Exploring New Zealand prescription data using sequence symmetry analyses for predicting adverse drug reactions.

WHAT IS KNOWN AND OBJECTIVE: Prescription sequence symmetry analyses (PSSA) is a ubiquitous tool employed in pharmacoepidemiological research to predict adverse drug reactions (ADRs). Several studies have reported the advantage of PSSA as a method that can be applied to a large prescription database with computational ease. The objective of this study was to validate New Zealand (NZ) prescription database as a potential source for identifying ADRs using the PSSA method. METHODS: We analysed de-identified individual-level prescription data for people aged 65 years and above for the period 2005 to 2014 from the pharmaceutical collections supplied by the NZ Ministry of Health. We selected six positive controls that have been previously investigated and reported for causing ADRs. The six positive controls identified were amiodarone (repeated twice), frusemide, simvastatin, lithium and fluticasone. Amiodarone and lithium have been reported to induce thyroid dysfunction. Simvastatin reported to cause muscle cramps while fluticasone is well documented to cause oral candidiasis. Thyroxine was identified as a marker drug to treat hypothyroidism associated with amiodarone and lithium. Carbimazole was identified as a marker drug to treat hyperthyroidism associated with amiodarone use. Quinine sulphate was identified as a marker drug to treat muscle cramps associated with statins. In addition, we also analysed six negative controls that are unlikely to be associated with ADRs. The main outcome measure is to determine associations with ADRs using adjusted sequence ratios (ASR), and 95% confidence intervals RESULTS AND DISCUSSION: Our analyses confirmed a significant signal for all six positive controls. Significant positive associations were noted for amiodarone [ASR = 3·57, 95% CI (3·17-4·02)], and lithium chloride induced hypothyroidism [ASR = 3·43, 95% CI (2·55-4·70)]. Amiodarone was also strongly associated with hyperthyroidism [ASR = 8·81 95% CI (5·86-13·77)]. Simvastatin was associated with muscle cramps [ASR = 1·69, 95% CI (1·61-1·77)]. Fluticasone was positively associated with oral candidiasis [ASR = 2·34, 95% CI (2·19-2·50)]. Frusemide was associated with hypokalaemia [ASR = 2·94, 95% CI (2·83-3·05]). No strong associations were noted for the negative pairs. It is important to highlight that PSSA automatically controls for all confounding factors including unknown and unmeasured confounding variables, plus the effect of temporal trend in prescriptions, and hence allows a more robust ADR detection especially when confounding factors are difficult to determine or measure. WHAT IS NEW AND CONCLUSION: New Zealand prescription database can be a potential source to identify ADRs engaging the PSSA method, and this could complement pharmacovigilance surveillance in NZ. The PSSA can be an important method for post-marketing surveillance and monitoring of ADRs which have relatively short latency. However, the predictive validity of PSSA will be compromised in certain scenarios, particularly when sample size is small, when new drugs are in the market and data are sparse.

The effect of increasing heel height on lower limb symmetry during the back squat in trained and novice lifters.

BACKGROUND: Symmetry during lifting is considered critical for allowing balanced power production and avoidance of injury. This investigation assessed the influence of elevating the heels on bilateral lower limb symmetry during loaded (50% of body weight) high-bar back squats. METHODS: Ten novice (mass 67.6 ± 12.4 kg, height 1.73 ± 0.10 m) and ten regular weight trainers (mass 66.0 ± 10.7 kg, height 1.71 ± 0.09 m) were assessed while standing on both the flat level floor and on an inclined board. Data collection used infra-red motion capture procedures and two force platforms to record bilateral vertical ground reaction force (GRFvert) and ankle, knee and hip joint kinematic and kinetic data. Paired t-tests and statistical parametric mapping (SPM1D) procedures were used to assess differences in discrete and continuous bilateral symmetry data across conditions. RESULTS: Although discrete joint kinematic and joint moment symmetry data were largely unaffected by raising the heels, the regular weight trainers presented greater bilateral asymmetry in these data than the novices. The one significant finding in these discrete data showed that raising the heels significantly reduced maximum knee extension moment asymmetry (P = 0.02), but in the novice group only. Time-series analyses indicated significant bilateral asymmetries in both GRFvert and knee extension moments mid-way though the eccentric phase for the novice group, with the latter unaffected by heel lift condition. There were no significant bilateral asymmetries in time series data within the regular weight training group. CONCLUSIONS: This investigation highlights that although a degree of bilateral lower limb asymmetry is common in individuals performing back squats, the degree of this symmetry is largely unaffected by raising the heels. Differences in results for discrete and time-series symmetry analyses also highlight a key issue associated with relying solely on discrete data techniques to assess bilateral symmetry during tasks such as the back squat.