Giuseppe Migliara

Are community-based nurse-led self-management support interventions effective in chronic patients? Results of a systematic review and meta-analysis

The expansion of primary care and community-based service delivery systems is intended to meet emerging needs, reduce the costs of hospital-based ambulatory care and prevent avoidable hospital use by the provision of more appropriate care. Great emphasis has been placed on the role of self-management in the complex process of care of patient with long-term conditions. Several studies have determined that nurses, among the health professionals, are more recommended to promote health and deliver preventive programs within the primary care context. The aim of this systematic review and meta-analysis is to assess the efficacy of the nurse-led self-management support versus usual care evaluating patient outcomes in chronic care community programs. Systematic review was carried out in MEDLINE, CINAHL, Scopus and Web of Science including RCTs of nurse-led self-management support interventions performed to improve observer reported outcomes (OROs) and patients reported outcomes (PROs), with any method of communication exchange or education in a community setting on patients >18 years of age with a diagnosis of chronic diseases or multi-morbidity. Of the 7,279 papers initially retrieved, 29 met the inclusion criteria. Meta-analyses on systolic (SBP) and diastolic (DBP) blood pressure reduction (10 studies—3,881 patients) and HbA1c reduction (7 studies—2,669 patients) were carried-out. The pooled MD were: SBP -3.04 (95% CI -5.01—-1.06), DBP -1.42 (95% CI -1.42—-0.49) and HbA1c -0.15 (95% CI -0.32–0.01) in favor of the experimental groups. Meta-analyses of subgroups showed, among others, a statistically significant effect if the interventions were delivered to patients with diabetes (SBP) or CVD (DBP), if the nurses were specifically trained, if the studies had a sample size higher than 200 patients and if the allocation concealment was not clearly defined. Effects on other OROs and PROs as well as quality of life remain inconclusive.

Which Lynch syndrome screening programs could be implemented in the “real world”? A systematic review of economic evaluations

PurposeLynch syndrome (LS) screening can significantly reduce cancer morbidity and mortality in mutation carriers. Our aim was to identify cost-effective LS screening programs that can be implemented in the “real world.”MethodsWe performed a systematic review of full economic evaluations of genetic screening for LS in different target populations; health outcomes were estimated in life-years gained or quality-adjusted life-years.ResultsOverall, 20 studies were included in the systematic review. Based on the study populations, we identified six categories of LS screening program: colorectal cancer (CRC)–based, endometrial cancer–based, general population–based, LS family registry–based, cascade testing–based, and genetics clinic–based screening programs. We performed an in-depth analysis of CRC-based LS programs, classifying them into three additional subcategories: universal, age-targeted, and selective. In five studies, universal programs based on immunohistochemistry, either alone or in combination with the BRAF test, were cost-effective compared with no screening, while in two studies age-targeted programs with a cutoff of 70 years were cost-effective when compared with age-targeted programs with lower age thresholds.ConclusionUniversal or <70 years–age-targeted CRC-based LS screening programs are cost-effective and should be implemented in the “real world.”

Familial Hypercholesterolemia: A Systematic Review of Guidelines on Genetic Testing and Patient Management

Background Familial hypercholesterolemia (FH) is an autosomal-dominant hereditary disorder of lipid metabolism that causes lifelong exposure to increased LDL levels resulting in premature coronary heart disease and, if untreated, death. Recent studies have shown its prevalence to be higher than previously considered, which has important implications for the mortality and morbidity of associated cardiovascular disease (CVD). Several clinical tools are used worldwide to help physicians diagnose FH, but nevertheless most patients remain undetected. This systematic review of guidelines aims to assess the role of genetic testing in the screening, diagnosis, and management of patients affected by heterozygous or homozygous FH and to identify related health-care pathways. Methods We performed a systematic review of the literature; inclusion criteria were English or Italian guidelines focusing on genetic testing. The guidelines were included and evaluated for their content and development process using the Appraisal of Guidelines for Research and Evaluation II instrument. Results Ten guidelines were considered eligible, and all were judged to be of good quality, with slight differences among them. The most common indications for performing genetic tests were high levels of cholesterol, or physical findings consistent with lipid disorder, in the subject or in the family history. Subsequent screening of family members was indicated when a mutation had been identified in the index patient. Regarding patient management, the various guidelines agreed that intensive treatment with lipid-lowering medications should begin as quickly as possible and that lifestyle modifications should be an integral part of the therapy. Conclusion Since the early detection of affected patients is beneficial for effective prevention of CVD, genetic testing is particularly useful for identifying family members via cascade screening and for distinguishing between heterozygous and homozygous individuals, the latter of which require more extreme therapeutic intervention.

Toll-Like Receptor 2 Mediates In Vivo Pro- and Anti-inflammatory Effects of Mycobacterium Tuberculosis and Modulates Autoimmune Encephalomyelitis

Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll-like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 proinflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participated directly to a putative binding pocket for sugars and cadherins. The distinct pro- and anti-inflammatory actions impacted severity, extent of remission, and distribution of the lesions within the central nervous system of experimental autoimmune encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.

Association between Human Papilloma Virus (HPV) vaccination and risk of Multiple Sclerosis: A systematic review

ABSTRACT INTRODUCTION: The vaccination against Humanpapilloma Virus (HPV) is an effective strategy to prevent high-risk HPV infection and subsequent cervical carcinogenesis. Although the safety profile has been ascertained, the relation with the development of central nervous system (CNS) autoimmune disorders (AD) appears still controversial. Multiple Sclerosis (MS) is the most common cause of chronic neurological impairment in young people, typically striking females. The main purpose of this review was to assess the association between HPV vaccination and MS. METHODS: The systematic review of the literature was carried out using 5 search engines: MEDLINE, SCOPUS, ISI WEB OF KNOWLEDGE, GOOGLE SCHOLAR and ClinicalTrial.gov. The web search was updated on January 2017. PRISMA checklist was adopted to address the content of the systematic review. The measures of outcome were reported as relative risk (RR) in cohort studies and odds ratio (OR) in case-control studies. RESULTS: The systematic review identified 5 observational studies, 9 reviews, and 1 randomized clinical trials (RCT) pooled analysis. The RR of MS onset detected by cohort studies ranged from 1.54 (95%CI, 0.04–8.59) to 1.37 (95%CI, 0.74–3.20). Concerning case-control studies, the OR spanned from 0.3, (95%CI 0.1–0.9) to 1.60 (95%CI = 0.79–3.25) for the group exposed to HPV vaccination. No result was significant. CONCLUSION: This review showed no significant association between HPV vaccination and MS. The low statistical power of the studies agreed with the low incidence of MS disease among general population. In order to overcome the shortcoming the research may be extended to the entire pattern of CNS ADs.

Striatal presynaptic dopaminergic dysfunction in gambling disorder: A 123I-FP-CIT SPECT study

Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment‐seeking GD subjects and 17 healthy controls in terms of striatal DAT availability, and we explore its association with reward‐based decision making. We performed 123I‐FP‐CIT Single‐photon emission computed tomography (SPECT) and correlated DAT binding ratios in the bilateral caudate and putamen with gambling symptoms (G‐SAS, PG‐YBOCS) and behaviors, as well as other psychometric variables (anhedonia and impulsivity). Gambling disorder (GD) subjects were also administered a computerized version of the Iowa gambling task (IGT) to assess reward‐based decision making. We found reduced DAT availability in GD subjects compared with healthy controls (−13.30% in right caudate, −11.11% in right putamen, −11.44% in left caudate, and −11.46% in the left putamen). We also found that striatal DAT availability was inversely correlated with days spent gambling and IGT performance in GD subjects. These results provide evidence for a presynaptic dopaminergic dysfunction in striatal regions of GD subjects. Functional DAT down‐regulation possibly sustains the transition towards compulsive gambling addiction, characterized both by hyperdopaminergic and hypodopaminergic states in the context of a sensitized dopaminergic system.

The Role of Magnetic Resonance Imaging–Diffusion Tensor Imaging in Predicting Pain Related to Endometriosis: A Preliminary Study

OBJECTIVES To evaluate the sacral nerve root features by the means of magnetic resonance imaging-diffusion tensor imaging (MRI-DTI) tractography in women with endometriosis and/or adenomyosis, and to analyze the correlations among DTI abnormalities, pain symptoms, and endometriotic lesions found at surgery. DESIGN A cross-sectional, observational study (Canadian Task Force classification II-2). SETTING University hospital. PATIENTS Women (n = 76) with clinical suspicion of endometriosis. INTERVENTIONS Before surgery, dysmenorrhea, deep dyspareunia, and noncyclic pelvic pain (NCPP) were assessed using a 10-point visual analog scale. MRI enabled a 3-dimensional reconstruction of S1, S2, and S3. Fractional anisotropy was calculated for each root. Laparoscopic treatment of endometriosis was performed in 56 patients. MEASUREMENTS AND MAIN RESULTS Our findings revealed correlations among sacral root reconstruction by MRI-DTI, pain symptoms, and laparoscopic findings. DTI of sacral roots revealed a regular and homogeneous appearance in 17 patients (25.8%) and abnormalities in microstructure reconstruction, with fiber irregularities and disorganization and loss of the simple unidirectional course, in 44 patients (66.7%). At laparoscopy, ovarian endometriomas were found in 82.1% of the patients, and deeply infiltrating endometriosis (DIE) were found in 57.1%. Endometriosis was staged according to the revised American Society for Reproductive Medicine classification. Pathological DTI findings were significantly associated with the severity of dysmenorrhea and NCPP, pain duration, presence of tubo-ovarian and cul-de-sac adhesions, and DIE. CONCLUSION The presence of pathological DTI findings of the sacral nerve roots correlates with the type of pain, adhesions, and DIE. At present, DTI can be useful for providing a better understanding of pain; however, DTI could become a useful tool in therapeutic planning for patients with endometriosis.