Category: Statistics

Arthritis Res Ther. 2021 Sep 7;23(1):235. doi: 10.1186/s13075-021-02608-6.

ABSTRACT

BACKGROUND: Evidence on prognostic factors associated with progression to total hip replacement (THR) in hip osteoarthritis (OA) is for the most patient- and disease-specific characteristics either conflicting or inconclusive. Therefore, the objectives of this study of participants with hip OA enrolled in a structured program of supervised education and exercise therapy were to describe the rate of THR and to identify prognostic factors for receiving THR within the following 2 years.

METHODS: Participants aged ≥ 45 years with hip OA enrolled in Good Life with osteoArthritis in Denmark (GLA:D®) from July 2014 to March 2017 were included. Potential prognostic factors included demographic and disease-specific baseline characteristics and measures of physical activity and quality of life (QoL). Information on THR was retrieved from The Danish National Patient Registry. A multivariable Cox proportional hazards model was developed.

RESULTS: Of 3657 included participants, 30% received a THR within 2 years. Of the 100 participants already wait-listed for THR, 60% had the procedure. Of 22 candidate prognostic factors, 14 were statistically significant for receiving THR. Factors associated with a faster rate of THR included being “male” (HR 1.43), having “self-reported radiographic hip OA” (HR 2.32), being “wait-listed for THR” (HR 2.17), and having a higher “pain intensity” (HR 1.01). In contrast, faster “walking speed” (HR 0.64), better “hip-related QoL” (HR 0.98), and having “three or more comorbidities” (HR 0.62) were predictive of a slower rate of THR.

CONCLUSION: During the 2-year follow-up period, 30% of the cohort received a THR. Notably, 40% of those wait-listed for THR when entering the program did not receive THR within 2 years. A number of baseline prognostic factors for receiving THR were identified.

PMID:34493331 | DOI:10.1186/s13075-021-02608-6

Antimicrob Resist Infect Control. 2021 Sep 8;10(1):132. doi: 10.1186/s13756-021-00997-6.

ABSTRACT

BACKGROUND: Monitoring pathogens of bloodstream infections (BSI) and their antibiotic susceptibility is important to guide empiric antibiotic treatment strategies and prevention programs. This study assessed the epidemiology of BSI and antibiotic resistance patterns at the German Federal State of Thuringia longitudinally.

METHODS: A surveillance network consisting of 26 hospitals was established to monitor BSIs from 01/2015 to 12/2019. All blood culture results, without restriction of age of patients, of the participating hospitals were reported by the respective microbiological laboratory. A single detection of obligate pathogens and a repeated detection of coagulase-negative staphylococci, Bacillus spp., Corynebacterium spp., Micrococcus spp. and Propionibacterium spp., within 96 h were regarded as a relevant positive blood culture. If one of the aforementioned non-obligate pathogens has been detected only once within 96 h, contamination has been assumed. Logistic regression models were applied to analyse the relationship between resistance, year of BSI and hospital size. Generalized estimating equations were used to address potential clustering.

RESULTS: A total of 343,284 blood cultures (BC) of 82,527 patients were recorded. Overall, 2.8% (n = 9571) of all BCs were classified as contaminated. At least one relevant pathogen was identified in 13.2% (n = 45,346) of BCs. Escherichia coli (25.4%) was the most commonly detected pathogen, followed by Staphylococcus aureus (15.2%), Staphylococcus epidermidis (8.1%) and Klebsiella pneumoniae (4.6%). In S. aureus, we observed a decline of methicillin resistance (MRSA) from 10.4% in 2015 to 2.5% in 2019 (p < 0.001). The rate of vancomycin resistance in Enterococcus faecium (VRE) has increased from 16.7% in 2015 to 26.9% in 2019 (p < 0.001), with a peak in 2018 (42.5%). In addition, we observed an increase of Cefotaxime (3GC) resistance in E. coli from 10.7% in 2015 to 14.5% in 2019 (p = 0.007) whereas 3GC resistance in K. pneumoniae was stable (2015: 9.9%; 2019: 7.4%, p = 0.35). Carbapenem resistance was less than 1% for both pathogens. These patterns were robustly observed across sensitivity analyses.

CONCLUSIONS: We observed evidence for a decline in MRSA, an increase in VRE and a very low rate of carbapenem resistance in gram-negative bacteria. 3GC resistance in E. coli increased constantly over time.

PMID:34493334 | DOI:10.1186/s13756-021-00997-6

J Occup Med Toxicol. 2021 Sep 7;16(1):39. doi: 10.1186/s12995-021-00330-2.

ABSTRACT

BACKGROUND: The PLR (pupillary light reflex) can be a marker for pathological medical conditions, such as neurodegenerative or mental health disorders and diseases as well as marker for physiological alterations, such as age, sex or iris color. PLR alterations have been described in people after alcohol consumption, as well. However, the effect of sleep deprivation on PLR parameters is still under debate.

METHODS: The aim of this study was to investigate the feasibility of PLR measurements in sleep-deprived and alcohol-exposed participants. In addition, we wanted to identify PLR parameters that were altered by sleep deprivation and alcohol exposure.

RESULTS: Altogether n = 50 participants have been included in this study. Differences in the PLR parameters initial diameter (d_init), latency (∆t_lat), acceleration (∆t_a), contraction velocity (ϑ_con), quarter dilatation velocity (ϑ_1/4dil), half dilatation time (∆t_1/2), and the line integral (L(0.3500)) have been evaluated between baseline, sleep deprivation, as well as alcohol exposure. In a generalized linear mixed models design, we could observe statistically significant associations between the type of exposure and the PLR parameters half dilatation time and half dilatation time after the first light pulse (all p < 0.05). The participants’ latency showed a significant association in dependence of the type of exposure after the second light pulse (p < 0.05).

CONCLUSION: Our study delivers first promising results to further develop devices that may identify conditions that impair the ability to work or drive.

PMID:34493308 | DOI:10.1186/s12995-021-00330-2

Genome Biol. 2021 Sep 7;22(1):263. doi: 10.1186/s13059-021-02477-x.

ABSTRACT

With the recent increase in RNA sequencing efforts using large cohorts of individuals, surveying allele-specific gene expression is becoming increasingly frequent. Here, we report that, despite not containing explicit variant information, a list of genes known to be allele-specific in an individual is enough to recover key variants and link the individuals back to their genotypes and phenotypes. This creates a privacy conundrum.

PMID:34493313 | DOI:10.1186/s13059-021-02477-x

Genome Biol. 2021 Sep 7;22(1):262. doi: 10.1186/s13059-021-02478-w.

ABSTRACT

Local genetic correlation quantifies the genetic similarity of complex traits in specific genomic regions. However, accurate estimation of local genetic correlation remains challenging, due to linkage disequilibrium in local genomic regions and sample overlap across studies. We introduce SUPERGNOVA, a statistical framework to estimate local genetic correlations using summary statistics from genome-wide association studies. We demonstrate that SUPERGNOVA outperforms existing methods through simulations and analyses of 30 complex traits. In particular, we show that the positive yet paradoxical genetic correlation between autism spectrum disorder and cognitive performance could be explained by two etiologically distinct genetic signatures with bidirectional local genetic correlations.

PMID:34493297 | DOI:10.1186/s13059-021-02478-w

Thromb J. 2021 Sep 7;19(1):63. doi: 10.1186/s12959-021-00313-7.

ABSTRACT

BACKGROUND: DOAC detection is challenging in emergency situations. Here, we demonstrated recently, that modified thromboelastometric tests can reliably detect and differentiate dabigatran and rivaroxaban. However, whether all DOACs can be detected and differentiated to other coagulopathies is unclear. Therefore, we now tested the hypothesis that a decision tree-based thromboelastometry algorithm enables detection and differentiation of all direct Xa-inhibitors (DXaIs), the direct thrombin inhibitor (DTI) dabigatran, as well as vitamin K antagonists (VKA) and dilutional coagulopathy (DIL) with high accuracy.

METHODS: Following ethics committee approval (No 17-525-4), and registration by the German clinical trials database we conducted a prospective observational trial including 50 anticoagulated patients (n = 10 of either DOAC/VKA) and 20 healthy volunteers. Blood was drawn independent of last intake of coagulation inhibitor. Healthy volunteers served as controls and their blood was diluted to simulate a 50% dilution in vitro. Standard (extrinsic coagulation assay, fibrinogen assay, etc.) and modified thromboelastometric tests (ecarin assay and extrinsic coagulation assay with low tissue factor) were performed. Statistical analyzes included a decision tree analyzes, with depiction of accuracy, sensitivity and specificity, as well as receiver-operating-characteristics (ROC) curve analysis including optimal cut-off values (Youden-Index).

RESULTS: First, standard thromboelastometric tests allow a good differentiation between DOACs and VKA, DIL and controls, however they fail to differentiate DXaIs, DTIs and VKAs reliably resulting in an overall accuracy of 78%. Second, adding modified thromboelastometric tests, 9/10 DTI and 28/30 DXaI patients were detected, resulting in an overall accuracy of 94%. Complex decision trees even increased overall accuracy to 98%. ROC curve analyses confirm the decision-tree-based results showing high sensitivity and specificity for detection and differentiation of DTI, DXaIs, VKA, DIL, and controls.

CONCLUSIONS: Decision tree-based machine-learning algorithms using standard and modified thromboelastometric tests allow reliable detection of DTI and DXaIs, and differentiation to VKA, DIL and controls.

TRIAL REGISTRATION: Clinical trial number: German clinical trials database ID: DRKS00015704 .

PMID:34493301 | DOI:10.1186/s12959-021-00313-7

Int J Equity Health. 2021 Sep 7;20(1):200. doi: 10.1186/s12939-021-01527-x.

ABSTRACT

BACKGROUND: The evolving pandemic of coronavirus disease 2019 (COVID-19) has become a severe threat to public health, and the workplace presents high risks in terms of spreading the disease. Few studies have focused on the relationship between workplace policy and individual behaviours. This study aimed to identify inequalities of workplace policy across occupation groups, examine the relationship of workplace guidelines and measures with employees’ behaviours regarding COVID-19 prevention.

METHODS: A cross-sectional online survey using a structured questionnaire was conducted to gather employees’ access to workplace guidelines and measures as well as their personal protection behaviours. Statistical associations between these two factors in different occupations were examined using multiple ordinal logistic regressions.

RESULTS: A total of 1048 valid responses across five occupational groups were analysed. Manual labourers reported lower availability of workplace guidelines and measures (76.9% vs. 89.9% for all, P = 0.003). Employees with available workplace guidelines and measures had higher compliance of hand hygiene, wearing masks, and social distancing, and this association was more significant among managers/administrators and manual labourers.

CONCLUSIONS: Protection of the quantity and quality of employment is important. Awareness about the disease and its prevention among employers and administrators should be promoted, and resources should be allocated to publish guidelines and implement measures in the workplace during the pandemic. Both work-from-home arrangement and other policies and responses for those who cannot work from home including guidelines encouraging the health behaviours, information transparency, and provision of infection control materials by employers should be established to reduce inequality. Manual labourers may require specific attention regarding accessibility of relevant information and availability of medical benefits and compensation for income loss due to the sickness, given their poorer experience of workplace policy and the nature of their work. Further studies are needed to test the effectiveness of specific workplace policies on COVID-19 prevention.

PMID:34493292 | DOI:10.1186/s12939-021-01527-x

Mol Brain. 2021 Sep 7;14(1):135. doi: 10.1186/s13041-021-00840-4.

ABSTRACT

AIM: Experimental animals, such as non-human primates (NHPs), mice, Zebrafish, and Drosophila, are frequently employed as models to gain insights into human physiology and pathology. In developmental neuroscience and related research fields, information about the similarities of developmental gene expression patterns between animal models and humans is vital to choose what animal models to employ. Here, we aimed to statistically compare the similarities of developmental changes of gene expression patterns in the brains of humans with those of animal models frequently used in the neuroscience field.

METHODS: The developmental gene expression datasets that we analyzed consist of the fold-changes and P values of gene expression in the brains of animals of various ages compared with those of the youngest postnatal animals available in the dataset. By employing the running Fisher algorithm in a bioinformatics platform, BaseSpace, we assessed similarities between the developmental changes of gene expression patterns in the human (Homo sapiens) hippocampus with those in the dentate gyrus (DG) of the rhesus monkey (Macaca mulatta), the DG of the mouse (Mus musculus), the whole brain of Zebrafish (Danio rerio), and the whole brain of Drosophila (D. melanogaster).

RESULTS: Among all possible comparisons of different ages and animals in developmental changes in gene expression patterns within the datasets, those between rhesus monkeys and mice were highly similar to those of humans with significant overlap P-value as assessed by the running Fisher algorithm. There was the highest degree of gene expression similarity between 40-59-year-old humans and 6-12-year-old rhesus monkeys (overlap P-value = 2.1 × 10^{– 72}). The gene expression similarity between 20-39-year-old humans and 29-day-old mice was also significant (overlap P = 1.1 × 10^{– 44}). Moreover, there was a similarity in developmental changes of gene expression patterns between 1-2-year-old Zebrafish and 40-59-year-old humans (Overlap P-value = 1.4 × 10^{– 6}). The overlap P-value of developmental gene expression patterns between Drosophila and humans failed to reach significance (30 days Drosophila and 6-11-year-old humans; overlap P-value = 0.0614).

CONCLUSIONS: These results indicate that the developmental gene expression changes in the brains of the rhesus monkey, mouse, and Zebrafish recapitulate, to a certain degree, those in humans. Our findings support the idea that these animal models are a valid tool for investigating the development of the brain in neurophysiological and neuropsychiatric studies.

PMID:34493287 | DOI:10.1186/s13041-021-00840-4

BMC Med. 2021 Sep 8;19(1):204. doi: 10.1186/s12916-021-02080-8.

ABSTRACT

BACKGROUND: Disordered fetal adrenal steroidogenesis can cause marked clinical effects including virilization of female fetuses. In postnatal life, adrenal disorders can be life-threatening due to the risk of adrenal crisis and must be carefully managed. However, testing explicit adrenal steroidogenic inhibitory effects of therapeutic drugs is challenging due to species-specific characteristics, and particularly the impact of adrenocorticotropic hormone (ACTH) stimulation on drugs targeting steroidogenesis has not previously been examined in human adrenal tissue. Therefore, this study aimed to examine the effects of selected steroidogenic inhibitors on human fetal adrenal (HFA) steroid hormone production under basal and ACTH-stimulated conditions.

METHODS: This study used an established HFA ex vivo culture model to examine treatment effects in 78 adrenals from 50 human fetuses (gestational weeks 8-12). Inhibitors were selected to affect enzymes critical for different steps in classic adrenal steroidogenic pathways, including CYP17A1 (Abiraterone acetate), CYP11B1/2 (Osilodrostat), and a suggested CYP21A2 inhibitor (Efavirenz). Treatment effects were examined under basal and ACTH-stimulated conditions in tissue from the same fetus and determined by quantifying the secretion of adrenal steroids in the culture media using liquid chromatography-tandem mass spectrometry. Statistical analysis was performed on ln-transformed data using one-way ANOVA for repeated measures followed by Tukey’s multiple comparisons test.

RESULTS: Treatment with Abiraterone acetate and Osilodrostat resulted in potent inhibition of CYP17A1 and CYP11B1/2, respectively, while treatment with Efavirenz reduced testosterone secretion under basal conditions. ACTH-stimulation affected the inhibitory effects of all investigated drugs. Thus, treatment effects of Abiraterone acetate were more pronounced under stimulated conditions, while Efavirenz treatment caused a non-specific inhibition on steroidogenesis. ACTH-stimulation prevented the Osilodrostat-mediated CYP11B1 inhibition observed under basal conditions.

CONCLUSIONS: Our results show that the effects of steroidogenic inhibitors differ under basal and ACTH-stimulated conditions in the HFA ex vivo culture model. This could suggest that in vivo effects of therapeutic drugs targeting steroidogenesis may vary in conditions where patients have suppressed or high ACTH levels, respectively. This study further demonstrates that ex vivo cultured HFAs can be used to evaluate steroidogenic inhibitors and thereby provide novel information about the local effects of existing and emerging drugs that targets steroidogenesis.

PMID:34493283 | DOI:10.1186/s12916-021-02080-8

Eur J Dent. 2021 Sep 7. doi: 10.1055/s-0041-1726161. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the effect of interval time after acidic beverage intake and brushing on roughness and hardness of resin composite.

MATERIALS AND METHODS: Nanofilled resin composites were tested as per interval time (no interval, 15 or 30 minutes) between aging media (isotonic, sports drink) and brushing. Specimens (n = 9) were subjected to three cycles daily for 5 days with immersion in beverage followed by simulated brushing (585 strokes). The brushing (control) group was submitted only in brushing cycles. Roughness and microhardness were analyzed in the baseline and end of the experiment. Surface morphology was analyzed by using scanning electron microscopy (SEM).

STATISTICAL ANALYSIS: Data were analyzed by one-way ANOVA and Tukey’s honestly significant difference (α = 0.05).

RESULTS: Roughness was higher in no interval group and lower in 30 minutes and control. The 15 minutes present no statistical difference between control, 30 minutes and no interval. The hardness not present difference between groups. The SEM showed the no interval more roughness than 15 and 30 minutes, control and baseline.

CONCLUSION: The interval time between erosive and abrasive challenge is important to preserve the smoothness surface of composite resin.

PMID:34492727 | DOI:10.1055/s-0041-1726161