Tag: pubmed

Diabetes Care. 2022 Jun 13:dc211789. doi: 10.2337/dc21-1789. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify novel biomarkers of cardiovascular disease (CVD) risk in type 2 diabetes (T2D) via a hypothesis-free global metabolomics study, while taking into account renal function, an important confounder often overlooked in previous metabolomics studies of CVD.

RESEARCH DESIGN AND METHODS: We conducted a global serum metabolomics analysis using the Metabolon platform in a discovery set from the Joslin Kidney Study having a nested case-control design comprising 409 individuals with T2D. Logistic regression was applied to evaluate the association between incident CVD events and each of the 671 metabolites detected by the Metabolon platform, before and after adjustment for renal function and other CVD risk factors. Significant metabolites were followed up with absolute quantification assays in a validation set from the Joslin Heart Study including 599 individuals with T2D with and without clinical evidence of significant coronary heart disease (CHD).

RESULTS: In the discovery set, serum orotidine and 2-piperidinone were significantly associated with increased odds of incident CVD after adjustment for glomerular filtration rate (GFR) (odds ratio [OR] per SD increment 1.94 [95% CI 1.39-2.72], P = 0.0001, and 1.62 [1.26-2.08], P = 0.0001, respectively). Orotidine was also associated with increased odds of CHD in the validation set (OR 1.39 [1.11-1.75]), while 2-piperidinone did not replicate. Furthermore, orotidine, being inversely associated with GFR, mediated 60% of the effects of declining renal function on CVD risk. Addition of orotidine to established clinical predictors improved (P < 0.05) C statistics and discrimination indices for CVD risk (ΔAUC 0.053, rIDI 0.48, NRI 0.42) compared with the clinical predictors alone.

CONCLUSIONS: Through a robust metabolomics approach, with independent validation, we have discovered serum orotidine as a novel biomarker of increased odds of CVD in T2D, independent of renal function. Additionally, orotidine may be a biological mediator of the increased CVD risk associated with poor kidney function and may help improve CVD risk prediction in T2D.

PMID:35696261 | DOI:10.2337/dc21-1789

Int J Prosthodont. 2022 Jun 6. doi: 10.11607/ijp.7942. Online ahead of print.

ABSTRACT

PURPOSE: To compare the changes in quality of life in edentulous patients with single implants supporting mandibular overdentures with two different attachment types before implant placement and after 6 and 24 months.

MATERIALS AND METHODS: Eighty edentulous patients were recruited, and all patients completed the validated Oral Health Impact Profile (OHIP)-EDENT-19 questionnaire before implant surgery. A single implant was placed in the midline of the edentulous mandibles. All implants were allowed to heal for 3 months. After the healing period, randomization into one of two groups was accomplished using sealed envelopes: group A (ball attachment) and group B (locator attachment). The same questionnaire was completed 6 and 24 months postplacement. Mann-Whitney U test for independent samples was used to compare the two groups, while Freidman test was used for comparison within each group. Two-sided P values less than .05 were considered statistically significant.

RESULTS: There was an improvement in all domains of the OHIP-EDENT-19 scores at the 6- and 24-month follow-ups for both groups. The social disability domain showed a statistically significant improvement for group A at 6 and 24 months postplacement (P = .004, .005). Within group A, there was a statistically significant improvement within all seven domains (P = .001); while in group B, four domains (functional limitation, physical pain, psychosocial discomfort, and physical disability) and the total score (P = .001) showed a statistically significant improvement.

CONCLUSION: Both attachments improved the patients’ quality of life at 24 months postplacement. The ball attachment demonstrated a significant improvement regarding the social effects of the prostheses.

PMID:35696234 | DOI:10.11607/ijp.7942

Am J Hematol. 2022 Jun 13. doi: 10.1002/ajh.26627. Online ahead of print.

ABSTRACT

The best stem cell source for T-cell replete HLA-haploidentical transplantation with post-transplant cyclophosphamide (PTCy) remains to be determined. In this EBMT retrospective study we analyzed the impact of stem cell source on leukemia-free survival (LFS) in adult patients with primary refractory or relapsed acute myeloid leukemia (AML) given grafts from HLA-haploidentical donors with PTCy as graft-versus-host disease (GVHD) prophylaxis. A total of 668 patients (249 bone marrow (BM) and 419 peripheral blood stem cells (PBSC) recipients) met the inclusion criteria. The use of PBSC was associated with a higher incidence of grade II-IV (HR = 1.59, P = 0.029) and grade III-IV (HR = 2.08, P = 0.013) acute GVHD. There was a statistical interaction between patient age and the impact of stem cell source for LFS (P < 0.01). In multivariate Cox models, among patients <55 years, the use of PBSC versus BM resulted in comparable LFS (HR = 0.82, P = 0.2). In contrast, in patients ≥55 years of age, the use of PBSC versus BM was associated with higher non-relapse mortality (NRM) (HR = 1.7, P = 0.01), lower LFS (HR = 1.37, P = 0.026) and lower overall survival (OS) (HR = 1.33, P = 0.044). In conclusions, our data suggest that in patients ≥55 years of age with active AML at HLA-haploidentical transplantation, the use of BM instead of PBSC as stem cell source results in lower NRM and better LFS. In contrast among younger patients, the use of PBSC results in at least a comparable LFS. This article is protected by copyright. All rights reserved.

PMID:35696192 | DOI:10.1002/ajh.26627

J Exp Psychol Gen. 2022 Jun 13. doi: 10.1037/xge0001245. Online ahead of print.

ABSTRACT

Human language is unique among animal communication systems, in part because of its dual patterning in which meaningless phonological units combine to form meaningful words (phonological structure) and words combine to form sentences (lexicosyntactic structure). Although dual patterning is well recognized, its emergence in language development has been scarcely investigated. Chief among questions still unanswered is the extent to which development of these separate structures is independent or interdependent, and what supports acquisition of each level of structure. We explored these questions by examining growth of lexicosyntactic and phonological structure in children with normal hearing (n = 49) and children with hearing loss who use cochlear implants (n = 56). Multiple measures of each kind of structure were collected at 2-year intervals (kindergarten through eighth grade), and used to construct latent scores for each type of structure. Growth curve analysis assessed (a) the relative independence of development for each level of structure; (b) interactions between these two levels of structure in real-time language processing; and (c) contributions to growth of each level of structure made by auditory input, socioeconomic status (as proxy for linguistic experience), and speech motor control. Findings suggested that phonological and lexicosyntactic structure develop largely independently. Auditory input, socioeconomic status, and speech motor control help shape these language structures, with the last two factors exerting stronger effects for children with cochlear implants. Only for children with cochlear implants were interdependencies in real-time processing observed, reflecting compensatory mechanisms likely present to help them handle the disproportionately large phonological deficit they exhibit. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35696175 | DOI:10.1037/xge0001245

JAMA Netw Open. 2022 Jun 1;5(6):e2216778. doi: 10.1001/jamanetworkopen.2022.16778.

ABSTRACT

IMPORTANCE: Assessment of the quality of initial care is necessary to target priority actions that can reduce the still high morbidity and mortality due to community-onset severe bacterial infections (COSBIs) among children.

OBJECTIVE: To study the prevalence, characteristics, and determinants of suboptimal care in the initial management of COSBIs.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, population-based, cohort study and confidential enquiry was conducted between August 2009 and January 2014 in western France, a region accounting for 15% of the French pediatric population (1 968 474 children aged 1 month to 16 years) and including 6 pediatric intensive care units (PICUs) and 35 emergency departments. Participants included all children aged 1 month to 16 years who died before PICU admission or were admitted to a PICU with a COSBI (ie, bacterial sepsis, including meningitis, purpura fulminans, and pulmonary, osteoarticular, intra-abdominal, cardiac, and soft-tissue severe infections). Data were analyzed from March to June 2020.

EXPOSURES: Suboptimal care determined according to evaluation of 8 types of care: (1) the delay in seeking care by family, (2) the physician’s evaluation of severity, (3) the patient’s referral at the first consultation with signs of severity, (4) the timing and (5) dosage of antibiotic treatment, (6) the timing and (7) volume of fluid bolus administration, and (8) the clinical reassessment after fluid bolus.

MAIN OUTCOMES AND MEASURES: Two experts assessed the quality of care before death or PICU admission as optimal, possibly suboptimal, or certainly suboptimal. The consequences and determinants of certainly suboptimal care were identified with multinomial logistic regression and generalized linear mixed models.

RESULTS: Of the 259 children included (median [IQR] age, 24 [6-66] months; 143 boys [55.2%]), 27 (10.4%) died, and 25 (9.6%) had severe sequelae at PICU discharge. The quality of care was certainly suboptimal in 89 cases (34.4%). Suboptimal care was more frequent in children with sequelae (adjusted odds ratio [aOR], 5.61; 95% CI, 1.19-26.36) and less frequent in children who died (aOR, 0.16; 95% CI, 0.04-0.65) vs those surviving without sequelae. Factors independently associated with suboptimal care were age younger than 5 years (aOR, 3.15; 95% CI, 1.25-7.90), diagnosis of sepsis with no source (aOR, 5.77; 95% CI, 1.64-20.30) or meningitis (aOR, 3.39; 95% CI, 1.15-9.96) vs other severe infections, and care by a primary care physician (aOR, 3.22; 95% CI, 1.17-8.88) vs a pediatric hospital service.

CONCLUSIONS AND RELEVANCE: This study found that suboptimal care is frequent in the initial management of COSBI and is associated with severe sequelae. The paradoxical association with reduced risk of death may be explained by an insufficient adjustment on bacterial or host intrinsic factors. Management could be optimized by improving the quality of primary care, especially for young children.

PMID:35696162 | DOI:10.1001/jamanetworkopen.2022.16778

JAMA Intern Med. 2022 Jun 13. doi: 10.1001/jamainternmed.2022.2115. Online ahead of print.

ABSTRACT

IMPORTANCE: Prior evidence suggests that plasma and platelet transfusions from female and parous donors are associated with adverse clinical outcomes, which has led to the predominant use of male donors for plasma and platelets in many countries. However, studies on red blood cell transfusions have been conflicting.

OBJECTIVE: To determine whether blood donor sex and parity affect mortality of patients undergoing transfusion with red blood cells.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used nationwide blood bank and health register data in Sweden and involved a natural experiment created by donor sex and parity being concealed and randomly allocated. Patients were included if they were 18 to 90 years old, did not have a history of blood transfusion, and received a transfusion between January 1, 2010, and December 31, 2017. Patients were followed up from their first red blood cell transfusion until death, emigration, or end of study (June 30, 2018). Data analysis was performed between June 15 and December 15, 2021.

EXPOSURES: (1) Female vs male donors and (2) parous or nonparous female vs male donors.

MAIN OUTCOMES AND MEASURES: Overall survival up to 2 years estimated using inverse probability-weighted Kaplan-Meier estimates and relative risk for additional transfusions within 24 hours.

RESULTS: Among the 368 778 included patients (mean [SD] age, 66.3 [17.7] years; 57.3% female), 2-year survival differences comparing red blood cell transfusions from female and parous donors to male donors were -0.1% (95% CI, -1.3% to 1.1%) and 0.3% (95% CI, -0.6% to 1.2%), respectively. No statistically significant survival differences were observed regardless of patient sex or age. Median (IQR) hemoglobin counts for female donors (13.5 [13.0-14.0] g/dL) were lower than for male donors (14.9 [14.4-15.5] g/dL). Red blood cell transfusions from female donors were associated with a relative risk of 1.12 (95% CI, 1.08-1.17) for additional transfusions within 24 hours but not after adjusting for donor hemoglobin counts (relative risk, 1.03; 95% CI, 0.98-1.08). Pretransfusion patient characteristics were naturally distributed as-if randomized.

CONCLUSIONS AND RELEVANCE: In this nationwide cohort study involving a natural experiment, after accounting for the lower hemoglobin values in blood from female donors, patients undergoing transfusion with blood from female or parous donors did not have higher 2-year mortality compared with recipients of blood from male donors.

PMID:35696128 | DOI:10.1001/jamainternmed.2022.2115

Transl Vis Sci Technol. 2022 Jun 1;11(6):12. doi: 10.1167/tvst.11.6.12.

ABSTRACT

PURPOSE: To report the long-term observations of the electrode-tissue interface and perceptual stability in humans after chronic stimulation with a 44-channel suprachoroidal retinal implant.

METHODS: Four subjects (S1-4) with end-stage retinitis pigmentosa received the implant unilaterally (NCT03406416). Electrode impedances, electrode-retina distance (measured using optical coherence tomography imaging), and perceptual thresholds were monitored up to 181 weeks after implantation as the subjects used the prosthesis in the laboratory and in daily life. Stimulation charge density was limited to 32 µC/cm2 per phase.

RESULTS: Electrode impedances were stable longitudinally. The electrode-retina distances increased after surgery and then stabilized, and were well-described by an asymptotic exponential model. The stabilization of electrode-retina distances was variable between subjects, stabilizing after 45 weeks for S1, 63 weeks for S2, and 24 weeks for S3 (linear regression; Pgradient > 0.05). For S4, a statistically significant increase in electrode-retina distance persisted (P < 0.05), but by the study end point the rate of increase was clinically insignificant (exponential model: 0.33 µm/wk). Perceptual electrical thresholds were stable in one subject, decreased over time in two subjects (linear model; P < 0.05), and increased slightly in one subject but remained within the predefined charge limits (P = 0.02).

CONCLUSIONS: Chronic stimulation with the suprachoroidal retinal prosthesis over 3 years resulted in stable impedances, small individual changes in perceptual electrical thresholds, and no clinically significant increase in electrode-retina distances after a period of settling after surgery.

TRANSLATIONAL RELEVANCE: Chronic stimulation with the 44-channel suprachoroidal retinal implant with a charge density of up to 32 µC/cm2 per phase is suitable for long-term use in humans.

PMID:35696133 | DOI:10.1167/tvst.11.6.12

Trans R Soc Trop Med Hyg. 2022 Jun 13:trac053. doi: 10.1093/trstmh/trac053. Online ahead of print.

ABSTRACT

Previous epidemiologic evidence suggests a protective effect of Toxoplasma gondii infection against multiple sclerosis (MS) development; however, inconsistent findings have been reported in this regard. Therefore, we performed an updated meta-analysis of observational studies to investigate the association of To. gondii infection with MS development. We searched all articles published in PubMed, Scopus, Embase and Web of Science databases as of 20 December 2021. A random effects meta-analysis model was used to generate the pooled OR at 95% CIs. The heterogeneity between studies was assessed using I2 and Cochran’s Q statistics. Moreover, the likelihood of publication bias was determined by Egger’s regression test. A total of 11 studies were eligible for meta-analysis, including 1172 MS cases and 1802 controls. Our findings indicated that 29.8% (95% CI 22.8 to 37.2%) of MS patients were seropositive for To. gondii infection, compared with 34.2% (95% CI 21.9 to 47.6%) of control subjects. The estimated pooled OR was 0.79 (95% CI 0.49 to 1.26), suggesting a non-significant negative association between To. gondii infection and MS development (p>0.05). The current study does not support the significant protective role of To. gondii infection on MS development. Our findings imply that further well-designed epidemiological and mechanistic studies are warranted to ascertain the possible association between To. gondii infection and MS and to exclude the potential confounders.

PMID:35696089 | DOI:10.1093/trstmh/trac053

Pharmacoeconomics. 2022 Jun 13. doi: 10.1007/s40273-022-01155-5. Online ahead of print.

ABSTRACT

This technical note discusses how dummy and effects coding of categorical respondent characteristics in a class membership probability function should be interpreted by researchers employing a latent class analysis to explore preference heterogeneity in a discrete-choice experiment. Previous work highlighted issues arising from such coding when interpreting an alternative specific constant that represents an opt-out alternative or current situation in a discrete-choice experiment and did not fully address how this coding impacts the interpretation of parameters resulting from the membership probability function in a latent class analysis. Although latent class membership probability could be predicted separately for each respondent or subgroup of respondents, conclusions are often drawn directly from the model estimation using the full sample, which requires correctly interpreting the estimated parameters. In these cases, the misinterpretation that may arise if the problem is ignored could impact the policy conclusions and recommendations drawn based on the discrete-choice experiment results. This note provides an example comparing dummy and effects coding used to model respondent characteristics in the membership probability function in a discrete-choice experiment aimed to explore preferences for the treatment of chronic pain in the USA.

PMID:35696072 | DOI:10.1007/s40273-022-01155-5

Infection. 2022 Jun 13. doi: 10.1007/s15010-022-01859-y. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the severity of symptoms, duration of infection and viral loads of health-care workers (HCWs) who tested positive for Coronavirus disease 2019 (COVID-19) during Omicron’s prevalence, in regard to vaccination and previous infection.

METHODS: During 2 weeks of highest rate of COVID-19 cases in Bosnia and Herzegovina, the positive nasopharyngeal swabs were analysed in 141 HCWs by reverse transcription quantitative PCR, targeting four different genes: RdRp, E, N and nsp14. Uniformed questionnaire was used to collect relevant sociodemographic and epidemiological data from HCWs divided into four groups: unvaccinated/not previously infected (group 1); unvaccinated/previously infected (group 2); vaccinated/not previously infected (group 3); and vaccinated/previously infected (group 4).

RESULTS: We observed that occurrence of fever and smell or taste loss were more frequent in group 1 (86.4% and 25%) and group 3 (76.9% and 19.2%), in comparison to group 2 (64.4% and 6.7%) and group 4 (69.2% and 3.8%), (p = 0.023 and p = 0.003). Although statistically not significant, group 2 (61.9%), group 3 (65.4%), and group 4 (70.8%) experienced negativization within 7 days of positive RT-qPCR test, whereas 51.2% of HCWs from group 1 tested negative later on. There is no significant difference between all four groups regarding Ct values of analysed genes.

CONCLUSION: During Omicron’s prevalence, the vaccination had less substantial effect on symptomatic disease among HCWs, while fever and loss of smell or taste were considerably less likely to occur upon reinfection. Since viral loads and negativization periods do not seem to significantly vary, irrespective of pre-existing immunity, systemic vaccination and mask-wearing should still be considered among HCWs.

PMID:35696057 | DOI:10.1007/s15010-022-01859-y