Tag: statistics

Acta Obstet Gynecol Scand. 2022 Feb 23. doi: 10.1111/aogs.14334. Online ahead of print.

ABSTRACT

INTRODUCTION: Occult or untreated gestational diabetes (GDM) is a well-known risk factor for adverse perinatal outcomes and may contribute to antepartum stillbirth. We assessed the impact of screening for GDM on the rate of antepartum stillbirths in non-anomalous pregnancies by conducting a population-based study in 974 889 women in Austria.

MATERIAL AND METHODS: Our database was derived from the Austrian Birth Registry. Inclusion criteria were singleton live births and antepartum stillbirths ≥24⁺⁰ gestational weeks, excluding fetal congenital malformations, terminations of pregnancy and women with pre-existing type 1 or 2 diabetes. Main outcome measures were (a) overall stillbirth rates and (b) stillbirth rates in women at high risk of GDM (i.e., women with a body mass index ≥30 kg/m² , history of previous intrauterine fetal death, GDM, previous macrosomic offspring) before (2008-2010, “phase I”) and after (2011-2019, “phase II”) the national implementation of universal GDM screening with a 75 g oral glucose tolerance test in Austrian pregnant women by 2011.

RESULTS: In total, 940 373 pregnancies were included between 2008 and 2019, of which 2579 resulted in intrauterine fetal deaths at 33.51 ± 5.10 gestational weeks. After implementation of the GDM screening, a statistically significant reduction in antepartum stillbirth rates among non-anomalous singletons was observed only in women at high risk for GDM (4.10‰ [95% confidence interval (CI) 3.09-5.43] in phase I vs. 2.96‰ [95% CI 2.57-3.41] in phase II; p = 0.043) but not in the general population (2.76‰ [95% CI 2.55-2.99] in phase I vs. 2.74‰ [95% CI 2.62-2.86] in phase II; p = 0.845). The number needed to screen with the oral glucose tolerance test to subsequently prevent one case of (non-anomalous) intrauterine fetal death was 880 in the high-risk and 40 000 in the general population.

CONCLUSIONS: The implementation of a universal GDM screening programme in Austria in 2011 has not led to any significant reduction in antenatal stillbirths among non-anomalous singletons in the general population. More international data are needed to strengthen our findings.

PMID:35195277 | DOI:10.1111/aogs.14334

Cancer. 2022 Feb 23. doi: 10.1002/cncr.34154. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer cachexia is a syndrome characterized by anorexia and decreased body weight. This study evaluated the efficacy and safety of anamorelin, an orally active, selective ghrelin receptor agonist, in patients with cancer cachexia and a low body mass index (BMI).

METHODS: This multicenter, open-label, single-arm study enrolled Japanese patients with non-small cell lung cancer or gastrointestinal cancer with cancer cachexia (BMI < 20 kg/m² , involuntary weight loss > 2% in the last 6 months, and anorexia). Patients were administered 100 mg of anamorelin once daily for up to 24 weeks. The primary end point was a composite clinical response (CCR) at 9 weeks, which was defined as an increase in body weight of ≥5% from the baseline, an increase of ≥2 points in the score of the 5-item Anorexia Symptom Scale of the Functional Assessment of Anorexia/Cachexia Therapy, and being alive.

RESULTS: One hundred two patients were eligible and enrolled. The means and standard deviations for age and BMI were 71.0 ± 8.2 years and 17.47 ± 1.48 kg/m² , respectively. The CCR rate at 9 weeks was 25.9% (95% confidence interval [CI], 18.3%-35.3%), which met the primary end point with a lower 95% CI exceeding the prespecified minimum of 8%. Improvements in body weight and anorexia were durable and were accompanied by improvements in patients’ global impression of change for appetite/eating-related symptoms and overall condition. Adverse drug reactions occurred in 37 of 101 treated patients (36.6%), with the most common being glycosylated hemoglobin increases, constipation, and peripheral edema.

CONCLUSIONS: Anamorelin improved body weight and anorexia-related symptoms in patients with cancer cachexia and a low BMI with durable efficacy and favorable safety and tolerability.

LAY SUMMARY: Anamorelin is a drug that stimulates appetite and promotes weight gain. This clinical trial was aimed at determining its efficacy and safety in Japanese cancer patients with a low body mass index and cachexia, a syndrome associated with anorexia and weight loss. Anamorelin was found to improve body weight and anorexia-related symptoms in these patients, and these effects were durable for up to 24 weeks. Moreover, anamorelin was generally well tolerated. These findings suggest that anamorelin is a valuable treatment option for patients with cancer cachexia and a low body mass index.

PMID:35195274 | DOI:10.1002/cncr.34154

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