Clinical Decision Support Systems in Hospitalized Older Patients: An Exploratory Analysis in a Real-Life Clinical Setting.

BACKGROUND: Inappropriate prescribing is associated with negative patient outcomes. In hospitalized patients, the use of Clinical Decision Support Systems (CDSSs) may reduce inappropriate prescribing and thereby improve patient-related outcomes. However, recently published large clinical trials (OPERAM and SENATOR) have shown negative results on the use of CDSSs and patient outcomes and strikingly low acceptance of recommendations. OBJECTIVE: The purpose of the present study was to investigate the use of a CDSS in a real-life clinical setting of hospitalized older patients. As such, we report on the real-life pattern of this in-hospital implemented CDSS, including (i) whether generated alerts were resolved; (ii) whether a recorded action by the pharmacist led to an improved number of resolved alerts; and (iii) the natural course of generated alerts, in particular of those in the non-intervention group; as these data are largely lacking in current studies. METHODS: Hospitalized patients, aged 60 years and older, admitted to Zuyderland Medical Centre, the Netherlands, in 2018 were included. The evaluation of the CDSS was investigated using a database used for standard care. Alongside demographic and clinical data, we also collected the total numbers of CDSS alerts, the number of alerts 'handled' by the pharmacist, those that resulted in an action by the pharmacist, and finally the outcome of the alerts at day 1 and day 3 after the alert was generated. RESULTS: A total of 3574 unique hospitalized patients, mean age 76.7 (SD 8.3) years and 53% female, were included. From these patients, 8073 alerts were generated, of which 7907 (97.9% of total) were handled by the pharmacist (day 1). In 51.6% of the alerts handled by the pharmacist, an action was initiated, resulting in 36.1% of the alerts resolved after day 1, compared with 27.3% if the pharmacist did not perform an action (p < 0.001). On day 3, in 52.6% of the alerts an action by the pharmacist was initiated, resulting in 62.4% resolved alerts, compared with 48.0% when no action was performed (p < 0.001). In the category renal function, the percentages differed significantly between an action versus no action of the pharmacist at day 1 and at day 3 (16.6% vs 10.6%, p < 0.001 [day 1]; 29.8% vs 19.4%, p < 0.001 [day 3]). CONCLUSION: This study demonstrates the pattern and natural course of clinical alerts of an in-hospital implemented CDSS in a real-life clinical setting of hospitalized older patients. Besides the already known beneficial effect of actions by pharmacists, we have also shown that many alerts become resolved without any specific intervention. As such, our study provides an important insight into the spontaneous course of resolved alerts, since these data are currently lacking in the literature.

Control in the Hospital by Extensive Clinical rules for Unplanned hospitalizations in older Patients (CHECkUP); study design of a multicentre randomized study.

BACKGROUND: Due to ageing of the population the incidence of multimorbidity and polypharmacy is rising. Polypharmacy is a risk factor for medication-related (re)admission and therefore places a significant burden on the healthcare system. The reported incidence of medication-related (re)admissions varies widely due to the lack of a clear definition. Some medications are known to increase the risk for medication-related admission and are therefore published in the triggerlist of the Dutch guideline for Polypharmacy in older patients. Different interventions to support medication optimization have been studied to reduce medication-related (re)admissions. However, the optimal template of medication optimization is still unknown, which contributes to the large heterogeneity of their effect on hospital readmissions. Therefore, we implemented a clinical decision support system (CDSS) to optimize medication lists and investigate whether continuous use of a CDSS reduces the number of hospital readmissions in older patients, who previously have had an unplanned probably medication-related hospitalization. METHODS: The CHECkUP study is a multicentre randomized study in older (≥60 years) patients with an unplanned hospitalization, polypharmacy (≥5 medications) and using at least two medications from the triggerlist, from Zuyderland Medical Centre and Maastricht University Medical Centre+ in the Netherlands. Patients will be randomized. The intervention consists of continuous (weekly) use of a CDSS, which generates a Medication Optimization Profile, which will be sent to the patient's general practitioner and pharmacist. The control group will receive standard care. The primary outcome is hospital readmission within 1 year after study inclusion. Secondary outcomes are one-year mortality, number of emergency department visits, nursing home admissions, time to hospital readmissions and we will evaluate the quality of life and socio-economic status. DISCUSSION: This study is expected to add evidence on the knowledge of medication optimization and whether use of a continuous CDSS ameliorates the risk of adverse outcomes in older patients, already at an increased risk of medication-related (re)admission. To our knowledge, this is the first large study, providing one-year follow-up data and reporting not only on quality of care indicators, but also on quality-of-life. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register on October 14, 2018, identifier: NL7449 (NTR7691). https://www.trialregister.nl/trial/7449 .

Fall incidents in nursing home residents: development of a predictive clinical rule (FINDER).

OBJECTIVES: To develop (part I) and validate (part II) an electronic fall risk clinical rule (CR) to identify nursing home residents (NH-residents) at risk for a fall incident. DESIGN: Observational, retrospective case-control study. SETTING: Nursing homes. PARTICIPANTS: A total of 1668 (824 in part I, 844 in part II) NH-residents from the Netherlands were included. Data of participants from part I were excluded in part II. PRIMARY AND SECONDARY OUTCOME MEASURES: Development and validation of a fall risk CR in NH-residents. Logistic regression analysis was conducted to identify the fall risk-variables in part I. With these, three CRs were developed (ie, at the day of the fall incident and 3 days and 5 days prior to the fall incident). The overall prediction quality of the CRs were assessed using the area under the receiver operating characteristics (AUROC), and a cut-off value was determined for the predicted risk ensuring a sensitivity ≥0.85. Finally, one CR was chosen and validated in part II using a new retrospective data set. RESULTS: Eleven fall risk-variables were identified in part I. The AUROCs of the three CRs form part I were similar: the AUROC for models I, II and III were 0.714 (95% CI: 0.679 to 0.748), 0.715 (95% CI: 0.680 to 0.750) and 0.709 (95% CI: 0.674 to 0.744), respectively. Model III (ie, 5 days prior to the fall incident) was chosen for validation in part II. The validated AUROC of the CR, obtained in part II, was 0.603 (95% CI: 0.565 to 0.641) with a sensitivity of 83.41% (95% CI: 79.44% to 86.76%) and a specificity of 27.25% (95% CI 23.11% to 31.81%). CONCLUSION: Medication data and resident characteristics alone are not sufficient enough to develop a successful CR with a high sensitivity and specificity to predict fall risk in NH-residents. TRIAL REGISTRATION NUMBER: Not available.

Validation of an automated delirium prediction model (DElirium MOdel (DEMO)): an observational study.

OBJECTIVES: Delirium is an underdiagnosed, severe and costly disorder, and 30%-40% of cases can be prevented. A fully automated model to predict delirium (DEMO) in older people has been developed, and the objective of this study is to validate the model in a hospital setting. SETTING: Secondary care, one hospital with two locations. DESIGN: Observational study. PARTICIPANTS: The study included 450 randomly selected patients over 60 years of age admitted to Zuyderland Medical Centre. Patients who presented with delirium on admission were excluded. PRIMARY OUTCOME MEASURES: Development of delirium through chart review. RESULTS: A total of 383 patients were included in this study. The analysis was performed for delirium within 1, 3 and 5 days after a DEMO score was obtained. Sensitivity was 87.1% (95% CI 0.756 to 0.939), 84.2% (95% CI 0.732 to 0.915) and 82.7% (95% CI 0.734 to 0.893) for 1, 3 and 5 days, respectively, after obtaining the DEMO score. Specificity was 77.9% (95% CI 0.729 to 0.882), 81.5% (95% CI 0.766 to 0.856) and 84.5% (95% CI 0.797 to 0.884) for 1, 3 and 5 days, respectively, after obtaining the DEMO score. CONCLUSION: DEMO is a satisfactory prediction model but needs further prospective validation with in-person delirium confirmation. In the future, DEMO will be applied in clinical practice so that physicians will be aware of when a patient is at an increased risk of developing delirium, which will facilitate earlier recognition and diagnosis, and thus will allow the implementation of prevention measures.

Supporting clinical rules engine in the adjustment of medication (SCREAM): protocol of a multicentre, prospective, randomised study.

BACKGROUND: In the nursing home population, it is estimated that 1 in every 3 patients is polymedicated and given their considerable frailty, these patients are especially prone to adverse drug reactions. Clinical pharmacist-led medication reviews are considered successful interventions to improve medication safety in the inpatient setting. Due to the limited available evidence concerning the benefits of medication reviews performed in the nursing home setting, we propose a study aiming to demonstrate a positive effect that a clinical decision support system, as a health care intervention, may have on the target population. The primary objective of this study is to reduce the number of patients with at least one event when using the clinical decision support system compared to the regular care. These events consist of hospital referrals, delirium, falls, and/or deaths. METHOD/DESIGN: This study is a multicentre, prospective, randomised study with a cluster group design. The randomisation will be per main nursing home physician and stratified per ward (somatic and psychogeriatric). In the intervention group the clinical decision support system will be used to screen medication list, laboratory values and medical history in order to obtain potential clinical relevant remarks. The remarks will be sent to the main physician and feedback will be provided whether the advice was followed or not. In the control group regular care will be applied. DISCUSSION: We strongly believe that by using a clinical decision support system, medication reviews are performed in a standardised way which leads to comparable results between patients. In addition, using a clinical decision support system eliminates the time factor to perform medication reviews as the major problems related to medication, laboratory values, indications and/or established patient characteristics will be directly available. In this way, and in order to make the medication review process complete, consultation within healthcare professionals and/or the patient itself will be time effective and the medication surveillance could be performed around the clock. TRIAL REGISTRATION: The Netherlands National Trial Register NTR5165 . Registered 2nd April 2015.

The support of medication reviews in hospitalised patients using a clinical decision support system.

OBJECTIVES: First, to estimate the added value of a clinical decision support system (CDSS) in the performance of medication reviews in hospitalised elderly. Second, to identify the limitations of the current CDSS by analysing generated drug-related problems (DRPs). METHODS: Medication reviews were performed in patients admitted to the geriatric ward of the Zuyderland medical centre. Additionally, electronically available patient information was introduced into a CDSS. The DRP notifications generated by the CDSS were compared with those found in the medication review. The DRP notifications were analysed to learn how to improve the CDSS. RESULTS: A total of 223 DRP strategies were identified during the medication reviews. The CDSS generated 70 clinically relevant DRP notifications. Of these DRP notifications, 63 % (44) were also found during the medication reviews. The CDSS generated 10 % (26) new DRP notifications and conveyed 28 % (70) of all 249 clinically relevant DRPs that were found. Classification of the CDSS generated DRP notifications related to 'medication error type' revealed that 'contraindications/interactions/side effects' and 'indication without medication' were the main categories not identified during the manual medication review. The error types 'medication without indication', 'double medication', and 'wrong medication' were mostly not identified by the CDSS. CONCLUSIONS: The CDSS used in this study is not yet sufficiently advanced to replace the manual medication review, though it does add value to the manual medication review. The strengths and weaknesses of the current CDSS can be determined according to the medication error types.

The development of an automated ward independent delirium risk prediction model.

Background A delirium is common in hospital settings resulting in increased mortality and costs. Prevention of a delirium is clearly preferred over treatment. A delirium risk prediction model can be helpful to identify patients at risk of a delirium, allowing the start of preventive treatment. Current risk prediction models rely on manual calculation of the individual patient risk. Objective The aim of this study was to develop an automated ward independent delirium riskprediction model. To show that such a model can be constructed exclusively from electronically available risk factors and thereby implemented into a clinical decision support system (CDSS) to optimally support the physician to initiate preventive treatment. Setting A Dutch teaching hospital. Methods A retrospective cohort study in which patients, 60 years or older, were selected when admitted to the hospital, with no delirium diagnosis when presenting, or during the first day of admission. We used logistic regression analysis to develop a delirium predictive model out of the electronically available predictive variables. Main outcome measure A delirium risk prediction model. Results A delirium risk prediction model was developed using predictive variables that were significant in the univariable regression analyses. The area under the receiver operating characteristics curve of the "medication model" model was 0.76 after internal validation. Conclusions CDSSs can be used to automatically predict the risk of a delirium in individual hospitalised patients' by exclusively using electronically available predictive variables. To increase the use and improve the quality of predictive models, clinical risk factors should be documented ready for automated use.

Development of a computer system to support medication reviews in nursing homes.

The frail elderly populations of nursing homes frequently use drugs and suffer from considerable comorbidities. Medication reviews are intended to support evidence based prescribing and optimise therapy. However, literature is still ambiguous regarding the optimal method and the effects of medication reviews. Innovative computerised systems may support the medication reviews in the future. We are developing a clinical decision support system (CDSS) that, independently of the prescribing software, continuously monitors all prescribed drugs while taking into account co-medication, laboratory-data and co-morbidities. The CDSS will be developed in five phases: (1) development of the computerised system, (2) development of the clinical rules, (3) validation of the CDSS, (4) randomised controlled trial, and (5) feasibility for implementation in different nursing homes. The clinical decision support system aims at supporting the traditional medication review.

[A patient with a life-threatening disulfiram-ethanol reaction]. / Een patiënt met een levensbedreigende disulfiram-ethanolreactie.

BACKGROUND: Disulfiram is a substance often used to treat alcohol dependency. The agent may be effective when used as supportive therapy. Disulfiram causes an accumulation of acetaldehyde when alcohol is consumed, which results in unpleasant sensations such as warmth, nausea, vomiting and headache. CASE DESCRIPTION: A patient was brought into the emergency ward with a suspected alcohol intoxication. As it turned out, she had experienced a severe disulfiram-ethanol reaction which had led to hypotensive shock; extensive abnormalities were seen on the ECG. The patient was admitted to the intensive care unit. High-dose norepinephrine treatment was needed to bring the blood pressure back to normal. The use of disulfiram was only discovered at a later stage. CONCLUSION: In rare cases, a disulfiram-ethanol reaction can lead to life-threatening situations. Descriptions of toxicity at acetaldehyde levels of 5 mg/l are found in the literature. In this article, we describe a life-threatening reaction which developed at a level between only 2.3-3.0 mg/l. This case shows that the provision of information on a patient's use of medications and adequate communication are just as important as toxicological screening in the laboratory.

[Unexplained fever after exposure to rats: rat bite fever or Haverhill fever]. / Onbegrepen koorts na rattenexpositie: rattenbeetziekte of 'Haverhill fever'.

A 24-year old man presented himself to the emergency ward with complaints of fever, nausea, headache, muscle ache and chest pain. Two weeks before presentation he had been bitten by a pet rat. We determined that he had bacteraemia caused by a Streptobacillus moniliformis infection, which led to the development of an illness called rat bite fever. S. moniliformis is a pleomorphic gram-negative rod-shaped bacterium that is considered part of the normal nasopharyngeal flora in rats. It is the cause of two similar illnesses: rat bite fever and Haverhill fever. Clinicians should consider these infections in the work-up of unexplained fever or sepsis, certainly in the presence of known exposure to rats. Treatment consists of antibiotics.

Influence of substrate conductivity on circulation reversal in evaporating drops.

Nonuniform evaporation from sessile droplets induces radial convection within the drop, which produces the well-known "coffee-ring" effect. The evaporation also induces a gradient in temperature and consequently a gradient in surface tension, generating a Marangoni flow. Here we investigate theoretically and experimentally the thermal Marangoni flow and establish criteria to gauge its influence. An asymptotic analysis indicates that the direction of the flow depends on the relative thermal conductivities of the substrate and liquid, k_{R} identical withk_{S}/k_{L}, reversing direction at a critical contact angle over the range 1.45

Latency- and Defense-Related Ultrastructural Characteristics of Apple Fruit Tissues Infected with Botryosphaeria dothidea.

ABSTRACT Apple fruit tissues infected with Botryosphaeria dothidea were examined by transmission electron microscopy using susceptible cv. Fuji and resistant cv. Jonathan. Immature (green) and mature (red) fruits of cv. Fuji with restricted or expanding lesions were also examined to reveal subcellular characteristics related with latent and restricted disease development. In infected susceptible mature fruits, cytoplasmic degeneration and organelle disruption commonly occurred, accompanying cell wall dissolution around invading hyphae. Cell wall dissolution around invading hyphae in subepidermis was rare in immature, red halo-symptomed cv. Fuji and resistant cv. Jonathan fruits. In infected immature fruits of cv. Fuji, presumably at the latent state of disease development, cellular degeneration was less severe, and invading hyphae contained prominent microbody-lipid globule complexes or the deposition of thin electron-dense outer layer around cell wall of intercellular hyphae. Both mature fruits with red halos and resistant apple fruits formed cell wall protuberances at the outside of cell walls. In addition, electron-dense extramural layers were formed in the resistant apple fruits. Aberrant hyphal structures such as intrahyphal hyphae were found only in resistant fruit tissues, indicating the physiologically altered fungal growth. These ultrastructural changes of host tissues and fungal hyphae may reflect the pathogenesis of apple white rot under varying conditions of apple fruits.

Reduction of aflatoxins by Korean soybean paste and its effect on cytotoxicity and reproductive toxicity--part 1. Inhibition of growth and aflatoxin production of Aspergillus parasiticus by Korean soybean paste (Doen-jang) and identification of the active component.

The inhibitory effect of methanol extract of Korean soybean paste on the mold growth and aflatoxin production of a toxigenic strain of Aspergillus parasiticus ATCC 15517 was studied using different concentrations of the extract in yeast-extract sucrose broth. While inhibition in mold growth due to increasing the concentration of the extract was observed, the more remarkable effect was the inhibition of aflatoxin production. Reduction of mycelial weight as a result of addition of the extract was observed to range between 1.5 to 12.9% while reduction of aflatoxin production quantified by high-performance liquid chromatography ranged from 14.3 to 41.7%. Five percent of the extract significantly reduced aflatoxin production at the end of the incubation period (P < 0.05), although the effect on mycelial growth was less pronounced. This study indicates that soybean paste could also be an effective inhibitor of aflatoxin production even though mycelial growth may be permitted. The main active component identified by gas chromatography-mass spectroscopy was linoleic acid.

Isolated left main coronary ostial stenosis: intraoperative transesophageal echocardiography during surgical angioplasty.

OBJECTIVE: We hypothesized that transesophageal echocardiography could be used to image the repair of a left ostium or main coronary artery following surgical angioplasty. METHODS AND RESULTS: Six patients, all women, were found to have isolated left main coronary ostial stenosis. We performed preoperative transesophageal echocardiography (TEE) in three and intraoperative TEE in four of six patients. Their mean age was 48 years. They presented with severe angina (Class III or IV) with a short duration (6.8 +/- 7.8 months). They had a low incidence of risk factors while histopathologic examinations showed typical atherosclerosis in all four patients. Preoperative two-dimensional echocardiography demonstrated left main coronary ostial stenosis in three patients. We clearly observed the patency of the pericardial or saphenous venous patch with basal short-axis scan on two-dimensional and color Doppler echocardiography in all four patients after weaning them from cardiopulmonary bypass and finished operation without complications. CONCLUSIONS: Our study shows that TEE can be used to image the repair of a left ostium or main coronary artery following surgical angioplasty and provide the surgeon with the required information about the adequacy of the repair.

A case of primary hepatic actinomycosis.

Actinomycosis is a chronic suppurative and granulomatous disease characterized histologically by sulfur granules with extensive necrosis, fibrosis and sinus formation. Depending on the site of primary infection, actinomycosis is generally classified as cervicofacial, thoracic and abdominal type. The liver is known to be the primary site of infection in 15% with abdominal actinomycosis. The authors have experienced a case of liver abscess in a 24-year-old male. The sono-guided aspiration biopsy revealed findings of infiltration of neutrophils and characteristics sulfur granules by light microscopy. This case was thought to represent an instance of liver actinomycosis. Although there have been a lot of reports on actinomycosis of the liver in other countries, only 3 cases were reported in Korea.

Isolated left main coronary ostial stenosis in Oriental people: operative, histopathologic and clinical findings in six patients.

OBJECTIVES: This study was performed to determine whether there are differences in the operative, histopathologic, angiographic and clinical findings of isolated ostial stenosis between Oriental and western patients. BACKGROUND: Angiographic, clinical and histologic findings in isolated ostial stenosis have been reported in western but not in Oriental patients. METHODS: Six patients, all women (0.88% of a total of 684 patients who underwent coronary angiography between March 1989 and July 1991), were found to have isolated left main coronary ostial stenosis. We performed surgical ostial angioplasty with the autologous pericardial or saphenous venous patch and biopsy at the aortic arteriotomy site in four of the six patients. RESULTS: All six patients presented with severe angina (angina class III or IV) of short duration (mean +/- SD 6.2 +/- 6.2 months) and had a very low incidence of risk factors, although histopathologic examination showed typical atherosclerosis in four of the six patients. They were young to middle-aged women (mean 45 +/- 3 years) except for Patient 6 (62 years). Exercise duration was short and ST segment depression, accompanied by typical angina, was observed in many leads in the warm-up period or stage I. Despite the crucial location of the lesion, most patients had well preserved left ventricular function and normal wall motion. There was no angiographically definable collateral circulation from either ipsilateral or contralateral vessels except for grade I collateral circulation in Patient 5. Operative findings demonstrated mostly yellow atheroma in the aortic wall and left coronary ostium. Coronary angiography showed only ostial stenosis of the left coronary artery in all six patients, but operative findings documented atheromatous change in the left main coronary artery in two of the six. CONCLUSIONS: The clinical, angiographic, histopathologic and operative findings of Oriental patients were similar to those reported in western patients, but the incidence of isolated left main coronary ostial stenosis was higher in the Oriental group. Angiographically definable isolated coronary ostial stenosis may often not be true isolated ostial stenosis.

[Prophylactic and therapeutic studies on intestinal giant-cystic disease of the Israel carp caused by Thelohanellus kitauei. I. Course of formation and vanishment of the cyst].

In an attempt to develop prophylactic and therapeutic measures of the intestinal giant-cystic disease caused by Thelohanellus kitauei in the Israel carp, Cyprinus carpio nudus, pathological observations were conducted upon the carps which were hatched in May 1988 and raised in a net cage fish farm at the Soyang lake, managed by Horim Fisheries for the period of 21 months with 1-2 months interval. After a gross inspection of the carps, necropsy was carried out periodically in order to clarify the pathological changes in various internal organs and muscular tissues. Also, the prevalence of the disease was checked during the period from 1988 to 1990. Gross inspections revealed that the infected carps showed some degree of fading in body and gill color, back-emaciation symptoms, reddish anus accompanying erosion and relaxation and pot-belly, as well as discharge of yellowish white mucoid material from the anus. However, most carps died eventually of intestinal obstruction. Other significant necropsy findings included cyst formation of various size in the intestinal mucosa, ascites, anemic condition through internal organs and muscular tissues, hyperemia and dilation of intestines with decreased tension, thinness and fragility, and full contents of semi-fluid or yellowish white mucoid material in the intestinal canals. Based on the morphological characteristics of the spores found in the cysts, parasitic location in the intestines, macro- and microscopic findings of the lesions, the parasites were identified as Thelohanellus kitauei Egusa et Nakajima, 1981. Although monthly changes of water temperature were distinct, the extrusion rates of the polar filaments of the spores stayed constant throughout the year with an exception of a lower rate in July. The lesions initiated from mucosa and submucosa in early July became large swellings and then complete mature forms following the peracute course. From late August the upper cysts were gradually opened and most of the spores were dispersed from anus into the surrounding water through December but only a few lasted until next April. The cysts were completely recovered until next September. Comparing the incidence and prevalence of the disease by year tremendous infection and death rates were checked in the first prevalent year, 1988, but the rates were significantly decreased in the second year, and showed an almost normal status in the third year, 1990. As the above summarized results showed, the disease entity might come to an end in three years after the first prevalent year, however, the spores must be strictly prevented because they could be infective in the water for one year.

[Increased primary success rate in coronary angioplasty using a guide wire with attached balloon (microprobe)]. / Erhöhte primäre Erfolgsrate bei der Koronarangioplastie durch Einsatz eines ballonarmierten Führungsdrahtes (Microprobe).

In 15 cases of 350 consecutive coronary angioplasties conventional low profile balloon catheters did not traverse the stenosis or occlusion over the guide-wire. A balloon on a wire device ("Microprobe", 2 mm) passed the stenosis or occlusion easily with a good primary result in 14 cases. The angioplasty procedure could then be completed with a larger standard balloon catheter. Use of the balloon on a wire device expands the technical facilities of angioplasty and increases the primary success rate in technically difficult cases.