Category: Statistics

Eur Heart J. 2022 Feb 23:ehac093. doi: 10.1093/eurheartj/ehac093. Online ahead of print.

ABSTRACT

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations.

METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS.

CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.

TAKE-HOME MESSAGE: The incorporation of polygenic risk into clinical care setting may provide a valuable risk stratification guidance to identify high-risk individuals for targeted intervention in primary prevention of CAD.

PMID:35195259 | DOI:10.1093/eurheartj/ehac093

BJS Open. 2022 Jan 6;6(1):zrac003. doi: 10.1093/bjsopen/zrac003.

ABSTRACT

BACKGROUND: Perioperative FLOT (fluorouracil plus leucovorin, oxaliplatin, and docetaxel) chemotherapy is a recent regimen used to treat resectable oesophagogastric (OG) adenocarcinoma, associated with improved overall survival versus earlier chemotherapy strategies. This study compared short-term perioperative morbidity in a large tertiary centre series of FLOT to a matched cohort receiving ECX/ECF (epirubicin, cisplatin, capecitabine (X) or 5-fluorouracil (F)).

METHODS: Consecutive patients completing four perioperative cycles of FLOT and proceeding to surgery with resectable OG adenocarcinoma were included. This was matched to patients from a historic ECX/ECF cohort from the same institution. A propensity score was calculated, and a secondary analysis using a propensity-matched group performed.

RESULTS: Cohorts were matched by tumour location and operations performed. In total there were 129 (64.5 per cent) oesophageal and 71 (35.5 per cent) gastric resections (FLOT 57 oesophageal, 43 gastric; ECF/ECX 64 oesophageal, 36 gastric). The median length of stay after surgery was 12 days in the FLOT group versus 15 in ECF/ECX (P = 0.035). There were no significant differences in overall perioperative complications and, specifically, no difference in OG anastomotic leaks, analysed by site (gastric (FLOT 0/79 (0 per cent) versus ECX 2/79 (2.5 per cent); P = 0.123), oesophageal (FLOT 4/121 (3.3 per cent) versus ECX 5/121 (4.1 per cent); P = 0.868) or type of surgery (open FLOT 1/121 (0.8 per cent) versus ECX 3/121 (2.5 per cent); P = 0.368; minimally invasive (FLOT 3/121 (2.5 per cent) versus ECX 2/121 (1.7 per cent); P = 0.555)). There was no statistical difference in leak-related return to theatre, 30-day (FLOT 0 (0 per cent) versus ECX 3/100 (3.0 per cent); P = 0.081), or 90-day (FLOT 0 (0 per cent) versus ECX 2/100 (2.0 per cent); P = 0.155) mortality.

CONCLUSION: In terms of surgical complications, FLOT and ECX/ECF were equally safe in patients undergoing resection for OG adenocarcinoma.

PMID:35195263 | DOI:10.1093/bjsopen/zrac003

Nephrol Dial Transplant. 2022 Feb 23:gfac010. doi: 10.1093/ndt/gfac010. Online ahead of print.

ABSTRACT

BACKGROUND: Non-dialytic conservative care (CC) has been proposed as a treatment option for patients with kidney failure. This systematic review and meta-analysis aims to compare survival outcomes between dialysis and CC in studies where patients made an explicit treatment choice.

METHODS: Five databases were systematically searched from origin up to February 25th, 2021 for studies comparing survival outcomes among patients choosing dialysis versus CC. Adjusted and unadjusted survival rates were extracted and meta-analysis performed where applicable. Risk of bias analysis was performed according to the Cochrane Risk Of Bias In Non-randomised Studies – of Interventions (ROBINS-I).

RESULTS: Twenty-two cohort studies were included covering 21,344 patients. Most studies were prone to selection bias and confounding. Patients opting for dialysis were generally younger, had less comorbid conditions, functional impairments and frailty than patients who chose CC. Unadjusted median survival from treatment decision or eGFR <15mL/min/1.73m2 ranged between 20-67 months for dialysis and 6-31 months for CC. Meta-analysis of twelve studies that provided adjusted hazard ratios (HRs) for mortality showed a pooled adjusted HR of 0.47 (95% CI 0.39-0.57) for patients choosing dialysis compared to CC. In subgroups of patients with higher age or severe comorbidities, the reduction of mortality risk remained statistically significant, although analyses were unadjusted.

CONCLUSIONS: Patients opting for dialysis have an overall lower mortality risk compared to patients opting for CC. However, high risk of bias and heterogeneous reporting preclude definitive conclusions and results cannot be translated to an individual level.

PMID:35195249 | DOI:10.1093/ndt/gfac010

Biol Open. 2022 Feb 15;11(2):bio059016. doi: 10.1242/bio.059016. Epub 2022 Feb 23.

ABSTRACT

Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) offer an attractive platform for cardiovascular research. Patient-specific iPSC-CMs are very useful for studying disease development, and bear potential for disease diagnostics, prognosis evaluation and development of personalized treatment. Several monolayer-based serum-free protocols have been described for the differentiation of iPSCs into cardiomyocytes, but data on their performance are scarce. In this study, we evaluated two protocols that are based on temporal modulation of the Wnt/β-catenin pathway for iPSC-CM differentiation from four iPSC lines, including two control individuals and two patients carrying an SCN5A mutation. The SCN5A gene encodes the cardiac voltage-gated sodium channel (Nav1.5) and loss-of-function mutations can cause the cardiac arrhythmia Brugada syndrome. We performed molecular characterization of the obtained iPSC-CMs by immunostaining for cardiac specific markers and by expression analysis of selected cardiac structural and ionic channel protein-encoding genes with qPCR. We also investigated cell growth morphology, contractility and survival of the iPSC-CMs after dissociation. Finally, we performed electrophysiological characterization of the cells, focusing on the action potential (AP) and calcium transient (CT) characteristics using patch-clamping and optical imaging, respectively. Based on our comprehensive morpho-functional analysis, we concluded that both tested protocols result in a high percentage of contracting CMs. Moreover, they showed acceptable survival and cell quality after dissociation (>50% of cells with a smooth cell membrane, possible to seal during patch-clamping). Both protocols generated cells presenting with typical iPSC-CM AP and CT characteristics, although one protocol (that involves sequential addition of CHIR99021 and Wnt-C59) rendered iPSC-CMs, which were more accessible for patch-clamp and calcium transient experiments and showed an expression pattern of cardiac-specific markers more similar to this observed in human heart left ventricle samples.

PMID:35195246 | DOI:10.1242/bio.059016

Arq Bras Cardiol. 2022 Jan;118(1):115-373. doi: 10.36660/abc.20211012.

NO ABSTRACT

PMID:35195219 | DOI:10.36660/abc.20211012

Arq Neuropsiquiatr. 2022 Feb 21:S0004-282X2022005003207. doi: 10.1590/0004-282X-ANP-2021-0034. Online ahead of print.

ABSTRACT

BACKGROUND: Although facial muscle weakness is common in patients with Facioscapulohumeral Muscular Dystrophy (FSHD), the literature is scarce on the speech and swallowing aspects.

OBJECTIVE: To investigate speech and swallowing patterns in FSHD and assess the correlation with clinical data.

METHODS: A cross-sectional study was conducted. Patients with clinical confirmation of FSHD and aged above 18 years were included and paired with healthy control individuals by age and gender. Individuals who had neurological conditions that could interfere with test results were excluded. The following assessments were applied: speech tests (acoustic and auditory-perceptual analysis); swallowing tests with the Northwestern Dysphagia Patient Check Sheet (NDPCS), the Eat Assessment Tool (EAT-10), the Speech Therapy Protocol for Dysphagia Risk (PARD), and the Functional Oral Intake Scale (FOIS); disease staging using the modified Gardner-Medwin-Walton scale (GMWS); and quality of life with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The correlation between test results and clinical data was verified by non-parametric statistics.

RESULTS: Thirteen individuals with FSHD and 10 healthy controls were evaluated. The groups presented significant differences in the motor bases of phonation and breathing. Regarding swallowing, two (15%) individuals presented mild dysphagia and seven (53.8%) showed reduced facial muscles strength. These results were not correlated with duration of the disease, age at symptoms onset, and quality of life. Dysphagia was related to worsening disease severity.

CONCLUSIONS: FSHD patients presented mild dysarthria and dysphagia. Frequent monitoring of these symptoms could be an important way to provide early rehabilitation and better quality of life.

PMID:35195226 | DOI:10.1590/0004-282X-ANP-2021-0034

Arq Bras Cardiol. 2022 Jan;118(1):88-94. doi: 10.36660/abc.20200921.

ABSTRACT

BACKGROUND: Atrial fibrillation is a public health problem associated with a fivefold increased risk of stroke or death. Analyzing costs is important when introducing new therapies and must be reconsidered in special situations, such as the novel coronavirus pandemic of 2020.

OBJECTIVE: This study aimed to evaluate the costs related to anticoagulant therapy in a one-year period, and the quality of life of atrial fibrillation patients treated in a public university hospital.

METHODS: Patient costs were those related to the anticoagulation and calculated by the average monthly costs of warfarin or direct oral anticoagulants (DOACs). Patient non-medical costs (eg., food and transportation) were calculated from data obtained by questionnaires. The Brazilian SF-6D was used to measure the quality of life. P-values < 0.05 were considered statistically significant.

RESULTS: The study population consisted of 90 patients, 45 in each arm (warfarin vs direct oral anticoagulants). Costs were 20% higher in the DOAC group ($55,532.62 vs $46,385.88), and mainly related to drug price ($23,497.16 vs $1,903.27). Hospital costs were higher in the warfarin group ($31,088.41 vs $24,604.74) and related to outpatient visits. Additionally, non-medical costs were almost twice higher in the warfarin group ($13,394.20 vs $7,430.72). Equivalence of price between the two drugs could be achieved by a 39% reduction in the price of DOACs. There were no significant group differences regarding quality of life.

CONCLUSIONS: Total costs were higher in the group of patients taking DOACs than those taking warfarin. However, a nearly 40% reduction in the price of DOACs could make it feasible to incorporate these drugs into the Brazilian public health system.

PMID:35195214 | DOI:10.36660/abc.20200921

Arq Bras Cardiol. 2022 Jan;118(1):77-87. doi: 10.36660/abc.20200890.

ABSTRACT

BACKGROUND: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities.

OBJECTIVES: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients.

METHODS: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05.

RESULTS: Mean LV ejection fraction was not different between the groups. The E/e’ ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027).

CONCLUSIONS: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

PMID:35195213 | DOI:10.36660/abc.20200890

Arq Bras Cardiol. 2022 Jan;118(1):52-58. doi: 10.36660/abc.20200669.

ABSTRACT

BACKGROUND: Serum Complement C1q/tumor necrosis factor-related protein-3 (CTRP3) levels and the relationship with atrial fibrillation (AF) in stable coronary artery disease (CAD) are not clearly known.

OBJECTIVE: The aim of this study was to investigate the change in serum CTRP3 levels and its relationship with paroxysmal AF in stable CAD.

METHOD: The study included 252 patients with CAD and 50 age-sex matched healthy control subjects. Serum CTRP3 levels were measured in addition to routine anamnesis, physical examination, laboratory and echocardiography examinations. The patients were divided into groups with and without CAD and CAD patients with and without paroxysmal AF. Statistical significance was accepted as p<0.05.

RESULTS: Serum CTRP3 levels were found to be significantly lower in patients with CAD than in the control group (p<0.001). AF was detected in 38 patients (15.08%) in the CAD group. The frequency of hypertension and female gender, hs-CRP, blood urea nitrogen, creatinine levels and left atrial end-diastolic (LAd) diameter were higher (p<0.05 for each one), and CTRP3 levels were lower in patients with AF (p <0.001). In the logistic regression analysis, serum CTRP3 levels and LAd diameters were independently determined the patients with AF (p<0.01 for each one). In this analysis, we found that every 1 ng/mL reduction in CTRP3 levels increased the risk of AF by 10.7%. In the ROC analysis of CTRP3 values for detecting patients with AF, the area under the ROC curve for CTRP3 was 0.971 (0.951-991) and was statistically significant (p<0.001). When the CTRP3 cut-off value was taken as 300 ng/mL, it was found to predict the presence of AF with 87.9% sensitivity and 86.8% specificity.

CONCLUSION: Serum CTRP3 levels were significantly reduced in patients with stable CAD and decreased CTRP3 levels were closely related to the presence of paroxysmal AF in these patients.

PMID:35195208 | DOI:10.36660/abc.20200669

Arq Bras Cardiol. 2022 Jan;118(1):68-74. doi: 10.36660/abc.20201060.

ABSTRACT

BACKGROUND: Despite the high proportion of octogenarians with acute pulmonary embolism, there is little information indicating the optimal management strategy, mainly therapeutic measures, such as lytic therapy.

OBJECTIVES: The number of elderly patients diagnosed with acute pulmonary embolism increases constantly. However, the role of thrombolytic treatment is not clearly defined among octogenarians. Our objective is to evaluate the effectiveness of lytic therapy in octogenarian patients diagnosed with pulmonary embolism.

METHODS: One hundred and forty eight subjects (70.3% women, n=104) aged more than eighty years were included in the study. The patients were divided in two groups: thrombolytic versus non-thrombolytic treatment. In-hospital mortality rates and bleeding events were defined as study outcomes. P-value <0.05 was considered as statistical significance.

RESULTS: In-hospital mortality decreased significantly in the thrombolytic group compared to the non-thrombolytic group (10.5% vs. 24.2% p=0.03). Minor bleeding events were more common in the arm that received thrombolytic treatment, but major hemorrhage did not differ between the groups (35.1% vs. 13.2%, p<0.01; 7% vs. 5.5% p=0.71, respectively). High PESI score (OR: 1.03 95%CI; 1.01-1.04 p<0.01), thrombolytic therapy (OR: 0.15 95%CI; 0.01-0.25, p< 0.01) and high troponin levels (OR: 1.20 95%CI; 1.01-1.43, p=0.03) were independently associated with in-hospital mortality rates in the multivariate regression analysis.

CONCLUSION: Thrombolytic therapy was associated with reduced in-hospital mortality at the expense of increased overall bleeding complications in octogenarians.

PMID:35195211 | DOI:10.36660/abc.20201060