|Year : 2016 | Volume
| Issue : 2 | Page : 876-880
The effect of diabetes with pharmacotherapy for breast cancer on care resource use
Toshiki Maeda1, Akira Babazono1, Takumi Nishi1, Hiroki Miyazaki1, Kazumitsu Tamaki2, Masashi Fujii3
1 Department of Healthcare Administration and Management, Graduate School of Healthcare Sciences, Kyushu University, Fukuoka, Japan
2 Division of Internal Medicine, Okinawa Chubu Hospital 281, Miyazato, Uruma, Okinawa, Japan
3 Department of Management, Okinawa Chubu Hospital 281, Miyazato, Uruma, Okinawa, Japan
|Date of Web Publication||25-Jul-2016|
Department of Healthcare Administration and Management, Graduate School of Healthcare Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582
Source of Support: None, Conflict of Interest: None
Introduction: The aim of this study was to quantify the effects of diabetes with pharmacotherapy-treated breast cancer on care resource use.
Materials and Methods: The study was designed as a single institutional retrospective cohort study using hospital administrative data. The subjects were 152 patients admitted to a hospital from 2008 to 2012 diagnosed with breast cancer, and who underwent pharmacotherapy. We identified diabetes group and nondiabetes group in addition to other variables and quantified the effects of diabetes with breast cancer patients undergoing pharmacotherapy on care resource use, using a multilevel linear regression model.
Results: Diabetes was significantly correlated to both longer length of stay (coefficient standard error: 0.75 [0.19], P < 0.001) and higher total hospital charge (0.72 [0.18], P < 0.001), controlled for age, pharmacotherapeutic agent, steroid use, admission route, procedures, and postpharmacotherapy events.
Conclusion: This study showed that diabetes itself is a risk factor for greater care resource use after controlling for confounding factors. Pharmacotherapy for breast cancer may influence poor glycemic control, thus leading to greater care resource use. Early detection and careful monitoring of diabetes are essential in malignancy to eliminate this burden on the health care system.
Keywords: Breast cancer, care resource use, diabetes mellitus, pharmacotherapy
|How to cite this article:|
Maeda T, Babazono A, Nishi T, Miyazaki H, Tamaki K, Fujii M. The effect of diabetes with pharmacotherapy for breast cancer on care resource use. J Can Res Ther 2016;12:876-80
|How to cite this URL:|
Maeda T, Babazono A, Nishi T, Miyazaki H, Tamaki K, Fujii M. The effect of diabetes with pharmacotherapy for breast cancer on care resource use. J Can Res Ther [serial online] 2016 [cited 2020 Aug 9];12:876-80. Available from: http://www.cancerjournal.net/text.asp?2016/12/2/876/172119
| > Introduction|| |
With an aging population, diabetes has been increasing in Japan. The number of diabetic, prediabetic, and total diabetic patients have been estimated at 9.5 million, 11 million, and 20.5 million, respectively. Thus, it has been suggested that possibly one-quarter of the Japanese population has diabetes or glucose intolerance. It has been reported that those with diabetes incur greater health care costs than those without diabetes; therefore, an increase in the number of diabetic patients will escalate health care costs in Japan.
In addition, the number of patients with malignancy has been increasing because of the aging population. In particular, the number of patients with breast cancer has increased remarkably, and breast cancer is, at present, the most prevalent cancer among women in Japan. It has been reported that hyperglycemia is a risk factor for breast cancer, for which the main therapies are surgery, pharmacotherapy, and radiotherapy. It is well-known that hyperglycemia in surgical patients delays wound healing , and increases the likelihood of postsurgical infection , and cardiovascular events., Some recent studies have reported that pharmacotherapy, including hormonal and chemotherapeutic agents for breast cancer, may influence poor glycemic control;, thus, pharmacotherapy for breast cancer with diabetes could be a further burden for the Japanese health care system. However, there have been few studies examining the effects on care resource use of diabetes with malignancy.
The aim of this study was to quantify the effects of diabetes with pharmacotherapy-treated breast cancer on care resource use.
| > Materials and Methods|| |
Definition of subjects
We used hospital administrative data, Diagnosis Procedure Combination (DPC) data from a single institute. This hospital is a 550-bed emergency center and is a core institute in the region. The DPC system is adopted mainly by acute health care facilities, and it covers more than 90% of acute in-patient care in Japan. The DPC data contain anonymous charge data, clinical data, and care process data, which can be analyzed to improve the quality of care among Japanese care facilities. We identified 163 patients >18-year-old admitted to Okinawa Chubu Hospital (OCH) from 2008 to 2012, falling within the C50 category of the International Classification of Diseases, 10th Revision (ICD 10) corresponding to breast cancer treated with pharmacotherapy. We excluded 11 patients who underwent surgery during their admission, leaving 152 patients as subjects. The definition of diabetes corresponded with those in categories E10–E14 of the ICD 10. As the design of this study was retrospective cohort and the data were hospital administrative data, we did not need to obtain informed consent according to Ethical Standards for Research in Japan. This project was approved by the Institutional Review Board of the hospital.
Definition of variables
We categorized the patients into ages <65 years; nonelderly group and ≥65 years; elderly group. Moreover, we identified the use of steroids and the admission route (planned or urgent admission). We classified pharmacotherapeutic agents into hormones, molecular-targeting drugs (MTDs), and chemotherapeutic agents, using Japanese pharmaceutical classification. We identified those who had also had a blood transfusion during admission that could be a confounding factor. In addition, we identified the patients who had had postpharmacotherapy infections, postpharmacotherapy complications, and in-hospital mortality, which also may have affected care resource use.
The definition of infection was where patients had been administered antibiotics subsequently to pharmacotherapy. The definition of complication was where patients had had sequelae documented in the DPC form  and corresponding to the Charlson comorbidity index.
The indices of care resource use were evaluated by total hospital charge (TC) and length of stay (LOS). TC (US$1= ¥100) included physician fees, instrumentation costs, costs of laboratory or imaging tests, and administration costs billed during admission. We used TC as a proxy for healthcare cost.
We performed Chi-square analysis for categorical variables, and the Kruskal–Wallis test for continuous variables, in the descriptive analysis. The distributions of both LOS and TC were right-skewed; therefore, these values were log-transformed in this model. We employed log LOS and log TC as dependent variables. Independent variables were diabetes group (reference: Nondiabetes group), age ≥65 years (reference: <65 years), hormones, MTDs (reference: Chemotherapeutic agents), steroid use, urgent admission (reference: Planned admission), blood transfusion, postpharmacotherapeutic infections, postpharmacotherapeutic complications, and in-hospital mortality. We then performed multilevel linear regression analyses using data year as the random intercept in addition to each dependent variable and other independent variables.
All statistical analyses were performed using PASW Statistics 18 (SPSS Inc., Chicago, IL, USA) and STATA Stata 13 (StataCorp, College Station, TX, USA). We used “mixed” for multilevel linear regression.
All reported P values were two-tailed, and the level of significance was set at 0.05.
| > Results|| |
[Table 1] shows patients' characteristics by the groups. The percentage of patients aged ≥65 years with diabetes group was 76.7% higher than the 63.9% of patients in that age group without diabetes, although there was no statistical significance (P = 0.186). Hormone therapy formed the bulk of pharmacotherapy, although there was no significant difference by type of pharmacotherapy (P = 0.608). The proportions of steroid use in comorbid diabetes and the noncomorbid diabetes groups were 30.0% and 40.2%, respectively. There was no significant difference (P = 0.305), although the comorbid diabetes group tended to use steroids less. The proportions of patients undergoing blood transfusions in the diabetes group and nondiabetes groups were 36.7% and 8.2%, respectively; this difference was significant (P < 0.001). There was a significant difference in the proportion of postpharmacotherapeutic infection: 16.7% in the comorbid diabetes group versus 5.7% in the noncomorbid diabetes group (P = 0.047). There was a significant difference between the proportion of postpharmacotherapy complications in the diabetes group (30.0%) and the nondiabetes group (13.1%) (P = 0.025). There was no significant difference in in-hospital mortality (P = 0.983). With regard to care resource use, LOS in-patients in the diabetes group were significantly longer than that of patients in nondiabetes group, and the medians (interquartile range) of LOS were 27.5 (26.0%) and 5 (14.3%), respectively (P < 0.001). The TC of patients in the diabetes group was significantly higher than that of patients in the nondiabetes group (P < 0.001). The medians (interquartile range) of TC (in dollars) in the diabetes and the nondiabetes groups were 15162.15 (15270.2) and 3526.5 (7560.8), respectively.
[Table 2] shows the results of multilevel linear regression analyses. Diabetes was significantly related to both longer LOS (coefficient standard error: 0.75 [0.19], P < 0.001) and higher TC (0.72 [0.18], P < 0.001), after controlling for age, pharmacotherapeutic agents, steroid use, admission route, procedures, and postpharmacotherapeutic events. Being aged ≥65 years was significantly correlated with both shorter LOS (−0.54 [0.16], P = 0.001) and lower TC (−0.55 [0.15], P < 0.001) than being aged <65 years. The use of MTDs was significantly related to shorter LOS (−0.92 [0.30], P = 0.002), whereas there was no significant relationship with TC. There was no significant relationship between hormone use and both LOS and TC. Steroid use was significantly related to shorter LOS (−0.39 [0.15], P = 0.010), whereas there was no significant relationship with TC. Urgent admission (0.51 [0.17], P = 0.002; reference planned admission) showed a significant relationship with longer LOS, whereas there was no significant relationship with TC. Blood transfusion was significantly related to both longer LOS (0.56 [0.23], P = 0.016) and higher TC (0.50 [0.23], P = 0.026). Postpharmacotherapeutic infection was significantly related to both longer LOS (0.98 [0.28], P < 0.001) and higher TC (0.83 [0.27], P = 0.002). Complications had no relationship with either LOS or TC. In-hospital mortality was significantly correlated with longer LOS (0.96 [0.29], P = 0.001) and higher TC (0.63 [0.28], P = 0.026).
| > Discussion|| |
This study demonstrated that diabetes with breast cancer treated with pharmacotherapy was significantly related to greater care resource use. Some studies have reported that diabetes is associated with higher health care spending. The American Diabetic Association reported that health care spending for a patient with diabetes was 2.3 times higher than that of the patient without diabetes. Patients with diabetes used more care resources because they were older and had more complications and greater comorbidity. However, this study showed that diabetes itself is a risk factor for greater care resource use after controlling for confounding factor.
There are specific problems encountered in the use of chemotherapeutic agents in diabetes. Chemotherapeutic regimens used in breast cancer treatment often induce nausea, vomiting, and loss of appetite. Therefore, steroid use in addition to a 5HT3 inhibitor for anti-emesis is recommended. Such nausea, vomiting, loss of appetite, and steroid use for anti-emesis causes instability of blood sugar that could lead to greater care resource use. In addition, diabetic patients often have lower physiologic reserves; therefore, poorer clearance of a drug might lead to a more severe adverse reaction than usual. In fact, some studies have reported that the combination of diabetes and chemotherapy results in a higher risk of diarrhea,, mucositis, laboratory data abnormality, and infection; these complications specific to chemotherapy might lead to greater care resource use. In addition, the preparation for these complications may also be related to greater care resource use.
Furthermore, it has been reported that abnormal glucose metabolism might lead to abnormal cellular growth and regulation; thus, hyperglycemia itself could be a risk factor for patients with malignancy. Moreover, although hormonal and chemotherapeutic agents can lead to menopause, it has been reported that menopause induces a metabolic abnormality similar to glucose intolerance., Therefore, poorer glucose control and hyperglycemia induced by cancer treatment might lead to greater care resource use.
This study demonstrated that the incidence of postpharmacotherapeutic infections and complications in the diabetes group was significantly higher than those in the nondiabetes group, by univariate analyses. However, the number of events was so small that we could not perform multivariate analysis to obtain more robust results. Further studies are needed to clarify the relationship between cancer patients with diabetes and postpharmacotherapeutic events.
The limitations of this study are as follows. The study used hospital administrative data; therefore, laboratory tests including fast blood sugar and HbA1c were not available. As a result, we could not consider control status of diabetes. In addition, other clinical informations such as body mass index, cancer stage, and the patients' socioeconomic status which also could affect the results were not used because of limitations of the information source. Furthermore, the subjects in this study were limited to hospital in-patients.
| > Conclusion|| |
This study showed that diabetes itself is a risk factor for greater care resource use, after controlling for confounding factor. Pharmacotherapy for breast cancer may influence poor glycemic control, possibly leading to greater care resource use. Early detection and careful monitoring of diabetes are essential in cases of malignancy to eliminate the burden to the health care system.
We would like to express our appreciation to Masashi Fujii, who had helped in data collection and provided valuable assistance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care 2013;36:1033-46.
Health Labor and Welfare Statistics Association. J Health Welf Stat 2013-2014;60:164.
Richardson LC, Pollack LA. Therapy insight: Influence of type 2 diabetes on the development, treatment and outcomes of cancer. Nat Clin Pract Oncol 2005;2:48-53.
Marhoffer W, Stein M, Maeser E, Federlin K. Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes. Diabetes Care 1992;15:256-60.
McMurry JF Jr. Wound healing with diabetes mellitus. Better glucose control for better wound healing in diabetes. Surg Clin North Am 1984;64:769-78.
Ramos M, Khalpey Z, Lipsitz S, Steinberg J, Panizales MT, Zinner M, et al.
Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg 2008;248:585-91.
Ambiru S, Kato A, Kimura F, Shimizu H, Yoshidome H, Otsuka M, et al.
Poor postoperative blood glucose control increases surgical site infections after surgery for hepato-biliary-pancreatic cancer: A prospective study in a high-volume institute in Japan. J Hosp Infect 2008;68:230-3.
Mangano DT, Browner WS, Hollenberg M, Li J, Tateo IM. Long-term cardiac prognosis following noncardiac surgery. The study of perioperative Ischemia Research Group. JAMA 1992;268:233-9.
Poldermans D, Boersma E, Bax JJ, Thomson IR, van de Ven LL, Blankensteijn JD, et al.
The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999;341:1789-94.
Ferrara A, Karter AJ, Ackerson LM, Liu JY, Selby JV. Northern California Kaiser Permanente Diabetes Registry. Hormone replacement therapy is associated with better glycemic control in women with type 2 diabetes: The Northern California Kaiser Permanente Diabetes Registry. Diabetes Care 2001;24:1144-50.
Lipscombe LL, Fischer HD, Yun L, Gruneir A, Austin P, Paszat L, et al.
Association between tamoxifen treatment and diabetes: A population-based study. Cancer 2012;118:2615-22.
Matsuda S, Ishikawa KB, Kuwabara K, Fujimori K, Fushimi K, Hashimoto H. Development and use of the Japanese case-mix system. Eurohealth 2009;14:25-30.
Matsuda S. Casemix as a tool for transparency of medical services. Jpn J Soc Secur Policy 2007;6:43-53.
Kubo T, Fujino Y, Murata A, Ichimiya Y, Kuwabara K, Fujimori K, et al.
Prevalence of type 2 diabetes among acute inpatients and its impact on length of hospital stay in Japan. Intern Med 2011;50:405-11.
Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 2004;57:1288-94.
Kuwabara K, Imanaka Y, Matsuda S, Fushimi K, Hashimoto H, Ishikawa KB, et al.
Impact of age and procedure on resource use for patients with ischemic heart disease. Health Policy 2008;85:196-206.
Meyerhardt JA, Heseltine D, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, et al.
Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803. J Clin Oncol 2006;24:3535-41.
Vokes EE, Ratain MJ, Mick R, McEvilly JM, Haraf D, Kozloff M, et al.
Cisplatin, fluorouracil, and leucovorin augmented by interferon alfa-2b in head and neck cancer: A clinical and pharmacologic analysis. J Clin Oncol 1993;11:360-8.
Weiser MA, Cabanillas ME, Konopleva M, Thomas DA, Pierce SA, Escalante CP, et al.
Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer 2004;100:1179-85.
Azim HA Jr, de Azambuja E, Colozza M, Bines J, Piccart MJ. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Ann Oncol 2011;22:1939-47.
[Table 1], [Table 2]