Category: Nevin Manimala

J Appl Biomech. 2022 Jan 19:1-9. doi: 10.1123/jab.2021-0162. Online ahead of print.

ABSTRACT

Trochlear groove geometry and the location of the tibial tubercle, where the patellar tendon inserts, have both been associated with patellofemoral instability and can be modified surgically. Although their effects on patellofemoral biomechanics have been investigated individually, the interaction between the two is unclear. The authors’ aim was to use statistical shape modeling and musculoskeletal simulation to examine the effect of patellofemoral geometry on the relationship between tibial tubercle location and patellofemoral function. A statistical shape model was used to generate new knee geometries with trochlear grooves ranging from shallow to deep. A Monte Carlo approach was used to create 750 knee models by randomly selecting a geometry and randomly translating the tibial tubercle medially/laterally and anteriorly. Each knee model was incorporated into a musculoskeletal model, and an overground walking trial was simulated. Knees with shallow trochlear geometry were more sensitive to tubercle medialization with greater changes in lateral patella position (-3.0 mm/cm medialization shallow vs -0.6 mm/cm deep) and cartilage contact pressure (-0.51 MPa/cm medialization shallow vs 0.04 MPa/cm deep). However, knees with deep trochlear geometry experienced greater increases in medial cartilage contact pressure with medialization. This modeling framework has the potential to aid in surgical decision making.

PMID:35045394 | DOI:10.1123/jab.2021-0162

Urol Int. 2022 Jan 19:1-13. doi: 10.1159/000520813. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of the study was to identify nursing management-associated factors correlated with urinary tract infection (UTI) in residents from nursing homes.

METHODS: The data of 3,393 nursing homes were extracted from LTCfocus database. Variables statistically correlated with UTI rate were identified by Spearman correlation analysis. Tobit regression model was used for finding the factors associated with UTI rate.

RESULTS: The number of beds (β = 0.03, 95% CI: 0.02-0.05), number of occupied beds/the total number of beds (β = 0.05, 95% CI: 0.03-0.07), number of admissions/total number of beds (β = 0.27, 95% CI: 0.11-0.43), the proportions of residents whose primary support is Medicare (β = 0.03, 95% CI: 0.01-0.06), women residents (β = 0.04, 95% CI: 0.02-0.06), White residents (β = 0.02, 95% CI: 0.01-0.03), patients with bladder incontinence (β = 0.03, 95% CI: 0.02-0.05), hypertension patients (β = 0.03, 95% CI: 0.01-0.05), and long-stay residents with daily pain (β = 0.16, 95% CI: 0.12-0.19), hospitalizations per resident year (β = 0.76, 95% CI: 0.30-1.21), and average daily census (β = -0.02, 95% CI: -0.03 to 0.00) were factors associated with UTI rate.

CONCLUSIONS: Nursing homes with more females, White people, and patients with bladder incontinence, hypertension, or daily pain should be cared more and the number of occupied beds and admissions should be controlled to reduce the occurrence of UTI.

PMID:35045413 | DOI:10.1159/000520813

Contemp Clin Trials. 2022 Jan 16:106681. doi: 10.1016/j.cct.2022.106681. Online ahead of print.

ABSTRACT

IMPORTANCE: The COVID-19 pandemic has impacted clinical research due to safety measures such as social distancing and lockdowns. However, developing treatments for COVID-19 relies on conducting clinical trials. Using telemedicine or virtual methods may support ongoing trials and limit the pandemic’s impact on clinical research.

OBJECTIVE: To examine the use of virtual methods among ongoing and discontinued COVID-19 clinical trials.

DESIGN: In this cross-sectional analysis, we performed a systematic search of ClinicalTrials.gov for COVID-19 related trials registered since the pandemic began. In masked, duplicate fashion, authors extracted data from included studies, noting whether trialists reported using telecommunication, virtualization, or remote data collection to deliver interventions and monitor outcome measures. The authors also coded the use of virtual methods for recruitment, enrollment, or follow-up visits. Chi-square tests and Kruskal-Wallis tests were used to assess differences in the use of virtual methods between ongoing and discontinued studies and differences between intervention types.

RESULTS: Our search returned 2549 clinical trials, of which 2383 were included. Of included studies, 2109 (88.5%) were ongoing and 274 (11.5%) were discontinued. Overall, 519 (24.6%) ongoing COVID-19 trials reported using virtual methods for trial conduct and 43 (15.7%) discontinued trials reported using virtual methods. There was a statistically significant difference in the rate of reporting virtual methods between discontinued and ongoing trials (X²₁ = 27.2, P < .001). Studies listed as Behavioral or Other were more likely to report using virtual methods for delivering interventions compared to other intervention types (X²₁ = 751.88, P < .001).

CONCLUSIONS AND RELEVANCE: The COVID-19 pandemic has necessitated an unprecedented need for safe and efficient clinical trial conduct. Nearly a quarter of ongoing COVID-19 clinical trials in our sample reported using virtual methods for supporting trial progress. Ongoing trials were more likely to report virtual methods compared to discontinued trials. Developing strategies that allow for continuing trials during emergencies may limit trial disruption. Exploring and developing remote trial methods may continue to be valuable in light of emerging COVID-19 variants and may persist beyond the pandemic.

PMID:35045363 | DOI:10.1016/j.cct.2022.106681

Pract Radiat Oncol. 2022 Jan 16:S1879-8500(22)00002-9. doi: 10.1016/j.prro.2021.12.012. Online ahead of print.

ABSTRACT

PURPOSE: We analyze the cost-effectiveness of standard palliative external beam radiation (EBRT, 8 Gy in 1 fraction), stereotactic body radiation therapy (SBRT, 24 Gy in 2 fractions), and radiofrequency ablation (RFA) for painful spinal metastases. Single-fraction SBRT (delivering 24 Gy) is also assessed.

METHODS AND MATERIALS: A Markov state transition model was constructed. Key model parameters were derived from prospective clinical trial data. Strategies were compared using the incremental cost-effectiveness ratio (ICER), with effectiveness in quality-adjusted life years (QALYs) and a willingness-to-pay (WTP) threshold of $100,000 per QALY gained. Costs included both hospital and professional costs using 2020 Medicare reimbursement.

RESULTS: The base case demonstrated that 2-fraction SBRT was not cost-effective compared to single-fraction EBRT, with an ICER of $194,145/QALY gained. RFA was a dominated treatment strategy (more costly and less effective) in this model. Probabilistic sensitivity analysis demonstrated that EBRT was favored in 66% of model iterations. If median survival were improved after SBRT, two-fraction SBRT became cost-effective, with ICER of $80,394, $57,062, and $47,038 for 3, 6, and 9-month improvements in survival. Because two-fraction SBRT data reported 18% of patients with indeterminant pain response at 3 months, and two-fraction SBRT is infrequently used in clinical practice, single-fraction SBRT data was also assessed. Single-fraction SBRT delivering 24 Gy was cost-effective compared to single-fraction EBRT, with an ICER of $92,833/QALY gained.

CONCLUSIONS: For appropriately chosen patients, single-fraction SBRT is more cost-effective than conventional EBRT or RFA. Conventional EBRT remains a cost-effective treatment for patients with poor expected survival.

PMID:35045365 | DOI:10.1016/j.prro.2021.12.012

EBioMedicine. 2022 Jan 16;75:103810. doi: 10.1016/j.ebiom.2021.103810. Online ahead of print.

ABSTRACT

BACKGROUND: V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.

METHODS: We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 × 10⁵ median Tissue Culture Infectious Dose [TCID₅₀]), one or two injections of a high dose vaccine (1 × 10⁶ TCID₅₀), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immunogenicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298.

FINDINGS: Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment-related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiving the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine.

INTERPRETATION: While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.

PMID:35045362 | DOI:10.1016/j.ebiom.2021.103810

Eur J Radiol. 2022 Jan 11;148:110155. doi: 10.1016/j.ejrad.2022.110155. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study is to investigate the diagnostic ability of diffusion kurtosis imaging (DKI) -derived parameters combining with clinical data as risk factors for EMVI’s involvement status in rectal adenocarcinoma.

MATERIALS AND METHODS: Preoperative MR examination including DKI and conventional diffusion-weighted imaging (DWI) was performed on 154 rectal adenocarcinoma patients enrolled in this respective study. K_mean, D_mean, and apparent diffusion coefficient (ADC) values were calculated. Clinical information, serum tumor markers, MR and pathological assessment of EMVI were recorded. The Shapiro-Wilk test, two-sample t-test, Mann-Whitney U test, Spearman’s rank-order correlation, univariate and multivariate logistic regression analyses were used for statistical analysis. Receiver operating characteristic (ROC) curve analyses were performed to identify risk factors in EMVI involvement.

RESULTS: Of the 154 patients, pEMVI-positive rectal tumors had significantly higher Kmean values, lower ADC_mean values compared to pEMVI-negative rectal tumors. K_mean values positively correlated with mrEMVI scores, whereas ADC_mean values showed a negative correlation with mrEMVI scores. However, there was no significant correlation between the Dmean values and the mrEMVI scores. Univariate analysis demonstrated increased Kmean values, decreased ADCmean values, nodal involvement, an advanced tumor stage, and a G2 tumor grade were significantly related to the pEMVI of rectal adenocarcinoma. The multivariate analysis demonstrated that the Kmean values, lymph node involvement and an advanced tumor stage (T3) were independent risk factors for EMVI.

CONCLUSION: The potential for diffusion kurtosis imaging as a biomarker for evaluating the EMVI of rectal cancer is feasible, especially given DKI’s capability of detecting tumor heterogeneity noninvasively.

PMID:35045353 | DOI:10.1016/j.ejrad.2022.110155

Neuron. 2022 Jan 11:S0896-6273(21)01036-9. doi: 10.1016/j.neuron.2021.12.019. Online ahead of print.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling of motor neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes that represent a 5-fold increase in recovered heritability. Extensive conservation, transcriptome, network, and rare variant analyses demonstrated the functional significance of candidate genes in healthy and diseased motor neurons and brain tissues. Genetic convergence between common and rare variation highlighted KANK1 as a new ALS gene. Reproducing KANK1 patient mutations in human neurons led to neurotoxicity and demonstrated that TDP-43 mislocalization, a hallmark pathology of ALS, is downstream of axonal dysfunction. RefMap can be readily applied to other complex diseases.

PMID:35045337 | DOI:10.1016/j.neuron.2021.12.019

Sci Total Environ. 2022 Jan 16:153182. doi: 10.1016/j.scitotenv.2022.153182. Online ahead of print.

ABSTRACT

Non-planned agricultural land abandonment is affecting natural hydrological processes. This is especially relevant in vulnerable arid karstic watersheds, where water resources are scarce but vital for sustaining natural ecosystems and human settlements. However, studies assessing the spatiotemporal evolution of the hydrological responses considering land-use changes and precipitation cycles for long periods are rare in karstic environments. In this research, we selected a representative karstic watershed in a Mediterranean semiarid domain, since in this belt, karst environments are prone to land degradation processes due to human impacts. Geographic Information Systems-based tools and hydrological modeling considering daily time steps were combined with temporal analysis of climate variables (wavelet analysis) to demonstrate possible interactions and vulnerable responses. Observed daily flow data were used to calibrate/validate these hydrological models by applying statistic indicators such as the NSE efficiency and a self-developed index (the ANSE index). This new index could enhance goodness-of-fit measurements obtained with traditional statistics during the model optimization. We hypothesize that this is key to adding new inputs to this research line. Our results revealed that: i) changes in the type of sclerophyllous vegetation (Quercus calliprinos, ilex, rotundifolia, suber, etc.) from 81.5% during the initial stage (1990) to natural grasslands by 81.6% (2018); and, ii) decreases in agricultural areas (crops) by approximately 60% and their transformation into coniferous forests, rock outcrops, sparsely natural grasslands, etc. in the same period. Consequently, increases in the curve number (CN) rates were identified as a result of land abandonment. As a result, an increase in peak flow events jointly with a relevant decrease of the average flow rates (water scarcity) in the watershed was predicted by the HEC-HMS model and verified through the observed data. This research provides useful information about the effects of anthropogenic changes in the hydrodynamic behaviour of karstic watersheds and water resource impacts, especially key in water-scarce areas that depict important hazards for the water supply of related populations and natural ecosystems.

PMID:35045347 | DOI:10.1016/j.scitotenv.2022.153182

Am Heart J. 2022 Jan 16:S0002-8703(22)00006-0. doi: 10.1016/j.ahj.2022.01.006. Online ahead of print.

ABSTRACT

BACKGROUND: Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM.

METHODS: 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation.

RESULTS: Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, p = 0.006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055 – 4.015], p = 0.034 with respect to non-ischemic LGE).

CONCLUSIONS: The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

PMID:35045326 | DOI:10.1016/j.ahj.2022.01.006

J Clin Epidemiol. 2022 Jan 16:S0895-4356(22)00013-0. doi: 10.1016/j.jclinepi.2022.01.008. Online ahead of print.

ABSTRACT

OBJECTIVES: Among ID studies seeking to make causal inferences and pooling individual-level longitudinal data from multiple infectious disease cohorts, we sought to assess what methods are being used, how those methods are being reported, and whether these factors have changed over time.

STUDY DESIGN AND SETTING: Systematic review of longitudinal observational infectious disease studies pooling individual-level patient data from 2+ studies published in English in 2009. 2014, or 2019. This systematic review protocol is registered with PROSPERO (CRD42020204104).

RESULTS: Our search yielded 1,462 unique articles. Of these, 16 were included in the final review. Our analysis showed a lack of causal inference methods and of clear reporting on methods and the required assumptions.

CONCLUSION: There are many approaches to causal inference which may help facilitate accurate inference in the presence of unmeasured and time-varying confounding. In observational ID studies leveraging pooled, longitudinal IPD, the absence of these causal inference methods and gaps in the reporting of key methodological considerations suggests there is ample opportunity to enhance the rigor and reporting of research in this field. Interdisciplinary collaborations between substantive and methodological experts would strengthen future work.

PMID:35045316 | DOI:10.1016/j.jclinepi.2022.01.008