Assessment of implementation strategies adopted for antimicrobial stewardship interventions in long-term care facilities: a systematic review.

BACKGROUND: The implementation of antimicrobial stewardship (AMS) interventions in long-term care facilities (LTCFs) is influenced by multi-level factors (resident, organizational, and external) making their effectiveness sensitive to the implementation context. OBJECTIVES: This study assessed the strategies adopted for the implementation of AMS interventions in LTCFs, whether they considered organizational characteristics, and their effectiveness. DATA SOURCES: Electronic databases until April 2022. STUDY ELIGIBILITY CRITERIA: Articles covering implementation of AMS interventions in LTCFs. ASSESSMENT OF RISK OF BIAS: Mixed Methods Appraisal Tool for empirical studies. METHODS OF DATA SYNTHESIS: Data were collected on AMS interventions and context characteristics (e.g. type of facility, staffing, and residents). Implementation strategies and outcomes were mapped according to the Expert Recommendations for Implementing Change (ERIC) framework and validated taxonomy for implementation outcomes. Implementation and clinical effectiveness were assessed according to the primary and secondary outcomes results provided in each study. RESULTS: Among 48 studies included in the analysis, 19 (40%) used implementation strategies corresponding to one to three ERIC domains, including education and training (n = 36/48, 75%), evaluative and iterative strategies (n = 24/48, 50%), and support clinicians (n = 23/48, 48%). Only 8/48 (17%) studies made use of implementation theories, frameworks, or models. Fidelity and sustainability were reported respectively in 21 (70%) and 3 (10%) of 27 studies providing implementation outcomes. Implementation strategy was considered effective in 11/27 (41%) studies, mainly including actions to improve use (n = 6/11, 54%) and education (n = 4/11, 36%). Of the 42 interventions, 18/42 (43%) were deemed clinically effective. Among 21 clinically effective studies, implementation was deemed effective in four and partially effective in five. Two studies were clinically effective despite having non-effective implementation. CONCLUSIONS: The effectiveness of AMS interventions in LTCFs largely differed according to the interventions' content and implementation strategies adopted. Implementation frameworks should be considered to adapt and tailor interventions and strategies to the local context.

Olfactory Pathology in Central Nervous System Demyelinating Diseases.

Olfactory dysfunction is common in multiple sclerosis (MS). Olfactory bulb and tract pathology in MS and other demyelinating diseases remain unexplored. A human autopsy cohort of pathologically confirmed cases encompassing the spectrum of demyelinating disease (MS; n = 17), neuromyelitis optica [(NMO); n = 3] and acute disseminated encephalomyelitis [(ADEM); n = 7] was compared to neuroinflammatory [herpes simplex virus encephalitis (HSE); n = 3], neurodegenerative [Alzheimer's disease (AD); n = 4] and non-neurologic (n = 8) controls. For each case, olfactory bulbs and/or tracts were stained for myelin, axons and inflammation. Inferior frontal cortex and hippocampus were stained for myelin in a subset of MS and ADEM cases. Olfactory bulb/tract demyelination was frequent in all demyelinating diseases [MS 12/17 (70.6%); ADEM 3/7 (42.9%); NMO 2/3 (66.7%)] but was absent in HSE, AD and non-neurologic controls. Inflammation was greater in the demyelinating diseases compared to non-neurologic controls. Olfactory bulb/tract axonal loss was most severe in MS where it correlated significantly with the extent of demyelination (r = 0.610, P = 0.009) and parenchymal inflammation (r = 0.681, P = 0.003). The extent of olfactory bulb/tract demyelination correlated with that found in the adjacent inferior frontal cortex but not hippocampus. We provide unequivocal evidence that olfactory bulb/tract demyelination is frequent, can occur early and is highly inflammatory, and is specific to demyelinating disease.

Vegetation correlates of gibbon density in the peat-swamp forest of the Sabangau catchment, Central Kalimantan, Indonesia.

Understanding the complex relationship between primates and their habitats is essential for effective conservation plans. Peat-swamp forest has recently been recognized as an important habitat for the Southern Bornean gibbon (Hylobates albibarbis), but information is scarce on the factors that link gibbon density to characteristics of this unique ecosystem. Our aims in this study were firstly to estimate gibbon density in different forest subtypes in a newly protected, secondary peat-swamp forest in the Sabangau Catchment, Indonesia, and secondly to identify which vegetation characteristics correlate with gibbon density. Data collection was conducted in a 37.1 km(2) area, using auditory sampling methods and vegetation "speed plotting". Gibbon densities varied between survey sites from 1.39 to 3.92 groups/km(2). Canopy cover, tree height, density of large trees and food availability were significantly correlated with gibbon density, identifying the preservation of tall trees and good canopy cover as a conservation priority for the gibbon population in the Sabangau forest. This survey indicates that selective logging, which specifically targets large trees and disrupts canopy cover, is likely to have adverse effects on gibbon populations in peat-swamp forests, and calls for greater protection of these little-studied ecosystems.

Protection against hepatocyte mitochondrial dysfunction delays fibrosis progression in mice.

Accumulating evidence indicates that oxidative stress is involved in the physiopathology of liver fibrogenesis. However, amid the global context of hepatic oxidative stress, the specific role of hepatocyte mitochondrial dysfunction in the fibrogenic process is still unknown. The aim of this study was to determine whether a targeted protection of hepatocytes against mitochondrial dysfunction could modulate fibrosis progression. We induced liver fibrogenesis by chronic carbon tetrachloride treatment (3 or 6 weeks of biweekly injections) in transgenic mice expressing Bcl-2 in their hepatocytes or in normal control mice. Analyses of mitochondrial DNA, respiratory chain complexes, and lipid peroxidation showed that Bcl-2 transgenic animals were protected against mitochondrial dysfunction and oxidative stress resulting from carbon tetrachloride injury. Picrosirius red staining, alpha-smooth muscle actin immunohistochemistry, and real-time PCR for transforming growth factor-beta and collagen alpha-I revealed that Bcl-2 transgenic mice presented reduced fibrosis at early stages of fibrogenesis. However, at later stages increased nonmitochondrial/nonhepatocytic oxidative stress eventually overcame the capacity of Bcl-2 overexpression to prevent the fibrotic process. In conclusion, we demonstrate for the first time that specific protection against hepatocyte mitochondrial dysfunction plays a preventive role in early stages of fibrogenesis, delaying its onset. However, with the persistence of the aggression, this protection is no longer sufficient to impede fibrosis progression.

Evaluation of the immunogenicity of pBudCE4.1 plasmids encoding mycolyl-transferase Ag85A and phosphate transport receptor PstS-3 from Mycobacterium tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), remains a major health problem. The only currently available vaccine, BCG, confers only variable protection and an improved vaccine is urgently needed. Administration of DNA vaccines encoding the secreted mycolyl-transferase Ag85A and the surface-exposed phosphate transport receptor PstS-3 elicit an immune response capable of protecting mice challenged with Mtb. In order to combine the protection against Mtb infection induced by these two DNA vaccines, we have cloned Ag85A and PstS-3 in pBudCE4.1 vector, in which antigenic expression is controlled by two independent promoters. (BALB/cxC57BL/6)F1 mice were vaccinated with this combination vaccine and immune responses were compared to those induced by vaccination with plasmids encoding the single antigens on pBudCE4.1 or pV1J.ns-tPA backbone. Antibody and Th1 type cytokine responses against Ag85A were comparable, whereas responses against PstS-3 were clearly lower in mice vaccinated with the combination plasmid, suggesting antigenic competition with the mycolyl-transferase being the dominant antigen.