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PLOS One logoLink to PLOS One
. 2020 Dec 11;15(12):e0243614. doi: 10.1371/journal.pone.0243614

The rising complexity and burden of multimorbidity in a middle-income country

Shamini Prathapan 1, Gunasekara Vidana Mestrige Chamath Fernando 2,3,*, Anne Thushara Matthias 4, Yashodara Bentota Mallawa Arachchige Charuni 4, Herath Mudiyanselage Gayan Abeygunawardhana 3, Batheegama Gamarachchige Gayasha Kavindi Somathilake 2
Editor: Andrea Gruneir5
PMCID: PMC7732070  PMID: 33306724

Abstract

Background

The limited knowledge on aetiology, epidemiology and risk factors for multimorbidity especially evident from low and middle-income countries curtail the development and implementation of sustainable healthcare models. Sri Lanka, boasting for one of South Asia’s most efficient public health systems that is accessible free-of-charge by the citizens is presently transitioning from lower-middle to upper-middle-income tier. Faced with the triple burden of disease, it is imperative for Sri Lanka to incorporate an integrated model to manage multimorbidity.

Methods

A descriptive cross-sectional study was carried out in medical clinics of a tertiary care hospital and a University primary care department. Data were extracted on to a form from the clinical records of patients over the age of 20 years with at least one non-communicable disease (NCD) and analysed.

Results

Multimorbidity was present among 64.1% of patients (n = 1600). Nearly 44.44% of the patients aged 20–35 years have a minimum of two disorders, and by the time they reach 50 years, nearly 64% of the patients have two or more non-communicable diseases. Nearly 7% of those aged over 65 years were diagnosed with four or more disorders. A fourth of the sample was affected by co-morbid diabetes mellitus and hypertension, whereas the combinations of coronary heart disease with hypertension and diabetes mellitus were also found to be significantly prevalent. A salient revelation of the binomial logistic regression analysis was that the number of disorders was positively correlated to the presence of mental disorders 7.25 (95% CI = 5.82–8.68).

Conclusion

Multimorbidity is highly prevalent among this population and seemingly has a detrimental effect on the psychological wellbeing of those affected. Therefore, the need for horizontal integration of all primary to tertiary care disciplines, including mental health, to manage multimorbidity by policymakers is emphasized as a priority task.

Introduction

Management of the rising prevalence of chronic illnesses is one of the biggest challenges facing many countries worldwide. Individual diseases dominate healthcare delivery in many countries around the world and especially in Sri Lanka. People with multimorbidity—those with two or more chronic morbidities—require a more comprehensive approach [1].

Life expectancy has improved dramatically over recent decades. Between 2000 and 2016, global life-expectancy at birth, for both sexes combined increased from 66.5 to 72.0 years [2], and currently exceeds the age of 75 years in nearly 60 countries. However, the number of people with or at risk of long-term conditions, such as diabetes, mental health conditions, and cancer is also proliferating. People living with a chronic condition often have multiple rather than a single condition. As such, multimorbidity is common and has been rising in prevalence over recent years. In the UK, a large study revealed that more than 40% of the population (all ages included) had at least one long-term condition, and almost 25% of the entire population had more than one long-term condition [3].

Multimorbidity is becoming progressively more common with advancing age [46]. It is associated with high mortality, reduced functional status, and increased use of both inpatient and ambulatory health care [4]. The prevalence of multimorbidity in the world varies widely. In a systematic analysis of the prevalence of multimorbidity in high-income countries and low and middle-income countries, it was found that more than 50% of those older than 65 years had multimorbidity and that females were affected more [7].

Data on multimorbidity in South Asia is limited. With the increases seen in aging populations in Asian countries, South Asia is experiencing more multimorbidity than ever before [8, 9]. The prevalence of multimorbidity in South Asia varies from 4.5% to 83% [10]. The prevalence of multimorbidity in India, another South Asian country has been estimated to be 24% [9]. The only study done in Sri Lanka to date on multimorbidity has found a prevalence of 25.4% for cardiometabolic multimorbidity [11]. This has been conducted in rural Sri Lankan community setting. The prevalence of multimorbidity in an urban or a hospital setting in Sri Lanka has not been evaluated before.

Multimorbidity is a threat to patient safety [12]. Patients with multimorbidity are at a greater risk of safety issues for many reasons. Some of the reasons are polypharmacy, which may lead to poor medication adherence and adverse drug events, complex management regimens, more frequent and complex interactions with health care services leading to greater susceptibility to failures of care delivery and coordination, the need for clear communication and patient-centred care due to complex patient needs, demanding self-management regimens and competing priorities, more vulnerability to safety issues due to poor health, advanced age, cognitive impairment, limited health literacy and comorbidity of depression or anxiety. People have both physical and mental health issues simultaneously [13]. One systematic review that included 86 studies found that people with mixed mental and physical multimorbidity had the highest risk of active patient safety incidents and precursors of safety incidents [14].

The health care needs of patients with multimorbidity are complex. The successful management of them requires a shift away from specialism and more towards generalism. The association between sex, age and prevalence of specific chronic diseases is not established in Sri Lanka. A better understanding of the epidemiology of multimorbidity is necessary to develop interventions to prevent it, reduce its burden, and align healthcare services more closely with patients’ needs. Assessing the multimorbidity will help put Sri Lanka onto the track of Universal Health Coverage. This study gives new information on the prevalence of multimorbidity in Sri Lanka. We aimed to examine the characteristics of individuals with multimorbidity (diagnosed with two or more NCDs) in terms of age, gender, socioeconomic dimensions and co-existing mental health disorders.

Materials and methods

Written approvals to all the study procedures were sought from the Ethics Review Committee of the Faculty of Medical Sciences, University of Sri Jayewardenepura (ERC No:35/19). The investigators ensured that the study was conducted following the guidelines set out in the terms of reference and general management procedures of the said Ethics Review Committee, based on the International Guidelines on Biomedical Research of the World Health Organization (WHO) and the Council for the International Organizations of Medical Sciences (CIOMS). Consent was not obtained as there was no direct patient interaction and exclusively the anonymized data were extracted from the clinical records.

A descriptive cross-sectional study was carried out in the Colombo District of Sri Lanka. Sri Lanka is an Island located in the Indian Ocean, with a midyear population estimated to be with 22.235 million inhabitants. The allopathic system of healthcare in Sri Lanka comprises of a public and a private sector. The public sector services are available island-wide, whilst the private sector is based on market demand, and mostly concentrated in the urban areas of Sri Lanka. Free access to health care is a priority of the government of Sri Lanka, who has committed to maintaining this policy for the last two to three decades.

This study was carried out in the medical clinics of a tertiary care teaching hospital in Sri Lanka and a University primary care department (Family Practice Centre). These two study settings were selected as the patients in the suburbs of the University are cared in a coordinated manner between these two institutions through a referral and back-referral system, where a secondary level hospital rarely has any involvement. The tertiary level teaching hospital is managed by the central Ministry of Health, whereas the University managed the primary care department. Both these University-operated institutions are located in the southern part of Colombo, the commercial capital of Sri Lanka.

Data extraction was limited to the clinical records of adult patients (18 years or older) with a minimum of one non-communicable disease (NCD) diagnosed by either a consultant physician or a consultant family physician, and the most recent encounter occurred during the year 2019. Clinic records lacking any one of the following information; i.e. the age, the sex, area, drugs administered were excluded.

The study population was divided into four age groups; 18–35 years, 36–50 years, 51–65 years, 66 and more years. Since many NCDs were considered for multimorbidity, a prevalence (p) of 50% was used to obtain the largest sample size at 95% confidence level with 5% margin of error (e) using the equation n = Z2 p q/e2. A sample size of 384 was obtained for one age group of adults in order to extract data from a finite number of records while also yielding a sufficient statistical power. Therefore, a sample size of 1600 was obtained from both settings, 800 records from each setting with including all four age groups.

All clinic records from the 1st of January 2019 were scrutinized until the sample size was achieved. Investigators collected data from the clinical records of the two settings. Personally Identifiable Information (PII) pertaining to the patient, such as name or address was not extracted, and the anonymized records of each patient were assigned an alphanumeric identifier and kept in the safe custody of the investigators. A data extraction form (Annexure 1) was used to extract the data from clinic records.

Frequencies, percentages with 95% Confidence intervals (95% CI) and cross-tabulations were obtained using the R software tool whereas both R (R version 3.3.3 (2017-03-06) RStudio Version 1.3.959 © 2009–2020 RStudio, PBC "Middlemist Red" (3a09be39, 2020-05-18) for Windows Mozilla/5.0 (Windows NT 10.0; Win64; x64) AppleWebKit/537.36 (KHTML, like Gecko) QtWebEngine/5.12.6 Chrome/69.0.3497.128 Safari/537.36)and SPSS (IBM SPSS Statistics Version 20 IBM Corp. (2017). IBM SPSS Statistics for Windows. Armonk, NY: IBM Corp. Retrieved from https://hadoop.apache.org) software were used for the graphical display for descriptive analysis. Binary logistic regression was carried out after confirming that the data satisfied the relevant assumptions to examine associations between mental health and multimorbidity, restricting the analysis to those aged 20 years and older because mental health morbidities in children are rare. Adjusted odds ratios (ORs) and 95% CIs were used to report the analysis with the help of SPSS and R software.

Results

The total sample size was 1600, of which approximately half were women (54%). Exactly equal proportions of patient records were included from primary care (n1 = 800) and tertiary care (n2 = 800) settings. The predominant age group was 51–65 years that accounted for 44% (n = 704), closely followed by the older persons over the age of 65 years (38%) as represented in Table 1.

Table 1. Socio-Demographical details among the group of patients.

Variable Categories Number of patients (n = 1600) (%)
Gender Female 863 (54%)
Male 736 (46%)
Age 20–35 Years 54 (3%)
36–50 Years 226 (14%)
51–65 Years 706 (44%)
Over 66 Years 614 (38%)

Among the patients, 52.4% (n = 838) had diabetes mellitus, followed by 46.9% (n = 750) with hypertension. Table 2 illustrates the numbers and percentages of patients affected by individual NCDs.

Table 2. Prevalence of common non-communicable diseases among the group of patients.

Disease Total number affected (n = 1600) Gender Age Percentage prevalence (95% CI) (n = 1600)
Male Female 20–35 Years 36–50 Years 51–65 Years Over 66 Years
Diabetes mellitus 838 395 (47%) 443 (53%) 26 (3%) 134 (16%) 367 (44%) 311 (37%) 52.4% (49.9% - 54.8%)
Hypertension 751 345 (46%) 406 (54%) 18 (2%) 110 (15%) 330 (44%) 293 (39%) 46.9% (44.5% - 49.4%)
Coronary heart disease (CHD) 438 226 (52%) 212 (48%) 16 (4%) 59 (13%) 196 (45%) 167 (38%) 27.4% (25.2% - 29.6%)
Bronchial asthma 167 77 (46%) 90 (54%) 02 (1%) 21 (13%) 77 (46%) 67 (40%) 10.4% (8.9% - 11.9%)
Arthritis 125 55 (44%) 70 (56%) 04 (3%) 12 (10%) 53 (42%) 56 (45%) 7.8% (6.5%– 9.1%)
Hypo-hyperthyroidism 122 59 (48%) 63 (52%) 04 (3%) 22 (18%) 52 (43%) 44 (36%) 7.6% (6.3%– 8.9%)
Peptic ulcer disease 53 17 (32%) 36 (68%) 03 (6%) 04 (8%) 20 (38%) 26 (49%) 3.3% (2.4% - 4.2%)
Mental disorders (e.g. depression, anxiety, dementia) 51 26 (51%) 25 (49%) 02 (4%) 06 (12%) 21 (41%) 22 (43%) 3.2% (2.3%– 4.0%)
Heart failure 50 27 (54%) 23 (46%) 00 (0%) 08 (16%) 18 (36%) 24 (48%) 3.1% (2.3%– 4.0%)
Chronic kidney disease (CKD) 47 25 (53%) 22 (47%) 03 (6%) 04 (9%) 23 (49%) 17 (36%) 2.9% (2.1%– 3.8%)
Chronic obstructive airway disease 40 19 (48%) 21 (53%) 00 (0%) 09 (23%) 15 (38%) 16 (40%) 2.5% (1.7%– 3.3%)
Stroke/ Transient ischaemic attack 39 16 (41%) 23 (59%) 00 (0%) 09 (23%) 18 (46%) 12 (31%) 2.4% (1.7%– 3.2%)
Epilepsy 30 12 (40%) 18 (60%) 01 (3%) 02 (7%) 17 (57%) 10 (33%) 1.9% (1.2%– 2.5%)
Atrial fibrillation 18 07 (39%) 11 (61%) 00 (0%) 02 (11%) 09 (50%) 07 (39%) 1.1% (0.6%– 1.6%)
Chronic liver disease 15 06 (40%) 09 (60%) 00 (0%) 00 (0%) 07 (47%) 08 (53%) 0.9% (0.5%– 1.4%)
Cancer 13 04 (31%) 09 (69%) 00 (0%) 02 (15%) 08 (62%) 03 (23%) 0.8% (0.4%– 1.3%)
Interstitial lung disease 2 02 (100%) 00 (0%) 00 (0%) 00 (0%) 01 (50%) 01 (50%) 0.13% (0%– 0.3%)

Multimorbidity was present among 1026 (64.13%) of this group of patients. None younger than 20 years were found among the collected records. Nevertheless, it was an unfortunate yet a salient finding that by the time the population reached 20–35 years, 44.44% (24/54) of the patients have a minimum of two disorders and by the time they reached 50 years nearly 64% (178/280) of the patients have two or more non-communicable diseases. It was also evident in Fig 1 that by the time the population reached the age of 65 years, nearly 7% (41/614) have four or more disorders.

Fig 1. Multimorbidity of diseases in different age groups.

Fig 1

A significantly higher proportion of women (i.e. 5% more, Pearson Chi-Square = 6.97, p = 0.031) was affected by multimorbidity as compared to men (statistically significant association at a confidence level of 95%). Even solitary morbidities were found to be more prevalent among the females as represented in Fig 2.

Fig 2. Multimorbidity and its association with sex.

Fig 2

The major NCDs that contributed to multimorbidity as illustrated in Fig 3 were diabetes mellitus, hypertension, followed by coronary heart disease. Smaller associations were also evident between diseases such as bronchial asthma and arthritis.

Fig 3. Non-communicable diseases in multimorbidity.

Fig 3

The comorbidities most commonly associated with each other were diabetes mellitus with hypertension (25%), followed by hypertension with coronary heart disease (12%) and diabetes mellitus with coronary heart disease (11%). Moreover, the combination of all three diseases diabetes mellitus with hypertension and coronary heart disease was also found to be comparatively common (7%) among the group of patients as represented in Table 3.

Table 3. Prevalence of common multimorbidities among the group of patients.

Most Common Multimorbidities Number affected (n = 1600) (%) Gender Age
Female (%) Male (%) 20–35 years (%) 36–50 years (%) 51–65 years (%) Over 66 years (%)
Diabetes Mellitus & Hypertension 400 (25%) 218 (54.5%) 182 (45.5%) 08 (2%) 66 (16.5%) 178 (44.5%) 148 (37%)
Hypertension & Coronary Heart Disease 194 (12%) 98 (50.5%) 96 (49.5%) 04 (2.1%) 24 (12.4%) 92 (47.4%) 74 (38.1%)
Diabetes Mellitus & Coronary Heart Disease 177 (11%) 85 (48%) 92 (52%) 04 (2.3%) 25 (14.1%) 92 (52%) 56 (31.6%)
Diabetes Mellitus, Hypertension & Coronary Heart Disease 108 (7%) 55 (50.9%) 53 (49.1%) 01 (0.9%) 13 (12%) 60 (55.6%) 34 (31.5%)

The mean number of disorders among patients with mental health diseases were 1.94 (± 0.95). The mean age of the patients with mental disorders was 61.31 years with a standard deviation of 12.16. The percentages of patients with mental disorders were nearly equal in relation to the male and female categories (51% vs 49%). Of all with mental disorders, 52.9% of the patients visited the tertiary health care facility, whereas 47.1% visited the primary care facility. Logistic regression analysis (Table 4) confirmed that as the number of disorders (multimorbidity) increases, the risk of developing any mental disorders increases by 7.25 (95% CI = 5.82–8.68). This was the only variable found to be significant through the regression analysis at 95% confidence level (p-value = 0.00 < 0.05).

Table 4. Logistic Regression analysis for mental health disorder by age, sex and number of physical disorders.

Any mental health disorder
Standardized Coefficients (95% CI) Adjusted OR (95% CI) p-value
Age (in years) 0.21 (0.19, 0.24) 1.00 (0.98, 1.03) 0.80
Male (Vs Female) 0.34 (-0.25, 0.93) 1.13 (0.63, 2.03) 0.69
Tertiary Care (Vs Primary Health Care) 0.31 (-0.28, 0.91) 1.12 (0.62, 2.02) 0.71
Multimorbidity (number of disorders) 1.98 (0.9, 2.85) 7.25 (5.82, 8.68) 0.001

NB: The covariates used in the adjusted OR model are Age, Gender, Health Care Setting and the Number of health

disorders (multimorbidity)

Discussion

This study gives valuable insights into the complexity of multimorbidity in Sri Lanka. To the best of our knowledge, the study is first of its kind to utilize a large sample to examine the burden, pattern and correlates multimorbidity among the adult population in Sri Lanka. This study is unique as it covers both primary and tertiary care settings.

It is known that multimorbidity is significantly associated with age. This finding was consistent across several studies, including those involving LMICs especially in India [8, 15]. In our study, the predominant age group was 51–65 years that accounted for 44% of the study population and closely followed by the older persons over the age of 65 years (38%). With advancing age, the number of comorbidities increases.

Multimorbidity is, however, not restricted to older patients. Being socioeconomically disadvantaged such as belonging to Lower middle-income countries (LMIC), speeds up the process of acquiring multimorbidity. Therefore, the population in countries such as Sri Lanka fall prey to multimorbidity earlier in life. In our study, 44% percent of patients aged 20–35 had two or more illnesses, which is alarming for a developing country like Sri Lanka. An Indian study also shows that multimorbidity is prevalent among the young population as well [15]. In a study carried out in Australia (North West Adelaide Health Study), 4% of the 20–39 year age group, 15.0% of the 40–59 age group had multimorbidity [16]. Assuming multimorbidity is a problem of the aged undermines the real magnitude of the problem. This questionable assumption could have a serious economic impact for LMIC countries, including in healthcare resource allocation to subsets of the population. The rising burden of diseases as people age will pose a significant burden on an LMIC’s development. Identifying that younger age groups are also affected should prompt to find active solutions for holistic care provision to this age group as they are not entitled by default to the care available to the geriatric population. This finding has important practical implications. Recently in Sri Lanka, several steps have been taken by policymakers to reduce risk factors that account for NCD’s such as smoking, physical inactivity and unhealthy dietary patterns. The modification of these risk factors should begin at younger ages. At the policy level, screening for NCD’s has been made mandatory for state-sector health care workers to get their promotions and increments. Similarly, modifications have been made in the school curricula to improve physical activity. An area of each town has been designated to host a walking, play or physical activity area to promote physical activity. All these measures will target younger individuals who belong to or constitute the future active workforce.

There is a female predominance in multimorbidity in worldwide studies even when gynaecological diseases are not taken into account as morbidity. An extensive systematic review indicated that women had a greater prevalence of multimorbidity as compared to men [17]. There is growing evidence that women use more healthcare facilities, particularly government-funded free healthcare, compared to men. This could be one reason for the gender difference [17, 18]. Another reason could be due to the gender-based inequities in the health sector of Sri Lanka. The Sri Lankan health care system has been traditionally designed to support maternal and child health outcomes over the years and Sri Lanka has achieved remarkable success in the field of maternal and child health care.

In our study, the commonest comorbidities found were diabetes and hypertension, of which diabetes was the commonest. Diabetes is a global public health concern and a common comorbidity in patients with hypertension [19, 20]. In urban South Asians context, diabetes and hypertension are most commonly encountered in other populations in the region [8]. The clustering of diabetes with hypertension and diabetes with coronary heart disease is also alarming. This clustering of disorders is well established in the past [21, 22]. Identifying clustering is essential as they signify underlying pathophysiology and risk factors to be similar, and the interventions to reduce the incidence of these illnesses also can take a similar approach. Our interventions could target individuals suffering from a given index disease such as diabetes who develop successive conditions such as CHD, stroke or CKD. Identifying and effective management of the initial condition could potentially lead to a lower incidence of the successive conditions.

In 2017, about 425 million people had diabetes worldwide, and approximately 80% lived in low- and middle-income countries [23]. The burden diabetes places on health care system are enormous due to its complications. The rising prevalence of diabetes in urban South Asia is attributed to the sedentary lifestyles and greater consumption of fast food rich in sugar and saturated fats that are supplemented by globalization [24, 25]. Having identified diabetes to be this common in an urban setting in Sri Lanka, necessary remedial steps for primary prevention can be implemented.

As Sri Lanka undergoes an epidemiological transition, mental health plays an integral part in morbidity and mortality of chronic diseases [26]. One of the most significant burdens of multimorbidity is its association with mental disorders. Our study confirmed that as the number of disorders increases, the risk of developing any mental disorders increases by 7.25 (95% CI = 5.82–8.68) and was the only variable that was significant in the regression analysis. Several studies in the past have also revealed that higher number of chronic conditions was associated with the poorer self-rated health, functional health measured using activities of daily living and instrumental activities of daily living and WHOQoL tools. This was reported in a study conducted across China, India, Russia, South Africa Mexico and Ghana [27]. In an Indian study, 66% of the older population was distressed physically, psychologically or both. Further, it was recognized that the number of morbidities was linked to poorer psychological wellbeing and increased disability [28]. A sizeable Scottish study published in the Lancet, also revealed that the prevalence of a mental disorder increased with the number of diseases [3]. Several other studies in Asia have also highlighted that rising multimorbidity affects mental health [29, 30].

Sri Lanka has a curative healthcare system, in which patients with specific diseases are cared for in selected specialized institutions (example: cancer care hospitals). This could have led to the low proportion of patients with cancer or with any other specific diseases. In a meta-analysis on multimorbidity conducted in the South Asian setting it was revealed that none of the included studies was undertaken in a primary care setting [10]. Subsequently, a handful of studies had been done, inclusive of primary care [31]. This will be one of the few studies done in the primary care setting in South Asia assessing multimorbidity. As primary care plays an equally important role as tertiary care in health provision [10], these results will serve as an eye-opener.

In countries like Sri Lanka and other LMIC’s, the dual burden of infectious disease and non-communicable diseases are pushing the health systems into peril. These countries have to continue to battle against infectious diseases while focusing on emerging multimorbidity [32]. Empowering of health systems to deal with multimorbidity requires training of healthcare workers to recognize the risk factors and offering health care advice to minimize the risks.

Our study shows that multimorbidity is indeed a problem in South Asia. Greater emphasis needs to be placed on further research into the area with the hope of providing better patient-centred care to those affected with multimorbidity. As the medical community is shifting into finer subspecialties a greater emphasis needs to be placed on treating patients as a whole as two or more chronic illness seems to cluster with an alarming rate in patients all over the globe. This change which requires horizontal integration needs to take place starting from medical school onwards and extend to the patient’s bedside [21]. As Sri Lanka continues to battle the epidemic of NCDs, our current national NCD program should be tailor-made to care for patients with multiple morbidities. This will avoid fragmented care.

Strengths and limitations

Being a descriptive study, ours has a few limitations that deserve mention. We relied on the details available in the clinic records without attempting to confirm the diagnosis by directly inquiring the patients’ symptomatology. Hence, the accuracy of the diagnosis cannot be vouched entirely on. Certain diseases may have missed being diagnosed at all, and the patients who do not present to health care facilities for consultation have also been missed. Furthermore, a few more records were excluded owing to the lack of certain important demographic and disease-related information. Their exclusion could have biased our results to some extent. Third, the proportion of persons in our cohort with multimorbidity is based on the conditions we chose to define multimorbidity. We did not consider the severity of conditions or treatment given for conditions in this study. We also did not measure health outcomes, such as mortality and hospital admissions.

Although multimorbidity is very common in Sri Lanka and elsewhere in the world, it is not yet known how best to organise health services in order to manage these patients optimally. Details about the continuity of care and health service providers in the lifetime of the patients would have helped us to gain more insights into how health care should be organized to deliver optimal care. Information such as the number of visits to each health care provider, utilization of health services by patients would have provided us more details about health care service utilization that would have been useful in the interpretative exercise.

Our study also has several strengths. It provides for the first time in Sri Lanka, a detailed description of multimorbidity in both primary and tertiary care. The large sample size is also one important attribute. Besides, the large sample size allowed us to stratify patients into different age groups and also to see if certain diseases clustered. Identification of clustering is crucial as it has both policy and clinical implications. Provided the tertiary care study setting is one of the largest hospitals on the island, the results can be generalized to the country to a large extent. The inclusion of mental health conditions is also a vital feature of this study that constitutes a critical aspect of multimorbidity.

Supporting information

S1 Checklist. STROBE statement—Checklist of items that should be included in reports of cross-sectional studies.

(DOCX)

S1 Data

(XLSX)

S1 File

(DOCX)

S2 File

(DOCX)

Acknowledgments

We wish to acknowledge the Departments of Medicine and Family Medicine of the Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka for allowing to utilize the patient records for research purposes.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

Alana T Brennan

23 Jul 2020

PONE-D-20-13239

The rising complexity of Multimorbidity in a middle income country

PLOS ONE

Dear Dr. Fernando,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Sep 06 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Alana T Brennan

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

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2. Please ensure you have thoroughly discussed any potential limitations of this study within the Discussion section, including the impact of potentially confounding factors.

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5. Please ensure that you refer to Figure 3 in your text as, if accepted, production will need this reference to link the reader to the figure.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This article describes multi-morbidity in Sri Lanka based on data from a primary care center and a tertiary hospital. The article aims at adding to the literature by revising the characteristics of multi-NCD morbidity in Sri Lanka. The authors also look at the predictors of mental health in the selected population. The manuscript could be improved as suggested below.

MAJOR ISSUES

Overall.

1. Needs language revision – needs significant improvement on English

2. Not a clear research question/hypothesis. For instance, the stated goal is to describe multi morbidity however data is presented on association between multi-morbidity and mental health outcomes. It is not clear if mental health conditions is the outcome variable, if so, the hypothesis should be clearly stated.

Introduction

o The goal of the study is not clear. Is the goal to describe the characteristics of people diagnosed with NCD (i.e., age and sex [gender]?) or to describe the characteristics of people diagnosed with 2 or more NCDs?

Methods

Sample size: Description of sample size estimation is not clear

o If the study is descriptive in nature, what is the significance level for? Is this an analytical or descriptive study?

� Needs to provide rationale for not including all patients in the registry and limiting it to a sample size calculation.

� Were the people excluded different than those that remained in the study?

MINOR ISSUES

Overall

• Data was collected only for individuals over 20 years of age but no rationale is provided for this selection.

Abstract.

• Conclusions not supported by data

• Abstract needs to be rewritten

• Reorder the introduction

• Not clear why only regression for mental health.

Figures and tables.

• Figure 3 is not high resolution and not clear

• No need for tables under figures 1 and 2

Introduction

o Might need some reformatting of paragraphs

• Methods

o Selection of clinic/hospital needs to be better justified (is it representative of the population, why? If not, how to avoid bias)

o Again, provide rationale for selecting only individuals over 20 years.

o Needs to add rationale behind selecting diagnosis for inclusion.

o Formatting of age groups is different (line 109)

o Provide rationale for age groups

Methods. A. Sample Size

o Is the data extraction form provided?

Data analysis

� Why restricting to age 18 and older when the eligibility states age 20 and older?

o Suggest to use either SPSS or R. Indicate version, year, etc. full software citation.

• Results

o Not clear what is meant by “by the time they reach half the decade” – it would be best to describe the age group.

o The use of “increase” in line 148 suggests a baseline. I suggest to consider use another term that more accurately describes the comparision being made.

o Use n= XXX as opposed to XX/1600

o How does the proportion of multimorbidity relates to original size of age groups (an adjusted rate might be useful)?

• Discussion

o Could be more focused.

o Needs to better discuss the strengths and limitations of the study.

Reviewer #2: "The rising complexity of Multimorbidity in a middle income country " emphasizes important health issues. Below are some suggestions to strengthen the manuscript

Comments

1. Methods section: Please add subsections and reorganize as necessary to improve clarity and readability

2. Methods (line 109) please justify why these age categories were used, if possible referencing previous studies for compatibility

3. Methods (line 128) states the analysis was restricted " to those aged 18 years and older", however line 101 states "patients over 20 years ...". Please correct or clarify.

4. Table 2 Please clarify in the footnote which covariates were uncluded in the adjusted OR model. Would it be possible to present unadjusted and adjusted. Could additional factors be included in the adjusted model?

5. It is clear ethical approval was obtained from the relevant institute. Patient data was anonymous. Did patients give permission to the institute to use their data?

6. Please carefully check English language usage throughout the text.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Decision Letter 1

Andrea Gruneir

8 Oct 2020

PONE-D-20-13239R1

The rising complexity of Multimorbidity in a middle income country

PLOS ONE

Dear Dr. Fernando,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR:

The reviewers and I both noted that you have done a nice job addressing the previous comments. There are some additional suggestions, in particular those raised by Reviewer 3, that would greatly strengthen the manuscript, if addressed. Please note, too, the suggestions for modifying the title and changing the language describing the mental health findings to better reflect the work you have done.

==============================

Please submit your revised manuscript by Nov 22 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Andrea Gruneir

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Thank you for addressing almost all comments. Please additionally add subsection headers within the methods section

Reviewer #3: Examples of literature on MM in Intro and Discussion are largely from high income countries - when there are a reasonable number of publications from lower income countries that might be more appropriate.

Table 1 is useful, but could be more useful to have info by age and sex, plus a similar table of most common multimorbidities. Would want table of patient sociodemographic characteristics. The authors could please specify which variables were included in the adjusted regression analyses?

More details about the regression analyses are needed - describing the stepped process by which you did both sets of regression analyses - and especially the analysis including mental health variables.

And the conclusions about mental health need to be tempered - this is a cross-sectional study "...as the number of disorders increases, the risk of developing any mental disorders increases..."

The term "elderly" is considered pejorative, please instead use older persons, older adult, older population.

One of the biggest findings here is the high prevalence in 'young" age groups. This could be part of another analysis - (narrower age groups (20-29, 30-39, etc) and look at age of diagnosis - but for this publication, authors could emphasize this interesting finding about high MM prevalence in young age groups.

Finally, the title is misleading - it describes the burden of multimorbidity in a sample of patients, not its complexities.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Decision Letter 2

Andrea Gruneir

13 Nov 2020

PONE-D-20-13239R2

The rising complexity and burden of multimorbidity in a middle-income country

PLOS ONE

Dear Dr. Fernando,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR:

Thank you for taking the time to revise and resubmit your manuscript. I think that you have done a nice job of addressing the Reviewers' comments throughout the text. I would just like to see some modifications to the tables so that they are easier to read. In all tables, it would be helpful to have the sample size shown within the column headers so that the denominator for each cell is clear. For Table 2, you should consider having a total column (where you can show the prevalence of each condition for the full sample) and then the prevalence stratified by each sex and age; you sort of have this but you need the denominator for each column and perhaps a bit more cleaning up. You may want to consider similar adjustments to Table 3. There is a fair bit of data in your study and anything you can do to help your readers understand it would be useful.

==============================

Please submit your revised manuscript by Dec 28 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Andrea Gruneir

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Decision Letter 3

Andrea Gruneir

25 Nov 2020

The rising complexity and burden of multimorbidity in a middle-income country

PONE-D-20-13239R3

Dear Dr. Fernando,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Andrea Gruneir

Academic Editor

PLOS ONE

Additional Editor Comments (optional): Thank you for your patience and for continuing to make revisions to this manuscript. I think that there are still some modifications to your tables that are required to make them as readable as possible, but also that there is no reason to hold back your manuscript at this point. Congratulations on this work!

Reviewers' comments:

Acceptance letter

Andrea Gruneir

2 Dec 2020

PONE-D-20-13239R3

The rising complexity and burden of multimorbidity in a middle-income country

Dear Dr. Fernando:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Andrea Gruneir

Academic Editor

PLOS ONE

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    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files.


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