Frequency and acceptance of clinical decision support system-generated STOPP/START signals for hospitalised older patients with polypharmacy and multimorbidity

Background The Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) instrument is used to evaluate the appropriateness of medication in older people. STOPP/START criteria have been converted into software algorithms and implemented in a clinical decision support system (CDSS) to facilitate their use in clinical practice. Objective Our objective was to determine the frequency of CDSS-generated STOPP/START signals and their subsequent acceptance by a pharmacotherapy team in a hospital setting. Design and Methods Hospitalised older patients with polypharmacy and multimorbidity allocated to the intervention arm of the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) trial underwent a CDSS-assisted structured medication review in four European hospitals. We evaluated the frequency of CDSS-generated STOPP/START signals and the subsequent acceptance of these signals by a trained pharmacotherapy team consisting of a physician and pharmacist after evaluation of clinical applicability to the individual patient, prior to discussing pharmacotherapy optimisation recommendations with the patient and attending physicians. Multivariate linear regression analysis was used to investigate potential patient-related (e.g. age, number of co-morbidities and medications) and setting-related (e.g. ward type, country of inclusion) determinants for acceptance of STOPP and START signals. Results In 819/826 (99%) of the patients, at least one STOPP/START signal was generated using a set of 110 algorithms based on STOPP/START v2 criteria. Overall, 39% of the 5080 signals were accepted by the pharmacotherapy team. There was a high variability in the frequency and the subsequent acceptance of the individual STOPP/START criteria. The acceptance ranged from 2.5 to 75.8% for the top ten most frequently generated STOPP and START signals. The signal to stop a drug without a clinical indication was most frequently generated (28%), with more than half of the signals accepted (54%). No difference in mean acceptance of STOPP versus START signals was found. In multivariate analysis, most patient-related determinants did not predict acceptance, although the acceptance of START signals increased in patients with one or more hospital admissions (+ 7.9; 95% confidence interval [CI] 1.6-14.1) or one or more falls in the previous year (+ 7.1; 95% CI 0.7-13.4). A higher number of co-morbidities was associated with lower acceptance of STOPP (- 11.8%; 95% CI - 19.2 to - 4.5) and START (- 11.0%; 95% CI - 19.4 to - 2.6) signals for patients with more than nine and between seven and nine co-morbidities, respectively. For setting-related determinants, the acceptance differed significantly between the participating trial sites. Compared with Switzerland, the acceptance was higher in Ireland (STOPP: + 26.8%; 95% CI 16.8-36.7; START: + 31.1%; 95% CI 18.2-44.0) and in the Netherlands (STOPP: + 14.7%; 95% CI 7.8-21.7). Admission to a surgical ward was positively associated with acceptance of STOPP signals (+ 10.3%; 95% CI 3.8-16.8). Conclusion The involvement of an expert team in translating population-based CDSS signals to individual patients is essential, as more than half of the signals for potential overuse, underuse, and misuse were not deemed clinically appropriate in a hospital setting. Patient-related potential determinants were poor predictors of acceptance.Future research investigating factors that affect patients' and physicians' agreement with medication changes recommended by expert teams may provide further insight for implementation in clinical practice. Registration ClinicalTrials.gov Identifier: NCT02986425.Geriatrics in primary carePublic Health and primary car

Optimizing therapy to prevent avoidable hospital admissions in multimorbid older adults (OPERAM): cluster randomised controlled trial

OBJECTIVETo examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital.DESIGNCluster randomised controlled trial.SETTING110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors.PARTICIPANTS2008 older adults (>= 70 years) with multimorbidity (>= 3chronic conditions) and polypharmacy (>= 5 drugs used long term).INTERVENTIONClinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing.MAIN OUTCOME MEASUREPrimary outcome was first drug related hospital admission within 12 months.RESULTS2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had >= 1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths).CONCLUSIONSInappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes.Algorithms and the Foundations of Software technolog

Effects of N fertilizer on root growth in Zea "mays" L. seedlings

This paper reports the effects of different nitrogen (N) fertilizer levels on the growth of maize (Zea mays L.) under field conditions. The N supply was found to influence the growth of the plants, especially the roots. A high N supply significantly inhibited root elongation, and was associated with reduced root dry weight compared to controls and to plants grown with smaller supplies of N. However, no differences were seen in lateral primary root density under the different N supply conditions, nor did plant N concentration increase with high N supply. In conclusion, a high N supply not only wastes resources and pollutes the environment, it may also inhibit root growth.Se llevaron a cabo experimentos de campo para estudiar el efecto de los niveles de fertilizante de nitrógeno (N) sobre el crecimiento de maíz (Zea mays L.). Los resultados demostraron que el suministro de nitrógeno puede influir en el crecimiento de las plantas, especialmente en las raíces. En condiciones de campo, un elevado suministro de N inhibió significativamente la elongación de las raíces. El peso seco de las raíces que crecieron bajo un elevado suministro de N disminuyó comparado con controles o con plantas que crecieron con niveles inferiores de N. Sin embargo, la densidad de las raíces laterales primarias se mantuvo constante cuando las plantas crecieron con diversos niveles de N, y la concentración interna de N de las plantas no aumentó con un elevado suministro de N en el suelo. Un aporte elevado de N no solo desperdicia recursos y contamina el medio ambiente, sino que también puede impedir el crecimiento de las raíces

The effect of down-regulation of Smad3 by RNAi on hepatic stellate cells and a carbon tetrachloride-induced rat model of hepatic fibrosis

Searching for effective Smad3 gene-based gene therapies for hepatic fibrosis, we constructed siRNA expression plasmids targeting the rat Smad3 gene and then delivered these plasmids into hepatic stellate cells (HSCs). The effect of siRNAs on the mRNA levels of Smad2, Smad3, Smad4, and collagens I-&#945;1, III-&#945;1 and IV-&#945;1 (Col&#945;1, Col3&#945;1, Col4&#945;1, respectively) was determined by RT-PCR. Eighty adult male Sprague-Dawley rats were randomly divided into three groups. Twice a week for 8 weeks, the untreated hepatic fibrosis model (N = 30) and the treated group (N = 20) were injected subcutaneously with 40% (v/v) carbon tetrachloride (CCl4)-olive oil (3 mL/kg), and the normal control group (N = 30) was injected with olive oil (3 mL/kg). In the 4th week, the treated rats were injected subcutaneously with liposome-encapsulated plasmids (150 µg/kg) into the right liver lobe under general anesthesia once every 2 weeks, and the untreated rats were injected with the same volume of buffer. At the end of the 6th and 8th weeks, liver tissue and sera were collected. Pathological changes were assessed by a semi-quantitative scoring system (SSS), and a radioimmunoassay was used to establish a serum liver fibrosis index (type III procollagen, type IV collagen, laminin, and hyaluronic acid). The mRNA expression levels of the above cited genes were reduced in the HSCs transfected with the siRNA expression plasmids. Moreover, in the treated group, fibrosis evaluated by the SSS was significantly reduced (P < 0.05) and the serum indices were greatly improved (P < 0.01). These results suggest that Smad3 siRNA expression plasmids have an anti-fibrotic effect

Use of ‘velocity projection’ to estimate the variation of sea-surface height from HF Doppler radar current measurements

The technique of ‘velocity projection’ (J. Geophys. Res. 106 (2001) 6973) is used to estimate the sea-surface height field and its change over time from measurements of surface velocity made using a shore-based HF Doppler radar over a 30×30-km region of the continental shelf located near the mouth of the Chesapeake Bay (USA). Projected current profiles are compared with measured currents from an array of acoustic Doppler current profilers, and the consistency and sensitivity of the projections to model assumptions are also examined. Using projected values of the local surface slope, a model sea-surface η( x, y) is least-squares fit over the study region at each measurement time. The error associated with these fits provides an internal check on the validity of the projection results. The slope of the model sea-surface shows a set-up toward the mouth of the Chesapeake Bay during downwelling-favorable winds and a counterclockwise rotation over the tidal cycle that is consistent with linear, shallow-water dynamics. A time series of sea-level difference extracted from the η maps shows a dominant M 2 tidal signal that compares well with measurements of bottom pressure made at two moorings. With proper attention to limits of applicability, such projection-based sea-surface slope fields (as well as other projection results) may be useful in diagnostic calculations or as nowcasts for use with prognostic models

GaAs-based near-infrared up-conversion device fabricated by wafer fusion

Reported for the first time is a full GaAs-based room-temperature near-infrared (NIR) up-conversion device fabricated by wafer-fusing a GaNAsSb/GaAs pin photodetector (PD) with a GaAs/AlGaAs light-emitting diode (LED). NIR photons with wavelengths in the range 1.3-1.6m were up-converted to 0.87m. \ua9 2011 The Institution of Engineering and Technology.Peer reviewed: YesNRC publication: Ye