Development and external validation of a prognostic model for time to readmission or death in multimorbid patients.

OBJECTIVE: To develop and externally validate a prognostic model built on important factors predisposing multimorbid patients to all-cause readmission and/or death. In addition to identify patients who may benefit most from a comprehensive clinical pharmacist intervention. METHODS: A multivariable prognostic model was developed based on data from a randomised controlled trial investigating the effect of pharmacist-led medicines management on readmission rate in multimorbid, hospitalised patients. The derivation set comprised 386 patients randomised in a 1:1 manner to the intervention group, i.e. with a pharmacist included in their multidisciplinary treatment team, or the control group receiving standard care at the ward. External validation of the model was performed using data from an independent cohort, in which 100 patients were randomised to the same intervention, or standard care. The setting was an internal medicines ward at a university hospital in Norway. RESULTS: The number of patients who were readmitted or had died within 18 months after discharge was 297 (76.9 %) in the derivation set, i.e. the randomized controlled trial, and 69 (71.1 %) in the validation set, i.e. the independent cohort. Charlson comorbidity index (CCI; low, moderate or high), previous hospital admissions within the previous six months and heart failure were the strongest prognostic factors and were included in the final model. The efficacy of the pharmaceutical intervention did not prove significant in the model. A prognostic index (PI) was constructed to estimate the hazard of readmission or death (low, intermediate or high-risk groups). Overall, the external validation replicated the result. We were unable to identify a subgroup of the multimorbid patients with better efficacy of the intervention. CONCLUSIONS: A prognostic model including CCI, previous admissions and heart failure can be used to obtain valid estimates of risk of readmission and death in patients with multimorbidity.

Effect of integrated medicines management on the quality of drug treatment in hospitalised multimorbid patients - a secondary endpoint analysis of a randomised controlled trial.

OBJECTIVES: To investigate the effect of integrated medicines management provided to hospitalised multimorbid patients on the quality of drug treatment at discharge measured as the mean number of potential prescribing omissions and potentially inappropriate medicines. METHODS: Multimorbid patients ≥18 years, using a minimum of four regular drugs from a minimum of two therapeutic drug classes, were recruited from the Internal Medicine ward, Oslo University Hospital, Norway, from August 2014 to March 2016 and randomly assigned, 1:1, to the intervention or control group. Intervention patients received integrated medicines management throughout the hospital stay. Control patients received standard care. This paper reports the results of a pre-specified secondary endpoint analysis of a randomised controlled trial; the difference between the intervention and control group at discharge in the mean number of potential prescribing omissions and potentially inappropriate medicines, measured with START-2 and STOPP-2 criteria, respectively. The difference between the groups was calculated using rank analysis. KEY FINDINGS: In total, 386 patients were analysed. Integrated medicines management reduced the mean number of potential prescribing omissions at discharge, compared to the control group, 1.34 versus 1.57, respectively (mean difference 0.23, 95% CI 0.07-0.38, P = 0.005, adjusted for values at admission). There was no difference in the mean number of potentially inappropriate medicines at discharge (1.84 versus 1.88, respectively; mean difference 0.03, 95% CI -0.18 to 0.25, P = 0.762, adjusted for values at admission). CONCLUSIONS: Integrated medicines management delivered to multimorbid patients during a hospital stay led to an improvement in undertreatment. No effect on deprescribing of inappropriate treatment was seen.

On the Ethics of Withholding and Withdrawing Unwarranted Diagnoses.

The number of diagnoses and the number of persons having diagnoses have increased substantially, and studies indicate that diagnoses are given or upheld even if they are unwarranted, that is, that they do not satisfy professionally accepted diagnostic criteria. In this article, the authors investigate the ethics of withholding and withdrawing unwarranted diagnoses. First, they investigate ethical aspects that make it difficult to withhold and to withdraw such diagnoses. Second, they scrutinize whether there are psychological factors, both in persons/patients and healthcare professionals, making it difficult to withdraw and withhold unwarranted diagnoses. Lastly, they use recent elements of the withholding-versus-withdrawing treatment debate in medical ethics to investigate whether there are any differences between withholding and withdrawing treatment and withdrawing and withholding unwarranted diagnoses. The authors conclude that it is crucial to acknowledge and address all these issues to reduce and avoid unwarranted diagnoses.

Effect of pharmacist-led inhaler technique assessment service on readmissions in hospitalized COPD patients: a randomized, controlled pilot study.

OBJECTIVE: To investigate the effect of pharmacist-led inhaler technique assessment service on readmissions and CAT-score in hospitalized COPD patients. Furthermore, to provide an effect estimate for sample size calculations for future studies and to gain experience on the feasibility of such studies. METHODS: A randomized controlled pilot study. Patients were randomized 1:1 to intervention or standard care. The primary endpoint was the difference in time to first readmission after hospital discharge between the treatment groups. RESULTS: There was no statistically significant effect on the time to readmission (median 41 days in the intervention group (19 patients) and 95 days in the control group (20 patients), HR 1.74, 95% CI 0.81-3.75, p = 0.16). There was no statistically significant difference between the groups in CAT-score 2 months after discharge, median scores being 25.5 and 24 in the intervention and the control group, respectively (p = 0.29). There was, however, a reduction of 3.5 units in CAT-score from baseline to 2 months after discharge in the intervention group, compared to no change in the control group. CONCLUSION: Pharmacist-led inhaler technique training had no effect on time to readmission or CAT-score. Future studies in larger populations should consider focusing on patients with less severe COPD, exploring CAT-score as a primary endpoint, consider stratifying for important baseline variables and evaluate the acceptability of the intervention. TRIAL REGISTRATION: Date of registration 01/10/2018. CLINICALTRIALS: gov identifier: NCT03691324.

Dediagnosing - a novel framework for making people less ill.

Diagnosing constitutes a substantial part of healthcare work and triggers a wide range of actions including the prescription of medicines. Dediagnosing is proposed as a novel framework for removing diagnoses that do not contribute to the reduction of persons' suffering and should be introduced to make people less ill. Dediagnosing comes together with other efforts to reduce overuse, such as deimplementation, deprescribing, decommissioning, and disinvestment. Because diagnoses may influence identity construction and social rights, dediagnosing must be conducted in close collaboration with the patient.

Effect of medicines management versus standard care on readmissions in multimorbid patients: a randomised controlled trial.

OBJECTIVE: To investigate the effect of pharmacist-led medicines management in multimorbid, hospitalised patients on long-term hospital readmissions and survival. DESIGN: Parallel-group, randomised controlled trial. SETTING: Recruitment from an internal medicine hospital ward in Oslo, Norway. Patients were enrolled consecutively from August 2014 to the predetermined target number of 400 patients. The last participant was enrolled March 2016. Follow-up until 31 December 2017, that is, 21-40 months. PARTICIPANTS: Acutely admitted multimorbid patients ≥18 years, using minimum four regular drugs from minimum two therapeutic classes. 399 patients were randomly assigned, 1:1, to the intervention or control group. After excluding 11 patients dying in-hospital and 2 erroneously included, the primary analysis comprised 386 patients (193 in each group) with median age 79 years (range 23-96) and number of diseases 7 (range 2-17). INTERVENTION: Intervention patients received pharmacist-led medicines management comprising medicines reconciliation at admission, repeated medicines reviews throughout the stay and medicines reconciliation and tailored information at discharge, according to the integrated medicines management model. Control patients received standard care. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was difference in time to readmission or death within 12 months. Overall survival was a priori the clinically most important secondary endpoint. RESULTS: Pharmacist-led medicines management had no significant effect on the primary endpoint time to readmission or death within 12 months (median 116 vs 184 days, HR 0.82, 95% CI 0.64 to 1.04, p=0.106). A statistically significantly increased overall survival was observed during 21-40 months follow-up (HR 0.66, 95% CI 0.48 to 0.90, p=0.008). CONCLUSIONS: Pharmacist-led medicines management had no statistically significant effect on time until readmission or death. A statistically significant increased overall survival was seen. Further studies should be conducted to investigate the effect of such an intervention on a larger scale. TRIAL REGISTRATION NUMBER: NCT02336113.

Prevalence and risk factors of drug-related hospitalizations in multimorbid patients admitted to an internal medicine ward.

BACKGROUND: Knowledge of risk factors for drug-related hospitalizations (DRHs) is limited. AIM: To examine the prevalence of DRHs and the relationships between DRHs and various variables in multimorbid patients admitted to an internal medicine ward. METHODS: Multimorbid patients ≥ 18 years, using minimum of four regular drugs from minimum two therapeutic classes, were included from the Internal Medicine ward, Oslo University Hospital, Norway, from August 2014 to March 2016. Clinical pharmacists prospectively conducted medicines reconciliations and reviews to reveal drug-related problems (DRPs). Blinded for identified DRPs, an interdisciplinary group retrospectively made comprehensive, clinical assessments of each patient case to classify hospitalizations as drug-related (DRH) or non-drug-related (non-DRH). Age, sex distribution, Charlson Comorbidity Index (CCI), renal function, aberrant genotype frequencies, body-mass index, number of drugs, proportion of patients which received assistance for drug administration from the home care service, and/or through multidose-dispensed drugs, and occurrence of specific DRP subgroups, were compared separately between patients with DRHs versus non-DRHs, followed by multiple logistic regression analysis. RESULTS: Hospitalizations were classified as drug-related in 155 of the 404 included patients (38%). Factors significantly associated with DRHs were occurrence of adverse effect DRPs (adjusted odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4-8.0), adherence issues (OR 2.9, 1.1-7.2), home care (OR 1.9, 1.1-3.5), drug monitoring DRPs (OR 1.9, 1.2-3.0), and CCI score ≥6 (OR 0.33, 0.14-0.77). Frequencies of aberrant genotypes did not differ between the patient groups, but in 41 patients with DRHs (26.5%), gene-drug interactions influenced the assessments of DRHs. CONCLUSION: DRHs are prevalent in multimorbid patients with adverse effect DRPs and adherence issues as the most important risk factors.

Effect of teaching and checklist implementation on accuracy of medication history recording at hospital admission.

BACKGROUND: Medication discrepancies at hospital admission is an extensive problem and knowledge is limited regarding improvement strategies. OBJECTIVE: To investigate the effect of teaching and checklist implementation on accuracy of medication history recording during hospitalization. METHOD: Patients admitted to an internal medicine ward were prospectively included in two consecutive periods. Between the periods, non-mandatory teaching lessons were provided and a checklist assisting medication history recording implemented. Discrepancies between the recorded medications at admission and the patient's actual drug use, as revealed by pharmacist-conducted medication reconciliation, were compared between the periods. The primary endpoint was difference between the periods in proportion of patients with minimum one discrepancy. Difference in median number of discrepancies was included as a secondary endpoint. RESULTS: 56 and 119 patients were included in period 1 (P1) and period 2 (P2), respectively. There was no significant difference in proportion of patients with minimum one discrepancy in P2 (68.9 %) versus P1 (76.8 %, p = 0.36), but a tendency of lower median number of discrepancies was observed in P2 than P1, i.e. 1 and 2, respectively (p = 0.087). CONCLUSION: More powerful strategies than non-mandatory teaching activities and checklist implementation are required to achieve sufficient improvements in medication history recording during hospitalization.

Severity and management of drug-drug interactions in acute geriatric patients.

BACKGROUND: Previous studies have investigated the prevalence of drug-drug interactions (DDIs) among the elderly in different care settings, but data describing the frequency and management of DDIs among acute geriatric patients appear to be absent. OBJECTIVE: The aim of this study was to investigate the severity and interdisciplinary management of DDIs in patients admitted to an acute geriatric ward. METHODS: The study was conducted at Oslo University Hospital, Norway, over a period of 19 weeks in 2010/11. On admission and daily during the hospital stay, prescribed medications were reviewed by pharmacists to identify DDIs with the aid of web-based databases. DDIs defined to be of potential clinical relevance, i.e., those classified as "major" (generally avoid) or "moderate" (precautions recommended), were following assessments by pharmacists presented at interdisciplinary meetings with geriatricians and nurses, and discussed in relation to the possible implementation of monitoring actions or changes in prescribing. The odds for prescribing changes were compared in relation to DDI type ("pharmacokinetic" vs. "pharmacodynamic") and severity ("major" vs. "moderate"). The project group retrospectively assessed the possible causal relationships between hospitalizations and DDIs. RESULTS: The pharmacists identified 245 DDIs of major (n = 13) or moderate (n = 232) severity in 80 (63.5 %) of the 126 patients included on admission and/or during hospitalization. In 94 of 162 cases where the pharmacists alerted the geriatricians (58.0 %), prescribing changes or monitoring actions were implemented. Prescribing changes (n = 38) were performed significantly more often for major than for moderate DDIs [odds ratio (OR) 3.8; 95 % confidence interval (CI) 1.2-12.2, p = 0.03], and significantly more often for pharmacokinetic than for pharmacodynamic DDIs (OR 4.9; 95 % CI 2.2-10.9, p < 0.01). For 28 of 126 patients (22.2 %), a causal relationship between hospitalizations and DDIs was assessed as "possible". CONCLUSIONS: The present study shows that acute geriatric patients are frequently exposed to DDIs for which active management is recommended in order to avoid unfavorable clinical outcomes. The integration of pharmacists into interdisciplinary teams could prevent potentially severe DDIs in the elderly.