scholarly journals Linear mixed model helps to quantify PSA profile and predict disease progression

2009 ◽  
Vol 6 (2) ◽  
pp. 62-62
2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Tu ◽  
Lingmin Wu ◽  
Lihui Zheng ◽  
Shangyu Liu ◽  
Lishui Sheng ◽  
...  

Background: Current treatment guidelines for arrhythmogenic right ventricular cardiomyopathy (ARVC) mainly emphasize on prevention of ventricular arrhythmic events. Despite the progressive nature of ARVC, therapeutic options focusing on decelerating disease progression are scarce.Methods and Results: This retrospective observational cohort study included 311 patients [age, 39.1 ± 14.4 years; male, 233 (74.9%)] with a definite diagnosis of ARVC as determined by the 2010 Task Force Diagnostic Criteria. Among them, 113 patients (36.3%) received ACEI/ARB treatment. Disease progression was evaluated according to repeat transthoracic echocardiograms with a linear mixed model. Patients receiving ACEI/ARB treatment were associated with slower disease progression reflected by a gradual decrease in tricuspid annular plane systolic excursion than those not receiving ACEI/ARB treatment (0.37 vs. 0.61 mm per year decrease, P < 0.001) and slower dilation of right ventricular outflow tract (0.57 vs. 1.06 mm per year increased, P = 0.003). Cox proportional hazard regression models were used to evaluate the association between life-threatening ventricular tachycardia events and ACEI/ARB treatment. A reduced risk of life-threatening ventricular arrhythmia was associated with ACEI/ARB treatment compared to that without ACEI/ARB treatment (adjusted HR: 0.71, 95% CI: 0.52–0.96, P = 0.031).Conclusions: ACEI/ARB treatment is associated with slower disease progression and lower risk of life-threatening ventricular arrhythmia in patients with ARVC. Delaying disease progression may pave way for reducing life-threatening ventricular arrhythmia risk.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Xia ◽  
Wenjing Zhang ◽  
Yu Xu ◽  
Bin Wang ◽  
Zhiquan Yuan ◽  
...  

Abstract Background The receptor of severe respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2, is more abundant in kidney than in lung tissue, suggesting that kidney might be another important target organ for SARS-CoV-2. However, our understanding of kidney injury caused by Coronavirus Disease 2019 (COVID-19) is limited. This study aimed to explore the association between kidney injury and disease progression in patients with COVID-19. Methods A retrospective cohort study was designed by including 2630 patients with confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China) from 1 February to 13 April 2020. Kidney function indexes and other clinical information were extracted from the electronic medical record system. Associations between kidney function indexes and disease progression were analyzed using Cox proportional-hazards regression and generalized linear mixed model. Results We found that estimated glomerular filtration rate (eGFR) and creatinine clearance (Ccr) decreased in 22.0% and 24.0% of patients with COVID-19, respectively. Proteinuria was detected in 15.0% patients and hematuria was detected in 8.1% of patients. Hematuria (HR 2.38, 95% CI 1.50–3.78), proteinuria (HR 2.16, 95% CI 1.33–3.51), elevated baseline serum creatinine (HR 2.84, 95% CI 1.92–4.21) and blood urea nitrogen (HR 3.54, 95% CI 2.36–5.31), and decrease baseline eGFR (HR 1.58, 95% CI 1.07–2.34) were found to be independent risk factors for disease progression after adjusted confounders. Generalized linear mixed model analysis showed that the dynamic trajectories of uric acid was significantly related to disease progression. Conclusion There was a high proportion of early kidney function injury in COVID-19 patients on admission. Early kidney injury could help clinicians to identify patients with poor prognosis at an early stage. Graphic abstract


Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011090
Author(s):  
Simina Ticau ◽  
Gautham V. Sridharan ◽  
Shira Tsour ◽  
William L. Cantley ◽  
Amy Chan ◽  
...  

ObjectiveTo identify changes in the proteome associated with onset and progression of ATTRv amyloidosis, we performed an observational, case-controlled study which compared proteomes of patients with ATTRv amyloidosis and healthy controls.MethodsPlasma levels of >1,000 proteins were measured in patients with ATTRv amyloidosis with polyneuropathy who received either placebo or patisiran in the APOLLO study and in healthy controls. The impact of patisiran on the time profile of each protein was determined by linear mixed model at 0, 9, and 18 months. Neurofilament light chain (NfL) was further assessed using an orthogonal quantitative approach.ResultsLevels of 66 proteins were significantly changed with patisiran vs placebo, with NfL change most significant (p < 10−20). Analysis of changes in protein levels demonstrated that the proteome of patisiran-treated patients trended toward healthy controls at 18 months. Healthy controls' NfL levels were 4-fold lower than in patients with ATTRv amyloidosis with polyneuropathy (16.3 vs 69.4 pg/mL, effect: −53.1 pg/mL, 95% CI [–60.5 to −45.9]). NfL levels at 18 months increased with placebo (99.5 vs 63.2 pg/mL, 36.3 pg/mL, [16.5–56.1]) and decreased with patisiran treatment (48.8 vs 72.1 pg/mL, −23.3 pg/mL, [–33.4 to −13.1]) from baseline. At 18 months, improvement in modified Neuropathy Impairment Score +7 following patisiran significantly correlated with reduced NfL (R = 0.43, [0.29–0.55]).ConclusionsFindings suggest NfL may serve as a biomarker of nerve damage and polyneuropathy in ATTRv amyloidosis, may enable earlier diagnosis of patients with ATTRv amyloidosis, and facilitate monitoring of disease progression.Classification of evidenceThis study provides Class III evidence that NfL levels may enable earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and facilitate monitoring of disease progression.


2019 ◽  
Author(s):  
Simina Ticau ◽  
Gautham V Sridharan ◽  
Shira Tsour ◽  
William L Cantley ◽  
Amy Chan ◽  
...  

SummaryBackgroundHereditary transthyretin-mediated (hATTR) amyloidosis is a rare, progressively debilitating, and fatal disease caused by deposition of aggregated transthyretin amyloid in multiple organs and tissues. Highly variable disease penetrance has made it difficult to predict disease onset and progression. Clinically validated, non-invasive plasma biomarkers may facilitate earlier diagnosis and aid monitoring of disease progression.MethodsPlasma levels of >1000 proteins were measured in patients with hATTR amyloidosis with polyneuropathy who received either placebo or patisiran in the phase 3 APOLLO study (NCT01960348) and in a cohort of healthy individuals. The impact of patisiran treatment on the time profile of each protein was determined by a linear mixed model at 0, 9, and 18 months. Neurofilament light chain (NfL) protein was further assessed using an orthogonal quantitative approach.FindingsA significant change in the levels of 66 proteins was observed with patisiran vs placebo, with change in NfL, a marker of neuronal damage, most significant (p<10−20). Analysis of the changes in protein levels demonstrated that the proteome of patients treated with patisiran trended towards healthy individuals at 18 months. Plasma NfL levels in healthy controls were four-fold lower than in patients with hATTR amyloidosis with polyneuropathy (16·3 [SD 12·0] pg/mL vs 69·4 [SD 42·1] pg/mL, p<10−16). Levels of NfL at 18 months increased with placebo (99·5 [SD 60·1] pg/mL) and decreased with patisiran treatment (48·8 [SD 29·9] pg/mL). At 18 months, improvement in modified Neuropathy Impairment Score+7 (mNIS+7) in patisiran-treated patients significantly correlated with a reduction in NfL levels (R=0·43, p<10−7).InterpretationThe observed correlation of NfL reduction with patisiran treatment and improvement in mNIS+7 suggests it may serve as a biomarker of nerve damage and polyneuropathy in hATTR amyloidosis. This biomarker may enable earlier diagnosis of polyneuropathy in patients with hATTR amyloidosis and facilitate monitoring of disease progression.


2019 ◽  
Vol 56 (11) ◽  
pp. 765-768 ◽  
Author(s):  
Xiao Deng ◽  
Bin Xiao ◽  
John Carson Allen ◽  
Ebonne Ng ◽  
Jia Nee Foo ◽  
...  

BackgroundData on the long-term motor outcomes of genome-wide association study (GWAS)-linked Parkinson disease (PD) carriers are useful for clinical management.ObjectivesTo characterise the association between GWAS-linked PARK16 gene variant and disease progression in PD over a 9-year time frame.MethodsOver a 9-year period, carriers of PARK16 rs11240572 variant and non-carriers were followed up and evaluated using the modified Hoehn and Yahr (H&Y) staging scale and Unified Parkinson’s Disease Rating Scale (UPDRS) part III. A longitudinal, linear mixed model was performed to compare the changes of H&Y staging scale, UPDRS motor score and UPDRS subscores between the two groups.ResultsA total of 156 patients (41 PARK16 carriers and 115 non-carriers) were evaluated and followed up for up to 9 years. Using longitudinal linear mixed model analysis, there was a greater rate of deterioration in the motor function as measured by the UPDRS scores compared with non-carriers after 5 years from the date of diagnosis (p=0.009). In addition, we demonstrated that PARK16 variant carriers had worse gait scores (p=0.043) and greater motor progression than non-carriers after 6 years based on the modified H&Y staging scale (p=0.040).ConclusionsIn a 9-year longitudinal study, we demonstrated that PD PARK16 variant carriers exhibited greater motor progression after 5 years of disease compared with non-carriers, suggesting that GWAS-linked gene variants may influence disease progression over time. Closer monitoring and management of these higher risk patients can facilitate a better quality of life.


2020 ◽  
Author(s):  
James L. Peugh ◽  
Sarah J. Beal ◽  
Meghan E. McGrady ◽  
Michael D. Toland ◽  
Constance Mara

2020 ◽  
Vol 641 ◽  
pp. 159-175
Author(s):  
J Runnebaum ◽  
KR Tanaka ◽  
L Guan ◽  
J Cao ◽  
L O’Brien ◽  
...  

Bycatch remains a global problem in managing sustainable fisheries. A critical aspect of management is understanding the timing and spatial extent of bycatch. Fisheries management often relies on observed bycatch data, which are not always available due to a lack of reporting or observer coverage. Alternatively, analyzing the overlap in suitable habitat for the target and non-target species can provide a spatial management tool to understand where bycatch interactions are likely to occur. Potential bycatch hotspots based on suitable habitat were predicted for cusk Brosme brosme incidentally caught in the Gulf of Maine American lobster Homarus americanus fishery. Data from multiple fisheries-independent surveys were combined in a delta-generalized linear mixed model to generate spatially explicit density estimates for use in an independent habitat suitability index. The habitat suitability indices for American lobster and cusk were then compared to predict potential bycatch hotspot locations. Suitable habitat for American lobster has increased between 1980 and 2013 while suitable habitat for cusk decreased throughout most of the Gulf of Maine, except for Georges Basin and the Great South Channel. The proportion of overlap in suitable habitat varied interannually but decreased slightly in the spring and remained relatively stable in the fall over the time series. As Gulf of Maine temperatures continue to increase, the interactions between American lobster and cusk are predicted to decline as cusk habitat continues to constrict. This framework can contribute to fisheries managers’ understanding of changes in habitat overlap as climate conditions continue to change and alter where bycatch interactions could occur.


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