Tag: statistics

Am J Trop Med Hyg. 2021 Sep 27:tpmd200617. doi: 10.4269/ajtmh.20-0617. Online ahead of print.

ABSTRACT

In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under age 3 years. In addition to diarrhea, these children also experience subclinical episodes that have been shown to affect growth and cognitive function. In this study, we screened polymorphisms in the promoter and exon1 regions of the mannose binding lectin 2 (MBL2) gene, as well as single nucleotide polymorphisms (SNPs) described in toll-like receptors (TLR) TLR1, TLR2, TLR4, and TLR9 and TIR domain-containing adaptor protein (TIRAP) genes among children with cryptosporidial diarrhea (cases) and children who only experienced asymptomatic (subclinical) cryptosporidiosis (controls). Among the polymorphisms screened, the variant allele B at codon 54 (rs1800450) of the MBL2 gene was associated with susceptibility to cryptosporidial diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.1-4.5). When plasma MBL levels were compared, 72% of cases were found to be deficient compared with 32% among controls (OR = 5.09). Among TLR polymorphisms screened, multivariate analysis showed that heterozygous genotypes of TLR4 896A/G (rs4986790, OR = 0.33, 95% CI: 0.11-0.98) and TIRAP 539 C/T (rs8177374, OR = 0.19, 95% CI: 0.06-0.64) SNPs were associated with protection from cryptosporidial diarrhea. Although not statistically significant, these findings suggest that polymorphisms of MBL2 and TLR genes influence susceptibility to symptomatic cryptosporidial diarrhea even in settings with high exposure levels. Further studies to validate these findings in a larger cohort and to understand the role of these polymorphisms in mediating innate and adaptive immune responses to cryptosporidial infection are necessary.

PMID:34583337 | DOI:10.4269/ajtmh.20-0617

Am J Trop Med Hyg. 2021 Sep 27:tpmd210412. doi: 10.4269/ajtmh.21-0412. Online ahead of print.

ABSTRACT

The COVID-19 pandemic poses serious threats to global health, and the emerging mutation in SARS-CoV-2 genomes is one of the major challenges of disease control. Considering the growth of epidemic curve and the circulating SARS-CoV-2 variants in Brazil, the role of locally prevalent E484K and N501Y substitutions in contributing to the epidemiological outcomes is of public health interest for investigation. We developed a likelihood-based statistical framework to reconstruct reproduction numbers, estimate transmission advantage associated with different SARS-CoV-2 variants regarding the marking (identifying) 484K and 501Y substitutions (including Alpha, Zeta, and Gamma variants) in Brazil, and explored the interactive effects of genetic activities on transmission advantage marked by these two mutations. We found a significant transmission advantage associated with the 484K/501Y variants (including P.1 or Gamma variants), which increased the infectivity significantly by 23%. In contrast and by comparison to Gamma variants, E484K or N501Y (including Alpha or Zeta variants) substitution alone appeared less likely to secure a concrete transmission advantage in Brazil. Our finding indicates that the combined impact of genetic activities on transmission advantage marked by 484K/501Y outperforms their independent contributions in Brazil, which implies an interactive effect in shaping the increase in the infectivity of COVID-19. Future studies are needed to investigate the mechanisms of how E484K and N501Y mutations and the complex genetic mutation activities marked by them in SARS-CoV-2 affect the transmissibility of COVID-19.

PMID:34583340 | DOI:10.4269/ajtmh.21-0412

JMIR Public Health Surveill. 2021 Sep 18. doi: 10.2196/30648. Online ahead of print.

ABSTRACT

BACKGROUND: Modelling COVID-19 transmission at live events and public gatherings is essential to control the probability of subsequent outbreaks and communicate to participants their personalised risk. Yet, despite the fast-growing body of literature on COVID transmission dynamics, current risk models either neglect contextual information on vaccination rates or disease prevalence or do not attempt to quantitatively model transmission.

OBJECTIVE: This paper attempts to bridge this gap by providing informative risk metrics for live public events, along with a measure of their uncertainty.

METHODS: Building upon existing models, our approach ties together three main components: (a) reliable modelling of the number of infectious cases at the time of the event, (b) evaluation of the efficiency of pre-event screening, and (c) modelling of the event’s transmission dynamics and their uncertainty along using Monte Carlo simulations.

RESULTS: We illustrate the application of our pipeline for a concert at the Royal Albert Hall and highlight the risk’s dependency on factors such as prevalence, mask wearing, or event duration. We demonstrate how this event held on three different dates (August 20th 2020, January 20th 2021, and March 20th 2021) would likely lead to transmission events that are similar to community transmission rates (0.06 vs 0.07, 2.38 vs 2.39, and 0.67 vs 0.60, respectively). However, differences between event and background transmissions substantially widen in the upper tails of the distribution of number of infections (as denoted by their respective 99th quantiles: 1 vs 1, 19 vs 8, and 6 vs 3 for our three dates), further demonstrating that sole reliance on vaccination and antigen testing to gain entry would likely significantly underestimate the tail risk of the event.

CONCLUSIONS: Despite the unknowns surrounding COVID-19 transmission, our estimation pipeline opens the discussion on contextualized risk assessment by combining the best tools at hand to assess the order of magnitude of the risk. Our model can be applied to any future event and is presented in a user-friendly R Shiny interface [88]. Finally, we discuss our model’s limitations, as well as avenues for model evaluation and improvement.

PMID:34583317 | DOI:10.2196/30648

Am J Trop Med Hyg. 2021 Sep 27:tpmd210218. doi: 10.4269/ajtmh.21-0218. Online ahead of print.

ABSTRACT

Identifying the effects of environmental change on the transmission of vectorborne and zoonotic diseases is of fundamental importance in the face of rapid global change. Causal inference approaches, including instrumental variable (IV) estimation, hold promise in disentangling plausibly causal relationships from observational data in these complex systems. Valle and Zorello Laporta recently critiqued the application of such approaches in our recent study of the effects of deforestation on malaria transmission in the Brazilian Amazon on the grounds that key statistical assumptions were not met. Here, we respond to this critique by 1) deriving the IV estimator to clarify the assumptions that Valle and Zorello Laporta conflate and misrepresent in their critique, 2) discussing these key assumptions as they relate to our original study and how our original approach reasonably satisfies the assumptions, and 3) presenting model results using alternative instrumental variables that can be argued more strongly satisfy key assumptions, illustrating that our results and original conclusion-that deforestation drives malaria transmission-remain unchanged.

PMID:34583331 | DOI:10.4269/ajtmh.21-0218

Parkinsonism Relat Disord. 2021 Sep 8;91:109-114. doi: 10.1016/j.parkreldis.2021.09.004. Online ahead of print.

ABSTRACT

BACKGROUND: There are no widely accepted criteria to aid the physician in diagnosing BSP.

OBJECTIVE: To validate recently proposed diagnostic criteria for blepharospasm in a larger and geographically diverse population and to develop a screening system for blepharospasm.

METHODS: Video-recordings from 211 blepharospasm patients and 166 healthy/disease controls were examined by 8 raters. Agreement for presence of orbicularis oculi spasms, sensory trick, and increased blinking was measured by k statistics. Inability to voluntarily suppress the spasms was asked by the examiner but not captured in the video. Patients/controls were also requested to fill a self-administered questionnaire addressing relevant blepharospasm clinical aspects. The diagnosis at each site was the gold standard for sensitivity/specificity.

RESULTS: All the study items yielded satisfactory inter/intra-observer agreement. Combination of items rather than each item alone reached satisfactory sensitivity/specificity. The combined algorithm started with recognition of spasms followed by sensory trick. In the absence of a sensory trick, including “increased blinking” or “inability to voluntarily suppress the spasms” or both items yielded 88-92% sensitivity and 79-83% specificity. No single question of the questionnaire yielded high sensitivity/specificity. Serial application of the questionnaire to our blepharospasm and control subjects and subsequent clinical examination of subjects screening positive by the validated diagnostic algorithms yielded 78-81% sensitivity and 83-91% specificity.

CONCLUSION: These results support the use of proposed diagnostic criteria in multi-ethnic, multi-center cohorts. We also propose a case-finding procedure to screen blepharospasm in a given population with less effort than would be required by examination of all subjects.

PMID:34583301 | DOI:10.1016/j.parkreldis.2021.09.004

Parkinsonism Relat Disord. 2021 Sep 21;91:115-120. doi: 10.1016/j.parkreldis.2021.09.015. Online ahead of print.

ABSTRACT

INTRODUCTION: The non-motor symptoms (NMSs) of Parkinson’s disease (PD) significantly impact the patient’s health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A_2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD.

METHODS: Patients with PD and ≥1 NMS and ‘wearing-off’ with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model.

RESULTS: Overall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score.

CONCLUSION: NMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.

PMID:34583302 | DOI:10.1016/j.parkreldis.2021.09.015

J Environ Manage. 2021 Sep 25;301:113820. doi: 10.1016/j.jenvman.2021.113820. Online ahead of print.

ABSTRACT

Soil salinization is a widespread problem affecting global food production. Phytoremediation is emerging as a viable and cost-effective technology to reclaim salt-affected soil. However, its efficiency is not clear due to the uncertainty of plant responses in saline soils. The main objective of this paper is to propose a phytoremediation dynamic model (PDM) for salt-affected soil within the process-based biogeochemical denitrification-decomposition (DNDC) model. The PDM represents two salinity processes of phytoremediation: plant salt uptake and salt-affected biomass growth. The salt-soil-plant interaction is simulated as a coupled mass balance equation of water and salt plant uptake. The salt extraction ability by plant is a combination of salt uptake efficiency (F) and transpiration rate. For water filled pore space (WFPS), the statistical measures RMSE, MAE, and R² during the calibration period are 2.57, 2.14, and 0.49, and they are 2.67, 2.34, and 0.56 during the validation period, respectively. For soil salinity, RMSE, MAE, and R² during the calibration period are 0.02, 0.02, and 0.92, and 0.06, 0.04, and 0.68 during the validation period, respectively, which are reasonably good for further scenario analysis. Over the four years, cumulative salt uptake varied based on weather conditions. At the optimal salt uptake efficiency (F = 20), cumulative salt uptake from soil was 16-90% for alfalfa, 11-70% for barley, and 10-80% for spring wheat. While at the lowest salt uptake efficiency (F = 40), cumulative salt uptake was nearly zero for all crops. Although barley has the highest peak transpiration flux, alfalfa and spring wheat have greater cumulative salt uptake because their peak transpiration fluxes occurred more frequently than in barley. For salt-tolerant crops biomass growth depends on their threshold soil salinity which determines their ability to take up salt without affecting biomass growth. In order to phytoremediate salt-affected soil, salt-tolerant crops having longer duration of crop physiological stages should be used, but their phytoremediation effectiveness will depend on weather conditions and the soil environment.

PMID:34583281 | DOI:10.1016/j.jenvman.2021.113820

Am J Otolaryngol. 2021 Sep 16;43(1):103243. doi: 10.1016/j.amjoto.2021.103243. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the role of social and geographic factors on the likelihood of receiving transoral robotic surgery (TORS) or non-robotic transoral endoscopic surgery treatment in early stage oropharyngeal squamous cell carcinoma (OPSCC).

MATERIALS AND METHODS: The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 M0 OPSCC (AJCC v.7) who underwent treatment from 2010 to 2016. Demographics, tumor characteristics, treatment type, social, and geographic factors were all collected. Univariate analysis and multivariate logistic regression were then performed.

RESULTS: Among 9267 identified patients, 1774 (19.1%) received transoral robotic surgery (TORS), 1191 (12.9%) received transoral endoscopic surgery, and 6302 (68%) received radiation therapy. We found that lower cancer stage, lower comorbidity burden and HPV- positive status predicted a statistically significant increased likelihood of receiving surgery. Patients who reside in suburban or small urban areas (>1 million population), were low-to- middle income, or rely on Medicaid were less likely to receive surgery. Patients that reside in Medicaid-expansion states were more likely to receive TORS (p > .0001). Patients that reside in states that expanded Medicaid January 2014 and after were more likely to receive non-robotic transoral endoscopic surgery (p > .0001).

CONCLUSIONS: Poorer baseline health, lower socioeconomic status and residence in small urban areas may act as barriers to accessing minimally invasive transoral surgery while residence in a Medicaid-expansion state may improve access. Barriers to accessing robotic surgery may be greater than accessing non-robotic surgery.

PMID:34583290 | DOI:10.1016/j.amjoto.2021.103243

Environ Pollut. 2021 Sep 21;291:118217. doi: 10.1016/j.envpol.2021.118217. Online ahead of print.

ABSTRACT

Chlorpyrifos, an organophosphate (OP) insecticide, is prevalent in aquatic systems globally and is often implicated in aquatic toxicity during storm events. Chlorpyrifos induces toxicity by inhibition of acetylcholinesterase (AChE) activity, which has been related to alterations to fish swimming performance. Resistance to organophosphate insecticides, including chlorpyrifos, is prevalent in populations of the epibenthic amphipod Hyalella azteca in areas with known OP exposure. Previous studies have demonstrated an elevated bioaccumulation potential of insecticide-resistant prey items, however the potential for trophic transfer of chlorpyrifos from OP-resistant prey items and associated neurotoxic effects in fish predators has not been studied. Consequently, the present study aimed to determine the potential for trophic transfer of chlorpyrifos from OP-resistant H. azteca to a known predator, the inland silverside, Menidia beryllina at two temperatures (18 and 23 °C) to simulate temperature changes associated with global climate change (GCC). Fish were fed either ¹⁴C-chlorpyrifos-dosed H. azteca or control animals for 7 d, after which total bioaccumulation, percent parent chlorpyrifos, brain AChE activity and swimming performance (ramp-U_crit) were determined. Fish fed chlorpyrifos-dosed H. azteca bioaccumulated chlorpyrifos ranging from 29.9 to 1250 ng/g lipid, demonstrating the potential for trophic transfer. Lower bioaccumulation and greater biotransformation were observed in M. beryllina at 23 °C as compared to 18 °C, though this was not statistically significant. A significant 36.5% reduction in brain AChE activity was observed in fish fed chlorpyrifos-dosed H. azteca at 23 °C only, which may be attributed to increased biotransformation of parent chlorpyrifos to more potent AChE-inhibiting metabolites. Dietary chlorpyrifos exposure had no significant effect on swimming performance in M. beryllina, though ramp-U_crit was significantly increased by 25% at 23 as compared to 18 °C. These findings confirm the potential for trophic transfer of chlorpyrifos from OP-resistant prey to fish predators and the potential for elevated temperatures to exacerbate the neurotoxic effects of chlorpyrifos.

PMID:34583267 | DOI:10.1016/j.envpol.2021.118217

Placenta. 2021 Sep 20;115:87-96. doi: 10.1016/j.placenta.2021.09.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be identified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. We evaluate the performance of oxidative stress-associated potential biomarkers for FGR and PE, and their relationship with clinical characteristics.

METHODS: A prospective clinical pilot study was performed in healthy controls and women with pregnancies complicated by severe FGR with or without PE. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Placentas were examined microscopically. Descriptive statistics and receiver operating characteristics statistics were performed.

RESULTS: Mothers with both severe FGR and PE had significantly reduced FT levels (p < 0.001) and PlGF levels (p < 0.001), and increased levels of plasma IMA (p < 0.05), sFlt (p < 0.001), leptin (p < 0.05) and sRAGE (p < 0.01) compared to women with FGR only. Systemic FT levels were significantly inversely associated with blood pressure (p < 0.01) and plasma IMA (p < 0.001), leptin (p = 0.01) and sRAGE (p < 0.001). Systemic FT and leptin showed significant discriminative ability to differentiate mothers with both FGR and PE from mothers with uncomplicated pregnancies or pregnancies complicated by FGR only.

DISCUSSION: There is a significant discriminative capacity of FT, IMA, leptin and sRAGE that harbor potential as biomarkers of pregnancies complicated by combined FGR and PE.

PMID:34583270 | DOI:10.1016/j.placenta.2021.09.013