Tag: nevin manimala

Cancer Med. 2021 Jul 11. doi: 10.1002/cam4.3870. Online ahead of print.

ABSTRACT

Recent studies defined a potentially important role of the microbiome in modulating pancreatic ductal adenocarcinoma (PDAC) and responses to therapies. We hypothesized that antibiotic usage may predict outcomes in patients with PDAC. We retrospectively analyzed clinical data of patients with resectable or metastatic PDAC seen at MD Anderson Cancer from 2003 to 2017. Demographic, chemotherapy regimen and antibiotic use, duration, type, and reason for indication were recorded. A total of 580 patients with PDAC were studied, 342 resected and 238 metastatic patients, selected retrospectively from our database. Antibiotic use, for longer than 48 hrs, was detected in 209 resected patients (61%) and 195 metastatic ones (62%). On resectable patients, we did not find differences in overall survival (OS) or progression-free survival (PFS), based on antibiotic intake. However, in the metastatic cohort, antibiotic consumption was associated with a significantly longer OS (13.3 months vs. 9.0 months, HR 0.48, 95% CI 0.34-0.7, p = 0.0001) and PFS (4.4 months vs. 2 months, HR 0.48, 95% CI 0.34-0.68, p = <0.0001). In multivariate analysis, the impact of ATB remained significant for PFS (HR 0.59, p = 0.005) and borderline statistically significant for OS (HR 0.69, p = 0.06). When we analyzed by chemotherapy regimen, we found that patients who received gemcitabine-based chemotherapy as first-line therapy (n = 118) had significantly prolonged OS (HR 0.4, p 0.0013) and PFS (HR 0.55, p 0.02) if they received antibiotics, while those receiving 5FU-based chemotherapy (n = 98) had only prolonged PFS (HR 0.54, p = 0.03). Antibiotics-associated modulation of the microbiome is associated with better outcomes in patients with metastatic PDAC.

PMID:34250759 | DOI:10.1002/cam4.3870

Acad Emerg Med. 2021 Jul 12. doi: 10.1111/acem.14343. Online ahead of print.

ABSTRACT

BACKGROUND: Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time-sensitive, life-threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries.

METHODS: We conducted a four-center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC.

RESULTS: We enrolled 1 of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, 7 (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months.

CONCLUSIONS: In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.

PMID:34250690 | DOI:10.1111/acem.14343

Health Econ. 2021 Jul 11. doi: 10.1002/hec.4387. Online ahead of print.

ABSTRACT

This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically powerful; (ii) there is a robust total effect of birth weight on income for men but not for women; (iii) the total effect of birth weight on income for men is partly mediated via height but not via BMI; and (iv) the share of the total effect mediated via height is substantial, of approximately 56%.

PMID:34250692 | DOI:10.1002/hec.4387

Health Econ. 2021 Jul 11. doi: 10.1002/hec.4383. Online ahead of print.

ABSTRACT

In response to the Covid-19 outbreak, the Italian Government imposed an economic lockdown on March 22, 2020, and ordered the closing of all non-essential economic activities. This paper estimates the causal effects of this measure on mortality by Covid-19 and on mobility patterns. The identification of the causal effects exploits the variation in the active population across municipalities induced by the economic lockdown. The difference-in-differences empirical design compares outcomes in municipalities above and below the median variation in the share of active population before and after the lockdown within a province, also controlling for municipality-specific dynamics, daily shocks at the provincial level, and municipal unobserved characteristics. Our results show that the intensity of the economic lockdown is associated with a statistically significant reduction in mortality by Covid-19 and, in particular, for age groups between 40 and 64 and older (with larger and more significant effects for individuals above 50). Back of the envelope calculations indicate that 4793 deaths were avoided, in the 26 days between April 5 and April 30, in the 3518 municipalities which experienced a more intense lockdown. Several robustness checks corroborate our empirical findings.

PMID:34250694 | DOI:10.1002/hec.4383

Transfus Med. 2021 Jul 11. doi: 10.1111/tme.12800. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare knowledge, attitudes and risk perception related to blood donation and transfusion in Trinidad and Tobago and Bahamas.

BACKGROUND: Trinidad and Tobago and the Bahamas are two Caribbean countries whose national blood transfusion systems are heavily reliant (76.2% and 76%) on family replacement donors. The Pan American Health Organisation/World Health Organisation recommends blood collection from exclusively voluntary nonremunerated donors on the grounds that family replacement donor-based blood systems are unsafe and inadequate compared to those based on voluntary nonremunerated blood donors.

METHODS/MATERIALS: A 23-item questionnaire was distributed online by snowball sampling in these two countries to assess knowledge, attitudes, risk perception and behaviour. SPSS version 24 was used for interpretative and descriptive data analysis, chi-square to measure significance and linear regression the strength of associations. p < 0.05 was used to define statistical significance.

RESULTS: Four hundred and fifty three (453) responses were obtained from Trinidad and Tobago and 101 from the Bahamas. Knowledge and positive attitudes were high in both countries (75.5% vs. 80.2%, p < 0.001 and 96.6% vs. 100%, p < 0.001). A substantial proportion of respondents held the perception that the local blood donation system was safe or very safe (26.4 and 61.4%, p < 0.001) that was linked to the misconception that the prevalent method of blood donation was voluntary nonremunerated (27.8 and 51.4%, p < 0.001). Concerns about receiving blood were underpinned by mistrust of transfusion-related procedures.

CONCLUSION: A social interface to transfer information between blood transfusion services and the community could encourage voluntary nonremunerated blood donation and reduce concerns about receiving transfusion.

PMID:34250655 | DOI:10.1111/tme.12800

Hum Brain Mapp. 2021 Jul 11. doi: 10.1002/hbm.25589. Online ahead of print.

ABSTRACT

Despite recent progress in the analysis of neuroimaging data sets, our comprehension of the main mechanisms and principles which govern human brain cognition and function remains incomplete. Network neuroscience makes substantial efforts to manipulate these challenges and provide real answers. For the last decade, researchers have been modelling brain structure and function via a graph or network that comprises brain regions that are either anatomically connected via tracts or functionally via a more extensive repertoire of functional associations. Network neuroscience is a relatively new multidisciplinary scientific avenue of the study of complex systems by pursuing novel ways to analyze, map, store and model the essential elements and their interactions in complex neurobiological systems, particularly the human brain, the most complex system in nature. Due to a rapid expansion of neuroimaging data sets’ size and complexity, it is essential to propose and adopt new empirical tools to track dynamic patterns between neurons and brain areas and create comprehensive maps. In recent years, there is a rapid growth of scientific interest in moving functional neuroimaging analysis beyond simplified group or time-averaged approaches and sophisticated algorithms that can capture the time-varying properties of functional connectivity. We describe algorithms and network metrics that can capture the dynamic evolution of functional connectivity under this perspective. We adopt the word ‘chronnectome’ (integration of the Greek word ‘Chronos’, which means time, and connectome) to describe this specific branch of network neuroscience that explores how mutually informed brain activity correlates across time and brain space in a functional way. We also describe how good temporal mining of temporally evolved dynamic functional networks could give rise to the detection of specific brain states over which our brain evolved. This characteristic supports our complex human mind. The temporal evolution of these brain states and well-known network metrics could give rise to new analytic trends. Functional brain networks could also increase the multi-faced nature of the dynamic networks revealing complementary information. Finally, we describe a python module (https://github.com/makism/dyconnmap) which accompanies this article and contains a collection of dynamic complex network analytics and measures and demonstrates its great promise for the study of a healthy subject’s repeated fMRI scans.

PMID:34250674 | DOI:10.1002/hbm.25589

Epilepsia. 2021 Jul 12. doi: 10.1111/epi.16993. Online ahead of print.

ABSTRACT

OBJECTIVE: Discontinuation of antiepileptic drugs (AEDs) in seizure-free patients is an important goal because of possible long-term side effects and the social stigma burden of epilepsy. The purpose of this work was to assess seizure recurrence risk after suspension of AEDs, to evaluate predictors for recurrence, and to investigate the recovery of seizure control after relapse. In addition, the accuracy of a previously published prediction model of seizure recurrence risk was estimated.

METHODS: Seizure-free patients with epilepsy who had discontinued AEDs were retrospectively enrolled. The frequency of seizure relapses after AED withdrawal as well as prognosis after recurrence were assessed and the predictive role of baseline clinical-demographic variables was evaluated. The aforementioned prediction model was also validated and its accuracy assessed at different seizure-relapse probability levels.

RESULTS: The enrolled patients (n = 133) had been followed for a median of 3 years (range 0.8-33 years) after AED discontinuation; 60 (45%) of them relapsed. Previous febrile seizures in childhood (hazard ratio [HR] 3.927; 95% confidence interval [CI] 1.403-10.988), a seizure-free period on therapy of less than 2 years (HR 2.313; 95% CI 1.193-4.486), and persistent motor deficits (HR 4.568; 95% CI 1.412-14.772) were the clinical features associated with relapse risk in univariate analysis. Among these variables, only a seizure-free period on therapy of less than 2 years was associated with seizure recurrence in multivariate analysis (HR 2.365; 95% CI 1.178-4.7444). Pharmacological control of epilepsy was restored in 82.4% of the patients who relapsed. In this population, the aforementioned prediction model showed an unsatisfactory accuracy.

SIGNIFICANCE: A period of freedom from seizure on therapy of less than 2 years was the main predictor of seizure recurrence. The accuracy of the previously described prediction tool was low in this cohort, thus suggesting its cautious use in real-world clinical practice.

PMID:34250596 | DOI:10.1111/epi.16993

Epilepsia. 2021 Jul 12. doi: 10.1111/epi.16998. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to determine whether two commonly prescribed antiseizure medications (ASMs), levetiracetam (LEV) and oxcarbazepine (OXC), were associated with an increased risk of fragility fracture in children with epilepsy when initiating therapy during a crucial period of bone development, namely, pre- and midpuberty.

METHODS: Claims data from January 1, 2009 to December 31, 2018 were extracted from the Optum Clinformatics Data Mart. Children aged 4-13 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline (e.g., pre-ASM exposure) and 4 years of follow-up. Children with epilepsy who were ASM naïve were grouped based on whether ASM treatment initiation included LEV or OXC. The comparison group included children without epilepsy and without ASM exposure. Crude incidence rate (IR; n per 1000 person-years) and IR ratio (IRR; with 95% confidence interval [CI]) were estimated for nontrauma fracture (NTFx), a claims-based proxy for fragility fracture, for up to 4 years of follow-up. Cox proportional hazards regression estimated the hazard ratio (HR; with 95% CI) after adjusting for demographic variables, motor impairment, and baseline fracture.

RESULTS: The crude IR (95% CI) of NTFx was 21.5 (21.2-21.8) for non-ASM-users without epilepsy (n = 271 346), 19.8 (12.3-27.2) for LEV (n = 358), and 34.4 (21.1-47.7) for OXC (n = 203). Compared to non-ASM-users, the crude IRR of NTFx was similar for LEV (IRR = .92, 95% CI = .63-1.34) and elevated for OXC (IRR = 1.60, 95% CI = 1.09-2.35); the crude IRR of NTFx was elevated for OXC compared to LEV (IRR = 1.74, 95% CI = 1.02-2.99). The findings were consistent after adjusting for covariates, except when comparing OXC to LEV (HR = 1.71, 95% CI = .99-2.93), which was marginally statistically insignificant (p = .053).

SIGNIFICANCE: Initiating OXC, but not LEV, therapy among 4-13-year-olds with epilepsy is associated with an elevated risk of fragility fracture. Studies are needed to determine whether these children could benefit from adjunct bone fragility therapies.

PMID:34250606 | DOI:10.1111/epi.16998

Eur J Neurosci. 2021 Jul 11. doi: 10.1111/ejn.15386. Online ahead of print.

ABSTRACT

Recent studies have proposed that one can summarize brain activity into dynamics among a relatively small number of hidden states and that such an approach is a promising tool for revealing brain function. Hidden Markov models (HMMs) are a prevalent approach to inferring such neural dynamics among discrete brain states. However, the impact of assuming Markovian structure in neural time series data has not been sufficiently examined. Here, to address this situation and examine the performance of the HMM, we compare the model with the Gaussian mixture model (GMM), which is with no temporal regularization and thus a statistically simpler model than the HMM, by applying both models to synthetic time series generated from empirical resting-state functional magnetic resonance imaging (fMRI) data. We compared the GMM and HMM for various sampling frequencies, lengths of recording per participant, numbers of participants, and numbers of independent component signals. We find that the HMM attains a better accuracy of estimating the hidden state than the GMM in a majority of cases. However, we also find that the accuracy of the GMM is comparable to that of the HMM under the condition that the sampling frequency is reasonably low (e.g., TR = 2.88 or 3.60 s) or the data is relatively short. These results suggest that the GMM can be a viable alternative to the HMM for investigating hidden-state dynamics under this condition.

PMID:34250639 | DOI:10.1111/ejn.15386

J Forensic Sci. 2021 Jul 12. doi: 10.1111/1556-4029.14791. Online ahead of print.

ABSTRACT

The current standard technique for cardiopulmonary resuscitation (CPR), initially described in the early 1960s, has quickly become the expected response for all persons found without a pulse or respiration. Despite the potentially lifesaving properties of external cardiac massage, the mainstay of resuscitation, it consists of repeated blunt force trauma to the chest, which can lead to extensive traumatic skeletal and nonskeletal injuries. Numerous autopsy-based studies have documented the incidence and patterns of rib and sternal fractures associated with attempted CPR, but there is relatively little data on the incidence and severity of nonskeletal CPR-related injuries. We reviewed reports from 1878 autopsies performed between September 2017 and December 2019 (inclusive), for documentation of CPR-related injuries. Among these cases, there were 93 cases with resuscitation-related nonskeletal injuries. The most common type of injury identified were visceral contusions, documented in 57.0% of cases. These contusions predominantly involved the heart, lungs, neck soft tissue, and surrounding structures. Resuscitation-related lacerations were seen in 17.2% of the cases, most predominantly involving the pericardium, heart, and liver. Statistical analysis of the data demonstrated that lacerations were more likely to be seen in females and with associated sternal fractures. Additionally, hemothoraces were present in 34.4% of cases and hemopericardium was seen in 8.6% of cases. This study provides additional documentation of the range, severity, and incidence of various types of resuscitation-related visceral injuries to better assist autopsy pathologists in distinguishing these injuries from other antecedent traumatic injuries.

PMID:34250595 | DOI:10.1111/1556-4029.14791