We review the state of the art in meta-analysis and data pooling following the evolution of the statistical models employed.
Starting from a classic definition of meta-analysis of published data, a ...set of apparent antinomies which characterized the development of the meta-analytic tools are reconciled in dichotomies where the second term represents a possible generalization of the first one. Particular attention is given to the generalized linear mixed models as an overall framework for meta-analysis. Bayesian meta-analysis is discussed as a further possibility of generalization for sensitivity analysis and the use of priors as a data augmentation approach.
We provide relevant examples to underline how the need for adequate methods to solve practical issues in specific areas of research have guided the development of advanced methods in meta-analysis.
We show how all the advances in meta-analysis naturally merge into the unified framework of generalized linear mixed models and reconcile apparently conflicting approaches. All these complex models can be easily implemented with the standard commercial software available.
New approaches to cope with clinical and psychosocial aspects of type 2 diabetes (T2DM) are needed; gender influences the complex interplay between clinical and non-clinical factors. We used data ...from the BENCH-D study to assess gender-differences in terms of clinical and person-centered measures in T2DM.
Clinical quality of care indicators relative to control of HbA1c, lipid profile, blood pressure, and BMI were derived from electronic medical records. Ten self-administered validated questionnaires (SF-12 Health Survey; WHO-5 well-being index; Problem Areas in Diabetes (PAID) 5, Health Care Climate Questionnaire, Patients Assessment of Chronic Illness Care, Diabetes Empowerment Scale, Diabetes Self-care Activities, Global Satisfaction for Diabetes Treatment, Barriers to Taking Medications, Perceived Social Support) were adopted as person-centered outcomes indicators.
Overall, 26 diabetes clinics enrolled 2,335 people (men: 59.7%; women: 40.3%). Lower percentages of women reached HbA1c levels < =7.0% (23.2% vs. 27.8%; p = 0.03), LDL-cholesterol < 100 mg/dl (48.3 vs. 57.8%; p = 0.0005), and BMI <27 Kg/m2 (27.2 vs. 31.6%; p = 0.04) than men. Women had statistically significant poorer scores for physical functioning, psychological well-being, self-care activities dedicated to physical activities, empowerment, diabetes-related distress, satisfaction with treatment, barriers to medication taking, satisfaction with access to chronic care and healthcare communication, and perceived social support than men; 24.8% of women and 8.8% of men had WHO-5 < =28 (likely depression) (p < 0.0001); 67.7% of women and 55.1% of men had PAID-5 > 40 (high levels of diabetes-related distress) (p < 0.0001). At multivariate analysis, factors associated with an increased likelihood of having elevated HbA1c levels (≥8.0%) were different in men and women, e.g. having PAID-5 levels >40 was associated with a higher likelihood of HbA1c ≥8.0% in women (OR = 1.15; 95%CI 1.05-1.25) but not in men (OR = 1.00; 95%CI 0.93-1.08).
In T2DM, women show poorer clinical and person-centered outcomes indicators than men. Diabetes-related distress plays a role as a correlate of metabolic control in women but not in men. The study provides new information about the interplay between clinical and person-centered indicators in men and women which may guide further improvements in diabetes education and support programs.
Hamartomatous polyposis syndromes (HPS) are inherited conditions associated with high cancer risk. They include the Peutz-Jeghers and the PTEN hamartoma tumor syndromes, which are caused by mutations ...in the LKB1 and PTEN genes, respectively. Estimation of cancer risk is crucial in order to optimize surveillance, but no prognostic markers are currently available for these conditions. Our study relies on a 'signal transduction' hypothesis based on the crosstalk between LKB1/AMPK and PI3K/PTEN/Akt signaling at the level of the tumor suppressor protein FoxO3A. Interestingly, the FOXO3A rs2802292 G-allele was shown to be associated with longevity, reduced risk of aging-related diseases and increased expression of FoxO3A mRNA.
We typed rs2802292 in 150 HPS unrelated patients and characterized the expression of FoxO3A by quantitative PCR and immunoblot analysis in human intestinal cell lines.
We found a significantly higher risk for malignancies in females and TT genotype carriers compared to patients having at least one G-allele. Subgroup analysis for each HPS syndrome revealed a G-allele-associated beneficial effect on cancer risk occurring mainly in males. Molecular characterization of human intestinal cell lines showed that the G-allele significantly correlated with increased basal expression of FoxO3A mRNA and protein.
Our results suggest an inverse correlation between the protective allele (G) copy number and cancer risk, and might be useful to optimize surveillance in HPS patients. Further investigations are needed to confirm our hypothesis and to ascertain whether differences in therapeutic response exist across genotypes.
In Italy, the SINERGIA CCM was developed in the diabetes outpatient clinic of Cusano Milanino 4. In this model, self-monitoring blood glucose (SMBG) represents the key tool for patient engagement; ...within the empowerment philosophy, patients undergo an educational process, which incorporates interactive teaching strategies designed to involve patients in problem-solving and address their clinical, cultural and psychosocial needs. Following a preliminary evaluation of the SINERGIA impact in an observational cohort of over 1000 patients with T2DM cared for by the Cusano Milanino center 4, the Self-Care Study was designed as a multicenter, national, randomized (1:1), open-label, parallel group, controlled clinical trial of a duration of 12 months to compare SINERGIA models versus usual care.
One of the causes of permanent disability in chronic multiple sclerosis patients is the inability of oligodendrocyte progenitor cells (OPCs) to terminate their maturation program at lesions. To ...identify key regulators of myelin gene expression acting at the last stages of OPC maturation we developed a drug repositioning strategy based on the mouse immortalized oligodendrocyte (OL) cell line Oli-neu brought to the premyelination stage by stably expressing a key factor regulating the last stages of OL maturation. The Prestwick Chemical Library registered of 1,200 FDA-approved compound(s) was repositioned at three dosages based on the induction of Myelin Basic Protein (MBP) expression. Drug hits were further validated using dosage-dependent reproducibility tests and biochemical assays. The glucocorticoid class of compounds was the most highly represented and we found that they can be divided in three groups according to their efficacy on MBP up-regulation. Since target identification is crucial before bringing compounds to the clinic, we searched for common targets of the primary screen hits based on their known chemical-target interactomes, and the pathways predicted by top ranking compounds were validated using specific inhibitors. Two of the top ranking compounds, Halcinonide and Clobetasol, act as Smoothened (Smo) agonists to up-regulate myelin gene expression in the Oli-neuM cell line. Further, RxRgamma activation is required for MBP expression upon Halcinonide and Clobetasol treatment. These data indicate Clobetasol and Halcinonide as potential promyelinating drugs and also provide a mechanistic understanding of their mode of action in the pathway leading to myelination in OPCs. Furthermore, our classification of glucocorticoids with respect to MBP expression provides important novel insights into their effects in the CNS and a rational criteria for their choice in combinatorial therapies in de-myelinating diseases.
The aim of this study was to evaluate long-term effectiveness and safety of liraglutide in real world.
A diabetes clinic in Italy systematically collected data of all patients treated with ...liraglutide. Generalized hierarchical linear regression models for repeated measures were applied to assess trends over time of HbA1c, fasting plasma glucose (FPG), body weight, blood pressure and lipid profile.
Overall, 255 patients (mean age: 63.5±9.7 years, men: 56.9%, mean diabetes duration: 12.0±8.1 years) were treated with liraglutide during 36 months. Mean HbA1c levels decreased by -1.0±0.1% (P<0.0001), FPG by -46±6 mg/dL (P<0.0001), and body weight by -3.9±0.8 Kg (P<0.0001). HbA1c reduction was inversely related to diabetes duration, while body weight reduction was directly related to baseline BMI. Significant improvements in HDL-cholesterol and triglycerides levels were also documented. Trends of improvement in systolic blood pressure (SBP) levels were also found, with significant reduction in patients with baseline SBP≥140 mmHg. Treatment was well-tolerated by the vast majority of the patients. Neither severe hypoglycemia nor pancreatitis occurred. Drop-out rate was of 28.2%. Main causes of drop-out were gastrointestinal side effects and lack of efficacy.
Our analysis documents a prolonged effectiveness and safety of liraglutide, even after three years of treatment. In addition to significant improvement in glycemic control and body weight, liraglutide also provides additional benefits on cardiovascular risk profile, while minimizing the risk of hypoglycemia. However, magnitude of benefits reflects specific patient characteristics that deserve further investigation.
Learning from data in the quaternion domain enables us to exploit internal dependencies of 4D signals and treating them as a single entity. One of the models that perfectly suits with ...quaternion-valued data processing is represented by 3D acoustic signals in their spherical harmonics decomposition. In this paper, we address the problem of localizing and detecting sound events in the spatial sound field by using quaternion-valued data processing. In particular, we consider the spherical harmonic components of the signals captured by a first-order ambisonic microphone and process them by using a quaternion convolutional neural network. Experimental results show that the proposed approach exploits the correlated nature of the ambisonic signals, thus improving accuracy results in 3D sound event detection and localization.
Women with adenomyosis are at higher risk of endometriosis recurrence after surgery. This study was to assess if the lymphatic vessel network drained from the uterus to near organs where ...endometriosis foci lied.
A prospective, observational study, Canadian Task Force Classification II-2, was conducted at Sacro Cuore Don Calabria Hospital, Negrar, Italy. 104 white women aged 18-43 years were enrolled consecutively for this study. All patients underwent laparoscopy for endometriosis and a tubal dye test was carried out.
Evidence of dye dissemination through the uterine wall and outside the uterus was noted in 27 patients (26%) with adenomyosis as it permeated the uterine wall and a clear passage of the dye was shown in the pelvic lymphatic vessels regardless whether the tubes were unobstructed. Histological assessment of the uterine biopsies confirmed adenomyosis.
Adenomyosis is characterized by ectatic lymphatics that allow the drainage of intrauterine fluids (the dye and, perhaps, menstrual blood) at minimal intrauterine pressure from the uterine cavity though the lymphatic network to extrauterine organs. Certainly, this may not be the only explanation for endometriosis dissemination but the correlation between the routes of the dye drainage and location of endometriosis foci is highly suggestive.
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