A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response.

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. RESULTS: Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. CONCLUSIONS: Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566.

European standards for undergraduate medical education in general practice; a blueprint - for action.

There is compelling evidence that general practice (GP) is the most effective form of healthcare. However, healthcare policy appears independent of evidence and GP is woefully under-resourced in all countries, and this affects recruitment. Recruitment to GP is proportional to the quantity and quality of undergraduate experience and national and transnational guidelines can improve undergraduate experiences by defining both the desired quantity and quality. There is good evidence that these professionally developed guidelines can be effective in changing Government policy if they are used as a touchstone to collaborate with policymakers.EURACT (European Academy of Teachers in General Practice / Family Medicine) have therefore developed transnational guidelines covering the European region. The guidelines cover the desired quantity, quality and support for undergraduate experience. Three main design principles have been used. Firstly, it is democratic. Secondly it is evidence-based, using extensive literature searching, situational analysis and surveys. Finally, it adopts a 'principles-based approach'. Generalist medicine is articulated as a series of interconnected principles that integrate and then re-focus specialist medicine to achieve the enhanced patient-orientated outcomes of primary-care. This way of articulating generalist practice delivers general principles, which can be used as learning outcomes, that are adaptable to a wide range of learning environments. Most clinical learning documents are irrelevant and are destined for dusty drawers or forgotten digital files. We therefore encourage primary care educators to use these guidelines to work with policy-makers at all levels to advocate for change, strengthening primary care education at local, national and international levels.

Early clinical exposure in undergraduate medical education: A questionnaire survey of 30 European countries.

PURPOSE: Fifteen years ago, a European survey demonstrated widespread adoption of early clinical exposure (ECE) programmes but little emphasis in the curricula of medical schools. We now repeat the survey in light of the ample emerging data suggesting multiple positive outcomes of ECE. METHODS: Online cross-sectional survey in European medical schools conducted by the EURACT Basic Medical Education Committee in 2021. Descriptive quantitative analyses and a thematic analysis approach were used. RESULTS: Eighy-nine (48%) medical schools in 30 European countries responded. ECE was used in 65 (73%) of the medical schools, and 88% of ECE programmes took place in primary care. The median total time spent on the ECE programme was 5 days. Teaching methods covered unstructured learning opportunities such as observation or shadowing doctors, as well as work-based learning whilst seeing real patients or reflecting on own encounters. Learning goals included knowledge, skills, and attitudes. More than half of the respondents expressed barriers to implementing or expanding ECE. CONCLUSIONS: Compared to the previous survey, there was no significant change in the adoption or curricular emphasis of ECE programmes. Institutional attitudes towards certain disciplines and a lack of willingness to experiment with new teaching methods may be partially responsible.

Progress Update: Development of Palliative Care From 2017 to 2020 in Five Countries in Eurasia.

CONTEXT: In the early 2000s, palliative care was largely unknown in the Eurasian region. For a period of twenty years starting around 2002, Open Society Foundations (OSF) supported palliative care pioneers in the region to establish palliative care services, train health providers, and advocate for the integration into health services. OBJECTIVES: To report on the development of palliative care in Armenia, Georgia, Moldova, Tajikistan and Ukraine during the period 2017-2021 and explore the impact of OSF's sustained funding for palliative care in these countries. Activities and developments to 2017 were described in country-specific papers in 2018. METHODS: A retrospective case study analysis was used to examine how palliative care developed in each country. We reviewed theories of change, funding and advocacy strategies, implemented activities and interventions, and their outputs and outcomes, and compared them to legal, policy and service developments in practice. RESULTS: By the mid-2010s, each country had laid the foundations for rolling out palliative care-basic policies and guidelines were in place; palliative care medications were available; key health providers were trained; and training capacity and models of care had been created-but service availability remained limited. In subsequent years, advocates increasingly embraced public advocacy to hold governments accountable for meeting their commitments and to include palliative care in universal health insurance. By 2021, Armenia, Moldova, and Ukraine had significantly scaled up service availability and palliative care was firmly embedded in universal health coverage in Moldova and Ukraine whereas progress in Georgia and Tajikistan was more modest. CONCLUSION: Experiences in these countries suggest that a strategy that initially emphasizes training, technical assistance, and engagement to create the building blocks for palliative care combined with or followed by public advocacy and campaigning to demand roll out of services can result in significant advances. Continued progress, however, is not guaranteed, especially considering the COVID-19 pandemic and dwindling donor support.

Palliative Care Development in Georgia.

Georgia has established the foundational measures for a national palliative care program-policy, education, drug availability, and implementation. Amendments to legislation needed to develop palliative care have been approved. Palliative care has been recognized as a subspecialty in oncology, critical care, internal medicine, and surgery. The National Plan for Palliative Care for 2011-2016 was approved. Opioids, especially oral morphine, are available on a limited basis for patients at home, but oral morphine is not available for patients in the hospital. Prescribing regulations have changed and all physicians are allowed to prescribe and the length of a prescription is now seven days rather than three days previously. Unfortunately, patients and families must still pick up their opioid medications at pharmacies in the police station. Opioids for cancer patients in inpatient units or at home are free. Palliative care education has been incorporated into both undergraduate and postgraduate medical and nursing education and a number of physicians have received specialist training abroad. Palliative Care Standards and Guidelines have been developed; and palliative care services, although insufficient to meet the need, are available for patients at home, as inpatients and a children's hospice opened in 2017.

Overview of the gaps in the health care legislation in Georgia: short-, medium-, and long-term priorities.

BACKGROUND: After gaining independence following the dissolution of the Soviet Union, Georgia has aspired to become the region's leader in progressive legal reform. Particularly in the realm of health care regulation, Georgia has proceeded with extensive legislative reforms intended to modernize its health care system, and bring it in line with international standards. OBJECTIVES/METHODS: As part of a larger project to improve human rights in patient care, we conducted a study designed to identify gaps in the current Georgian health care legislation. Using a cross-site research framework based on the European Charter of Patients' Rights, an interdisciplinary working group oversaw a comprehensive review of human rights legislation pertinent to health care settings using various sources, such as black letter law, expert opinions, court cases, research papers, reports, and complaints. RESULTS: The study identified a number of serious inconsistencies, gaps, and conflicts in the definition and coverage of terms used in the national legislative canon pertinent to human rights in patient care. These include inconsistent definitions of key terms "informed consent" and "medical malpractice" across the legislative landscape. Imprecise and overly broad drafting of legislation has left concepts like patient confidentiality and implied consent wide open to abuse. The field of health care provider rights was entirely missing from existing Georgian legislation. DISCUSSION: To our knowledge, this is the first study of its kind in Georgia. Gaps and inconsistencies uncovered were categorized based on a short-, medium-, and long-term action framework. Results were presented to key decision makers in Georgian ministerial and legislative institutions. Several of the major recommendations are currently being considered for inclusion into future legal reform.