Prescription auditing and assessment of medication adherence patterns in patients with diabetic foot ulcer

Abstract

Background

Diabetic foot ulcer (DFU) is a serious infectious disease, which can be managed very well through proper medication, but if left untreated it may lead to amputation of the affected area leading to permanent immobility which will compromise the patient’s quality of life.

Objective

To carry out prescription auditing and to assess medication adherence patterns among DFU patients.

Materials and methods

A prospective interview-based study was carried out in the surgery department among inpatients aged above 18 years diagnosed with a DFU. A disease specific medication adherence questionnaire consisting of 15 questions was developed, validated and implemented among 65 patients. All the relevant data were analyzed and subjected to statistical analysis.

Results

The majority (49.2%) of the population had an intermediate adherence pattern followed by high adherence (43%) during the first visit, later the reassessment after the counseling, reports a gradual increase in adherence pattern. Prescription auditing reveals the intensity of drug burden, on an average a prescription might carry 8 drugs and more than 95.3% of prescribed drugs were in injectable form.

Conclusion

This study highlights the depth of drug burden through prescription auditing and the necessity of proper patient counseling and educating the patient about the importance of medication adherence for limiting disease progression.

Introduction

A diabetic foot ulcer (DFU) is the most common complication of uncontrolled type II diabetes mellitus, characterized by a group of conditions called neuropathy, ischemia, and infection leading to tissue damage called diabetic gangrene [1]. The global DFU prevalence was 18.84%, higher in males than females [2]. In India, DFU harms 15% of diabetics over the course of their lives, with 50% becoming infected and requiring hospitalization and 20% requiring amputation. Moreover, 50% DFU patients who get amputated once suffer another amputation within the next 2 years [3, 4]. Increasing age, uncontrolled diabetes mellitus, prolonged standing, and working barefoot in the field, and slow healing wounds in extremities are the most common factors contributing to DFU [4].

Research has proven that diet and medications play a crucial role in managing diabetes mellitus, but adherence to both is a great challenge in fulfilling the goal of a diabetic-free society [5]. Disease-specific adherence questionnaire plays a key role in assessing the adherence pattern in patients, thereby understanding the patient’s perspective about the drugs as well as diseases [5]. The alarming signs of increased antimicrobial resistance and poor health outcome, along with the exponential increase in drug use, highlight the necessity of proper prescription auditing in order to evaluate the quality and rationality of medical care provided to the patient through cross-verification and maintain proper accountability of the drugs in each encounter [6]. There exists a dearth of DFU-specific medication adherence questionnaire as well as only a few prescription auditing studies have been conducted on the DFU population, so through this study, we developed and validated a DFU-specific questionnaire which will help us to understand the patients’ perspectives and to evaluate the rationality through prescription auditing.

Methodology

A prospective interview-based study was conducted in the General surgery department for a period of 6 months and patients who met the eligibility criteria were enrolled in the study. Ethical approval for the study was obtained from the Institutional Ethics Committee prior to the study (Letter reference no: IEC/TOMCHRC/123/2019-20).

Sampling size calculation

A sample size of 65 was calculated using the following sample size equations, considering the prevalence of 14.3%, [7] with confidence limits 95% and with a margin of error 5%.

$$\mathrm{X}={\mathrm{Z}}^2\mathrm{P}(1-\mathrm{P})/{\mathrm{e}}^2$$

Inclusion criteria

Inpatients of the adult age group (above 18 years) of both genders diagnosed with diabetic foot ulcers and patients who received antibiotics and anti-diabetics as their treatment plan for DFU were included.

Development and validation of medication adherence questionnaire

After an extensive literature review, we realized the lack of a DFU-specific medication adherence questionnaire applicable in the Indian population setting. Initially, we documented the information from different medication adherence questionnaires mainly focused on the diabetes population.

Based on the data from available resources, we formulated objective type 15 DFU-specific medication adherence questions in the English language, of which the first 10 questions focused on diabetes medication and the other 5 on antibiotics. The questionnaire was finalized by the research team and subjected to the validation process later, which was evaluated by 10 experts (various health professionals) and 5 lay persons (including patients). Prior to the evaluation, researchers explain the study’s purpose to the expert panel members along with the validation criteria. The content validity index (CVI) and scale of Content validity index (S-CVI) were scored based on the four-point measuring parameters like relevance, clarity, simplicity, and ambiguity. According to the comments and scoring from the evaluators the questions were reframed. The scores obtained for each question were recorded in Microsoft Excel, the reliability / internal consistency was estimated using Cronbach’s alpha and its coefficient should be 0.7 or greater, which indicates acceptable internal consistency. The revised questionnaire was re-evaluated for construct validity and test-retest reliability, later translated into the local vernacular language (Kannada), and verification and language correction of the questionnaire was done by a bilingual professional.

Scoring of medication adherence questionnaire

The 15-item objective-type medication adherence questionnaire consists of 4 choices of answers, based on the patient’s answer scores assigned as follows: Strongly agree = 4, Agree = 3, Disagree = 2, Strongly disagree = 1. The overall scoring of the questionnaire is out of 60, and based on the overall scores secured, patients will be segregated into 3 different medication adherence groups 15–30 as high, 31–45 as intermediate, and 46–60 as low.

Prescription auditing

An effective tool in evaluating the appropriateness of medication use by the careful review of each prescription and documentation of the details in data collection as well as in excel. Later the individual drugs were categorized based on the WHO-Anatomical Therapeutic Chemical Classification (WHO-ATC) code. The general prescribing tendencies of the given setting independent of the diagnosis were evaluated using the WHO core prescribing indicators, which mainly focused on the 6 core elements as follows:

1. The Average number of drugs per prescription is used to measure the degree of poly-pharmacy, calculated by dividing the total number of medications prescribed, by the number of prescriptions surveyed, but it is not relevant to the patient actually receiving the drugs.

2. Percentage of drugs prescribed in the generic name is used to evaluate the tendency to prescribe by generic name. Percentage, calculated by dividing the number of drugs prescribed by generic name by the total number of drugs prescribed, multiplied by 100.

3. Percentage of prescriptions with an antibiotic prescribed helps to identify the percentage of prescriptions containing antibiotics. This was computed by dividing the total number of patients who received one or more antibiotics by the total number of prescription and multiplying by 100 to get a percentage.

4. Percentage of prescriptions with an injection can be estimated by dividing the number of prescriptions with injectables divided by the total number of prescriptions, multiplied by 100.

5. Percentage of drugs prescribed from the essential drug list was estimated to evaluate the degree to which practices lie in with the national drug policy by comparing the prescribing pattern with the national essential drug list or formulary. To calculate the percentage, divide the total number of essential drugs prescribed as per formulary divided by the total number of drugs prescribed and multiply by 100.

Results

A total of 65 prescriptions that satisfy the inclusion criteria were included in the study and subjected to critical evaluation. Male (78.4%) predominance was observed, and the patients aged 61–70 years were more infected (38.46%) with the DFU. The majority of them were from the lower socioeconomic class (50.76%) and with a low educational level, especially below the fifth grade (40%). Farmers were most infected (40%), followed by housewives (18.46%). Detailed information about the demographics is given in Table 1, and details about the area of infection are specified in Table 2.

Table 1.

Demographic details of the patients

Age (years)	No: of patients (n = 65) (%)
30–40	2 (3.07)
41–50	14 (21.53)
51–60	20 (27.76)
61–70	25 (38.46)
71–80	4 (6.14)
Socio-economic status	No: of patients (%)
Upper class (> 20001Rs/month)	4 (6.15)
Middle class (10001-20000Rs/month)	10 (15.38)
Lower class(< 10000Rs/month)	51 (78.46)
Education status	No: of patients (%)
Primary education	26 (40)
High school	19 (29.23)
PUC	7 (10.76)
Degree	3 (4.61)
Illiterate	10 (15.38)
Occupation	No: of patients (%)
Professional	5  (7.68)
Skilled worker	8 (12.30)
Semi-skilled	9 (13.84)
Unskilled worker	31 (47.69)
Unemployed	12 (18.46)

Table 2.

Distributions of patients based on infection-affected area

Left foot n = 65 (%)	Right foot n = 65 (%)	Both n = 65 (%)
19 (29.23%)	35 (53.84%)	7 (10.76%)

Out of the 65 prescriptions analyzed, 572 drugs were prescribed, with an average of 8.8 drugs per prescription. The analysis of the WHO prescribing indicator shows that only 18.5% of drugs were prescribed under the generic name. Almost every prescription contains one or more antibiotics, of which more than 95.3% were injectable formulation. Only 33.9% of the drugs were prescribed, according to the essential drug list or formulary.

The number of antibiotics prescribed is mentioned in Table 3 reports that 38.4% of DFU patients were administered two antibiotics, while 35.8% were prescribed more than two antibiotics this shows an inappropriate prescription of antibiotics without any culture sensitivity tests. Distributions of commonly prescribed drugs with ATC code are given Table 4 shows that among analgesics and anti-inflammatory drugs category, tramadol (3.4%) followed by acetaminophen (2.7%) was commonly prescribed. Among insulin preparations, human insulin (6.6%) and by insulin glargine (2.6%) was prescribed more. The most commonly prescribed oral hypoglycemic agents were found to be metformin (2.9%) and glimepiride (1.5%). The most common category found among antibacterial agents were ceftriaxone (5.2%) followed by metronidazole (3.4%), a combination of amoxicillin- clavulanic acid (2.7%), ciprofloxacin (2.2%) and linezolid (2.2%). Considering the distribution of multivitamins, mostly prescribed were chymotrypsin (2.2%), followed by vitamin B complex (1.7%) and cyanocobalamine (1.5%).

Table 3.

Showing the number of antibiotics prescribed per encounter/ patient

Parameters	No. of patients (n = 65)	Percentage %
Single antibiotic	14	21.5
Two antibiotics	25	38.4
> 2 Antibiotics	23	35.8

Table 4.

Distributions of commonly prescribed drugs with ATC code

Drug group	Individual drugs	ATC code	Number	%
Antibiotics	Ceftriaxone Amoxicillin + clauvlanic acid Ciprofloxacin Piperacillin tazobactum Linezolid Amikacin Meropenem Clotrimoxazole Cefpirom Cefotaxime Metronidazole Clintamicin Gentamicin Amoxicillin	J01DD04 J01CR02 J01MA02 J01CR05 J01XX08 S01AA21 J01DH02 A01AB18 J01DE02 J01DD01 J01XD01 J01FF01 S01AA11 J01CA04	30 16 13 9 13 4 1 2 1 8 20 2 3 1	5.2 2.7 2.2 1.5 2.2 0.6 0.17 0.34 0.1 1.3 3.4 0.34 0.52 0.17
Insulin	Isophane insulin Human insulin Insulin glargine	A10AC A10AD01 A10AE04	10 38 15	1.7 6.6 2.6
Oral hypoglycemic agents	Metformin Glimepiride Glimepiride + metformin + voglibose Glibenclamide Repaglinide Glimepiride + pioglitazone + metformin Glimepiride + metformin Teneglyptin Teneglyptin + metformin	A10BA02 A10BB12 A10BB01 A10BX02 A10BH08	17 9 3 3 1 4 6 1 1	2.9 1.5 0.52 0.52 0.17 0.6 1.04 0.17 0.17
Multivitamin	Cyanocobalamine Vitamin b complex Methylcobalamine Chymotrypsin Protein powder Dextrose normal saline Vitamin C	B03BA51 A11EA B03BA05 S01KX01 V06DE V04CA02	9 10 2 13 2 2 2	1.5 1.7 0.34 2.2 0.34 0.34 0.34
Analgesics	Tramadol Acetaminophen Tramadol + Acetaminophen Diclofenac + Paracetamol Diclofenac Aceclofenac Aspirin	N02AX02 NO2BE01 N02AJ13 M01AB55 M01AB05 M01AB16 B01AC06	20 14 16 5 4 3 3	3.4 2.7 2.7 0.87 0.6 0.52 0.52

In addition to the commonly prescribed drugs for DFU mentioned above, other drugs for the symptomatic relief are also prescribed such as anti-emetics, proton pump inhibitors, leukotriene receptor antagonists, wound dressing aids, and antiseptic solutions

The administration of medication adherence questionnaires reveals that about 30.7% of patients had difficulty remembering to remember taking their medications, and 33.8% of patients forgot their medications while traveling. Also, 41.5% report very low medication adherence or stoppage of insulin due to physical discomfort. Details about the medication adherence questions and patient scoring are given in Table 5.

Table 5.

Scoring of medication adherence questionnaire

SL No.	Questions	Strongly disagree (Score-1) n (%)	Disagree (Score-2) n (%)	Agree (Score-3) n (%)	Strongly agree (Score-4) n (%)
Q1	Do you have difficulty to remember taking all your blood sugar medications?	1 (1.53%)	3 (4.61%)	24 (36.9%)	20 (30.7%)
Q2	Do you sometimes forget to take your medications when you travel or leave your house?	14 (21.5%)	7 (10.7%)	22 (33.8%)	22 (33.8%)
Q3	Do you sometimes stop taking your medications when you feel your blood sugar level is controlled other than from being instructed by a doctor?	35 (53.8%)	11 (16.9%)	14 (21.5%)	5 (7.69%)
Q4	Have you ever felt distressed for strictly following your high blood sugar treatment and stopped the medications completely?	32 (49.3%)	11 (16.9%)	16 (24.6%)	6 (9.2%)
Q5	Do you make your own modifications in the timing of antidiabetic drugs or insulin prescribed?	27 (41.5%)	21 (32.3%)	8 (12.3%)	9 (13.8%)
Q6	Have you ever taken one or more tablets/ administered one or more units of insulin for diabetes on your own initiative, because of feeling worsening of the condition?	33 (50.7%)	11 (16.9%)	10 (1.3%)	11 (16.9%)
Q7	Have you ever stopped taking your insulin due to pain or other physical discomfort caused by its method of taking?	17 (26.1%)	8 (12.3%)	13 (20%)	27 (41.5%)
Q8	Do you fail to plan ahead and refill your medicines before they run out?	29 (44.6%)	10 (15.3%)	14 (21.5%)	12 (18.4%)
Q9	Have you ever stopped taking your anti diabetic medication/insulin prescribed due to low financial status?	17 (26.1%)	5 (7.6%)	17 (26.1%)	26 (40%)
Q10	Have you ever stopped taking your anti diabetic medication/insulin because it interferes with your meal plan?	33 (50.7%)	16 (24.6%)	9 (13.8%)	7 (10.7%)
Q11	Do you fail to complete the course of antibiotics?	31 (47.6%)	9 (13.8%)	17 (26.1%)	8 (12.3%)
Q12	Do you buy antibiotics without medical prescription?	41 (63.07%)	11 (16.9%)	9 (13.8%)	4 (6.1%)
Q13	Do you take missed dose along with scheduled dose when you forget to take medicine on time?	42 (64.6%)	11 (16.9%)	6 (9.2%)	6 (9.2%)
Q14	Do you use leftover antibiotics when your wound is feeling worse?	43 (66.1%)	7 (10.7%)	6 (92%)	9 (13.8%)
Q15	Have you ever stopped taking any antibiotics due to its side effects?	23 (35.3%)	13 (20%)	18 (27.6%)	11 (16.9%)

The majority of patients had intermediate medication adherence (49.2%) during their first visit, while only 4.67% had low adherence. Patient counseling was provided to the patients and reassessed after 14 days in the follow-up visit; reports that the majority of patients n = 64 (98.4%) had a high level of drug adherence which is shown in Table 6. The positive impact of patient counseling on medication adherence pattern is represented in Table 7.

Table 6.

Categorisation of patients based on medication adherence scoring

Scoring	1st visit score n = 65 (%)	2nd visit score n = 65 (%)
High (15–30)	28 (43.07%)	64 (98.4%)
Intermediate (31–45)	32 (49.2%)	1 (1.5%)
Low (46–60)	5 (7.69%)	0

Table 7.

Impact of counselling on medication adherence before and after counselling

Parameters	Mean Score Before counselling	Mean Score After Counselling	T- test	P value
Medication adherence	32.06 ± 7.312	16.6154 ± 2.79895	18.051	< 0.05*

*Paired t-test; significant if p < 0.05, high score indicates low medication adherence

Discussion

A total of 65 patients were enrolled in the study, and male predominance 51(78.4%) was observed. Majority of them were above 50 years of which 38.46% them were aged between 61–70yrs. More than 78.46% of the patients belongs to the low socioeconomic status (SES), and mainstream of them were unskilled workers 31(47.69%). Nearly 40% of our population had only a basic primary level education and about 15.38% were illiterate.

The dire impact of drug burden is clearly evident in our study, about 572 drugs were prescribed within 65 prescriptions which reflects that an average of about 8.8 drugs were involved per prescriptions. Almost every prescription carries the antibiotics followed by analgesics, oral hypoglycemic agents and insulin. More than 95.5% antibiotics were prescribed as injectable and the most preferred was ceftriazone and metronidazole, while among the antidiabetic drugs insulin and biguanides were preferred.

The administration of medication adherence questionnaire in our study population reveals that majority of the patients maintain moderate or intermediate adherence pattern (49.2%) followed by high which show significant improvement in the follow-up visit after patient counselling, where more than 98.4% had high medication adherence pattern.

The demographics and clinical characteristics of our study population were similar to other studies [8–11]. In studies conducted by Saranya et al. [8] and Wong et al. [9] reports that people aged above 60 years were prone to developing infection. The male predominance is observed even in the study conducted by Chomi et al. [10] suggesting the ratio of 1.4 males to 1 female can get affected by DFU. Our study depicts a high number of people belonging to low socioeconomic class might be the patients come from rural background, which was found similar to the study conducted by Kumarasinghe A et al. [11]  were half of the population belongs to low SES.

In our study population more than 40% of DFU affected persons were farmers, which might be due to the unhealthy practices they follow such as long-standing, barefoot walking which increases exposure to contaminants which was found similar to the study by Bedilu Deribe et al. [12] shows that farmers are 6.54 times more likely to develop DFU as compared to others employed in white-collar jobs.

The higher incidence of DFU among illiterate and less educated people demonstrates correlation of education on occurrence and progression of DFU, states that unawareness about the disease as well as the poor foot care practices plays a crucial role in the severity of DFU. But in a study by Pal Bikramjit et al. [13] highlights a contrasting results that more than 40% of their study population were graduates and settled in urban area developed DFU.

The prescription auditing showcase an ample evidence that irrational drug use can surge the economic burden of the public. The severity of DFU, comorbidities and geriatric age might be the reason for the inappropriate prescribing pattern involving polypharmacy that is around 8 drugs per prescription. As per WHO average number of drugs per prescription should be within the ideal range of 1.6–1.8, but this study reports a large deviation from the range which was found similar in study conducted by Shanmugapriya et al. [14] where an average number of 3 drugs were prescribed [15].

The high medication cost might be the reason for the drastic decline in medication adherence which was in line with the study conducted by Divya et al. [16] states that exceeding cost of antidiabetic medication is considered a problematic issue regarding affordability.

To overcome the drug burden, the practice of generic name prescribing, promoting the rational drug use, and the use of combination drug therapy are essential. But in this study only few prescription follows the generic prescribing pattern whereas studies by Tulika Singh et al. [6] and Karthikeyan et al. [17] report 85.8% and 40.01% of generic prescribing.

A study by Wang et al. [18] found that the generic prescribing of medication by experienced doctors is very less. An essential drug list (EDL) and formulary will aid in the selection of the appropriate drug. The studies by Tulika Singh et al. [6] report that about 88.3% of prescribed drugs were from the EDL, while in this study only 33.9% of the drugs were chosen from EDL.

Moreover, the irrational prescribing of antibiotics that too in parenteral route is too high in this study, may be they have preferred the empirical therapy but the chances of antibiotic resistance is vast, which can be minimized by initiating the culture sensitivity analysis at the time of admission itself and switching to the definite therapy accordingly. Even some prescriptions contains two antimicrobial agents which was found similar to the study conducted by Zachariah et al. [19] which shows 45.23% have two drugs combination while Debasis Bandyopadhyay et al. [12] study reports only 28.89% prescriptions containing antibiotics.

Ceftriazone and metronidazole was the preferred choice of antibiotics among DFU in our study whereas in the study by Mounika et al. [20] involving 187 patients with diabetes-associated infections azithromycin is preferred more followed by ceftriaxone. While the choice of oral hypoglycemic agent in DFU was found to be biguanides followed by sulphonylureas both in our settings as well as in studies conducted by Mounika et al. [20] and Athira Pillai et al. [21] Multivitamin therapy was common in the majority of them which includes vitamin B complex (1.7%) and cyanocobalamine 1.5% along with proteolytic enzyme preparation chymotrypsin 2.2% whereas in a study conducted by Saranya et al. [8]shows that vitamin C (35.32%) prescribed more followed by vitamin B complex (20.1%) later, iron and folic acid (19.02%).

Medication adherence plays a vital role in diabetic foot ulcers, the chance of reinfection can be minimized to a greater extent by maintaining the blood glucose level through medications. Various questionnaires are available for evaluating medication adherence, but the specific questionnaire for the DFU is lacking, so we developed and validated DFU specific medication adherence questionnaire. Implementation of this questionnaire in our study population reveals that the majority of them lays in the moderate medication adherence patterns which was in line with the study conducted by Vivek Gaurang Vyas [22] using the MMAS-8 questionnaire in 251 subjects shows that more than 70% of them follows moderate adherence followed by 27.89% with low adherence pattern. Three months after the patient counselling the reassessment report states an exponential increase in medication adherence, which is about 99.40% moderate adherence and only 1% of them with low medication adherence which was in line with the other south Indian study conducted by Maheshwari et al. [23] states that proper patient counselling is directly linked with the improvement in the medication adherence pattern.

Strength

This study reflects the unaffordability of essential medication which is considered as the primary cause of low medication adherence pattern, ultimately leading to prolonged patient suffering. The implementation of proper hospital policies for the rational drug use as well as proper patient education about the disease and drugs plays a key role in the proper management of DFU.

Limitations

The small sample size only reflects medication adherence pattern of very specific population with DFU it can be extended by comparing various patients suffering from different diabetic’s complications. By extending the timely follow-up, will help to evaluate how changes in medication adherence pattern is associated with the patient’s quality of life.

Conclusion

This study highlights the necessity of proper education programs as well as strong hospital policies to rationalize the overall prescribing pattern and thereby reduce the economic burden on the patients due to non-medication adherence as well as improper drug use. The awareness of the patient about the disease condition and its proper management methods plays a key role in limiting the progression of the disease.

Data Availability

The data used to support the study findings are represented within the article, in order to protect the study participant’s privacy other data cannot be disclosed.

Declarations

Conflict of interest

Nil.