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.

Discontinuation of statins in a population of older New Zealanders with limited life expectancy.

Discontinuation of statins may be considered for older individuals with a cancer, multi-morbidity, approaching end-of-life and in primary prevention. The aim of this study is to investigate the relationship between the rates of statin discontinuation in the last 12 months of life and a diagnosis of cancer, and in individuals using statins for primary or secondary prevention. A case-control study of matched cases and controls. Matching was based on age, Charlson comorbidity index scores and socioeconomic status. Prescription and diagnostic data for 20,482 individuals who were aged over 75 years, were in their last 12 months of life and were receiving statins during the study period (1 January 2007 to 31 December 2012). After propensity score matching, we identified 4832 cases with a diagnosis of cancer and 4809 matched controls. We used Cox regression to test the relationship between the relative risk of statin discontinuation and a diagnosis of cancer, and in individuals using statins for primary or secondary prevention. Statins were discontinued in 70.4% of older adults with a diagnosis of cancer and 55.8% of those without cancer (P < 0.05). The Cox regression analysis supports that a diagnosis of cancer can increase the rate of statin discontinuation compared with individuals without a diagnosis of cancer regardless of whether statins were used for primary or secondary prevention (P < 0.05). The findings from this study support that statins are likely to be discontinued in the last year of life in older people with limited life expectancy from cancer, even if statins were indicated for secondary prevention of cardiovascular disease.

An upper-body can improve the stability and efficiency of passive dynamic walking.

The compass-gait walker proposed by McGeer can walk down a shallow slope with a self-stabilizing gait that requires no actuation or control. However, as the slope goes to zero so does the walking speed, and dynamic gait stability is only possible over a very narrow range of slopes. Gomes and Ruina have results demonstrating that by adding a torso to the compass-gait walker, it can walk passively on level-ground with a non-infinitesimal constant average speed. However, the gait involves exaggerated joint movements, and for energetic reasons horizontal passive dynamic walking cannot be stable. We show in this research that in addition to collision-free walking, adding a torso improves stability and walking speed when walking downhill. Furthermore, adding arms to the torso results in a collision-free periodic gait with natural-looking torso and limb movements. Overall, in contrast to the suggestions that active control may be needed to balance an upper-body on legs, it turns out that the upper and lower bodies can be integrated to improve the stability, efficiency and speed of a passive dynamic walker.