Psychometric Properties of a Machine Learning-Based Patient-Reported Outcome Measure on Medication Adherence: Single-Center, Cross-Sectional, Observational Study.

BACKGROUND: Medication adherence plays a critical role in controlling the evolution of chronic disease, as low medication adherence may lead to worse health outcomes, higher mortality, and morbidity. Assessment of their patients' medication adherence by clinicians is essential for avoiding inappropriate therapeutic intensification, associated health care expenditures, and the inappropriate inclusion of patients in time- and resource-consuming educational interventions. In both research and clinical practices the most extensively used measures of medication adherence are patient-reported outcome measures (PROMs), because of their ability to capture subjective dimensions of nonadherence. Machine learning (ML), a subfield of artificial intelligence, uses computer algorithms that automatically improve through experience. In this context, ML tools could efficiently model the complexity of and interactions between multiple patient behaviors that lead to medication adherence. OBJECTIVE: This study aimed to create and validate a PROM on medication adherence interpreted using an ML approach. METHODS: This cross-sectional, single-center, observational study was carried out a French teaching hospital between 2021 and 2022. Eligible patients must have had at least 1 long-term treatment, medication adherence evaluation other than a questionnaire, the ability to read or understand French, an age older than 18 years, and provided their nonopposition. Included adults responded to an initial version of the PROM composed of 11 items, each item being presented using a 4-point Likert scale. The initial set of items was obtained using a Delphi consensus process. Patients were classified as poorly, moderately, or highly adherent based on the results of a medication adherence assessment standard used in the daily practice of each outpatient unit. An ML-derived decision tree was built by combining the medication adherence status and PROM responses. Sensitivity, specificity, positive and negative predictive values (NPVs), and global accuracy of the final 5-item PROM were evaluated. RESULTS: We created an initial 11-item PROM with a 4-point Likert scale using the Delphi process. After item reduction, a decision tree derived from 218 patients including data obtained from the final 5-item PROM allowed patient classification into poorly, moderately, or highly adherent based on item responses. The psychometric properties were 78% (95% CI 40%-96%) sensitivity, 71% (95% CI 53%-85%) specificity, 41% (95% CI 19%-67%) positive predictive values, 93% (95% CI 74%-99%) NPV, and 70% (95% CI 55%-83%) accuracy. CONCLUSIONS: We developed a medication adherence tool based on ML with an excellent NPV. This could allow prioritization processes to avoid referring highly adherent patients to time- and resource-consuming interventions. The decision tree can be easily implemented in computerized prescriber order-entry systems and digital tools in smartphones. External validation of this tool in a study including a larger number of patients with diseases associated with low medication adherence is required to confirm its use in analyzing and assessing the complexity of medication adherence.

Pharmaceutical consultation to detect drug interactions in patients treated with oral chemotherapies: A descriptive cross-sectional study.

OBJECTIVE: The development of oral chemotherapy (OC) has led to the recent establishment of multidisciplinary programmes involving pharmacists. We evaluated the utility of our local programme for detecting potential interactions with OCs, particularly drug-drug interactions (DDIs) and herbal-drug interactions (HDIs). METHODS: We performed a single-centre retrospective descriptive study of patients on OC attending a pharmaceutical consultation (PC) during a seven-month period. These consultations included the use of various complementary tools/databases to search for interactions. RESULTS: We analysed 308 treatments taken by 42 consecutive patients. Fifty-four potential interactions with OCs were detected in 26% (n = 79) of the treatments taken by patients: 46 DDIs (32 minor, 12 major, 2 contraindicated) and eight HDIs. Five interventions associated with interactions were suggested by pharmacists during the consultations (4 were taken into account by oncologists). The total mean time spent on each PC for an individual patient was 80 minutes (36 minutes of preparation, 44 minutes with the patient). CONCLUSION: This pilot study highlights the importance of studying interactions in such patients, and of the expertise of pharmacists for detecting interactions, which were found in more than one in four treatment lines. The further development of such activities, which already take up considerable amounts of time, is therefore warranted.

Effectiveness of a 'do not interrupt' vest intervention to reduce medication errors during medication administration: a multicenter cluster randomized controlled trial.

BACKGROUND: The use of a 'do not interrupt' vest during medication administration rounds is recommended but there have been no controlled randomized studies to evaluate its impact on reducing administration errors. We aimed to evaluate the impact of wearing such a vest on reducing such errors. The secondary objectives were to evaluate the types and potential clinical impact of errors, the association between errors and several risk factors (such as interruptions), and nurses' experiences. METHODS: This was a multicenter, cluster, controlled, randomized study (March-July 2017) in 29 adult units (4 hospitals). Data were collected by direct observation by trained observers. All nurses from selected units were informed. A 'Do not interrupt' vest was implemented in all units of the experimental group. A poster was placed at the entrance of these units to inform patients and relatives. The main outcome was the administration error rate (number of Opportunities for Error (OE), calculated as one or more errors divided by the Total Opportunities for Error (TOE) and multiplied by 100). RESULTS: We enrolled 178 nurses and 1346 patients during 383 medication rounds in 14 units in the experimental group and 15 units in the control group. During the intervention period, the administration error rates were 7.09% (188 OE with at least one error/2653 TOE) for the experimental group and 6.23% (210 OE with at least one error/3373 TOE) for the control group (p = 0.192). Identified risk factors (patient age, nurses' experience, nurses' workload, unit exposition, and interruption) were not associated with the error rate. The main error type observed for both groups was wrong dosage-form. Most errors had no clinical impact for the patient and the interruption rates were 15.04% for the experimental group and 20.75% for the control group. CONCLUSIONS: The intervention vest had no impact on medication administration error or interruption rates. Further studies need to be performed taking into consideration the limitations of our study and other risk factors associated with other interventions, such as nurse's training and/or a barcode system. TRIAL REGISTRATION: The PERMIS study protocol (V2-1, 11/04/2017) was approved by institutional review boards and ethics committees (CPP Ile de France number 2016-A00211-50, CNIL 21/03/2017, CCTIRS 11/04/2016). It is registered at ClinicalTrials.gov (registration number: NCT03062852 , date of first registration: 23/02/2017).

Conditional prescriptions of oral antihypertensive drugs for the management of hypertension urgencies in the inpatient setting: An observational study.

WHAT IS KNOWN AND OBJECTIVES: The management of hypertension urgencies during hospitalization may generally not necessitate urgent care. However, physicians frequently prescribe 'as needed' antihypertensive drugs for which administration is triggered by blood pressure thresholds. The lack of rationale for this hospital practice led us to study oral conditional antihypertensive (OCA) prescriptions. We aimed to estimate the prevalence of OCA prescriptions and to establish their characteristics. METHODS: In our institution, prescriptions are computerized. The study was retrospectively performed using a hospital clinical data warehouse over a 5-year period. RESULTS AND DISCUSSION: The prevalence of OCA prescriptions was 6.9% among subjects treated with an antihypertensive drug. The median duration of these prescriptions was 4 days, until the day of the patient discharge in 78.8% stays. The calcium channel inhibitors were the main (79.9%) pharmacological class prescribed, with mostly prescriptions of nicardipine. OCA prescriptions were associated with another antihypertensive medication in 58.8% of the prescriptions; for 19.3%, it was a medication belonging to the same pharmacological class than the OCA drug prescribed. Regarding the computerized drafting, 39.6% of the conditional prescriptions were considered uninterpretable. At least one administration by nurses concerned 65.1% of the OCA prescriptions. The mean SBP and DBP before the initiation of an OCA drug was 142.9 ± 28.2 and 75.8 ± 24.5 mm Hg, respectively, relative to 143.0 ± 24.9 and 77.6 ± 19.9 mm Hg after the initiation (P = .8 for SBP and P = .06 for DBP). WHAT IS NEW AND CONCLUSION: The originality of this study lies in the use of a clinical data warehouse to evaluate OCA prescriptions in hospital. These prescriptions are current, often uninterpretable and mostly ordered until patient discharge. Such drug orders could be associated with an increased risk of iatrogenic events and/or administration errors. This underlies the need for developing decision support tools and computerized protocols to manage hypertension urgencies.

Pharmaceutical interventions to improve safety of chemotherapy-treated cancer patients: A cross-sectional study.

PURPOSE: Cancer chemotherapy is a high-risk process. To improve patient safety, a systematic pharmaceutical analysis of chemotherapy prescriptions is performed in our institution. The aim of this study was to assess the impact of pharmaceutical interventions (PIs) on the safety of patient chemotherapy prescriptions. METHODS: This prospective cross-sectional study was conducted in an 800-bed university hospital with oncology departments. All chemotherapy prescriptions were included and PIs were collected prospectively during one month. The clinical impact of PIs was scored by an expert panel of oncologists and pharmacists, using the Hatoum scale. Univariate and multivariate analysis were conducted to identify factors associated with a higher frequency of PIs. RESULTS: Of 1346 prescriptions included, 129 required a PI (9.6% (95% CI: 8.1-11.4)). Most PIs were scored as having at least a significant impact for patient safety (69.8% (95% CI: 60.4-76.9)). The frequency of PIs was significantly associated with tumour site (p = 0.04) and weekday of prescription (p = 0.005). Multivariate analysis identified factors independently associated with PI performance, including pancreas and biliary tract cancers (odds ratio = 2.8 (95% CI: 1.4-5.3)), ovary cancers (odds ratio = 2.4 (95% CI: 1.2-4.8)) and head and neck cancers (odds ratio = 2.4 (95% CI: 1.1-5.1)) and the day 1 of the protocol with a cytotoxic agent (odds ratio = 3.7 (95% CI: 1.1-11.1)). CONCLUSIONS: Oncology pharmacists have a critical role in the safety of chemotherapy prescriptions. The coordination between healthcare professionals and access to patient data seem essential to improve the PIs' relevance and their clinical impact on patient safety.

Identifying homogeneous healthcare use profiles and treatment sequences by combining sequence pattern mining with care trajectory clustering in kidney cancer patients on oral anticancer drugs: A case study.

OBJECTIVE: We evaluated the ability of a coupled pattern-mining and clustering method to identify homogeneous groups of subjects in terms of healthcare resource use, prognosis and treatment sequences, in renal cancer patients beginning oral anticancer treatment. METHODS: Data were retrieved from the permanent sample of the French medico-administrative database. We applied the CP-SPAM algorithm for pattern mining to healthcare use sequences, followed by hierarchical clustering on principal components (HCPC). RESULTS AND CONCLUSION: We identified 127 individuals with renal cancer with a first reimbursement of an oral anticancer drug between 2010 and 2017. Clustering identified three groups of subjects, and discrimination between these groups was good. These clusters differed significantly in terms of mortality at six and 12 months, and medical follow-up profile (predominantly outpatient or inpatient care, biological monitoring, reimbursement of supportive care drugs). This case study highlights the potential utility of applying sequence-mining algorithms to a large range of healthcare reimbursement data, to identify groups of subjects homogeneous in terms of their care pathways and medical behaviors.

Association Between Exposure to Effervescent Paracetamol and Hospitalization for Acute Heart Failure: A Case-Crossover Study.

We investigated whether effervescent paracetamol, as an important source of nondietary sodium and fluid load, is associated with a transient increase in the risk of hospitalization for acute heart failure (AHF). We conducted a unidirectional case-crossover study using data from the 1 in 97th representative sample from the French health care database. Subjects aged ≥18 years, hospitalized for AHF during the 2014-2016 period, were included. Exposure to effervescent paracetamol was compared between a risk period (ie, 15 days immediately before admission for AHF) and 3 earlier 15-day control periods, to test a possible trigger effect of effervescent paracetamol intake on AHF. Adjusted odds ratios (aORs) were estimated with a conditional logistic regression. We identified 4301 patients hospitalized for AHF. We found that 5.7% of AHF subjects were exposed to effervescent paracetamol during the risk period, as compared with 4.1% during the control periods (aOR, 1.56 [95% confidence interval [CI], 1.27-1.90]; P < .001). This association was also found in the subgroup of subjects with hypertension (aOR, 1.45 [95%CI, 1.13-1.87]; P = .004, n = 2648) and in the subgroup of subjects aged ≥83 years (aOR, 1.70 [95%CI: 1.28-2.24], P < .001, n = 2238). A similar analysis, considering exposure to noneffervescent paracetamol, did not support the existence of an indication bias likely to explain the association observed for effervescent paracetamol. This study suggests an association between effervescent paracetamol and admission for AHF and should be confirmed with other complementary study designs.

Contribution of BKCa channels to vascular tone regulation by PDE3 and PDE4 is lost in heart failure.

Aims: Regulation of vascular tone by 3',5'-cyclic adenosine monophosphate (cAMP) involves many effectors including the large conductance, Ca2+-activated, K+ (BKCa) channels. In arteries, cAMP is mainly hydrolyzed by type 3 and 4 phosphodiesterases (PDE3, PDE4). Here, we examined the specific contribution of BKCa channels to tone regulation by these PDEs in rat coronary arteries, and how this is altered in heart failure (HF). Methods and results: Concomitant application of PDE3 (cilostamide) and PDE4 (Ro-20-1724) inhibitors increased BKCa unitary channel activity in isolated myocytes from rat coronary arteries. Myography was conducted in isolated, U46619-contracted coronary arteries. Cilostamide (Cil) or Ro-20-1724 induced a vasorelaxation that was greatly reduced by iberiotoxin (IBTX), a BKCa channel blocker. Ro-20-1724 and Cil potentiated the relaxation induced by the ß-adrenergic agonist isoprenaline (ISO) or the adenylyl cyclase activator L-858051 (L85). IBTX abolished the effect of PDE inhibitors on ISO but did not on L85. In coronary arteries from rats with HF induced by aortic stenosis, contractility and response to acetylcholine were dramatically reduced compared with arteries from sham rats, but relaxation to PDE inhibitors was retained. Interestingly, however, IBTX had no effect on Ro-20-1724- and Cil-induced vasorelaxations in HF. Expression of the BKCa channel α-subunit, of a 98 kDa PDE3A and of a 80 kDa PDE4D were lower in HF compared with sham coronary arteries, while that of a 70 kDa PDE4B was increased. Proximity ligation assays demonstrated that PDE3 and PDE4 were localized in the vicinity of the channel. Conclusion: BKCa channels mediate the relaxation of coronary artery induced by PDE3 and PDE4 inhibition. This is achieved by co-localization of both PDEs with BKCa channels, enabling tight control of cAMP available for channel opening. Contribution of the channel is prominent at rest and on ß-adrenergic stimulation. This coupling is lost in HF.

The impact of interventions by pharmacists collected in a computerised physician order entry context: a prospective observational study with a 10-year reassessment.

AIMS OF THE STUDY: This study assesses clinical interventions by pharmacists prospectively collected from medical and surgical wards, notably the acceptance of interventions, computerised physician order entry (CPOE)related problems, the potential impact of interventions on patient safety evaluated by a multidisciplinary committee, and their evolution over the 10 years since a first assessment. METHODS: A prospective observational study covering 13 months was conducted in a French teaching hospital with a patient information system that integrates an electronic health record (EHR) with a CPOE. Interventions by pharmacists were prospectively recorded using CPOE. All interventions were reviewed by two pharmacists. We assessed the interventions, the possible implications of the CPOE in prescribing errors, and the acceptance of interventions by physicians. A committee reviewed the potential clinical impact for patients. The results were compared with the same outcomes collected 10 years ago in the same hospital. RESULTS: A total of 2141 interventions by pharmacists were reviewed. Among them, 1589 (74.1%) were accepted by physicians. Regarding the potential clinical impact, a total of 1136 (53%) interventions concerned prescriptions that were potentially significant or serious for patients and 42 (2%) of them were potentially life-threatening. Ten years earlier, the acceptance rate was 23%. Moreover, 14.7% of errors were attributed to the use of the software, whereas 10 years earlier the rate of errors was 49%. CONCLUSIONS: The acceptance rate and frequency of CPOE-related errors were better than 10 years before, which is encouraging and shows the importance of regular training and collaboration with healthcare givers to reduce errors. The routine analysis of interventions by pharmacists with medical staff feedback should continue to improve their relevance and effectiveness.

Evaluation of exposure to effervescent drugs in a large health check-up population in France: a cross-sectional study.

OBJECTIVES: The relationship between high dietary sodium intake and hypertension is well established. Some drugs are associated with high-sodium content, particularly effervescent tablets (ETs). Despite a possible cardiovascular risk associated with the use of such drugs, observational data describing exposure to ETs in ambulatory subjects are lacking.This study aims to estimate the prevalence of exposure to ETs and to highlight factors associated with this exposure in a large French health check-up population. DESIGN: This was a cross-sectional study. SETTING AND PARTICIPANTS: Participants were French individuals who underwent medical check-ups at the Investigations Préventives et Cliniques centre between April and June 2017. RESULTS: In total, 1043 subjects were included in the study. The prevalence of exposure to ETs in the last 30 days was 26.9% (95% CI 24.2% to 29.6%). Exposure was frequent (ie, two ETs per week or more in the last 30 days) for 7.3% of subjects. Self-medication was the major source of exposure (93.8%). Paracetamol, aspirin, vitamins and betaine accounted for 95.3% of the ETs used. The factors associated with this exposure by multivariate analysis were: male gender, Overseas French origin, depression and body mass index ≥25 kg/m2. A diagnosis of hypertension or treatment with diuretics were not protective factors against exposure to ETs. CONCLUSION: Exposure to ETs is frequent in the general population, particularly through self-medication. Clinical conditions associated with low-salt requirements were not associated with lower exposure to ETs, suggesting a lack of awareness by practitioners and patients about this iatrogenic issue.

Cardiovascular risk associated with high sodium-containing drugs: A systematic review.

BACKGROUND: Excess dietary sodium is associated with increased blood pressure (BP). Some drugs are associated with high sodium intake (in particular effervescent tablets), but the cardiovascular risk associated with such high sodium-containing drugs (HSCD) is largely underevaluated. OBJECTIVES: To summarize the evidence for a potential cardiovascular risk associated with exposure to HSCD, and to highlight possible risk factors associated with this iatrogenic issue; in general and/or specific populations. METHODS: We conducted a systematic review, by searching electronic databases including MEDLINE, EMBASE, Web of Science, CENTRAL and grey literature between 1960 and 2015. We included studies that reported modification of cardiovascular parameters or incidence/prevalence of cardiovascular outcomes, between a group of subjects exposed to HSCD relative to a non-exposed group. The threshold used to identify HSCD was 391 mg/day. We did not consider studies evaluating exposure to sodium as an active ingredient or those focusing on dialysis solutions or enteral/parenteral nutrition. Study quality was assessed using the EPHPP tool. RESULTS: A total of eight studies met our inclusion criteria. Four reported results for short-term exposure to HSCD (≤ 7 days) on BP fluctuations. One study reported an elevation of BP (associated sodium intake: 1,656 mg/day). Four studies evaluated a long-term exposure (≥ 2 years or discontinuation of a chronic treatment). Two studies reported iatrogenic risk. For these studies, drug associated sodium intake was high (> 1,500 mg/day) in patients with comorbidities (in particular, diabetes mellitus and hypertension). CONCLUSION: Despite numerous study limitations, this systematic review suggests three potential synergistic risk factors for cardiovascular complications after exposure to HSCD: a high sodium intake (≥ 1,500 mg/day), a long duration of exposure, and the presence of comorbidities. Further studies are required to characterize this iatrogenic risk. TRIAL REGISTRATION: PROSPERO CRD42016047086.