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Background Falls remain a common and debilitating problem in hospitals worldwide. The aim of this study was to investigate the effects of falls prevention interventions on falls rates and the risk of falling in hospital. Design Systematic review and meta-analysis. Participants Hospitalised adults. Intervention Prevention methods included staff and patient education, environmental modifications, assistive devices, policies and systems, rehabilitation, medication management and management of cognitive impairment. We evaluated single and multi-factorial approaches. Outcome measures Falls rate ratios (rate ratio: RaR) and falls risk, as defined by the odds of being a faller in the intervention compared to control group (odds ratio: OR). Results There were 43 studies that satisfied the systematic review criteria and 23 were included in meta-analyses. There was marked heterogeneity in intervention methods and study designs. The only intervention that yielded a significant result in the meta-analysis was education, with a reduction in falls rates (RaR = 0.70 [0.51–0.96], P = 0.03) and the odds of falling (OR = 0.62 [0.47–0.83], P = 0.001). The patient and staff education studies in the meta-analysis were of high quality on the GRADE tool. Individual trials in the systematic review showed evidence for clinician education, some multi-factorial interventions, select rehabilitation therapies, and systems, with low to moderate risk of bias. Conclusion Patient and staff education can reduce hospital falls. Multi-factorial interventions had a tendency towards producing a positive impact. Chair alarms, bed alarms, wearable sensors and use of scored risk assessment tools were not associated with significant fall reductions.

Background/Objectives: We investigated the impact of ceasing routine falls risk assessment tool (FRAT) completion and instead used clinical reasoning to select fall mitigation strategies. Design: Two-group, multi-site cluster-randomized active-control non-inferiority trial. Setting: Hospital wards. Participants: Adult inpatients admitted to participating hospitals (n = 10 hospitals, 123,176 bed days). Intervention: Hospitals were randomly assigned (1:1) to a usual care control group that continued to use a historical FRAT to assign falls risk scores and accompanying mitigation strategies, or an experimental group whereby clinicians did not assign risk scores and instead used clinical reasoning to select fall mitigation strategies using a decision support list. Measurements: The primary measure was between-group difference in mean fall rates (falls/1000 bed days). Falls were identified from incident reports supplemented by hand searches of medical records over three consecutive months at each hospital. The incidence rate ratio (IRR) of monthly falls rates in control versus experimental hospitals was also estimated. Results: The experimental clinical reasoning approach was non-inferior to the usual care FRAT that assigned fall risk ratings when compared to a-priori stakeholder derived and sensitivity non-inferiority margins. The mean fall rates were 3.84 falls/1000 bed days for the FRAT continuing sites and 3.11 falls/1000 bed days for experimental sites. After adjusting for historical fall rates at each hospital, the IRR (95%CI) was 0.78 (0.64, 0.95), where IRR < 1.00 indicated fewer falls among the experimental group. There were 4 and 3 serious events in the control and experimental groups, respectively. Conclusion: Replacing a FRAT scoring system with clinical reasoning did not lead to inferior fall outcomes in the short term and may even reduce fall incidence.

Antiepileptic drug (AED) associated teratogenicity has been well documented in the literature. The risk of physical birth defects during the first trimester of pregnancy is increased threefold for most AEDs and over ten-fold for the most teratogenic AED, valproate. Despite this risk, women require long term treatment to stop or reduce the occurrence of seizures and the consequent harm to both mother and foetus, including the possibility of sudden unexpected death in epilepsy. The mechanism resulting in this teratogenicity, and in particular why some women are more susceptible to have children with AED induced birth defects is incompletely elucidated. In recent years there has been emerging evidence that AEDs may be interacting with genomic factors to result in birth defects. These genomic factors may be susceptibility alleles in the mother or father, de novo mutations in the child or epigenetic factors such as alterations in DNA methylation in the mother or child. The studies reported in this thesis aim to a) develop an animal model of valproate induced defects that closely mimics a human clinical setting and can be used to better understand the pathogenesis of AED induced defects, and b) identify genomic markers of AED induced defects using whole genome analysis of human samples and determining if having epilepsy is a contributing factor to the onset of these defects. For aim a) the development of the animal model entailed using an epileptic strain of rats, Genetic Absence Epilepsy Rats from Strasbourg, determining a dose at which dietary valproate is therapeutic, mating the rats and conducting a morphological assessment of both internal and external defects. For aim b) human samples were collected and subjected to whole genome analysis, including whole exome sequencing and DNA methylation scans. Additionally, birth defect rates for non-epileptic women in the Australian Pregnancy Register were also separately quantified. The human samples for investigations were co