Adverse drug events caused by three high-risk drug-drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study.

AIMS: Knowledge about adverse drug events caused by drug-drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+ ) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. METHODS: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. RESULTS: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). CONCLUSION: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.

[Should it be mandatory to document off-label prescription in the patient's medical file?] / Off-label voorschrijven verplicht vastleggen in het patiëntendossier?

When patients are treated with a drug that is not registered for the intended indication the prescriber must inform the patient on the benefits and risks of this off-label prescription. In the patient file the prescriber should make a note that the patient was informed. In daily practice prescribers are reluctant to do this, with the motivation that informing patients on benefits and risks of pharmacotherapy is done for all drug treatments, and that this is not different for off-label prescriptions.

Determinants of epidemiologic transition in rural Africa: the role of socioeconomic status and drinking water source.

BACKGROUND: Many African countries experience a protracted epidemiologic transition, different from the classical transition in western societies. The factors driving this protracted transition are largely unknown. In northeast Ghana, we studied an ongoing epidemiologic transition and investigated the effects of socioeconomic status and drinking water source on the transition. METHODS: During a 9-year period, we followed a cohort of almost 30 000 individuals and collected information on mortality and fertility rates. In addition, using the standards set out by the WHO, we obtained the causes of death by verbal autopsy. Individuals were stratified according to their socioeconomic status and the households' use of an improved or unimproved drinking water source. RESULTS: Mortality rates decreased by -5.0% annually (p<0.001) and the main cause of death shifted from infectious to non-infectious diseases (p=0.014). General fertility rates and child-women ratios decreased annually by -12.7% (p<0.001) and -11.9% (p<0.001), respectively. There was no difference in the decline of mortality and fertility depending on socioeconomic status or drinking water source. CONCLUSIONS: Factors other than socioeconomic status and drinking water source are responsible for the observed declines in mortality and fertility observed during the protracted epidemiologic transition. Identifying the specific determinants of the ongoing transition is of importance, as they could be targeted in order to further improve public health in rural African countries.

Seasonal variation in child and old-age mortality in rural Ghana.

BACKGROUND: Mortality in tropical countries varies considerably from season to season. As many of these countries have seen mortality moving from child to old-age mortality, we have studied seasonal variation in child and old-age mortality in a rural area in Ghana that currently undergoes an epidemiologic transition. METHODS: In an annual survey from 2002 through to 2011, we followed 29 642 individuals and obtained the cause and month of death from 1406 deceased individuals by making use of verbal autopsies. RESULTS: When comparing the seasons, we observed a trend for higher mortality during the wet season. When comparing separate months, we observed 34% more deaths than expected in September (95% CI 1.04-1.69; p = 0.024) at the end of the wet season and 43% more deaths in April (95% CI 1.13-1.80; p = 0.004) at the end of the dry season, while there were 42% less deaths than expected in December (95% CI 0.52-0.70; p = 0.003), shortly after the wet season. Cause-specific analysis indicated that the peak at the end of the wet season was due to excess mortality from infectious diseases in children and older people alike, whereas the peak in old-age mortality at the end of the dry season was due to non-infectious causes in older people only. CONCLUSIONS: Taken together, our data suggest that during the epidemiologic transition, mortality not only shifts from child to old-age and from infectious to non-infectious, but also from the wet to the dry season.

Arts and ageing; life expectancy of historical artists in the Low Countries.

Practising arts has been linked to lowering stress, anxiety and blood pressure. These mechanisms are all known to affect the ageing process. Therefore, we examine the relation between long-term involvement in arts and life expectancy at age 50 (LE50), in a cohort of 12,159 male acoustic, literary and visual artists, who were born between 1700 and 1899 in the Low Countries. We compared the life expectancy at age 50 of the various artists with the elite and middle class of that time. In the birth cohorts before 1850, acoustic (LE50:14.5-19.5) and literary artists (LE50:17.8-20.8) had a similar life expectancy at age 50 compared to the elite (LE50:18.0-19.0). Only visual artists (LE50:15.5-17.1) had a lower life expectancy at age 50 compared to the elite at that time. For the most recent birth cohorts from 1850 through 1899, the comparison between artists and the elite reversed and acoustic and literary artist had a lower life expectancy at age 50, while visual artists enjoyed a similar life expectancy at age 50. Although artists belonged to the middle socioeconomic class and lived predominantly in urban areas with poor living conditions, they had a life expectancy similar to the elite population. This is in line with observed favourable effects of practicing arts on health in the short-term. From our historical analysis, we hypothesize several mechanisms through which artistic creativity could influence the ageing process and life expectancy. These hypotheses, however, should be formally tested before any definite conclusions on effects of arts on ageing can be drawn.