Pediatr Nephrol DOI 10.1007/s00467-014-2760-4
ORIGINAL ARTICLE
Implementation of clinical pharmacy services in a pediatric dialysis unit Radwa El Borolossy & Lamia El Wakeel & Ihab El Hakim & Osama Badary
Received: 4 October 2013 / Revised: 7 January 2014 / Accepted: 8 January 2014 # IPNA 2014
Abstract Background End-stage renal disease patients on hemodialysis are on complex drug regimens consisting of multiple medications, many of which are administered in several doses per day. Consequently, such patients are at high risk for developing drug therapy-related problems (DTRPs). The aim of this study was to detect DTRPs in children undergoing hemodialysis and to assess and evaluate the impact of interventions by the clinical pharmacist on the clinical outcome of children undergoing hemodialysis. Methods Fifty hemodialysis outpatients were randomly divided into two groups (25 each): the control group and the test group. During the 9-month study period, patients in the control group received the usual medical care, and those in the test group received pharmaceutical care 3 times weekly in addition to the usual medical care. Results After 9 months of pharmaceutical care implementation, the test group showed a significant decline in systolic and diastolic blood pressure (p=0.0001), serum phosphorus level (p=0.006) and parathyroid hormone level (p=0.001) versus their baseline values and versus the control. The serum Ca*P product level of the test group decreased (p=0.001) after intervention versus baseline. Serum calcium level significantly R. El Borolossy : L. El Wakeel (*) : O. Badary Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, 4 street 292, New Maadi, New Maadi, Cairo, Egypt e-mail: [email protected] R. El Borolossy e-mail: [email protected] O. Badary e-mail: [email protected] I. El Hakim Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt e-mail: [email protected]
increased in test group (p=0.02) and decreased in the control group (p = 0.001) versus the respective baseline values. Satisfaction with the renal treatment significantly improved in the test group (p=0.0001) versus the control group after 9 months of pharmaceutical care implementation based on Renal Treatment Satisfaction Questionnaire scores. Conclusions Pharmacist-initiated pharmaceutical care improved the satisfaction and biochemical findings of patients on hemodialysis. Keywords Hemodialysis . Drug therapy-related problems . Pharmaceutical care
Introduction End-stage renal disease (ESRD) is a serious public health problem in the pediatric population and is associated with excessive mortality and multiple complications, all of which severely impact patients’ quality of life [1]. In the past two decades the incidence of ESRD in children has steadily increased. Globally, the prevalence of ESRD in children is reported to be approximately 18.5–58.3 per million children [2]. The authors of the 2007 report of the European Renal Association/European Dialysis and Transplant (ESPN/EDTA) Registry concluded that the overall incidence rate of renal replacement therapy (RRT) among children under the age of 15 years was 6.5 per million in the age-related population and that the overall prevalence of pediatric RRT was 33.6 per million in this population [3]. ESRD patients usually require life-long health care and strict pharmaco-therapeutic monitoring [4]. Hemodialysis (HD) is often preferred for children aged >5 years. In contrast, peritoneal dialysis (PD) is offered to younger children, especially those aged 16 years. The Ethics Committee of the Faculty of Pharmacy, Ain Shams University approved the study protocol. The study was performed in accordance with the Declaration of Helsinki. Statistical analysis was performed using the SPSS statistical program (v.20; SPSS, Chicago, IL). Data were expressed as the median and interquartile range for quantitative non-parametric measures, as the mean and standard deviation (SD) for parametric data, and as numbers and percentage for categorical data. The paired student t test, unpaired student t test, Mann– Whitney test, Wilcoxon test, and chi-square test were used for data analysis. The probability of error of 0.05 was considered to be significant, and 0.001 to be highly significant.
Results At baseline, there was no significant difference between both patient groups in terms of demographics, clinical characteristics, laboratory and clinical parameters, or RTSQ score (Tables 1, 2). Serum phosphorus levels were significantly higher (p= 0.017) in the test group than in the control group at baseline.
Table 1 Baseline demographics and clinical characteristics of the study groups
After 9 months of implementation of pharmaceutical care service by the clinical pharmacist the following three parameters were assessed: DTRPs, laboratory and clinical measurements, and RTSQ score. Drug therapy-related problems Out of a total of 300 medication errors reported, 74 DTRPs were identified in the intervention group, which were classified into the following categories: drug interactions (40.5 %), non-compliance to medications (20.3 %), inadequate knowledge about drugs and diseases (13.5 %), improper drug selection (10.8 %), sub-therapeutic doses (10.8 %), and improper drug dosage forms (4.1 %). Based on these data, 0.329 DTRPs occurred per patient per month. Table 3 shows the DTRPs that were identified in the intervention group and the percentage of interventions accepted by the attending physician and implemented. Laboratory and clinical parameters Following implementation of the intervention, patients in the intervention (test) group had significantly lower systolic and diastolic BP levels (p=0.0001) and significantly lower serum phosphorus (p= 0.006) and PTH levels (p=0.001) than patients in the control group; they also had a significantly higher serum calcium level (p=0.011) Patients in the test group showed a highly significant decrease in systolic and diastolic BP (p=0.0001) and in serum Ca*P product (p=0.001), serum PTH (p= 0.001), and serum phosphorus (p=0.0011) levels and a significant increase in serum calcium (p=0.02) versus their baseline values (Table 4).
Baseline evaluation
Control group (n=25)
Intervention group (n=25)
p value
11.5±0.6 (8–18)
10.8±0.64 (7–17)
0.17
13 (52 %) 12 (48 %) 29.2±1.85
14 (56 %) 11 (44 %) 32.3±1.95
0.6 0.24
17 (68 %) 3 (12 %) 1 (4 %) 2(8 %) 2(8 %)
14 (56 %) 3 (12 %) 2 (8 %) 3(12 %) 3(12 %)
Comorbidities associated with renal disease: n (%) -Hypertension 20 (80 %) -Congestive heart failure 2 (8 %) -Heartburn 3 (12 %)
21 (84 %) 3 (12 %) 1 (4 %)
Demographic data Age, yearsa Sex, n (%) Male Female Weight, kg (mean±SD) Clinical characteristics Cause of ESRD, n (%) -Nephritic syndrome -Chronic tubulointersitial nephritis -Obstructive uropathy -Polycystic kidney -Vesicouretric reflux n, Number of patients; ESRD, end-stage renal disease a
Data presented as the mean ± standard deviation (SD) with the range in parenthesis
0.83
0.76
Pediatr Nephrol Table 2 Baseline laboratory and clinical parameters of the study groups Baseline evaluation
Control group (n = 25)
Intervention group (n = 25)
p value
Systolic BP (mmHg) Diastolic BP (mmHg) PTH (μg/dl) Calcium (mg/dl)
168.08±6.52 90.96±6.61 245±394.75 9.1±2.025
166.8±8.94 91.2±6.17 575±855.5 8.6±2.05
0.254 0.79 0.107 0.667
Phosphorus (mg/dl) Ca*P(mg2/dl2) RTSQ (total score)
5.65±2.83 48.65±30.55 24±5
6.8±2.4 43.24±24.65 24±3
0.017 0.271 0.604
BP, Blood pressure; PTH, parathyroid hormone; Ca*P, calcium–phosphorus product; RTSQ, Renal Treatment Satisfaction Questionnaire Data for all parameters are presented as the median ± IQR
In contrast, at the end of the 9-month study period, patients in the control group showed a significant increase in their phosphorus (p=0.0012) and PTH serum levels (p=0.001) and a significant decrease in calcium serum levels (p=0.001) as compared to their baseline levels. No change was evident in either the systolic and diastolic BP or the Ca*P product level as compared to their baseline values (Table 4). Renal Treatment Satisfaction Questionnaire The RTSQ score significantly improved in the test group (p=0.0001) versus the control after 9 months of pharmaceutical care implementation (Table 4; Fig. 1).
Discussion Several studies have demonstrated that hemodialysis patients are at a high risk for DTRPs and that despite all interventions
DTRPs continue to exist at a high frequency in these medically complex patients [12–14]. In our study, 74 DTRPs were identified in 25 patients over the 9-month study period, including drug interactions, non-compliance to medications, inadequate knowledge about drugs and disease, improper drug selection, sub-therapeutic doses, and improper use of drug dosage forms. Kaplan and colleagues [12] conducted a study aimed at characterizing DTRPs in chronic HD patients and identified a total of 216 potential DTRPs in 30 hemodialysis patients over a 2-month period. These authors identified the following problems: drug underutilization, drug–drug interactions, drug required to be added to the treatment regimen, and drug required to be deleted from the treatment regimen. In this study, 224 comments/recommendations on drug therapy were made by the pharmacist, of which 76 % were accepted. These interventions included alteration of dosage, adding/ discontinuing/changing medications, and altering dosage form [12]. In a similar study, Tang and colleagues [13] identified 205 DTRPs in 55 patients undergoing HD, including drug overdose, drug requiring therapeutic drug monitoring, drug–drug interactions. A total of 205 interventions were recorded over a 6-month time frame, of which the medical team accepted 91.7 % [13]. Grabe and associates [14] discussed DTRPs that were evaluated in a single HD unit. Over the course of 1 month, these authors identified 126 DTRPs in 49 patients undergoing HD, with 102 recommendations (81 %) being accepted by the prescriber [14]. Comparison of the results of our study with those of these three studies in terms of the occurrence of DTRPs presenting as a problem per patient per month shows that there were 0.329 problems per patient per month among the patients in our intervention group; in comparison, Tang et al. reported 0.62 [13], Grabe et al. reported 2.57 [14], and Kaplan et al. reported 3.6 problems per patient per month [12]. The
Table 3 Drug therapy-related problems in the intervention group and the percentage of interventions accepted by the attending physician and implemented Drug therapy related problems
Interventions
Percentage of acceptance
Moderate drug interactions in the prescribed medications (n=30) Patient non-compliance to the treatment (n=15)
Patients were monitored and educated to avoid any hazards to the patient condition Patients were educated about the appropriate dose, frequency, and importance of continued drug therapy Patients were informed about the role of each drug in the treatment of ESRD The physicians were informed about the appropriate dosage form, and dosage form was changed The physicians were informed about the appropriate strength, and the strength was changed The physicians were informed about the appropriate medication, and the medication was changed
100 %
Inadequate knowledge about the role of each drug in the treatment of ESRD (n=10) Inappropriate dosage form of oral digoxin (n=3) Inappropriate dose of calcium supplement (n=8) Inappropriate medications to treat high phosphorus levels (n=8) ESRD, end stage renal disease
n, Number of drug therapy-related problems (DTRPs) in the test group
98 % 96 % 100 % 95 % 100 %
Pediatr Nephrol Table 4 Laboratory and clinical parameters of both groups before and after the intervention Laboratory and clinical parameters
Systolic BP(mmHg) Diastolic BP (mmHg) Serum calcium (mg/dl) Serum phosphorus (mg/dl) Serum PTH (mcg/dl) Serum Ca*P(mg2/dl2) RTSQ (total score)
Control group
Intervention group
Before
After
p value
Before
After
p value
168.08±6.52 90.96±6.16 9.1±2.025 5.65±2.83
166.5±6.86 91.96±6.3 7.3±2.575 6.75±2.85
0.173 0.480 0.001** 0.0012**
166.8±8.94 91.2 ±6.17 8.6±2.05 6.8±2.4
135.1±11.7 78.92±5.17 9.1±1.85 5.2±1.5
0.0001** 0.0001** 0.02* 0.0011**
245±394.75 47.45±27.9 24±5
649±652.5 48.65±30.5 25±4
0.001** 0.19 0.676
575±855.5 57.3±37.9 24±3
200±301 43.2±24.6 56±1
0.001** 0.001** 0.0001**
BP, blood pressure; PT4, parathyroid hormone; Ca*P, Calcium-phosphorus product; RTSQ, Renal Treatment Satisfaction Questionaire *p ≤ 0.05 is considered to be significant; **p≤0.001 is considered to be highly significant n, Number of patients Data are presented as the median ± IQR
discrepancy in the occurrence rate of DTRPs in our study and those in these other three studies could be attributed to the difference in age and number of patients, types and numbers of medications prescribed, types and number of interventions, and differences in study design. All of the above-mentioned studies indicate the potential risks of DTRPs on HD patients and the mandatory need for endorsement of clinical pharmacy services in HD units to help identify and reduce DTRPs. Our result show a significant decline in systolic and diastolic BP in patients in the intervention group, who received the pharmaceutical care service, compared to the control patients. These results are in accordance with those of Chisholm et al. [16] who reported a significant reduction in both mean systolic and diastolic blood pressure in the test group after 12
Fig. 1 Boxplot of median total score of the Renal Treatment Satisfaction Questionnaire (RTSQ) in the control group and test groups at baseline and at the end of the study
months of implementation of clinical pharmacist interventions. Leung et al. [17] also reported a significant reduction in both mean systolic and diastolic blood pressure in patients who had received pharmaceutical care for 2 years. In the current study, serum phosphorus levels significantly declined in the test group after the interventions were implemented, while the control group showed a significant increase in phosphorus levels. Yokum et al. [18] observed findings similar to ours, reporting a significant decrease in mean serum phosphorus levels 4 months after the implementation of clinical pharmacist interventions [18]. Regarding PTH level, at baseline there was no significant difference in serum PTH level between the intervention group and the control group. We attributed this to the extremely wide distribution of the values in the control group (SD 394.75 pg/ ml). After interventions had been implemented in the test group there was a significant decrease in serum PTH versus the control. The serum Ca*P levels in the intervention group showed a significant decline from baseline following the implementation of the intervention; in contrast, those of the control group did not fall. Our results are in accordance with those of Yokum et al. [18] who reported a significant reduction in the mean serum Ca*P product level 4 months after implementation of the pharmaceutical care service. Assessment of patient satisfaction showed a significantly improved satisfaction score in the intervention group versus the control group. The improvement shown in the biochemical parameters and satisfaction score can be attributed to the intensified three times weekly clinical pharmacist interventions and patient monitoring. These interventions led to a reduction in drug interactions, an appropriate use of medications, a strict drug monitoring for a better use of the drug dosage form, accurate dosage adjustments, and an improvement in patients
Pediatr Nephrol
compliance to medication. The positive impact of the clinical pharmacist’s interventions was quite evident in our study due to the general lack of clinical pharmacy services in HD units in Egypt. Consequently, most the recommended interventions were valuable, needed, and in the best interest of the patients; the result was improved biochemical parameters, compliance, and satisfaction with treatment. The limitations to our study include the initial resistance of the patients and caregivers to the educational services offered, which initially lead to a decreased compliance and mandated a more through and intense educational approach. In addition, the low and variable socioeconomic status of the patients also mandated an intensive and tailored educational approach to improve compliance.
Conclusions The presence of the clinical pharmacist as an integral member of the multidisciplinary chronic kidney disease team of physicians, nurses, and dieticians is highly recommended for the implementation of pharmaceutical care services which inevitably can lead to pharmacotherapy optimization, prevention of drug hazards, and improvement in patients’ clinical outcome and overall quality of life. Financial support None. Conflict of interest None
References 1. Harambat J, Stralen KV, Kim JJ, Tizard EJ (2012) Epidemiology of chronic kidney disease in children. Pediatr Nephrol 27:363–373 2. U.S. Renal Data System (USRDS) (2012) 2012 Annual Data Report (vol. 1: Atlas of chronic kidney disease in the United States; vol. 2: atlas of end-stage renal disease in the United States). USRDS Coordinating Center, Minneapolis
3. Stralen KJV, Tizard EJ, Verrina E, Schaefer F (2010) Demographics of pediatric renal replacement therapy in Europe: 2007 annual report of the ESPN/ERA-EDTA registry. Pediatr Nephrol 25:1379–1382 4. Shroff R, Ledermann S (2009) Long-term outcome of chronic dialysis in children. Pediatr Nephrol 24:463–474 5. Fischbach M, Edefonti A, Schroder C, Watson A (2005) Hemodialysis in children: General practical guidelines. Pediatr Nephrol 20:1054–1066 6. Sathvik BS, Mangasuli S, Narahari MG, Gurudev KC, Parthasarathi G (2007) Medication knowledge of hemodialysis patients and influence of clinical pharmacist-provided education on their knowledge. Indian J Med Sci 69:232–240 7. Ibrahim N, Wang I, Patey I, Tomlin S, Sinho M, Jani Y (2013) Drug– related problems in children with chronic kidney disease. Pediatr Nephrol 28:25–31 8. Cipolle RJ, Strand LM, Morley PC (1998) Pharmaceutical care practice, 2nd edn. McGraw Hill, New York 9. Joy MS, Dehort RM, Gilmartin C, Hachey DM, Hudson JQ, Pruchnicki M, Dirno P, Grabe DW, Sasean J, Zillich AJ (2010) Clinical pharmacist as multidisciplinary health care providers in the management of chronic kidney disease. Am J Kidney Dis 45:1105– 1118 10. Manley HJ, Drayer DK, Muther RS (2003) Medication-related problem type and appearance rate in ambulatory hemodialysis patients. BMC Nephrol 4:10–15 11. Gunar S, Rosa LG (2011) Clinical pharmacy activities in chronic kidney disease and end stage renal disease patients: a systemic literature review. BMC Nephrol 12:34–40 12. Kaplan B, Mason NA, Shimp LA, Ascione FJ (1994) Chronic haemodialysis patients. Part II: reducing drug related problems through application of the focused drug therapy review program. Ann Pharmacother 28:320–324 13. Tang I, Varhnos D, Hatoum H, Lau A (1993) Effectiveness of clinical pharmacist interventions in a haemodialysis unit. Clin Ther 15:459–464 14. Grabe DW, Bailie GR, Eisele G (1997) Evaluation of drug related problems in an outpatient haemodialysis unit and the impact of a clinical pharmacist. Clin Nephrol 47:117–121 15. Barendse SM, Speight J, Bradely C (2005) The renal treatment satisfaction questionnaire (RTSQ): a measure of satisfaction with treatment for chronic kidney failure. Am J Kidney Dis 45:572–579 16. Chisholm MA, Mulloy LL, Jagadeesan M (2002) Effect of clinical pharmacy services on the blood pressure of African American renal transplant patients. Ethn Dis 12:392–397 17. Leung WY, So WY, Tong PC (2005) Effect of structured care by a pharmacist diabetes specialist team in patients with type 2 diabetic nephropathy. Am J Med 118:1414–1418 18. Yokum D, Glass G, Cheung CF (2008) Evaluation of phosphate management protocol to achieve optimum serum phosphate levels in hemodialysis patients. J Ren Nutr 18:521–529
ORIGINAL ARTICLE
Implementation of clinical pharmacy services in a pediatric dialysis unit Radwa El Borolossy & Lamia El Wakeel & Ihab El Hakim & Osama Badary
Received: 4 October 2013 / Revised: 7 January 2014 / Accepted: 8 January 2014 # IPNA 2014
Abstract Background End-stage renal disease patients on hemodialysis are on complex drug regimens consisting of multiple medications, many of which are administered in several doses per day. Consequently, such patients are at high risk for developing drug therapy-related problems (DTRPs). The aim of this study was to detect DTRPs in children undergoing hemodialysis and to assess and evaluate the impact of interventions by the clinical pharmacist on the clinical outcome of children undergoing hemodialysis. Methods Fifty hemodialysis outpatients were randomly divided into two groups (25 each): the control group and the test group. During the 9-month study period, patients in the control group received the usual medical care, and those in the test group received pharmaceutical care 3 times weekly in addition to the usual medical care. Results After 9 months of pharmaceutical care implementation, the test group showed a significant decline in systolic and diastolic blood pressure (p=0.0001), serum phosphorus level (p=0.006) and parathyroid hormone level (p=0.001) versus their baseline values and versus the control. The serum Ca*P product level of the test group decreased (p=0.001) after intervention versus baseline. Serum calcium level significantly R. El Borolossy : L. El Wakeel (*) : O. Badary Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, 4 street 292, New Maadi, New Maadi, Cairo, Egypt e-mail: [email protected] R. El Borolossy e-mail: [email protected] O. Badary e-mail: [email protected] I. El Hakim Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt e-mail: [email protected]
increased in test group (p=0.02) and decreased in the control group (p = 0.001) versus the respective baseline values. Satisfaction with the renal treatment significantly improved in the test group (p=0.0001) versus the control group after 9 months of pharmaceutical care implementation based on Renal Treatment Satisfaction Questionnaire scores. Conclusions Pharmacist-initiated pharmaceutical care improved the satisfaction and biochemical findings of patients on hemodialysis. Keywords Hemodialysis . Drug therapy-related problems . Pharmaceutical care
Introduction End-stage renal disease (ESRD) is a serious public health problem in the pediatric population and is associated with excessive mortality and multiple complications, all of which severely impact patients’ quality of life [1]. In the past two decades the incidence of ESRD in children has steadily increased. Globally, the prevalence of ESRD in children is reported to be approximately 18.5–58.3 per million children [2]. The authors of the 2007 report of the European Renal Association/European Dialysis and Transplant (ESPN/EDTA) Registry concluded that the overall incidence rate of renal replacement therapy (RRT) among children under the age of 15 years was 6.5 per million in the age-related population and that the overall prevalence of pediatric RRT was 33.6 per million in this population [3]. ESRD patients usually require life-long health care and strict pharmaco-therapeutic monitoring [4]. Hemodialysis (HD) is often preferred for children aged >5 years. In contrast, peritoneal dialysis (PD) is offered to younger children, especially those aged 16 years. The Ethics Committee of the Faculty of Pharmacy, Ain Shams University approved the study protocol. The study was performed in accordance with the Declaration of Helsinki. Statistical analysis was performed using the SPSS statistical program (v.20; SPSS, Chicago, IL). Data were expressed as the median and interquartile range for quantitative non-parametric measures, as the mean and standard deviation (SD) for parametric data, and as numbers and percentage for categorical data. The paired student t test, unpaired student t test, Mann– Whitney test, Wilcoxon test, and chi-square test were used for data analysis. The probability of error of 0.05 was considered to be significant, and 0.001 to be highly significant.
Results At baseline, there was no significant difference between both patient groups in terms of demographics, clinical characteristics, laboratory and clinical parameters, or RTSQ score (Tables 1, 2). Serum phosphorus levels were significantly higher (p= 0.017) in the test group than in the control group at baseline.
Table 1 Baseline demographics and clinical characteristics of the study groups
After 9 months of implementation of pharmaceutical care service by the clinical pharmacist the following three parameters were assessed: DTRPs, laboratory and clinical measurements, and RTSQ score. Drug therapy-related problems Out of a total of 300 medication errors reported, 74 DTRPs were identified in the intervention group, which were classified into the following categories: drug interactions (40.5 %), non-compliance to medications (20.3 %), inadequate knowledge about drugs and diseases (13.5 %), improper drug selection (10.8 %), sub-therapeutic doses (10.8 %), and improper drug dosage forms (4.1 %). Based on these data, 0.329 DTRPs occurred per patient per month. Table 3 shows the DTRPs that were identified in the intervention group and the percentage of interventions accepted by the attending physician and implemented. Laboratory and clinical parameters Following implementation of the intervention, patients in the intervention (test) group had significantly lower systolic and diastolic BP levels (p=0.0001) and significantly lower serum phosphorus (p= 0.006) and PTH levels (p=0.001) than patients in the control group; they also had a significantly higher serum calcium level (p=0.011) Patients in the test group showed a highly significant decrease in systolic and diastolic BP (p=0.0001) and in serum Ca*P product (p=0.001), serum PTH (p= 0.001), and serum phosphorus (p=0.0011) levels and a significant increase in serum calcium (p=0.02) versus their baseline values (Table 4).
Baseline evaluation
Control group (n=25)
Intervention group (n=25)
p value
11.5±0.6 (8–18)
10.8±0.64 (7–17)
0.17
13 (52 %) 12 (48 %) 29.2±1.85
14 (56 %) 11 (44 %) 32.3±1.95
0.6 0.24
17 (68 %) 3 (12 %) 1 (4 %) 2(8 %) 2(8 %)
14 (56 %) 3 (12 %) 2 (8 %) 3(12 %) 3(12 %)
Comorbidities associated with renal disease: n (%) -Hypertension 20 (80 %) -Congestive heart failure 2 (8 %) -Heartburn 3 (12 %)
21 (84 %) 3 (12 %) 1 (4 %)
Demographic data Age, yearsa Sex, n (%) Male Female Weight, kg (mean±SD) Clinical characteristics Cause of ESRD, n (%) -Nephritic syndrome -Chronic tubulointersitial nephritis -Obstructive uropathy -Polycystic kidney -Vesicouretric reflux n, Number of patients; ESRD, end-stage renal disease a
Data presented as the mean ± standard deviation (SD) with the range in parenthesis
0.83
0.76
Pediatr Nephrol Table 2 Baseline laboratory and clinical parameters of the study groups Baseline evaluation
Control group (n = 25)
Intervention group (n = 25)
p value
Systolic BP (mmHg) Diastolic BP (mmHg) PTH (μg/dl) Calcium (mg/dl)
168.08±6.52 90.96±6.61 245±394.75 9.1±2.025
166.8±8.94 91.2±6.17 575±855.5 8.6±2.05
0.254 0.79 0.107 0.667
Phosphorus (mg/dl) Ca*P(mg2/dl2) RTSQ (total score)
5.65±2.83 48.65±30.55 24±5
6.8±2.4 43.24±24.65 24±3
0.017 0.271 0.604
BP, Blood pressure; PTH, parathyroid hormone; Ca*P, calcium–phosphorus product; RTSQ, Renal Treatment Satisfaction Questionnaire Data for all parameters are presented as the median ± IQR
In contrast, at the end of the 9-month study period, patients in the control group showed a significant increase in their phosphorus (p=0.0012) and PTH serum levels (p=0.001) and a significant decrease in calcium serum levels (p=0.001) as compared to their baseline levels. No change was evident in either the systolic and diastolic BP or the Ca*P product level as compared to their baseline values (Table 4). Renal Treatment Satisfaction Questionnaire The RTSQ score significantly improved in the test group (p=0.0001) versus the control after 9 months of pharmaceutical care implementation (Table 4; Fig. 1).
Discussion Several studies have demonstrated that hemodialysis patients are at a high risk for DTRPs and that despite all interventions
DTRPs continue to exist at a high frequency in these medically complex patients [12–14]. In our study, 74 DTRPs were identified in 25 patients over the 9-month study period, including drug interactions, non-compliance to medications, inadequate knowledge about drugs and disease, improper drug selection, sub-therapeutic doses, and improper use of drug dosage forms. Kaplan and colleagues [12] conducted a study aimed at characterizing DTRPs in chronic HD patients and identified a total of 216 potential DTRPs in 30 hemodialysis patients over a 2-month period. These authors identified the following problems: drug underutilization, drug–drug interactions, drug required to be added to the treatment regimen, and drug required to be deleted from the treatment regimen. In this study, 224 comments/recommendations on drug therapy were made by the pharmacist, of which 76 % were accepted. These interventions included alteration of dosage, adding/ discontinuing/changing medications, and altering dosage form [12]. In a similar study, Tang and colleagues [13] identified 205 DTRPs in 55 patients undergoing HD, including drug overdose, drug requiring therapeutic drug monitoring, drug–drug interactions. A total of 205 interventions were recorded over a 6-month time frame, of which the medical team accepted 91.7 % [13]. Grabe and associates [14] discussed DTRPs that were evaluated in a single HD unit. Over the course of 1 month, these authors identified 126 DTRPs in 49 patients undergoing HD, with 102 recommendations (81 %) being accepted by the prescriber [14]. Comparison of the results of our study with those of these three studies in terms of the occurrence of DTRPs presenting as a problem per patient per month shows that there were 0.329 problems per patient per month among the patients in our intervention group; in comparison, Tang et al. reported 0.62 [13], Grabe et al. reported 2.57 [14], and Kaplan et al. reported 3.6 problems per patient per month [12]. The
Table 3 Drug therapy-related problems in the intervention group and the percentage of interventions accepted by the attending physician and implemented Drug therapy related problems
Interventions
Percentage of acceptance
Moderate drug interactions in the prescribed medications (n=30) Patient non-compliance to the treatment (n=15)
Patients were monitored and educated to avoid any hazards to the patient condition Patients were educated about the appropriate dose, frequency, and importance of continued drug therapy Patients were informed about the role of each drug in the treatment of ESRD The physicians were informed about the appropriate dosage form, and dosage form was changed The physicians were informed about the appropriate strength, and the strength was changed The physicians were informed about the appropriate medication, and the medication was changed
100 %
Inadequate knowledge about the role of each drug in the treatment of ESRD (n=10) Inappropriate dosage form of oral digoxin (n=3) Inappropriate dose of calcium supplement (n=8) Inappropriate medications to treat high phosphorus levels (n=8) ESRD, end stage renal disease
n, Number of drug therapy-related problems (DTRPs) in the test group
98 % 96 % 100 % 95 % 100 %
Pediatr Nephrol Table 4 Laboratory and clinical parameters of both groups before and after the intervention Laboratory and clinical parameters
Systolic BP(mmHg) Diastolic BP (mmHg) Serum calcium (mg/dl) Serum phosphorus (mg/dl) Serum PTH (mcg/dl) Serum Ca*P(mg2/dl2) RTSQ (total score)
Control group
Intervention group
Before
After
p value
Before
After
p value
168.08±6.52 90.96±6.16 9.1±2.025 5.65±2.83
166.5±6.86 91.96±6.3 7.3±2.575 6.75±2.85
0.173 0.480 0.001** 0.0012**
166.8±8.94 91.2 ±6.17 8.6±2.05 6.8±2.4
135.1±11.7 78.92±5.17 9.1±1.85 5.2±1.5
0.0001** 0.0001** 0.02* 0.0011**
245±394.75 47.45±27.9 24±5
649±652.5 48.65±30.5 25±4
0.001** 0.19 0.676
575±855.5 57.3±37.9 24±3
200±301 43.2±24.6 56±1
0.001** 0.001** 0.0001**
BP, blood pressure; PT4, parathyroid hormone; Ca*P, Calcium-phosphorus product; RTSQ, Renal Treatment Satisfaction Questionaire *p ≤ 0.05 is considered to be significant; **p≤0.001 is considered to be highly significant n, Number of patients Data are presented as the median ± IQR
discrepancy in the occurrence rate of DTRPs in our study and those in these other three studies could be attributed to the difference in age and number of patients, types and numbers of medications prescribed, types and number of interventions, and differences in study design. All of the above-mentioned studies indicate the potential risks of DTRPs on HD patients and the mandatory need for endorsement of clinical pharmacy services in HD units to help identify and reduce DTRPs. Our result show a significant decline in systolic and diastolic BP in patients in the intervention group, who received the pharmaceutical care service, compared to the control patients. These results are in accordance with those of Chisholm et al. [16] who reported a significant reduction in both mean systolic and diastolic blood pressure in the test group after 12
Fig. 1 Boxplot of median total score of the Renal Treatment Satisfaction Questionnaire (RTSQ) in the control group and test groups at baseline and at the end of the study
months of implementation of clinical pharmacist interventions. Leung et al. [17] also reported a significant reduction in both mean systolic and diastolic blood pressure in patients who had received pharmaceutical care for 2 years. In the current study, serum phosphorus levels significantly declined in the test group after the interventions were implemented, while the control group showed a significant increase in phosphorus levels. Yokum et al. [18] observed findings similar to ours, reporting a significant decrease in mean serum phosphorus levels 4 months after the implementation of clinical pharmacist interventions [18]. Regarding PTH level, at baseline there was no significant difference in serum PTH level between the intervention group and the control group. We attributed this to the extremely wide distribution of the values in the control group (SD 394.75 pg/ ml). After interventions had been implemented in the test group there was a significant decrease in serum PTH versus the control. The serum Ca*P levels in the intervention group showed a significant decline from baseline following the implementation of the intervention; in contrast, those of the control group did not fall. Our results are in accordance with those of Yokum et al. [18] who reported a significant reduction in the mean serum Ca*P product level 4 months after implementation of the pharmaceutical care service. Assessment of patient satisfaction showed a significantly improved satisfaction score in the intervention group versus the control group. The improvement shown in the biochemical parameters and satisfaction score can be attributed to the intensified three times weekly clinical pharmacist interventions and patient monitoring. These interventions led to a reduction in drug interactions, an appropriate use of medications, a strict drug monitoring for a better use of the drug dosage form, accurate dosage adjustments, and an improvement in patients
Pediatr Nephrol
compliance to medication. The positive impact of the clinical pharmacist’s interventions was quite evident in our study due to the general lack of clinical pharmacy services in HD units in Egypt. Consequently, most the recommended interventions were valuable, needed, and in the best interest of the patients; the result was improved biochemical parameters, compliance, and satisfaction with treatment. The limitations to our study include the initial resistance of the patients and caregivers to the educational services offered, which initially lead to a decreased compliance and mandated a more through and intense educational approach. In addition, the low and variable socioeconomic status of the patients also mandated an intensive and tailored educational approach to improve compliance.
Conclusions The presence of the clinical pharmacist as an integral member of the multidisciplinary chronic kidney disease team of physicians, nurses, and dieticians is highly recommended for the implementation of pharmaceutical care services which inevitably can lead to pharmacotherapy optimization, prevention of drug hazards, and improvement in patients’ clinical outcome and overall quality of life. Financial support None. Conflict of interest None
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