Rare Chronic Diseases Research Articles

Lung diseases in children

Lung diseases belong to the most common acute and chronic childhood diseases. With specific diagnostics and therapy the outcome of many congenital and acquired pulmonary diseases in children and adults can be substantially improved. The aim of this review is the presentation and evaluation of important lung diseases in children taking recent developments into consideration. This article presents a review of the literature on selected acute and chronic lung diseases in children and adolescents. Acute pneumonia remains one of the most frequent causes of mortality in children worldwide. Antibiotic treatment has reduced the morbidity and mortality in Western industrialized countries; however, the treatment of complications, such as pleural empyema and lung abscesses remains challenging. With a prevalence of 10 %, asthma has evolved into the most common chronic disease in children and adolescents in Germany. Using anti-inflammatory inhalation therapy, effective control of asthma symptoms can be achieved in most patients. Cystic fibrosis (CF) remains the most common fatal inherited disease among Caucasians. More than 90 % of the mortality and morbidity of CF are caused by an early onset and progressive chronic obstructive lung disease. Approval of the first causal mutation-specific pharmacotherapy for a subgroup of patients with CF represents a milestone in individualized therapy of lung diseases. The pathogenesis of other rare chronic lung diseases including interstitial lung diseases (ILD) is still mostly unknown. Continuous improvement in the diagnostics and therapy is crucial to further improve the management and outcome of acute and chronic lung diseases in children. Pediatric pulmonology, as an interdisciplinary subspecialty at the interface of pediatrics, pulmonology and infectious diseases, plays a key role in the translation of scientific progress into clinical practice.

Enzyme replacement and substrate reduction therapy for Gaucher disease

Enzyme replacement and substrate reduction therapy for Gaucher disease

A Study to Assess the Awareness of the Biosimilars among Ukrainian Physicians

Biologics have revolutionized the treatment for severe chronic illness and rare diseases. They represent the fastest growing segment in the pharmaceutical industry. However due to high of innovator biologics, the alternate options such as biosimilars have emerged. The impending patent cliff, rising healthcare costs and increasing awareness of biosimilars among physicians are crucial factors which will drive biosimilar uptake in future. Europe has demonstrated its faith in biosimilar treatment and EMA has approved several biosimilars since 2006. Over the years, Ukraine has been a favourable market for branded generics and its evolving regulatory landscape for biosimilar approval is an indication of its preparedness to embrace biosimilars. The current survey attempts to assess the awareness of the biosimilars among Ukrainian physicians.

Longitudinal changes in health-related quality of life for chronic diseases: an example in hemophilia A.

Patients with well-managed rare chronic diseases such as hemophilia maintain a stable health state and health-related quality of life (HrQoL) that may be affected by acute events. Longitudinal HrQoL assessments analyzed using multivariate multilevel (MVML) modelling can determine the impact of such events on individuals (within-person effect) and identify factors influencing within-population differences (between-person effect). To demonstrate the application of MVML modelling in a longitudinal study of HrQoL in hemophilia A. Using data on 136 adults and 125 children from a two-year observational cohort study of burden of illness in US hemophilia A patients, MVML modelling determined the effect of time-invariant (sociodemographic and clinical characteristics) and time-varying factors (bleeding frequency, emergency room visits, and missed work/school days) on within-person and between-person HrQoL changes. HrQoL was assessed using the SF-12 health survey (adults) and PedsQL inventory (children) at baseline, then every 6months. In children, within-person (p < 0.0001) and between-person (p < 0.0001) psychosocial functioning was reduced by each additional bleed and missed day (within-person: p = 0.0089; between-person: p = 0.0060). Within-person physical functioning was reduced by each additional bleed (p < 0.0001), emergency room (ER) visit (p = 0.0284), and missed day (p = 0.0473). Between-persons, additional missed days (p < 0.0001) significantly decreased physical functioning. In adults, each additional missed day reduced SF-12 Health Survey mental (p = 0.0025) and physical (p = 0.0093) component summary scores. Each additional bleed also decreased physical component summary (PCS) significantly (p = 0.0093). This study demonstrated the applicability of MVML modelling in identifying time-invariant and time-varying factors influencing HrQoL in a rare chronic disease population. Small but significant within-person and between-person changes in HrQoL with each additional acute event experienced were identified, which if frequent, could have a large cumulative impact. The results suggest that MVML modelling may be applied to future studies of longitudinal change in HrQoL in other rare chronic disease populations.

Empowerment Weekends for young adults

SoMA is the German patient organization for people with an anorectal malformation (children born without an anus or with an anus ending in a wrong location) and Hirschsprung’s disease. Anorectal malformations may be associated with further malformations (e.g. bladder, sexual organs, spine, or cardiac defects) and the patients often face lifelong problems such as incontinence. Because of the lack of medical centres and as physicians for adults, who do not know much about the treatment, there are special problems during transition. Due to legal retention periods for medical reports a retrospective access is often impossible. But precise medical reports are of high importance, and the patients should know their correct diagnosis and what kind of surgery they went through. For that reason SoMA in 2009 started with the project Empowerment Weekend (seminar “My own medical file”) for a maximum of eight teenagers between 14 and 25 years. They bring their personal medical reports and in a one-to-one discussion a paediatric surgeon looks through the reports and explains to the patient the individual malformation. They look for possible gaps in the diagnosis, the follow-up is discussed, and further examinations may be recommended. There is an individual psychological counselling, a lecture by the paediatric surgeon, a nurse shows different medical devices for the follow-up, there is a pedagogical offer under the direction of the SoMA social worker, and time for some leisure programme. After the weekend each participant has an own folder with all the medical files, and he or she understands the malformation and is in a position to explain it to others. SoMA has evaluated the first three seminars, and the youngsters indicated an increase in their self-esteem and that they now have a better knowledge of their malformation. Mistakes concerning the diagnosis were also discovered during the seminars In 2011 the seminars got awarded the “Care prize” from a private German health insurance company, and from ACHSE, the German National Alliance for chronic rare diseases.

Understanding the role of social media in online health: A global perspective on online social support

Around the globe, people are increasingly using social media for the provision of online social support. Online social support may be especially relevant for parents who have children that are afflicted with rare chronic diseases such as MECP2 Duplication Syndrome. Despite increasing evidence that online social support enhances a person’s psychological well-being, there is little research that seeks to understand how and why various forms of social media facilitate social support. This study develops a theoretical framework from the existing psychosocial and media theories that describes the relationship between social media and social support. This paper concludes with implications for health information systems design.

Stochastic differential equation modeling the prevalence of rare chronic diseases with an application to systemic lupus erythematosus

In this article we describe a system of stochastic differential equations to model the age‐specific prevalence of rare chronic diseases from incidence and mortality rates. As an application, the age profile of the prevalence of systemic lupus erythematosus in England and Wales in1995 is calculated. The results are in good agreement with the observed epidemiological measures.

Evaluation of a prototype electronic personal health record for patients with idiopathic thrombocytopenic purpura

BackgroundPatients with rare diseases often lack information about the disease itself and appropriate health care, leading to poor quality of life. Personal health records provide health information which can then be shared between multiple health care providers. Personal health records may also offer a tool for capturing patients’ reported outcomes, thus enhancing their empowerment and improving communication with health care professionals. We conducted a pilot study to evaluate the usability of Sanoia, a freely accessible personal health record, which was customized for patients with the rare disease, idiopathic thrombocytopenic purpura (ITP).MethodsThe Sanoia interface was expanded with ITP-specific tools. A prospective study was conducted at the referent center to evaluate the usability of this new interface (referred to here as the “tool”) by patients. Forty-three patients were randomized into groups to use or to not use the tool. Its use was evaluated by a specific questionnaire and by surveying individual patient adherence profiles. Evaluation of health-related quality of life using the ITP patient assessment questionnaire, was performed at baseline and after 1, 3, and 6 months via postal mail.ResultsThe groups were similar at inclusion in terms of characteristics, including global quality of life. During the study period, the tool was used to update the personal records of 19/28 patients (68%), with a median of two connections to the tool (range 1–12) plus access by various health care professionals (n = 22). In addition, 15/19 (78%) patients used the “personal notes” section at least once. We observed no significant changes in quality of life between patients with or without the tool during the study period.ConclusionThis pilot study demonstrates the good usability of the new customized Sanoia interface for patients with ITP. Additional studies will increase its usability further, and its interface could be adapted for use with other rare chronic diseases.

The Liege Acromegaly Survey (LAS): A new software tool for the study of acromegaly

Acromegaly is a chronic rare disease associated with negative pathological effects on multiple systems and organs. We designed a new informatics tool to study data from patients with acromegaly, the Liege Acromegaly Survey (LAS). This relational database permits the inclusion of anonymous historical and prospective data on patients and includes pathophysiology, clinical features, responses to therapy and long term outcomes of acromegaly. We deployed the LAS in a validation study at a single center in order to study the characteristics of patients with acromegaly diagnosed at our center from 1970–2011. A total of 290 patients with acromegaly were included (147 males and 143 females). There was a linear relationship between age at diagnosis and the date of diagnosis, indicating that older patients are being diagnosed with acromegaly more frequently. A majority presented with macroadenomas (77.5%) and the median diameter was 14mm. Patients with macroadenomas were significantly younger than patients with microadenomas (P=0.01). GH values at diagnosis decreased with the age of the patients (P=0.01) and there was a correlation between GH values and tumor size at diagnosis (P=0.02). No correlation existed between insulin-like growth factor 1 (IGF-1) levels and tumor characteristics. The prevalence of diabetes was 21.4% in this population and 41.0% had hypertension. The presence of hypertension and diabetes were significantly associated with one another (P<0.001). There was a linear relation between initial GH and IGF-1 levels at diagnosis and those obtained during SSA analog treatment and the lowest GH and IGF-1 values following SSA therapy were obtained in older patients (GH: P<0.001; IGF-1: P<0.001). The LAS is a new relational database that is feasible to use in the clinical research setting and permits ready pooling of anonymous patient data from multiple study sites to undertake robust statistical analyses of clinical and therapeutic characteristics.

Primary Immunodeficiency Disease

Patient-centered chronic care management is a new model for the management of rare chronic diseases such as primary immunodeficiency disease (PIDD). This approach emphasizes helping patients become experts on the management of their disease as informed, involved, and interactive partners in healthcare decisions with providers. Because only a few patients are affected by rare illnesses, these patients are forced to become knowledgeable about their disease and therapies and to seek treatment from a healthcare team, which includes physicians and nurse specialists who are equipped to manage the complexity of the disease and its comorbidities. Importantly, therapy for PIDD can be self-administered at home, which has encouraged the transition toward a proactive stance that is at the heart of patient-centered chronic care management. We discuss the evolution of therapy, the issues with the disease, and challenges with its management within the framework of other chronic disease management programs. Suggestions and rationale to move case management of PIDD forward are presented with the intent that sharing our experiences will improve process and better manage outcomes in this patient population. The patient-centered model for the management of PIDD is applicable to the primary care settings, where nurse case managers assist patients through education, support them and their families, and facilitate access to community resources in an approach, which has been described as "guided care." The model also applies specifically to immunology centers where patients receive treatment or instruction on its self-administration at home. Patient-centered management of PIDD, with its emphasis on full involvement of patients in their treatment, has the potential to improve compliance with treatment, and thus patient outcomes, as well as patients' quality of life. The patient-centered model expands the traditional model of chronic disease management, which relies on evidence-based medicine, provider expertise, clinical information systems, and patient education. This approach supports patient self-management with strategies that empower and prepare them for their role as expert patients.

Laser Light May Improve the Symptoms of Oral Lesions of Cicatricial Pemphigoid: A Case Report

The aim of this work is to report the handling of a patient suffering from cicatricial pemphigoid (CP) treated with laser phototherapy (LPT) and systemic steroids. CP is a group of rare chronic autoimmune blistering diseases that predominately affect the mucous membranes and occasionally the skin. The gingiva is most commonly involved, followed by the palate and the buccal mucosa. High-dosage systemic steroids are widely used for its treatment. LPT has been shown to improve wound healing and relieve pain. Its efficacy depends on the amount of energy delivered to the tissue, exposure time, and delivery method. A white 47-y-old man with CP who used systemic steroids for the previous 5 y was examined at our clinic. Extra- and intraoral examination revealed classic signs of the condition. LPT (GaAlAs diode laser, 660 nm wavelength, 30 mW, continuous wave, diameter approximately 3 mm, 60 J/cm(2) per session) was used in association with the steroids. LPT was performed in a punctual contact manner every other day on the oral mucosa. Maintenance of the treatment was carried out weekly because interruption of the LPT resulted in the recurrence of the lesions. At the time that this report was written, the patient had been undergoing twice weekly treatments for 6 months without signs of lesion recurrence. Concomitant use of systemic steroids and LPT showed a positive effect on controlling oral CP lesions and on improving both oral health and the quality of life of the patient.

PatientsLikeMe: ALS patients sharing experiences and personal health information online

AbstractThe literature provides increasing evidence of the benefits of social support groups on the psychosocial functioning and health‐related quality of life of chronically‐ill patients. Social support groups have been found to improve coping, enhance the quality of life, facilitate health decision making, and in some cases, increase survival time among chronic disease patients. Patients benefit from a strong sense of shared experiences in a cooperative and symbiotic environment. Information and communication technologies have extended the capabilities of social support groups, enabling patients to share information across barriers of geography and time, benefitting especially those suffering from rare chronic diseases who may not find similar support groups within their immediate communities. Online environments also, in some cases, provide a measure of anonymity and opportunity for people to disclose sensitive health information without embarrassment while also allowing them access to a wider variety of information resources.PatientsLikeMe (PLM) is an online community that uses Web 2.0 technologies to allow its members to share not only social support but also their symptomatology, treatment, medication, and outcome information with other members. The first of its kind, PatientsLikeMe has extended the capabilities of online social support groups by introducing powerful tools for sharing and analyzing personal health information. The website currently supports 2,300 patients with chronic diseases like ALS (Lou Gehrig's Disease), Multiple Sclerosis (MS), and Parkinson's Disease.The current study focuses on a qualitative analysis of the ALS community within PLM. ALS (amyotrophic lateral sclerosis), or Lou Gehrig's disease, is a rare and incurable life‐altering disease affecting approximately 30,000 Americans. This fatal, neurodegenerative disease attacks the nerves and muscles, resulting in the progressive loss of voluntary motor function and, eventually, difficulties in speaking, swallowing, and breathing. While ALS contributes to the weakening of voluntary motor functioning and eventual paralysis, most patients are still able to think clearly and rely on a variety of assistive technologies to aid in communication. The ability to communicate with others is an important aspect of patients' ability to cope with their disease and remain active participants in their own care.

Linking the world with training and research for improving haemophilia care

Linking the world with training and research for improving haemophilia care

Prevalence of zebras in general practice: Data from the Continuous Morbidity Registration Nijmegen

Objective: To explore the prevalence of rare diseases in the Continuous Morbidity Registration (CMR) Nijmegen, and to discuss methodological difficulties in the study of rare diseases in general practice. Methods: We selected all diseases with a prevalence <0.5/1000 patients/year between 1986 and 2006 in the CMR, and we compared the results with rare diseases in the Orphanet database of rare diseases. Results: We retrieved 71 codes of rare diseases: 15 referred to trauma or intoxications; the remaining 51 could be subdivided into malignancies, specific infections, diseases of short duration, and chronic diseases. Twenty (36%) of these 56 diseases were also listed in the Orphanet database (mostly malignancies and chronic diseases).Conclusion: Although in the literature emphasis is placed on rare chronic diseases, the general practitioner is also confronted with many rare diseases of shorter duration. The CMR is not yet feasible for studying diseases with an extremely low prevalence.

Enfermedades raras: Concepto, epidemiología y situación actual en España

Rare diseases are those whose prevalence is below 5 cases per 10,000 inhabitants in the European Community. Most cases are diagnosed during paediatric age due to their genetic origin, while some others are congenital malformations. Nevertheless, a higher prevalence is seen during adulthood as most of the former diseases are very severe and patients die during childhood. At the same time, higher survival rates are related to some chronic rare diseases in adults. The Spanish Network of Research Epidemiology for Rare Diseases (REpIER) developed the first atlas showing the geographical distribution of rare diseases in Spain, assessed the Spanish rare disease registries, contributed to the further development of regional plans on rare diseases, as well as to social and health actions, and established the real group of needs to be solved. These have been included in the Communication of the European Commission on Rare Diseases as well as in the Spanish Senate Presentation.

A Word From Our Moderator

To the Editor: In their Commentary, Dr Kraemer and colleagues draw attention to the importance of moderators of treatmentoutcomes, theoftenunsatisfactorywaythesearedealt with (if at all) in randomized clinical trials (RCTs), and the potentially seriousconsequencesof thisneglectonpatientcare. They propose that every RCT should include a search for putative moderators of treatment outcome. Although acknowledgingthatpositiveresultsof suchanalysesrarelyprovideproof of theexistenceof thesemoderators, they stress that the importanceresides inthehypotheses that theanalysesgenerate.These hypotheses can then be tested in subsequent adequately poweredandpopulatedRCTs.However, itmaytakeyears todesign, acquire adequate funding for, and execute such an RCT. As an alternative, conducting N-of-1 trials can be valuable to further investigate information on moderators of treatment outcome. As a hypothetical example, suppose an RCT had been conducted to test the efficacy of drug treatment of primary Raynaud phenomenon, that no overall benefit of the drug had been found, but analysis of putative moderators of treatment outcome had suggested that women might respond favorably, although this result was not statistically significant. Women with Raynaud phenomenon could then be included in N-of-1 trials, in which they would be treated in a double-blind crossover design with multiple treatment pairs with either the drug or a placebo in random order. The presence or absence of differences in symptom scores during treatment would then prove or disprove the effectiveness of this drug for the patient. Pooling the results of all of these N-of-1 trials may substantiate that sex is a moderator of treatment outcome. Moreover, comparison of responders and nonresponders in these N-of-1 trials may be used to identify additional moderators of treatment outcome. This approach may obviate the need for RCTs, which would be a great boon in the case of rare chronic diseases. It has an additional advantage in that daily patient care can be integrated with clinical research. N-of-1 trials have their own limitations. They are not applicable to surgical or acute medical conditions. However, for chronic medical conditions, they may be invaluable in the quest for “tailored therapy,” one of the holy grails of clinical medicine.

A hierarchical aggregate data model with spatially correlated disease rates.

The aggregate data study design (Prentice and Sheppard, 1995, Biometrika 82, 113-125) estimates individual-level exposure effects by regressing population-based disease rates on covariate data from survey samples in each population group. In this work, we further develop the aggregate data model to allow for residual spatial correlation among disease rates across populations. Geographical variation that is not explained by model predictors and has a spatial component often arises in studies of rare chronic diseases, such as breast cancer. We combine the aggregate and Bayesian disease-mapping models to provide an intuitive approach to the modeling of spatial effects while drawing correct inference regarding the exposure effect. Based on the results of simulation studies, we suggest guidelines for use of the proposed model.

Cost-of-illness of scleroderma: The case for rare diseases

Objective: To determine the societal costs of scleroderma (SSc), a rare chronicconnective tissue disease that affects approximately 98,000 Americans. Lack of reliable national databases limit rare disease cost studies, and this study suggests methods of using multiple data sources to assess the costs of rare diseases. Methods: Primary and secondary data sources were used to calculate directand indirect costs of SSc, including discounted lifetime mortality and morbidity costs. A prevalence-based, human capital approach was used. Sensitivity analyses were used to vary parameters that are uncertain, such as prevalence, mortality, and labor costs. Results: Annual direct and indirect costs of SSc in the United States are $1.5 billion. Morbidity represents the major cost burden, with costs of $819 million (56%) of total costs. The current value of lifetime earnings lost was $179 million (12%) or $300,000 per death. Direct costs were $462 million (32%) or $4,731 per person annually, indicating that costs are spread over the long disease duration. Conclusions: This study provides one model for the assessment of rare diseasecosts. Triangulation of data sources and sensitivity analyses are important for determining the costs of rare diseases. The high cost of SSc, despite its low prevalence, suggests that the burden of rare chronic diseases can be high. The high morbidity costs reflect the young age of onset of the disease as well as the need for treatments to decrease morbidity costs. Local shared databases and national surveys are needed to improve cost estimates of rare diseases.