Real world evidence: Perspectives from a European Society of Cardiology Cardiovascular Round Table with contribution from the European Medicines Agency.

Real world data (RWD) refers to healthcare information that is routinely collected in electronic healthcare records (EHR), hospital and pharmacy records, patient and disease registries, and health insurance databases. The collection and analysis of this vast amount of data is an important complement to that obtained from conventional randomised controlled trials (RCT). Real world data has been used for healthcare quality improvements, to conduct clinical trials, to support drug and device development, and to inform medical guidelines. The utility of RWD may be facilitated by common data models, which standardise format and content, and allow data from different health systems to be analysed together. The European Society of Cardiology (ESC) supports the use of RWD in collaboration with national cardiac societies, regulatory authorities, and industry to encourage continuous quality of care improvements at the hospital and country level, to conduct registry-based randomised clinical trials (R-RCT) and to facilitate safety surveillance of novel drugs and devices. The European Medicines Agency (EMA) is developing systems and processes to enable the use of RWD that can help in trial planning, defining clinical contexts, and enhancing outcome assessments. RWD can also contribute to the measurement of the impact of regulatory actions, such as contraindications or restriction of indications by looking at medicines use patterns over time across European Member States. A number of other initiatives from the European Commission and the EMA are underway to strengthen the EU's health security framework, and foster the collection and utilisation of RWD.

An Opportunity to Harmonise the Approach to Patients' Care Pathways for Rare and Complex Diseases: RarERN Path™.

As a matter of fact, organisation always matters when discussing about healthcare, since it is fundamental in order to ensure the delivery of the most appropriate care to patients in the most appropriate way. Unfortunately, the pandemic brought by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) imposed a huge reorganisation of the healthcare systems, with several repercussions on the care of several chronic conditions, that were in many cases discontinued. This was the case of rare diseases (RDs), conditions that even under normal circumstances can experience diagnostic delays and difficulties in receiving appropriate care. The context of the European Reference Networks (ERNs) represents one of the most appropriate settings for the creation of organisational reference models for patient care pathways (PCP). As a matter of fact, the main mission of ERNs is to improve the care of patients with RDs in Europe through a patient-centred approach, thanks to real multistakeholder involvement. For this reason, in the last years, an extensive effort has been made towards the creation of a methodological approach aimed at providing organisational reference models for PCP in RDs across the different Member States. In fact, in order to develop the reference model, a structured methodology was created to enable the design of the PCP based on a deep sharing of expertise on high-quality care and characterised by a strong patient-centred approach: RarERN Path™. Among the different stakeholders that need to be involved in planning strategic actions to ensure care also during an emergency, patients' representatives, healthcare professionals, hospital managers, and experts in healthcare organisations play a crucial role.

An EU approach to health system performance assessment: Building trust and learning from each other.

EU countries have recently joined forces to carry out common work on health systems performance assessment (HSPA). After the signature of the Tallinn Charter in 2008, a small group of countries brought the issue of HSPA on the EU agenda; this led the European commission and member states to set up an expert group on HSPA in 2014. This group started by facilitating the exchange of best practices and lessons learnt, with an eye to avoiding duplications with activities of international organisations. While progressing on its work, the group broadened its scope: it stepped into concrete work on policy priorities such as the assessment of quality of care, integrated care and primary care. It also moved into the organisation of country-tailored events and of advocacy activities. We identify three main strength factors of the EU expert group on HSPA. First, it is built through a bottom-up participatory approach, which promotes a sense of ownership by the members. Second, it developed a flexible and pragmatic attitude, which makes it able to constantly adapt to emerging needs and priorities. Finally, the group positioned itself in a niche that was still to be exploited: the identification of ways to translate HSPA findings into effective policy making.

European silver paper on the future of health promotion and preventive actions, basic research and clinical aspects of age-related disease.

The current article is a statement of the meeting with international and multidisciplinary participation, held in Wroclaw, Poland on September 11-13, 2008. The meeting was devoted to working out a position focusing on the challenge for individuals, health care systems, biological, psychosocial, epidemiological, medical, and public health sciences in the ageing populations of the twenty-first century. The statement is presented as an overview, in tabular format, of the current European situation regarding basic biological research on ageing, health promotion and preventive action, clinical care for older people, and recommendations for future actions.

Silver paper: the future of health promotion and preventive actions, basic research, and clinical aspects of age-related disease--a report of the European Summit on Age-Related Disease.

BACKGROUND. In September 2008, under the French Presidency of the European Union and with the support of the Polish Minister of Health, a European Summit on Age-Related Disease was organised inWroclaw (Poland). At this meeting, European politicians, gerontologists and geriatricians gathered to discuss a common approach to future challenges related to age-related disease. Politicians and decision-makers from the European Union and Ministers of Health and their deputies from many European countries raised the problems and difficulties to be tackled in a growing population with a high burden of disease, and asked scientists to write a consensus document with recommendations for future actions and decisions. Scientists and clinicians worked in parallel in three different groups, on health promotion and preventive actions, basic research in age-related disease, and clinical aspects of disease in older people. Beforehand, the format of the paper with recommendations was discussed, and it was finally agreed that, for a better understanding by decision- makers, it would be divided in two different columns: one with facts that were considered settled and agreed by most experts (under the heading We know), and a second with recommendations related to each fact (We recommend). No limit on the number of topics to be discussed was settled. After careful and detailed discussion in each group, which in most cases included the exact wording of each statement, chairpersons presented the results in a plenary session, and new input from all participants was received, until each of the statements and recommendations were accepted by a large majority. Areas with no consensus were excluded from the document. Immediately after the Summit, the chairpersons sent the document both to the main authors and to a list of experts (see footnote) who had made presentations at the summit and agreed to review and critically comment on the final document, which is presented below. As regards the scientific aspects of the planning of the Summit, several organisations, under the leadership of the EUGMS, were asked both to review the program and to suggest names of speakers and participants. After the Summit, the Boards of these organizations (European Union Geriatric Medicine Society (EUGMS), International Association of Gerontology and Geriatrics-European Region (IAGGER), European Association of Geriatric Psychiatry (EAGP), International Society of Gerontechnology (ISG) and International Society for the Study of the Aging Male (ISSAM) agreed to consider the document as an official paper, and help with its dissemination. The name Silver Paper was used, recalling the grey or silvery hair of our older citizens, as an easy reference. It has been sent officially to several bodies of the European Union and to Health Ministers of most European countries; and will be published in other languages in local journals. Its declared intention is to foster changes in policies which may, in the future, reduce the burden of disease in old age.

Metal-nucleic acid cages.

Metal-nucleic acid cages are a promising new class of materials. Like metallo-supramolecular cages, these systems can use their metals for redox, photochemical, magnetic and catalytic control over encapsulated cargo. However, using DNA provides the potential to program pore size, geometry, chemistry and addressability, and the ability to symmetrically and asymmetrically position transition metals within the three-dimensional framework. Here we report the quantitative construction of metal-DNA cages, with the site-specific incorporation of a range of metals within a three-dimensional DNA architecture. Oligonucleotide strands containing specific environments suitable for transition-metal coordination were first organized into two DNA triangles. These triangles were then assembled into a DNA prism with linking strands. Metal centres were subsequently incorporated into the prisms at the pre-programmed locations. This unprecedented ability to position transition metals within a three-dimensional framework could lead to metal-DNA hosts with applications for the encapsulation, sensing, modification and release of biomolecules and nanomaterials.

Rearrangement of molybdocene tetraoxotetrasulfide Cp2MoS4O4 to Give [(Cp2MoS2H)2](HSO4)2: a novel proton-stabilized molybdocene disulfide dimer.

Cp(2)MoS(4), 1, in CH(2)Cl(2) undergoes extensive oxidation by m-CPBA at -78 degrees C to give a 1,1,4,4-tetroxide, 2 (59%). Tetraoxide 2 rearranges at room temperature to give an unusual sulfur-atom protonated molybdocene disulfide dimer [(Cp(2)MoS(2)H)(2)](HSO(4))(2), 3. Crystal data for 3 are P, a = 6.751(2) Angstroms, b = 9.865(4) Angstroms, c = 11.549(5) Angstroms, alpha = 109.95(3) degrees, beta = 96.11(3) degrees, gamma = 108.22(3) degrees, V = 666.9(4) Angstroms(3), and Z = 1. The dimer was also obtained directly when the oxidation was conducted at 0 degree C in DMF. Under basic conditions, the dimer is cleaved to give molybdocene disulfide Cp(2)MoS(2), while treatment of the latter with acid converts it to the dimer 3.

[Menopausal changes in circadian heart rate variability]. / Menopauzalne zmiany dobowej zmiennosci rytmu serca.

OBJECTIVES: Presence of cardiovascular symptoms in perimenopausal period is suggested to be associated with the decrease of cardiac autonomic nervous system (cANS) regulatory function. AIM: Aim of the study was to evaluate whether menopause affects circadian heart rate variability (HRV). METHOD: 42 healthy women were divided into two equal groups: premenopausal (age 43 +/- 7 years) and postmenopausal (age 53 +/- 3 years, 3.25 +/- 1.6 years after the last menstruation). Menopausal status was verified by plasma estradiol and FSH activities. In both groups the outpatient 24-hrs ECG recordings were carried out. The HRV parameters (SDNN, pNN50, r-MSSD, nLF, nHF) were analysed within the day-time (6 a.m. - 10 p.m.) and the night-time (10 p.m. - 6 a.m.) ECG. RESULTS: Day-time recordings showed higher SDNN (128 +/- 23 vs. 104 +/- 36, p = 0.01), pNN50 (18 +/- 8.3 vs. 7 +/- 4.4 p < 0.001), nLF (74 +/- 11 vs. 33 +/- 5 p < 0.01) in the premenopausal patients and higher nHF in the postmenopausal women (39 +/- 3.4 vs. 26 +/- 11, p < 0.01). In the night-time recordings we observed higher pNN50 (24 +/- 20 vs. 13 +/- 10, p = 0.01) and nLF (66.5 +/- 17 vs. 37 +/- 5.8, p < 0.01) in the premenopausal patients with nHF higher in the postmenopausal group (44 +/- 5.7 vs. 31.4 +/- 17, p < 0.01). In the premenopausal women higher r-MSSD and nHF values were observed at the night time (respectively p = 0.03 and p = 0.04). Simultaneously higher night-time values of pNN50 (p = = 0.03) and nHF (p = 0.001) were noted in the postmenopausal group. CONCLUSIONS: Lower time HRV parameters suggest decreased parasympathetic regulation of the heart. Lower nLF indicates impairment of the arterial baroreceptor reflexes, whereas the increase of nHF requests further studies.

Insertion of SO(2) into the S-S bond of Cp(2)MoS(2) and Cp(2)MoS(2)O to give molybdocene dithiosulfate and bis(O-alkylthiosulfates).

Cp(2)MoS(2), 3, reacts with SO(2) in CH(2)Cl(2)/EtOH mixtures to give Cp(2)MoS(3)O(2), 4, wherein the SO(2) has inserted into the S-S bond to give a dithiosulfate ligand. Crystal data for 4: P2(1)/n, a = 7.6782(6) A, b = 14.580(3) A, c = 10.2730(10) A, beta = 92.04(1) degrees, V = 1149(3) A(3), Z = 4. Cp(2)MoS(2)O, 5, reacts with SO(2) in CH(2)Cl(2) to give low yields of 4 plus other identified products. 5 reacts with SO(2) in MeOH and EtOH to give the corresponding bis(O-alkylthiosulfate), 6a and 6b, respectively. Crystal data for 6a: P 1 macro, a = 8.3226(13) A, b = 8.4736(11) A, c = 12.382(2) A, alpha = 87.803(11) degrees, beta = 77.758(11) degrees, gamma = 86.383(12) degrees, V = 851.4(2) A(3), Z = 2.