Nevin Manimala

Sex Health. 2024 Aug;21:SH24056. doi: 10.1071/SH24056.

ABSTRACT

Background Sexual transmission accounts for a substantial proportion of HIV infections. Although some countries are experiencing an upward trend in HIV infections, there has been a lack of studies assessing the global burden of HIV/AIDS acquired through sexual transmission. We assessed the global, regional, and national burdens of HIV/AIDS acquired through sexual transmission from 1990 to 2019. Methods Data on deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALY) of HIV/AIDS acquired through sexual transmission in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study (GBD) 2019. The burdens and trends were evaluated using the age-standardised rates (ASR) and estimated annual percentage change (EAPC). Results Globally, HIV/AIDS acquired through sexual transmission accounted for ~695.8 thousand (95% uncertainty interval 628.0-811.3) deaths, 33.0million (28.7-39.9) YLLs, 3.4million (2.4-4.6) YLDs, and 36.4million (32.2-43.1) DALYs in 2019. In 2019, Southern sub-Saharan Africa (11350.94), Eastern sub-Saharan Africa (3530.91), and Western sub-Saharan Africa (2037.74) had the highest ASR of DALYs of HIV/AIDS acquired through sexual transmission per 100,000. In most regions of the world, the burden of HIV/AIDS acquired through sexual transmission has been increasing from 1990 to 2019, mainly in Oceania (EAPC 17.20, 95% confidence interval 12.82-21.75), South Asia (9.00, 3.94-14.30), and Eastern Europe (7.09, 6.35-7.84). Conclusions HIV/AIDS acquired through sexual transmission results in a major burden globally, regionally, and nationally.

PMID:39146461 | DOI:10.1071/SH24056

J Head Trauma Rehabil. 2024 Aug 12. doi: 10.1097/HTR.0000000000000967. Online ahead of print.

ABSTRACT

OBJECTIVES: Alexithymia an emotional processing deficit that interferes with a person’s ability to recognize, express, and differentiate emotional states. Study objectives were to (1) determine rates of elevated alexithymia among people with moderate-to-severe traumatic brain injury (TBI) 1-year post-injury, (2) identify demographic and injury-related variables associated with high versus low-average levels of alexithymia, and (3) examine associations among alexithymia with other aspects of emotional functioning and life satisfaction.

SETTING: Data were collected during follow-up interviews across four TBI Model System (TBIMS) centers.

PARTICIPANTS: The sample consisted of 196 participants with moderate-to-severe TBI enrolled in the TBIMS. They were predominately male (77%), White (69%), and had no history of pre-injury mental health treatment (66.3%).

DESIGN: Cross-sectional survey data were obtained at study enrollment and 1-year post-injury.

MAIN MEASURES: Toronto Alexithymia Scale-20 (TAS-20) as well as measures of anger, aggression, hostility, emotional dysregulation, post-traumatic stress, anxiety, depression, resilience and life satisfaction. Sociodemographic information, behavioral health history and injury-related variables were also included.

RESULTS: High levels of alexithymia (TAS-20 score > 1.5 standard deviation above the normative mean) were observed for 14.3%. Compared to individuals with low/average levels of alexithymia, the high alexithymia group tended to have lower levels of education. At 1-year follow-up, high TAS-20 scores were strongly associated with emotional dysregulation and post-traumatic stress; moderately associated with anger, hostility, depression, anxiety, lower resilience and lower satisfaction with life; and weakly associated with aggression.

CONCLUSION: These findings provide further evidence that alexithymia is associated with poor emotional functioning and life satisfaction after TBI. Longitudinal studies are needed to determine if alexithymia is a risk factor that precipitates and predicts worse emotional outcomes in the TBI population. This line of work is important for informing treatment targets that could prevent or reduce of psychological distress after TBI.

PMID:39146446 | DOI:10.1097/HTR.0000000000000967

Scand J Clin Lab Invest. 2024 Aug 15:1-6. doi: 10.1080/00365513.2024.2392126. Online ahead of print.

ABSTRACT

Vitamin B1 (thiamine pyrophosphate (TPP)) and B6 (pyridoxal 5′- phosphate (PLP)) deficiencies pose significant health risks. The current measurement method employs High-Performance Liquid Chromatography (HPLC), though, Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) is considered a more sensitive and selective analytical method. However, there is a lack of LC-MS/MS-based reference intervals. Moreover, none of the existing reference intervals are established in Danish populations. Therefore, the aim of this study was to establish a reference interval for whole blood concentrations of TPP and PLP in Danish blood donors using LC-MS/MS. Blood samples were collected from healthy Danish blood donors and analysed using the reagent kit, MassChrom^® Vitamins B1 and B6 in whole blood (Chromsystems Instruments & Chemicals GmbH, Munich, Germany) for quantitative determination of both TPP and PLP concentration in whole blood, using LC-MS/MS. Reference intervals were determined with non-parametric methods as the 2.5th and 97.5th percentile and presented with 90% confidence intervals (CI). In total 120 blood donors were included. The concentrations of TTP or PLP were not statistically different between sexes just as age did not affect the concentrations, hence, combined reference intervals were employed. The resulting reference intervals are: TPP, nmol/L: 101.0 (90% CI: 96.4-108.5) – 189.0 (90% CI: 184.7-192.0) and PLP, nmol/L: 64.0 (90% CI: 60.9-66.7) – 211.8 (90% CI: 168.3-231.0). In conclusion, reference intervals for whole blood TTP and PLP in a healthy Danish population were established based on a LC-MS/MS method. Furthermore, the reference intervals were not affected by age or sex.

PMID:39146443 | DOI:10.1080/00365513.2024.2392126

PLoS Biol. 2024 Aug 15;22(8):e3002758. doi: 10.1371/journal.pbio.3002758. Online ahead of print.

ABSTRACT

In disciplines from biology to climate science, a routine task is to compute a correlation between a pair of time series and determine whether the correlation is statistically significant (i.e., unlikely under the null hypothesis that the time series are independent). This problem is challenging because time series typically exhibit autocorrelation and thus cannot be properly analyzed with the standard iid-oriented statistical tests. Although there are well-known parametric tests for time series, these are designed for linear correlation statistics and thus not suitable for the increasingly popular nonlinear correlation statistics. There are also nonparametric tests that can be used with any correlation statistic, but for these, the conditions that guarantee correct false positive rates are either restrictive or unclear. Here, we describe the truncated time-shift (TTS) test, a nonparametric procedure to test for dependence between 2 time series. We prove that this test correctly controls the false positive rate as long as one of the time series is stationary, a minimally restrictive requirement among current tests. The TTS test is versatile because it can be used with any correlation statistic. Using synthetic data, we demonstrate that this test performs correctly even while other tests suffer high false positive rates. In simulation examples, simple guidelines for parameter choices allow high statistical power to be achieved with sufficient data. We apply the test to datasets from climatology, animal behavior, and microbiome science, verifying previously discovered dependence relationships and detecting additional relationships.

PMID:39146390 | DOI:10.1371/journal.pbio.3002758

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