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Nevin Manimala Statistics

Effect of butyrate, a bacterial byproduct, on the viability and ICAM-1 expression/production of human vascular endothelial cells: role in infectous pulpal/periapical diseases

Int Endod J. 2021 Aug 22. doi: 10.1111/iej.13614. Online ahead of print.

ABSTRACT

AIM: To investigate the effects of butyric acid (BA), a metabolic product generated by pulp and root canal pathogens, on the viability and intercellular adhesion molecule-1 (ICAM-1) production of endothelial cells, which are crucial to angiogenesis and pulpal/periapical wound healing.

METHODOLOGY: Endothelial cells were exposed to butyrate with/without inhibitors. Cell viability, apoptosis, and reactive oxygen species (ROS) were evaluated using an MTT assay, PI/Annexin V, and DCF fluorescence flow cytometry, respectively. RNA and protein expression was determined using a polymerase chain reaction assay and Western blotting or immunofluorescent staining. Soluble ICAM-1 (sICAM-1) was measured using an enzyme-linked immunosorbent assay. The quantitative results were expressed as Mean ± standard error (SE) of the mean. The data were analyzed using a paired Student t-test where necessary. A p-value ≤0.05 was considered to indicate a statistically significant difference between groups.

RESULTS: Butyrate (>4 mM) inhibited cell viability and induced cellular apoptosis and necrosis. It inhibited cyclin B1 but stimulated p21 and p27 expression. Butyrate stimulated ROS production and hemeoxygenase-1 (HO-1) expression as well as activating the Ac-H3, p-ATM, p-ATR, p-Chk1, p-Chk2, p-p38, and p-Akt expression of endothelial cells. Butyrate stimulated ICAM-1 mRNA/protein expression and significant sICAM-1 production (p<0.05). Superoxide dismutase, 5z-7oxozeaenol, SB203580, and compound C (p<0.05), but not ZnPP, CGK733, AZD7762, or LY294002 attenuated butyrate cytotoxicity to endothelial cells. Notably, little effect on butyrate-stimulated sICAM-1 secretion was found. Valproic acid, phenylbutyrate, and trichostatin (three histone deacetylase inhibitors) significantly induced sICAM-1 production (p<0.05).

CONCLUSION: BA inhibited proliferation, induced apoptosis, stimulated ROS and HO-1 production, and increased ICAM-1 mRNA expression and protein synthesis in endothelial cells. Cell viability affected by BA was diminished by some inhibitors; however, the increased sICAM-1 secretion by BA was not affected by any of the tested inhibitors. These results facilitate understanding of the pathogenesis, prevention, and treatment of pulpal/periapical diseases.

PMID:34420220 | DOI:10.1111/iej.13614

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Nevin Manimala Statistics

Discharge destination after hip fracture: findings from the Irish hip fracture database

Eur Geriatr Med. 2021 Aug 22. doi: 10.1007/s41999-021-00556-7. Online ahead of print.

ABSTRACT

PURPOSE: Although home continues to be the place from which the majority of patients are admitted, less than one third of patients are Discharged Directly Home (DDH) following hip fracture. Once ready for discharge, DDH as opposed to Discharge to an Alternative Location (DAL), i.e., community care, rehabilitation facility or long-term care, is a high priority for patients and clinicians alike. Not only is DDH integral to the quality of life of patients, it is also an essential driver of the socioeconomic cost of hip fracture care.

METHODS: We analysed 21,819 cases in the Irish Hip Fracture Database from 2013 to 2019. Descriptive and analytical statistics were conducted.

RESULTS: 29% (n = 6476) of patients were DDH during the study period. On multivariate analysis, the odds of DDH decreased as age increased (OR 0.28, p < 0.01, 95% CI 0.24-0.34). Patients who were independently mobile prior to fracture were 47% more likely to be DDH (OR 1.47, p < 0.01, 95% CI 1.29-1.68). Those mobilised early post operatively were 24% more likely to be DDH (OR 1.24, p < 0.01, 95% CI 1.06-1.45). Patients who waited > 72 h prior to surgery were 30% less likely to be DDH (OR 0.70, p < 0.01, 95% CI 0.56-0.88).

CONCLUSION: The authors identified patient characteristics that increased the likelihood of DDH, i.e., younger patients independently mobile prior to fracture, who received timely surgery and early post-operative mobilisation. The Irish Hip Fracture Standards (IHFS) incorporate 2 out the 3 modifiable factors identified, which reinforces the importance of the IHFS in improving patient outcomes.

PMID:34420192 | DOI:10.1007/s41999-021-00556-7

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Nevin Manimala Statistics

Rejoinder: Estimating vaccine efficacy over time after a randomized study is unblinded

Biometrics. 2021 Aug 22. doi: 10.1111/biom.13539. Online ahead of print.

NO ABSTRACT

PMID:34420208 | DOI:10.1111/biom.13539

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Nevin Manimala Statistics

Optical coherence tomography tissue coverage and characterization at six months after implantation of bioresorbable scaffolds versus conventional everolimus eluting stents in the ISAR-Absorb MI trial

Int J Cardiovasc Imaging. 2021 Aug 21. doi: 10.1007/s10554-021-02251-x. Online ahead of print.

ABSTRACT

PURPOSE: Data regarding vessel healing by optical coherence tomography (OCT) after everolimus-eluting bioresorbable scaffolds (BRS) or everolimus-eluting metallic stent (EES) implantation in acute myocardial infarction (AMI) patients is scarce. We compared OCT findings after BRS or EES implantation in patients with AMI enrolled in a randomized trial.

METHODS: In ISAR-Absorb MI, AMI patients were randomized to BRS or EES implantation, with 6-8 month angiographic follow-up. This analysis includes patients who underwent OCT during surveillance angiography. Tissue characterization was done using grey-scale signal intensity analysis. The association between OCT findings and target lesion failure (TLF) at 2 years was investigated.

RESULTS: OCT was analyzed in 103 patients (2237 frames, 19,827 struts) at a median of 216 days post-implantation. Of these, 70 were treated with BRS versus 32 with EES. Pre-(92.8 vs. 68.7%, p = 0.002) and post-dilation (51.4 vs. 12.5%, p < 0.001) were more common in BRS as compared to EES. Strut coverage was higher in BRS vs. EES (97.5% vs. 90.9%, p < 0.001). Mean neointimal thickness was comparable in both groups [85.5 (61.9, 124.1) vs. 69.5 (32.7, 127.5) µm, respectively, p = 0.20]. Mature neointimal regions were numerically more common in BRS (43.0% vs. 24.6%; p = 0.35); this difference was statistically significant in ST-elevation myocardial infarction patients (40.9% vs. 21.1%, p = 0.03). At two-years, 8 (7.8%) patients experienced TLF. Mean neointimal area [0.61 (0.21, 1.33) vs. 0.41 (0.11, 0.75) mm2, p = 0.03] and mean neointimal coverage [106.1 (65.2, 214.8) vs. 80.5 (53.5, 122.1) µm, p < 0.01] were higher, with comparable tissue maturity, in lesions with versus without TLF.

CONCLUSIONS: In selected patients who underwent OCT surveillance 6-8 months after coronary intervention for AMI with differing implantation characteristics depending on the device type used, vessel healing was more advanced in BRS compared with EES, particularly in the STEMI subgroup.

PMID:34420177 | DOI:10.1007/s10554-021-02251-x

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Nevin Manimala Statistics

Rationale, design and population description of the CREDENCE study: cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records

Eur J Epidemiol. 2021 Aug 22. doi: 10.1007/s10654-021-00795-9. Online ahead of print.

ABSTRACT

The cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records (CREDENCE) study is a unique prospectively designed investigation of cardiovascular risk in two large contemporary cohorts of people with type 2 diabetes from New Zealand (NZ) and China. The study was designed to derive equivalent cardiovascular risk prediction equations in a developed and a developing country, using the same epidemiological and statistical methodology. Two similar cohorts of people with type 2 diabetes were identified from large general population studies in China and New Zealand, which had been generated from longitudinal electronic health record systems. The CREDENCE study aims to determine whether cardiovascular risk prediction equations derived in patients with type 2 diabetes in a developed country are applicable in a developing country, and vice versa, by deriving and validating equivalent diabetes-specific cardiovascular risk prediction models from the two countries. Baseline data in CREDENCE was collected from October 2004 in New Zealand and from January 2010 in China. In the first stage of CREDENCE, a total of 93,207 patients (46,649 from NZ and 46,558 from China) were followed until December 31st 2018. Median follow-up was 7.0 years (New Zealand) and 5.7 years (China). There were 5926 (7.7% fatal) CVD events in the New Zealand cohort and 3650 (8.8% fatal) in the Chinese cohort. The research results have implications for policy makers, clinicians and the public and will facilitate personalised management of cardiovascular risk in people with type 2 diabetes worldwide.

PMID:34420154 | DOI:10.1007/s10654-021-00795-9

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Nevin Manimala Statistics

What drives green development in China: public pressure or the willingness of local government?

Environ Sci Pollut Res Int. 2021 Aug 22. doi: 10.1007/s11356-021-16059-8. Online ahead of print.

ABSTRACT

With China already committing to peak carbon dioxide emissions before 2030 and achieving carbon neutrality before 2060, green development is urgent. It is necessary to clarify the driving mechanism of green development to design the path of green development scientifically. From the internal perspective of the green development system, this paper divides the green development power into external power and internal power. The external power is the political pressure formed by the public’s green demands. The internal power is the endogenous power of green development transformed by the political promotion willingness of local government leaders. The research shows that (1) the green demands from the public and the accompanying political pressure can form the driving force of green development. (2) The political promotion intention has not been transformed into the endogenous driving force to promote green development in the research period. (3) The external driving force of public appeal is closely related to economic development, income and consumption levels, and education. This paper enriches the research literatures on the driving mechanism of green development and provides theoretical and practical exploration for the driving path of green development.

PMID:34420168 | DOI:10.1007/s11356-021-16059-8

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Nevin Manimala Statistics

Risk factors for hypertensive phase after Ahmed glaucoma valve implantation

Int Ophthalmol. 2021 Aug 22. doi: 10.1007/s10792-021-02009-3. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the risk factors and the clinical characteristics of the hypertensive phase (HP) after Ahmed glaucoma valve (AGV) implantation.

METHODS: This retrospective study included 60 eyes of 57 patients who underwent AGV implantation and with at least 1-year follow-up. HP was defined as intraocular pressure (IOP) > 21 mmHg in the first 3 months after the surgery. Independent samples t-test and Chi-square test were used to compare differences in patients with the HP and the non-HP groups. Univariable and multivariable logistic regression analyses were used to determine the risk factors for the development of the HP. Statistical significance was assumed at p < 0.05 level.

RESULTS: HP was observed in 31 eyes (51.7%) with an average peak IOP of 27.6 ± 4.5 mmHg (range 22-40 mmHg). The resolution of HP was noted in 27 eyes (87.1%) at the 3rd month postoperative visit. The number of glaucoma medications at the last postoperative visit and IOP values from 1 month to 1 year were significantly higher in the HP group (all p < 0.05). Patients with traumatic glaucoma showed the highest rate (83.3%) of HP development. In the multivariable analysis, a preoperative IOP > 30 mmHg (p = 0.03, OR:5.82; reference: ≤ 25 mmHg) and younger age (41-64 years, p = 0.02, OR:8.49; ≤ 40 years, p = 0.001, OR:19.62; reference: ≥ 65 years) were independently associated with the occurrence of HP.

CONCLUSION: Hypertensive phase was observed in half of the patients undergoing AGV implantation. A higher mean preoperative IOP and younger age were risk factors for HP development. Although the majority resolved at the 3-month visit, eyes with HP had higher mean IOPs and required more IOP lowering medications.

PMID:34420122 | DOI:10.1007/s10792-021-02009-3

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Nevin Manimala Statistics

Missing data strategies for the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Alliance A091105 and COMET-2

Qual Life Res. 2021 Aug 21. doi: 10.1007/s11136-021-02968-1. Online ahead of print.

ABSTRACT

PURPOSE: Missing scores complicate analysis of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) because patients with and without missing scores may systematically differ. We focus on optimal analysis methods for incomplete PRO-CTCAE items, with application to two randomized, double-blind, placebo-controlled, phase III trials.

METHODS: In Alliance A091105 and COMET-2, patients completed PRO-CTCAE items before randomization and several times post-randomization (N = 64 and 107, respectively). For each trial, we conducted between-arm comparisons on the PRO-CTCAE via complete-case two-sample t-tests, mixed modeling with contrast, and multiple imputation followed by two-sample t-tests. Because interest lies in whether CTCAE grades can inform missing PRO-CTCAE scores, we performed multiple imputation with and without CTCAE grades as auxiliary variables to assess the added benefit of including them in the imputation model relative to only including PRO-CTCAE scores across all cycles.

RESULTS: PRO-CTCAE completion rates ranged from 100.0 to 71.4% and 100.0 to 77.1% across time in A091105 and COMET-2, respectively. In both trials, mixed modeling and multiple imputation provided the most similar estimates of the average treatment effects. Including CTCAE grades in the imputation model did not consistently narrow confidence intervals of the average treatment effects because correlations for the same PRO-CTCAE item between different cycles were generally stronger than correlations between each PRO-CTCAE item and its corresponding CTCAE grade at the same cycle.

CONCLUSION: For between-arm comparisons, mixed modeling and multiple imputation are informative techniques for handling missing PRO-CTCAE scores. CTCAE grades do not provide added benefit for informing missing PRO-CTCAE scores. ClinicalTrials.gov Identifiers: NCT02066181 (Alliance A091105); NCT01522443 (COMET-2).

PMID:34420143 | DOI:10.1007/s11136-021-02968-1

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Nevin Manimala Statistics

Randomized controlled trials published on patients with hernias have a high percentage of unreproducible statistics

Hernia. 2021 Aug 22. doi: 10.1007/s10029-021-02488-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Surgeons rely on randomized controlled trials (RCT) to compare the effectiveness of treatments. RCTs require careful planning and substantial effort to complete. Because of the careful study design, statistics performed are often easy to reproduce such as Chi-squared or t-test. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon.

METHODS: RCTs pertaining to hernias were identified in PubMed using the search terms “hernia” and “randomized controlled trial.” Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. Discordance between the obtained p-value from our analysis and the published p-value was assessed. Primary outcome was the number of studies that reported p-values that crossed the level of statistical significance (p-value = 0.05) but on reproduction analysis did not.

RESULTS: Of the 100 included RCTs, five reported p-values that crossed the “p = 0.05” threshold that our team was unable to reproduce using the statistical test reported in the manuscript. An additional three studies reported p-values that crossed the “p = 0.05” threshold that our team was unable to reproduce using the appropriate statistical test (i.e., Fisher’s exact test when all expected cell counts < 5). All eight studies published p-values < 0.05, whereas, our re-analysis demonstrated p ≥ 0.05.

CONCLUSION: Eight percent of the RCTs analyzed in this study reported p-values < 0.05 that on reproduction analysis was ≥ 0.05. The next steps should be to determine reasons for discordance and how to prevent this from happening.

PMID:34420111 | DOI:10.1007/s10029-021-02488-4

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Nevin Manimala Statistics

Is prevention of suicide worth less? A comparison of the value per statistical life

Eur J Health Econ. 2021 Aug 21. doi: 10.1007/s10198-021-01361-6. Online ahead of print.

ABSTRACT

This paper compares the value per statistical life (VSL) in the context of suicide prevention to that of prevention of traffic fatalities. We conducted a contingent valuation survey with questions on willingness to pay (WTP) in both contexts by administering a web questionnaire to 1038 individuals aged 18 to 80. We conjectured that WTP for a given impact on the number of fatalities would be lower for suicide prevention because suicide, at least to some degree, is the result of individuals’ own decisions. However, this hypothesis was not supported by the within- or between-sample estimates of WTP or by responses to direct questions. Hence, no support is provided for the use of a lower valuation of the impact of suicide prevention than for risk-reducing programs in other fields, such as traffic safety. This implies that the same VSL should be used for evaluating suicide prevention interventions and for risk-reducing programs in other policy areas and funds for the prevention of fatalities should be directed to the area with the lowest cost per life saved.

PMID:34420119 | DOI:10.1007/s10198-021-01361-6