||Pharmaceutical care and detection of severe iatrogenic hypoglycemia risk in elderly patients with diabetes mellitus
||Institute of Clinical Pharmacy and Pharmaceutical sciences
Sequence Symmetry Analysis
老年糖尿病的高盛行率已經是全球性的問題，人口老化更是驅動老年糖尿病患急速上升的原因之一。許多研究顯示藥事照護可提供許多的益處，而藥物引起的低血糖更是對於老年糖尿病患照護上最需擔心的事情。對稱分析法(sequence symmetry analysis)是一種用於風險訊號偵測的案例式與個體內比較之分析方法，應可用於有效率地偵測引起低血糖的高風險藥物。
本研究以隨機對照試驗(randomized controlled trial) 探討藥事照護改善老年糖尿病患醣化血色素(HbA1c)的實證結果及對於醫療花費的負擔評估。此外，對於降血糖藥物(antidiabetic drugs)和老年糖尿病患常用非降血糖藥物(non-antidiabetic drugs)引起低血糖的風險，本研究運用對稱分析法予以偵測，並使用巢式病例對照研究來驗證對稱分析法的結果。
Background: Diabetes in older adults was a critical health problem regarding global diabetes prevalence and the aging of the overall population is a significant driver of the diabetes epidemic. Pharmaceutical care in diabetes management has shown benefits in this frail group. Meanwhile, drug-induced hypoglycemia was the most concerned complication in diabetes care of elderly patients. Sequence symmetry analysis (SSA) is a case-only and within individual comparisons tool for signal detection. Drugs with high hypoglycemia risk could be detected by this method efficiently.
Objective: This study aimed to investigate the effect of pharmaceutical care by conducting a randomized controlled trial to assess improvement of HbA1c levels and the change of medical expenses. Meanwhile, to assess hypoglycemia risk of drugs commonly used in elderly diabetic patients a sequence symmetry analysis was employed to detect the high risk non-antidiabetic drugs (hrNADDs), which were further verified by nested case control study.
Methods: We conducted a randomized controlled trial from August 2011 to February 2012 in Nantou Hospital, Ministry of Health and Welfare, Taiwan, R.O.C. 100 patients with type 2 diabetes with poor glycemic control (HbA1c levels of ≥9.0%) and aged ≥65 years were involved over 6 months. Participants were randomly assigned to a standard-care (control, n = 50) or pharmaceutical-care (intervention, n = 50) group. Pharmaceutical care was provided by a certified diabetes-educator pharmacist and HbA1c levels improvement and medical expenses were evaluated. SSA and nested case control study were conducted using Longitudinal Health Insurance Databases of diabetes datasets established by the NHRI from 1999 to 2012. To evaluate the clinically important hypoglycemia risk after exposure antidiabetic drugs (ADDs) or high risk non-antidiabetic drugs (hrNADDs) in elderly diabetic patients.
Results: Randomized controlled trial demonstrated that a pharmacist intervention program providing pharmaceutical care services to poorly-controlled, ambulatory elderly patients with DM could improve HbA1c levels, while medical expenses were not significantly increased. Drug-induced hypoglycemia in elderly diabetic patients could also be well-evaluated by SSA. Our study results indicated that severe hypoglycemia was observed in one antipyretic (acetylsalicylic acid), two -blockers (propranolol and labetalol), two antibacterials (sulfamethoxazole/trimethoprim and chloramphenicol), two tetracyclines (doxycycline and minocycline), two antifungals (ketoconazole and fluconazole), three lipid-lowering drugs (bezafibrate, gemfibrozil and fenofibrate) and two antidepressants (trazodone and venlafaxine) in elderly diabetic patients. The nested case control study provided evidence that exposure to fibrates (fenofibrate, bezafibrate, and gemfibrozil) was found to be associated with higher odds of hypoglycemia.
Conclusion: Including pharmacists in multidisciplinary diabetes care teams and provide pharmaceutical care for elderly diabetic patients would be helpful in poorly-controlled, ambulatory elderly patients with DM to improve control of HbA1c levels. Drug-induced hypoglycemia was detected clinical significantly in 7 ADDs and 14 hrNADDs by SSA. In population-based nested case-control study, fibrates were significantly associated with hypoglycemia. Prescribers should be cautious as severe hypoglycemia may occur after initiation of these high risk drugs to elderly diabetic patients.
CHAPTER ONE-OVERVIEW 1
CHAPTER TWO- Pharmaceutical care in elderly diabetic patients 4
Section 1 – Background 4
Section 2 – Methods 5
Section 3 – Results 9
Section 4 – Discussion 11
Section 5 – Conclusion 14
CHAPTER THREE- Detection of severe iatrogenic hypoglycemia risk using sequence symmetry analysis 15
Section 1 – Background 15
Section 2 – Methods 17
Section 3 – Results 23
Section 4 – Discussion 25
Section 5 – Conclusion 35
CHAPTER FOUR- Risk of hypoglycemia in elderly patients with diabetes mellitus treated with fibrates: a Nested Case-Control Study 36
Section 1 – Background 36
Section 2 – Methods 37
Section 3 – Results 40
Section 4 – Discussion 41
Section 5 – Conclusion 44
CHAPTER FIVE - OVERALL CONCLUSION 45
TABLES AND FIGURES 57
Table 1. Baseline characteristics of patients 57
Table 2. Comparison of HbA1c levels and payment points before and after intervention 58
Table 3. Comparison of medical expense (NTD) and pharmaceutical care cost before and after intervention 59
Table 4. Costs of pharmaceutical care 60
Table 5. Antidiabetic drugs (ADDs) for Sequence Symmetry Analysis (SSA) 61
Table 6. High risk non-antidiabetic drugs (hrNADDs) for Sequence Symmetry Analysis (SSA) 62
Table 7. SSA results of antidiabetic drugs (ADDs) 64
Table 8. SSA results of high risk non-antidiabetic drugs (hrNADDs) 65
Table 9. Characteristics of Patients with Hypoglycemia Compared with Controls 69
Table 10. Matched Conditional Logistic Regression Analysis of Hypoglycemic Risk in Case Patients versus Controls 70
Figure 1. Study flowchart of randomized controlled trial 71
Figure 2. Flowchart of study cohort selection in SSA 72
Figure 3. SSA results of OHA 73
Figure 4. A study flow diagram for the nested case control study 74
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