Tag: pubmed

Diabetologia. 2021 Dec 24. doi: 10.1007/s00125-021-05635-9. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Type 2 diabetes is a growing global public health challenge. Investigating quantitative traits, including fasting glucose, fasting insulin and HbA_1c, that serve as early markers of type 2 diabetes progression may lead to a deeper understanding of the genetic aetiology of type 2 diabetes development. Previous genome-wide association studies (GWAS) have identified over 500 loci associated with type 2 diabetes, glycaemic traits and insulin-related traits. However, most of these findings were based only on populations of European ancestry. To address this research gap, we examined the genetic basis of fasting glucose, fasting insulin and HbA_1c in participants of the diverse Population Architecture using Genomics and Epidemiology (PAGE) Study.

METHODS: We conducted a GWAS of fasting glucose (n = 52,267), fasting insulin (n = 48,395) and HbA_1c (n = 23,357) in participants without diabetes from the diverse PAGE Study (23% self-reported African American, 46% Hispanic/Latino, 40% European, 4% Asian, 3% Native Hawaiian, 0.8% Native American), performing transethnic and population-specific GWAS meta-analyses, followed by fine-mapping to identify and characterise novel loci and independent secondary signals in known loci.

RESULTS: Four novel associations were identified (p < 5 × 10^-9), including three loci associated with fasting insulin, and a novel, low-frequency African American-specific locus associated with fasting glucose. Additionally, seven secondary signals were identified, including novel independent secondary signals for fasting glucose at the known GCK locus and for fasting insulin at the known PPP1R3B locus in transethnic meta-analysis.

CONCLUSIONS/INTERPRETATION: Our findings provide new insights into the genetic architecture of glycaemic traits and highlight the continued importance of conducting genetic studies in diverse populations.

DATA AVAILABILITY: Full summary statistics from each of the population-specific and transethnic results are available at NHGRI-EBI GWAS catalog ( https://www.ebi.ac.uk/gwas/downloads/summary-statistics ).

PMID:34951656 | DOI:10.1007/s00125-021-05635-9

Soc Psychiatry Psychiatr Epidemiol. 2021 Dec 24. doi: 10.1007/s00127-021-02215-5. Online ahead of print.

ABSTRACT

PURPOSE: It is unclear how hospitals are responding to the mental health needs of the population in England, against a backdrop of diminishing resources. We aimed to document patterns in hospital activity by psychiatric disorder and how these have changed over the last 22 years.

METHODS: In this observational time series analysis, we used routinely collected data on all NHS hospitals in England from 1998/99 to 2019/20. Trends in hospital admissions and bed days for psychiatric disorders were smoothed using negative binomial regression models with year as the exposure and rates (per 1000 person-years) as the outcome. When linear trends were not appropriate, we fitted segmented negative binomial regression models with one change-point. We stratified by gender and age group [children (0-14 years); adults (15 years +)].

RESULTS: Hospital admission rates and bed days for all psychiatric disorders decreased by 28.4 and 38.3%, respectively. Trends were not uniform across psychiatric disorders or age groups. Admission rates mainly decreased over time, except for anxiety and eating disorders which doubled over the 22-year period, significantly increasing by 2.9% (AAPC = 2.88; 95% CI: 2.61-3.16; p < 0.001) and 3.4% (AAPC = 3.44; 95% CI: 3.04-3.85; p < 0.001) each year. Inpatient hospital activity among children showed more increasing and pronounced trends than adults, including an increase of 212.9% for depression, despite a 63.8% reduction for adults with depression during the same period.

CONCLUSION: In the last 22 years, there have been overall reductions in hospital activity for psychiatric disorders. However, some disorders showed pronounced increases, pointing to areas of growing need for inpatient psychiatric care, especially among children.

PMID:34951652 | DOI:10.1007/s00127-021-02215-5

Eur J Trauma Emerg Surg. 2021 Dec 24. doi: 10.1007/s00068-021-01857-z. Online ahead of print.

ABSTRACT

INTRODUCTION: In spiral fractures of the tibia, the stability of an osteosynthesis may be significantly increased by additive cerclages and, according to biomechanical studies, be brought into a state that allows immediate full weight bearing. As early as 1933, Goetze described a minimally invasive technique for classic steel cerclages. This technique was modified, so that it can be used for modern cable cerclages in a soft part saving way.

METHOD: After closed reduction, an 8 Fr redon drain is first inserted in a minimally invasive manner, strictly along the bone and placed around the tibia via 1 cm incisions on the anterolateral and dorsomedial tibial edges using a curette and a tissue protection sleeve. Via this drain, a 1.7 mm cable cerclage can be inserted. The fracture is then anatomically reduced while simultaneously tightening the cerclage. Subsequently, a nail or a minimally invasive plate osteosynthesis is executed using the standard technique. Using the hospital documentation system, data of patients that were treated with additional cerclages for tibial fractures between 01/01/2014 and 06/30/2020 were subjected to a retrospective analysis for postoperative complications (wound-healing problems, infections and neurovascular injury). Inclusion criteria were: operatively treated tibial fractures, at least one minimally invasive additive cerclage, and age of 18 years or older. Exclusion criteria were: periprosthetic or pathological fractures and the primary need of reconstructive plastic surgery. SPSS was used for statistical analysis.

RESULTS: 96 tibial shaft spiral fractures were treated with a total of 113 additive cerclages. The foregoing resulted in 10 (10.4%) postoperative wound infections, 7 of which did not involve the cerclage. One lesion of the profundal peroneal nerve was detected, which largely declined after cerclage removal. In 3 cases, local irritation from the cerclage occurred and required removal of material.

CONCLUSION: In the described technique, cerclages may be inserted additively at the tibia in a minimally invasive manner and with a few complications, thus significantly increasing the stability of an osteosynthesis. How this ultimately affects fracture healing is the subject of an ongoing study.

PMID:34951655 | DOI:10.1007/s00068-021-01857-z

Depress Anxiety. 2021 Dec 24. doi: 10.1002/da.23231. Online ahead of print.

ABSTRACT

BACKGROUND: Although cognitive behavioral therapy (CBT) is effective in the treatment of anxiety disorders, few evidence-based alternatives exist. Autonomy enhancing treatment (AET) aims to decrease the vulnerability for anxiety disorders by targeting underlying autonomy deficits and may therefore have similar effects on anxiety as CBT, but yield broader effects.

METHODS: A multicenter cluster-randomized clinical trial was conducted including 129 patients with DSM-5 anxiety disorders, on average 33.66 years of age (SD = 12.57), 91 (70.5%) female, and most (92.2%) born in the Netherlands. Participants were randomized over 15-week groupwise AET or groupwise CBT and completed questionnaires on anxiety, general psychopathology, depression, quality of life, autonomy-connectedness and self-esteem, pre-, mid-, and posttreatment, and after 3, 6, and 12 months (six measurements).

RESULTS: Contrary to the hypotheses, effects on the broader outcome measures did not differ between AET and CBT (d = .16 or smaller at post-test). Anxiety reduction was similar across conditions (d = .059 at post-test) and neither therapy was superior on long term.

CONCLUSION: This was the first clinical randomized trial comparing AET to CBT. The added value of AET does not seem to lie in enhanced effectiveness on broader outcome measures or on long term compared to CBT. However, the study supports the effectiveness of AET and thereby contributes to extended treatment options for anxiety disorders.

PMID:34951503 | DOI:10.1002/da.23231

J Cardiovasc Electrophysiol. 2021 Dec 24. doi: 10.1111/jce.15337. Online ahead of print.

ABSTRACT

BACKGROUND: Early arrhythmia recurrence within the three-month blanking period is a common event that historically has been attributed to reversible phenomena. While its’ mechanistic links remain obscure, accumulating evidence support the argument of shortening the blanking period. We aimed to elucidate the association between early and late arrhythmia recurrence after atrial fibrillation cryoablation.

METHODS: The MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating early and late arrhythmia recurrence rates in patients undergoing cryoablation for AF. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was late arrhythmia recurrence.

RESULTS: Early arrhythmia recurrence was found predictive of decreased arrhythmia-free survival after evaluating 3975 patients with paroxysmal or persistent atrial fibrillation who underwent cryoablation (OR: 5.31; 95% CI: 3.75-7.51). This pattern remained unchanged after sub-analyzing atrial fibrillation type (paroxysmal; OR: 7.16; 95% CI: 4.40-11.65 and persistent; OR: 7.63; 95% CI: 3.62-16.07) as well as cryoablation catheter generation (first generation; OR: 5.15, 95% CI: 2.39-11.11 and advanced generation; OR: 5.83, 95% CI: 3.68-9.23). Studies permitting anti-arrhythmic drug utilization during blanking period or examining early recurrence as a secondary outcome were found to be a significant source of statistical heterogeneity.

CONCLUSION: Our findings suggest that early arrhythmia recurrence is predictive of late outcomes after cryoablation for atrial fibrillation. Identifying which patients deserve earlier re-intervention is an open research avenue. This article is protected by copyright. All rights reserved.

PMID:34951496 | DOI:10.1111/jce.15337

Biometrics. 2021 Dec 24. doi: 10.1111/biom.13615. Online ahead of print.

ABSTRACT

While most statistical methods for the analysis of longitudinal data have focused on retrospective models of association, new advances in mobile health data have presented opportunities for predicting future health status by leveraging an individual’s behavioral history alongside data from similar patients. Methods that incorporate both individual-level and sample-level effects are critical to using this data to its full predictive capacity. Neural networks are powerful tools for prediction, but many assume input observations are independent even when they are clustered or correlated in some way, such as in longitudinal data. Generalized linear mixed models (GLMM) provide a flexible framework for modeling longitudinal data but have poor predictive power particularly when the data is highly nonlinear. We propose a generalized neural network mixed model (GNMM) that replaces the linear fixed effect in a GLMM with the output of a feed-forward neural network. The model simultaneously accounts for the correlation structure and complex nonlinear relationship between input variables and outcomes, and it utilizes the predictive power of neural networks. We apply this approach to predict depression and anxiety levels of schizophrenic patients using longitudinal data collected from passive smartphone sensor data.

PMID:34951484 | DOI:10.1111/biom.13615

Artif Organs. 2021 Dec 24. doi: 10.1111/aor.14141. Online ahead of print.

ABSTRACT

BACKGROUND: M101 is an extracellular hemoglobin isolated from a marine lugworm and is present in the medical device HEMO₂ life®. The clinical investigation OXYOP was a paired kidney analysis (n = 60) designed to evaluate the safety and performance of HEMO₂ life® used as an additive to preservation solution in renal transplantation. The secondary efficacy endpoints showed less delayed graft function (DGF) and better renal function in the HEMO₂ life® group but due to the study design cold ischemia time (CIT) was longer in the contralateral kidneys.

METHODS: An additional analysis was conducted including OXYOP patients and patients from the ASTRE database (n = 6584) to verify that the decrease in DGF rates observed in the HEMO₂ life® group may not be due solely to the shorter CIT but also to HEMO₂ life® performance. Kaplan-Meier estimate curves of cumulative probability of achieving a creatinine level below 250 µmol/L were generated and compared in both groups. A Cox model was used to test the effect of the explanatory variables (use of HEMO₂ life® and CIT). Finally, a bootstrap strategy was used to randomly select smaller samples of patients and test them for statistical comparison in the ASTRE database.

RESULTS: Kaplan-Meier estimate curves confirmed the existence of a relation between DGF and CIT and Cox analysis showed a benefit in the HEMO₂ life® group regardless of the associated CIT. Boostrap analysis confirmed these results.

CONCLUSIONS: The present study suggested that the better recovery of renal function observed among kidneys preserved with HEMO₂ life® in the OXYOP study is a therapeutic benefit of this breakthrough innovative medical device.

PMID:34951495 | DOI:10.1111/aor.14141

J Biomech Eng. 2021 Dec 24. doi: 10.1115/1.4053362. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple biomechanical shoulder simulators have been described in the literature, with a trend toward increasing complexity to better simulate clinical scenarios. Our objective was to develop an advanced, novel shoulder joint simulator and compare outcomes at two separate institutions, for a typical shoulder joint motion simulation.

METHODS: Identical shoulder simulators were developed & deployed at both institutions. Eight cadaveric upper extremities were tested by simulating actively controlled, arm elevation in the plane of the scapula for two sequential test conditions (intact and non-destructive simulated cuff-tear), each repeated for a total of five trials. Muscle forces and joint translations were recorded for both conditions. The intact condition was repeated following simulated cuff-tear to assess effect of testing order. Statistical analyses were aimed at assessing repeatability and reproducibility of results within specimens, between specimens, and between institutions.

RESULTS: The highest average forces were observed for the middle deltoid (233N or 32.5% body weight), followed by infraspinatus (99.0N), and posterior deltoid (93.7N) muscles. Differentiation between test conditions was unhindered by variability between repeated trials. Data from testing repeated over time, and between the two institutions were not significantly different.

CONCLUSIONS: The novel shoulder simulator produced repeatable results with low trial-to-trial variation and outcomes were comparable between the two institutions. The results demonstrated a consistent response in muscle forces and humeral translation for the simulated rotator cuff tear condition. Such advanced shoulder simulators could thus be used for evaluating and optimizing surgical interventions and implant strategies.

PMID:34951458 | DOI:10.1115/1.4053362

Occup Med (Lond). 2021 Dec 24:kqab153. doi: 10.1093/occmed/kqab153. Online ahead of print.

ABSTRACT

BACKGROUND: Research has shown that of the myriad services available to veterans in the UK, very few have been independently evaluated. This report presents the results of a randomized controlled trial assessing the impact of Time Line Therapy™ delivered by the Warrior Programme (a third-sector organization).

AIMS: This study was aimed to determine if the intervention is effective in reducing emotional and functional difficulties in ex-service personnel.

METHODS: A mixed-design analysis of variance model was used to investigate whether the Warrior Programme had a statistically significant impact on self-reported scores. The intervention and control group provided data on measures prior to and immediately after the intervention, and at 3-month follow-up.

RESULTS: Those in the intervention group (n = 23) reported statistically significant improvements in self-reported scores immediately following intervention: the Clinical Outcomes in Routine Evaluation (CORE) scores (CORE global distress mean difference [MD] = 45.0, 95% confidence interval [CI] 31-60) (CORE subjective well-being MD = 5.9, 95% CI 3.5-8.3) (CORE functioning MD = 16.7, 95% CI 11.4-21.9) (CORE problems/symptoms MD = 19.4, 95% CI 13.1-25.7), general self-efficacy (MD = -9.8, 95% CI -13.6 to -6.8), anxiety (MD = 8.6, 95% CI 5.2-12.1), depression (MD = 10, 95% CI 6.6-13.5), post-traumatic stress disorder (MD = 26.3, 95% CI 17-25) and functional impairment (MD = 11.1, 95% CI 5.3-16.8) over time, compared to the control group (n = 29). However, score improvement was not sustained over time or statistically significant at follow-up.

CONCLUSIONS: The Warrior Programme was effective in reducing emotional and functional difficulties in ex-service personnel immediately after the intervention, but the effect was not sustained at 3-month follow-up.

PMID:34951474 | DOI:10.1093/occmed/kqab153

Curr Alzheimer Res. 2021 Dec 22. doi: 10.2174/1567205019666211222151851. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study is to examine the association of olfactory function and genetic predisposition of Alzheimer’s disease (AD) with cognitive performance in adults.

METHODS: A total of 2049 Chinese adults from Rugao Longevity and Ageing Study (RuLAS, n=1460, mean age 78 years) and Central China Cohort (CCC, n=589, mean age 48 years) were included in this study. A standard interview-based survey, clinical information, and blood samples were collected in both cohorts. Olfactory function in terms of olfactory identification was measured by the brief version of the Chinese Smell Identification Test consisted of 18 full points. Cognitive performance was measured by the Chinese version of the Mini-mental State Examination. A genetic risk score (GRS) was calculated from 5 single nucleotide polymorphisms, which were robustly related to Alzheimer’s disease in Caucasians and cognitive performance in our Chinese population.

RESULTS: In the pooled analyses, participants at the lowest quartile of olfactory function had significantly higher odds of cognitive impairment (adjusted odds ratio [95% CI] =1.45 [1.00 to 2.09], Ptrend =0.005), and such association was stronger among participants with a stronger genetic predisposition of Alzheimer’s disease (β coefficient±SE, -0.06±0.03 in participants with a lower GRS vs. -0.19±0.05 in those with a higher GRS, respectively, Pinteraction=0.01). Similar associations were observed in RuLAS (P-trend=0.06) and in CCC (P-trend<0.001).

CONCLUSION: In this study, a decreased olfactory function was associated with worse cognitive performance in adults, especially among participants with a higher genetic risk of Alzheimer’s disease. Further studies are warranted to evaluate the causal relationship between olfaction and cognitive performance.

PMID:34951364 | DOI:10.2174/1567205019666211222151851