Nevin Manimala

Vet Parasitol. 2021 Jul 3;298:109516. doi: 10.1016/j.vetpar.2021.109516. Online ahead of print.

ABSTRACT

On the Northern Tablelands of New South Wales, Australia, endemic Theileria orientalis infection of cattle has been reported on farms where no ticks have been observed, raising the question of how Theileria is transmitted in these areas. To investigate the potential role of mechanical transmission by insects, the present study investigated the seasonal dynamics of biting fly species trapped between December 2017 and May 2019 on six cattle farms in the region where the presence of Theileria was confirmed. These flies, sucking lice collected from these farms and pools of Culicoides species affecting cattle also trapped in the region were subjected to qPCR detection of T. orientalis. Eleven species from eight genera of biting flies were collected using unbaited Nzi traps. Tabanid species were present in all farms, with Dasybasis oculata (43.6 %) and D. circumdata (27.6 %) being the most abundant and widespread species. The effect of season on the mean count per trapping event was statistically significant and highest in the summer months for Lilaea fuliginosa and D. oculata, and the autumn months for D. circumdata, with no seasonal effect on the abundance of the undescribed Dasybasis spp. No biting flies were trapped during the winter months. Sucking (Linognathus vituli and Haematopinus eurysternus) and biting (Bovicola bovis) cattle lice were also collected from all farms with the latter detected in only one farm. PCR screening for T. orientalis of trapped hematophagous insects resulted in parasite detection in the tabanid and Stomoxyini flies, biting midges and sucking lice with the highest proportion of positive samples for Haematopinus eurysternus (4/4 pools) and H. irritans exigua (6/15 individuals). The detection of the parasite in these potential vectors indicates a possible role in the mechanical transmission of T. orientalis and may partly explain the ubiquitous presence of Theileria in areas where ticks are absent.

PMID:34271315 | DOI:10.1016/j.vetpar.2021.109516

ESMO Open. 2021 Jul 13;6(4):100217. doi: 10.1016/j.esmoop.2021.100217. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib.

PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were ≥18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission + partial remission + stable disease) at 12 weeks on pazopanib. A Simon’s two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks.

RESULTS: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome.

CONCLUSION: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.

PMID:34271307 | DOI:10.1016/j.esmoop.2021.100217

Stat Med. 2021 Aug 15;40(18):4164-4165. doi: 10.1002/sim.9073.

NO ABSTRACT

PMID:34270812 | DOI:10.1002/sim.9073

Stat Med. 2021 Aug 15;40(18):4161-4163. doi: 10.1002/sim.9074.

NO ABSTRACT

PMID:34270811 | DOI:10.1002/sim.9074

Biom J. 2021 Jul 16. doi: 10.1002/bimj.202100089. Online ahead of print.

ABSTRACT

Our paper differs from previous literature in two ways: 1.We think in terms of clinical consequences, what benefits patients, what harms patients. Our main message is: using a not logic-respecting efficacy measure can potentially harm patients in a randomized controlled trial (RCT), as we prove analytically, and demonstrate with the OAK blood-based tumor mutational burden (bTMB) study. 2.We follow nature, which mixes effects within each treatment arm. Our secondary message is that following nature to mix within each treatment arm first before calculating any efficacy measure between treatments resolves issues. For example, following natural mixing to prove ratio of time is logic-respecting avoids the issue that weights of efficacy measures are implicit solution to an equation that depends on the unknown prognostic effect. More importantly, coding subgroup mixable estimation (SEM) by mixing within each treatment arm first and then calculating efficacy will make marginal and conditional efficacy agree, for logic-respecting efficacy measures (be it a ratio or a difference), no matter the outcome is continuous, binary, or time-to-event. One does not have to choose between marginal and conditional.

PMID:34270810 | DOI:10.1002/bimj.202100089

Biom J. 2021 Jul 16. doi: 10.1002/bimj.202100046. Online ahead of print.

ABSTRACT

We analyze data from a clinical trial investigating the effect of an on-demand drug for women with low sexual desire. These data consist of a varying number of measurements/events across patients of when the drug was taken, including data on a patient-reported outcome consisting of five items measuring an unobserved construct (latent variable). Traditionally, these data are aggregated prior to analysis by composing one sum score per event and averaging this sum score over all observed events. In this paper, we explain the drawbacks of this aggregating approach. One drawback is that these averages have different standard errors because the variance of the underlying events differs between patients and because the number of events per patient differs. Another drawback is the implicit assumption that all items have equal weight in relation to the latent variable being measured. We propose a multilevel structural equation model, treating the events (level 1) as nested observations within patients (level 2), as alternative analysis method to overcome these drawbacks. The model we apply includes a factor model measuring a latent variable at the level of the event and at the level of the patient. Then, in the same model, the latent variables are regressed on covariates to assess the drug effect. We discuss the inferences obtained about the efficacy of the on-demand drug using our proposed model. We further illustrate how to test for measurement invariance across grouping covariates and levels using the same model.

PMID:34270801 | DOI:10.1002/bimj.202100046

Int J Cancer. 2021 Jul 16. doi: 10.1002/ijc.33740. Online ahead of print.

ABSTRACT

Evidence for the human health effects of pesticides is needed to inform risk assessment. We studied the relationship between occupational insecticide use and risk of non-Hodgkin lymphoma (NHL) by pooling data from nine case-control studies participating in the InterLymph Consortium, including 7909 cases and 8644 controls from North America, the European Union, and Australia. Insecticide use was coded using self-report or expert assessment, for insecticide groups (e.g., organophosphates, pyrethroids) and active ingredients (e.g., malathion, permethrin). Associations with insecticides were estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CI) for all NHL and NHL subtypes, with adjustment for study site, demographic factors, and use of other pesticides. Occupational insecticide use, overall, was not associated with risk of NHL. Use of organophosphate insecticides was associated with increased risk of all NHL and the subtype follicular lymphoma, and an association was found with diazinon, in particular (ever use: OR=2.05, 95% CI: 1.24-3.37). The carbamate insecticide, carbaryl, was associated with risk of all NHL, and the strongest associations were found with T-cell NHL for ever-use (OR=2.44, 95% CI: 1.13-5.28) and longer duration (>8 years vs. never: OR=2.90, 95% CI: 1.02-8.25). There was no association of NHL with other broad groups of insecticides, including organochlorine and pyrethroids, and some inverse associations were estimated in relation to historical DDT use. Our findings contribute to the totality of evidence available to help inform risk decisions by public health and regulatory agencies – of importance given continued, widespread use of organophosphate and carbamate insecticides. This article is protected by copyright. All rights reserved.

PMID:34270795 | DOI:10.1002/ijc.33740

Radiat Res. 2021 Jul 16. doi: 10.1667/RADE-21-00079.1. Online ahead of print.

ABSTRACT

This commentary considers research needs for radiofrequency (RF) energy above 6 GHz, including in the “high band” of 5G New Radio (NR) communications systems that exists just beneath the mm-wave band (30-300 GHz). As of late 2020, approximately 100 RF bioeffects studies have been published involving exposures above 6 GHz, encompassing a wide range of exposure levels and frequencies. A majority of these studies report statistically significant effects of exposure, many at exposures within international safety limits. This commentary examines 31 genetic damage studies involving RF exposures above 6 GHz in the context of two sets of quality-assessment criteria: 1. “Risk of bias” (RoB) criteria used for systematic reviews of health-related studies; and 2. a broader set of criteria for research quality from a different scholarly approach (metascience). The 31 studies report several statistically significant effects of exposure on different markers for genetic damage. These effects, if real, would have great potential significance for carcinogen risk assessment. However, the studies as a group have significant technical weaknesses, including small size, failure to meet multiple RoB criteria, naïve use of statistics, and lack of prespecified hypotheses and methods of analysis, all of which increase the chances of false discovery. Here we propose a “carrot” (adequate funding to support high-quality research) and a “stick” (more stringent review of bioeffects manuscripts, including explicit instructions to reviewers to assess study quality) approach to increase the reliability of RF bioeffects studies to facilitate health agency reviews of this socially controversial topic.

PMID:34270779 | DOI:10.1667/RADE-21-00079.1

Phys Ther. 2021 Jul 16:pzab177. doi: 10.1093/ptj/pzab177. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the static balance of children with sensorineural hearing loss (SNHL) according to the degrees of SNHL and the function of the vestibular system.

METHODS: This cross-sectional study was conducted in public schools located in Caruaru, Pernambuco state, Brazil, with 130 children (65 with normal hearing and 65 with SNHL as documented by air and bone conduction audiometry) of both sexes and between 7 and 11 years old. Static balance was assessed by a stabilometric analysis using a force platform consisting of the circular area of center-of-pressure (COP) displacement of the children, evaluated in 3 positions: bipedal support with feet together and parallel (PF), tandem feet (TF), and 1 foot (OF), carried out under 2 sensory conditions each, with eyes open and eyes closed. After balance assessments, the children with SNHL received examinations of auditory and vestibular functions-through audiometry and computerized vectoelectronystagmography, respectively-to compose the groups according to degrees of SNHL and vestibular function.

RESULTS: The children with severe and profound SNHL demonstrated more static balance instabilities than the children with normal hearing in 5 positions assessed with eyes open (PF, TF, and OF) and eyes closed (PF and TF). The same phenomenon occurred in children with SNHL and associated vestibular dysfunction in all of the positions assessed with eyes open and eyes closed (PF, TF, and OF).

CONCLUSION: The larger the degree of SNHL, the greater the balance instability of the children. The children with SNHL and associated vestibular dysfunction showed the highest balance instabilities in this study.

IMPACT: Children with larger degrees of SNHL and associated vestibular dysfunction might require prolonged periods to rehabilitate their balance.

PMID:34270771 | DOI:10.1093/ptj/pzab177

J Parasitol. 2021 Jul 1;107(4):554-561. doi: 10.1645/21-28.

ABSTRACT

Parasite infection pressure is suggested to be a strong driver of transmission within ecosystems. We tested if infection pressure drives seroprevalence in intermediate host species for Toxoplasma gondii. We defined Toxoplasma infection pressure to intermediate host species as the combined influence of cat abundance, environmental conditions, and its prevalence in the cat population. We sampled and tested 2 species of rodent and collated information on Toxoplasma seroprevalence in koalas, wallabies, kangaroos, and sheep. All species were sampled using equivalent methods, within a 2-yr period, and from adjacent regions of low and high Toxoplasma infection pressure. The seroprevalence of Toxoplasma in kangaroos scaled with infection pressure, but we observed no statistical difference in seroprevalence for any other species between these 2 regions. Within the region of low infection pressure, Toxoplasma seroprevalence did not differ between species. However, within the region of high Toxoplasma infection pressure, we observed large variation in seroprevalence between species. Our results demonstrate that infection pressure is not sufficient by itself, but merely necessary, to drive Toxoplasma seroprevalence in intermediate host species. Where Toxoplasma seroprevalence in an intermediate host species is already low, further reducing infection pressure will not necessarily further decrease seroprevalence in those species. This has important ramifications for the mitigation of parasite infections and suggests that reductions in Toxoplasma infection pressure, intended to reduce infections, may be most effective and applicable to species that are known to experience high rates of infection.

PMID:34270758 | DOI:10.1645/21-28