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Nevin Manimala Statistics

Point-of-care detection and differentiation of anticoagulant therapy – development of thromboelastometry-guided decision-making support algorithms

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

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Similarities of developmental gene expression changes in the brain between human and experimental animals: rhesus monkey, mouse, Zebrafish, and Drosophila

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

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Unequal availability of workplace policy for prevention of coronavirus disease 2019 across occupations and its relationship with personal protection behaviours: a cross-sectional survey

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

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The effects of selected inhibitors on human fetal adrenal steroidogenesis differs under basal and ACTH-stimulated conditions

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

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Effect of Interval Time between Corrosive and Abrasive Challenges on a Nanoparticulate Composite Resin

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

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Comparative Analysis of COVID-19 Outbreak and Changes in Neurosurgical Emergency Patients

J Korean Neurosurg Soc. 2021 Sep 8. doi: 10.3340/jkns.2021.0056. Online ahead of print.

ABSTRACT

OBJECTIVE: COVID-19 has spread worldwide since the first case was reported in Wuhan, China, in December 2019. Our institution is a regional trauma and emergency center in the northern Gyeonggi Province. The changing trend of patient care in the emergency room of this hospital likely reflects the overall trend of patients in the area. In the present study, whether changes in the surrounding social environment following the outbreak of COVID-19 changed the incidence of neurosurgical emergency patients and whether differences in practice existed were investigated.

METHODS: The overall trend was analyzed from January 2020 which is before the outbreak of COVID-19 to September 2020. To remove bias due to seasonal variation, the previous 2 year’s records during the same period were reviewed and compared. Confirmed COVID-19 patients in the northern Gyeonggi Province were identified using data released by the government. And patients who came to the emergency department with head trauma and stroke were identified.

RESULTS: Based on the present study results, the total number of neurosurgery emergency patients decreased over the study period. In the trauma patient group, the number of patients not involved in traffic accidents significantly decreased compared with patients involved in traffic accidents. Among the stroke cases, the rate of ischemic stroke was lower than hemorrhagic stroke, although a statistically significant difference was not observed. Meanwhile, an increase in the risk of mortality associated with trauma or stroke cases was not observed during the COVID-19 outbreak compared with the same time period in the previous year.

CONCLUSION: Due to the occurrence of COVID-19, non-essential activities have decreased and trauma cases not associated with traffic accidents appeared to decrease. Due to the decrease in overall activity, the number of stroke patients has also decreased. This trend is expected to continue even in the post-COVID-19 era, and accordingly, the results from the present study are relevant especially if the current situation continues.

PMID:34492750 | DOI:10.3340/jkns.2021.0056

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Early Antibiotic Exposure in Low-Risk Late Preterm and Term Infants

Am J Perinatol. 2021 Sep 7. doi: 10.1055/s-0041-1735220. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to examine the epidemiology of antibiotic exposure and early onset sepsis (EOS) in late preterm and term infants born via cesarean section with rupture of membranes less than 10 minutes.

STUDY DESIGN: Retrospective review of 1,187 late preterm and term infants born at Brooke Army Medical Center between January 1, 2012 and August 29, 2019. Subjects were assessed for factors related to antibiotic treatment. Statistical analysis was performed to compare infants treated with antibiotics versus observation.

RESULT: An early blood culture was obtained from 234 (19.7%) infants; 170 (14.3%) were treated with antibiotics. Infants treated with antibiotics were significantly younger (p < 0.0001), smaller (p < 0.0001), more often diagnosed with respiratory distress (p < 0.0001), and were more frequently admitted to the neonatal intensive care unit (p < 0.0001). There were no cases of culture proven EOS.

CONCLUSION: Although this population lacks risk factors for the development of EOS, a significant percentage was treated with antibiotics. This population may benefit from future antibiotic stewardship efforts.

KEY POINTS: · This population is at risk for respiratory morbidity.. · There were no cases of culture proven early onset sepsis.. · This is a group of interest for antibiotic stewardship..

PMID:34492723 | DOI:10.1055/s-0041-1735220

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Efficacy of Individualized Homeopathic Medicines in Plantar Fasciitis: Double-blind, Randomized, Placebo-Controlled Clinical Trial

Homeopathy. 2021 Sep 7. doi: 10.1055/s-0041-1731383. Online ahead of print.

ABSTRACT

INTRODUCTION: Plantar fasciitis (PF) is a chronic degenerative condition causing marked thickening and fibrosis of the plantar fascia, and collagen necrosis, chondroid metaplasia and calcification. There is little convincing evidence in support of various approaches, including homeopathy, for treating PF. This study was undertaken to examine the efficacy of individualized homeopathic medicines (IHMs) compared with placebo in the treatment of PF.

METHODS: A double-blind, randomized, placebo-controlled trial was conducted at the outpatient departments of Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, West Bengal, India. Patients were randomized to receive either IHMs or identical-looking placebo in the mutual context of conservative non-medicinal management. The Foot Function Index (FFI) questionnaire, as an outcome measure, was administered at baseline, and every month, up to 3 months. Group differences (unpaired t-tests) and effect sizes (Cohen’s d) were calculated on an intention-to-treat sample. The sample was analyzed statistically after adjusting for baseline differences.

RESULTS: The target sample size was 128; however, only 75 could be enrolled (IHMs: 37; Placebo: 38). Attrition rate was 9.3% (IHMs: 4, Placebo: 3). Differences between groups in total FFI% score favored IHMs against placebo at all the time points, with large effect sizes: month 1 (mean difference, -10.0; 95% confidence interval [CI], -15.7 to -4.2; p = 0.001; d = 0.8); month 2 (mean difference, -14.3; 95% CI, -20.4 to -8.2; p <0.001; d = 1.1); and month 3 (mean difference, -23.3; 95% CI, -30.5 to -16.2; p <0.001; d = 1.5). Similar significant results were also observed on three FFI sub-scales (pain%, disability%, and activity limitation%). Natrum muriaticum (n = 14; 18.7%) and Rhus toxicodendron and Ruta graveolens (n = 11 each; 14.7%) were the most frequently prescribed medicines. No harms, serious adverse events, or intercurrent illnesses were recorded in either of the groups.

CONCLUSION: IHMs acted significantly better than placebo in the treatment of PF; however, the trial being underpowered, the results should be interpreted as preliminary only. Independent replications are warranted.

TRIAL REGISTRATION: CTRI/2018/10/016014.

PMID:34492725 | DOI:10.1055/s-0041-1731383

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A Retrospective Comparative Analysis of Latissimus Dorsi (LD) Flap Versus Thoracodorsal Artery Perforator (TDAP) Flap in Total Breast Reconstruction with Implants: A Pilot Study

J Reconstr Microsurg. 2021 Sep 7. doi: 10.1055/s-0041-1735508. Online ahead of print.

ABSTRACT

INTRODUCTION: In breast surgery, an autologous flap combined with implant may reduce the risk or repair the soft-tissue defects in several cases. Traditionally, the preferred flap is the myocutaneous latissimus dorsi (LD) flap. In the perforator flap era, the evolution of LD flap is the thoracodorsal artery perforator (TDAP) flap. The aim of this study is the comparison between LD flap and TDAP flap with implants in terms of early complications and shoulder function.

METHODS: We performed a retrospective cohort study in accordance with the STROBE guidelines. Between January 1 2015 and January 1 2020, 27 women underwent a unilateral total breast reconstruction with LD or TDAP flap combined with an implant at our institution. 15 women were operated with LD flap and 12 with TDAP flap. The most frequent indications for intervention were results of mastectomy and radiation-induced contracture. We evaluated several data in terms of clinical and demographical characteristics, operative and perioperative factors, and follow-up variables. We assessed shoulder function through the Disability of the Arm, Shoulder and Hand Questionnaire (DASH).

RESULTS: The rate of complications was significantly lower in the TDAP group compared with the LD group (16.7% vs 60.0%, p = 0.047. Table 3). Although the small sample size limited further detailed statistical analyses, we particularly noticed no cases of donor site seroma in the TDAP group, as compared with four in the LD group. Patients in the TDAP group had an ∼11-point lower mean DASH score compared with the LD group (9.8 vs 20.5). This difference was statistically significant (p = 0.049).

CONCLUSIONS: TDAP flap seems to be a reliable technique for soft-tissue coverage in total breast reconstruction with implants. In comparison with the traditional LD flap, it could be a more favorable option in terms of less complications and better quality of life.

PMID:34492716 | DOI:10.1055/s-0041-1735508

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Association between biological maturity, body constitution and physical fitness with performance on a rowing ergometer in elite youth female rowers

Sportverletz Sportschaden. 2021 Sep 7. doi: 10.1055/a-1532-4597. Online ahead of print.

ABSTRACT

BACKGROUND: There is a gap in the literature regarding predictors of rowing performance in young rowers. Therefore, the aim of this study was to investigate associations between parameters of biological maturity, body constitution and physical fitness with rowing performance in young female elite rowers.

METHODS: A total of 26 female rowers aged 13.1 ± 0.5 years (maturity offset: + 2.2 ± 0.5 years from peak height velocity; training volume: 10 hours/week) volunteered to participate in this study. During the performance tests in March 2016/2017, biological maturity (e. g. maturity offset), body constitution (e. g. body height/mass, lean body mass, body fat mass) and physical fitness were assessed. Physical fitness tests included the assessment of muscle strength (1-RM bench pull, leg press, maximal handgrip strength), muscle power (standing long jump test), muscular endurance (trunk muscle endurance test [Bourban test]), dynamic balance (Y-balance test) and change-of-direction speed (multistage shuttle run). Finally, rowing performance was analysed using a 700-m rowing ergometer test. A linear regression analysis was computed for the models (1) biological maturity, (2) biological maturity and body constitution, and (3) biologic maturity, body constitution, and physical fitness.

RESULTS: The statistical analysis showed significant (p≤ 0.01) medium-to-large sized correlations (0.57 ≤r≤ 0.8) between biological maturity, body constitution (e. g. body height/mass, lean body mass) and physical fitness (e. g. 1-RM bench pull, maximal handgrip strength, Bourban test) with rowing performance. Model 3 with the predictors body constitution (i. e. lean mass) and muscular endurance (i. e. Bourban test) showed the largest explained variance for 700-m rowing ergometer performance (R² = 0.94, Akaike information criterion [AIC] = 82.1). Explained variance of model 3 was higher compared with model 1 (R² = 0.6, AIC = 131.5) and model 2 (R² = 0.63, AIC = 111.6).

CONCLUSIONS: As a result of this study, coaches involved in junior rowing should focus on characteristics such as biological maturity, body constitution and physical fitness (muscle strength, muscular endurance) during talent development as these correlated highly with rowing ergometer performance.

PMID:34492718 | DOI:10.1055/a-1532-4597