A Trans-Atlantic Perspective on Stagnation in Clinical Translation of Antimicrobial Strategies for the Control of Biomaterial-Implant-Associated Infection

Current regulatory requirements impede clinical translation and market introduction of many new antimicrobial combination implants and devices, causing unnecessary patient suffering, doctor frustration, and costs to healthcare payers. Regulatory requirements of antimicrobial combination implants and devices should be thoroughly revisited and their approval allowed based on enrichment of benefit demonstrations from high-risk patient groups and populations or device components to facilitate their clinical translation. Biomaterial implant and devices equipped with antimicrobial strategies and approved based on enrichment claims should be mandatorily enrolled in global registry studies supervised by regulatory agencies for a minimum five-year period or until statistically validated evidence for noninferiority or superiority of claims is demonstrated. With these recommendations, this trans-Atlantic consortium of academicians and clinicians takes its responsibility to actively seek to relieve the factors that stagnate downward clinical translation and availability of antimicrobial combination implants and devices. Improved dialogue between the various key players involved in the current translational blockade, which include patients, academicians and doctors, policymakers, regulatory agencies, manufacturers, and healthcare payers, is urgently needed.</p

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases

Combination antibiotic therapy for community-acquired pneumonia

Community-acquired pneumonia (CAP) is a common and potentially serious illness that is associated with morbidity and mortality. Although medical care has improved during the past decades, it is still potentially lethal. Streptococcus pneumoniae is the most frequent microorganism isolated. Treatment includes mandatory antibiotic therapy and organ support as needed. There are several antibiotic therapy regimens that include β-lactams or macrolides or fluoroquinolones alone or in combination. Combination antibiotic therapy achieves a better outcome compared with monotherapy and it should be given in the following subset of patients with CAP: outpatients with comorbidities and previous antibiotic therapy, nursing home patients with CAP, hospitalized patients with severe CAP, bacteremic pneumococcal CAP, presence of shock, and necessity of mechanical ventilation. Better outcome is associated with combination therapy that includes a macrolide for wide coverage of atypical pneumonia, polymicrobial pneumonia, or resistant Streptococcus pneumoniae. Macrolides have shown different properties other than antimicrobial activity, such as anti-inflammatory properties. Although this evidence comes from observational, most of them retrospective and nonblinded studies, the findings are consistent. Ideally, a prospective, multicenter, randomized trial should be performed to confirm these findings

Severe pneumococcal pneumonia: impact of new quinolones on prognosis

<p>Abstract</p> <p>Background</p> <p>Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP) requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments.</p> <p>Methods</p> <p>Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU), between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4) community-acquired pneumonia due to non penicillin-resistant <it>Streptococcus pneumoniae </it>and treated with a β-lactam combined with a fluoroquinolone.</p> <p>Results</p> <p>We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1%) died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004), age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01) and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03).</p> <p>Conclusion</p> <p>Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.</p

Banff 2022 liver group meeting report: monitoring long term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participantsincluded hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists.Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimisation and long-term structural changes.Potential revision of the rejection classification scheme to better accommodate and communicate lateT cell-mediated rejection patterns and related structural changes, such as nodular regenerativehyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression tomatch the heterogeneity of patient settings will be central to improving long-term patient survival.Such personalised therapeutics are in turn contingent on better understanding and monitoring ofallograft status within a rational decision-making approach, likely to be facilitated in implementationwith emerging decision support tools. Proposed revisions to rejection classification emerging fromthe meeting include incorporation of interface hepatitis and fibrosis staging. These will be opened toonline testing, modified accordingly and subject to consensus discussion leading up to the next Banffconference