Prescribing, deprescribing and potential adverse effects of proton pump inhibitors in older patients with multimorbidity: an observational study.

BACKGROUND: Proton pump inhibitors (PPIs) contribute to polypharmacy and are associated with adverse effects. As prospective data on longitudinal patterns of PPI prescribing in older patients with multimorbidity are lacking, we sought to assess patterns of PPI prescribing and deprescribing, as well as the association of PPI use with hospital admissions over 1 year in this population. METHODS: We conducted a prospective, longitudinal cohort study using data from the Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM) trial, a randomized controlled trial testing an intervention to reduce inappropriate prescribing (2016-2018). This trial included adults aged 70 years and older with at least 3 chronic conditions and prescribed at least 5 chronic medications. We assessed prevalence of PPI use at time of hospital admission, and new prescriptions and deprescribing at discharge, and at 2 months and 1 year after discharge, by intervention group. We used a regression with competing risk for death to assess the association of PPI use with readmissions related to their potential adverse effects, and all-cause readmission. RESULTS: Overall, 1080 (57.4%) of 1879 patients (mean age 79 yr) had PPI prescriptions at admission, including 496 (45.9%) patients with a potentially inappropriate indication. At discharge, 133 (24.9%) of 534 patients in the intervention group and 92 (16.8%) of 546 patients in the control group who were using PPIs at admission had deprescribing. Among 680 patients who were not using PPIs at discharge, 47 (14.6%) of 321 patients in the intervention group and 40 (11.1%) of 359 patients in the control group had a PPI started within 2 months. Use of PPIs was associated with all-cause readmission (n = 770, subdistribution hazard ratio 1.31, 95% confidence interval 1.12-1.53). INTERPRETATION: Potentially inappropriate use of PPI, new PPI prescriptions and PPI deprescribing were frequent among older adults with multimorbidity and polypharmacy. These data suggest that persistent PPI use may be associated with clinically important adverse effects in this population.

Development and validation of a new prognostic index for mortality risk in multimorbid adults.

CONTEXT: Multimorbidity is highly prevalent among older adults and associated with a high mortality. Prediction of mortality in multimorbid people would be clinically useful but there is no mortality risk index designed for this population. Our objective was therefore to develop and internally validate a 1-year mortality prognostic index for older multimorbid adults. METHODS: We analysed data of the OPERAM cohort study in Bern, Switzerland, including 822 adults aged 70 years or more with multimorbidity (3 or more chronic medical conditions) and polypharmacy (use of 5 drugs or more for >30 days). Time to all-cause mortality was assessed up to 1 year of follow-up. We performed a parametric Weibull regression model with backward stepwise selection to identify mortality risk predictors. The model was internally validated and optimism corrected using bootstrapping techniques. We derived a point-based risk score from the regression coefficients. Calibration and discrimination were assessed by the calibration slope and C statistic. RESULTS: 805 participants were included in the analysis. During 1-year of follow-up, 158 participants (20%) had died. Age, Charlson-Comorbidity-Index, number of drugs, body mass index, number of hospitalizations, Barthel-Index (functional impairment), and nursing home residency were predictors of 1-year mortality in a multivariable model. Using these variables, the 1-year probability of dying could be predicted with an optimism-corrected C statistic of 0.70. The optimism-corrected calibration slope was 0.93. Based on the derived point-based risk score to predict mortality risk, 7% of the patients classified at low-risk of mortality, 19% at moderate-risk, and 37% at high-risk died after one year of follow-up. A simpler mortality score, without the Charlson-Comorbidity-Index and Barthel-Index, showed reduced discriminative power (optimism-corrected C statistic: 0.59) compared to the full score. CONCLUSION: We developed and internally validated a mortality risk index including for the first-time specific predictors for multimorbid adults. This new 1-year mortality prediction point-based score allowed to classify multimorbid older patients into three categories of increasing risk of mortality. Further validation of the score among various populations of multimorbid patients is needed before its implementation into practice.

Comparison of 6 Mortality Risk Scores for Prediction of 1-Year Mortality Risk in Older Adults With Multimorbidity.

Importance: The most appropriate therapy for older adults with multimorbidity may depend on life expectancy (ie, mortality risk), and several scores have been developed to predict 1-year mortality risk. However, often, these mortality risk scores have not been externally validated in large sample sizes, and a head-to-head comparison in a prospective contemporary cohort is lacking. Objective: To prospectively compare the performance of 6 scores in predicting the 1-year mortality risk in hospitalized older adults with multimorbidity. Design, Setting, and Participants: This prognostic study analyzed data of participants in the OPERAM (Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People) trial, which was conducted between December 1, 2016, and October 31, 2018, in surgical and nonsurgical departments of 4 university-based hospitals in Louvain, Belgium; Utrecht, the Netherlands; Cork, Republic of Ireland; and Bern, Switzerland. Eligible participants in the OPERAM trial had multimorbidity (≥3 coexisting chronic diseases), were aged 70 years or older, had polypharmacy (≥5 long-term medications), and were admitted to a participating ward. Data were analyzed from April 1 to September 30, 2020. Main Outcomes and Measures: The outcome of interest was any-cause death occurring in the first year of inclusion in the OPERAM trial. Overall performance, discrimination, and calibration of the following 6 scores were assessed: Burden of Illness Score for Elderly Persons, CARING (Cancer, Admissions ≥2, Residence in a nursing home, Intensive care unit admit with multiorgan failure, ≥2 Noncancer hospice guidelines) Criteria, Charlson Comorbidity Index, Gagné Index, Levine Index, and Walter Index. These scores were assessed using the following measures: Brier score (0 indicates perfect overall performance and 0.25 indicates a noninformative model); C-statistic and 95% CI; Hosmer-Lemeshow goodness-of-fit test and calibration plots; and sensitivity, specificity, and positive and negative predictive values. Results: The 1879 patients in the study had a median (IQR) age of 79 (74-84) years and 835 were women (44.4%). The median (IQR) number of chronic diseases was 11 (8-16). Within 1 year, 375 participants (20.0%) died. Brier scores ranged from 0.16 (Gagné Index) to 0.24 (Burden of Illness Score for Elderly Persons). C-statistic values ranged from 0.62 (95% CI, 0.59-0.65) for Charlson Comorbidity Index to 0.69 (95% CI, 0.66-0.72) for the Walter Index. Calibration was good for the Gagné Index and moderate for other mortality risk scores. Conclusions and Relevance: Results of this prognostic study suggest that all 6 of the 1-year mortality risk scores examined had moderate prognostic performance, discriminatory power, and calibration in a large cohort of hospitalized older adults with multimorbidity. Overall, none of these mortality risk scores outperformed the others, and thus none could be recommended for use in daily clinical practice.

Pharmacist interventions to improve hypertension management: protocol for a systematic review of randomised controlled trials.

INTRODUCTION: Hypertension management remains a major public health challenge in primary care. Innovative interventions to improve blood pressure (BP) control are needed. One approach is through community-based models of care with the involvement of pharmacists and other non-physician healthcare professionals. Our objective is to systematically review the evidence of the impact of pharmacist care alone or in collaboration with other healthcare professionals on BP among hypertensive outpatients compared with usual care. Because these interventions can be complex, with various components, the effect size may differ between the type of interventions. One major focus of our study will be to assess carefully the heterogeneity in the effects of these interventions to identify which ones work best in a given healthcare setting. METHODS AND ANALYSIS: Systematic searches of the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica (Embase) and Central Register of Controlled Trials (CENTRAL) databases will be conducted. Randomised controlled trials assessing the effect of pharmacist interventions on BP among outpatients will be included. Examples for pharmacist interventions are patient education, feedback to physician and medication management. The outcome will be the change in BP or BP at follow-up or BP control. Results will be synthesised descriptively and, if appropriate, will be pooled across studies to perform meta-analyses. If feasible, we will also perform a network meta-analysis to compare interventions that have not been compared directly head-to-head by using indirect evidence. Heterogeneity in the effect will be evaluated through prespecified subgroup and stratified analyses, accounting notably for the type and intensity of interventions, patients' characteristics and healthcare setting. ETHICS AND DISSEMINATION: Ethical approval is not required as the results will be drawn from currently available published literature. Outcomes of the review will be shared through peer-reviewed journal and used for implementation policy. PROSPERO REGISTRATION NUMBER: CRD42021279751.

Development and validation of a life expectancy estimator for multimorbid older adults: a cohort study protocol.

BACKGROUND: Older multimorbid adults have a high risk of mortality and a short life expectancy (LE). Providing high-value care and avoiding care overuse, including of preventive care, is a serious challenge among multimorbid patients. While guidelines recommend to tailor preventive care according to the estimated LE, there is no tool to estimate LE in this specific population. Our objective is therefore to develop an LE estimator for older multimorbid adults by transforming a mortality prognostic index, which will be developed and internally validated in a prospective cohort. METHODS AND ANALYSIS: We will analyse data of the Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People cohort study in Bern, Switzerland. 822 participants were included at hospitalisation with age of 70 years or older, multimorbidity (three or more chronic medical conditions) and polypharmacy (use of five drugs or more for >30 days). All-cause mortality will be assessed during 3 years of follow-up. We will apply a flexible parametric survival model with backward stepwise selection to identify the mortality risk predictors. The model will be internally validated using bootstrapping techniques. We will derive a point-based risk score from the regression coefficients. We will transform the 3-year mortality prognostic index into an LE estimator using the Gompertz survival function. We will perform a qualitative assessment of the clinical usability of the LE estimator and its application. We will conduct the development and validation of the mortality prognostic index following the Prognosis Research Strategy (PROGRESS) framework and report it following the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) statement. ETHICS AND DISSEMINATION: Written informed consent by patients themselves or, in the case of cognitive impairment, by a legal representative, was required before enrolment. The local ethics committee (Kantonale Ethikkommission Bern) has approved the study. We plan to publish the results in peer-reviewed journals and present them at national and international conferences.