Tag: pubmed

Sci Rep. 2021 Oct 1;11(1):19558. doi: 10.1038/s41598-021-98945-2.

ABSTRACT

To evaluate the acoustic emissions (AE) and kinematic instability (KI) of the osteoarthritic (OA) knee joints, and to compare these signals to radiographic findings. Sixty-six female and 43 male participants aged 44-67 were recruited. On radiography, joint-space narrowing, osteophytes and Kellgren-Lawrence (KL) grade were evaluated. Based on radiography, 54 subjects (the study group) were diagnosed with radiographic OA (KL-grade ≥ 2) while the remaining 55 subjects (KL-grade < 2) formed the control group. AE and KI were recorded with a custom-made prototype and compared with radiographic findings using area-under-curve (AUC) and independent T-test. Predictive logistic regression models were constructed using leave-one-out cross validation. In females, the parameters reflecting consistency of the AE patterns during specific tasks, KI, BMI and age had a significant statistical difference between the OA and control groups (p = 0.001-0.036). The selected AE signals, KI, age and BMI were used to construct a predictive model for radiographic OA with AUC of 90.3% (95% CI 83.5-97.2%) which showed a statistical improvement of the reference model based on age and BMI, with AUC of 84.2% (95% CI 74.8-93.6%). In males, the predictive model failed to improve the reference model. AE and KI provide complementary information to detect radiographic knee OA in females.

PMID:34599226 | DOI:10.1038/s41598-021-98945-2

Nat Commun. 2021 Oct 1;12(1):5759. doi: 10.1038/s41467-021-25910-y.

ABSTRACT

Lassa fever is a longstanding public health concern in West Africa. Recent molecular studies have confirmed the fundamental role of the rodent host (Mastomys natalensis) in driving human infections, but control and prevention efforts remain hampered by a limited baseline understanding of the disease’s true incidence, geographical distribution and underlying drivers. Here, we show that Lassa fever occurrence and incidence is influenced by climate, poverty, agriculture and urbanisation factors. However, heterogeneous reporting processes and diagnostic laboratory access also appear to be important drivers of the patchy distribution of observed disease incidence. Using spatiotemporal predictive models we show that including climatic variability added retrospective predictive value over a baseline model (11% decrease in out-of-sample predictive error). However, predictions for 2020 show that a climate-driven model performs similarly overall to the baseline model. Overall, with ongoing improvements in surveillance there may be potential for forecasting Lassa fever incidence to inform health planning.

PMID:34599162 | DOI:10.1038/s41467-021-25910-y

NPJ Genom Med. 2020 Oct 2;5(1):42. doi: 10.1038/s41525-020-00149-6.

ABSTRACT

The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use these data as a surrogate for that of the Brazilian population. This lack of transferability is mainly due to differences between ancestry proportions of Brazilian and other admixed American populations. To address the issue, a coalition of research centres created the Brazilian Initiative on Precision Medicine (BIPMed). In this study, we aim to characterise two datasets obtained from 358 individuals from the BIPMed using two different platforms: whole-exome sequencing (WES) and a single nucleotide polymorphism (SNP) array. We estimated allele frequencies and variant pathogenicity values from the two datasets and compared our results using the BIPMed dataset with other public databases. Here, we show that the BIPMed WES dataset contains variants not included in dbSNP, including 6480 variants that have alternative allele frequencies (AAFs) >1%. Furthermore, after merging BIPMed WES and SNP array data, we identified 809,589 variants (47.5%) not present within the 1000 Genomes dataset. Our results demonstrate that, through the incorporation of Brazilian individuals into public genomic databases, BIPMed not only was able to provide valuable knowledge needed for the implementation of precision medicine but may also enhance our understanding of human genome variability and the relationship between genetic variation and disease predisposition.

PMID:34599191 | DOI:10.1038/s41525-020-00149-6

Noise Health. 2021 Jul-Sep;23(110):87-93. doi: 10.4103/nah.NAH_81_20.

ABSTRACT

BACKGROUND: For many young people, exposure to music from personal audio system use may represent a significant component of daily noise dose. Moreover, there is increasing concern for the hearing of those who listen at high volumes. The purpose of this study was to determine the noise levels experienced on commuter buses, and to investigate how these impact on the volume-setting behavior of young adult personal audio system users.

METHODS: A questionnaire was used to probe transport use, personal audio system-listening behaviors and the extent of understanding about noise-induced hearing loss. The influence of bus noise on volume-setting behavior was determined by measuring, in a lab setting, the sound-level preferences of participants when listening to their favorite song, a generic song, or a podcast in the absence and presence of various levels of bus noise, simulated using output-adjusted recordings made of bus noise. Statistical analysis was conducted using analysis of variance.

RESULTS: While the bus noise itself was below 85 dB Leq, as the sound level of the buses increased, so did the percentage of commuters who were found to exceed the equivalent of 8 hours of exposure at 85 dB Leq.

IMPLICATIONS: Investment in buses with lower noise levels or the use of noise-canceling or noise-occluding headphones would help to reduce the likelihood of noise-induced hearing loss for bus commuters.

PMID:34599112 | DOI:10.4103/nah.NAH_81_20

Blood Cancer J. 2021 Oct 1;11(10):163. doi: 10.1038/s41408-021-00555-8.

ABSTRACT

VIALE-C compared the safety and efficacy of venetoclax or placebo plus low-dose cytarabine (+LDAC) in patients with untreated AML ineligible for intensive chemotherapy. Overall, 211 patients were enrolled (n = 143, venetoclax; n = 68, placebo). At the primary analysis, the study did not meet its primary endpoint of a statistically significant improvement in overall survival (OS), however, ~60% of patients had been on study for ≤6-months. Here, we present an additional 6-months of follow-up of VIALE-C (median follow-up 17.5 months; range 0.1-23.5). Median OS was (venetoclax +LDAC vs. placebo +LDAC) 8.4 vs. 4.1 months (HR = 0.70, 95% CI 0.50,0.99; P = 0.040); a 30% reduction in the risk of death with venetoclax. Complete response (CR)/CR with incomplete hematologic recovery (CRi) rates were 48.3% vs. 13.2%. Transfusion independence rates (RBC) were 43% vs.19% and median event-free survival was 4.9 vs. 2.1 months (HR = 0.61; 95% CI 0.44,0.84; P = 0.002). These results represent improved efficacy over the primary analysis. Incidence of grade ≥3 adverse events were similar between study arms and overall safety profiles were comparable to the primary analysis. These data support venetoclax +LDAC as a frontline treatment option for patients with AML ineligible for intensive chemotherapy.This trial was registered at www.clinicaltrials.gov as #NCT03069352.

PMID:34599139 | DOI:10.1038/s41408-021-00555-8

Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):e2108492118. doi: 10.1073/pnas.2108492118.

ABSTRACT

The problem of optimizing over random structures emerges in many areas of science and engineering, ranging from statistical physics to machine learning and artificial intelligence. For many such structures, finding optimal solutions by means of fast algorithms is not known and often is believed not to be possible. At the same time, the formal hardness of these problems in the form of the complexity-theoretic NP-hardness is lacking. A new approach for algorithmic intractability in random structures is described in this article, which is based on the topological disconnectivity property of the set of pairwise distances of near-optimal solutions, called the Overlap Gap Property. The article demonstrates how this property 1) emerges in most models known to exhibit an apparent algorithmic hardness; 2) is consistent with the hardness/tractability phase transition for many models analyzed to the day; and, importantly, 3) allows to mathematically rigorously rule out a large class of algorithms as potential contenders, specifically the algorithms that exhibit the input stability (insensitivity).

PMID:34599090 | DOI:10.1073/pnas.2108492118

Noise Health. 2021 Jul-Sep;23(110):81-86. doi: 10.4103/nah.NAH_42_20.

ABSTRACT

OBJECTIVE: We made hypotheses that tinnitus will appear more likely in patients with sudden deafness with superior hearing in unaffected ear or with more severe acute hearing loss.

METHODS: A retrospective cohort study was performed. Five hundred forty-one patients were identified with idiopathic sudden sensorineural hearing loss (ISSHL) from January 1995 to August 2006. The exclusion criteria for this study were as follows: bilateral sudden hearing loss and Meniere disease, previous tinnitus or bilateral tinnitus at initial evaluation, and onset of hearing loss less than 7 days. The cohort enrolled 454 patients. The enrolled patients were classified into two groups: patient with acute onset tinnitus in the affected ear and patients without tinnitus at initial visit. Main outcome measures were patient age, the presence or absence of vertigo and tinnitus, audiometric patterns, the severity of hearing loss, and hearing in the unaffected ear.

RESULTS: Better contralateral hearing (n = 220 versus n = 72, P < 0.001) and younger age (48 versus 55 years, P < 0.001) were independently associated with the acute onset of tinnitus in patients with ISSHL. The degree of asymmetry between the ears did not differ significantly between patients with and without tinnitus. The sex, presence of vertigo, shape of audiogram, and severity of hearing loss were not correlated with tinnitus occurrence.

CONCLUSIONS: Tinnitus triggered by ISSHL was more frequent in patients with better contralateral hearing and of a younger age, irrespective of the severity of hearing loss on the affected side or the asymmetry between the ears.

PMID:34599111 | DOI:10.4103/nah.NAH_42_20

J Rheumatol. 2021 Oct 1:jrheum.210742. doi: 10.3899/jrheum.210742. Online ahead of print.

ABSTRACT

OBJECTIVE: The Covid-19 pandemic has created multiple uncertainties regarding rheumatic diseases or their treatment and susceptibility or severity of the viral disease.

METHODS: To address these questions as they relate to spondyloarthritis, we created a longitudinal survey from April 10, 2020 to April 26, 2021. 4723 world-wide subjects with spondyloarthritis and 450 household contacts participated. 3064 of the respondents were from the US and 70.4% of them provided longitudinal data. To control for the duration of potential risk of Covid-19, the rate of contracting Covid-19 was normalized for person months of exposure.

RESULTS: In an analysis of US subjects who provided longitudinal data, the incident rate ratio for the 159 (out of 2157) subjects who tested positive for Covid-19 was 1.16 compared to the US population as adjusted for age and sex (range 0.997 to 1.361, p=0.059). A paired evaluation using patients and household members did not show a statistically significant effect to indicate a predisposition to develop Covid-19 as a result of spondyloarthritis or its treatment. Our data failed to show that any class of medication commonly used to treat spondyloarthritis significantly affected the risk to develop Covid-19 or the severity of Covid-19.

CONCLUSION: These data do not exclude a small increased risk to develop Covid-19 as a result of spondyloarthritis, but the risk, if it exists, is low and not consistently demonstrated. The data should provide reassurance to patients and to rheumatologists about the risk that Covid-19 poses to patients with spondyloarthritis.

PMID:34599048 | DOI:10.3899/jrheum.210742

Clin Cancer Res. 2021 Oct 1:clincanres.2199.2021. doi: 10.1158/1078-0432.CCR-21-2199. Online ahead of print.

ABSTRACT

PURPOSE: The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is approved in the US for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in BRCA+ mCRPC patients identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2.

EXPERIMENTAL DESIGN: Patients had progressed after next-generation androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized.

RESULTS: TRITON2 enrolled 115 BRCA+ patients identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the three assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different to patients identified as BRCA+ by tissue testing.

CONCLUSION: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

PMID:34598946 | DOI:10.1158/1078-0432.CCR-21-2199

BMJ Open. 2021 Oct 1;11(10):e055219. doi: 10.1136/bmjopen-2021-055219.

ABSTRACT

INTRODUCTION: Hyperthyroidism is a common condition affecting up to 3% of the UK population. Treatment improves symptoms and reduces the risk of atrial fibrillation and stroke that contribute to increased mortality. The most common symptom is weight loss, which is reversed during treatment. However, the weight regain may be excessive, contributing to increased risk of obesity. Current treatment options include antithyroid drugs, radioiodine and thyroidectomy. Whether there are differences in either weight change or the long-term cardiometabolic risk between the three treatments is unclear.

METHODS AND ANALYSIS: The study will establish the natural history of weight change in hyperthyroidism, investigate the risk of obesity and risks of cardiometabolic conditions and death relative to the treatment. The data on patients diagnosed with hyperthyroidism between 1 January 1996 and 31 December 2015 will come from Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office of National Statistics Death Registry. The weight changes will be modelled using a flexible joint modelling, accounting for mortality. Obesity prevalence in the general population will be sourced from Health Survey for England and compared with the post-treatment prevalence of obesity in patients with hyperthyroidism. The incidence and time-to-event of major adverse cardiovascular events, other cardiometabolic outcomes and mortality will be compared between the treatments using the inverse propensity weighting model. Incidence rate ratios of outcomes will be modelled with Poisson regression. Time to event will be analysed using Cox proportional hazards model. A competing risks approach will be adopted to estimate comparative incidences to allow for the impact of mortality.

ETHICS AND DISSEMINATION: The study will bring new knowledge on the risk of developing obesity, cardiometabolic morbidity and mortality following treatment for hyperthyroidism to inform clinical practice and public health policies. The results will be disseminated via open-access peer-reviewed publications and directly to the patients and public groups (Independent Scientific Advisory Committee protocol approval #20_000185).

PMID:34598995 | DOI:10.1136/bmjopen-2021-055219