Data_Sheet_1_Time trends in the incidence of essential tremor: Evidences from UK and France primary care data.docx

IntroductionAlthough essential tremor (ET) is considered a common adult movement disorder, evidence on its incidence is still scant. This study aims at estimating ET incidence in two European countries, namely, the UK and France.MethodsIncident cases of ET were identified within the Health Improvement Network (THIN®) database between 1st January 2014 and 31 December 2019. Yearly crude and standardized incidence rates (IR) were estimated across the study period for both countries. Poisson regression models were built to assess temporal trends in IRs and differences between sexes and age classes.ResultsIn total, 4,970 and 4,905 incident cases of ET were identified in the UK and France, respectively. The yearly average crude IR (per 100,000 person-years) was 18.20 (95%CI: 15.09–21.32) in UK and 21.42 (17.83–25.00) in France, whereas standardized ones were 19.51 (18.97–20.01) and 19.50 (18.97-20.05). Regression analyses showed slightly increasing trends in both countries, higher incidence among males, and a significant increase with age. Yearly average IR increased from 3.96 (0.95–6.97) and 5.28 (1.12–9.44) in subjects aged 80 year in UK and France.ConclusionsStandardized ET incidence was comparable in the UK and France, showing a slight increase in both countries, reporting a higher value among people aged 60 years and older. This study outlines the need to conduct future studies to estimate the burden of ET in terms of disease control and healthcare resource utilization.</p

Adjusted odds ratios (and 95% confidence intervals) of upper gastrointestinal complications associated with current use of bisphosphonates within various patient subgroups. AIFA-BEST project, Italy, 2003–2007.

<p>Odds ratios estimated with conditional logistic regression model. Estimates concerning main analysis were unadjusted and adjusted for use of other drugs and for the number hospitalizations in the 60-day period prior the index date. Estimates concerning subgroup analysis were obtained by including the interaction terms combining the effect of current use of BPs together with BPs type and regimen dispensed during the current period, concurrent use of other drugs and number hospitalizations in the 60-day period prior the index date. P-values concern comparison of BPs effect across patient subgroups or along increasing number of hospitalizations. BPs: Bisphosphonates.</p

Modelled influence of a hypothetical confounder unaccounted for in the adjustments already performed in the main analysis according with the direction of its effect on the outcome (i.e. positive and negative associations as reported in boxes A and B, respectively), and with its prevalence in the study population (p). AIFA-BEST project, Italy, 2003–2007.

<p>The graphs indicate what combinations of confounder – UGIC and confounder – current BPs exposure would be required to make statistically significant the observed association between current use of BPs and hospitalization for UGIC. For an explanation see the “Sensitivity analysis”, subsection of the “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073159#s2" target="_blank">Methods</a>” section. BPs: Bisphosphonates. UGIC: Upper gastrointestinal complication.</p

Selected tracts of the 862 cases of upper gastrointestinal complications and 15,505 matched controls.

†<p>Measured over the 30-day period prior the index date.</p>‡<p>Measured over the 60-day period prior the index date. Hospital admissions considered in this count does not include hospitalization for UGIC.</p>*<p>According to chi-square test or chi-square test for trend (number of previous hospitalizations).</p><p>AIFA-BEST project, Italy, 2003–2007.</p

Study flow-diagram. AIFA-BEST project, Italy, 2003–2007.

<p>BPs: Bisphosphonates.</p

Influences of diagnostic criteria for upper gastrointestinal complications (panel A), length of time-window for current use of bisphosphonates (panel B), and of controlling for protopathic bias (panel C) on the observed odds ratio for upper gastrointestinal complications associated with current use of bisphosphonates. AIFA-BEST project, Italy, 2003–2007.

<p>Estimates are adjusted for use of other drugs and number of hospitalizations in the 60-day period prior the index date. Details for diagnostic criteria are reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073159#pone.0073159.s001" target="_blank">Appendix S1</a>. For an explanation of methods for controlling protopathic bias see the “Sensitivity analysis”, subsection of the “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073159#s2" target="_blank">Methods</a>” section. BPs: Bisphosphonates.</p

Modelled influence of the inclusion of prevalent BPs users on the true association between current BPs and UGIC risk. AIFA-BEST project, Italy, 2003–2007.

<p>The graph indicates the trend of the true effect of BPs current use on the UGIC risk (e.g. the odds ratio which we would have observed if only incident users were included) according to different values of the BPs – UGIC association among prevalent users. For an explanation see the “Sensitivity analysis”, subsection of the “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073159#s2" target="_blank">Methods</a>” section. BPs: Bisphosphonates. UGIC: Upper gastrointestinal complication.</p

Three-tier triage system (detection, filtering, and substantiation) for detecting ‘prime suspects’.

<p>Three-tier triage system (detection, filtering, and substantiation) for detecting ‘prime suspects’.</p

Drugs potentially associated with acute myocardial infarction^†.

<p>Drugs potentially associated with acute myocardial infarction^†.</p

Central role of histamine in drug-induced acute myocardial infarction via Kounis syndrome.

<p>Aside from its direct vasoconstricting and thrombus-generating effects, histamine also potentiates the platelet aggregating response to adrenaline (dotted outline).</p