Diabetes and the risk of cardiovascular events and all-cause mortality among older adults: an individual participant data analysis of five prospective studies.

BACKGROUND: Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults. METHODS: We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality. Secondary outcomes were the components of the composite. We evaluated CHD risk equivalence by comparing outcomes between individuals with T2D but no CHD versus CHD but no T2D. RESULTS: The median age of participants was 71 years, 20% had T2D and 17% had CHD at baseline. A total of 29,474 participants (36%) experienced the composite outcome. Baseline T2D was associated with higher risk of cardiovascular events or all-cause mortality versus no T2D (HR 1.44, 95% CI [1.40-1.49]). The association was weaker in individuals aged ≥75 years versus 65-74 years (HR 1.32 [1.19-1.46] vs. 1.56 [1.50-1.62]; p-value for interaction = .032). Compared to individuals with CHD but no T2D, individuals with T2D but no CHD had a similar risk of the composite outcome (HR 0.95 [0.85-1.07]), but a lower risk of cardiovascular events (HR 0.76 [0.59-0.98]). CONCLUSIONS: T2D was associated with increased risk of cardiovascular events and all-cause mortality in older adults, but T2D without CHD conferred lower risk of cardiovascular events compared to CHD without T2D. Our results suggest that T2D should not be considered a CHD risk equivalent in older adults.

The Dutch list of essential drugs for undergraduate medical education: A modified Delphi study.

AIMS: Prescribing errors among junior doctors are common in clinical practice because many lack prescribing competence after graduation. This is in part due to inadequate education in clinical pharmacology and therapeutics (CP&T) in the undergraduate medical curriculum. To support CP&T education, it is important to determine which drugs medical undergraduates should be able to prescribe safely and effectively without direct supervision by the time they graduate. Currently, there is no such list with broad-based consensus. Therefore, the aim was to reach consensus on a list of essential drugs for undergraduate medical education in the Netherlands. METHODS: A two-round modified Delphi study was conducted among pharmacists, medical specialists, junior doctors and pharmacotherapy teachers from all eight Dutch academic hospitals. Participants were asked to indicate whether it was essential that medical graduates could prescribe specific drugs included on a preliminary list. Drugs for which ≥80% of all respondents agreed or strongly agreed were included in the final list. RESULTS: In all, 42 (65%) participants completed the two Delphi rounds. A total of 132 drugs (39%) from the preliminary list and two (3%) newly proposed drugs were included. CONCLUSIONS: This is the first Delphi consensus study to identify the drugs that Dutch junior doctors should be able to prescribe safely and effectively without direct supervision. This list can be used to harmonize and support the teaching and assessment of CP&T. Moreover, this study shows that a Delphi method is suitable to reach consensus on such a list, and could be used for a European list.

The impact of a summative national prescribing assessment and curriculum type on the development of the prescribing competence of junior doctors.

PURPOSE: The primary aim of this study was to investigate the effect of including the Dutch National Pharmacotherapy Assessment (DNPA) in the medical curriculum on the level and development of prescribing knowledge and skills of junior doctors. The secondary aim was to evaluate the relationship between the curriculum type and the prescribing competence of junior doctors. METHODS: We re-analysed the data of a longitudinal study conducted in 2016 involving recently graduated junior doctors from 11 medical schools across the Netherlands and Belgium. Participants completed three assessments during the first year after graduation (around graduation (+ / - 4 weeks), and 6 months, and 1 year after graduation), each of which contained 35 multiple choice questions (MCQs) assessing knowledge and three clinical case scenarios assessing skills. Only one medical school used the DNPA in its medical curriculum; the other medical schools used conventional means to assess prescribing knowledge and skills. Five medical schools were classified as providing solely theoretical clinical pharmacology and therapeutics (CPT) education; the others provided both theoretical and practical CPT education (mixed curriculum). RESULTS: Of the 1584 invited junior doctors, 556 (35.1%) participated, 326 (58.6%) completed the MCQs and 325 (58.5%) the clinical case scenarios in all three assessments. Junior doctors whose medical curriculum included the DNPA had higher knowledge scores than other junior doctors (76.7% [SD 12.5] vs. 67.8% [SD 12.6], 81.8% [SD 11.1] vs. 76.1% [SD 11.1], 77.0% [12.1] vs. 70.6% [SD 14.0], p < 0.05 for all three assessments, respectively). There was no difference in skills scores at the moment of graduation (p = 0.110), but after 6 and 12 months junior doctors whose medical curriculum included the DNPA had higher skills scores (both p < 0.001). Junior doctors educated with a mixed curriculum had significantly higher scores for both knowledge and skills than did junior doctors educated with a theoretical curriculum (p < 0.05 in all assessments). CONCLUSION: Our findings suggest that the inclusion of the knowledge focused DNPA in the medical curriculum improves the prescribing knowledge, but not the skills, of junior doctors at the moment of graduation. However, after 6 and 12 months, both the knowledge and skills were higher in the junior doctors whose medical curriculum included the DNPA. A curriculum that provides both theoretical and practical education seems to improve both prescribing knowledge and skills relative to a solely theoretical curriculum.

Association between diabetes overtreatment in older multimorbid patients and clinical outcomes: an ancillary European multicentre study.

BACKGROUND: Diabetes overtreatment is a frequent and severe issue in multimorbid older patients with type 2 diabetes (T2D). OBJECTIVE: This study aimed at assessing the association between diabetes overtreatment and 1-year functional decline, hospitalisation and mortality in older inpatients with multimorbidity and polypharmacy. METHODS: Ancillary study of the European multicentre OPERAM project on multimorbid patients aged ≥70 years with T2D and glucose-lowering treatment (GLT). Diabetes overtreatment was defined according to the 2019 Endocrine Society guideline using HbA1c target range individualised according to the patient's overall health status and the use of GLT with a high risk of hypoglycaemia. Multivariable regressions were used to assess the association between diabetes overtreatment and the three outcomes. RESULTS: Among the 490 patients with T2D on GLT (median age: 78 years; 38% female), 168 (34.3%) had diabetes overtreatment. In patients with diabetes overtreatment as compared with those not overtreated, there was no difference in functional decline (29.3% vs 38.0%, P = 0.088) nor hospitalisation rates (107.3 vs 125.8/100 p-y, P = 0.115) but there was a higher mortality rate (32.8 vs 21.4/100 p-y, P = 0.033). In multivariable analyses, diabetes overtreatment was not associated with functional decline nor hospitalisation (hazard ratio, HR [95%CI]: 0.80 [0.63; 1.02]) but was associated with a higher mortality rate (HR [95%CI]: 1.64 [1.06; 2.52]). CONCLUSIONS: Diabetes overtreatment was associated with a higher mortality rate but not with hospitalisation or functional decline. Interventional studies should be undertaken to test the effect of de-intensifying GLT on clinical outcomes in overtreated patients.

Do we become better prescribers after graduation: A 1-year international follow-up study among junior doctors.

AIM: The aim of this study was to investigate how the prescribing knowledge and skills of junior doctors in the Netherlands and Belgium develop in the year after graduation. We also analysed differences in knowledge and skills between surgical and nonsurgical junior doctors. METHODS: This international, multicentre (n = 11), longitudinal study analysed the learning curves of junior doctors working in various specialties via three validated assessments at about the time of graduation, and 6 months and 1 year after graduation. Each assessment contained 35 multiple choice questions (MCQs) on medication safety (passing grade ≥85%) and three clinical scenarios. RESULTS: In total, 556 junior doctors participated, 326 (58.6%) of whom completed the MCQs and 325 (58.5%) the clinical case scenarios of all three assessments. Mean prescribing knowledge was stable in the year after graduation, with 69% (SD 13) correctly answering questions at assessment 1 and 71% (SD 14) at assessment 3, whereas prescribing skills decreased: 63% of treatment plans were considered adequate at assessment 1 but only 40% at assessment 3 (P < .001). While nonsurgical doctors had similar learning curves for knowledge and skills as surgical doctors (P = .53 and P = .56 respectively), their overall level was higher at all three assessments (all P < .05). CONCLUSION: These results show that junior doctors' prescribing knowledge and skills did not improve while they were working in clinical practice. Moreover, their level was under the predefined passing grade. As this might adversely affect patient safety, educational interventions should be introduced to improve the prescribing competence of junior doctors.

Performance of a trigger tool for detecting drug-related hospital admissions in older people: analysis from the OPERAM trial.

BACKGROUND: identifying drug-related hospital admissions (DRAs) in older people is difficult. A standardised chart review procedure has recently been developed. It includes an adjudication team (physician and pharmacist) screening using 26 triggers and then performing causality assessment to determine whether an adverse drug event (ADE) occurred (secondary to an adverse drug reaction, overuse, misuse or underuse) and whether the ADE contributed to hospital admission (DRA). OBJECTIVE: to assess the performance of those triggers in detecting DRA. DESIGN: retrospective study using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people) trial. SETTINGS: four European medical centres. SUBJECTS: multimorbid (≥ 3 chronic medical conditions) older (≥ 70 years) inpatients with polypharmacy (≥ 5 chronic medications) were enrolled in the OPERAM trial (N = 2,008) and followed for 12 months. We included patients with ≥1 adjudicated hospitalisation during the follow-up. METHODS: the positive predictive value (PPV; number of DRAs identified by trigger/number of triggers) was calculated for each trigger and for the tool as a whole. RESULTS: of 1,235 hospitalisations adjudicated for 832 patients, 716 (58%) had at least one trigger; an ADE was identified in 673 (54%) and 518 (42%) were adjudicated as DRAs. The overall PPV of the trigger tool for detecting DRAs was 0.66 [0.62-0.69]. CONCLUSIONS: this tool performs well for identifying DRAs in older people. Based on our results, a revised version of the tool was proposed but will require external validation before it can be incorporated into research and clinical practice.

Statins After Ischemic Stroke in the Oldest: A Cohort Study Using the Clinical Practice Research Datalink Database.

[Figure: see text].

Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs.

BACKGROUND: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. METHODS: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. RESULTS: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. CONCLUSION: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.

Prevalence of drug-drug interactions in older people before and after hospital admission: analysis from the OPERAM trial.

BACKGROUND: Drug-drug interactions (DDIs) are highly prevalent in older patients but little is known about prevalence of DDIs over time. Our main objective was to assess changes in the prevalence and characteristics of drug-drug interactions (DDIs) during a one-year period after hospital admission in older people, and associated risk factors. METHODS: We conducted a sub-study of the European OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people), which assessed the effects of a structured medication review (experimental arm) compared to usual care (control arm) on reducing drug-related hospital readmissions. All OPERAM patients (≥70 years, with multimorbidity and polypharmacy, hospitalized in four centers in Bern, Brussels, Cork and Utrecht between December 2016 and October 2018, followed over 1 year) who were alive at hospital discharge and had full medication data during the index hospitalization (at baseline i.e., enrolment at admission, and at discharge) were included. DDIs were assessed using an international consensus list of potentially clinically significant DDIs in older people. The point-prevalence of DDIs was evaluated at baseline, discharge, and at 2, 6 and 12 months after hospitalization. Logistic regression models were performed to assess independent variables associated with changes in DDIs 2 months after baseline. RESULTS: Of the 1950 patients (median age 79 years) included, 1045 (54%) had at least one potentially clinically significant DDI at baseline; point-prevalence rates were 58, 57, 56 and 57% at discharge, and 2, 6 and 12 months, respectively. The prevalence increased significantly from baseline to discharge (P < .001 [significant only in the control group]), then remained stable over time (P for trend .31). The five most common DDIs -all pharmacodynamic in nature- accounted for 80% of all DDIs and involved drugs that affect potassium concentrations, centrally-acting drugs and antithrombotics. At 2 months, DDIs had increased in 459 (27%) patients and decreased in 331 (19%). The main factor predictive of a change in the prevalence of DDIs was hyperpolypharmacy (≥10 medications). CONCLUSIONS: DDIs were very common; their prevalence increased during hospitalization and tended to remain stable thereafter. Medication review may help control this increase and minimize the risk of adverse drug events.

Opportunities for changes in the drug product design to enhance medication safety in older people: Evaluation of a national public portal for medication incidents.

AIMS: Medication safety requires urgent attention in hospital pharmacy. This study evaluated the medication-related problems/errors as reported to the Dutch medication incident registry and disseminated for information to pharmacists. Through analysis by an expert panel we aimed to better understand which problems could have been mitigated by the drug product design. Additionally, the (wider) implications of the problems for current hospital/clinical practice were discussed. METHODS: Items were extracted from the public Portal for Patient Safety. Items were included if relevant for older people and connected with the drug product design and excluded if they should reasonably have been intercepted by compliance to routine controls or well-known professional standards in pharmaceutical care. To explore any underreporting of well-known incidents, it was investigated if different medication-related problems could be observed in a regional hospital practise over a 1-month period. For 6 included items (cases), the implications for hospital/clinical practise were discussed in an expert panel. RESULTS: In total, 307 items were identified in the Portal for Patient Safety; all but 14 were excluded. Six cases were added from daily hospital practice. These 20 cases commonly related to confusing product characteristics, packaging issues such as the lack of a single unit package for an oncolytic product, or incorrect or incomplete user instructions. CONCLUSION: Medication registries provide important opportunities to evaluate real-world medication-related problems. However, underreporting of well-known problems should be considered. The product design can be used as an (additional) risk mitigation measure to support medication safety in hospital practice.

Measurement properties of EQ-5D-3L and EQ-5D-5L in recording self-reported health status in older patients with substantial multimorbidity and polypharmacy.

BACKGROUND: The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy. METHODS: Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person's EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living. RESULTS: 224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon's evenness index score of 0.86) than the EQ-5D-3L (Shannon's evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index. CONCLUSION: Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures.

Intervention protocol: OPtimising thERapy to prevent avoidable hospital Admission in the Multi-morbid elderly (OPERAM): a structured medication review with support of a computerised decision support system.

BACKGROUND: Several approaches to medication optimisation by identifying drug-related problems in older people have been described. Although some interventions have shown reductions in drug-related problems (DRPs), evidence supporting the effectiveness of medication reviews on clinical and economic outcomes is lacking. Application of the STOPP/START (version 2) explicit screening tool for inappropriate prescribing has decreased inappropriate prescribing and significantly reduced adverse drug reactions (ADRs) and associated healthcare costs in older patients with multi-morbidity and polypharmacy. Therefore, application of STOPP/START criteria during a medication review is likely to be beneficial. Incorporation of explicit screening tools into clinical decision support systems (CDSS) has gained traction as a means to improve both quality and efficiency in the rather time-consuming medication review process. Although CDSS can generate more potential inappropriate medication recommendations, some of these have been shown to be less clinically relevant, resulting in alert fatigue. Moreover, explicit tools such as STOPP/START do not cover all relevant DRPs on an individual patient level. The OPERAM study aims to assess the impact of a structured drug review on the quality of pharmacotherapy in older people with multi-morbidity and polypharmacy. The aim of this paper is to describe the structured, multi-component intervention of the OPERAM trial and compare it with the approach in the comparator arm. METHOD: This paper describes a multi-component intervention, integrating interventions that have demonstrated effectiveness in defining DRPs. The intervention involves a structured history-taking of medication (SHiM), a medication review according to the systemic tool to reduce inappropriate prescribing (STRIP) method, assisted by a clinical decision support system (STRIP Assistant, STRIPA) with integrated STOPP/START criteria (version 2), followed by shared decision-making with both patient and attending physician. The developed method integrates patient input, patient data, involvement from other healthcare professionals and CDSS-assistance into one structured intervention. DISCUSSION: The clinical and economical effectiveness of this experimental intervention will be evaluated in a cohort of hospitalised, older patients with multi-morbidity and polypharmacy in the multicentre, randomized controlled OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multi-morbid elderly), which will be completed in the last quarter of 2019. TRIAL REGISTRATION: Universal Trial Number: U1111-1181-9400 Clinicaltrials.gov: NCT02986425, Registered 08 December 2016. FOPH (Swiss national portal): SNCTP000002183. Netherlands Trial Register: NTR6012 (07-10-2016).

The effect of providing prescribing recommendations on appropriate prescribing: A cluster-randomized controlled trial in older adults in a preoperative setting.

AIMS: The Systematic Tool to Reduce Inappropriate Prescribing is a method to assess patient's medication and has been incorporated into a clinical decision support system: STRIP Assistant. Our aim was to evaluate the effect of recommendations generated using STRIP Assistant on appropriate prescribing and mortality in a preoperative setting. METHODS: This cluster-randomized controlled trial was carried out at the preoperative geriatric outpatient clinic. Residents who performed a comprehensive geriatric assessment were randomized to the control group and intervention group in a 1:1 ratio. Visiting patients aged 70 years or older on 5 or more medications were included. INTERVENTION: prescribing recommendations were generated by a physician using STRIP Assistant and given to the resident. Control group residents performed a medication review according to usual care. PRIMARY OUTCOME: number of medication changes made because of potential prescribing omissions (PPOs), potentially inappropriate medications (PIMs), and suboptimal dosages according to the prescribing recommendations. Secondary outcome: 3-month postoperative mortality. RESULTS: 65 intervention and 59 control patients were included, attended by 34 residents. Significantly more medication changes because of PPOs and PIMs were made in the intervention group than in the control group (PPOs 26.2% vs 3.4%, odds ratio 0.04 [95% confidence interval 0.003-0.46] P < .05; PIMS 46.2% vs 15.3% odds ratio 0.14 [95% confidence interval 0.07-0.57] P < .005). There were no differences in dose adjustments or in postoperative mortality. CONCLUSION: Prescribing recommendations generated with the help of STRIP Assistant improved appropriate prescribing in a preoperative geriatric outpatient clinic but did not affect postoperative mortality.

International core outcome set for clinical trials of medication review in multi-morbid older patients with polypharmacy.

BACKGROUND: Comparisons of clinical trial findings in systematic reviews can be hindered by the heterogeneity of the outcomes reported. Moreover, the outcomes that matter most to patients might be underreported. A core outcome set can address these issues, as it defines a minimum set of outcomes that should be reported in all clinical trials in a particular area of research. The objective in this study was to develop a core outcome set for clinical trials of medication review in multi-morbid older patients with polypharmacy. METHODS: Firstly, eligible outcomes were identified through a systematic review of trials of medication review in older patients (≥65 years) and interviews with 15 older patients. Secondly, an international three-round Delphi survey in four countries involving patients, healthcare professionals, and experts was conducted to validate outcomes to be included in the core outcome set. Consensus meetings were conducted to validate the results. RESULTS: Of the 164 participants invited to take part in the Delphi survey, 150 completed Round 1, including 55 patients or family caregivers, 55 healthcare professionals, and 40 experts. A total of 129 participants completed all three rounds. Sixty-four eligible outcomes were extracted from 47 articles, 32 clinical trial protocols, and patient interviews. Thirty outcomes were removed and one added after Round 1, 18 outcomes were removed after Round 2, and seven after Round 3. Results were discussed during consensus meetings. Consensus was reached on seven outcomes, which constitute the core outcome set: drug-related hospital admissions; drug overuse; drug underuse; potentially inappropriate medications; clinically significant drug-drug interactions; health-related quality of life; pain relief. CONCLUSIONS: We developed a core outcome set of seven outcomes which should be used in future trials of medication review in multi-morbid older patients with polypharmacy.

Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients.

OBJECTIVES: To investigate whether diabetes and glucose dysregulation (hyperglycemia and/or hypoglycemia) are associated with ICU delirium. DESIGN: Prospective cohort study. SETTING: Thirty-two-bed mixed intensive care in a tertiary care center. PATIENTS: Critically ill patients admitted to the ICU with transitions of mental status from awake and nondelirious to delirious or remaining awake and nondelirious on the next day. Patients admitted because of a neurologic illness were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study population consisted of 2,745 patients with 1,720 transitions from awake and nondelirious to delirious and 11,421 nontransitions remaining awake and nondelirious. Generalized mixed effects models with logit link function were performed to study the association between diabetes mellitus, glucose dysregulation, and delirium, adjusting for potential confounders. Diabetes was not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73-1.18). In all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI, 1.15-1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.65; 95% CI, 1.12-2.28) compared with normoglycemia were associated with transition to delirium. Hypoglycemia was not associated with transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73-3.71). In patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted, 1.41; 95% CI, 1.16-1.68) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07-2.89) were associated with transition to delirium. In patients with diabetes, glucose dysregulation was not associated with ICU delirium. CONCLUSIONS: Diabetes mellitus was not associated with the development of ICU delirium. For hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted. Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same day were associated with ICU delirium but only in patients without diabetes. Our study supports the institution of measures to prevent glucose dysregulation in nondiabetic ICU patients and contributes to the understanding of the determinants of delirium.

Prophylactic Use of Haloperidol and Changes in Glucose Levels in Hospitalized Older Patients.

BACKGROUND: Treatment with antipsychotic drugs has been associated with glucose dysregulation in older outpatients, especially in the early stage of therapy. The underlying mechanism is, however, unclear. The aim of this study was to investigate changes in glucose levels during haloperidol use compared with the use of placebo among older hospitalized patients. METHODS: This substudy was part of a larger multicenter, randomized, double blind, placebo-controlled clinical trial among hospitalized patients aged 70 years and older who had an increased risk of in-hospital delirium. Patients who were admitted to the Jeroen Bosch Hospital in 's-Hertogenbosch between June 2014 and February 2015 were invited to participate in the study. Participating patients were randomized for treatment and given 1 mg of haloperidol or a placebo twice daily for a maximum of 7 consecutive days (14 doses). Exclusion criteria for this substudy were the use of corticosteroids and changes in diabetes medication. Random blood samples to determine glucose levels were collected before day 1 and on day 6 of the study. Student independent sample t test was used to determine differences in glucose changes between both groups. RESULTS: Twenty-nine patients were included (haloperidol, n = 14; placebo, n = 15). The mean glucose level for placebo users was 139.3 mg/dL (SD, 50.1) on day 1 and 140.8 mg/dL (SD, 45.7) on day 6, and the mean glucose level for haloperidol users was 139.9 mg/dL (SD, 71.0) on day 1 and 150.2 mg/dL (SD, 39.1) on day 6. The difference was not statistically significant (P = 0.685). CONCLUSIONS: Short-term prophylactic use of haloperidol was not associated with changes in glucose levels in older hospitalized patients compared with those given a placebo in this small study.

Identification of behaviour change techniques in deprescribing interventions: a systematic review and meta-analysis.

AIMS: Deprescribing interventions safely and effectively optimize medication use in older people. However, questions remain about which components of interventions are key to effectively reduce inappropriate medication use. This systematic review examines the behaviour change techniques (BCTs) of deprescribing interventions and summarizes intervention effectiveness on medication use and inappropriate prescribing. METHODS: MEDLINE, EMBASE, Web of Science and Academic Search Complete and grey literature were searched for relevant literature. Randomized controlled trials (RCTs) were included if they reported on interventions in people aged ≥65 years. The BCT taxonomy was used to identify BCTs frequently observed in deprescribing interventions. Effectiveness of interventions on inappropriate medication use was summarized in meta-analyses. Medication appropriateness was assessed in accordance with STOPP criteria, Beers' criteria and national or local guidelines. Between-study heterogeneity was evaluated by I-squared and Chi-squared statistics. Risk of bias was assessed using the Cochrane Collaboration Tool for randomized controlled studies. RESULTS: Of the 1561 records identified, 25 studies were included in the review. Deprescribing interventions were effective in reducing number of drugs and inappropriate prescribing, but a large heterogeneity in effects was observed. BCT clusters including goals and planning; social support; shaping knowledge; natural consequences; comparison of behaviour; comparison of outcomes; regulation; antecedents; and identity had a positive effect on the effectiveness of interventions. CONCLUSIONS: In general, deprescribing interventions effectively reduce medication use and inappropriate prescribing in older people. Successful deprescribing is facilitated by the combination of BCTs involving a range of intervention components.