Androgen Antagonists ; therapeutic use ; Anilides ; therapeutic use ; Antineoplastic Agents, Hormonal ; therapeutic use ; Bone Neoplasms ; complications ; secondary ; Goserelin ; therapeutic use ; Humans ; Male ; Middle Aged ; Nitriles ; therapeutic use ; Prostatic Neoplasms ; complications ; drug therapy ; Purpura, Thrombotic Thrombocytopenic ; drug therapy ; etiology ; Tosyl Compounds ; therapeutic use

INTRODUCTIONSensori-neural hearing loss (SNHL) is a frequent complication of conventional radiotherapy for head and neck tumours, especially nasopharyngeal carcinoma. To manage radiation-induced ototoxicity appropriately, an understanding of the cellular and molecular basis of this complication is necessary.

MATERIALS AND METHODSA medline search of relevant literature was done, focusing on the radiation-induced cellular and molecular processes that lead to hair cell death in the cochlea.

RESULTSRadiation-induced SNHL occurs in the cochlea, with the retro-cochlear pathways remaining functionally intact. By simulating radiotherapy regimes used clinically, radiation-induced cochlear cell degeneration in the absence of damage to the supporting structures and blood vessels has been demonstrated in animals. This could be due to apoptotic cochlear cell death, which has been shown to be associated with p53 upregulation and intra-cellular reactive oxygen species (ROS) generation. Oxidative stress may initiate the upstream processes that lead to apoptosis and other cell death mechanisms.

CONCLUSIONSA model of radiation-induced SNHL based on a dose and ROS-dependent cochlear cell apoptosis, is proposed. This model supports the feasibility of cochlear implantation, should one be clinically indicated. It can explain clinical observations such as radiation-induced SNHL being dose-dependent and affects the high frequencies more than the lower frequencies. It also opens up the possibility of preventive strategies targeted at different stages of the apoptotic process. Antioxidants look promising as effective agents to prevent radiation-induced ototoxicity; they target upstream processes leading to different cell death mechanisms that may co-exist in the population of damaged cells.

Animals ; Cell Death ; Cell Line ; Cochlea ; radiation effects ; Genes, p53 ; Hair Cells, Auditory ; radiation effects ; Hearing Loss, Sensorineural ; etiology ; genetics ; physiopathology ; Humans ; Mice ; Radiation Injuries ; complications ; Reactive Oxygen Species ; metabolism

INTRODUCTIONAntimicrobial stewardship programmes (ASP) can reduce antibiotic use but patient safety concerns exist. We evaluated the safety of prospective carbapenem review and feedback and its impact on carbapenem use and patient outcomes.

MATERIALS AND METHODSAfter 3 months implementation of our ASP, we compared patients with and without acceptance of ASP recommendations on the use of carbapenems. Primary outcome was 30-day mortality. Secondary outcomes included duration of carbapenem use, length of hospitalisation, clinical response, microbiological clearance, 30-day readmission and mortality at discharge.

RESULTSOf 226 recommendations for 183 patients, 59.3% was accepted. De-escalation, switching to oral antibiotics and antibiotic cessation comprised 72% of recommendations. Patients with acceptance of ASP recommendations had lower 30-day mortality and higher end-of-therapy clinical response despite shorter carbapenem duration (P <0.05). Predictors of 30-day mortality were Pitt bacteraemia score (adjusted odds ratio [aOR] 1.39, 95% confidence interval [CI], 1.11 to 1.74; P = 0.004) and non-acceptance of ASP recommendations (aOR 2.84, 95% CI, 1.21 to 6.64; P = 0.016).

CONCLUSIONOur prospective carbapenem review and feedback mainly comprising of reducing carbapenem use is safe.

Carbapenems ; therapeutic use ; Drug Utilization ; standards ; Feedback ; Guideline Adherence ; statistics & numerical data ; Humans ; Patient Safety ; Pharmaceutical Services ; Treatment Outcome