Determinants of MSK health and disability--social determinants of inequities in MSK health.

Best Practice & Research Clinical Rheumatology 28 (2014) 411e433

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Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh

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Determinants of MSK health and disability e Social determinants of inequities in MSK health Francis Guillemin a, *, Erin Carruthers b, Linda C. Li b, c a b c

University of Lorraine, EA 4360 APEMAC, Nancy F-54500, France Arthritis Research Centre of Canada, Richmond, BC, Canada University of British Columbia, Department of Physical Therapy, Vancouver, BC, Canada

a b s t r a c t Keywords: Inequity Inequality Determinants Musculoskeletal disorders Osteoarthritis Rheumatoid arthritis

Even in most egalitarian societies, disparities in care exist to the disadvantage of some people with chronic musculoskeletal (MSK) disorders and related disability. These situations translate into inequality in health and health outcomes. The goal of this chapter is to review concepts and determinants associated with health inequity, and the effect of interventions to minimize their impact. Health inequities are avoidable, unnecessary, unfair and unjust. Inequities can occur across the health care continuum, from primary and secondary prevention to diagnosis and treatment. There are many ways to define and identify inequities, according for instance to ethical, philosophical, epidemiological, sociological, economic, or public health points of view. These complementary views can be applied to set a framework of analysis, identify determinants and suggest targets of action against inequity. Most determinants of inequity in MSK disorders are similar to those in the general population and other chronic diseases. People may be exposed to inequity as a result of policies and rules set by the health care system, individuals' demographic characteristics (e.g., education level), or some behavior of health professionals and of patients. Osteoarthritis (OA) represents a typical chronic MSK condition. The PROGRESS-Plus framework is useful for identifying the important role that place of residence, race and ethnicity, occupation, gender, education, socioeconomic status, social capital and networks, age, disability and sexual orientation may have in creating or maintaining inequities in this disease. In rheumatoid arthritis (RA), a

* Corresponding author. E-mail address: [email protected] (F. Guillemin).

http://dx.doi.org/10.1016/j.berh.2014.08.001 1521-6942/© 2014 Elsevier Ltd. All rights reserved.

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F. Guillemin et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 411e433

consideration of international data led to the conclusion that not all RA patients who needed biologic therapy had access to it. The disparity in care was due partly to policies of a country and a health care system, or economic conditions. We conclude this chapter by discussing examples of interventions designed for reducing health inequity. © 2014 Elsevier Ltd. All rights reserved.

1. Introduction Even in most egalitarian societies, disparities in care exist and may affect people with chronic musculoskeletal (MSK) disorders and related disability. These may translate into inequality in health and health outcomes. Access to appropriate prevention and care for chronic MSK disorders is not only necessary, but is a basic human right. The insufficient integration of this concept in research on determinants of disease progression and prevention underlines the need for research. To measure inequity and its determinants, it is essential to have indicators of inequity. In the past 10 years, there has been an increase in initiatives to promote awareness about inequity in health and health care. The Cochrane methodology group introduced a framework to detect and report determinants of health inequity in all systematic reviews [1,2]. A developing area of measurement is Patient Reported Outcome (PRO). The Outcome Measures in Rheumatology (OMERACT) initiative introduced health equity considerations in development of such instruments in 2012 [3]. This includes a specific attention dedicated to measuring health literacy and ensuring cross-cultural equivalence of PRO, irrespective of socioeconomic status and language. The goal of this chapter is to review concepts and determinants associated with health inequity, and the effect of interventions to minimize their impact. Inequality versus inequity Whitehead [4] asserted that health inequalities are inequity if they are avoidable, unnecessary, unfair and unjust. In 2003, Braveman [5] proposed that health equity was a state of absence of systematic disparities in health (or its social determinants) between the advantaged and disadvantaged social groups. As such, health equity is a fundamental ethical principle of social justice. Norheim [6] pointed out in 2009 that health inequalities that are amenable to human intervention were unfair and should be mitigated. Differences in care occur between countries and are determined by several factors including the wealth of the countries and their health system. These differences do not make one necessarily more inequitable than the other, though unequal. When differences occur within a country, within a specific health care system, it leads to more perceived inequities, as people become more aware of the discrepancy. This phenomenon usually broadens with increasing public discourse and media attention. One should distinguish between inequalities in needs and inequity in supply of health services and treatment. Health inequalities in needs refer to a situation where individuals are in need of more care when severely ill or less care when less ill. Health inequity, on the other hand, refers to the availability of health services and treatment based on individuals' personal, financial and socioeconomic characteristics rather than their health status and needs. Hence, health inequity is a fundamental injustice in delivery of care to people with similar health conditions. Much confusion exists in the literature between inequalities and inequities. Often, researchers are unable to distinguish the two concepts because they don't know the actual needs of the population of interest. The approach is reduced to considering subgroups with more or less precise limits of identification/definition, and to surmise that because there is imbalance, the inequality is almost synonymous to inequity. Unfortunately, it will not be possible to solve the issue, unless considering patient's situations individually, and then identifying the person to a subgroup at risk of inequity. This may apply to clinical practice, but cannot generalize to a population, particularly in epidemiological or intervention studies.


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A good measure of inequality in a population is the concentration index, derived from the Gini coefficient, a measure of statistical dispersion intended to represent the income distribution of a nation's residents. The concentration index applied to ill-health provides a means of quantifying the degree of income-related inequality in a specific health variable [7]. It relates income distribution in this population to the distribution of their needs. It can also illustrate how one can measure if the curve relating needs to resources used departs from linearity and concentrates in some groups of population who become advantaged groups. If the supply of health care concentrates in wealthy categories, it describes a pro-rich income-related inequality (Fig.1). A horizontal inequity describes how resources are unequally distributed to people with equal needs. It is a form of inequity measured when all needs of a population are equal. Points of view There are many ways to define and identify inequities according to ethical, philosophical, sociological, epidemiological, economic, or public health points of view. Researchers with ethical and philosophical points of view differentiate between inequality, which identifies difference in care provision based on needs, and inequity, which focuses on justice in care provision. On the other hand, sociologists focus on identifying inequities and developing hypotheses for studying relevant determinants. Epidemiologists take the point of view that focuses on identifying determinants of inequity and their impact using experimental designs, quantitative analysis, and risk indicators. In contrast, economists approach the subject by analyzing resource consumption and economical modeling of health care systems at the macro (national) and micro (patient) levels. Researchers in public health are interested in identifying sources of inequity by means of population data, system-based approach, and these analyses are oriented towards developing action to reduce inequities in vulnerable groups. The points of view of the different disciplines propose a comprehensive framework of analysis for identifying determinants and providing evidence to guide actions against inequity. Determinants Most determinants of inequity in MSK disorders are similar to those in the general population and other chronic diseases. In this chapter, we will focus on osteoarthritis (OA), a model of chronic MSK disease, and rheumatoid arthritis (RA), a common chronic inflammatory disorder, in which access to expensive biological therapies is crucial to some patients.

Fig. 1. Ill-health concentration curve.

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Population data People in society are exposed to inequity by demographic characteristics, societal factors and living conditions that determine to some degree the risk of disease, disability and lower quality of life. These factors are common to the general population, and therefore apply to people suffering from chronic MSK disorders, independently of other more specific factors. There are many determinants of inequity currently identified. First, the health care system may be a source of inequity. In Ireland [8] the evolution over the last 15 years has documented a change from a pro-rich inequity distribution of care in 1997 to a pro-poor distribution for accessing specialist and general practitioners in 2001. A similar trend was observed in Italy, caused mainly by income and regional variations and by educational attainment and insurance [9]. In Thailand, health care use tends to favor the poor, especially at the primary care level after implementing a universal coverage policy [10]. Personal factors may also play a role. For example, access to hip and knee replacement surgery is different between men and women, with women over 3 times less likely to undergo arthroplasty despite equal willingness and need [11]. Access to hip and knee OA treatment is also associated with education level, income, place of residence and personal factors. Overall, the highest access group are men between the ages of 60 and 84. On the other hand, access tends to be low among people living in rural communities and of non-white ethnicity [12]. Education is a strong determinant of differences in health. It has been shown to determine a remarkably homogeneous gradient of prevalence at the disadvantage of low educated people across age classes for a large number of chronic disease groups in Europe (Table 1) [13]. Health professionals and patients may have an influence on each other's behaviors. This sometimes may be a catalyst of inequity. A decline in inequality for hip replacement over 1990e2003 was observed in Finland despite structural features (uneven availability, co-payments, plurality of provisions) due to directed service expansion and the behavior changes of health professionals and patients [14]. In Ontario Canada, Glazier [15] found no issue in access to primary care physicians based on people's level Table 1 Education differences (low vs high education) for chronic disease groups in Europe. Chronic disease groups

Stroke Diseases of the nervous system Diabetes mellitus Arthritis Hypertension Stomach/duodenum ulcer Genitourinary diseases Headache/migraine Osteoarthrosis Liver/gall diseases Chronic respiratory diseases Heart disease Back and spinal cord disorders Cancer Kidney stones and other kidney diseases Skin diseases Allergy a

OR (95% CI) Total

Men (Aged 25e79)

Women (Aged 25e79)

Men and women (25e59 years)

Men and women (60e79 years)

1.64 (1.40e1.93)a 1.63 (1.51e1.77)a

1.70 (1.35e2.14)a 1.57 (1.40e1.77)a

1.56 (1.25e1.96)a 1.57 (1.41e1.75)a

1.89 (1.43e2.51)a 1.81 (1.64e1.99)a

1.53 (1.27e1.86)a 1.33 (1.17e1.52)a

1.60 1.56 1.42 1.40

(1.43e1.80)a (1.40e1.73)a (1.34e1.50)a (1.22e1.60)a

1.30 1.50 1.10 1.41

(1.11e1.51)a (1.27e1.77)a (1.00e1.22) (1.19e1.67)a

2.19 1.46 1.52 1.56

(1.82e2.63)a (1.26e1.68)a (1.42e1.62)a (1.25e1.95)a

1.64 2.04 1.55 1.37

(1.38e1.94)a (1.76e2.36)a (1.43e1.67)a (1.15e1.62)a

1.57 1.17 1.30 1.46

(1.34e1.84)a (1.01e1.36)a (1.20e1.40)a (1.16e1.83)a

1.35 1.35 1.34 1.26 1.24

(1.24e1.47)a (1.27e1.43)a (1.21e1.49)a (1.08e1.46)a (1.15e1.33)a

1.29 1.18 1.32 1.10 1.33

(1.13e1.48)a (1.06e1.32)a (1.12e1.55)a (0.87e1.40) (1.20e1.48)a

1.53 1.29 1.29 1.30 1.19

(1.36e1.72)a (1.20e1.39)a (1.12e1.48)a (1.07e1.58)a (1.07e1.33)a

1.51 1.28 1.51 1.31 1.13

(1.35e1.69)a (1.20e1.37)a (1.30e1.75)a (1.07e1.60)a (1.03e1.25)a

1.15 1.62 1.20 1.19 1.42

(1.00e1.31) (1.42e1.84)a (1.03e1.38)a (0.95e1.49) (1.26e1.61)a

1.22 (1.10e1.35)a 1.19 (1.11e1.29)a

1.18 (1.04e1.34)a 1.33 (1.19e1.49)a

1.51 (1.28e1.79)a 1.05 (0.94e1.16)

1.29 (1.09e1.53)a 1.29 (1.18e1.41)a

1.18 (1.04e1.33)a 0.98 (0.86e1.13)

1.13 (0.98e1.30) 1.11 (0.95e1.31)

0.96 (0.78e1.20) 1.03 (0.83e1.27)

1.22 (1.02e1.46)a 1.34 (1.04e1.72)a

1.64 (1.36e1.99)a 1.17 (0.95e1.45)

0.77 (0.64e0.93)a 1.03 (0.80e1.33)

0.99 (0.91e1.08) 0.73 (0.66e0.81)a

0.99 (0.86e1.14) 0.67 (0.57e0.79)a

0.98 (0.87e1.11) 0.72 (0.63e0.82)a

0.98 (0.88e1.09) 0.69 (0.61e0.78)a

1.03 (0.86e1.23) 0.82 (0.68e0.99)a

Confidence interval excludes 1.


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of education, but they noted an inequity in access to specialist care in frequency of visit and bypassing primary care in a system where there is universal health care coverage. The EUMUSC.net project has recently proposed facilitators to implementing standards of care in OA and RA. It examined the following: accessibility of recommendations, knowledge, agreement with the content of the recommendations, cultural background, personal attitude towards recommendations, motivation, organization, environmental factors, time resources, economical resources and outcome expectancy. This was built on the model developed by Cabana in 1999 [16]. The results showed that economical resources, time resources, environment and culture were not very valued as facilitators but that outcome expectancy, belief of the doctors, motivation, attitude, agreement, knowledge of patient and accessibility were contributing the most to positive physician behaviors [17]. Inequity can affect a variety of patient outcomes. Among them, the concept of health-related quality of life (HRQoL) considers the patient's perspective as an essential component of the health care relationship. Patients' reports of their health is, however, diverse, as social factors such as age, gender and professional status are likely to impact health self-perception and reporting. Social aspects of HRQoL have been explored using epidemiological HRQoL data issued from two national surveys in France [18,19] which showed the existence of social determinants of HRQoL. Four social indicators have been identified, independent of age and gender, as determinants of HRQoL, including: 1) married or living with a common law partner, 2) level of education, 3) occupational status and 4) net household income [20]. OA: a model of chronic disease OA represents a typical chronic MSK condition. The effectiveness of interventions for OA, however, investigated in clinical trials or observational studies, has been limited in some subgroups of less advantaged populations. Disparities in health and health care have been demonstrated in a wide range of chronic diseases, including OA. OA is a major cause of chronic pain and disability [21,22] contributing to 3.4% and 1.7% of the total disease burden in the developed and developing world [23]. This burden is expected to increase in most countries because of the obesity epidemic and the aging population. In developed countries, the prevalence of knee OA in people age 60 and above is projected to grow to 35% by 2020 in obese persons [24]. Both prevalence and severity are higher in populations with lower socioeconomic status, non-white groups and women, after accounting for the effect of obesity [25]. In 2011, Borkhoff et al. published a systematic review of determinants of accessing appropriate treatments and interventions to reduce the burden of OA [26]. The PROGRESS framework and the further developed PROGRESS-Plus framework nicely summarize multidimensional components that may affect health and health care equity (see Target actions against inequity below). This framework is useful for identifying populations at higher risk of inequity, and has been used successfully to identify disparity in care for people with OA [27,28]. Place of residence People living in inner-city or rural areas have higher prevalence of OA than in urban populations in the US and in Russia, but not in Australia (OR ¼ 1.0 [0.8e1.2] in men and 0.9 [0.7e1.1] in women) [25]. Race and ethnicity Compared to Caucasians, the prevalence of OA in African-Americans and Hispanics was found to be almost two times higher (Caucasians: 25%, African-Americans: 44%, Hispanics: 40%) [29], especially for severe OA [30,31]. In the US and Canada, the white-to-black ratio for total joint arthroplasty (TJA) was approximately 3.0e5.1 in men and 1.5 to 2.0 in women [32]. Non-infection-related and infection-related complications after knee arthroplasty were higher among black patients compared with white patients (RR ¼ 1.50 [1.08e2.10] and RR ¼ 1.42 [1.06e1.90], respectively). Hispanic patients had a significantly higher risk of infection-related complications after knee arthroplasty (RR ¼ 1.64 [1.08e2.49]) relative to otherwise similar white patients. No difference was observed for hip arthroplasty [33]. There were also death-rate racial disparities as seen in the national data in the US [34].

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Occupation The prevalence and severity of OA was higher in unemployed vs employed populations, in unprofessional vs professional occupations, and 1.2 to 2.9 times higher in blue-collar vs all other workers in Canada, Russia, and France. Gender/sex Several studies, including the recent Global Burden of Disease (GDB) study 2010 [35], report that women have a higher prevalence of OA [25,36e39], but lower rates of TJA and a greater unmet need for TJA compared to men [11]. One study showed that women have a greater reliance on the use of acetaminophen, suggesting that the pain due to OA may be undertreated among women [40]. Interestingly, among people who are overweight, men are less likely to receive weight-loss advice as a part of OA management [41]. More strikingly, compared to a women, a man with similar symptoms was found 22 times more likely to receive a recommendation for total knee arthroplasty (TKA) from an orthopedic surgeon and twice more likely to receive the recommendation from a family physician [42]. It should be noted that women tended to receive TJA at a more advanced stage of their disease and so they benefited less from the procedure. Education This determinant has been evidenced in a number of developed countries and is associated with access to health care services in developing countries [43]. In people with severe OA, those who had less than high school education were less likely to be offered TJA [44], compared to those who completed post-secondary education (OR ¼ 1.57 [1.17-2.11]) [45]. Also, people with lower education were less likely to receive advice on exercise [41], and when it was received, instruction and monitoring were delivered in a less comprehensive manner [46]. Socioeconomic status The same was reported for socioeconomic status and lower income (OR ¼ 1.83 [1.24e2.70] for $20,000 versus >$40,000), which were independently associated with a greater likelihood of having the potential need for arthroplasty [45]. Social capital and networks A study conducted in the US showed that individuals without a partner were less likely to consult an orthopedic surgeon for TJA [47]. Age The same study observed the same disparities in people aged over 80 years compared to their younger counterparts [47]. There is a well documented effect of age on prevalence, as well as increasing severity with aging, but no specific time trend or generation effect has been evidenced, after accounting for the obesity epidemic. Disability Disability has been integrated in previous factors as severity. It is here more a consequence of the disease. A study in Canada found that people who were overweight but experienced less disability from hip/knee OA were less likely to receive weight management advice, compared to their more disabled counterparts, after adjusting for confounding variables [41]. Sexual orientation A recent study in the US Hispanic population from the BFFRS System showed that bisexual women were at 4 times higher odds (OR ¼ 4) of arthritis, and lesbians at 5 times higher risk of disability [48]. Barriers to equitable health care are multifactorial and can exist at the system level, physician level and patient level. The system level includes health insurance, geographic proximity and transportation; the physician level includes cultural competence and bias, and patientephysician interaction; and the patient level includes factors such as patient preferences and health literacy.


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Importance of developing interventions A major challenge is that interventions with good evidence of effectiveness are most likely to benefit those who are more amenable to follow them (i.e. less exposed to disadvantage, since they are of higher socioeconomic status, education, and wealth). Hence, much effort should be placed on sustaining interventions targeting those most in need, which means specific design, recruitment, and attention. A review on the effectiveness of self-management and education interventions found 10 relevant studies that demonstrated reduction of inequity in reaching the target population [26]. These interventions targeted 9 disadvantaged groups with OA and demonstrated improvement in their disease knowledge, self-help skills, exercise behavior, symptom management, pain, disability and overall health. Seven studies compared disadvantaged groups to a control group or in a one-group pre-post study. One study compared the effect of a video patient decision aid about treatment options in African-American men and white men and found the aid helped reduce the disparities in knowledge and expectation between the two groups (gap intervention research). RA: review on access to biologic therapy Research from around the world has shown that not all RA patients receive and have access to biologic therapy equitably. Since the year 2000, a number of biologic therapies have been launched in the market and have progressively become a landmark in the treatment of early aggressive inflammatory rheumatic diseases, such as RA, because of their strong efficacy in the short and midterm. In the early years, little was known about the overall practices of prescriptions of these drugs. In 2009, the first large study, the QUEST-RA study, was conducted in 25 countries including European countries and the USA, and the authors drew attention to the semi-ecological correlation between gross domestic product per capita and DAS28 disease activity scores of RA patients [49] (Fig. 2). This cross-sectional study comparing the types of treatment in high GDP countries to low GDP countries, found that biologics had different effect in different countries. For instance, in high GDP countries patients who took biologics and those who did not had the same average DAS28 score of 3.7, suggesting that the disease activity of biologic users was as well controlled as the non-users. This indicated that access to biologics was adequate. When looking at the low GDP countries, however, there were two striking differences. First, patients who did not receive biologic treatment had significantly higher disease activity (DAS28 ¼ 5.2) than those who did receive biologic treatment (DAS28 ¼ 4.4). Second, people in low GDP countries had higher DAS28 scores than those in the high GDP countries. Since patients' response to medications is associated with the baseline health status, findings form this study suggests that people in low GDP countries may not have access to biologics until the disease is at a more advanced stage. The UK national audit office also evaluated how people with RA were considered in different European and North American countries, with the national prevalence varying from 0.53% to 2.45% [50]. The availability of rheumatologists was the highest in France (1/25,000) and the lowest in Ireland (1/ 227,000). They showed that the criteria used for diagnosis varied across countries and that guidelines were not applied similarly and consistently. For example, Germany, France, the Netherlands, Ireland, Spain and the USA do not regularly apply clinical practice guidelines. The maximum time between referral and treatment varied from 15 days to 18 weeks. In Germany, France and Spain, patients had direct access to a rheumatologist, while other countries required a specialist referral from a GP (gatekeeper). The variability in service delivery contributed to inequalities across countries. Kobelt and colleagues published a comprehensive report on the diagnosis, frequency and determinants of health care utilization using the IMS Health data collected from 13 countries. On average, 12% of RA patients were on biologics; however, they observed a large variation across countries, from almost 30% in Norway to almost 0% in Bulgaria. Belgium and Ireland were also high consumers with 30% of patients prescribed biologics [51]. They analyzed data from the beginning of the century and found an increase in the proportion of patients on biologic treatment in these 13 countries, with a drastic and very early start of prescription in Norway and Belgium, while the use in Austria was the lowest and almost decreasing in recent years. The authors analyzed the eligibility criteria and found that the cut-off points of DAS28 scores required to consider biologics vary from 8.2 to 5.6. The number of previous DMARD treatments required before initiating biologic therapy varies from 0 to 2, with or

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Fig. 2. Access to treatment with biologic disease modifying anti rheumatic drugs in European Region. AL, Albania; AM, Armenia; AT, Austria; BA, Bosnia and Herzegovina; BE, Belgium; BG, Bulgaria; BY, Belarus; CH, Switzerland; CY, Cyprus; CZ, Czech Republic; DE, Germany; DK, Denmark; EE, Estonia, ES, Spain; FI, Finland; FR, France; GB, the UK; GE, Georgia; GR, Greece; HR, Croatia; HU, Hungary; IE, Ireland; IS, Iceland; IT, Italy; KZ, Kazakhstan; LT, Lithuania; LU, Luxemburg; LV, Latvia; MD, Moldova; ME, Montenegro; MK, Macedonia; MT, Malta; NL, Netherlands; NO, Norway; PL, Poland; PT, Portugal; RO, Romania; RS, Serbia; RU, Russia; SE, Sweden; SK, Slovakia; SL, Slovenia; TR, Turkey; UA, Ukraine; UK, United Kingdom.

without methotrexate. The median time on previous DMARDs varied from 2 to 6 months on each drug and the evaluation of effect was expected after 2e6 months. They also examined the affordability and found that the prices were highest in Germany and lowest in Estonia and Norway. Interestingly, compared to Germany, the relative health expenditure per capita was almost twice in Luxembourg and almost a quarter in Lithuania. The results also showed that biologics were the most affordable in Austria, France, Luxembourg, the Netherlands, and Switzerland, and the lowest in Romania, Poland, Lithuania and Hungary. A number of factors played a role and the two most important ones were the macro-economic conditions and treatment guidelines, with limited use of guidelines being a consequence of a low GDP, restrictive treatment guidelines, budget restrictions, administrative hurdles and access to specialists.


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Considering only rheumatic diseases, the guidelines for use of biologics were applied in very different manners depending on the disease. Emery et al. [52] showed that the guidelines for initiation of anti-TNF therapy in RA showed considerable differences according to disease duration and disease activity level. In contrast, the review of the literature in 23 countries worldwide conducted by van den Berg et al. [53] showed that the recommendations for ankylosing spondylitis were very similar around the world and informed by the Assessment of SpondyloArthritis (ASAS) recommendations which may have contributed to such similarities. Regarding access to rheumatologists, the EULAR recommendations suggest that one should be waiting 6 weeks after the first symptom. France has only a partial gatekeeper system and thus offers the possibility of comparing pathways for accessing rheumatologists. Fautrel et al., looking at the data from the ESPOIR cohort study and accounting for clinical variations, showed that while the severity of the disease (persistence of fever, high HAQ score) increased the likelihood of satisfying the EULAR recommendations, the higher density of general practitioners, as well as the possibility of having direct access to the rheumatologists, independently increased the likelihood of receiving treatment within 6 weeks (64% more than those with referral from GP) [54]. The comparison of data from different registries in the USA, Canada and Europe showed that there were at least 4 types (of criteria) of differences observed in the practice in these registries: 1) eligibility criteria, and they showed that the mean DAS28 was very similar across Canada in the 3 sources but was higher in countries like Spain, or even Czech Republic or in Britain, 2) type of insurance, 3) reference to physician and 4) physician preference. A 2011 survey conducted by Putrik, Boonen and colleagues identified a number of variations in criteria regulating treatment with reimbursed biologic therapies across 46 European countries [55]. They employed a drug access score incorporating disease duration (any requirement 0, no requirement 1), number of failed DMARDs (more than 2 (0), 2 (1), less than 2 (2)) and disease activity (DAS28 < 3.2 (0), DAS28 3.2 (1), no requirement (2)) and found that countries like Spain, Portugal, Ireland, Denmark, Austria, Norway and Switzerland had a very high level of access while Bosnia-Herzegovina, Ukraine, Bielorussia and Russia had a very low level of access. A moderate level of access was found in the UK, Poland and Turkey. They went further into the investigation by running a second survey the same year, using the EUMUNET network and QUEST-RA sources [56]. They conducted a study using the WHO model, wherein access was dependent on the availability based on the number of reimbursed biologic DMARDs. Affordability was measured by the average annual price for all biologic DMARDs and the acceptability, i.e. identified barriers for prescribers and the administrative system or in their belief in the efficacy of the drug, and for patients in the access to treatment, their financial wealth, their trust in the drug and trust in the system. Using these criteria, they developed another score for access to the drug and then the picture was slightly different (Fig. 3). All the Nordic countries, Italy and Spain showed a rather good access to the treatment. The Benelux countries, France, Germany, Romania, and Turkey were average. Portugal, the Netherlands and all the Eastern and Balkan countries had a very low access to treatment. When they correlated this data with the GDP per capita, they also found a significant correlation, the wealthier the countries having the better access. The most recent analysis of IMS health sales data was conducted at Rochester, Minnesota (Crowson C, Gabriel S, unpublished data presented at ACR 2013). It also demonstrated inequalities using the GBD study, which provided sex-specific RA prevalence from the 2004 WHO estimates, updated from the GDB systematic review conducted in Australia. The number of patients was derived by multiplying the prevalence rates by the 2011 adult population of each country, because the drug sale could be partly converted into patients by adjusting to the average weights of each sex in each country obtained from Wikipedia. Their preliminary data analysis showed the average prevalence by different WHO regions and the proportion of patients treated with various DMARDs, as well as those on biologics in 12 countries including Brazil and China. The results showed both a heterogeneity in the total number of patients treated with a DMARD and in the proportion of patients treated with biologics, varying from 20% to 60% in Japan for developing country, and very low rate in Brazil, China and Russia. Another publication issued in the 2013 report from the Norwegian School of Economics analyzed, using the same IMS health sales data from 2000 to 2009, the consumption of anti-TNF drugs in defined

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Fig. 3. Access to treatment with biologic disease modifying anti rheumatic drugs in European Region. AL, Albania; AM, Armenia; AT, Austria; BA, Bosnia and Herzegovina; BE, Belgium; BG, Bulgaria; BY, Belarus; CH, Switzerland; CY, Cyprus; CZ, Czech Republic; DE, Germany; DK, Denmark; EE, Estonia, ES, Spain; FI, Finland; FR, France; GB, the UK; GE, Georgia; GR, Greece; HR, Croatia; HU, Hungary; IE, Ireland; IS, Iceland; IT, Italy; KZ, Kazakhstan; LT, Lithuania; LU, Luxemburg; LV, Latvia; MD, Moldova; ME, Montenegro; MK, Macedonia; MT, Malta; NL, Netherlands; NO, Norway; PL, Poland; PT, Portugal; RO, Romania; RS, Serbia; RU, Russia; SE, Sweden; SK, Slovakia; SL, Slovenia; TR, Turkey; UA, Ukraine; UK, United Kingdom.

daily dose [57]. The first model showed that the consumption was highest with Remicade and decreased with Enbrel and Humira, that Norway was the highest consumer, that the consumption was increasing by 20% each year over the period, and that there was some seasonal effect. When introducing the number of indications approval did not change the model but showed that the consumption increased when the number of indications approved increased, and that the consumption decreased when the prices increased. Finally, the third model, still maintaining the same covariates except the disappearance of the seasonal effect, showed that the consumption increased in wealthier countries (GDB per capita) and when the health expenditure expressed as a percentage of GDB was also increasing. This is very interesting because it shows that combination of factors within and between countries is concurring to this heterogeneity.


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In conclusion, the available data are only estimates and do not represent exact individual consumption (which is not only governed by sale but also true consumption and adherence). This analysis, however, shows that there are a number of inequalities between and within countries related to a variety of factors, including differences in the use of guidelines, reimbursement criteria, access to specialist which depends on the system, type of insurance coverage, the prescriber's belief in drug efficacy, the patient's trust in the drug and the patient's trust in the health care system, biological variation in response to therapy that are individual, and free choice of individuals themselves. If these inequalities reveal to be avoidable and unfair, it may lead to inequities and therefore represent a potential target for interventions to reduce health disparities.

Interventions to address health inequity in RA Several recent studies specifically examined: 1) the effect of RA treatments in disadvantaged populations, or 2) interventions for improving access to effective treatment by these populations (Table 2). According to the PROGRESS framework, place of residence can be a barrier to accessing effective treatment. Furthermore, treatment effectiveness may be less established in some populations due to geographic locations and socioeconomic status. In 2011, Ishaq et al. [58] published a study that aimed to improve access to effective RA treatment by patients from low socioeconomic groups in the peripheral areas of Pakistan. Participants were randomly assigned to receive methotrexate or leflunomide. Although the leflunomide group experienced earlier improvement in RA disease activity (within four months), the methotrexate group showed more improvement at one year. Since methotrexate was less expensive, findings from this study offer evidence of a viable and effective RA therapy for the lower socioeconomic groups. Kim et al. [59] conducted another RCT to examine the efficacy and safety of early DMARD/biologic therapy in patients with moderate and severe RA in the AsiaePacific region, where biologics are only offered after patients have failed several DMARDs. They found that the combined therapy was more effective than the usual DMARD therapy. Results of this study lay the ground work for moving toward earlier use of biologics in this population. In another study, Hsieh et al. [60] examined the benefits of a supervised aerobic exercise program versus a home aerobic exercise program in Chinese patients with RA, in whom the evidence of exercise intervention is sparse. Although both groups improved in aerobic capacity, the supervised group adhered better to the exercise regimen. Since adherence is a key determinant of the success of exercise interventions [61], Hsieh's findings provide evidence to design exercise programs for this ethnic population. In some countries, such as the USA, access to some treatment is largely dependent on having insurance coverage through employers. For patients with severe RA, however, disability can jeopardize their ability to continue working. To prevent work disability, and thereby, preventing a barrier to access coverage for treatments, Macedo et al. [62] designed a comprehensive program to reduce the risk of work loss for patients with RA. The results were favorable for improving patients' work productivity, function, disease activity and ability to cope with the disease. This program is an example of an intervention that supports access to treatment for a disadvantaged population due to disability. Several studies also examined the use of non-pharmacologic interventions to address special needs of different groups. For example, women with RA frequently experienced stress and depression. Exercise and physical activity have been shown to improve mood [63], however, little was known about the effect of yoga, a type of exercise that was popular among women. To address this knowledge gap, Bosch [64] conducted a pre-post pilot study on a 10-week Hatha yoga program in women with RA. Although no significant difference was found in participants' diurnal cortisol patterns (a measure of stress level), an improvement in disease activity, pain and depression was observed. Finally, knowledge about RA is an essential component of patient self-management, but for people with a language barrier, their ability to access appropriate information and resources is severely limited. To address this disparity, Kumar [65] conducted interviews with immigrants from the Indian subcontinent in the UK and found that having a trained patient volunteer providing languageappropriate peer support and education was essential for patients accessing information. Rudd et al. [66] also conducted an RCT to explore the use of plain language patient education material for people

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Table 2 Characteristics of 7 studies evaluating interventions to improve health care quality for disadvantaged populations with rheumatoid arthritis. PROGRESS-Plus Target of the factor intervention

Type of intervention

Intervention description

Study design

Setting of intervention

Study population

Impact of intervention (þ/0/- outcome)

Bosch et al., 2009, USA

Gender/sex

Women with RA

Exercise intervention

Hatha yoga program (75 min, 3x per week, 10 weeks) under the instruction of a registered nurse/ certified yoga therapist

Pre-test/ Post-test

Office of a board-certified rheumatologist in Arizona, USA

- Improved physical function measured by HAQ - Decreased disease activity, enhanced balance and decreased perception of pain and depression - No significant difference in diurnal cortisol patterns - No change in resting heart rate

Female Chinese patients with RA

Exercise intervention

Supervised Aerobic Randomized Taiwan. Exercise (SAE) program Controlled SAE program under the instruction of Trial conducted by a a PT and a physiatrist; PT (does not Home Aerobic Exercise specify location); (HAE) program after HAE program being instructed once conducted by a PT. Both are 60 min, at home. 3x per week, for 8 weeks.

Yoga group: N ¼ 9, mean age 56y, mean RA duration 20y. Control group: N ¼ 7, mean age 67y, mean RA duration 17y. Both groups: 100% female SAE group: N ¼ 15, mean age 54y, mean RA duration 8y. HAE group: N ¼ 15, mean age 51y, mean RA duration 8y. Both groups: 100% female 100% Chinese

Hsieh et al., Gender/sex; 2009, Taiwan Race/ethnicity/ culture

Exercise Tolerance: - Within-group comparison: SAE induced significant improvement in VO2, MET, work, O2 pulse and systolic BP at peak cardiovascular response, and VO2, MET at ventilator threshold, but HAE did not. - Between-group comparison: Statistically significant difference was observed between the SAE and HAE groups for the variables above

Disease-related measures - Within-group comparison: SAE induced significant improvement in global pain intensity, ADL pain scale, grip strength, walking time, and global self-assessment. HAE induced significant improvement in global pain intensity, ADL pain scale, and walking time.


Author, year, country

Ishaq et al., 2011, Pakistan

Socioeconomic status

Patients from low socioeconomic groups residing in the peripheral areas of a developing country like Pakistan

Treatment with DMARDs (Leflunomide versus Methotrexate)

Patients were randomly Double blind assigned to a leflunomide randomized or a methotrexate group. clinical trial The objective was to demonstrate that the two DMARDs are equally effective in RA. Hence, patients in lower socioeconomic groups can be safely and effectively treated with the cheaper option.

Department of Medicine, Jinnah Medical College Hospital, Korangi, Karachi, Pakistan

Leflunomide group: N ¼ 129, mean age 58y, mean RA duration 4y, 71% female Methotrexate group: N ¼ 111, mean age 59y, mean RA duration 4y, 71% female

-

-

-

Kim et al., 2012, Korea

Race/ethnicity/ culture

Patients with moderate to severe RA from the Asiae Pacific region

Treatment with biologics (etanercept þ methotrexate versus usual DMARD þ methotrexate)

Patients were randomly assigned to subcutaneous etanercept 25 mg twice weekly combined with oral MTX or usual DMARD þ MTX therapy in a 2:1 ratio.

Phase 4, randomized, open-label, activecomparator, paralleldesign, outpatient, multicenter study

Hong Kong, India, Korea, Malaysia, Philippines, Taiwan and Thailand

ETN þ MTX group: N ¼ 197, mean age 48y, mean RA duration 6.5y, 91.4% female DMARD þ MTX group: N ¼ 103, mean age 49y, mean RA duration 6.9y, 88.4% female

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(continued on next page)


-

There were no significant within group changes for number of swollen or tender joints, HAQ, AIMS-depression, AIMSanxiety, ESR, CRP, and RF in either SAE or HAE groups. Between-group comparison: There were no significant differences between groups for any of the disease related measures. Both leflunomide and methotrexate resulted in significant improvements in four primary clinical efficacy end-points (TJC, SJC, MD global, patient global) after one year of treatment Methotrexate treatment resulted in significantly more improvement than leflunomide after one year of treatment A similar pattern of response was also seen in the secondary clinical efficacy end-points (morning stiffness, pain intensity, HAQ) after one year of treatment Over the duration of the 16wk study, significant differences in the ACR-N AUC favoring ETN þ MTX over usual DMARD þ MTX were observed (primary efficacy endpoints) More subjects taking ETN þ MTX than those taking usual DMARD þ MTX achieved responses of ACR 20, 50 and 70, low disease


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Table 2 (continued ) PROGRESS-Plus Target of the factor intervention



Study design


Study population


-

Kumar et al., 2011, UK

Race/ethnicity/ culture

Patients of South Asian origin with RA

Patient education/ Face-to-face educational Qualitative Social support support sessions were conducted in the patient's native language, designed to offer sympathetic listening, sharing problems, and suggesting educational material that may help in coping with the disease. A bilingual CD was given to the patient to listen to at home, providing information in lay terms about RA features, treatments and self-management approaches

The Birmingham Arthritis Resource Centre, Birmingham, UK

N ¼ 15, median age 48y, median RA duration 4y, 100% female

-

-

-


-

activity and remission and moderate or good EULAR responses (secondary efficacy endpoints) Significant improvements were found for HAQ-DI, pain VAS, and physician and patient global assessments in subjects taking ETN þ MTX compared with those taking DMARD þ MTX No new safety signals with ETN þ MTX therapy were reported Participants felt that availability of diseaserelated information was inadequate, and that currently available approaches to education (e.g. speaking with HCPs via interpreters, written information in English) were inadequate Session with trained patient volunteer was viewed very positively, including the ability to tell their story, speak directly in their own language, and connecting with someone who has been through the experience themselves Bilingual CD was viewed as a very useful tool, including its ability to break the language barrier, provide a clear understanding of RA and its management, and

Macedo et al., 2009, UK

Occupation/ work disability

Employed patients with RA at risk of work loss

Patient education/ Social support/ Provider education or skill development


The OT group was Prospective provided with 6 months RCT of comprehensive OT, as well as usual care. Intervention included an individualized assessment of the patient's medical history, work assessment, functional assessment, and a psychosocial assessment. An individualized treatment plan of 6e8 sessions was then formulated. Patients were referred to multidisciplinary team members and community services as required.

that they could replay the CD as needed. - Function: Improvements Rheumatoid OT group: in the OT group were Arthritis Centre N ¼ 16, mean significantly better than clinics, Guy's age 49y, mean those in the usual care and St. Thomas' RA duration 12y, group for all assessments of National Health 94% female. function. A greater Service Usual care group: proportion of the OT group Foundation Trust. N ¼ 16, mean age had clinically significant Interventions 53y, mean RA improvements in COPM conducted within duration 8y, performance and COPM the rheum or OT 94% female. satisfaction. The proportion department, the of OT patients with clinically home, or the meaningful improvements workplace in HAQ scores was not significantly greater than that of the usual care group. The proportion of the OT group moving into the low HAQ score range was no different than that of the usual care group. - Work productivity: Reduction in RA Work Instability Scale (WIS) in the OT group was significantly better than those in the usual care group. Improvement in VAS work satisfaction and VAS work performance scores were significantly greater in the OT group than in the usual care group. There were no significant differences between the two groups for work days missed per month or percentage of days missed per month. (continued on next page)

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Education Patients with (health literacy) RA, PsA and inflammatory polyarthritis with lower levels of formal education and health literacy


Patient education intervention


The Standard Care Group received usual care and a notebook containing Arthritis Foundation pamphlets about their type of arthritis, assessed at an 11th to 15th grade level. The Plain English Material Group

Study design

Randomized controlled single blind trial


An arthritis centre in an urban teaching hospital in Boston, MA.

Study population

Standard Care Group: N ¼ 63, mean age 60y, 78% female, 52% high school education, 25% ˂ 5y disease duration Individualized Care and Plain English Group,


- Coping: Reductions in AHI scores, AIMS2 pain subscale scores and quality of life measures EQ-5D Global and EQ-5D Index in the OT group were significantly greater than those in the usual care group. There were no significant differences between the 2 groups for the AIMS2 tension or AIMS2 mood scores. - Disease Activity: Reductions in VAS pain and DAS28 scores in the occupational therapy group were significantly greater than that of the usual care group. The proportion of occupational therapy patients with clinically meaningful improvements in DAS score was not significantly greater than that in the usual care group. The other disease status outcomes, fatigue and early morning stiffness, did not reach significance. - The intervention had a significant effect on self-efficacy in univariate analyses, but this effect was no longer significant in multivariate models - Multivariable models showed significantly better SF-36 mental status scores in the Individualized Care group as


Rudd et al., 2009, USA

PROGRESS-Plus Target of the factor intervention

426

Table 2 (continued )

combined due to slow recruitment: N ¼ 64, mean age 58y, 81% female, 48% high school education, 27% ˂ 5y disease duration

compared to the Standard Care group. - After adjustment for con founding variables, no significant difference between groups was seen in treatment adherence, self-efficacy, satisfaction with care, appointment keeping, self-reported health status with HAQ, and mental health with SF-36)


received usual care supplemented by a notebook containing all information in plain language, assessed with reading levels 5th-8th grade. The Individualized Care Group received usual care supplemented by the plain language materials as well as two appointments with an educator, who reviewed all the materials in the notebook.

427

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with low formal education. The intervention group showed significant improvement in their mental status, however no significant difference was found in the self-efficacy variables. Intervention by determinants Acknowledging the role of these determinants leads to promotion of specific actions to reduce their impact (socioeconomic factors), or to have direct action if they are modifiable (lifestyle factors). Some examples illustrate these interventions. Low literacy A review of MSK education interventions delivered in public health or community settings or in rheumatology clinics, suggested that educational programs delivered to people with low literacy level had a small effect on self-efficacy, and high quality evidence was lacking for those people [67]. Social marketing strategy Social marketing techniques, such as those used in health promotion, are useful to address lifestyle factors and individual behaviors. But the elements of context like type of society, or of health care system are probably not enough considered when using mass media communication. There is also a danger that these communication techniques may not reach the low socioeconomic populations or people with the least access to benefits from public health actions [68]. Therefore, caution should be taken to avoid the development of such cause of inequity. In a global context, action against social determinants of health has been identified as essential to tackle non-communicable diseases [69]. Target actions against inequity Knowledge of determinants does not imply direct action against determinants to reduce inequity. To this end, several initiatives have been proposed and tested in different conceptual frameworks. These frameworks are reviewed to help define future actions. Equity effectiveness loop Since actions against inequity are so complex, the measurement of their effectiveness is also complex. Tugwell and collaborators proposed a 6-step scheme for assessing and following over time using the equity effectiveness loop [70]. Taking the example of hip and knee replacement surgery for OA, they showed that using evidence-based epidemiological methods, researchers can assess and improve the effectiveness of diagnostic and therapeutic interventions against inequity in access to care. The expected efficacy has been demonstrated from controlled before and after studies to be 86% for improved quality of life after total joint replacement (TJR). Women and men with similar pre-operative disease severity derive similar benefit from such procedures [71], but access to the treatment is dependent upon having a doctor who considers TJR. Among appropriate candidates, only 33% of women and 42% of men reported ever having discussed this with a doctor [11]. It is also important that the recognition of the need for TJR is made by the patient's doctor (primary care physician ¼ diagnostic accuracy) and that the orthopedic surgeon recognizes the need for TJR and recommends surgery. Of 38 primary care physicians, 47% percent referred the men for TJR and 29% referred the women for TKR. Of 29 orthopaedic surgeons, 93% recommended TKR to the men and 38% to the women. This is differential provider compliance. In a survey from the same population-based cohort, 9% of men and 13% of women were willing to consider TJR. This is also differential consumer adherence [11]. Therefore multiplying efficacy by these 4 modifiers gives an actual effectiveness of 1.4% for men and 0.4% for women. Therefore, the Equity-Effectiveness Ratio is 3.5 which means that men receive 3.5 times greater benefits from TJR than women.


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Concept of self-efficacy The concept of self-efficacy as defined by Bandura is the perceived capability to perform specific actions required to achieve concrete goals [72]. Self-efficacy theory states that the strength of belief in one's capacity is a good predictor of motivation and behaviour. It can be enhanced through performance mastery, modeling, reinterpretation of physiological symptoms, and social persuasion, and enhanced self-efficacy can lead to improved behaviors, motivation, thinking patterns and emotional well-being. In a pragmatic approach, Lorig et al. developed a measurement scale to assess self-efficacy management [73]. It has been extensively tested in several chronic diseases in cross-sectional and longitudinal studies, and has proven useful in documenting baseline and monitoring changes in self-efficacy in patients following chronic diseases self-management programs [74]. Concept of agency Kivits et al. [20] observed that because HRQoL reports concern subjective health, they collect data at an individual level, leaving aside the structural level. It is indeed assumed that self-perception corresponds to an individual choice to estimate her/his health. An individual-structure approach would revise this conception by considering individuals as being agents permanently interacting with their social environment and, more specifically, its structural elements e process, actions and interactions at stake in the social world [75]. This approach is conceptualized by the notion of agency. Agency has been defined as the ability for people “to deploy a range of causal powers and translate it into their ability to produce an effect” [76]. This notion recognizes that every individual possesses resources to respond to elements of her/his social life which seemingly escape individual control; for example, socioeconomic context guiding professional trajectories. It is in that sense that this concept is more and more used in public health, as it assumes that each individual has the capacity to engage with her/his social environment. The concept of agency and the agency-structure approach are particularly highlighted in health inequalities studies [77]. In regards to social determinants of HRQoL, this approach would bring a new understanding of HRQoL data: poor or high quality of life in relation to health must also be understood as the social ability of individuals to engage with social aspects of health and illness. Framework for identifying inequity The PROGRESS framework for place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status and social capital and networks [27] and the more recent PROGRESSPlus framework which adds age, disability and sexual orientation [28] to this grid, have proven to be very useful filters to elicit all the determinants of inequality and inequity and demonstrate their interest [1]. A particular attention has been placed on monitoring these aspects in systematic reviews of interventions [78] and a new tool for reporting guidelines with a focus on health equity (PRISMAEquity) has been proposed [79]. Borkhoff et al. [26] analyzed the literature using this PROGRESS-Plus framework and demonstrated a number of commonalities across countries. They found a number of factors to be detrimental to health and health care equity in OA, including living in a rural area, being of a racial or ethnic minority, being unemployed or employed in a blue-collar job, being a women, being less educated, having lower income, living without a spouse or partner, and being elderly, all of them acting in a complex interrelationship. This framework has the advantage of covering most determinants of inequity in MSK health. It can also be applied to most other chronic diseases, since it includes determinants of inequity known in the general population. This is important to consider, since convergence of actions can result from commonalities across disciplines, as observed with diet or physical activity being determinants of many types of disease (primary, secondary or tertiary prevention of cardiovascular disease, stroke, obesity, etc.), giving more attention to essentials from a public health perspective.

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Conclusion There are major challenges to improving care for disadvantaged populations. Although some of the factors are not modifiable, health professionals and society should be aware of them and their impact on patients' ability to access the best available and the most appropriate care. We have summarized several interventions that were designed to mitigate the effect of health inequity for people with chronic MSK conditions; however, significant action is still needed to reduce these inequalities, many of them unrelated to the health care system. Finally, progress in medicine may not always favor the reduction of inequities. In the growing era of stratified medicine, and with the eruption of so-called personalized therapeutics, interventions may be so targeted e or accessible e to wealthier and more educated people, that they may become a potential threat to equity [80].

Practice points Health inequities associated with chronic musculoskeletal (MSK) conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA) are under-estimated and under-investigated. The PROGRESS-Plus framework (Place of residence, Race and ethnicity, Occupation, Gender, Religion, Education, Socioeconomic status, Social capital and networks; plus age, disability, and sexual orientation) can be used to identify determinants associated with health inequality in patients with chronic MSK conditions. People exposed to the PROGRESS-Plus determinants are at a higher risk of suboptimal care and poor health outcomes; hence, health professionals should pay special attention to ensure appropriate care is provided for these populations. Health care system reforms should incorporate a perspective on reducing such inequity in people living with chronic MSK conditions.

Research agenda Integrate PROGRESS-Plus variable measures in all observational or intervention research on chronic MSK conditions, including studies on the risk of disease occurrence and disease severity. Inequity may differ between countries. An identification of these gaps is needed, and could serve to develop appropriate actions. Develop a standardized measurement of PROGRESS or PROGRESS-Plus factors. Develop innovative interventions to reduce inequity, and assess their effectiveness in primary and secondary prevention as well as in treatment. Encourage exploratory analysis in intervention studies to assess the effects of interventions on patient subgroups who are at risk of health inequity.

Conflict of interest statement The authors declare no conflict of interest.

Acknowledgment We wish to thank Dr Sherine Gabriel whose previous thoughts and exchanges have been inspirational to this work.


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