|Year : 2021 | Volume
| Issue : 1 | Page : 4-12
Non-compliance in pediatric nephrotic syndrome
Ranjit Ranjan Roy, Md. Murad Chowdhury, Amit Kumar Datta, Modasseer M Hossain, Tahmina Jesmin, Abdullah Al Mamun, Mst. Shanjida Sharmim
Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
|Date of Submission||11-Sep-2021|
|Date of Acceptance||23-Sep-2021|
|Date of Web Publication||29-Dec-2021|
Prof. Ranjit Ranjan Roy
Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka
Source of Support: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, Conflict of Interest: None
Background: Non-compliance to medications and health advice significantly impact care of patients as well as impose financial burden in nephrotic syndrome (NS) patients. Aim: The aim of this article is to determine the cause and consequence of non-compliance in NS patients. Materials and Methods: This prospective study was conducted between March 2020 and February 2021 in the department of Pediatric Nephrology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Seventy-seven NS patients were recruited randomly. In-person interviews were conducted with attendents of patients, along with patients if possible. Clinical and laboratory data were collected from medical records. Residence, financial constraints, educational status, health advices (daily bed side urine test), relapses of disease, different types of immunosuppressive medications, etc. were provided for the cause of non-compliance. Consequences of non-compliance were observed through the experience of relapses, asthma attack or infection, and drug toxicity. Data were analyzed using SPSS software version 20. Results: A total of 77 patients were analyzed and among them 74.02% were non-compliant and 25.98% were compliant. Among the non-compliant patients, non-compliance to asthma medication, prednisolone, second-line immunosuppressive drugs, and third-line immunosuppressive drugs were 43.87%, 31.57%, 14.03%, and 10.53%, respectively. About 56.14% of the patients did not do bed side urine for albumin (BSUA). Remote location (63.15%), financial constraints (36.84%), low parental education (35.09%), ignorance (17.54%), and undetermined cause (17.50%) were observed as main contributing factors for non-compliance. Among study populations, 77.19% experienced more relapses in comparison to compliance (10%). Non-compliant patients experienced more asthma attack (70.17%, 40/57), pneumonia (63.2%), and steroid toxicity (36.8%) in comparison to the compliance group (45%, 36.8%, and 10%, respectively). About 31.57% of the non-compliant group had spent 30,000–70,000 taka in comparison to 5% in the compliance group and it was statistically significant (P = 0.031). Conclusion: Poor compliance to medications and health-related advices have diverse effects including frequent relapse, drug toxicity, higher rates of complications and hence increased healthcare cost. Remote location, ignorance, and idiopathic causes were major contributing factors behind non-compliance issue. Appropriate counseling might change this prevailing non-compliance scenario in future.
Keywords: Compliance, nephrotic syndrome, non-compliance
|How to cite this article:|
Roy RR, Chowdhury MM, Datta AK, Hossain MM, Jesmin T, Mamun AA, Sharmim M. Non-compliance in pediatric nephrotic syndrome. Paediatr Nephrol J Bangladesh 2021;6:4-12
|How to cite this URL:|
Roy RR, Chowdhury MM, Datta AK, Hossain MM, Jesmin T, Mamun AA, Sharmim M. Non-compliance in pediatric nephrotic syndrome. Paediatr Nephrol J Bangladesh [serial online] 2021 [cited 2022 May 18];6:4-12. Available from: http://www.pnjb-online.org/text.asp?2021/6/1/4/334121
| Introduction|| |
Compliance has been defined as the extent to which a person’s behavior coincides with medical or health advice, whereas a patient is addressed as non-compliant when he or she does not take a prescribed medication or follow a prescribed course of treatment or deliberately fail or refuse to comply. In comparison to non-compliance, “non-adherence” is the behavior in which a patient unintentionally fails to follow a plan.,
This compliant and non-compliant terms are more popular in the management of diseases, especially chronic diseases. Childhood chronic conditions such as bronchial asthma (BA), rheumatoid arthritis (RA), chronic kidney disease (CKD), hypertension (HTN), glomerulonephritis (GN), cystic fibrosis, etc. are required to follow multifaceted and comprehensive management regimens such as daily medications for timely as well as dietary or activity demands or restrictions.
Non-compliance to comprehensive management of chronic diseases such as medication schedules, dialysis, and nutritional regimens remains a significant barrier for the effective management of the population.
Evidence indicates that a greater proportion of chronic patients, especially CKD, were non-compliant to prescribed dialysis, medication, and dietary and fluid recommendations, causing ongoing challenges in the health care. It has been observed in diabetes mellitus (DM) patients that increased adherence level had meaningful declines in their rates of hospitalization and emergency department visits. Similarly in BA patients, it is observed that non-compliance to medications is directly related to increased mortality and frequent hospital admission with acute exacerbation and is termed as “cost problem” because of the increased rates of hospitalization that are needed to maintain lung function., Poor compliance to antihypertensive drugs leads to permanent and debilitating target organ damage including CKD, blindness, acute stroke syndrome, and acute coronary syndrome.
Treatment regimens may cause disruptions of normal life cycle such as frequent hospitalizations or treatment sessions; scheduled follow-up causes absences from school. Even parents also face so many obstacles such as stressful life, financial load, or quit from job to deal with treatment demands as families are responsible to follow treatment protocols.
Nephrotic syndrome (NS) is one of the most common CKDs in children, with a prevalence of approximately 16 cases per 100,000. The chronicity of NS is characterized with its relapse-remitting courses, which tends to resolve spontaneously following puberty. The main stay of treatment of NS is steroids and 80–90% of the patients will experience relapse of the disease. For half, the disease relapses frequently or patients become dependent on steroids to maintain remission. Approximately 7.4–19.6% is steroid-resistant (SRNS) with its poor renal outcome.,,
In 30–60% of the cases, NS is associated with BA and its relapse is frequently associated with poor control of BA, urinary tract infection (UTI), viral upper respiratory tract infection, pharyngitis, pneumonia, septicemia, peritonitis, and diarrhea. Continuing the long-term specialized therapy with intense outpatient follow-up and family participation for disease monitoring and treatment are fundamental goals for the successful management of NS in pediatric patients. It is evident that good compliance has a positive effect on clinical outcomes in DM, hypertension, and dyslipidemia.
The success of healthcare services is mostly dependent on the motivation and willingness of patients to follow the prescribed regimens. Treatment adherence contributes to clinical outcomes and is more complex among chronically ill children. If children and parents do not follow instructions adequately, health care is compromised even after giving the effective treatments. Nurten et al. had shown that non-compliance to dietary and fluid restrictions, hemodialysis (HD), and medication treatment has increased the risks of hospitalization and mortality significantly. It has been observed among adult CKD patients that non-adherence rates to dialysis range from 2% to 98%. Similarly in pediatric kidney transplant patients, the prevalence of non-adherence in developed countries can be as low as 30% and as high as 70%.
In developed countries, factors related to positive clinical outcomes are well described. Unfortunately in developing countries, strategies leading to successful health care in chronic ill patients are largely understudied and provide a series of barriers such as economic burden, educational status, gender issue, and access to healthcare services to achieve optimal health care. As pediatric patients go from childhood to adolescence, adherence may waver as patients find ways to manage their chronic illness.
It is essential to examine the influence on disease outcome in childhood NS. But non-adherence may cause treatment failure in pediatric chronic conditions. Unfortunately, there are few or no published data available about the aftermath of non-compliance to medication and health services in children with NS. With this view, this study has been aimed to identify the cause and consequence of non-compliance in NS patients.
| Materials and Methods|| |
Patients and procedures
NS patients aged ≥1 to <18 years were recruited randomly for this study focusing on the causes of non-compliance and its consequences after taking informed written consent.
Research subjects were NS cases who attended the inpatient ward and outpatient care of nephrology department of BSMMU from March 2020 to February2021 in the Department of Pediatric Nephrology of BSMMU, Dhaka, Bangladesh. The subjects met the inclusion criteria: steroid-sensitive (initial attack and relapse) and -resistant NS following the treatment protocol recommended by the pediatric nephrologist, and age at onset: ≤1.0 NS due to specific kidney disease (such as Henoch-Schönlein purpura, lupus erythematosus, or associated with hepatitis B or C), participation in another trial, children with congenital forms of NS, and patients who did not wish to participate in the study were excluded from the study.
A structured questionnaire contained individual data of each patient such as age, date of birth, gender, initial date of diagnosis, clinical characteristic, management, complication, medication check list, and home care for patients [daily monitoring of bed side urine test for albumin (BSUAlb), symptom, and immunosuppressive drugs taken].
The parents and guardians of the study populations were interviewed face to face by an expert pediatric nephrologist. Clinical and laboratory data were collected from medical records which were obtained by a well-designed questionnaire. Variables of interest included sex, age, residence, financial constraints, educational status, health advices (daily bed side urine test), relapses of disease, different types of immunosuppressive medications, etc. were provided for identifying the cause of non-compliance. Consequences of non-compliance were observed through the experience of relapses, asthma attack or infection, and drug toxicity.
Diagnosis of NS was based on generalized edema, massive proteinuria (>40 mg/m2/h), hypoalbuminemia (<2.5 g/dL), and hyperlipidemia. Frequent relapse NS (FRNS) was defined as four or more relapses in the previous 12 months. Steroid-dependent NS (SDNS) was defined as two consecutive relapses while on every alternate day steroid or within 14 days of stopping of oral steroid, whereas infrequent relapse NS (IFRNS) was defined as less than two relapses within the first 6 months of presentation or less than four relapses within 12 months’ period. Remission was defined when bed side urine albumin was nil for 3 consecutive days in early morning specimens. Relapse was defined as urine albumin 3+ or 4+ (or Up:Uc>2.0 mg/mg) for 3 consecutive days in early morning specimens in patients who were on remission. Children with NS have complete lack of remission, despite therapy with prednisone at 60 mg/m2/day for 4 weeks with three pulses of methylprednisolone at a dose of 1000 mg/1.73 m2 on every alternate day. Steroid toxicity manifested as growth retardation, osteoporosis, infections, diabetes, cataract, hypertension, hirsutism, and Cushingoid appearances. Educational status was classified as literate and illiterate on the basis of giving signature by themselves.
Data management and statistical analysis
The collected data were checked, tabulated, and then inserted into a computer. Nominal data such as patients’ gender, patients’ diagnosis, parental education of both father and mother, and socioeconomic status were described as percentages and χ2 test. Numerical data such as current patients’ age and compliance were expressed as mean ± SD and percentage as needed. The χ2 test (for categorical data) and Fisher’s exact test were done to compare financial status, educational status, and drug toxicity in compliant and non-compliant groups and P-value was considered to be significant if the difference was P < 0.05. Data were analyzed using SPSS software version 20.
Patients and their attendants who met the criteria had been asked for parental/guardian written informed consent. This research had been granted approval by the Institutional Review Board (IRB) of BSMMU.
Flow chart of the study
| Results|| |
In this prospective study, [Table 1] illustrated demographic and clinical characteristics of the study population (n = 77), in which mean age was 8.3 ± 4.2 and 59.74% were male children. About 31.17% mothers and 22.07% fathers were illiterate: 88.31% were working parents and 54.54% children were residing in the rural area. In the present study, out of 77 patients, 40.20%, 28.60%, 27.30%, and 3.90% of the patients were IFNS, FRNS, SDNS, and SRNS, respectively, whereas 63.60% of the children were in association with BA and 29.87% of the patients had experienced steroid toxicity.
|Table 1: Demographic and clinical characteristics of study population (n = 77)|
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In [Table 2], comparison between non-compliant and compliant children was observed among different variables such as residence, educational status of father and mother, monthly income, hospital expense of BA in association with NS and its different types of relapse and steroid toxicity. P-values were significant (P = 0.05) among residence, educational status of father and mother, low monthly income (10,000 taka), presence of BA in NS patients, increased number of relapse more than four times, and steroid toxicity and these were 0.010, 0.004, 0.004, 0.008, 0.034, and 0.001, respectively. About 35% of compliant patients’ monthly family income was between 30,000 and <40,000 taka; 31.57% of the non-compliant group had spent 30,000–70,000 taka in comparison to 5% in the compliance group and it was statistically significant (P=0.031). Steroid toxicity is more prevalent among non-compliant patients (36.8%) than compliant counterpart, which is statistically significant (P=0.04).
|Table 2: Comparison of difference between non-compliant and compliant patients|
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In [Figure 1], it was observed that out of 77 patients, 74.02% of the patients belonged to the non-compliant group either to medication and or to health-related advice and 25.98% were compliant.
|Figure 1: Distribution of patients (n = 77) according to compliance, whereas 74.02% of the patients belonged to the non-compliance group|
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In [Table 3], nine patients (15.79%) did not come for routine follow-up as per advise; rather, they took self-medication during relapses and 32 patients (56.14%) did not follow advise to perform bed side urine albumin test in the morning, which helps in the early detection of NS relapse.
|Table 3: Distribution of patients among non-compliance (n = 57) to health advice|
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[Figure 2] shows that non-compliance to asthma medication, prednisolone, second-line immunosuppressive drugs (levamisole, cyclophosphamide, mycophenolatemofetil, and azathioprine) and third-line immunosuppressive drugs (cyclosporin and tacrolimus) was 43.87%, 31.57%, 14.03%, and 10.53%, respectively.
|Figure 2: Percentage of non-compliance patients (n = 57) according to medication|
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Non-compliant patients had higher rates of infectious complications. In [Figure 3], the infection rate between non-compliant and compliant patients was observed. Among the non-compliance patients (n = 57), pneumonia, UTI, peritonitis, meningitis, and cellulitis were 63.2%, 7.0%, 10.0%, 3.0%, and 10%, respectively. In compliant patients, these variables were 36.8%, 3.0%, 5.0%, 0.0%, and 5.0%, respectively. P-value was significant in pneumonia among compliant and non-compliant patients (P = 0.044), but in UTI, peritonitis, meningitis, and cellulitis, P-values were insignificant (P-value of UTI 1.000; peritonitis 0.669; meningitis 1.000; cellulitis 0.669).
|Figure 3: Infection rate between non-compliant and compliant patients. Fisher’s exact test was done|
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Parental educational background, location of health services, financial condition, ignorance, and undetermined causes played a crucial role regarding compliance to medications and or health-related advice as found in this study.
In [Figure 4], causes of non-compliance were analyzed and remote location (63.15%), financial constraints (36.84%), low parental education (35.09%), ignorance (17.54%), and undetermined cause (17.50%) were observed as main contributing factors for non-compliance.
| Discussion|| |
Compliance to medications and health-related advice are the big issues in case of chronic disease management. In this study, it was found that 74.02% were non-compliant either to medication and or health-related advice. Similar findings have been reported in Aziz and Ibrahim’s study, in which 56% of the patients with chronic diseases such as hypertension, ischemic heart disease, diabetes, and BA were non-compliant.
Adherence in taking the medication is fundamental in the management of NS. In chronic diseases such as diabetes, adherence to medications is associated with better control of intermediate risk factors, less hospitalization, lower healthcare costs, and lower mortality., Zyczynski and Coyne also observed a linear decrease in hospitalization rates from 30% to 13% as medication compliance increased.
In the present study, among non-compliant patients, 43.87% were non-compliant to asthma medication, whereas 31.57% was in oral prednisolone which is the mainstay of medication in nephrotic child. A study identified that the non-compliant manner to steroid therapy can be accountable for multiple relapses. Similarly, Supramaniam also found that more than 59% of hypertensive patients did not adhere to the medications prescribed. But Setyawati et al. showed different findings in their work, in which 30 patients adhered to the prednisolone regimen and 15 were non-adherent to the regimen.
In our study, 15.78% did not come for follow up when they experienced relapse and 56.14% did not follow advice to perform bed side urine albumin test in the morning, which will helps in the early detection of relapse. Our study findings coincide with Diong et al.’s study, in which they executed that deficit in parental knowledge especially in home urine dipstick monitoring (health advice) and recognition of warning signs during relapse were the main issues of non-compliance.
Among compliant patients, only 10% had four or more relapses per year, whereas a significant number of non-compliant patients (77.19%) had experienced four or more relapses per year as well as drug toxicity also. This non-compliance either to medications and/or health-related advise ultimately leads to increased frequency of relapses and hospitalization. In the present study, 29.9% of the patients had features of steroid toxicity. It was more prevalent among non-compliant patients (36.8%). Frequent use of oral steroid for repeated relapses, in addition to self-medication, contributed to higher prevalence of steroid toxicity. The previous study in this regard noted that due to side effects of drugs patients face unnecessary tests, dosage adjustments, changes in the treatment plan, emergency department visits, or hospitalization, which ultimately result in increased cost of medical care.
The parental education system plays a crucial role in compliance to medications and/or health-related advice. Low literacy is associated with more hospitalizations, greater use of emergency care, less adherence to treatment recommendations, worse health status, and higher mortality rates. The parental education will help to know the disease’s nature and the treatment’s goal comprehensible for all families and that might have contributed to the remission status. Usually families with a low background in education may require more time to understand the messages. Several studies also had shown that repeated education-based program on patient or parent cognitive abilities increased the awareness and patient’s outcomes.
We also had almost similar observation. Among non-compliant parents, a significant portion of parents were illiterate (70.19%). Charnaya and Ann found that educational background of family was linked with non-compliance in NS leading to repeated hospitalizations and higher economic cost.
Non-adherence carries a huge economic burden and yearly expenditure for its consequences. Due to medication non-adherence, estimation of hospital costs is as high as 13.35 billion dollars annually in the USA alone. This study has revealed that 95% of the compliant patients had spent less than 30,000 taka per relapse, whereas 31.6% of the non-compliant patients had spent between 30,000 and 70,000 taka for each episode of relapse and are statistically significant (P =0.05). Various studies have reported that medication compliance is inversely associated with total healthcare costs per patient.,,,,
Our patient had to wait few more days after relapse to collect money and to settle other family urgent matter before they had to start for BSMMU hospital. Families were physically and financially exhausted. Out-of-pocket money has come from regular income, social contribution, borrowing, and selling belongings.
BA is a well-established precipitating factor for NS relapse and non-complaint patients experienced higher rate of relapses, repeated steroid therapy, and hence steroid toxicity., Among our study population, about 63.6% (49/77) of the patients had BA and 70.2% (40/57) of non-complaint patients had BA in comparison to complaint counterpart 45% (9/20), which is statistically significant. The present study revealed that the majority of non-compliant patients who had BA experienced frequent relapses and 43.87% of the patients were non-compliant to asthma medications including reliever and preventer nebulization, inhalers, and oral montelukast, which might play a significant role in repeated hospital admissions among non-complaint patients. In western population, non-compliance to asthma medications is quiet high around 50%.
Our parents did not know why they would not give asthma medications. Parents stopped medication as they felt better; this attitude may decrease their compliance to asthma drugs.
No single factor consistently influenced medication compliance. Various parameters influence medication compliance such as age, gender, community, remote location, income, parental education and occupation, number of children, number of family members, form of medicine, number of medicines, etc. Two-third patients could not come at the right time because of distant location of their residence to health facility.
Negligence and poverty play important roles in medication compliance. Poverty associated with low socioeconomic status can seriously affect the ability and motivation of an individual or family to manage chronic illness. In our study, we found that 36.8% of the non-compliant patients belong to lower socioeconomic background (monthly family income less than 10,000 taka, 1 dollar =85.5 taka). Poor financial condition and overall ignorance contributed more to non-compliance; 29.54% of total non-compliance was due to financial constraints and another 17.54% was due to ignorance or unknown etiology.
In our study, non-compliant patients had higher rates of infectious complications. About 63.2% of non-compliant patients had pneumonia, 10% had peritonitis, 7% had UTI, and 3% had meningitis. Antibiotics for infectious complications along with other costs during hospital stay are responsible for higher cost per relapse in non-compliant patients. Numerous studies have demonstrated that non-compliance with prescribed medication results in increased morbidity and mortality from a wide variety of illnesses, as well as increased healthcare costs., Sokol et al. reported that lowest hospitalization (13%) and less complication rates were observed in type 2 DM patients due to the highest level of medication compliance.
Non-compliance is associated with loss of productivity in terms of absence for schoolgoing children and number of days missed from work for parents attendants. But we could not report exact school day losses due to repeated hospital admissions in our patients, as schools were closed due to Covid-19 crisis. There were several limitations identified in our study such as study design, single-center study, small sample size, and no longitudinal follow-up had done. Data had been collected via interviewers, so biasness was also present indeed.
| Conclusion|| |
Poor compliance to medications and health-related advices in NS have diverse effects including frequent relapse, drug toxicity, and higher rates of complication; hence, increased healthcare cost, health facility, poverty, educational background, ignorance, and idiopathic causes were major contributing factors behind non-compliance issue. All intrusiveness control issues including patients as well as parental education should be addressed in intervention efforts to improve compliance in patients with NS. Appropriate counseling might change this prevailing non-compliant scenario in future.
Financial support and sponsorship
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflicts of interest
The authors declare that there is no conflict of interests regarding the publication of this paper.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]