ORIGINALES

 

Factors related with the appropriateness of pharmacological treatment in polypathological patients

Factores relacionados con la adecuación del tratamiento farmacológico en pacientes pluripatológicos

 

 

M. Galván Banqueri¹, E.R. Alfaro Lara², M. Rincón Gómez³, P.C. Rivas Covas⁴, M.D. Vega Coca¹ and M.D. Nieto Martín³

¹Clinical Pharmacy Specialist. Researcher. Health Technology Assessment Service. Andalusian Agency for Health Technology Assessment. Seville. Spain.
²Clinical Pharmacy Specialist. Researcher. Pharmacy Department. Hospital Universitario Virgen del Rocio. Seville. Spain.
³Internal Medicine Specialist. Internal Medicine Department. Hospital Universitario Virgen del Rocio. Seville. Spain.
⁴Resident. Internal Medicine Department. Hospital Universitario Virgen del Rocio. Seville. Spain.

Correspondence

 

 

---

ABSTRACT

Objective: To evaluate the association between the number of pharmacological inappropriateness and possible factors related with it.
Methods: All polyphatological patients of the IMPACTO project in a tertiary hospital were included (July 2010-March 2012). The pharmacist performed the interventions based on a combined strategy that included the modified MAI and the STOPP-START criteria. A greater number of interventions indicated smaller treatment appropriateness. In the analysis of the strength of association between two continuous variables the Pearson correlation coefficient was used. Test of Student's t or Mann-Whitney comparisons of quantitative data between two groups were applied. Subsequently, a multivariate analysis was performed to study possible variables which explain the inappropriateness of the pharmacological treatment.
Results: 242 patients were included. 838 inappropriateness were detected (average per patient of 3±2). The appropriateness was associated with: number of diagnoses, medications, and categories of polypathology, Charlson Comorbidity Index, sex, and categories A1 and B2. When diagnosing collinearity in the multivariate model, we observed that there was collinearity between "Charlson Comorbidity Index" and "number of categories of polypathological patients", so it was decided to conduct two multivariate models variables, one each. The number of drugs, the number of diagnoses and the gender remained significant in both multivariate models.
Conclusions: The appropriateness of pharmacological treatment decreases with increasing number of drugs and number of diagnoses, as well as female gender. However, both multivariate models explain a low percentage of variability in the number of inappropriateness.

Key words: Multimorbidity; Polyphatological; Appropriateness.

---

RESUMEN

Objetivo: evaluar la asociación entre el número de inadecuaciones farmacológicas y posibles factores relacionados con la misma.
Métodos: Se incluyeron todos los pacientes pluripatológicos del proyecto IMPACTO en un hospital de tercer nivel (Julio 2010-Marzo 2012). El farmacéutico realizó las intervenciones en base a una estrategia combinada que incluía el MAI modificado y los criterios STOPP-START. A mayor número de intervenciones menor adecuación del tratamiento. En los análisis de la fuerza de asociación entre dos variables continuas se utilizó el coeficiente de correlación de Pearson. Se aplicó el test de la t de Student o U de Mann-Whitney en comparaciones de datos cuantitativos entre dos grupos. Posteriormente, se realizó un análisis multivariante, para estudiar posibles variables que explicasen las inadecuaciones del tratamiento farmacológico.
Resultados: Se incluyeron un total de 242 pacientes. Se detectaron un total de 838 inadecuaciones, siendo la media por paciente de 3±2. La adecuación del tratamiento farmacológico se asoció con el número de diagnósticos, el número de medicamentos, el número de categorías de paciente pluripatológico, el índice de comorbilidad de Charlson, el sexo y las categorías A1 y B2. Al realizar el diagnóstico de colinealidad, en el modelo multivariante, de las variables se observó que existía colinealidad entre las variables "índice de comorbilidad de Charlson" y "número de categorías de paciente pluripatológico", por lo que se decidió realizar dos modelos multivariantes, uno con cada una de ellas. Se mantuvieron significativos con el multivariante y para ambos modelos el número de medicamentos, el número de diagnósticos y el sexo.
Conclusiones: La adecuación del tratamiento farmacológico disminuyó al aumentar el número de medicamentos y el número de diagnósticos, así como en mujeres. No obstante, ambos modelos multivariantes, explicaron un porcentaje de variabilidad del número de inadecuaciones leve.

Palabras clave: Multimorbilidad; Pluripatología; Adecuación.

---

 

Introduction

Appropriateness is a general term that includes a wide range of characteristics and behaviours related to the quality of the prescription¹. A prescription is considered adequate when there is clear evidence that supports its use for the given indication, is well tolerated and has a favourable cost-effectiveness profile².

Inappropriate prescribing also includes the use of drugs with incorrect duration, interactions and duplications. Additionally, in elderly patients, criteria should be considered such as prognosis, life expectancy and functional state so as to promote the use of treatments with better risk-benefit ratios^3,4.

Inappropriate drug prescribing in chronic patient is considered a public health issue related to morbidity, mortality and use of healthcare resources⁵.

Within this framework, polypathological patients are defined as those with two or more chronic diseases from a list of specific clinical categories that take into account the severity of or incapacity produced by the disease⁶. The prevalence of these patients is low in the general population, but can be high in the hospital setting⁷.

These patients are susceptible to suffer inadequate pharmacological treatment, since polypharmacy, high morbidity rates, and continuous health care transitions increase this risk^8,9.

Our research group, in a previous work¹⁰, identified by a panel of experts, following the Delphi methodology, potentially useful tools for appropriateness in this group of patients. As implicit method, the modified Medication Aproppriateness Index (MAI) was selected, and as explicit method, the Screening Tool of Older Person's potentially inappropriate Prescription/Screening Tool to Alert doctors to the Right (STOPP-START). Once we validated the modified MAI¹¹, our group applied this combined approach for assessing the appropriateness of the pharmacological treatment in a cohort of polypathological patients¹². The primary endpoint of this study was the number of inappropriateness detected. An average of 3 inappropriateness per patient was detected.

The main objective of this study was to evaluate the association between the number of pharmacological inappropriateness (number of interventions for the appropriateness of drug treatment performed by the pharmacist) and possible factors related with it.

 

Methods

All polyphatological patients in an integrated care project, IMPACTO project, in a tertiary hospital were included (July 2010-March 2012). This is a multidisciplinary macro project, whose main objective is to evaluate the clinical impact of a multilevel intervention model based on shared care between the internist of reference and the primary care service in a multicenter population of polypathological patients.

The pharmacist performed the interventions based on a combined strategy that included the modified MAI¹¹ and the STOPP-START¹³ criteria. Each intervention was considered as a pharmacological inappropriateness, so, a greater number of interventions indicated smaller treatment appropriateness.

For each of the patients was collected: age, sex, number of diagnoses, number and types of categories of inclusion as polypathological patients, number of drugs, Charlson Comorbidity Index, number of admissions at 3 and 12 previous months and number of interventions for the appropriateness of drug treatment performed by the pharmacist.

The dates were statistically analyzed in the IBM^® SPSS Statistic software (version 19.0 for Windows). The description of the qualitative variables was performed by distribution of absolute frequencies and percentages. Quantitative variables were described by mean and it standard deviation.

To analyze the association between the variable numbers of interventions with respect to the other quantitative variables the Pearson correlation coefficient was used. And to analyze qualitative variables the test of Student's t or Mann-Whitney was applied as they were normal or not (Kolmogorov-Smirnov). It was assumed that the differences were statistically significant when p <0.05.

With those variables significant association was obtained in the univariate analysis, we performed a multivariate analysis in order to study possible variables that explain inappropriateness of the drug therapy. We realized the collinearity diagnosis, in the multivariate model, in order to detect possible variables which were associated. Regression coefficients (B) and their confidence intervals (CI) at 95% were obtained. An assessment of the goodness of fit by the determination coefficient was performed, and the diagnosis of independence (Durbin-Watson) errors and verification of homogeneity and normality of these through the scatter plots.

 

Results

A total of 242 patients were included. Baseline characteristics are shown in Table 1.

The number of diagnoses, drugs, categories of inclusion as polypathological patients and Chalson index showed a statistically significant association with the number of interventions, being the Pearson correlation coefficient of 0.322 (p <0.001), 0.369 (p <0.001), 0.162 (p = 0.012) and 0.183 (p = 0.004) respectively.

The mean difference of interventions in women (3.82 ± 1.77) and in men (3.11 ± 1.88) was significant (p = 0.003). This also occurred with the category A1 (chronic heart failure), the presence (3.65 ± 1.86) versus the absence (3.00 ± 1.77) of the same was significant (p = 0.012); and with the category B2 (chronic renal disease), it presence implies a number of interventions of 3, 92 ± 1.99 and the absence of 3.16 ± 1.70 (p = 0.002).

When diagnosing collinearity in the multivariate model, the variables "Charlson Comorbidity Index" and "number of categories as polypathological patients", demonstrated collinearity between them so it was decided to conduct two multivariate models variables, one each. Both models are detailed in Table 2, and verification that the waste meets the assumption of homogeneity and follows a normal distribution is shown in the graphs in Figure 1.

The first predictive model based on the Charlson Comorbidity Index would be:

Number of interventions = -0.140 + 0.92 x number of diagnosis + 0.156 x number of drugs + 0.627 x sex + 0.297 x categorie of inclusion A1 + 0.468 x categorie of inclusion B2 + 0.055 x Charlson Comorbidity Index

And the second, based on the number of categories as polypathological patients:

Number of interventions = -0.69 + 0.95 x number of diagnosis + 0.157 x number of drugs + 0.599 x sex + 0.310 x categorie of inclusion A1 + 0.548 x categorie of inclusion B2 + 0.19 x number of categories as polypathological patients

Both models explain 23.4% and 23.3% respectively of the total variability in the number of interventions.

 

Discussion

In this study potential predictors of lower appropriateness of pharmacological treatment in a group of patients who, because of their vulnerability, are susceptible to numerous pharmacological inappropriateness, are evaluated⁸.

It is known that the appropriateness decreases with increasing number of drugs¹⁴. Importantly, in numerous studies, the polypharmacy has been identified as the main risk factor that determines the appearance of the incidents that gave rise to hospitalization or emergency care^15,16.

On the other hand, a relationship between inappropriateness and adverse drug reactions (ADRs) has been established. The risk of suffer an ADRs increases with age, due to physiological changes of the aging, changes in the pharmacokinetic and pharmacodynamic behavior of drugs, the influence of diseases, functional problems and social issues^17,18.

Despite the magnitude of the problem, there is no consensus nor is there solid scientific evidence to help prevent inappropriate prescribing, especially in older people. As far as the authors know this study is the first attempt to study variables related to a lower appropriateness in polypathological patients, hence its importance.

Our population of polypathological patients was characterized by an average of over 65 years of age, be considerably polymedicated (mean number of drugs per patient of 12) so as to present a high disease burden. This profile has previously been described in numerous publications^19,20.

In this study, when we did the diagnosis of collinearity, it was observed that it exits between "Charlson Comorbidity Index" and "number of categories of polypathological patients". This situation determined that two multivariate models were realized. This collinearity is logical because both variables are conceptually linked, as they determine in one or another way the disease burden.

The results of the multivariate analysis show that, for both models, variables such as the number of drugs or the number of diagnoses may determine the appropriateness, so that a greater number of drugs and number of diagnoses increases the presence of inappropriateness. This is reasonable and is in line with data available in the literature, pointing to polypathological patients as the most vulnerable among chronic patients. Moreover, being a woman seems to determine a greater presence of inappropriateness, although the clinical relevance of this difference between men and women is questionable, since the mean difference of interventions is one.

In one of the models (based on the number of categories as polypathological patients) the presence of category B2 (chronic kidney disease) determines a lower appropriateness. This can be justified based on the need for dose adjustment of drugs.

However, both models explain 23.4% and 23.3% respectively of the total variability in the number of interventions. More covariates would be necessary to arrive at an appropriate percentage which explains the variability of this variable.

Other studies, such as the REPOSI group, show results on the same line. Nobili et al 2011²¹, on the basis that the multimorbidity and polypharmacy are associated with hospitalization rates assessed whether certain groups of diseases carried a greater polypharmacy. The strongest association between clusters of diseases and polypharmacy was found for diabetes mellitus plus coronary heart disease plus cerebrovascular disease, diabetes plus coronary heart disease, and heart failure plus atrial fibrillation. In our study, the average of drugs per patient was approximately of 12, and the cardiac pathology constitutes the majority.

This study is not without limitations. First, the strategy developed for pharmaceutical interventions includes a clear subjective component, which is the modified MAI. Moreover, the study is conducted at local level in a tertiary hospital, which may influence the external validity of the results.

In conclusion, the appropriateness of pharmacological treatment decreases with increasing the number of drugs and the number of diagnoses, as well as in female gender. The presence of the B2 category also seems to determine a minor appropriateness. However, both multivariate models explain a low percentage of the variability in the number of interventions.

Given these results, new lines of research are open. A very interesting study could be whether interventions to improve the appropriateness of pharmacological treatment in patient's candidates to the same mean better health outcomes, ie, evaluate the effectiveness of these intervention models.

 

Bibliography

1. Pérez Fuentes MF, Castillo Castillo R, Rodríguez Toquero J, Martos Lopez E, Morales Mañero A. Adecuación del tratamiento farmacológico en población anciana polimedicada. Medicina de Familia. 2002; 1:23-8.         [ Links ]

2. Lu YC, Ross-Degnan D, Soumerai SB, Pearson SA. Interventions designed to improve the quality and efficiency of medication use in managed care: A critical review of the literatura-2001- 2007. Helth Services Research. 2008;8:75-86.         [ Links ]

3. Rochon PA, Gurwitz JH. Prescribing for seniors: Neither too much nor too little. JAMA. 1999; 282:113-5.         [ Links ]

4. Simonson W, Feinberg JL. Medication-related problems in the elderly: defining the issues and identifying solutions. Drugs Aging. 2005;22:559-69.         [ Links ]

5. Spinewine A, Schmader KE, Barber N, Hughes C, Lapane KL, Swine C, et al. Appropriate prescribing in elderly people: How well can it be measured and optimised? Lancet. 2007; 370:173-84.         [ Links ]

6. Ollero M, Álvarez TM, Barón FB, Bernabeu M, Codina A, Fernández A, et al. Integrated care process. Pluripathological patients Care. 2nd edición. Andalusia: Ministry of Health; 2007.         [ Links ]

7. Ramírez Duque N, Ollero Baturone M, Bernabeu Wittel M, Rincón Gómez M, Ortiz-Camuñez MA, García-Morillo JS. Clinical, functional, mental and sociofamiliar features in pluripathological patients. One-year prospective study in Primary Health Care. Rev Clin Esp 2008; 208:4-11.         [ Links ]

8. Santos Ramos B, Otero López MJ, Galván Banqueri M, Alfaro Lara ER, Vega Coca MD, Nieto Martín MD, et al. Health care models for patients with multiple chronic conditions and the role of the hospital pharmacy. Farm Hosp 2012; 36:506-17.         [ Links ]

9. Bernabeu-Wittel M, Ollero-Baturone M, Moreno-Gaviño L, Barón-Franco B, Fuertes A, Murcia-Zaragoza, J, et al. Development of a new predictive model for polypathological patients. The PRO-FUND index. Eur J Intern Med. 2011;22:311-7.         [ Links ]

10. Alfaro Lara ER, Vega Coca MD, Galván Banqueri M, Marin Gil N, Nieto Martín MD, Pérez Guerrero C, et al. Selection of tools for reconciliation, compliance and appropriateness of treatment in patients with multiple chronic conditions. Eur J Intern Med. 2012; 23:506-12.         [ Links ]

11. Galván-Banqueri M, de la Higuera-Vila Laura, Vega-Coca MD, Nieto-Martín MD, Pérez-Guerrero C, Santos-Ramos B. Reliability of a questionnaire for pharmacological treatment appropriateness in patients with multiple chronic conditions. Eur J Intern Med. 2013; 24:420-4.         [ Links ]

12. Galván-Banqueri M, González-Méndez A, Alfaro-Lara ER, Nieto-Martín MD, Pérez-Guerrero C, Santos-Ramos B. Evaluation of the appropriateness of pharmacotherapy in patients with high comorbidity. Aten Prim. 2013; 45: 235-43.         [ Links ]

13. Delgado Silveira E, Muñoz García M, Montero Errasquin B, Sánchez Castellano C, Gallagher PF, Cruz-Jentoft AJ. Inappropriate prescription in older patients: the STOPP/START criteria. Rev Esp Geriatr Gerontol. 2009; 44:273-9.         [ Links ]

14. Martín I, Gorroñogoitia A, Gómez J, Baztan JJ, Abianza P. El anciano frágil. Detección y tratamiento en AP. Aten Prim. 2010; 42: 388-93.         [ Links ]

15. Garfinkel D, Mangin D. Feasibility Study of a Systematic Approach for Discontinuation of Multiple Medications in Older Adults. Arch Intern Med. 2010; 170:1648-1654.         [ Links ]

16. Baena JM, Martínez MA, Tomás J. Selección de medicamentos en el anciano (I). Características diferenciales y criterios genéricos de selección. FMC. 2003; 10: 501-7.         [ Links ]

17. Onder G, Petrovic M, Tangiisuran B, Meinardi MC, Markito-Notenbomm NP, Sommers A, et al. Development and validation of a score to assess risk of adverse drug reactions among inhospital patients 65 years or older: the GerontoNet ADR risk score. Arch Intern Med. 2010; 170: 1142-8.         [ Links ]

18. Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol 2004; 57: 6-14.         [ Links ]

19. Bernabeu-Wittel M, Barón-Franco B, Murcia-Zaragoza J, Fuertes-Martín A, Ramos-Cantos C, Fernández-Moyano A, et al. A multi-institutional, hospital-based assessment of clinical, functional, sociofamilial and health-care characteristics of polypathological patients (PP). Arch Gerontol Geriatr. 2011;53:284-91.         [ Links ]

20. Ramírez-Duque N, Ollero-Baturone M, Bernabeu-Wittel M, Rincón-Gómez M, Ortiz-Camuñez MA, García-Morillo S. Clinical, functional, mental and sociofamiliar features in pluripathological patients. One-year prospective study in Primary Health Care. Rev Clin Esp. 2008;208:4-11.         [ Links ]

21. Nobili A, Marengoni A, Tettamanti M, Salerno F, Pasina L, Franchi C, et al. Association between clusters of diseases and polypharmacy in hospitalized elderly patients: Results from the REPOSI study. Eur J Intern Med. 2011; 22: 597-602.         [ Links ]

 

 

Correspondence:
Correo electrónico: mercedesgalvanbanqueri@gmail.com
(Mercedes Galván Banqueri).

Recibido el 9 de abril de 2014
Aceptado el 19 de junio de 2014.