Experiences of patients with Poland syndrome of diagnosis and care in Italy: a pilot survey

Poland Syndrome (PS) is a rare congenital condition characterized by unilateral, partial or complete lack of the pectoralis major. Various rib cage deformities, ipsilateral hand anomalies and ipsilateral breast hypoplasia or agenesis may be observed [1‐3]. According to the National Human Genome Research Institute, PS affects males three times more often than females and affects the right side of the body twice as often as the left [4]. The incidence ranges from one out of 7000 to one out of 100,000 live births [5]. Despite various hypotheses, the pathogenic mechanism underlying PS is still unknown [6, 7]. So, despite the greater access to comprehensive genetic testing, patients with PS, as individuals with only suspected genetic condition, often undertake the “diagnostic odyssey” characterized by years of clinical, radiological, genetic and laboratory testing. During their diagnostic odyssey, emotional distress and frustration in parents and adult patients have been observed [8‐11]. The parents of patients without a diagnosis feel uncertain about the future of their children because they lack information on how to manage the symptoms that arise. On the other hand, adult patients seeking a diagnosis hope to be able to improve their quality of life. The diagnosis, in fact, can be considered a starting point towards treatment options, thus reducing uncertainty [12]. Moreover, receiving a correct diagnosis and benefiting from appropriate genetic counseling is crucial for planning future pregnancies, both for parents and patients, through an informed choice about their reproductive options [13]. Early diagnosis also plays an important role in scheduling a timely therapeutic approach. Patients affected by PS, for example, need to correct hand deformities [14] during childhood to reduce functional impairment. Severe chest/breast asymmetries [2] need to be addressed during adolescence to avoid negative body perception which may lead to permanent insecurities and the development of body-image disorders [15].

To date, in Italy, PS is often unrecognized, and only two regions, both of which are in Northern Italy (Liguria and Lombardy), have formally published a specific Diagnostic and Therapeutic Care Paths (PDTA) and are able to offer patients complete and appropriate health services [16, 17]. There is little or no information on how well the healthcare needs of people living with PS in Italy are being met. Thus, the first aim of this study was to explore the experiences of a group of Italian patients affected by PS with regard to diagnosis and care. The second aim was to investigate the factors associated with diagnostic delay in Italy.

The study involved 72 PS patients from various Italian regions, who underwent examination (either their first or for follow-up) during two national meetings focused on patients affected by PS, which were held in Genova in 2016. While in the waiting room, adult patients (≥ 18 yo) and caregivers of underage patients were asked to fill in an anonymous, voluntary, self-administered, multiple-choice questionnaire (Table 1). The final version was composed of 26 questions (83 items) and was divided into “demographic information” (age, sex, region of origin, respondent) and 5 other sections: a) the first section “Diagnostic Path” referred to the timing of both the appearance of symptoms and confirmation of the diagnosis, to the healthcare facility and to the region where the diagnosis was confirmed; b) the second section “Quality of Care after Diagnosis” inquired about the respondents’ degree of difficulty in identifying a specialist for treatment, the perceived quality of healthcare services for PS, the impact of the difficulties they encountered, the presence of a reference healthcare provider during the treatment period and the feeling of being understood; c) the third section “Rights and Socio-economic Hardships encountered” asked respondents to indicate if and how they became aware of their health rights, if they took advantage of health-cost exemption and if it was sufficient, if they felt protected by the Italian NHS and if they had been forced to forgo some treatments; d) the fourth section “Collaboration among Health Care Professionals” asked respondents to rate the involvement of pediatricians, general practitioners and specialists in the diagnostic and therapeutic approach; e) the fifth section “Associative Support and Activities” investigated the perception of the usefulness of a patients’ association and the role of the Italian Association of Poland Syndrome (AISP) throughout the patients’ care path, their own personal registration and participation in association activities and, finally, the usefulness of medical meeting days dedicated to PS; f) the last section “Scientific Research” investigated the patients’ opinions on the scientific research activities promoted by the association.

The questionnaire was designed by a panel of experts on PS who were members of either the scientific committee (clinicians) or of the executive committee (patients or parents of affected patients who are volunteers of the association) of AISP. The questionnaire was specifically designed to detect the difficulties encountered by patients suffering from PS in the diagnostic and therapeutic care path in Italy and thus to develop targeted actions. Clinicians, supported by a bioethicist, drew up a draft of the survey composed of 41 questions and 150 items. The other experts (patients or parents of affected patients) were asked to rate each question and each item of the survey by assigning a score of 0, 1, 2 or 3 (0 = not pertinent and not explicit; 1 = not pertinent but explicit; 2 = pertinent but not explicit; 3 = pertinent and explicit). Those that were rated as “0” or “1” were removed, while those rated “2” were modified. In the end, 15 questions were removed and 8 items were modified. Given the originally envisioned internal use for which the questionnaire was created, no other validation or reliability methods were applied.

The study involved 72 PS patients or caregivers who were asked to fill in a questionnaire, 57 (23 adults, 34 minors) of whom provided enough information to warrant evaluation. The demographic and clinical characteristics of the study participants are summarized in Table 2. Briefly, the mean age at the time of filling in the questionnaire was 24.52 ± 16.91 years; 25 patients (43.86%) were males and 32 (56.14%) were females. The patients were all born in Italy and came from 14 of the 20 Italian regions. Just over half of the patients (N = 30) received their PS diagnosis in their own region, while 27 had been diagnosed outside their region of origin. The average age at diagnosis was around 14 years; the diagnosis was made at birth in only 31.58% of cases. Although the typical symptomatology of the syndrome appeared on average at an early age (4 months), only 23 patients (40.35%) had received an early diagnosis (within the first year of life). Despite the difficulties encountered in obtaining a diagnosis, 45.61% of those interviewed rated the overall quality of care received after diagnosis as good, while 28.07% considered it excellent. However, almost half of the respondents reported having suffered some consequences because of the difficulties they encountered in the diagnostic path, two thirds of whom (35.09%) reported them as being of a psychological nature. Almost all the patients reported having been informed of the existence of a specific exemption from payment of the costs related to their pathology; however, 29.82% reported that they had waived health care on account of costs and/or organizational issues. The interviewees acknowledged the important role of AISP in facilitating the healthcare path (73.68%) and considered AISP to be useful (91.23%), while a marginal role (not significant = 38.6%; absent = 40.35%) was attributed to general practitioners.

According to the World Health Organization (WHO) Constitution, “the enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being”. However, the decades-long diagnostic odysseys for many rare diseases patients has scarcely been studied [19]: guaranteeing that all people living with a rare disease may receive an accurate and prompt diagnosis is generally agreed upon as being an urgent need [20].

Previous studies have reported that available treatments and care for rare diseases are varied and heterogeneous, reflecting political, economic and geographic differences among countries [21]. The health care system in Italy is a regionally based national health service known as Servizio Sanitario Nazionale (SSN). While the national health service ensures that the general objectives and fundamental principles of the national health care system are met, the regional governments in Italy are responsible for ensuring the delivery of a benefits package to the population. They are autonomous and are responsible for organizing networks for patients with rare diseases [22].

The main aims of our study were to assess the potential link between the geographic origin of patients and time spent before obtaining a PS diagnosis, and to evaluate the quality of the received treatments. Data on patients’ experiences of diagnostic path reported in our research show a lower diagnostic threshold than those reported in the survey carried out by the European Organisation for Rare Diseases (Eurordis) on eight heterogeneous rare diseases in 2007 [23]. In particular, Italian patients with PS had to travel to a location outside of their home region to obtain the diagnosis almost twice as often as European rare diseases patients. We can assume that the diagnostic odyssey of Italian patients with PS is not only due to the lack of adequately trained healthcare professionals and dedicated health facilities in the area where patients affected by PS are born, but also to the the lack of knowledge about the services that are available for PS patients by health professionals even in regions where an official PDTA has already been released. Although appropriate clinical facilities are already in place, diagnosis can still be delayed, thus confirming the limited awareness by the general population.

Our data show that receiving a correct diagnosis in one’s own region is essential for the therapeutic continuity, which means that the patient can be appropriately followed-up by the regional health system. Italian patients affected by PS have reported similar experiences to those identified internationally among people living with rare diseases, their caregivers and families [24]. Failure to obtain a correct diagnosis is an onerous experience for patients and their families as they are forced to consult numerous physicians and to undergo many, often expensive, consultations and clinical tests, a situation which causes psychological distress and consequently, additional stress [25]. Furthermore, without a diagnosis, the patient’s medical or social needs may not receive adequate attention thereby creating the feeling of being “invisible” [26]. Taken together, these aspects affect the responsible participation by the patient in the therapeutic path that represents an important factor both for adults and for minors, which was recently enhanced in Italy by specific legislation [27, 28].

The positive correlation between logistic regression analysis and the patient’s engagement in AISP (which includes participation in social activities as well as access to a dedicated psychological support plan and to consultation with physicians specifically trained in PS) is absolutely in line with the litterature [29] and can be explained by items that include confidence and empathy, which may be pivotal in influencing subjective well-being rating more than any other clinical symptom of PS.

Our finding of a significant correlation between the patients’ decision to forgo follow-up healthcare programs and the patients’ region of origin corroborates the results of previous studies on rare diseases [30]. Accordingly, the physical distance from high-quality health services may directly impact upon the patient’s social, psychological, and occupational functioning. The ethical principles of non-discrimination, justice, equity and solidarity require adequate consideration, as does the protection of the needs of individuals with rare diseases and their families [31]. Taken together, the paucity of specific health policies for rare diseases, the scarcity of skills, the lack of a national support plan and of specific training programs result in delayed diagnoses, difficulties in accessing care, inadequate treatment, increased physical discomfort, socio-psychological issues for patients and their families and, finally, in a loss of confidence in the public health system [32]. The all too frequent difficulty in finding a specialist who can confirm the diagnosis, regardless of the patient’s region of origin, may partly be ascribed to the absence of a specific national plan and to the lack of exchange of knowledge and information within a structured and coordinated network. In line with previous studies, we agree that the lack of adequate information and training programs, as well as of a national medical network able to offer consultancy support, leaves the general practitioner with a marginal role and increases the number of self-diagnoses [24]. As already reported, drawing up multidisciplinary integrated paths is crucial in order to allow medical staff to share care protocols based on best practices and to ensure adequate and effective treatment for patients with a rare disease [33].

As confirmed by this study, patient advocacy organizations (PAOs) currently play a key role in the management of patients seeking a clinical reference, thereby improving the assistance and the quality of life of people living with a rare disease [34, 35]. Our study was designed with the cooperation of AISP to identify the main issues concerning the health services available to Italian patients with Poland syndrome. Based on the analysis of our data, in fact, AISP then took targeted actions to strengthen care services in southern and central Italy by organizing two informative clinical events in Puglia (“The network for care and research” - San Giovanni Rotondo (Foggia), 25th November, 2017) and in Emilia Romagna (“Open Day on Poland Syndrome” – Modena, 13th October, 2018). Involving health facilities which have all the medical specializations that are needed to support the affected patients eventually led to the birth of two new centres of reference for the diagnosis and treatment of patients with Poland Syndrome.

When interpreting our data, we have to consider some limitations. First of all, only patients with an overall good attitude towards being surveyed took part in the study and filled in the questionnaire exhaustively. Moreover, the sample size is rather small and does not include patients from all Italian regions. Furthermore, given the heterogeneity of the patients’ age, questionnaires were filled in by caregivers in case of minors, while adult patients filled in the questionnaire autonomously. Differences between self- and proxy-completed responses on health status surveys are well described in the literature [36, 37]. For example, some studies have reported that parents tend to assign a lower score on health-related quality of life questions regarding their children with a chronic health condition [38‐40]. However, the accuracy of the responses is strictly linked to the degree of confidence the proxy respondent has with the presented issues. In our study, the topics we investigated mainly concern objective questions whose answers are probably best known by the patients’ parents. Lastly, we did not thoroughly assess the real reasons for forgoing treatment by patients who had previously been receiving appropriate support. A further extension of this study based on qualitative interviews with patients, clinicians and other stakeholders (such as AISP members) will allow us to acquire more details and explanations of the phenomenon and will re-evaluate health services for Italian patients suffering from Poland syndrome taking into account the activity of the two new strategically located Italian reference centers.

This study underlines that the healthcare needs of people living with PS are not being fully met in Italy. Our analysis of patients’ experiences highlights many gaps and a lack of homogeneity in the diagnostic and therapeutic path of PS patients in our country. The implementation of an effective information network to promote research, stimulate clinical collaboration and improve the quality of life of people with rare diseases in general is, to date, predominantly supported by PAOs.

Adequate empowerment of PAOs within the National Health Service and the institutional bodies where health policies are defined would allow these volunteer associations to evolve from merely being a voice of the shortcomings of the public sector to a key player within the territory; this synergy would thus result in a greater application of the principle of subsidiarity.