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Nevin Manimala Statistics

Inflow Cannula Position as Risk Factor for Stroke in Patients with HeartMate 3 Left Ventricular Assist Devices

Artif Organs. 2022 Jan 3. doi: 10.1111/aor.14165. Online ahead of print.

ABSTRACT

BACKGROUND: A relation between left ventricular assist device inflow cannula malposition and pump thrombus has been reported. This study aimed to investigate if the pump position, derived from chest X-rays in HeartMate 3 (HM3) patients, correlates with neurological dysfunction (ND), ischemic stroke (IS), hemorrhagic stroke (HS) and survival.

METHODS: This analysis was performed on routinely acquired X-rays of 42 patients implanted with a HM3 between 2014 and 2017. Device position was quantified in patients with and without ND from frontal and lateral X-rays characterizing the inflow cannula (IC) and pump in relation to spine, diaphragm or horizontal line. The primary end-point was freedom from stroke and survival one-year after HM3 implantation stratified by pump position.

RESULTS: The analysis of X-rays, 33.5 (41.0) days postoperative, revealed a significant smaller IC angle of HM3 patients with ND vs. no ND (0.1±14.0° vs. 12.9±10.1°, p=0.005). Additionally, the IC angle in the frontal view, IS: 4.1 (20.9)° vs. no IS: 13.8 (7.5)°, p=0.004 was significantly smaller for HM3 patients with IS. Using ROC derived cut-off, IC angle <10° provided 75% sensitivity and 100% specificity (C-statistic=0.85) for predicting IS. Stratified by IC angle, freedom from IS at 12 months was 100% (>10°) and 60% (<10°) respectively (p=0.002). No significant differences were found in any end-point between patients with and without HS. One-year survival was significantly higher in patients with IC angle >10° vs. <10° (100% vs. 71.8%, p=0.012).

CONCLUSIONS: Inflow cannula malposition derived from standard chest X-rays serves as a risk factor for neurological dysfunction, ischemic stroke and worse survival in HM3 patients.

PMID:34978722 | DOI:10.1111/aor.14165

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Nevin Manimala Statistics

Comprehensive echocardiographic and speckle tracking strain analysis in rheumatic mitral stenosis patients before and after transvenous mitral commissurotomy

Int J Cardiovasc Imaging. 2022 Jan 3. doi: 10.1007/s10554-021-02518-3. Online ahead of print.

ABSTRACT

Percutaneous Transvenous Mitral Commissurotomy (PTMC) is the first line treatment for rheumatic mitral stenosis (MS). We sought to evaluate (1) changes in 2-dimensional (2D) echocardiographic and strain values and (2) differences in these values for patients in atrial fibrillation (AF) and sinus rhythm (SR) pre, immediately and 6 months post PTMC. Retrospective study of 136 patients who underwent PTMC between 2011 and 2021. We analyzed their 2D echocardiogram, Global Longitudinal Strain (GLS), Left Atrial Reservoir Strain (LAr-S) and Right Ventricle Free Wall Strain (RVFW-S) pre, immediately and 6 months post PTMC. At 6 months, mitral valve area increases from 0.94 ± 0.23 cm2 to 1.50 ± 0.42 cm2. Ejection fraction (EF) did not change post PTMC (pre; 55.56 ± 6.62%, immediate; 56.68 ± 7.83%, 6 months; 56.28 ± 7.00%, p = 0.218). Even though EF is preserved, GLS is lower pre-procedure; – 11.52 ± 3.74% with significant improvement at 6 months; – 15.16 ± 4.28% (p < 0.001). Tricuspid annular plane systolic excursion (TAPSE) improved at 6 months from 1.95 ± 0.43 to 2.11 ± 0.49 (p = 0.004). RVFW-S increases at 6 months from – 17.37 ± 6.03% to – 19.75 ± 7.19% (p = 0.011). LAr-S improved from 11.23 ± 6.83% pre PTMC to 16.80 ± 8.82% at 6 months (p < 0.001) post PTMC. Pre-procedure patients with AF have lower strain values (More LV, RV and LA dysfunction) with statistically significant difference for LAr-S (p < 0.001), GLS (p < 0.001) and RVFW-S (p < 0.001) than patients in SR. Patients with severe rheumatic MS have subclinical left and right ventricle dysfunction despite preserved EF and relatively normal TAPSE with significant improvement seen at 6 months post PTMC. AF patients have lower baseline strain values than SR patients.

PMID:34978670 | DOI:10.1007/s10554-021-02518-3

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Nevin Manimala Statistics

A comparison of statistical methods to predict the residual lifetime risk

Eur J Epidemiol. 2022 Jan 3. doi: 10.1007/s10654-021-00815-8. Online ahead of print.

ABSTRACT

Lifetime risk measures the cumulative risk for developing a disease over one’s lifespan. Modeling the lifetime risk must account for left truncation, the competing risk of death, and inference at a fixed age. In addition, statistical methods to predict the lifetime risk should account for covariate-outcome associations that change with age. In this paper, we review and compare statistical methods to predict the lifetime risk. We first consider a generalized linear model for the lifetime risk using pseudo-observations of the Aalen-Johansen estimator at a fixed age, allowing for left truncation. We also consider modeling the subdistribution hazard with Fine-Gray and Royston-Parmar flexible parametric models in left truncated data with time-covariate interactions, and using these models to predict lifetime risk. In simulation studies, we found the pseudo-observation approach had the least bias, particularly in settings with crossing or converging cumulative incidence curves. We illustrate our method by modeling the lifetime risk of atrial fibrillation in the Framingham Heart Study. We provide technical guidance to replicate all analyses in R.

PMID:34978669 | DOI:10.1007/s10654-021-00815-8

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Nevin Manimala Statistics

Esophageal abnormalities and the risk for gastroesophageal cancers-a histopathology-register-based study in Sweden

Eur J Epidemiol. 2022 Jan 3. doi: 10.1007/s10654-021-00833-6. Online ahead of print.

ABSTRACT

BACKGROUND: The poor survival of patients with gastroesophageal cancers may improve if additional esophageal precursor lesions to Barrett’s esophagus and squamous dysplasia are identified. We estimated the risk for gastroesophageal cancers among patients with various histopathological abnormalities in the esophagus, including Barrett’s esophagus, subdivided by histopathological types.

METHODS: Histopathology data from esophageal biopsies obtained 1979-2014 were linked with several national population-based registers in Sweden. Patients were followed from 2 years after the first biopsy date until cancer, death, emigration, esophagectomy/gastrectomy or end of follow-up, 31st of December 2016, whichever came first. We estimated standardized incidence ratios (SIRs) as measures of relative risk with the Swedish general population as reference.

RESULTS: In total 367 esophageal adenocarcinoma (EAC) cases were ascertained during 831,394 person-years of follow-up. The incidence rate (IR) for EAC was 0.1 per 1000 person-years for normal morphology, 0.2-0.5 for inflammatory changes, and 0.8-2.9 for metaplasia. The IR was 1.0 per 1000 person-years (95% confidence interval 0.7-1.3) among patients with non-dysplastic intestinal metaplasia, 0.9 (0.8-1.1) in non-dysplastic gastric/glandular metaplasia and 2.9 (2.0-4.2) among columnar metaplasia patients with low-grade dysplasia. The SIRs were 11.7 (95% confidence interval 8.6-15.5), 12.0 (10.0-14.2) and 30.2 (20.5-42.8), respectively. The SIRs for gastric cardia adenocarcinoma (GCA) were moderately elevated.

CONCLUSIONS: For the first time, we demonstrate that patients with esophageal inflammatory and other metaplastic abnormalities than Barrett’s esophagus have an increased risk of EAC and GCA compared to the general population. Moreover, patients with different histopathologic subtypes of Barrett’s esophagus have a comparable risk for EAC.

PMID:34978667 | DOI:10.1007/s10654-021-00833-6

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Nevin Manimala Statistics

Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis

Eur J Epidemiol. 2022 Jan 3. doi: 10.1007/s10654-021-00826-5. Online ahead of print.

ABSTRACT

BACKGROUND: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake.

METHODS: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank.

RESULTS: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: β = 0.022 (SE = 0.004, p < 0.001) and FVC: β = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: β = – 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: β = – 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant.

CONCLUSIONS: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.

PMID:34978666 | DOI:10.1007/s10654-021-00826-5

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Nevin Manimala Statistics

Are NOACs as safe and efficient as VKA regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?

Interact Cardiovasc Thorac Surg. 2022 Jan 3:ivab363. doi: 10.1093/icvts/ivab363. Online ahead of print.

ABSTRACT

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: ‘Are NOACs as safe and efficient as vitamin K antagonist regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?’ Altogether more than 324 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The RIVER and ENAVLE trials showed non-inferiority of rivaroxaban (regarding mean time free from composite of death, major cardiovascular events or major bleeding at 12 months) and edoxaban (composite of death, clinical thromboembolic events or asymptomatic intracardiac thrombosis; and major bleeding) when compared with vitamin K antagonist. These studies include a low number of patients within 3 months of index surgery and overall low statistical power regarding this particular subgroup of patients. Data derived from lower evidence studies are compatible with the aforementioned findings. The available evidence suggests that non-vitamin K antagonist anticoagulants are as safe and as efficient as vitamin K antagonist regarding thromboembolic prophylaxis and bleeding event rates in patients with surgical bioprosthesis and atrial fibrillation within 3 months of bioprosthesis implantation. However, this evidence is derived from a limited number of studies with important methodological limitations. Expanding non-vitamin K antagonist anticoagulant recommendation to the early postoperative period warrants more confirmatory research.

PMID:34977926 | DOI:10.1093/icvts/ivab363

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Nevin Manimala Statistics

Improvement in colorectal cancer outcomes over time is limited to patients with left-sided disease

J Cancer Res Clin Oncol. 2022 Jan 3. doi: 10.1007/s00432-021-03868-0. Online ahead of print.

ABSTRACT

PURPOSE: Incidence and mortality of colorectal cancer (CRC) declined over the last decades. However, survival depends on the primary tumor location. It is unknown if all progress in outcomes vary depending on left-sided (LCRC) versus right-sided (RCC) colorectal cancer. We compare incidence and mortality rates over time according to the primary tumor location.

METHODS: Data from the Austrian National Cancer Registry spanning from 1983 to 2018 were used to calculate annual incidence and mortality rates and survival stratified by primary tumor localization and stage. Joinpoint regression with linear regression models were used on different subgroups to identify significant changes of incidence- and mortality slopes.

RESULTS: A total of 168,260 (incidence dataset) and 87,355 cases (mortality dataset) were identified. Survival of disseminated RCC was worse compared to LCRC (HR 1.14; CI 1.106-1.169). Total and LCRC incidence and mortality rates declined steadily over time, whereas the rates of RCC did not. Incidence of disseminated RCC declined significantly less (slope – 0.07; CI – 0.086; – 0.055) than in LCRC (slope – 0.159; CI – 0.183; – 0.136); mortality rate of RCC was unchanged over time. Incidence and mortality of localized RCC remained unchanged over time, whereas both rates declined independently of stage in LCRC.

CONCLUSION: Colorectal cancer outcomes during the last 35 years have preferentially improved in LCRC but not in RCC, indicating that the progress made is limited to LCRC. It is necessary to define RCC as a distinct form of CRC and to focus on specific strategies for its early detection and treatment.

PMID:34977964 | DOI:10.1007/s00432-021-03868-0

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Nevin Manimala Statistics

Spin Statistics for Triplet-Triplet Annihilation Upconversion: Exchange Coupling, Intermolecular Orientation, and Reverse Intersystem Crossing

JACS Au. 2021 Oct 13;1(12):2188-2201. doi: 10.1021/jacsau.1c00322. eCollection 2021 Dec 27.

ABSTRACT

Triplet-triplet annihilation upconversion (TTA-UC) has great potential to significantly improve the light harvesting capabilities of photovoltaic cells and is also sought after for biomedical applications. Many factors combine to influence the overall efficiency of TTA-UC, the most fundamental of which is the spin statistical factor, η, that gives the probability that a bright singlet state is formed from a pair of annihilating triplet states. The value of η is also critical in determining the contribution of TTA to the overall efficiency of organic light-emitting diodes. Using solid rubrene as a model system, we reiterate why experimentally measured magnetic field effects prove that annihilating triplets first form weakly exchange-coupled triplet-pair states. This is contrary to conventional discussions of TTA-UC that implicitly assume strong exchange coupling, and we show that it has profound implications for the spin statistical factor η. For example, variations in intermolecular orientation tune η from to through spin mixing of the triplet-pair wave functions. Because the fate of spin-1 triplet-pair states is particularly crucial in determining η, we investigate it in rubrene using pump-push-probe spectroscopy and find additional evidence for the recently reported high-level reverse intersystem crossing channel. We incorporate all of these factors into an updated model framework with which to understand the spin statistics of TTA-UC and use it to rationalize the differences in reported values of η among different common annihilator systems. We suggest that harnessing high-level reverse intersystem crossing channels in new annihilator molecules may be a highly promising strategy to exceed any spin statistical limit.

PMID:34977890 | PMC:PMC8715495 | DOI:10.1021/jacsau.1c00322

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Nevin Manimala Statistics

Cohort Profile: The COVID-19 in Pregnancy in Scotland (COPS) dynamic cohort of pregnant women to assess effects of viral and vaccine exposures on pregnancy

Int J Epidemiol. 2022 Jan 3:dyab243. doi: 10.1093/ije/dyab243. Online ahead of print.

NO ABSTRACT

PMID:34977922 | DOI:10.1093/ije/dyab243

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Nevin Manimala Statistics

Capturing the transcription factor interactome in response to sub-lethal insecticide exposure

Curr Res Insect Sci. 2021;1:None. doi: 10.1016/j.cris.2021.100018.

ABSTRACT

The increasing levels of pesticide resistance in agricultural pests and disease vectors represents a threat to both food security and global health. As insecticide resistance intensity strengthens and spreads, the likelihood of a pest encountering a sub-lethal dose of pesticide dramatically increases. Here, we apply dynamic Bayesian networks to a transcriptome time-course generated using sub-lethal pyrethroid exposure on a highly resistant Anopheles coluzzii population. The model accounts for circadian rhythm and ageing effects allowing high confidence identification of transcription factors with key roles in pesticide response. The associations generated by this model show high concordance with lab-based validation and identifies 44 transcription factors putatively regulating insecticide-responsive transcripts. We identify six key regulators, with each displaying differing enrichment terms, demonstrating the complexity of pesticide response. The considerable overlap of resistance mechanisms in agricultural pests and disease vectors strongly suggests that these findings are relevant in a wide variety of pest species.

PMID:34977825 | PMC:PMC8702396 | DOI:10.1016/j.cris.2021.100018