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Nevin Manimala Statistics

Editorial: does anti-TNF ‘treatment persistence’ always equate to ‘effective treatment’? Only objective disease assessments can answer the question. Authors’ reply

Aliment Pharmacol Ther. 2021 Sep;54(5):720-721. doi: 10.1111/apt.16535.

NO ABSTRACT

PMID:34379834 | DOI:10.1111/apt.16535

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fuPCR as diagnostic method for the detection of rare fungal pathogens, such as Trichosporon, Cryptococcus and Fusarium

Med Mycol. 2021 Aug 11:myab045. doi: 10.1093/mmy/myab045. Online ahead of print.

ABSTRACT

Fungal respiratory tract colonisation is a common finding in patients with hematologic neoplasms due to immunosuppression inherent in the diseases and exacerbated by therapy. This greatly increases the risk of fungal infections of the lungs, which is associated with significant mortality. Therefore, reliable diagnostic methods with rapidly available results are needed to administer adequate antifungal therapy.We have established an improved method for fungal DNA extraction and amplification that allows simultaneous detection of fungal families based on a set of multiplexed real time PCR reactions (fuPCR). We analysed respiratory rinses and blood of 94 patients with haematological systemic diseases by fuPCR and compared it with the results of culture and serological diagnostic methods. 40 healthy subjects served as controls.Regarding Candida species, the highest prevalence resulted from microbiological culture of respiratory rinses and from detection of antibodies in blood serum in patients (61% and 47%, respectively) and in the control group (29% and 51%, respectively). Detection of other pathogenic yeasts, such as Cryptococcus and Trichosporon, and moulds, such as Fusarium, was only possible in patients by fuPCR from both respiratory rinses and whole blood and serum. These fungal species were found statistically significantly more frequent in respiratory rinses collected from patients after myeloablative therapy for stem cell transplantation compared to samples collected before treatment (p<<0.05i>).The results show that fuPCR is a valuable complement to culturing and its inclusion in routine mycological diagnostics might be helpful for early detection of pathophysiologically relevant respiratory colonisation for patients with hematologic neoplasms.

LAY ABSTRACT: We validated a set of PCR reactions (fuPCR) for use in routine diagnostic. In contrast to culture and serological methods, only by fuPCR pathogenic yeasts (Cryptococcus and Trichosporon) and moulds (Aspergillus and Fusarium) were detected in respiratory rinses and blood of haematological patients.

PMID:34379780 | DOI:10.1093/mmy/myab045

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Nevin Manimala Statistics

Acute sarcopenia changes following hospitalization: influence of pre-admission care dependency level

Age Ageing. 2021 Aug 9:afab163. doi: 10.1093/ageing/afab163. Online ahead of print.

ABSTRACT

INTRODUCTION: Hospitalization is associated with acute changes in sarcopenia status in older people, but the influencing factors are not fully understood. Pre-admission care dependency level as a risk factor has not yet been investigated.

OBJECTIVE: Evaluate if pre-admission care dependency level is an independent predictor of sarcopenia changes following hospitalization.

SETTING AND SUBJECTS: Data came from the Sarcopenia 9+ EAMA Project, a European prospective multi-centre study. For this study, 227 hospitalised older people were included from four different hospitals in Belgium, Spain and Poland, between 18 February 2019 and 5 September 2020.

METHODS: Sarcopenia status at admission and discharge were calculated using a combined score (desirability value) based on muscle mass (calf circumference), strength (grip) and function (walking speed). Ratio of admission to discharge status was the outcome (desirability ratio; 1.00 meaning no difference). Predictor variable was the pre-admission care dependency level, classified into three groups: independent older people living at home, dependent older people living at home and older people living in a care home. Linear regression models were applied, considering potential confounders.

RESULTS: Mean desirability ratio for dependent older people living at home (‘middle dependent group’) was lower (0.89) compared to independent older people (0.98; regression coefficient -0.09 [95% CI -0.16, -0.02]) and care home patients (1.05; -0.16 [95% CI -0.01, -0.31]). Adjusting for potential confounders or using another statistical approach did not affect the main results.

CONCLUSION: Dependent older people living at home were at higher risk of deterioration in sarcopenia status following hospitalization. In-depth studies investigating causes and potential interventions of these findings are needed.

PMID:34379741 | DOI:10.1093/ageing/afab163

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Demographic and socioeconomic inequalities in ideal cardiovascular health: A systematic review and meta-analysis

PLoS One. 2021 Aug 11;16(8):e0255959. doi: 10.1371/journal.pone.0255959. eCollection 2021.

ABSTRACT

BACKGROUND: In 2010, the American Heart Association introduced a new concept of ideal cardiovascular health (CVH) defined as the simultaneous presence of 7 favorable CVH metrics (smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting blood glucose). The objective of this study was to conduct a systematic literature review and meta-analysis of studies examining the prevalence of ideal CVH, and each of the ideal CVH metrics as well as the relationship between socio-demographic determinants and ideal CVH.

METHODS: A comprehensive literature search was conducted in Medline and Scopus databases for studies published between 1 January 2010 and 30 June 2020. A total of 50 studies including 2,148,470 participants were analyzed. Associations were estimated using DerSimonian-Laird random-effect models. Heterogeneity was investigated through subgroup analyses, Q-test, and I2 statistics.

RESULTS: This study showed a low prevalence of ideal CVH defining as 6 and 7 ideal metrics (3.3%). Among seven ideal CVH metrics, smoking was the best metric (71%), while the poorest CVH metric was a healthy diet (5.8%). Gender was a statistically significant moderator of ideal smoking (81% in females and 60% in males) and ideal blood pressure (42% in females and 30% in males). Females and young adults had better CVH status compared to males and older adults. Also, more educated and better-off individuals had a greater number of ideal CVH metrics.

CONCLUSIONS: To the best of our knowledge, this is the first systematic review on the relationship between participants’ socioeconomic status and ideal CVH. The results suggest that the prevalence of ideal CVH and most metrics was unsatisfactory. In order to achieve the improvement of the CVH metrics and the overall ideal CVH, nationwide prevention efforts at the population and individual levels are urgently needed.

PMID:34379696 | DOI:10.1371/journal.pone.0255959

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Nevin Manimala Statistics

Severe Sepsis: The Fragile Anatomy of Crude Mortality

Clin Infect Dis. 2021 Aug 11:ciab677. doi: 10.1093/cid/ciab677. Online ahead of print.

ABSTRACT

Clinical trials of severe sepsis that target crude (total) mortality as an end point do not have sufficient power to detect differences in mortality due to the intervention. We aim to discuss the importance of including the subcomponents of crude mortality in study design; estimate how sample size requirements change based on the proportion of attributable mortality; and how minor changes from predicted outcomes can affect results. We derived statistical curves to illustrate our points.

PMID:34379735 | DOI:10.1093/cid/ciab677

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Nevin Manimala Statistics

Reciprocal interplay between asporin and decorin: Implications in gastric cancer prognosis

PLoS One. 2021 Aug 11;16(8):e0255915. doi: 10.1371/journal.pone.0255915. eCollection 2021.

ABSTRACT

Effective patient prognosis necessitates identification of novel tumor promoting drivers of gastric cancer (GC) which contribute to worsened conditions by analysing TCGA-gastric adenocarcinoma dataset. Small leucine-rich proteoglycans, asporin (ASPN) and decorin (DCN), play overlapping roles in development and diseases; however, the mechanisms underlying their interplay remain elusive. Here, we investigated the complex interplay of asporin, decorin and their interaction with TGFβ in GC tumor and corresponding normal tissues. The mRNA levels, protein expressions and cellular localizations of ASPN and DCN were analyzed using real-time PCR, western blot and immunohistochemistry, respectively. The protein-protein interaction was predicted by in-silico interaction analysis and validated by co-immunoprecipitation assay. The correlations between ASPN and EMT proteins, VEGF and collagen were achieved using western blot analysis. A significant increase in expression of ASPN in tumor tissue vs. normal tissue was observed in both TCGA and our patient cohort. DCN, an effective inhibitor of the TGFβ pathway, was negatively correlated with stages of GC. Co-immunoprecipitation demonstrated that DCN binds with TGFβ, in normal gastric epithelium, whereas in GC, ASPN preferentially binds TGFβ. Possible activation of the canonical TGFβ pathway by phosphorylation of SMAD2 in tumor tissues suggests its role as an intracellular tumor promoter. Furthermore, tissues expressing ASPN showed unregulated EMT signalling. Our study uncovers ASPN as a GC-promoting gene and DCN as tumor suppressor, suggesting that ASPN can act as a prognostic marker in GC. For the first time, we describe the physical interaction of TGFβ with ASPN in GC and DCN with TGFβ in GC and normal gastric epithelium respectively. This study suggests that prevention of ASPN-TGFβ interaction or overexpression of DCN could serve as promising therapeutic strategies for GC patients.

PMID:34379688 | DOI:10.1371/journal.pone.0255915

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Pulmonary tumor embolism: A retrospective study over a 30-year period

PLoS One. 2021 Aug 11;16(8):e0255917. doi: 10.1371/journal.pone.0255917. eCollection 2021.

ABSTRACT

BACKGROUND: Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.

METHODS: We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE. We also analyzed the discrepancies between antemortem clinical and postmortem diagnosis in 1999, 2009 and 2019 by using the Goldman criteria. Goldman category major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival.

RESULTS: We found 20 (3%) cases with PTE out of the 658 autopsy cases with solid malignancies. Out of these 20 cases, urothelial carcinoma (30%, 6/20) and invasive ductal carcinoma of the breast (4/20, 20%) were the most common primary malignancies. Seven patients with shortness of breath died within 3-17 days (average 8.4±2.2 days) after onset of the symptoms. Pulmonary embolism was clinically suspected in seven out of twenty (35%, 7/20) patients before death, but only two patients (10, 2/20) were diagnosed by imaging studies before death. The rate of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019. Although the rate of Goldman category major 1 appeared decreasing, the difference was not statistically significant. The autopsy rate was significantly higher in 2019 (8.4%, 116/1386) than in 2009 (4.4%, 55/1240).

CONCLUSIONS: The incidence of PTE is uncommon. Despite the advances of the radiological techniques, radiological imaging studies did not detect the majority of PTEs. The discrepancy between the antemortem clinical and the postmortem diagnosis has not improved significantly over the past 30 years, emphasizing the value of autopsy.

PMID:34379693 | DOI:10.1371/journal.pone.0255917

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Nevin Manimala Statistics

Structured patterns of activity in pulse-coupled oscillator networks with varied connectivity

PLoS One. 2021 Aug 11;16(8):e0256034. doi: 10.1371/journal.pone.0256034. eCollection 2021.

ABSTRACT

Identifying coordinated activity within complex systems is essential to linking their structure and function. We study collective activity in networks of pulse-coupled oscillators that have variable network connectivity and integrate-and-fire dynamics. Starting from random initial conditions, we see the emergence of three broad classes of behaviors that differ in their collective spiking statistics. In the first class (“temporally-irregular”), all nodes have variable inter-spike intervals, and the resulting firing patterns are irregular. In the second (“temporally-regular”), the network generates a coherent, repeating pattern of activity in which all nodes fire with the same constant inter-spike interval. In the third (“chimeric”), subgroups of coherently-firing nodes coexist with temporally-irregular nodes. Chimera states have previously been observed in networks of oscillators; here, we find that the notions of temporally-regular and chimeric states encompass a much richer set of dynamical patterns than has yet been described. We also find that degree heterogeneity and connection density have a strong effect on the resulting state: in binomial random networks, high degree variance and intermediate connection density tend to produce temporally-irregular dynamics, while low degree variance and high connection density tend to produce temporally-regular dynamics. Chimera states arise with more frequency in networks with intermediate degree variance and either high or low connection densities. Finally, we demonstrate that a normalized compression distance, computed via the Lempel-Ziv complexity of nodal spike trains, can be used to distinguish these three classes of behavior even when the phase relationship between nodes is arbitrary.

PMID:34379694 | DOI:10.1371/journal.pone.0256034

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Nevin Manimala Statistics

Alcohol use and cardiometabolic risk in the UK Biobank: A Mendelian randomization study

PLoS One. 2021 Aug 11;16(8):e0255801. doi: 10.1371/journal.pone.0255801. eCollection 2021.

ABSTRACT

Observational studies suggest alcohol use promotes the development of some adverse cardiometabolic traits but protects against others including outcomes related to coronary artery disease. We used Mendelian randomization (MR) to explore causal relationships between the degree of alcohol consumption and several cardiometabolic traits in the UK Biobank. Using the well-established ADH1B Arg47His variant (rs1229984) and up to 24 additional SNPs recently found to be associated with alcohol consumption in an independent dataset as instruments, we conducted two-stage least squares and inverse weighted variance MR analyses, both as one-sample analyses in the UK Biobank and as two-sample analyses in external consortia. In the UK Biobank inverse variance weighted analyses, we found that one additional drink of alcohol per day was positively associated with systolic blood pressure (beta = 2.65 mmHg [1.40, 3.89]), hemorrhagic stroke (OR = 2.25 [1.41, 3.60]), and atrial fibrillation (OR = 1.26 [1.07, 1.48]), which were replicated in multivariable analyses. Alcohol was also associated with all cardiovascular disease and all-cause death. A positive association with myocardial infarction did not replicate in multivariable analysis, with suggestive mediation through blood pressure; similarly, a positive association between alcohol use with type 2 diabetes was mitigated by BMI in multivariable analysis. Findings were generally null in replication with two-sample analyses. Alcohol was not protective for any disease outcome with any analysis method, dataset, or strata. Stratifications by sex and smoking in the UK Biobank revealed higher point estimates of risk for several outcomes for men and mixed results for smoking strata, but no statistically significant heterogeneity. Our results are consistent with an overall harmful and/or null effect of alcohol on cardiometabolic health at all levels of use and suggest that even moderate alcohol use should not be promoted as a part of a healthy diet and lifestyle.

PMID:34379647 | DOI:10.1371/journal.pone.0255801

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Clinical features and outcome of Aeromonas sobria bacteremia in pediatric and adult patients with hematologic malignancies: A single-center retrospective study in Peru

PLoS One. 2021 Aug 11;16(8):e0255910. doi: 10.1371/journal.pone.0255910. eCollection 2021.

ABSTRACT

BACKGROUND: Previous studies have found that healthcare-associated bacteremia (HAB) by Aeromonas species is associated with mortality. However, there is limited data on this outcome in patients with hematologic malignancies. This study aimed to identify the clinical features of patients with malignant hematologic diseases diagnosed with Aeromonas sobria bacteremia and to evaluate whether the type of bacteremia, community-acquired bacteremia (CAB) or HAB, is associated with mortality.

METHODS: We retrospectively reviewed the clinical records of pediatric and adult patients between January 2000 and December 2017. Clinical characteristics were compared between CAB and HAB. Additionally, we stratified based on age group. Survival outcomes were assessed with Kaplan-Meier curves and a multivariate Cox regression analysis.

RESULTS: A total of 37 patients (median age 24 years) were identified; 23 (62%) had HAB and 14 (38%) had CAB. Overall, the most common presenting symptom was abdominal pain (41%). Acute lymphoblastic leukemia (n = 12/15, 80%) and acute myeloid leukemia (n = 8/22, 36%) were the primary hematologic malignancies in pediatric and adult patients, respectively. CAB patients had worse overall survival (OS) rates at 30 days in all (43% versus HAB 91%, p = 0.006) and adult patients (30% versus HAB 92%, p = 0.002). Cox regression analysis found that quick Sequential Organ Failure Assessment and CAB were statistically significant factors associated with mortality. Low antimicrobial-resistant was noted, except for ciprofloxacin (n = 5/37, 14%).

CONCLUSION: Our study found a worse OS among patients with hematologic malignancies and CAB by Aeromonas sobria. Our results suggest that patients with CAB present with a worse disease severity. These findings should aid clinicians to determine the survival prognosis in this population.

PMID:34379680 | DOI:10.1371/journal.pone.0255910