(8):e2427956. doi: 10.1001/jamanetworkopen.2024.27956.

ABSTRACT

IMPORTANCE: Depression is common in adults experiencing homelessness. It is unclear whether continued homelessness is associated with more depressive symptoms.

OBJECTIVE: To examine the association between residential status and depressive symptoms in adults aged 50 years or older experiencing homelessness at study entry.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed results from the Health Outcomes of People Experiencing Homelessness in Older Middle Age (HOPE HOME) project, which in 2013 began enrolling adults aged 50 years or older experiencing homelessness in Oakland, California, and conducted structured interviews every 6 months for a mean duration of 5.5 years through 2023 (for this cohort study). Eligible participants included those aged 50 years or older, able to speak English, and experiencing homelessness at enrollment. We analyzed data collected from 2013 to 2023.

EXPOSURES: The exposure of interest was residential status. At follow-up visits, residential status was categorized as (1) homelessness (meeting the HEARTH [Homeless Emergency Assistance and Rapid Transition to Housing] Act definition) or (2) housed (living in a noninstitutional environment and not meeting the HEARTH Act definition).

MAIN OUTCOMES AND MEASURES: The primary outcome was moderate to severe depressive symptoms (with Center for Epidemiologic Studies-Depression [CES-D] scale score ≥22). The augmented inverse probability of treatment weighting (AIPTW) approach was used to examine the association between continued homelessness and depressive symptoms. The AIPTW adjusted for the following variables: number of chronic health conditions, age, sex, visiting a health care practitioner, receiving outpatient mental health treatment, receiving mental health medication, exposure to abuse, substance use disorder, and binge drinking.

RESULTS: The cohort was composed of 450 participants, of whom 343 (76.2%) were males, and the mean (SD) age was 58.5 (5.2) years. Participants completed a median (IQR) of 8.9 (8-11) follow-up visits. With 1640 person-years of observation time, participants continued homelessness for 880 person-years (57.1%) and experienced being housed for 715 person-years (44.3%). Many participants (304 [78.0%]) were housed during at least 1 follow-up visit. The odds of a CES-D scale score of 22 or higher was significantly higher among participants who continued experiencing homelessness than among housed participants (marginal causal odds ratio, 1.08; 95% CI, 1.04-1.11; P < .001).

CONCLUSIONS AND RELEVANCE: This cohort study found that continued homelessness was associated independently with increased odds of depressive symptoms. Obtaining housing may have a favorable role in depression and overall well-being of older adults experiencing homelessness and may be considered as a mental health intervention.

PMID:39145977 | DOI:10.1001/jamanetworkopen.2024.27956