Tag: pubmed

BMC Pediatr. 2022 Jun 11;22(1):340. doi: 10.1186/s12887-022-03400-4.

ABSTRACT

BACKGROUND: We investigated risk factors for sustained virological non-suppression (viral load ≥ 1000 copies/ml on two tests 48 weeks apart) among children and adolescents accessing HIV care in public sector clinics in Harare, Zimbabwe and Blantyre, Malawi.

METHODS: Participants were enrolled between 2016 and 2019, were aged 6-19 years, living with HIV, had chronic lung disease (FEV z-score < -1) and had taken antiretroviral therapy (ART) for at least six months. We used multivariate logistic regression to identify risk factors for virological non-suppression after 48 weeks, among participants who were non-suppressed at enrolment.

RESULTS: At enrolment 258 participants (64.6%) were on first-line ART and 152/347 (43.8%) had virological non-suppression. After 48 weeks 114/313 (36.4%) were non-suppressed. Participants non-suppressed at baseline had almost ten times higher odds of non-suppression at follow-up (OR = 9.9, 95%CI 5.3-18.4, p < 0.001). Of those who were non-suppressed at enrolment, 87/136 (64.0%) were still non-suppressed at 48 weeks. Among this group non-suppression at 48 weeks was associated with not switching ART regimen (adjusted OR = 5.55; 95%CI 1.41-21.83); p = 0.014) and with older age. Twelve participants switched regimen in Zimbabwe and none in Malawi.

CONCLUSIONS: Viral non-suppression was high among this group and many with high viral load were not switched to a new regimen, resulting in continued non-suppression after 48 weeks. Further research could determine whether improved adherence counselling and training clinicians on regimen switches can improve viral suppression rates in this population.

TRIAL REGISTRATION: Secondary cohort analysis of data from BREATHE trial (Clinicaltrials.gov NCT02426112 ).

PMID:35690762 | DOI:10.1186/s12887-022-03400-4

BMC Musculoskelet Disord. 2022 Jun 11;23(1):566. doi: 10.1186/s12891-022-05520-5.

ABSTRACT

BACKGROUND: Rheumatic and musculoskeletal diseases (RMD) are associated with depression, fatigue, and disturbed sleep – symptoms that often impact behavior and activity. Patient reported outcomes (PROs) are a way of collecting information on the patient symptom experience directly from the individual. The purpose of this study was to measure and compare user smartphone sensor and activity data in adults with RMDs and assess associations with PROs.

METHODS: We invited adults with RMDs enrolled in the FORWARD Databank to participate by installing a custom app on their smartphone and answering PROs (pain, global, HAQ-II) questions daily and weekly over 3 years. Passive data collected included mobility distance, unique calls and text messages, call durations, and number of missed calls. Confounders included sociodemographic, clinical, passive phone behavior, and seasonal factors. Kappa statistics between PRO and flares were computed to measure agreement. The agreement between daily and weekly VAS pain was estimated using the intraclass (ICC) correlation of a two-way random effect model. The relationship between the weekly PRO outcomes and the passive phone data was analyzed with a linear mixed-effect model (LMM), including a random intercept for participant and slope for time in the study with an unstructured covariate structure.

RESULTS: Of the 446 participants, the mean (SD) age was 54 (12) years, most (65.5%) had rheumatoid arthritis (RA), the vast majority (91%) were female, and the US Northeast has the least representation (12%). Longer reaction times, interaction diversity, and higher mobility were associated with worse PROs while longer text messages were associated with better PROs. Participants in this study showed good levels of adherence which holds promise for future interventions using passive behavior measures in self-management and clinical follow-up.

CONCLUSION: This is the first study to examine passive smartphone behavior with PROs in RMDs and we found significant associations between these behaviors and important health outcomes of pain and function. As smartphone usage continues to change, future studies should validate and expand on our findings with a goal of finding changes in patient symptoms passively through mobile device monitoring.

PMID:35690753 | DOI:10.1186/s12891-022-05520-5

BMC Ophthalmol. 2022 Jun 11;22(1):262. doi: 10.1186/s12886-022-02480-1.

ABSTRACT

BACKGROUND: To evaluate changes in corneal biomechanical properties after long-term orthokeratology (OK) treatment and the factors affecting treatment outcomes.

METHODS: Twenty-four myopic teenagers who wore OK lenses for more than 1 year were included. Twenty-three individuals of the same age and with the same spherical equivalent wearing single-vision spectacles (SVS) were enrolled as controls. After routine eye examinations, corneal biomechanical properties and axial length were measured. Parameters were compared between groups.

RESULTS: Less axial elongation (AE) occurred in the OK group (P = 0.021). The OK group experienced a statistically significant decrease in the A1 deformation amplitude (P = 0.02), whole eye movement maximum (P = 0.026), and Ambrósio’s relational thickness to the horizontal profile (ARTh) (P < 0.001), and a statistically significant increase in the pachyslope (P < 0.001) and Corvis biomechanical index (P < 0.001). Smaller ARTh and a larger highest concavity deflection area resulted in a better refractive state. The inhibitory effect of AE was better for older patients with smaller ARTh.

CONCLUSIONS: Long-term OK treatment slowed myopia progression by reshaping the cornea. Smaller ARTh after OK lens wear indicated a better refractive state and slower AE and could predict OK lens treatment outcomes.

PMID:35690754 | DOI:10.1186/s12886-022-02480-1

BMC Neurol. 2022 Jun 11;22(1):216. doi: 10.1186/s12883-022-02730-1.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array (n = 15 participants per group (ALS or control)) and proteome profiling (n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjusted P values). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen’s d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100β, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.

PMID:35690735 | DOI:10.1186/s12883-022-02730-1

Genet Sel Evol. 2022 Jun 11;54(1):43. doi: 10.1186/s12711-022-00735-5.

ABSTRACT

BACKGROUND: If not accounted for, genotype x environment (G×E) interactions can decrease the accuracy of genetic evaluations and the efficiency of breeding schemes. These interactions are reflected by genetic correlations between countries lower than 1. In countries that are characterized by a heterogeneity of production systems, they are also likely to exist within country, especially when production systems are diverse, as is the case in South Africa. We illustrate several alternative approaches to assess the existence of G×E interactions for production traits and age at first calving in Holsteins in South Africa. Data from 257,836 first lactation cows were used. First, phenotypes that were collected in different regions were considered as separate traits and various multivariate animal models were fitted to calculate the estimates of heritability for each region and the genetic correlations between them. Second, a random regression approach using long-term averages of climatic variables at the herd level in a reaction norm model, was used as an alternative way to account for G×E interactions. Genetic parameter estimates and goodness-of-fit measures were compared.

RESULTS: Genetic correlations between regions as low as 0.80 or even lower were found for production traits, which reflect strong G×E interactions within South Africa that can be linked to the production systems (pasture vs total mixed ration). A random regression model including average rainfall during several decades in the herd surroundings gave the best goodness-of-fit for production traits. This can be related to a preference for total mixed ration on farms with limited rainfall. For age at first calving, the best model was based on a random regression on maximum relative humidity and maximum temperature in summer.

CONCLUSIONS: Our results indicate that G×E interactions can be accounted for when genetic evaluations of production traits are performed in South Africa, by either considering production records in different regions as different correlated traits or using a reaction norm model based on herd management characteristics. From a statistical point of view, climatic variables such as average rainfall over a long period can be included in a random regression model as proxies of herd production systems and climate.

PMID:35690732 | DOI:10.1186/s12711-022-00735-5

Clin Proteomics. 2022 Jun 11;19(1):21. doi: 10.1186/s12014-022-09358-w.

ABSTRACT

BACKGROUND: Roxadustat is a new oral anti-renal anemia medication that works by stabilizing hypoxia-inducible factor (HIF) which can activate the expression of more than 100 genes in addition to genes related to anemia. However, the more potential molecular targets of roxadustat are not completely clear. Therefore, it is essential to further reveal its molecular targets to guide its clinical applications.

METHODS: We performed label-free quantification and LC-MS/MS to study the proteomic alterations in serum exosome of renal anemia patients before and after roxadustat therapy. Results were validated by PRM.

RESULTS: A total of 30 proteins were significantly changed after treatment with roxadustat. Among these proteins, 18 proteins were up-regulated (and 12 were down-regulated). The results are statistically significant (P < 0.05). Then, we validated the result by PRM, the results confirmed that TFRC, HSPA8, ITGB3, COL1A2, and YWHAZ were markedly upregulated, while ITIH2 and CFH were significantly downregulated upon treatment with roxadustat.

CONCLUSIONS: TFRC and HSPA8 could be an important target of the action of roxadustat, and roxadustat may increase cardiovascular risk through its influence on platelet activation. Our results provide a theoretical basis for its wider clinical application and preventing expected side effects.

PMID:35690731 | DOI:10.1186/s12014-022-09358-w

BMC Emerg Med. 2022 Jun 11;22(1):105. doi: 10.1186/s12873-022-00654-0.

ABSTRACT

BACKGROUND: With more emergency visits, there is increasing pressure to provide emergency medical services globally and locally. This study aimed to investigate the epidemiological characteristics and the disease spectrum of patients presenting in the last three years to the Department of Emergency Medicine of Tianjin Medical University General Hospital, a tertiary hospital in Tianjin, China, to improve the services of the emergency medicine department.

METHODS: A retrospective study was conducted on all patients in the Department of Emergency Medicine of Tianjin Medical University General Hospital from Jan 1, 2017, 00:00:00 to Dec 31, 2020, 23:59:59, including variables like medical record number, gender, age, date of admission, principal diagnosis. The data were analyzed by SPSS statistical software; statistical charts were prepared by GraphPad Prism9.0 and SPSS 20.0; statistical tables were made by Microsoft Excel.

RESULTS: A total of 1,314,916 patients presented to the Department of Emergency Medicine of Tianjin Medical University General Hospital from Jan 1, 2017, 00:00:00 to Dec 31, 2020, 23:59:59. In terms of gender distribution, the male-female ratio was 0.78∶1. As for age distribution, patients aged 60-69 were the most (23.47%), and patients younger than 20 years were the least (2.80%). Concerning monthly data, the number of visits peaked during January and December. The distribution of daily visits showed the feature of three highs and a low. The top three prevalence diseases in the emergency disease spectrum were respiratory, cardiovascular, and digestive diseases. The respiratory system was the most common in patients with infectious diseases (200,912, accounting for 86.97%). Among the patients suffering from infectious diseases, the number of patients with respiratory infections peaked in 2019 (73,530) and was the lowest in 2020 (20,078).

CONCLUSIONS: From 2017 to 2019, the demand for emergency services in Tianjin Medical University General Hospital continued to increase, but it was greatly affected by COVID-19 in 2020. This emergency department is mainly for patients with respiratory system, circulatory system and digestive system diseases, and its treatment time is relatively centralized. The prevention of diseases for people of all ages, especially female patients and the elderly, should be strengthened, and emergency medical resources should be allocated reasonably according to the peak months and crowed periods of patients.

PMID:35690727 | DOI:10.1186/s12873-022-00654-0

BMC Cardiovasc Disord. 2022 Jun 11;22(1):263. doi: 10.1186/s12872-022-02705-7.

ABSTRACT

OBJECTIVES: Metabolic syndrome (MetS) increases the risk of new diabetes and cardiovascular disease. Night shift work (NSW) may influence metabolic disturbance and lead to MetS. This study aims to investigate the association between long-term NSW (≥ 10 years) and MetS combined with its components in male railway workers in southwest China.

METHODS: 11,023 male railway workers with long-term NSW of more than 10 years in the Physical Examination Center of the Affiliated Hospital of Chengdu University were enrolled. The basic data were collected by investigators and blood test results were collected. The primary outcome was the prevalence of metabolic syndrome. The results were analyzed using statistical software SPSS 22.0.

RESULTS: In total, 11,023 people over the age of 40 with more than 10 years of working experience were enrolled, and 4759 (43.2%) participants had a diagnosis of MetS. The basic data indicated that night shift workers tended to be younger, shorter working years, but with higher body mass index and longer hip circumference (p < 0.05). The adjusted analysis revealed that there was no significant association between NSW and metabolic syndrome (OR 1.03, 95% CI 0.94-1.12, p = 0.543). NSW was associated with SBP ≥ 130 mmHg (OR 1.11, 95% CI 1.02-1.21, p < 0.001) and waist circumference ≥ 90 cm (OR 1.11, 95% CI 1.02-1.21, p < 0.001).

CONCLUSIONS: Long-term night shift workers had a higher prevalence of MetS. However, long-term NSW is not associated with a significantly increased risk of metabolic syndrome in male railway workers in southwest China. Long-term NSW is associated with elevated SBP, and waist circumference increase.

PMID:35690716 | DOI:10.1186/s12872-022-02705-7

J Neurodev Disord. 2022 Jun 11;14(1):37. doi: 10.1186/s11689-022-09447-9.

ABSTRACT

BACKGROUND: In over half of pediatric cases, ADHD presents with comorbidities, and often, it is unclear whether the symptoms causing impairment are due to the comorbidity or the underlying ADHD. Comorbid conditions increase the likelihood for a more severe and persistent course and complicate treatment decisions. Therefore, it is highly important to establish an algorithm that identifies ADHD and comorbidities in order to improve research on ADHD using biorepository and other electronic record data.

METHODS: It is feasible to accurately distinguish between ADHD in isolation from ADHD with comorbidities using an electronic algorithm designed to include other psychiatric disorders. We sought to develop an EHR phenotype algorithm to discriminate cases with ADHD in isolation from cases with ADHD with comorbidities more effectively for efficient future searches in large biorepositories. We developed a multi-source algorithm allowing for a more complete view of the patient’s EHR, leveraging the biobank of the Center for Applied Genomics (CAG) at Children’s Hospital of Philadelphia (CHOP). We mined EHRs from 2009 to 2016 using International Statistical Classification of Diseases and Related Health Problems (ICD) codes, medication history and keywords specific to ADHD, and comorbid psychiatric disorders to facilitate genotype-phenotype correlation efforts. Chart abstractions and behavioral surveys added evidence in support of the psychiatric diagnoses. Most notably, the algorithm did not exclude other psychiatric disorders, as is the case in many previous algorithms. Controls lacked psychiatric and other neurological disorders. Participants enrolled in various CAG studies at CHOP and completed a broad informed consent, including consent for prospective analyses of EHRs. We created and validated an EHR-based algorithm to classify ADHD and comorbid psychiatric status in a pediatric healthcare network to be used in future genetic analyses and discovery-based studies.

RESULTS: In this retrospective case-control study that included data from 51,293 subjects, 5840 ADHD cases were discovered of which 46.1% had ADHD alone and 53.9% had ADHD with psychiatric comorbidities. Our primary study outcome was to examine whether the algorithm could identify and distinguish ADHD exclusive cases from ADHD comorbid cases. The results indicate ICD codes coupled with medication searches revealed the most cases. We discovered ADHD-related keywords did not increase yield. However, we found including ADHD-specific medications increased our number of cases by 21%. Positive predictive values (PPVs) were 95% for ADHD cases and 93% for controls.

CONCLUSION: We established a new algorithm and demonstrated the feasibility of the electronic algorithm approach to accurately diagnose ADHD and comorbid conditions, verifying the efficiency of our large biorepository for further genetic discovery-based analyses.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02286817 . First posted on 10 November 2014.

CLINICALTRIALS: gov, NCT02777931 . First posted on 19 May 2016.

CLINICALTRIALS: gov, NCT03006367 . First posted on 30 December 2016.

CLINICALTRIALS: gov, NCT02895906 . First posted on 12 September 2016.

PMID:35690720 | DOI:10.1186/s11689-022-09447-9

BMC Cardiovasc Disord. 2022 Jun 11;22(1):262. doi: 10.1186/s12872-022-02702-w.

ABSTRACT

BACKGROUND: Previous studies have observed inconsistent associations between coronavirus disease 2019 (COVID-19) and heart failure (HF), but these studies were prone to bias based on reverse causality and residual confounding factors. We aimed to investigate genetic liability between COVID-19 and heart failure using a bidirectional Mendelian randomization study.

METHODS: The causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and HF are determined by using a bidirectional Mendelian randomization analysis. We drew on summary statistics from the largest HF genome-wide association study (GWAS) meta-analysis on individuals of European ancestry, which included 47,309 HF patients and 930,014 controls. The inverse variance weighted (IVW), an adaption of the Egger regression (MR-Egger), the weighted median, and weighted model were conducted for the Mendelian randomization analysis to estimate a causal effect. To confirm the stability, we performed a “leave-one-out” approach for the sensitivity analysis.

RESULTS: Genetically predicted severe COVID-19 was not significantly associated with the risk of HF [odds ratio (OR), 1.003; 95% confidence interval (CI), 0.969-1.037; p = 0.867]. The IVW demonstrated that there was no association between genetically hospitalized COVID-19 infection and HF risk [OR, 1.009; 95% CI, 0.939-1.085; p = 0.797]. There was no evidence to support the association between genetically determined COVID-19 and the risk of HF [OR, 1.066; 95% CI, 0.955-1.190; p = 0.253]. In addition, genetically predicted HF was also not causally associated with COVID-19 [OR, 1.162; 95% CI, 0.824-1.639; p = 0.393]. MR-Egger analysis indicated no evidence of directional pleiotropy.

CONCLUSION: The current bidirectional Mendelian randomization analysis overcomes the limitations of observational studies. Our findings indicated that there is no causal association between COVID-19 and HF.

PMID:35690714 | DOI:10.1186/s12872-022-02702-w