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Research Article| Volume 19, 101210, January 2023

Out-of-pocket expenditure on non-communicable diseases during Covid-19. A cross-sectional study from a semi-urban area of Kannur, Kerala

  • Resmi Mathew
    Affiliations
    Department of Public Health, K S Hedge Medical Academy, NITTE (Deemed to be University), Mangaluru, Karnataka, India
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  • Jeby Jose Olickal
    Correspondence
    Corresponding author. Department of Public Health K S Hedge Medical Academy, NITTE (Deemed to be University), Mangaluru, 575018, Karnataka, India.
    Affiliations
    Department of Public Health, K S Hedge Medical Academy, NITTE (Deemed to be University), Mangaluru, Karnataka, India
    Search for articles by this author
Open AccessPublished:December 30, 2022DOI:https://doi.org/10.1016/j.cegh.2022.101210

      Abstract

      Introduction

      Non-communicable disease (NCD) care was drastically affected during the COVID-19 pandemic. Therefore, this study aimed to estimate the cost incurred for NCD care during the pandemic and also to compare the cost of care of private and public facility utilizers.

      Methods

      This community-based cross-sectional analytical study was conducted among 316 individuals aged 30 years and above from selected primary care facility service areas in Kannur district, Kerala. The total cost of illness for all NCDs was calculated from the patient's perspective and was estimated using a bottom-up approach. Direct, indirect, and total costs were summarized using the median with IQR. A median regression analysis was done to find the factors associated with total cost.

      Results

      The total median direct medical cost was ₹400.0 (120–2360.0), and the total median direct non-medical cost was ₹720.0 (300.0–1200.0). The total median cost of NCD care was ₹1200.0.0 (200.0–3990.0). There was a significant association between the place of NCD service utilization and cost. The cost of availing care from private [₹2497.5 (455.0–6490.0)] was much higher compared to public facilities [₹120.0 (0–1000.0)].

      Conclusion

      The expenditure on NCD care during COVID-19 was high and for a private facility utilizer, it was much higher compared to a government facility utilizer. Strengthening the services through subcentres can reduce travel expenses, hence the non-medical cost of NCD care.

      Keywords

      1. Introduction

      Non-communicable diseases (NCDs) impart premature mortality, morbidity, and a huge disease burden.
      • Song S.
      • Trisolini M.G.
      • Labresh K.A.
      • Smith S.C.
      • Jin Y.
      • Zheng Z.-J.
      Factors associated with county-level variation in premature mortality due to noncommunicable chronic disease in the United States, 1999-2017.
      The most important NCDs are systemic hypertension, type 2 diabetes mellitus, and coronary artery disease. The prevalence of these diseases is higher in low-middle-income countries compared to developed countries due to urbanization. The prevalence of hypertension in India is 30%
      • Ramakrishnan S.
      • Zachariah G.
      • Gupta K.
      • et al.
      Prevalence of hypertension among Indian adults: results from the great India blood pressure survey.
      and type 2 diabetes is 15% in rural India and 19% in urban India.
      • Ranasinghe P.
      • Jayawardena R.
      • Gamage N.
      • Sivanandam N.
      • Misra A.
      Prevalence and trends of the diabetes epidemic in urban and rural India: a pooled systematic review and meta-analysis of 1.7 million adults.
      The chronic nature of NCDs and the resultant economic burden on households of NCD patients in the form of out-of-pocket expenditure can cause impoverishment in all societies.
      • Verma V.R.
      • Kumar P.
      • Dash U.
      Assessing the household economic burden of non-communicable diseases in India: evidence from repeated cross-sectional surveys.
      The proportion of cost incurred out of total health care cost is higher for NCD care than for communicable diseases. They have a major impact on healthcare costs, productivity, and economic growth of individuals as well as the country.
      • Rohini C.
      • Research P.J.-W.O.
      2020 undefined. Prevalence and patterns of multi-morbidity in the productive age group of 30-69 years: a cross-sectional study in Pathanamthitta District, Kerala.
      A comprehensive and integrated national action led by governments is the only viable solution to this challenge.

      Noncommunicable diseases [Internet]. [cited 2022 Nov 7]. Available from: https://www.who.int/data/gho/data/themes/noncommunicable-diseases.

      However, proper utilization of NCD services from public facilities can reduce this OOPE (Out Of Pocket Expenditure) on NCDs.
      • Kataria I.
      • Siddiqui M.
      • Gillespie T.
      • et al.
      A research agenda for non-communicable disease prevention and control in India.
      Ayushman Bharat is a scheme by the Government of India to protect the poor and vulnerable populations from out-of-pocket expenditure.

      Ayushman Bharat - National health protection Mission| national portal of India [Internet]. [cited 2022 Nov 7]. Available from: https://www.india.gov.in/spotlight/ayushman-bharat-national-health-protection-mission.

      Similarly, Aardram is one of the four missions under the “Navakerala Program” launched by the Government of Kerala, aiming to completely transform the public health sector to be affordable to the community.

      Aardram - National health mission [Internet]. [cited 2022 Nov 7]. Available from: https://arogyakeralam.gov.in/2020/04/01/aardram/.

      The provision of more diagnostic and treatment services from public facilities like FHC can assure some financial risk protection. By increasing the NCD service utilization of the public healthcare system, the out-of-pocket expenditure on NCDs can be reduced.
      • Krishnan G.
      • Nair A.
      Primary health-care innovations with superior allusion to family health centers.
      During the COVID-19 pandemic, in order to control the spread of the disease, aggressive locked-down strategies were adopted by all countries. Therefore, the routine care of NCDs became interrupted and many patients who were on medication, especially the elderly population, put a halt on follow-up care.
      • Gopalan H.S.
      • Misra A.
      COVID-19 pandemic and challenges for socio-economic issues, healthcare and National Health Programs in India.
      Similarly, the pandemic contributed economic crisis as well by increasing the chances of complications.
      • Kaye A.D.
      • Okeagu C.N.
      • Pham A.D.
      • et al.
      Economic impact of COVID-19 pandemic on healthcare facilities and systems: international perspectives.
      Therefore, this study tries to find out the direct and indirect costs incurred by NCD patients during the COVID-19 pandemic.

      2. Materials and methods

      2.1 Ethical clearance

      This study protocol was reviewed and approved by the Institutional Ethics Committee K.S. Hegde Medical Academy (KSHEMA), Nitte Deemed to be University and the approval number is INST.EC/EC/147/2021-22. Prior permission was obtained from District Medical Officer (DMO) Kannur and Kalliasseri gram panchayat. Written informed consent was obtained from all the participants.

      2.2 Design and setting

      This cross-sectional study was conducted from October 2021 to July 2022 among individuals aged 30 years and above in the service areas of selected FHC (Family Health Centre) at a semi urban part of Kannur District, Kerala. FHCs are upgraded PHCs (Primary Health Centre) with improved infrastructure, service provision, and human resources, and due importance is given to the quality of care. Improved provisions for NCD screening and treatment through the pre-check counter, designated NCD clinics, laboratory services, ECG monitoring, and community-based NCD screening camps are provided by FHCs. FHCs enable a web-based appointment system (E-health) for patient reception to drug delivery and also have improved amenities in the OPDs.

      2.3 Sample size estimation and sampling technique

      The sample size was calculated for another objective of this project, assessing the NCD service utilization from public facilities and the calculated sample size was 387.
      • Bhagyalakshmi C.
      Health PK-A of M and, 2019 undefined. Utilization of noncommunicable disease services provided by public health facilities in Kasaragod, Kerala.
      Among 387, 316 participants utilized NCD services from public or private facilities and the sample size used for the current analysis is 316. Among the 34 FHCs in Kannur District, one FHC (Kalliasseri) was chosen by convenience sampling method. Out of 18 wards of Kalliasseri, two wards were chosen by simple random sampling. By proportionate sampling, required was selected.

      2.4 Method of data collection

      The student researcher and an Accredited Social Health Activist (ASHA) worker visited the household and interviewed the participants at their house. A validated semi-structured questionnaire was used. Content validity was done by three subject experts. The questionnaire included domains to capture the socio-demographic and behavioural data, questions to explore NCD service utilization for hypertension, diabetes, and Cardio Vascular Disease (CVD), and questions to know the cost of NCD care, from the patient's perspective.

      2.5 Cost calculation

      The total cost of illness for all NCDs was calculated from the patient's perspective and was estimated using a bottom-up approach. The total cost was calculated by adding total direct and indirect costs. Direct costs are directly attributable to the patient care for diagnosing a disease or while getting treated. Direct medical costs are the expenses incurred for laboratory tests and medications. The direct non-medical costs are the costs of meals en route to the hospital and travel. Indirect costs are not directly related to patient care or costs incurred not as a result of medical management of NCDs, like loss of wages for the patient and the caretaker.

      2.6 Statistical analysis

      The data were entered into EpiCollect 5 mobile application and analysis was done using STATA Version 14. Categorical variables such as gender, occupation, marital status, type of ration card, social class, and alcohol and tobacco use were summarized as frequencies in percentages. Continuous variables such as age and cost of care were summarized as mean (standard deviation), and median (interquartile range) based on the normality of the data. Direct, indirect, and total costs were summarized using median (interquartile range) or mean (standard errors). A simple and multiple median regression analysis was done to find the factors associated with the total cost. A p-value less than 0.05 was considered statistically significant.

      3. Results

      The mean (SD) age of the participants was 56.7 (±11.7) years. Among them, 70% (n = 221) of the participants were females, half of the participants (n = 154) had high school education, 71% (n = 223) were unemployed, and 84% (n = 265) were married. Around 66% (n = 209) of them had BPL ration card and 28% (n = 86) belonged to class 5 social class. Of all, 5% (n = 16) were alcohol users and 3% (n = 6) were using tobacco [Table 1].
      Table 1Socio-demographic and behavioural details of participants (N=316).
      Variablen%
      Age in years
      <454213.3
      45–6013241.8
      >6014245.0
      Gender
      Female22169.9
      Male9530.1
      Education
      Class 1-78928.2
      Class 8-1015448.7
      Class 11-124213.3
      Graduate and above319.8
      Occupation
      Unemployed22370.6
      Daily waged4514.2
      Retired319.8
      Monthly salaried175.4
      Marital status
      Married26584.0
      Widow/Widower4614.6
      Unmarried30.9
      Divorced20.6
      Type of ration card
      BPL20966.1
      APL10733.9
      Social class
      Class 1299.2
      Class 26319.9
      Class 36319.9
      Class 47523.7
      Class 58627.2
      Alcohol use
      Yes165.1
      No30094.9
      Tobacco use
      Yes82.5
      No30897.5
      BPL- Below Poverty Line, AP- Above Poverty Line.
      Out of the total respondents, 45% (n = 144) had self-reported hypertension, around 30% (n = 95) had self-reported diabetes and 6% (n = 21) had self-reported CVD. About, 37% (n = 119) reported any one NCD. The distribution of the cost of care among the service utilizers in the population is shown in Table 2. The average direct medical cost for NCD care in the population is ₹400.0 (120–2360.0), the average direct non-medical cost is ₹720.0 (300.0–1200.0), and the total cost is ₹1200.0.0 (200.0–3990.0). For a private facility utilizer, the average direct medical cost is ₹1740.0 (360.0–6000.0), the average direct non-medical cost is ₹650.0 (300.0–1200.0), and the total cost is ₹2890.0 (660.0–7540.0).
      Table 2Distribution of cost of care among NCD service utilizers from Government and private facilities (N = 316).
      VariableGovernment facility utilizers (N = 168)Private facility utilizers (N = 148)Overall (N = 316)
      n (%)Median (IQR)Mean (SE)n (%)Median (IQR)Mean (SE)n (%)Median (IQR) in INRMean (SE) in INR
      Direct medical cost
      Consultation86 (51.2)60.0 (10.0–60.0)49.2 (10.5)93 (62.8)300.0 (60.0–800.0)607.0 (75.0)179 (56.6)60.0 (30.0–400.0)339.1 (44.4)
      Medication5 (2.3)1250.0 (1200.0–1800.0)1454.8 (300.8)76 (51.4)4080.0 (1900.0–9300.0)6833.0(855.6)81 (25.6)3600.0 (1800.0–8400.0)6501.0 (815.6)
      Lab95 (30.1)120.0 (60.0–330.0)294.8 (45.7)122 (82.4)360.0 (160.0–660.0)606.0 (75.0)218 (68.9)240.0 (110.0–595.0)467.9 (47.6)
      Total111 (35.1)120.0 (60.0–390.0)356.1 (60.7)141 (95.3)1740.0 (360.0–6000)5369.5 (902.9)253 (80.0)400.0 (120.0–2360.0)3148.9 (527.0)
      Direct non-medical cost
      Travel64 (38.1)720.0 9360.0–1200.0)849.5 (78.8)97 (65.5)600.0 (300.0–1200.0)1010.5 (122.2)161 (50.9)700.0 (300.0–1200.0)946.5 (80.0)
      Meals (patient)1 (0.6)240.0 9240.0–240.0)240.0 (0)11 (7.4)300.0 (100.0–400.0)350.0 (81.7)12 (3.8)300.0 (150.0–400.0)340.8 (75.2)
      Meals (care taker)0 (0)001 (0.7)500.0 (500.0–500.0)500.0 (0)1 (0.3)500.0 (500.0–500.0)500.0 (0)
      Total65 (38.7)720.0 (360.0–1200.0)840.1 (78.1)98 (66.2)650.0 (300.0–1200.0)1044.6 (123.6)163 (51.6)720.0 (300.0–1200.0)963.1 (80.7)
      Indirect cost
      Loss of wages (patient)10 (6.0)144.0 (12.0–3960.0)1340.9 (609.2)7 (4.7)16.0 (9.0–4200.0)1749.3 (928.6)17 (5.4)144.0 (12.0–3960.0)1509.0 (508.4)
      Loss of wages (caretaker)0 (0)0011 (7.4)2000.0 (700.0–3600.0)1945.5 (439.3)11 (3.5)2000.0 (700.0–3600.0)1945.4 (439.3)
      Total10 (6.0)144.0 (12.0–3960.0)1742.7 (357.9)211000.0 (400.0–2016.0)1699.8 (383.3)31 (9.8)800.0 (144.0–3600.0)1584.0 (321.2)
      Total cost119 (70.8)360.0 (110.0–1440.0)911.2 (113.6)1412890.0 (660.0–7540.0)6349.0 (945.1)261 (82.6)1200.0 (200.0–3990.0)3842.0 (539.3)
      The distribution of the cost of care for NCD among the service utilizers is depicted in Table 3. The total direct medical cost comes to around 79% of total spending for NCD care. For a government facility utilizer, medication expense for NCD comes to around 7% of total spending. Similarly for private facility utilizer, the expense for medication was 58% of their total expenditure on NCD care. Out of the total expenditure on NCD care, 15% was spent on travel expenses. For government facility utilizers, 50% of the total cost and for private facility utilizers, 11% of the total cost was spent on travel.
      Table 3Distribution of cost for NCD service utilization among individuals (N = 316).
      UtilizationOverall (N = 316)Government (N = 168)Private (N = 168)
      Amount spent in INR% of total spendingAmount spent in INR% of total spendingAmount spent in INR% of total spending
      Total1002756100107588100895168100
      Consultation606906.142353.9564556.3
      Medication52658452.572746.851931058
      Laboratory charges10199510.22806026.1739358.3
      Travel15239215.25437050.59802211
      Meals (patient)40900.42400.238500.4
      Meals (caretaker)5000005000.1
      Loss of wages for patient256542.61340912.5122451.4
      Loss of wages for caretaker214002.100214002.4
      Direct medical cost79666979.43956936.875710084.6
      Direct nonmedical cost15698215.75461050.810237211.4
      Indirect cost491054.91340912.5356964
      INR- Indian Rupees.
      The median regression analysis of the cost of care for NCD care is depicted in Table 4. After adjusting to the covariates, individuals availed of NCD service from private facilities spent a significantly high amount on NCD care compared to government facility utilizers (₹2124, 95% CI = 1368.7–2879.2, p < 0.001).
      Table 4Multiple median regression analysis of factors associated with the cost of care on NCD (N = 316).
      VariableUnadjusted coefficient (95%CI)Adjusted coefficient (95%CI)P- value
      Age in years
      >601510 (721.32–2298.67)908 (−426.68–2242.68)0.182
      45–60150 (−645.46–945.46)214 (−1020.52–1448.52)0.733
      <45ReferenceReference
      Gender
      Male1170 (611.33–1728.66)400 (−543.34–1343.34)0.405
      FemaleReferenceReference-
      Education
      Class 1-7970 (11.45–1928.54)998 (−565.98–2561.98)0.210
      Class 8-10769 (−135.77–1673.77)806 (−621.31–2233.31)0.267
      Class 11-12235 (−853.30–1323.30)894 (673.37–2461.37)0.263
      Graduate and aboveReferenceReference-
      Occupation
      Daily waged−160 (−1477.55–1157.55)376 (−1497.50–2249.50)0.693
      Retired1720 (323.24–3116.76)770 (−1233.07–2773.07)0.450
      Unemployed410 (−754.48–1574.48)480 (−1203.30–2163.30)0.263
      Monthly salariedReferenceReference
      Social class
      Class 1−75 (−1156.50–1006.50598 (−863.21–2059.21)0.421
      Class 2700 (−135.21–1535.21)306 (−791.23–1403.23)0.584
      Class 3−60 (−895.21–775.21)−6 (−1106.08–1094.08)0.991
      Class 4430 (−365.71–1225.71)82 (−939.64–1103.64)0.875
      Class 5ReferenceReference
      Place of NCD care
      Private facility2395 (−368.31–608.31)2124 (1368.75–2879.24)<0.001
      Government facilityReferenceReference
      CI- Confidence Interval, Regression constant = −1582.

      4. Discussion

      This cross-sectional study was conducted among 316 participants in the Kannur district, Kerala to find the direct, indirect, and total costs incurred for NCD care. This study identified the proportion of known hypertension, diabetes mellitus, and CVD as 45%, 30%, and 6% respectively.
      In the study population, of the total cost, 80% was direct medical costs for NCD care, 16% was spent on direct non-medical costs, and 5% was spent on indirect costs. The results were comparable with a prevalence-based cost of illness study conducted in Bangladesh where the direct medical cost was 90% and the indirect medical costs spent was 9%.
      • Afroz A.
      • Alam K.
      • Ali L.
      • et al.
      Type 2 diabetes mellitus in Bangladesh: a prevalence based cost-of-illness study.
      This is also, similar to the results of a systematic review conducted in low and middle-income countries where the direct medical cost comprises the major share of the total cost of health care.
      • Kazibwe J.
      • Tran P.B.
      • Annerstedt K.S.
      The household financial burden of non-communicable diseases in low- and middle-income countries: a systematic review.
      In a similar study conducted at Thrissur, Kerala, to find out the health care utilization and OOPE, it was found that, median cost of total direct expenses for health was ₹5000 whereas median indirect cost was ₹500.
      • Vijayan S.
      • Puliyakkadi S.
      • of S.C.-I.J.
      2020 undefined. Health care utilization and out of pocket expenditure in a rural area of Kerala: a cross sectional study.
      In the current study, among the service utilizers, the median direct medical cost of NCD care was ₹400.0 (120–2360.0) and the median direct non-medical cost was ₹720.0 (300.0–1200.0). Also, the median total medical cost was ₹1200.0.0 (200.0–3990.0).
      In this study, individuals with NCD spent more than 50% of their total expenditure on medications and for a private facility utilizer, the spending on medication is more. Comparable findings were observed in a study conducted in Georgia
      • Gotsadze G.
      • Bennett S.
      • Ranson K.
      • Gzirishvili D.
      Health care-seeking behaviour and out-of-pocket payments in Tbilisi, Georgia.
      where, out of the total cost, more than 50% of individuals spent on medications and, the results were not identical to the findings of another study where 83% of total spending was on medication. In this study, around 10% of total was on laboratory expenses and this was identical with the results in another study where 9% of spending was on laboratory investigations.
      • Afroz A.
      • Alam K.
      • Ali L.
      • et al.
      Type 2 diabetes mellitus in Bangladesh: a prevalence based cost-of-illness study.
      The travel expenses for a government facility utilizer were high and the expenditure for medication was less compared to a private facility utilizer. This might me due to the availability of NCD medication from the government sector and inadequate service provision through peripheral centres like subcentres so that people had to travel.
      • Subramanian S.
      • Gakunga R.
      • Kibachio J.
      • et al.
      Cost and affordability of non-communicable disease screening, diagnosis and treatment in Kenya: patient payments in the private and public sectors.
      The expenditure on NCD care for a private facility utilizer was found to be much higher compared to a government facility utilizer and which constituted more cost for medication, consultation, and laboratory expenses with a median cost of ₹120 (0–1000.0) and ₹2497.5 (455.0–6490.0) respectively. The results obtained in a similar study conducted in Bangladesh and the current study were compared and the direct cost of NCD care was 320.1 USD 3.51 USD respectively.
      • Afroz A.
      • Alam K.
      • Ali L.
      • et al.
      Type 2 diabetes mellitus in Bangladesh: a prevalence based cost-of-illness study.
      Similarly, the median total cost of NCD care in Bangladesh and in the present study were 366.6 and 7.78 USD respectively. The cost of care on NCD was found to be high in the study conducted at Bangladesh as this study participants were exclusively diabetic patients. Here, in the present study the proportion of diabetic individuals were only 24% and that might be reason for the disparity in cost.
      This study identified that 52% of total spending is on medication and the results were not identical to the findings of another study where 83% of total spending was on medication. Around 10% of total was on laboratory expenses and this was identical with the results in another study where 9% of spending was on laboratory investigations.
      • Afroz A.
      • Alam K.
      • Ali L.
      • et al.
      Type 2 diabetes mellitus in Bangladesh: a prevalence based cost-of-illness study.
      Out of the total 80% of expenditure on NCD care as direct medical costs, a government facility utilizer spends 37% and a private facility utilizer spends 85%. Around 16% of the total cost is spent on direct non-medical expenses while availing of NCD care and was 51% for a government facility utilizer compared to 11% for a private facility utilizer. This points toward the availability of medication free of cost, consultation, and laboratory facilities at an affordable cost from a public facility.
      • Subramanian S.
      • Gakunga R.
      • Kibachio J.
      • et al.
      Cost and affordability of non-communicable disease screening, diagnosis and treatment in Kenya: patient payments in the private and public sectors.
      However, in order to avail of these services, the beneficiary has to travel to the facility from distant localities. This eventually increases the travel expenses and will result in a high direct non-medical cost. According to study conducted at Kerala, proximity to public facility to avail health care was identified as a determinant that increases OOPE.
      • Sanitha V.P.
      • Parida J.K.
      • Awasthi I.C.
      Health conditions, medication and hospitalisation preferences of elderly in Kerala.
      Hence, there is a need for the decentralization of health care delivery at the sub-center level through new initiatives like health and wellness centres so that people can easily avail services, especially services related to NCDs, and thereby reduce the direct non-medical expenses such as travel expenses while availing NCD care.
      In the current study, we identified a significant association between the place from where NCD service is availed and the cost of care on NCD. Compared to the median cost of ₹120.0(0–1000.0) for a government facility utilizer, an individual availing NCD care from a private facility spends a median cost of ₹2497.5 (455.0–6490.0) and individuals utilizing the private facilities for NCD care spent ₹2395 more compared to those who utilize NCD services from government facilities and the association was found to be statistically significant (p < 0.001). This finding is consistent with the observations in a study conducted in Kenya where the cost incurred from a public and private facility was 31USD and 129.7USD respectively.
      • Subramanian S.
      • Gakunga R.
      • Kibachio J.
      • et al.
      Cost and affordability of non-communicable disease screening, diagnosis and treatment in Kenya: patient payments in the private and public sectors.
      According to the National Health Accounts, the OOPE for healthcare is maximum in Kerala compared to other states and it is higher than the national average. As the health care utilization from private facilities increases, the OOPE also increases. This also indicates the importance of strengthening the public health care system in diagnosing and treating NCDs.
      There are a few limitations in the current study. The cost of NCD care is captured in this study as per the information given by the participant to the researcher. The data quality will vary according to the participant's memory of the expenditure incurred in the past year. Hence, there is a chance for memory or recall bias. Also, as a health care provider accompanied for data collection, the social desirability bias cannot be ruled out. As the current study used a questionnaire to collect the data using a direct interview method. The chances of suggestive errors cannot be avoided.

      5. Conclusions

      The expenditure on NCD care during COVID-19 was high, and the expenditure for a private facility utilizer was much higher than a government facility utilizer. The cost incurred on NCD care for a government facility utilizer is mainly for travel and a private facility utilizer spends out of pocket on NCD care for medication. With proper utilization of public facilities and improving awareness among beneficiaries, the out-of-pocket expenditure on health care can be reduced considerably.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

      Data availability

      The datasets analysed during the current study are available from the corresponding author on reasonable request.

      Declaration of competing interest

      None.

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