Thai Red Cross Society

Critical illness can affect antimicrobial pharmacokinetics and pharmacodynamics. Antimicrobial stewardship programs promote appropriate antimicrobial usage. This study aimed to compare the appropriateness of antibiotic dosing, therapeutic drug monitoring, and ICU mortality before and after antimicrobial stewardship program implementation in medical intensive care units.

This retrospective study was conducted at King Chulalongkorn Memorial Hospital, Thailand. Adults admitted to medical intensive care units from August 1, 2019, to July 31, 2021, who received selected antibiotics in the antimicrobial stewardship program were included. During the intervention period, general education as well as prospective audit with intervention and feedback were implemented by infectious disease pharmacist and clinical pharmacists. The appropriateness of dosing, therapeutic drug monitoring, and ICU mortality were compared before and after antimicrobial stewardship program implementation.

There were 269 patients (455 prescriptions) and 376 patients (604 prescriptions) in the pre- and post-antimicrobial stewardship program implementation groups, respectively. Meropenem was the commonly prescribed antibiotic in both groups. Overall, the appropriateness of dosing and therapeutic drug monitoring improved after antimicrobial stewardship program implementation (36% to 63.58%, p < 0.001). Infectious disease and clinical pharmacists provided 40 interventions with an 87.5% acceptance rate. The most common recommendation was maintenance dose adjustment (79.17% acceptance rate). ICU mortality (29.37% to 18.62%, p = 0.001) and length of hospital stay in the ICU (7 days to 5 days, p = 0.005) were lower in the post-antimicrobial stewardship program implementation group.

Pharmacist-led education and prospective audit and feedback on antibiotic dose optimization can improve appropriate antibiotic dosing and therapeutic drug monitoring with a high acceptance rate. We suggest implementing this strategy in other intensive care units such as surgical intensive care units. We still found some nonadherence to our dosing guidelines; additional strategies to optimize dosing should be evaluated.

Due to the possible influence of inflammation and gut microbiota in cancers.

Fc gamma receptor IIb deficient (FcGRIIb-/-) and cyclic GMP-AMP synthase deficient (cGAS-/-) mice, the model with hyperinflammation and hypo-inflammation, respectively, were subcutaneously injected with MC38 cells (a murine colon cancer cell line).

As such, the tumor burdens were most prominent in cGAS-/- mice, while FcGRIIb-/- mice demonstrated the least tumor sizes compared with wild-type (WT). Intra-tumoral mononuclear cells of FcGRIIb-/- (hematoxylin and eosin staining) were more prominent than other groups with the most dominant CD86-positive cells (mostly M1 proinflammatory macrophages) and the least CD206-positive cells (mostly M2 anti-inflammatory macrophages). While fecal microbiome analysis demonstrated a subtle difference among mouse strains with tumors at 24 days post-cancer injection, serum cytokines (TNF-α, IL-6, IL-1α, IFN-β, IFN-γ, IL-23, IL-12p70, GM-CSF, IL-27, and IL-17A) (fluorescence-encoded bead multiplex assay) and the expansion of immune cells in the spleens of FcGRIIb-/- mice (flow cytometry) were more prominent than others. With bone marrow-derived macrophages, prominent M1 (LPS) and M2 polarization (IL4 and cancer supernatant) in FcGRIIb-/- and cGAS-/- macrophages, respectively, were demonstrated using polymerase chain reaction and flow cytometry. The most prominent tumoricidal activity (percentage of F4/80-negative flexible780 viable dye-positive cells using flow cytometry) of LPS-stimulated FcGRIIb-/- macrophages compared with other groups supported dominant pro-inflammatory characteristics of FcGRIIb-/- macrophages.

In conclusion, the protective and promoting effects of FcGRIIb-/- and cGAS-/- mice, respectively, against cancers are partly related to macrophage functions with a subtle correlation to fecal microbiota, and FcGRIIb inhibitors and cGAS enhancers might be helpful for cancer adjuvant treatment.

Evaluating individuals with Parkinson's to determine if they have progressed to the advanced stage and may be suitable for transitioning from intermittent oral medications to continuous, device-aided therapy (DAT) involves considering multiple clinical factors. A key parameter in this assessment, and an indicator of a declining response to oral medication, is overall daily OFF time and the occurrence of unpredictable OFF episodes. OFF-periods are, however, complex and experienced differently by individual patients, so assessment of duration alone may not provide an accurate picture of the patient's lived experience and the challenges they face, information which can be helpful in deciding appropriate management. A range of useful screening tools are available to assist clinicians in determining if a patient has advanced disease and may be suitable for DAT, but these do not always capture the aspects of OFF periods that are the most important, or the most bothersome, to patients. To improve recognition, enhance patient-clinician communication, and achieve effective, personalized management of OFF periods, we propose expanding these tools to consider additional dimensions in three specific areas. First, incorporate patient insights into the personal and functional impact, including the severity of OFF periods, effects on daily activities, and the types and timing (daytime or nighttime) of episodes. Second, include specialist advice from clinicians to characterise the nature of these symptoms and determine suitable therapies. Finally, support this with objective information from PD diaries or technology-based monitoring.