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Background: The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease.Methods: During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021.Results: Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach.Conclusions: Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency. High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic. Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas. [ABSTRACT FROM AUTHOR]

Background: Clinical trials remain key to the development of evidence‐based medical practice. However, they are becoming increasingly complex, mainly in a multinational setting. To address these challenges, the European Union (EU) adopted the Clinical Trial Regulation EU No. 536/2014 (CTR). Once in force, the CTR will lead to more consistent rules and simplification of procedures for conducting clinical trials throughout the EU. Existing harmonization initiatives and "research infrastructures" for clinical trials may facilitate this process. This publication offers a snapshot of the current level of harmonization activities in academic clinical research in Europe. Methods: A survey was performed among the member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardized questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the harmonization of academic clinical research processes at national level, to facilitate the exchange of expertise and experience among countries, and to identify new fields of action. Results: Most scientific partners already have in place various working groups and harmonization activities at national level. Furthermore, they are involved in and open to sharing their know‐how and documents. Since harmonization was mainly a bottom‐up approach up until now, the extent and topics dealt with are diverse and there is only little cross‐networking and cross‐country exchange so far. Conclusions: Currently, the ECRIN member countries offer a very solid base and collaborative spirit for further aligning processes and exchanging best practices for clinical research in Europe. They can support a smooth implementation of the EU CTR and may act as single contact with consolidated expertise in a country. [ABSTRACT FROM AUTHOR]

Background: HIV-exposed uninfected (HEU) infants show a high rate of morbidity. We aimed to investigate on biomarkers of immune activation/microbial translocation in HEU infants, evaluating the impact that infections/malnutrition can have on biomarker levels during the first year of life.Methods: Clinical data of 72 Malawian infants were recorded monthly and correlated with levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FABP), analyzed longitudinally.Results: Levels of sCD14 and LBP showed a significant age-related increase. Higher levels of LBP (19.4 vs. 15.2 μg/ml) were associated with stunting, affecting 30% of the infants. The association remained statistically significant after adjusting for cytomegalovirus acquisition, malaria and respiratory infections (p = 0.031). I-FABP levels were significantly increased in infants experiencing gastrointestinal infections (1442.8 vs. 860.0 pg/ml, p = 0.018).Conclusion: We provide evidence that stunting is associated with an enhanced inflammatory response to microbial products in HEU children, suggesting that malnutrition status should be taken into consideration to better understand the alteration of the immune profile of HEU infants living in poor socioeconomic settings. [ABSTRACT FROM AUTHOR]

Summary: Background: Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. Aim: To investigate the impact of direct‐acting antiviral treatment on microbial translocation and T‐cell activation, in patients with hepatitis C‐related liver disease. Methods: We enrolled two groups of HCV‐infected patients undergoing direct‐acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct‐acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble‐CD14, lipopolysaccharide‐binding protein and intestinal fatty acid‐binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T‐cell activation was measured by expression of CD38+ HLA‐DR at the same time points, only in Group ≥F3. Results: There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble‐CD14 and lipopolysaccharide‐binding protein were significantly higher in both groups vs healthy controls. Baseline soluble‐CD14 correlated with glutamic‐oxalacetic transaminase (r = 0.384, P = 0.009) and glutamic‐pyruvic transaminase (r = 0.293, P = 0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T‐cell expression was significantly decreased by direct‐acting antiviral treatment. Relapsers (9%) showed higher soluble‐CD14 levels at baseline. Conclusion: Surrogate microbial translocation markers and T cell activation are increased in HCV‐infected patients with liver fibrosis and decrease during direct‐acting antiviral treatment. [ABSTRACT FROM AUTHOR]

Background: Evidence on the efficacy of palliative care in persons with severe multiple sclerosis (MS) is scarce. Objective: To assess the efficacy of a home-based palliative approach (HPA) for adults with severe MS and their carers. Methods: Adults with severe MS-carer dyads were assigned (2:1 ratio) to either HPA or usual care (UC). At each center, a multi-professional team delivered the 6-month intervention. A blind examiner assessed dyads at baseline, 3 months, and 6 months. Primary outcome measures were Palliative care Outcome Scale-Symptoms-MS (POS-S-MS) and Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW, not assessed in severely cognitively compromised patients). Results: Of 78 dyads randomized, 76 (50 HPA, 26 UC) were analyzed. Symptom burden (POS-S-MS) significantly reduced in HPA group compared to UC (p = 0.047). Effect size was 0.20 at 3 months and 0.32 at 6 months, and statistical significance was borderline in per-protocol analysis (p = 0.062). Changes in SEIQoL-DW index did not differ in the two groups, as changes in secondary patient and carer outcomes. Conclusion: HPA slightly reduced symptoms burden. We found no evidence of HPA efficacy on patient quality of life and on secondary outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Problem: Data on soluble CD14 (sCD14) during pregnancy and lactation are scarce. We assessed the levels of sCD14 in plasma and breastmilk of Malawian HIV‐positive women and evaluated the possible association with morbidity and mortality in the HIV‐exposed children. Method of study: One hundred and forty‐nine mother/child pairs were studied. Women received antiretroviral therapy from 26 weeks of gestation to at least 6 months of exclusive breastfeeding. sCD14 concentrations were determined using an enzyme‐linked immunosorbent assay. Results: sCD14 levels measured at 26 weeks of pregnancy (median: 1418 ng/mL, IQR: 1086‐1757) were inversely correlated to maternal CD4+ cell count (r = −.283, P = .001) and to neonatal birthweight (r = −.233, P = .008). At 6 months, sCD14 plasma levels were significantly higher compared to baseline (1993 ng/mL, IQR: 1482‐2604, P < .001), and breastmilk sCD14 levels (7668 ng/mL, IQR: 5495‐10207) were 4‐fold higher than in plasma (although the concentrations in the two compartments were not correlated). No association was found between sCD14 levels in plasma or breastmilk and morbidity or mortality in children. Conclusion: Higher sCD14 levels in HIV‐positive women were associated with a more compromised maternal immunological status and to a lower neonatal birthweight, but not to poorer clinical outcomes in the HIV‐exposed children. [ABSTRACT FROM AUTHOR]

Background Few studies have investigated wellbeing and burden in carers of people with severe multiple sclerosis (PwSMS). Objectives To assess the impact of providing care to PwSMS, and explore variables associated with perceived carer burden. Methods Cross-sectional assessment of health-related quality of life (HRQOL), mood symptoms (Hospital Anxiety and Depression Scale, HADS), and perceived carer burden (22-item Zarit Burden Interview, ZBI) in 78 PwSMS carers. Multivariate linear regression explored carer and PwSMS factors associated with ZBI score. Results Carers (61% women, mean age 60.2 years, 53% spouse/partner) had significantly lower HRQOL (all SF-36 scales) than the norm, especially for Role Limitation Emotional/Physical, and Emotional Wellbeing. Sixty-eight percent had pathologic (≥ 8) Anxiety, and 44% had pathologic Depression scores on HADS. Nonetheless, perceived carer burden was only moderate (mean ZBI score 35.6, SD 14.3). High carer anxiety (p < 0.0001), low household income (p = 0.009), and living with the PwSMS (p = 0.02) were independent predictors of perceived burden. Conclusions Caring for PwSMS has a detrimental effect on HRQOL and psychological wellbeing. High carer anxiety, low economic status, and living in predict higher burden. It is crucial to recognize PwSMS carers as full partners in the provision of care, and to respond to their own needs. [ABSTRACT FROM AUTHOR]

Background: Preliminary evidence suggests that palliative care may be useful for people with severe multiple sclerosis (MS). The aim of this study is to determine the effectiveness of a home-based palliative approach (HPA) for people with severe MS and their carers. Methods/design: This is a single-blind randomized controlled trial with a nested qualitative study. Seventy-five severe MS-carer dyads are being randomized (at three centers, one in each area of Italy) to HPA or usual care (UC) in a 2:1 ratio. Each center has a specially trained team consisting of four professionals (physician, nurse, psychologist, social worker). The team makes a comprehensive assessment of the needs of the dyads. HPA content is then agreed on, discussed with the patient's caring physician, and delivered over six months. The intervention is not intended to replace existing services. At later visits, the team checks the HPA delivery and reviews/modifies it as necessary. HPA and UC dyads are assessed at home by a blind examiner at baseline, and three and six months later; they also receive monthly telephone interviews. Dyads assigned to UC receive the examiner's visits and telephone interviews, but not the team visits. Primary outcome measures are changes in symptoms (Palliative care Outcome Scale-Symptoms-MS, POS-S-MS), and quality of life (the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), not assessed in patients with severe cognitive compromise) at three and six months. Other outcomes are changes in patient functional status and mood; changes in carer quality of life, mood and caregiving burden; costs; incorporation with standard care; unplanned hospital admissions; referrals to hospice; and deaths. The experience of participants will be evaluated qualitatively by individual semi-structured interviews (HPA patients and carers) and focus group meetings (HPA patients' caring physicians). Discussion: The results of our study will show whether the HPA is feasible and beneficial to people with severe MS and their carers living in the three Italian geographic areas. The nested qualitative study will add to the understanding of the strengths and limitations of the intervention. [ABSTRACT FROM AUTHOR]

Background: Few data on services for people with severe multiple sclerosis (MS) are available. The Palliative Network for Severely Affected Adults with MS in Italy (PeNSAMI) developed a home palliative care program for MS patients and carers, preceded by a literature review and qualitative study (here reported). Objective: To identify unmet needs of people with severe MS living at home by qualitative research involving key stakeholders, and theorize broad areas of intervention to meet those needs. Method: Data were collected from: at least 10 personal interviews with adults with severe MS (primary/secondary progressive, EDSS≥8.0); three focus group meetings (FGs) of carers of people with severe MS; and two FGs of health professionals (HPs). Grounded theory guided the analysis of interview and FG transcripts, from which the areas of intervention were theorized. Results: Between October 2012 and May 2013, 22 MS patients, 30 carers and 18 HPs participated. Forty-eight needs themes were identified, grouped into 14 categories and four domains. Seven, highly interdependent intervention areas were theorized. Patients had difficulties expressing needs; experiences of burden and loneliness were prominent, chiefly in dysfunctional, less affluent families, and among parent carers. Needs differed across Italy with requirements for information and access to services highest in the South. All participants voiced a strong need for qualified personnel and care coordination in day-to-day home care. Personal hygiene emerged as crucial, as did the need for a supportive network and preservation of patient/carer roles within family and community. Conclusions: Unmet needs transcended medical issues and embraced organizational and psychosocial themes, as well as health policies. The high interdependence of the seven intervention areas theorized is in line with the multifaceted approach of palliative care. At variance with typical palliative contexts, coping with disability rather than end-of-life was a major concern of patients and carers. [ABSTRACT FROM AUTHOR]

Background: Preliminary evidence suggests that palliative care may be useful for people with severe multiple sclerosis (MS). The aim of this study is to determine the effectiveness of a home-based palliative approach (HPA) for people with severe MS and their carers.Methods/design: This is a single-blind randomized controlled trial with a nested qualitative study. Seventy-five severe MS-carer dyads are being randomized (at three centers, one in each area of Italy) to HPA or usual care (UC) in a 2:1 ratio. Each center has a specially trained team consisting of four professionals (physician, nurse, psychologist, social worker). The team makes a comprehensive assessment of the needs of the dyads. HPA content is then agreed on, discussed with the patient's caring physician, and delivered over six months. The intervention is not intended to replace existing services. At later visits, the team checks the HPA delivery and reviews/modifies it as necessary. HPA and UC dyads are assessed at home by a blind examiner at baseline, and three and six months later; they also receive monthly telephone interviews. Dyads assigned to UC receive the examiner's visits and telephone interviews, but not the team visits. Primary outcome measures are changes in symptoms (Palliative care Outcome Scale-Symptoms-MS, POS-S-MS), and quality of life (the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), not assessed in patients with severe cognitive compromise) at three and six months. Other outcomes are changes in patient functional status and mood; changes in carer quality of life, mood and caregiving burden; costs; incorporation with standard care; unplanned hospital admissions; referrals to hospice; and deaths. The experience of participants will be evaluated qualitatively by individual semi-structured interviews (HPA patients and carers) and focus group meetings (HPA patients' caring physicians).Discussion: The results of our study will show whether the HPA is feasible and beneficial to people with severe MS and their carers living in the three Italian geographic areas. The nested qualitative study will add to the understanding of the strengths and limitations of the intervention.Trial Registration: The trial was registered with Current Controlled Trials (identifier: ISRCTN73082124) on 19 June 2014. [ABSTRACT FROM AUTHOR]