Impact of medication and psychological behaviour assessment by community pharmacists in type 2 diabetes mellitus patients after hospital stay

Drug related problem (DRPs) is a key factor which will affect the outcome of therapy and safety. The aim of the present study is to assess the DRPs in T2DM patients and psychological aspects of patients by community pharmacists to observe the rate of DRP. Prospective randomized controlled intervention study involved T2DM patients and conducted in two community pharmacies at Kanpur from January 2012 to December 2012. The assessment of DRPs was based on the PCNE. Changes in HBA 1C , LDL, BP, foot examinations, changes medical and medication utilization were studied. Using as control group, received usual care, and interventional group provided, intervened with use of the STG. Researcher provided the knowledge to community pharmacists and patients. Baseline and interventional data were collected at 0,3,6,9 and 12 months. Over 12 month study, participants’ average HBA 1C reduced from 8.9% at initial visit to 7.5%. During this time, the eye examination rate was raised from 31% to 48%, and the foot examination rate was raised from 35% to 50%. It may be concluded that the intervention of pharmacists showed very less significant influence on any of the intermediate health outcomes in T2DM.


Introduction
The type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterised by defects in insulin secretion and/or insulin resistance. It forms part of a cluster of cardiovascular risk factors seen in at higher rates in patients with T2DM, which is characterised as the metabolic syndrome. That includes central obesity, hypertension and/or dyslipidaemia etc. Patients with any illness or disease along with another precipitating co-morbidity condition often receive multiple medications which often lead to the occurrence of drug-related problems (DRPs). (Zaman Huri and Fun Wee, 2013) A DRP is an event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes. There is a high prevalence rate of DRPs that has been observed in T2DM patients. DRPs may lead to additional complications that may lead to significant morbidity or mortality, prolonged hospitalization, and increased health care expenditure. Several problems and causes of DRPs in T2DM patients with hypertension and factors influencing will be reported in the study. (Rashed. AN et al, 2012 and) To date, polypharmacy (≥5 concurrent medications), age status (≥ 65 years old), multiple medical conditions and renal impairment have been shown to be the most causing influencing factors.
Drug-related problems affect the outcomes on morbidity, mortality and cost which constitute a major public health problem. Most people with diabetes live in low-and middle-income countries like India, and these countries will also see the greatest increase over the next 19 years. The recently published ICMR-INDIAB national study reported that there are 62.4 million people with T2DM and 77 million people with pre-diabetes in India. These numbers are projected to increase to 101 million by the year 2030. (Whiting DR et al, 2011 and and Anjana RM, et al, 2011) The prevalence of diabetic retinopathy was 17.6%, microalbuminuria in 26.9% neuropathy was 26.1%, coronary artery disease (CAD) was 21.4% and peripheral vascular disease was 6.3%. (V. Mohan et al, 2013).

Objective
The objective of this study is to assess causes and factors of DRPs in T2DM patients with any comorbid conditions so as to enhance therapeutic outcome by implementing effective medication review and psychological aspects in the treatment plan.

Study Design
The study was designed as a prospective randomized controlled intervention involving 723 participants with a followup of one year. The intervention was performed by trained community pharmacists with the help of researchers. The Independent Human Ethics Committee in Ahmedabad (Approval No.: IRB00005741), India has approved the present study design, protocols, information letters and informed consent form.

Study Setup
The trial was conducted in 2 community pharmacies at Kanpur, Uttar Pradesh, India [Anna Hajare Medical Clinic and Anjali Hospital & Nursing Home, Kanpur.]. The present study was performed by 8 trained pharmacists in association with diabetologist. The patients were counseled in the both pharmacies randomly by the trained community pharmacists. Study Population 723 participants were enrolled into the study those regularly visit in the both pharmacies. Participants were between 20 and 75 years of age, the prescriptions which contain antidiabetic agent(s) prescribed from the TNSTG were only considered as eligible to participate in the study. The researcher was identified the prescription and obtained written informed consent from participants before study starts.

Inclusion criteria
Patients with diagnosis of T2DM for > 1 1.
year prior to entry in the study willing and able to complete the questionnaire and on pharmacotherapy Patients who are currently treated with a single 2.
or combination of injectable/oral antidiabetic drugs with or without insulin therapy Treatment type must be unchanged in the 3.
previous 3 months. However, dose modifications are allowed Patients who agree to participate in the study 4.
and give their written informed consent Patients aged between above 20 and below 75 5.
years old.

Exclusion criteria
Patients with type 1 diabetes.
hyperosmolar hyperglycaemic state. Patients with secondary diabetes, including disease 3.
of the exocrine pancreas, endocrinopathies. Patients with concurrent treatment involving 4.
systemic glucocorticoids. However, inhaled, locally injected and topical use of glucocorticoids is allowed. Patients suffering from severe cardiac, hepatic, 5.
renal diseases as judged by the investigator. Any condition of the patient which may have 6.
an impact on objective and outcome of the trial example: patients currently undergoing major/ minor surgical

Data collection
Demographic characteristics such as age, gender, education level, income, height, weight, and body mass index were recorded. Clinical characteristics such as duration of hospital stay, duration of T2DM, presence and duration of comorbidities and presence of diabetic complications. Laboratory results and concurrent medications were also collected.

Study procedures Medication review
In the intervention group medications of patients were reviewed by the trained community pharmacists by utilizing their prescription and the patient's medication evaluation profile. When prescribed by a medical specialist, details about the indication for the drug will be obtained from BNF (British National Formulary, 2010) and TNSTG (Standard Treatment Guidelines, 2010),. Participants were motivated to adhere for their therapy regimen though motivational interviews.
The authors identified and classified the DRPs by using PCNE. (PCNE Classification scheme for Drug related problems V5.01); PCNE is a recognized, which has been reviewed for several times and tested for its validity and reproducibility. In the present study, PCNE was classified for DRPs as 6 domains and utilized in identifying the probable reasons from the patient's prescription with the help of STGs and literatures also. The DRPs was assessed for the appropriateness of -drug indications, drug and dosage, probable drug interactions, ADR and contraindications with three references. Causes for DRP was assessed and intervened. Recommendation was communicated to the physician and changes made. The incidences of DRPs were discussed with the diabetologist and appropriate new therapy was initiated for those having DRPs. The interview on medication review was conducted for 10 -15 minutes for each patient to identify the complexity of the medication regimen and problems detected. The control group was given usual treatment.

Psychological Aspect treatment
The intervention group was provided with psychological aspect treatment (PAT) at baseline and 3, 6, 9 and 12 months by trained pharmacists, with a structured interview and motivational interviewing skills at both the study sites. The first session was conducted within one week of selection of participants for the study. The patient was informed on the contraindications, indications, side effects, administration and frequency of the medicine(s). Patients were counseled in-line with the motivational interviewing strategies to improve their medication adherence. OTC medicines were also taken into the consideration for medication review during the study period.

Workshop for Community Pharmacists
Four sessions were conducted for the community pharmacists who were participated in this study on the above parameters. They were explained about the background of medication review, DRP score forms and evaluation pattern during the sessions. The pilot study was conducted to minimize the variability while assessing DRP score and reviewing the medication among the trained pharmacists. The assessed review on medication by trained pharmacist was reassessed by a specialist in medication review. The trained pharmacist was expected to identify more DRPs in interventional than control group pharmacists who was not attended the workshop on medication review. The assessment was carried out similar to that of pilot study. During one day workshop all the pharmacists were explained on motivational interviewing and decision making as well as communication skills.

Outcome Measures Primary outcome measures
At the end of the study period researcher and coauthors calculated the incidences of DRP and compared the primary outcome with baseline, control and intervention groups by using a checklist which includes common drug problems. Among the enrolled patients DRPs were assessed and documented by conducting the structured interview and medication review was carried out the study participants (pharmacists).

Medication Adherence with Therapy
The 8-item self-report Morisky Medication Adherence Scale (MMAS) was used to assess medication adherence. (Morisky. DE et al, 1986) Secondary outcome measures Secondary outcomes include fasting plasma glucose level, hypoglycaemic episodes, morbidity, adverse effects and total incidence of patient visit to diabetiologist for consultation of probable drug related problem during the study period was measured. The incidence of clinic visit was obtained from the prescriptions. ADR causality assessment was carried out by using Naranjo's scale and assessed by the coauthors. (Naranjo. CA, et al, 1981) All participants completed 4 validated questionnaires during the study period. The first questionnaire was given to the participants 7 days initial to the first counselling. The second questionnaire was given at 6 months; the third questionnaire was given at 9 months and the fourth was given at 12 months.

Sample size
The incidence of DPRs was weighed with respect to primary outcome of the medication review and patient counseling. From the literature review, 25% of control group patients were encountered with DRPs and 30% of DRPs were decreased due to intervention. In a type 1 error of 0.05, a power of 90%, and a ratio of one between both groups of patients, multilevel randomisation resulting in a loss of power of 10%, a total of 800 patients was needed to show a statistically significant difference.

Statistical Analysis
Descriptive analysis was done for the demographic characteristics of patients and other control variables both groups. Difference was tested using chi-square or t-tests. To test the effect of the intervention a multilevel design was used. Medication event was clustered within patients, and patients are clustered within pharmacies. The primary outcome, the adherence, is the dependent variable. To assess the impact of the intervention, multilevel linear and logistic regression analysis was conducted to study differences in outcome measures among patients of the intervention and control groups.
All independent variables of importance, for example socio-demographic factors and medication regimen, are included in the model to adjust for these variables. Data are analysed with SigmaStat for Windows (Demo Version) and differences in changes among the group were measured with 95% confidence intervals.

Results
Over 12 month study, participants' average HBA 1C reduced from 8.9% at initial visit to 7.5%, average LDL was reduced from 124.1 mg/dL to 109.6 mg/dL, and average BP was reduced from 141.5 mm Hg to 132.7 mm Hg. During this time, the eye examination rate was raised from 31% to 48%, and the foot examination rate was raised from 35% to 50%. Only 48.25% of participants were satisfied diabetes care was better from 45.5% of participants in the highest range at baseline to 51.30% at this level after 12 months (  In the present study, the DRPs in TDM and comorbid patients observed are recorded in  *Only problems that have a frequency of more than one were included. The causes of the above mentioned DRPs in T2DM with hypertension were evident in 696 patients as shown in Table No. 3. The major causes assessed were due to drug and dose selection 47.55% (n=331), drug use process such as in appropriate timing of administration, drug under administered and patient unable to use the drug or dosage form as directed. The second major cause of the DRPs in these patients were patient/ psychological associated evident in 39.65% (n=276) of the patients, followed by drug use process in 14.65% (n=102). In 8.47% (n=59) it was due to lack of proper instructions for use of drugs, unawareness of the reason for drug treatment and unable to understand the local language. 6.6% (n=46) due to logistic issues such as prescribed drug not available (anymore) and prescribing errors.    62). This is a very serious factor and through monitoring is required during the period of therapy. Otherwise, the dosing related drug problems constitute to 16% and 5.9% of the overall DRPs in Malaysia and Australia respectively.

Drug Use Problems
These kinds of DRPs arise when the patient administers the wrong drug or does not take any drug. This can be drug use error, administration error and/or filling error in the pharmacy. Proper patient counseling or educating the patient about the disease and the need for treatment can help overcome this problem of medication adherence and discouraging the idea of self medication and over the counter medication can be effective in significantly reducing the risk of wrong medication.
Here the risk of potential non adherence was the major factor, 108 cases were recorded contributing to 14.94% of all the DRPs. The causes of DRP due to drug use (n=102) were inappropriate timing of administration and dosing intervals 18 out of 102, drug unused or under-administered were 73 0f 102 and 11 out of 102 were because patients were unable to use the medication as directed.12.9% and 3.8% was seen for potential non adherence in Malaysia and Australia respectively.

Potential Interactions
The potential drug-drug or drug-food interaction is a form of prescribing or drug-use error.96 cases were reported in the study. The interactions identified were mostly based on established literature and evidence recorded and complied in authenticated resources. The drug interactions contribute to about 13.28% of all the DRPs, where as in Australia and Malaysia they contribute to about 15.1% and 16.3% of the rest of the DRPs respectively.

Other Problems
The other problems reported in this study were 228, 31.53% of all the DRPs recorded. On further interviewing and assessing the data of those 288 cases, it was found that 190 of 228 had inadequate awareness about the health and disease, that could precipitate and cause long term effects, 24 of 228 were not satisfied with the therapy without any error of non adherence and 14 of 228 experienced failure of the therapy, however the reason couldn't be noticed. By contrast, the leading cause reported in Malaysia was inadequate awareness but in Australia it was therapy failure.

Conclusion:
The findings of the study have less significant improvement in their primary and secondary outcomes. It may be concluded, therefore, that the intervention pharmacists showed no demonstrable influence on any of the intermediate health outcomes relating to metabolic control or on therapeutic adherence in T2DM that was significantly different from that exerted by the control cohort of pharmacists.