No abstract

Background Patients with Parkinsonism are 1.5 times more likely than comparators to be hospitalised and have a significantly longer length of stay in hospital. Medication delays, inappropriate medication omission, and administration of contraindicated medications likely contribute to these poor outcomes. Education and hospital system interventions may reduce these errors. Aim To determine the effectiveness of a multimodal education and awareness campaign in reducing medication errors in patients with Parkinsonism at Hutt Hospital. Methods We performed an audit of hospital medication charts to establish the baseline medication error rate and patient outcomes over a 3‐month period. We then delivered an intervention consisting of staff education sessions, a sticker alert system and increased priority for pharmacist review of patient drug charts. We repeated the audit after the intervention. Results In the initial audit, the medication error rate was 22.5%, the clinical complication rate was 45% and one death was directly attributable to medication error. At follow up, the medication error and complication rates were 9.3% (absolute difference 13% (95% conflict of interest (CI) 10–16.4), P < 0.001) and 38% (absolute difference 7% (95% CI −19 to 34), P = 0.59), respectively, and there were no attributable deaths. The average length of stay before and after the intervention was 13 and 8 days respectively (absolute difference 5.7 days (95% CI −1.8 to 13.3), P = 0.135). Conclusions There was a high in‐hospital medication error rate for Parkinsonian patients. The intervention resulted in a statistically significantly improvement in the medication error rate. The estimated reductions in complication rate and length of stay may be clinically important. Similar interventions may be beneficial in other institutions.

Introduction/Aims: Sensory impairment secondary to dorsal root ganglion neuronopathy is common, although often subclinical, in X-linked spinal and bulbar muscular atrophy (SBMA).We investigated the hypothesis that nerves of SBMA patients show the same morphological changes on ultrasound as other inherited sensory neuronopathies and that these changes are distinct from those in axonal neuropathy. Methods:We compared the ultrasound cross-sectional areas (CSAs) of median, ulnar, sural, and tibial nerves of prospectively recruited SBMA patients with those of patients with acquired axonal neuropathy and healthy controls.We also compared the individual nerve CSAs of SBMA and neuropathy patients with our laboratory reference values.Results: There were 7 SBMA patients, 18 neuropathy patients, and 42 healthy controls.The nerve CSAs of the SBMA patients were significantly smaller than those of patients in the other two groups. The changes were most prominent in the upper limbs (p < .001), with the nerves of the SBMA patients being on average approximately half the size of the controls and a third the size of the neuropathy patients.On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one SBMA patient.Discussion: These ultrasound changes are similar to those reported in other inherited sensory neuronopathies and clearly different from the ultrasound findings in axonal neuropathy.Smaller nerves are possibly a distinctive finding in SBMA that may distinguish it from other motor neuron syndromes. Further studies are warranted to confirm this and determine the optimal sonographic protocol.

ObjectiveBecause clozapine and risperidone have been shown to reduce neuroinflammation in humans and mice, the Clozapine and Risperidone in Progressive Multiple Sclerosis (CRISP) trial was conducted to determine whether clozapine and risperidone are suitable for progressive multiple sclerosis (pMS).MethodsThe CRISP trial (ACTRN12616000178448) was a blinded, randomised, placebo-controlled trial with three parallel arms (n=12/arm). Participants with pMS were randomised to clozapine (100–150 mg/day), risperidone (2.0–3.5 mg/day) or placebo for 6 months. The primary outcome measures were safety (adverse events (AEs)/serious adverse events (SAE)) and acceptability (Treatment Satisfaction Questionnaire for Medication-9).ResultsAn interim analysis (n=9) revealed significant differences in the time-on-trial between treatment groups and placebo (p=0.030 and 0.025, clozapine and risperidone, respectively) with all participants receiving clozapine being withdrawn during the titration period (mean dose=35±15 mg/day). Participants receiving clozapine or risperidone reported a significantly higher rate of AEs than placebo (p=0.00001) but not SAEs. Specifically, low doses of clozapine appeared to cause an acute and dose-related intoxicant effect in patients with pMS who had fairly severe chronic spastic ataxic gait and worsening over all mobility, which resolved on drug cessation.InterpretationThe CRISP trial results suggest that patients with pMS may experience increased sensitivity to clozapine and risperidone and indicate that the dose and/or titration schedule developed for schizophrenia may not be suitable for pMS. While these findings do not negate the potential of these drugs to reduce multiple sclerosis-associated neuroinflammation, they highlight the need for further research to understand the pharmacodynamic profile and effect of clozapine and risperidone in patients with pMS.Trial registration numberACTRN12616000178448.

Objective: Because clozapine and risperidone have been shown to reduce neuroinflammation in humans and mice, the CRISP trial was conducted to determine whether clozapine and risperidone are suitable for progressive multiple sclerosis (pMS).Methods: The CRISP trial (ACTRN12616000178448) was a blinded, randomized, placebo-controlled trial with three parallel arms (n=12/arm). Participants with pMS were randomized to clozapine (100 to 150 mg/day), risperidone (2 to 3.5 mg/day), or placebo for six months. The primary outcome measures were safety (adverse events/serious adverse events) and acceptability (TSQM-9).Results: An interim analysis (n=9) revealed significant differences in the time-on-trial between treatment groups and placebo (p=0.030 and 0.025, clozapine and risperidone, respectively) with all participants receiving clozapine being withdrawn during the titration period (mean dose=35±15 mg/day). Participants receiving clozapine or risperidone reported a significantly higher rate of adverse events than placebo (p=0.00001) but not serious adverse events. Specifically, low doses of clozapine appeared to cause an acute and dose-related intoxicant effect in patients with pMS, who had fairly severe chronic spastic ataxic gait and worsening over all mobility, which resolved on drug cessation.Interpretation: The CRISP trial results suggest that pMS patients may experience increased sensitivity to clozapine and risperidone and indicate that the dose and/or titration schedule developed for schizophrenia may not be suitable for pMS. While these findings do not negate the potential of these drugs to reduce MS-associated neuroinflammation, they highlight the need for further research to understand the pharmacodynamic profile and effect of clozapine and risperidone in pMS patients.