Cost associated with hospitalization of non-adherent type 2 diabetes patients in a tertiary healthcare facility in Ibadan, Nigeria

Purpose: To estimate the cost of hospitalization associated with medication non-adherence among type 2 diabetes mellitus (T2DM) patients in a tertiary healthcare facility in Nigeria. Methods: Three hundred and fifty-four (354) medical records of T2DM patients admitted into the medical wards from 2013 to 2015 were used for the study. Medical records with history of medication non-adherence (MNA) prior to hospitalization as indicated by physicians were included in the study. Direct medical costs associated with the management of the patients during hospitalization were measured using out-of-pocket payer perspective. Pearson product moment correlation coefficient was used to determine the relationship between the variables, with p < 0.05 considered statistically significant. Results: Among the 354 admitted patients, 226 (63.8 %) had a record of MNA. The mean age was 57.5years ± 14.6. The majority of the patients (61.5 %) were either petty traders or artisans/selfemployed. Duration of hospitalization increased with increase in number of comorbid disease (Pearson product moment correlation r = 0.13 p = 0.05). Total cost incurred during hospitalization was US$146,669.3 (average, $ 650.1), of which more than one quarter was cost of medications. Cost of management and cost of laboratory investigations increased with increase in the number of co-morbid diseases (r = 0.24, p = 0.00; r = 0.2, p = 0.02, respectively). Cost of management also increased with increase in days of hospitalization (r = 0.2, p = 0.00). Conclusion: Cost of hospitalization related to non-adherence to medication is high among the studied population. There is need to work out strategies to enhance adherence among diabetes patients.


INTRODUCTION
Diabetes mellitus (DM) is a group of chronic medical conditions in which there is derangement of metabolism in the body. It could occur when there is absolute or low insulin production or resistance to the produced insulin, resulting in a sustained hyperglycaemic state [1]. The persistent hyperglycaemia and associated complications requires intensive care and visit to healthcare facilities, which increases the cost of care of the disease.
Globally, about 285 million people were living with DM in 2010. This was projected to double by 2030 [2]. In Nigeria, there is no nation-wide survey or any research within Nigeria with current report on the prevalence of diabetes in the country. The last national survey of non-communicable diseases (NCDs), carried out in 1997, reported 2.2 % as prevalence of diabetes in Nigeria [3]. However, the prevalence of T2DM has been high and is still increasing in Nigeria, with the country reported as having the highest burden of diabetes in Africa [4]. Globally, the number of patients with diabetes has been projected to double by 2050 [2]. Therefore, the prevalence of diabetes is high. This is a concern for both public health and public policy. Oral diabetes medications and insulin are the core agents for management of diabetes. However, about one-third of diabetic patients do not attain optimal benefit from the therapy due to medication non-adherence (MNA) [5].
Adherence with medication therapy is generally low among patients with chronic conditions such as diabetes [6]. In the United States, poor adherence to medication has been shown to lead to an estimate of 125,000 deaths annually and 33 to 69 % of medication-related hospital admissions [7,8]. Many studies have reported that MNA is associated with increase in inpatient admission, emergency department visit, and total diabetes-related cost [6,9]. Medication nonadherence (MNA) has been shown to cost $100 to $300 billion each year on avoidable hospitalization in the US when both direct and indirect costs are included, this represented 3 to 10 % of total US healthcare costs [8].
In 2010, 12 % of the health expenditures and US$ 1330 (ID 1478) per individual was anticipated to be spent on diabetes mellitus globally [10]. However, this expenditure was found to vary by age group, sex, region, and country's level of income [10]. Many factors can lead to poor medication adherence among patients. Nevertheless, high costs of medications and co-payments that some patients have to pay for medications prescribed for them have been shown to negatively effect adherence to medication [11].
The World Health Organisation claims that over the past decade, there was greater increase in the prevalence of diabetes in low-and middleincome countries than what was reported in highincome countries [12]. Past studies in Nigeria have been mainly on the burden of diabetes in the country [13,14]. Data on cost of hospitalization resulting from non-adherence to medication(s) among patients diagnosed with diabetes mellitus are scare. Therefore, this study estimated the cost associated with hospitalization among non-adherent T2DM patients in one of the largest tertiary healthcare institutions in southwestern Nigeria.

METHODS
This study involved collection of data from case notes of patients diagnosed with T2DM and admitted to the University College Hospital (UCH) Ibadan, Nigeria. They had a record of subjective assessment of the physician for nonadherence to medication as documented in their case notes at the point of admission (in 2013, 2014 and 2015) into the hospital.

Study population
Available information from the Record Department of UCH indicated that 354 patients were on admission during the 3-year period. Out of this figure, 226 had records of subjective assessment of physician for non-adherence to medication as documented in their case notes at the point of admission and were available for use for the study.

Data collection
The case notes of the patients admitted in the years 2013, 2014 and 2015 were retrieved from the Statistics Section of the Record Department in the University College Hospital (UCH). Each case note was well screened and anyone with a record of non-adherence to medication(s) as indicated by physician in the case note clerking was included in the study.
Three hundred and fifty-four (354) case notes were retrieved and 226 were found to have records of non-adherence to medication(s). The remaining 128 were those who had no record of non-adherence to therapy due to the fact that they were newly diagnosed cases and some others were admitted to the hospital as a result of other comorbid diseases but had good blood glucose control.
Data were retrieved from the case notes assessed for cost of non-adherence arising from cost of hospitalization. They included costs of investigations, medications, consumables, bed fee, oxygen use, procedures, physiotherapy services, dressings and of transportation. These were calculated as direct cost associated with their hospitalization resulting from nonadherence to medication(s).
The primary outcome variables were cost types (medications, diet, bed fee, laboratory investigations, procedures, use of other hospital facilities, and transportation fee) measured in the 2013, 2014 and 2015 USD exchange rate using the out-of-pocket perspective. Costs for each year were presented as cost for the population of patients admitted due to non-adherence to medication(s) before admission that year. Other variables included were age, sex, marital status, residence, and comorbidities.
The comorbidities included anaemia, stroke, heart failure, cardiovascular disease, hypertension, liver disease, diseases of the lung, renal failure (chronic and acute), peptic ulcer disease and bleeding; they were defined according to ICD-9 codes. The comorbidities were categorized as count of comorbidities, which was defined as 0, (that is none), 1, 2, and 3 or more. This count has been reported to be more efficient [5].
The cost items for this study included direct medical cost and non-medical cost. Direct medical cost included cost of medications (diabetes medication, hypertension, comorbid diseases), cost of all laboratory investigations related to disease state, bed fee, procedures (amputation), cost of blood transfusion, dressings, use of oxygen, physiotherapist service, nursing services.
The cost of medication was calculated using unit dose of medication used and summing up total cost of medication used for the period of hospitalization. The cost for all the direct medical cost was based on hospital tariff of each year studied. The non-medical cost was cost of transportation (to and fro from the hospital) based on National Union of Road Transport Workers' (NURTW's) tariff in the state.

Data analysis
Data were entered into SPSS version 23 and analysed. Pearson product moment correlation coefficient was used to determine the relationship between variables, with p < 0.05 considered statistically significant.

Ethical approval
Ethical approval was received from the UI/UCH Research Review Board on 14th April, 2015, with certification no. UI/UCH EC and registration no. NHREC/05/01/2008a. The international guideline for human studies used was the NIH guideline for human subject research protection. This guideline was borne in mind when collecting data retrospectively [15].

RESULTS
The total number of the available case notes of admitted patients primarily diagnosed with T2DM within the study period was 354. Those with a record of non-adherence to medication(s) which resulted in their hospitalization were 226, which was 63. As for the number of days on admission: 114 patients (50.4 %) were admitted for 1 -10 days; 90 (39.8 %) for 11-20 days; and 22 (9.7 %) patients for > 20 days. The mean duration of admission was 11.9 days (SD, 10.6) and mean HbA1c among the patients was 10.45 % (SD, 1.94 %.  The cost of management of the complications was 32.5 % of the total cost of management. The cost related to foot care included dressing of ulcer/wound for the 40 patients and amputation for the 24 patients (US$11,251.5), control of the blood glucose ($15,933.9) and use of antibiotics (US$6,441) was US$33,626.4, which was an average of US$842.1 per patient. The cost of management of DM foot was 22.1% of the total Cost-of-Illness (COI) for the 226 patients. The cost of management of chronic renal failure (CKD) among the 31 patients was estimated to be US$6,327.2, giving an average of US$204.1 per patient. The patients managed for CKD had some other costs of management added to their cost items. These included cost of anaemia, electrolyte imbalances, dialysis, and laboratory investigations related to the disease. The cost of management of retinopathy of 6 patients was US$754.7 and average of US$125.8 per patient.
The numbers of comorbid diseases was found to increase with increase in ages of patients (Pearson product moment correlation r = 0.3, p = 0.00). Duration of hospitalization increase with increase in number of comorbid disease (Pearson product moment correlation r = 0.13 p = 0.05).
Cost of management also increased with increase in days of admission (r = 0.2, p = 0.00), cost of laboratory investigation increased with increase in the number of comorbidities (r = 0.2, p = 0.02). Cost of management was found to increase with increase in comorbid diseases (Pearson product moment correlation r = 0.24, p = 0.00).

DISCUSSION
Diabetes has been shown to exert a heavy economic burden on patients, national health system and society at large, and the burden borne depends on the differences in the socioeconomic status, and social insurance policies of the countries the patient live in [10]. Nigeria currently has a health insurance scheme (National Health Insurance Scheme -NHIS), which mainly services civil servants in the country and few members of the private sector [17]. Although the scheme has put measures in place to extend its service to the informal sector of social health insurance programme, which includes rural dwellers, artisans and other people/community who are not public servants or uniformed officers, few people are enrolled in it.
In this study, the majority of the patients paid for healthcare out-of-pocket. Because they did not enroll with the NHIS, they privately funded their health care. This is supported by a previous study in Nigeria which reported that more than 90% of patients privately fund their healthcare bills [18]. Furthermore, the findings of this study support previous research which reported that patients diagnosed with and being managed for diabetes in low-income countries like Nigeria are responsible for payment of the bulk of their healthcare cost (out-of-pockets) because there are no financial risk protection mechanisms [19]. This implies that diabetes exerts a heavy economic burden on the patients and their relations, who have to help out in making funds available for the management of the condition. The need for more enlightenment of the public on the National Health Insurance Scheme, especially the informal sector, which will bring about a co-payment design and reduce patient's out-of-pocket payment, is highly essential.
Non-adherence to medication(s) has been shown to be responsible for 33 to 69% of medicationrelated hospital admissions in the US [8]. This is similar to the finding in this study, because more than one-third of the patients diagnosed with type 2 diabetes hospitalized during the period of study were due to non-adherence. The cost of hospitalization resulting from nonadherence to medication(s) among the studied population was high considering the fact that the expenditures of majority of these patients were out-of-pocket. In addition, most of these patients were from the low socioeconomic class comprising petty traders, retired workers, artisans and the unemployed, who have been shown in past studies in the same healthcare facility to have meagre income [14,18] and are, therefore, not financially strong to cope with the cost of their medications. Cost of medications has been reported to be a strong reason for non-adherence to medication(s) among the studied population [18].
In a previous study on cost of hospitalization of diabetes patients, laboratory costs rated highest when compared to other costs, like cost of medications [20]. In this study, cost of medications, both for diabetes and other comorbid conditions, accounted for the highest cost. Cost of laboratory investigations on the course of admission was one third of the total expenditure. Cost of laboratory investigation was found to increase with increase in the number of comorbid diseases. Some of these investigations would not have been recommended if the patient had adhered to the recommended medications and had not developed complication(s). Cost of other drugs used in the management of complications of DM was found to be more than one-quarter of the total cost of management on admission (Table 3). In addition, cost of other management attributed to the hospitalization resulting from the non-adherent behaviour of patient was high.
The average HbA1c (which was far higher than the normal value of < 7.0 %) at admission showed that the patients were not adherent to their medication(s). A previous study showed that haemoglobin A1c reduces with increase in adherence to diabetes medications use [21]. Besides, many of them would have developed complications before they were admitted, which also increases the cost of management. Cardiovascular complications tend to increase with increase in 1.0 % of HbA1c above normal or target level of 7.0 % [22]. The increase in comorbid disease with age has been reported [23] and this becomes worse in patients with poor clinical outcome (high HbA1c) who are in their advanced age and do not adhere to their medications.
Diabetic neuropathy was the most common complication among the participants but the cost of managing it was not as high as those with Diabetes Foot Ulcer (DFU). However, all the patients in this study with DFU also presented with diabetic neuropathy -a major risk factor for DM foot ulceration [24]. Cost was higher among patients managed for DFU as compared to other complications of DM. The average cost of managing DM foot in this study was found to be a little lower than ₦180,581.6 ($1051.1), which was reported in a previous study in Nigeria [24]. More than two-thirds of the DFU patients in that study had amputation, which accounted for the increase in the cost of management [24] compared to this study, where more than half of the DFU patients underwent amputation while on admission.
Another complication which invariably increased cost of management among the patients was chronic renal failure. However, the prevalence among the studied population was lower than the 11 % reported in a previous study in a hospital setting in Nigeria [25].

Limitations of the study
This was a retrospective study. There was no direct contact with the patients to establish report of medication non-adherence and reason(s) for their non-adherence to medication. The study relied on the accuracy and completeness of physician's subjective assessment of patients for non-adherence to medication(s) made available in the patients' case notes. There could have been some patients among those admitted that would have been missed out in the process of assessing their adherence to medication(s). Therefore, cost of hospitalization may be much higher than what was reported in the study. In addition, indirect costs (such as, mortality, caregivers, and productivity loss) on the parts of the patients and caregivers were not accounted for in this study, which would have increased the cost associated with hospitalization.

CONCLUSION
The cost of hospitalization associated with nonadherence to medication(s) for patients with T2DM is huge (average of $650.0), an amount too large for an individual in a country where a substantial number of its citizens live on < $57 monthly. It is suggested that healthcare providers and health policymakers should focus on factors associated with non-adherence among patients with the aim of resolving it through a proven intervention programme in order to reduce the cost associated with it.

DECLARATIONS
the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/rea d), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.