Reducing medication errors for hospital inpatients with Parkinsonism.

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.

The impact of an online adult headache guideline on headache referrals to the neurology clinic.

BACKGROUND: Headache is a common problem in primary care and one of the main reasons general practitioners (GP) consult the neurology service. We developed an online adult headache guideline (Supporting Information Appendix S1) for the greater Wellington Region as a resource for GP to guide identification of concerning headaches, initiation of prophylactic medications for migraine and management of analgesic overuse headache. AIMS: To examine the effectiveness of this adult headache guideline in reducing demand on the neurology outpatient service for headache patients that could readily be managed in primary care. METHODS: We reviewed electronic referrals to Wellington Hospital's neurology department before and after the implementation of the online headache guideline. The primary outcome was the proportion of referrals for headache. Secondary outcomes included proportion of referrals requiring clinic review, rate of pre-referral trial of headache prophylactic medication and medication overuse headache diagnosed at neurological consultation. RESULTS: Nine hundred neurology referrals before and 801 referrals after the publication of the online headache guideline were included. There was a statistically significant reduction in proportion of referrals for headache (15.4% vs 11.7%; P = 0.026). There was neither an increased rate of pre-referral adequate prophylactic medication trial (33.8% vs 27.7%; P = 0.320) nor fewer medication overuse headaches diagnosed during the neurology assessment (21.9% vs 25.0%; P = 0.674). CONCLUSION: The launch of an online headache guideline was associated with a reduction in demand on neurology service. Further education could improve the utilisation of this guideline, to avoid delays in prophylactic treatment and reduce the harm of medication overuse.

Craniectomy for acute disseminated encephalomyelitis.

A 17-year-old girl underwent emergency bifrontal craniectomy for severely raised intracranial pressure with brainstem compression, having developed acute disseminated encephalomyelitis (ADEM) following Epstein-Barr virus infection. We discuss the current evidence for craniectomy in both ADEM and infective encephalitis and propose an approach to management.

Climate suitability as a predictor of conservation translocation failure.

The continuing decline and loss of biodiversity has caused an increase in the use of interventionist conservation tools, such as translocation. However, many translocation attempts fail to establish viable populations, with poor release site selection often flagged as an inhibitor of success. We used species distribution models (SDMs) to predict the climate suitability of 102 release sites for amphibians, reptiles, and terrestrial insects and compared suitability predictions between successful and failed attempts. We then quantified the importance of climate suitability relative to 5 other variables frequently considered in the literature as important determinants of translocation success: number of release years, number of individuals released, life stage released, origin of the source population, and position of the release site relative to the species' range. Probability of translocation success increased as predicted climate suitability increased and this effect was the strongest among the variables we considered, accounting for 48.3% of the variation in translocation outcome. These findings should encourage greater consideration of climate suitability when selecting release sites for conservation translocations and we advocate the use of SDMs as an effective way to do this.

Idoneidad Climática como Pronosticador del Fracaso de la Reubicación por Conservación Resumen La continua declinación y pérdida de la biodiversidad ha ocasionado un incremento en el uso de herramientas intervencionistas de conservación como la reubicación. Sin embargo, muchos intentos de reubicación fracasan en el establecimiento de poblaciones viables, y generalmente se identifica a la mala selección de sitios de liberación como el inhibidor del éxito. Usamos modelos de distribución de especies (MDE) para predecir la idoneidad climática de 102 sitios de liberación para anfibios, reptiles e insectos terrestres y comparamos las predicciones de idoneidad entre los intentos fallidos y los exitosos. Después cuantificamos la importancia de la idoneidad climática en relación a otras cinco variables consideradas frecuentemente en la literatura como determinantes importantes del éxito de la reubicación: el número de años de liberaciones, el número de individuos liberados, la etapa de vida durante la liberación, la fuente de la población de origen y la posición del sitio de liberación en relación a la extensión de la especie. La probabilidad del éxito de la reubicación incrementó conforme aumentó la idoneidad climática pronosticada y este efecto fue el más fuerte entre las variables que consideramos, representando el 48.3% de la variación del resultado de la reubicación. Estos hallazgos deberían promover una mayor consideración de la idoneidad climática cuando se seleccionan sitios de liberación para reubicaciones por conservación y abogamos que el uso de los MDE es un método efectivo para hacer esto.

Safety and acceptability of clozapine and risperidone in progressive multiple sclerosis: a phase I, randomised, blinded, placebo-controlled trial.

OBJECTIVE: Because 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). METHODS: The 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). 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 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. INTERPRETATION: The 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 NUMBER: ACTRN12616000178448.

Neuromyelitis optica presenting as acute bilateral ptosis.

Acute bilateral ptosis can be a hallmark of several serious neurological conditions. We present the first case of acute bilateral near-complete ptosis secondary to neuromyelitis optica spectrum disorder. We suggest that clinicians should consider this disorder among the differential diagnosis of acute bilateral ptosis, especially if there are other brainstem signs.

Projected range contractions of European protected oceanic montane plant communities: focus on climate change impacts is essential for their future conservation.

Global climate is rapidly changing and while many studies have investigated the potential impacts of this on the distribution of montane plant species and communities, few have focused on those with oceanic montane affinities. In Europe, highly sensitive bryophyte species reach their optimum occurrence, highest diversity and abundance in the north-west hyperoceanic regions, while a number of montane vascular plant species occur here at the edge of their range. This study evaluates the potential impact of climate change on the distribution of these species and assesses the implications for EU Habitats Directive-protected oceanic montane plant communities. We applied an ensemble of species distribution modelling techniques, using atlas data of 30 vascular plant and bryophyte species, to calculate range changes under projected future climate change. The future effectiveness of the protected area network to conserve these species was evaluated using gap analysis. We found that the majority of these montane species are projected to lose suitable climate space, primarily at lower altitudes, or that areas of suitable climate will principally shift northwards. In particular, rare oceanic montane bryophytes have poor dispersal capacity and are likely to be especially vulnerable to contractions in their current climate space. Significantly different projected range change responses were found between 1) oceanic montane bryophytes and vascular plants; 2) species belonging to different montane plant communities; 3) species categorised according to different biomes and eastern limit classifications. The inclusion of topographical variables in addition to climate, significantly improved the statistical and spatial performance of models. The current protected area network is projected to become less effective, especially for specialised arctic-montane species, posing a challenge to conserving oceanic montane plant communities. Conservation management plans need significantly greater focus on potential climate change impacts, including models with higher-resolution species distribution and environmental data, to aid these communities' long-term survival.

Hypoventilation in glycine-receptor antibody related progressive encephalomyelitis, rigidity and myoclonus.

Glycine receptor (GlyR) antibodies have been identified in patients with rigidity and hyperekplexia, but the clinical phenotype associated with these antibodies has not been fully elucidated. The clinical features in two additional patients with GlyR antibodies are described. A 55-year-old man presented with stimulus-induced hyperekplexia and rigidity in the lower limbs and trunk. He initially responded to benzodiazepines, but presented after 18 months with severe, painful, prolonged spasms associated with supraventricular and ventricular arrhythmias, hypoventilation and oxygen desaturation requiring intubation. He improved following treatment with clonazepam, baclofen and immunomodulatory therapies. A 58-year-old woman presented with stiffness in the legs and hyperekplexia associated with hypoventilation, at times leading to loss of consciousness. She responded to benzodiazepines and has remained in remission. The clinical picture associated with GlyR antibodies includes autonomic dysfunction, cardiac arrhythmias and hypoventilation. It is important to recognise these serious complications early to limit mortality from this treatable condition.

The Appointment of a Huntington's Disease Nurse Specialist has Reduced Admission Rate and Improved Admission Quality.

We aimed to determine if the appointment of a Huntington's disease (HD) nurse specialist has influenced inpatient admission rates and admission quality at Auckland Hospital. We collated HD inpatient admission data for the 32 months before and after her appointment and compared the quality of cognition, mood, speech/swallowing and safety assessments between admissions where the nurse was and was not involved. After the appointment of the HD nurse there was a 51% reduction in average monthly HD admission rates (p = 0.0009). HD admissions specifically related to HD decreased by 54% (p = 0.005). There was also an improvement in the quality of admissions.

Antiviral agents 3. Discovery of a novel small molecule non-nucleoside inhibitor of hepatitis B virus (HBV).

The discovery of a small molecule non-nucleoside inhibitor of Hepatitis B Virus is described. During our work on conocurvone derived naphthoquinone 'trimers' for the treatment of HIV, we discovered a potent inhibitor 9 of Hepatitis B Virus in an antiviral screen. During attempts to resynthesis 9 for proof of concept studies, we altered the synthesis in order to attempt to reduced side reactions and difficult to remove by-products. As a result we discovered a small molecule 19 that also was a potent inhibitor of HBV. Importantly, this small molecule inhibitor of Hepatitis B Virus is also an inhibitor of Hepatitis B Virus resistant to 3TC, a bench mark of nucleoside analogues active in the treatment of Hepatitis B Virus. The development of 19 as an agent to treat HBV infections is discussed.

Antiviral agents 2. Synthesis of trimeric naphthoquinone analogues of conocurvone and their antiviral evaluation against HIV.

The synthesis of a new series of conocurvone analogues is presented that explores the importance of the pyran rings of conocurvone, their degree of unsaturation as well as the role of alkoxy functionalities as pyran ring replacements, for the inhibition of the HIV-1 integrase (IN) enzyme. Difficulties in synthesising a trimeric naphthoquinone where the central quinone bears a peri-dihydropyran ring was attributed to distortion of the electrophilic dihaloquinone successfully utilised in the past. Increased electron density could also be a factor in reducing reactivity. The desired central dihydropyran bearing trimeric naphthoquinone was successfully synthesised by using a more reactive bromo-tosyloxyquinone intermediate. A maleimide derivative, where the central quinone between the pendant hydroxyquinones was replaced, was successfully synthesised and although it exhibited comparable enzyme inhibitory activity it had negligible HIV inhibitory cellular activity. Compounds were assessed for activity in both in vitro assays using purified recombinant HIV-1 IN and demonstrated superior or comparable activity to conocurvone derivatives previously reported.

Increasing medical student interest in general practice in New Zealand: where to from here?

INTRODUCTION: To meet increasing health demands, increasing the proportion of local graduates entering general practice is imperative. METHODS: Students entering or exiting The University of Auckland's medical programme from 2006 to 2008 were invited to complete a tracking project survey. Levels of interest in general practice were determined along with characteristics associated with a greater or lesser interest in this career. RESULTS: 712 students replied--a response rate of 80%. At entry, 40% of students had a strong interest in a career in general practice, and at exit, 29% (P =0.003). A quarter at each time point had no interest. The proportion of domestic students born outside NZ or Australia was 160/376 (42.5%). There were significantly higher levels of interest in general practice among females, students born in NZ, and those from outside Auckland--especially rural origin. Flexibility in career was more important to students with a strong interest in general practice than those with no interest. DISCUSSION: Auckland medical students have levels of interest in general practice comparable with international data. Increasing this interest further may require admission of a greater proportion of students from those groups with higher interest levels, greater emphasis on the positive aspects of general practice, and on GPs as equals to other specialists.

Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs).

A series of phenylaminopyrimidines has been identified as inhibitors of Janus kinases (JAKs). Development of this initial series led to the potent JAK2/JAK1 inhibitor CYT387 (N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-benzamide). Details of synthesis and SAR studies of these compounds are reported.