Purpose
To identify the proportion of older adults with a high anticholinergic/sedative load and to identify patient subgroups based on type of central nervous system (CNS)‐active medication used.
...Methods
A cross‐sectional study of a nationwide sample of patients with anticholinergic/sedative medications dispensed by 1779 community pharmacies in the Netherlands (90% of all community pharmacies) in November 2016 was conducted. Patients aged older than 65 years with a high anticholinergic/sedative load defined as having a drug burden index (DBI) greater than 1 were included. Proportion of patients with a high anticholinergic/sedative load was calculated by dividing the number of individuals in our study population by the 2.4 million older patients using medications dispensed from study pharmacies. Patient subgroups based on type of CNS‐active medications used were identified with latent class analysis.
Results
Overall, 8.7% (209 472 individuals) of older adults using medications had a DBI greater than 1. Latent class analysis identified four patient subgroups (classes) based on the following types of CNS‐active medications used: “combined psycholeptic/psychoanaleptic medication” (class 1, 57.9%), “analgesics” (class 2, 17.9%), “antiepileptic medication” (class 3, 17.8%), and “anti‐Parkinson medication” (class 4, 6.3%).
Conclusions
A large proportion of older adults in the Netherlands had a high anticholinergic/sedative load. Four distinct subgroups using specific CNS‐active medication were identified. Interventions aiming at reducing the overall anticholinergic/sedative load should be tailored to these subgroups.
In this work, the biogeochemistry of marine sediments from the Kiel Bight, coastal SW Baltic Sea, is studied based on the abundance and isotopic composition of organic carbon and different forms of ...sedimentary sulphur. Active bacterial sulphate reduction, partly under sulphate-limiting conditions, is evident from paired δ³⁴S and δ¹⁸O values of pore water sulphate. The resulting pore water sulphide is partly precipitated as acid-volatile iron sulphide and subsequently forms sedimentary pyrite, partly serves in later diagenetic sulphurisation of organic matter, or remains dissolved in the pore water, all evident from the respective δ³⁴S values. Microbial sulphate turnover is associated with an apparent isotopic fractionation between dissolved sulphate and dissolved sulphide (Δ³⁴S) that varies between 46 and 66‰.
Diagenetic precipitates, such as dolomite, and the chemistry of residual deeply buried porewater often represent the only traces of past biogeochemical activity in marine sediments. A 600m thick ...sedimentary section, recently drilled at Integrated Ocean Drilling Program (IODP) Site U1341 on Bowers Ridge (southern Bering Sea), provides insight into such a 4.3Ma old paleo-diagenetic archive. Hard-lithified calcite–dolomite layers, and laminae of disseminated carbonate, were recovered in diatom-rich sediments over a depth range of 400m. Carbon isotope values of the diagenetic carbonates between −16.6 and −14.4‰ (VPDB) and strontium isotope ratios of dolomites close to past seawater values suggest carbonate precipitation induced by the production of dissolved inorganic carbon (DIC) during elevated rates of organic carbon mineralization, primarily via sulfate reduction, at shallow sediment depth below the paleo-seafloor. Diagenetic carbonates at 280–440m below seafloor were likely also produced by the intermittent onset of sulfate reduction coupled to the anaerobic oxidation of methane (AOM) at sulfate–methane transition zones (SMTZ). These microbially mediated processes do not occur in the sediment at this site at present but were likely connected to the presence of a methanogenic zone at 2.58–2.51Ma. A minimum in sulfate concentrations in modern porewaters and low sedimentary Ba/Al ratios resulting from former sulfate depletion are reminiscent of the presence of this large methanogenic zone. The minimum in sulfate concentrations is reflected in a minimum in magnesium concentrations, less radiogenic strontium and isotopically light calcium in the porewater. It is proposed that magnesium was removed from the porewater during carbonate precipitation and volcanic ash alteration which occurred in the former methanogenic zone and also released strontium with a less radiogenic isotope ratio and isotopically light calcium into the porewater. The isotopic composition of porewater calcium was also influenced by ammonium–calcium exchange on clay minerals and carbonate recrystallization. Our study elucidates the response of porewater element concentrations and isotopic profiles interlinked with the formation of diagenetic carbonates to changes in the deposition of organic carbon in sediments of deeper water sites (>2000m water depth) over prolonged timescales. It shows that variations in biogeochemical processes in response to changes in oceanographic conditions and a dynamic subseafloor biogeochemical zonation have to also be taken into account at these deep water sites for a global assessment of organic carbon burial fluxes and remineralization.
A systematic review and a meta‐analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism ...on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC‐homozygotes, T‐allele carriers required an 8.3% (95% confidence interval (CI): 5.6–11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
Clinical Pharmacology & Therapeutics (2012); 92 6, 746–756. doi:10.1038/clpt.2012.184
Sulfate-driven anaerobic oxidation of methane (SO4-AOM) and organiclastic sulfate reduction (OSR) in marine sediments commonly lead to the precipitation of authigenic pyrite with characteristic ...sulfur isotopic compositions. Yet, no reports on the iron isotopic composition of SO4-AOM generated pyrite exist to the best of our knowledge and the processes controlling the distribution of iron isotopes during this biogeochemical process are not understood. To investigate the mechanisms involved in iron isotope fractionation during SO4-AOM, we analyzed the isotopic composition of authigenic pyrite from two seafloor sites (HS148 and HS217) in the Shenhu gas hydrate area, South China Sea. The δ56Fe values of pyrite were found to vary from −0.349‰ to +0.267‰ in core HS148, and from −0.793‰ to +0.178‰ in core HS217 (relative to average igneous rock) with distinct trends towards higher values with increasing burial depth in both cores. The δ56Fe values correlate positively with the extent of pyritization (Fepy/FeHR) derived from a sequential iron extraction procedure. OSR was found to drive early diagenetic pyrite formation at shallow depth, resulting in relatively 56Fe depleted pyrite. Peaks in the extent of pyritization of 0.45 and 0.47 at ca. 6 and 7m below the sediment surface, respectively, correlate with high δ56Fe and high δ34S values, and are interpreted to reflect periods of enhanced SO4-AOM in paleo-sulfate methane transition zones (SMTZs). The great variability in iron isotopic composition and the observed trends are best explained as a function of the availability of dissolved sulfide, reflecting sulfide formation by OSR and SO4-AOM. The successive conversion of reactive iron to pyrite via sulfidization apparently resulted in the enrichment of 56Fe in the iron reservoir upon the preferential consumption of isotopically light iron, leading to the formation of successively 56Fe-enriched pyrite especially at or in close proximity to the SMTZ. Therefore, we hypothesize that the combined enrichment of heavy iron isotopes and 34S in authigenic pyrite is a possible tracer of SO4-AOM in modern and ancient sedimentary sequences.
OBJECTIVES: Identification of medication risk factors for a deteriorated renal function is important to prevent chronic renal damage. The objective of this study was to identify and confirm drug ...exposure as potential triggers for a deteriorated renal function among type 2 diabetes mellitus (T2DM) patients using real world data (RWD). METHODS: A nested case-control study within aT2DM cohort was conducted using the PHARMO Database Network. Between 1999 and 2014 cases with a deteriorated renal function were matched on sex, birth year and geographic region to controls without a decline in renal function. Date of renal decline among cases was set as index date; controls were assigned the index date of their matched cases. Exposure to drugs associated with renal function based on literature and drugs for which additional monitoring of safety is mandatory according to the European Medicines Agency in the 6 months before index date was compared between cases and controls. RESULTS: 3,179 cases were matched to 6,106 controls (50% male, mean±SD age 75±9).The following known medication triggers, based on literature, were associated with deteriorated renal function: anti-inflammatory drugs (OR 1.41 (95%CI 1.28-1.55)), contrast agents (OR 2.37 (95%CI 1.81-3.10)), antibiotics (OR 2.82 (95%CI 2.58-3.09), antihypertensives (OR 2.66 (95%CI 2.42-2.93)), PPI's (OR 2.45 (95%CI 2.24-2.67)) and statins (OR 1.35 (95%CI 1.23-1.48)). Among drugs requiring additional monitoring of safety, domperidone was associated with deterioration in renal function (OR 5.09 (95%CI 3.74-6.91)). CONCLUSIONS: Real world data is an important source for identification and confirmation of medication risk factors for deterioration in renal function.
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