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Chronicity, Multimorbidity, and Medication Appropriateness

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 12844

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Dr. Ignatios Ioakeim-Skoufa

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EpiChron Research Group, Aragon Health Research Institute (IIS Aragón), ES-50009 Zaragoza, Spain
Interests: multimorbidity; chronic diseases; public health; drug utilisation; pharmacovigilance; epidemiology; real-world evidence; AI in health
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Dr. Mercedes Aza-Pascual-Salcedo

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Primary Care Pharmacy, Aragon Health Service (SALUD), ES-50017 Zaragoza, Spain
Interests: multimorbidity; chronic diseases; drug utilisation; pharmacoepidemiology; pharmacovigilance; real-world data
Special Issues, Collections and Topics in MDPI journals

Dr. Helena Coelho

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Portuguese Society of Health Care Pharmacists (SPFCS), PT-3030-320 Coimbra, Portugal
Interests: drug utilization; pharmacoepidemiology; pharmacovigilance; operation strategy

Special Issue Information

Dear Colleagues,

Multimorbidity is extremely common in older people. However, its prevalence continuously rises in younger adults, highlighting the need for effective interventions to prevent its development and evolution at early ages. Large-scale epidemiologic studies are needed to characterize chronicity better and exhaustively analyze multimorbidity trajectories. It is also vital to study patterns of chronic polypharmacy and other clinical and pharmacological characteristics that are common amongst chronic patients, such as inappropriate medication, low adherence to treatment, drug-related adverse events, and drug–drug and drug–disease interactions. In the era of big data and emerging technologies, addressing chronicity is a significant priority for public health systems, healthcare professionals, and patients.

This Special Issue, “Chronicity, Multimorbidity, and Medication Appropriateness”, in the Journal of Clinical Medicine aims to cover the following areas: the characterization of chronicity, multimorbidity trajectories, and risk factors in all ages; drug utilization; patterns of chronic polypharmacy; medication adherence; adverse events; potentially inappropriate medication in chronic patients; and synergistic effects of the morbidity burden and medication use on health outcomes.

Dr. Ignatios Ioakeim-Skoufa
Dr. Mercedes Aza-Pascual-Salcedo
Dr. Helena Coelho
Guest Editors

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Keywords

multimorbidity
chronic diseases
drug utilization
polypharmacy
medication appropriateness
medication adherence
drug interactions
care models
chronic inflammation
interventions

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Published Papers (9 papers)

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16 pages, 1646 KiB

Open AccessArticle

The Assessment of the Safety Profile of Selective Serotonin Reuptake Inhibitors Versus Other Antidepressants: Drug–Drug Interaction Insights from EudraVigilance

by Carmen Maximiliana Dobrea, Claudiu Morgovan, Adina Frum, Anca Butuca, Adriana Aurelia Chis, Anca Maria Arseniu, Steliana Ghibu, Razvan Constantin Vonica, Felicia Gabriela Gligor, Ioana Rada Popa Ilie and Andreea Loredana Vonica Tincu

J. Clin. Med. 2025, 14(4), 1208; https://doi.org/10.3390/jcm14041208 - 12 Feb 2025

Viewed by 1049

Abstract

Depression persists as one of the illnesses described relentlessly through the centuries because it affects a large group of people. Background/Objectives: The treatment of depression consists of various therapeutic agents, among which selective serotonin reuptake inhibitors (SSRIs) are elective. As polypharmacy tends to become the norm in modern days, the study of the real-life occurrence of drug–drug interactions is imperative. The aim of this study was the evaluation of drug–drug interactions (DDIs) between antidepressant medicines, namely SSRIs (each representative) versus eleven representatives from other antidepressant classes. Methods: Based on the spontaneous safety reports (ICSRs) uploaded to EudraVigilance until the end of July 2024, the descriptive and the disproportionality analyses were performed, and results were interpreted in the context of pharmacologic variability. Results: SSRIs were the focus of 137,369 ICSRs while for the other antidepressants, namely amitriptyline, clomipramine, duloxetine, venlafaxine, mirtazapine, bupropion, trazodone, tianeptine, agomelatine, brexpiprazole, and esketamine, a total of 155,458 reports were registered. The most notable differences appeared in psychiatric adverse drug reactions. Except fluvoxamine (n = 463), the remaining SSRIs had a higher number of DDIs reported (n = 1049 for escitalopram and n = 1549 for sertraline) compared to other antidepressants. However, similar numbers of DDIs were reported for duloxetine (n = 1252) and venlafaxine (n = 1513). Sertraline unspecified DDIs were reported with a higher probability compared to all other drugs (e.g., esketamine ROR: 9.37, 95% CI: 5.17–16.96, tianeptine ROR: 4.08, 95% CI: 2.49–6.69, etc.). Conclusions: SSRIs, although known to influence various cytochrome P450 isoenzymes, have not shown higher inhibitory interactions compared to any of the drugs selected as reference. Sertraline appears in more reports concerning DDIs than the other antidepressants. Still, further real world studies related to the DDIs of SSRIs are needed to complete the relevant knowledge level. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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10 pages, 532 KiB

Open AccessArticle

Comorbid Attention-Deficit/Hyperactivity Disorder and Mood Disorder in a South African Sample of Substance Use Disorder Patients

by Ilse Truter, Judith Regnart and Anneke Meyer

J. Clin. Med. 2025, 14(3), 927; https://doi.org/10.3390/jcm14030927 - 31 Jan 2025

Viewed by 747

Abstract

Background: The brain reward circuitry is thought to underlie the co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) and to possibly impact mood disorders. This study aimed to establish if any difference existed in the severity of depression symptomology between SUD comorbidity with and without ADHD. Methods: A multi-centre, cross-sectional comparison study design drew study participants from substance use treatment facilities within South Africa. The participants were screened for ADHD and depression, with the selective application of a confirmatory ADHD diagnostic interview. The participants were diagnostically grouped according (SUD + ADHD, SUD − ADHD) to an application of a 2 x 2 x 3 ANOVA model. Results: A significant main effect of ADHD diagnosis and gender on depressive symptoms was identified. Post hoc analysis revealed that only male ADHD subjects had significantly higher scores on the Beck scale than non-ADHD males. Conclusions: Co-occurring disorder (COD) prevalence rates were higher than most other South African studies. The aggravation of ADHD on mood disorder symptom severity is consistent with the existing literature; however, further investigation is warranted to determine if the interaction of gender remains only significant for men with a lager sample size. The identified COD prevalence rate may contrast with other South Africa studies, emphasising the need for comprehensive psychiatric comorbidity screening in SUD treatment settings. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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15 pages, 556 KiB

Open AccessArticle

Validation of an Inhaled Therapy Beliefs Questionnaire in Patients with Chronic Obstructive Pulmonary Disease

by Francisca Muñoz-Cobos, Virginia P. Aguiar-Leiva, Carmen Argüello-Suárez, Paula Colacicchi, Luis Antonio Calleja-Cartón and Francisca Leiva-Fernández

J. Clin. Med. 2024, 13(8), 2281; https://doi.org/10.3390/jcm13082281 - 15 Apr 2024

Cited by 2 | Viewed by 1885

Abstract

Background: To carry out a validation questionnaire that assesses beliefs about inhaled treatments in patients with chronic obstructive pulmonary disease (COPD), as knowing patients’ beliefs could help to improve medication adherence and health outcomes. Methods: We evaluated data from 260 COPD patients from electronic medical record databases from five primary healthcare centers, in a descriptive, cross-sectional study with a sample size calculated for a 10-item questionnaire, with an estimated Cronbach’s alpha of 0.70 and a 95% confidence level. Study participants were selected via systematic random sampling. Variables: Ten-item Inhaled Therapy Beliefs Questionnaire, CCTI-Questionnaire v.2.0, time for completion, age, sex, educational level, spirometry severity (GOLD criteria), exacerbations (previous year), characteristics of inhaled treatment, and smoking habit. A two-year follow-up in a subsample of 77 patients from one health center was utilized. The Morisky–Green test, pharmacy dispensing data, test–retest (kappa coefficient), and an exploratory analysis of the adherence–belief relationship (ji-squared) were measured. Results: The 10-item questionnaire showed good viability (3 min completion time) when performed face-to-face or telephonically; its psychometric properties were acceptable, with an internal consistency (Cronbach’s alpha) score of 0.613. Three factors explained 47.58% of the total variance (p < 0.0001): use (factor 1), effects (factor 2), and objectives (factor 3) of inhalers. The two-year follow-up ultimately considered 58 out of the 77 patients (10 deceased, 4 unlocated, 2 mistakes, 2 no inhaled treatment, and 1 withdrawal). Non-adherence was 48.3% in terms of the Morisky–Green test; 31% in terms of pharmacy dispensing data; and 40.4% considering both methods. There was low test–retest reliability, indicated by items 4, 8, and 9 of the CCTI-Questionnaire (Kappa = 0.4, 0.26, and 0.34; p-value < 0.0001, 0.008, and 0.001, respectively). There was mild correlation between beliefs and adherence. Conclusions: The ten-item CCTI-Questionnaire v.2.0 demonstrated acceptable psychometric properties regarding feasibility, reliability, and content validity. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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23 pages, 794 KiB

Open AccessArticle

Drug Related Problems among Older Inpatients at a Tertiary Care Setting

by Porrawee Pramotesiri, Krongtong Putthipokin and Sirasa Ruangritchankul

J. Clin. Med. 2024, 13(6), 1638; https://doi.org/10.3390/jcm13061638 - 13 Mar 2024

Cited by 1 | Viewed by 2143

Abstract

Background: Older persons are more likely to have multiple chronic diseases, leading to the simultaneous use of many medications. This situation results in increased drug-related problems (DRPs), which are the causes of adverse health outcomes. Therefore, we aimed to evaluate the prevalence of and associated risk factors for exposure to >1 criterion of DRPs among older adults admitted to a tertiary care hospital. Methods: We conducted a cross-sectional study involving 357 participants aged ≥60 years admitted to Ramathibodi Hospital from 1 February 2022 to 30 November 2022. The participants were evaluated for baseline characteristics, medications and DRPs and were classified into two groups, according to their exposure to DRPs: patients with exposure to ≤1 criteria and patients with exposure to >1 criterion of DRPs. Multivariate logistic regression analysis was performed to determine the independent risk factors for exposure to >1 criterion of DRPs. Results: Overall, 205 (57.4%) patients experienced >1 criterion of DRPs. Approximately 67.8%, 71.7% and 7.6% of the participants were exposed to at least one potentially inappropriate medication (PIM), drug–drug interaction (DDI) and adverse drug events (ADE), respectively. The most frequently prescribed PIMs were proton pump inhibitors (PPIs) (17.3%). Antineoplastics (48.1%) were the most frequently drug class related to ADEs. Overall, 37% of the ADEs in the current study were considered preventable ADEs. After adjustment for potential confounders, polypharmacy and the use of proton pump inhibitors, hypoglycemics, diuretics, psycholeptics, psychoanaleptics and cardiac therapy medications were correlated with a higher risk of exposure to > 1 criterion of PIMs, DDIs or ADEs. Conclusions: Therefore, comprehensive medication reviews and careful medication prescriptions are recommended in the geriatric population. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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14 pages, 1411 KiB

Open AccessArticle

Morbidity among Adolescent Hypnotic Drug Users in Norway: An Observational Population-Based Study

by Mohammad Nouri Sharikabad, Svetlana Skurtveit, Hilchen Thode Sommerschild, Kristine Olsen, Ingeborg Hartz, Rikke Wesselhoeft, Vidar Hjellvik, Lars Johan Hauge and Marte Handal

J. Clin. Med. 2024, 13(4), 1075; https://doi.org/10.3390/jcm13041075 - 14 Feb 2024

Viewed by 1648

Abstract

We have previously shown that the use of hypnotic drugs increased among young Scandinavians during 2012–2018. This study aimed to explore psychiatric and somatic morbidity among adolescent hypnotic drug users in a cohort study of 13–17-year-old individuals during 2008–2018 in Norway. Data sources were (i) prescription data from the Norwegian Prescription Database linked to specialist health care diagnoses from the Norwegian Patient Registry and (ii) sleep disorder diagnoses from the Primary Health Care Database. Hypnotic drugs were defined as the sedative antihistamine alimemazine and the ATC group “Hypnotics and Sedatives” (N05C), excluding midazolam. In 2017, 2519 girls (16.5/1000) and 1718 boys (10.7/1000) were incident (new) users of hypnotic drugs. Most of these new users (82% of girls, 77% of boys) were referred to secondary health care, where the most frequent diagnoses were mental and behavioral disorders (51.8% of girls, 46.2% of boys), while only 3.2% received a specific sleep disorder diagnosis. The most common mental and behavioral disorders were “Neurotic stress-related disorders” among girls (27.4%) and “Behavioral and emotional disorders” among boys (23.6%). In conclusion, the trend of increasing hypnotic drug use among adolescents reflects the initiation of hypnotic drugs in a subgroup of the population with a higher disease burden, mainly due to psychiatric disorders, than the general population. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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11 pages, 244 KiB

Open AccessArticle

Potentially Inappropriate Prescribing and Potential Prescribing Omissions and Their Association with Adverse Drug Reaction-Related Hospital Admissions

by Ross Brannigan, John E. Hughes, Frank Moriarty, Emma Wallace, Ciara Kirke, David Williams, Kathleen Bennett and Caitriona Cahir

J. Clin. Med. 2024, 13(2), 323; https://doi.org/10.3390/jcm13020323 - 6 Jan 2024

Cited by 2 | Viewed by 2053

Abstract

Background: This study aimed to determine the prevalence of potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) and their association with ADR-related hospital admissions in patients aged ≥ 65 years admitted acutely to the hospital. Methods: Information on medications and morbidities was extracted from the Adverse Drug Reactions in an Ageing Population (ADAPT) cohort (N = 798: N = 361 ADR-related admissions; 437 non-ADR-related admissions). PIP and PPOs were assessed using Beers Criteria 2019 and STOPP/START version 2. Multivariable logistic regression (adjusted odds ratios (aOR), 95%CI) was used to examine the association between PIP, PPOs and ADR-related admissions, adjusting for covariates (age, gender, comorbidity, polypharmacy). Results: In total, 715 (90%; 95% CI 87–92%) patients had ≥1 Beers Criteria, 555 (70%; 95% CI 66–73%) had ≥ 1 STOPP criteria and 666 patients (83%; 95% CI 81–86%) had ≥ 1 START criteria. Being prescribed at least one Beers (aOR = 1.66, 95% CI = 1.00–2.77), or meeting STOPP (aOR = 1.07, 95% CI = 0.79–1.45) or START (aOR = 0.72; 95%CI = 0.50–1.06) criteria or the number of PIP/PPO criteria met was not significantly associated with ADR-related admissions. Patients prescribed certain drug classes (e.g., antiplatelet agents, diuretics) per individual PIP criteria were more likely to have an ADR-related admission. Conclusion: There was a high prevalence of PIP and PPOs in this cohort but no association with ADR-related admissions. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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21 pages, 1075 KiB

Open AccessSystematic Review

Electronic Health Records: A Gateway to AI-Driven Multimorbidity Solutions—A Comprehensive Systematic Review

by Ignatios Ioakeim-Skoufa, Celeste Cebollada-Herrera, Concepción Marín-Bárcena, Vitor Roque, Fátima Roque, Kerry Atkins, Miguel Ángel Hernández-Rodríguez, Mercedes Aza-Pascual-Salcedo, Ana Fanlo-Villacampa, Helena Coelho, Carmen Lasala-Aza, Rubén Ledesma-Calvo, Antonio Gimeno-Miguel and Jorge Vicente-Romero

J. Clin. Med. 2025, 14(10), 3434; https://doi.org/10.3390/jcm14103434 - 14 May 2025

Viewed by 244

Abstract

Background/Objectives: Artificial intelligence (AI) plays an important role in real-world health research. It can address the complexities of chronic diseases and their associated negative outcomes. This systematic review aims to identify the applications of AI that utilize real-world health data for populations with multiple chronic conditions. Methods: A systematic search was performed in MEDLINE and EMBASE following PRISMA guidelines. Studies were included if they applied AI methods using data from electronic health records for patients with multimorbidity. Results: Forty-four studies met the inclusion criteria. The review revealed AI applications identifying disease clusters, predicting comorbidities, and estimating health outcomes such as mortality, adverse drug reactions, and hospital readmissions. Commonly used AI techniques included clustering methods, XGBoost, random forest, and neural networks. These methods helped identify risk factors, predict disease progression, and optimize treatment plans. Conclusions: This study emphasizes the increasing role of AI in understanding and managing multimorbidity. Integrating AI into healthcare systems can enhance resource allocation, improve care delivery efficiency, and support personalized treatment strategies. However, further research is needed to overcome existing limitations, particularly the lack of standardized performance metrics, which affects model comparability. Future research should adhere to commonly recommended evaluation practices to improve reproducibility and meta-analysis. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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15 pages, 693 KiB

Open AccessSystematic Review

Charting the Pathways of Cardiometabolic Multimorbidity: A Systematic Review of Clinical Trajectories

by Ignatios Ioakeim-Skoufa, Rubén Ledesma-Calvo, Aida Moreno-Juste, Fátima Roque, Kerry Atkins, Miguel Ángel Hernández-Rodríguez, Mercedes Aza-Pascual-Salcedo, Francisca González-Rubio, Carmen Lasala-Aza, Óscar Esteban-Jiménez, Ana Avedillo-Salas, Celeste Cebollada-Herrera, Antonio Gimeno-Miguel and Jorge Vicente-Romero

J. Clin. Med. 2025, 14(8), 2615; https://doi.org/10.3390/jcm14082615 - 11 Apr 2025

Viewed by 490

Abstract

Background: Managing multimorbidity is a major challenge for healthcare systems. Cardiometabolic multimorbidity (CMM) is highly prevalent and linked to increased disease burden, functional decline, and mortality. While most studies focus on cross-sectional analyses, longitudinal approaches are essential for understanding disease progression and identifying patient groups who may benefit from targeted interventions. Objectives: This systematic review synthesises evidence from longitudinal studies on the incidence and progression of CMM, exploring transitions between multimorbidity clusters and their clinical implications. Methods: A systematic search was conducted in MEDLINE and EMBASE following PRISMA guidelines. Studies were included if they employed longitudinal designs and clustering techniques to assess multimorbidity evolution. The quality of evidence was evaluated using the GRADE system. Results: Ten studies met the inclusion criteria. CMM occurs across all age groups and both sexes, showing the highest mortality and functional decline rates. Patients with CMM frequently develop additional cardiometabolic conditions or transition to related clusters. Many also experience neurodegenerative and mental health disorders. Individuals from respiratory multimorbidity clusters often transition to CMM. Moreover, CMM is more prevalent in lower socioeconomic populations. Conclusions: Understanding multimorbidity trajectories enables targeted preventive strategies. Identifying patients with predictable progression can help design adequate and effective interventions, reduce health disparities, and improve healthcare outcomes. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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13 pages, 840 KiB

Open AccessSystematic Review

Polypharmacy Management in Chronic Conditions: A Systematic Literature Review of Italian Interventions

by Lara Perrella, Sara Mucherino, Manuela Casula, Maddalena Illario, Valentina Orlando and Enrica Menditto

J. Clin. Med. 2024, 13(12), 3529; https://doi.org/10.3390/jcm13123529 - 17 Jun 2024

Cited by 4 | Viewed by 1649

Abstract

Background: Potentially inappropriate polypharmacy (PIP) is among the major factors leading to adverse drug reactions, increased healthcare costs, reduced medication adherence, and worsened patient conditions. This study aims to identify existing interventions implemented to monitor and manage polypharmacy in the Italian setting. Methods: A systematic literature review (PROSPERO: CRD42023457049) was carried out according to the PRISMA statement guidelines. PubMed, Embase, ProQuest, and Web of Science were queried without temporal constraints, encompassing all published papers until October 2023. Inclusion criteria followed the PICO model: patients with polypharmacy; interventions to monitor/manage polypharmacy regimen versus no/any intervention; outcomes in terms of intervention effectiveness and cost variation. Results: After duplicate deletion, 153 potentially relevant publications were extracted. Following abstract and full-text screenings, nine articles met the inclusion criteria. Overall, 78% (n = 7) were observational studies, 11% (n = 1) were experimental studies, and 11% (n = 1) were two-phase studies. A total of 44% (n = 4) of the studies involved patients aged ≥ 65 years, while 56% (n = 5) were disease-specific. Monitoring was the most prevalent choice of intervention (67%; n = 6). Outcomes were mainly related to levels of polypharmacy (29%; n = 6) and comorbidities (29%; n = 6), effectiveness rates (14%; n = 3), and avoidable costs (9%; n = 2). Conclusions: This review outlines that Italy is still lacking in interventions to monitor/manage PIP, addressing an unmet need in developing patient-tailored strategies for reducing health-system burden. Full article

(This article belongs to the Special Issue Chronicity, Multimorbidity, and Medication Appropriateness)

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