Access to Care in Lyme Disease: Clinician Barriers to Providing Care.

Patients with persistent Lyme disease/chronic Lyme disease (PLD/CLD) encounter significant barriers to accessing medical care. Although this health inequity has been explored from the patient perspective, the obstacles clinicians encounter when providing care to this group of patients have not been examined. The primary goal of this study was to identify the challenges faced by clinicians who provide care for patients with PLD/CLD. Clinicians who treat PLD/CLD were surveyed regarding their professional backgrounds, general challenges to providing care, supply and demand constraints, insurance restrictions, and regulatory and legal challenges. Clinicians treating patients with PLD/CLD have developed substantial clinical expertise but encounter multiple clinical, regulatory and financial impediments to providing care. Clinician-encountered barriers may be powerful disincentives for providing care patients with PLD/CLD and make it difficult to retain and recruit clinicians who will care for the rapidly expanding PLD/CLD populations. Understanding these barriers and identifying potential solutions is essential to resolving the current supply/demand imbalance that makes it difficult for patients to receive the care they need to become well.

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease.

Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions - the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1-13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols.

Patient-powered research networks aim to improve patient care and health research.

The era of big data, loosely defined as the development and analysis of large or complex data sets, brings new opportunities to empower patients and their families to generate, collect, and use their health information for both clinical and research purposes. In 2013 the Patient-Centered Outcomes Research Institute launched a large national research network, PCORnet, that includes both clinical and patient-powered research networks. This article describes these networks, their potential uses, and the challenges they face. The networks are engaging patients, family members, and caregivers in four key ways: contributing data securely, with privacy protected; including diverse and representative groups of patients in research; prioritizing research questions, participating in research, and disseminating results; and participating in the leadership and governance of patient-powered research networks. If technical, regulatory, and organizational challenges can be overcome, PCORnet will allow research to be conducted more efficiently and cost-effectively and results to be disseminated quickly back to patients, clinicians, and delivery systems to improve patient health.

Disease management for chronically ill beneficiaries in traditional Medicare.

We summarize the Centers for Medicare and Medicaid Services' (CMS's) experience with disease management (DM) in fee-for-service Medicare. Since 1999, the CMS has conducted seven DM demonstrations involving some 300,000 beneficiaries in thirty-five programs. Programs include provider-based, third-party, and hybrid models. Reducing costs sufficient to cover program fees has proved particularly challenging. Final evaluations on twenty programs found three with evidence of quality improvement at or near budget-neutrality, net of fees. Interim monitoring covering at least twenty-one months on the remaining fifteen programs suggests that four are close to covering their fees. Characteristics of the traditional Medicare program present a challenge to these DM models.

Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006.

BACKGROUND: Case series have demonstrated that potentially lethal cutaneous squamous cell carcinomas arise in patients with recessive dystrophic epidermolysis bullosa (RDEB), although the magnitude of this risk is undefined. METHODS: Systematic case finding and data collection were performed throughout the continental United States (1986-2002) by the National EB Registry on 3280 EB patients to determine cumulative and conditional risks for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) within each major EB subtype, as well as the cumulative risk of death from each tumor. Study design was cross-sectional, with a nested randomly sampled longitudinal subcohort (N = 450). RESULTS: SCCs arose primarily in RDEB, especially the Hallopeau-Siemens subtype (RDEB-HS), first beginning in adolescence. Less frequently, SCCs occurred in junctional EB (JEB). Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively. In Herlitz JEB, the risk was 18.2% by age 25. SCC deaths occurred only in RDEB, with cumulative risks in RDEB-HS of 38.7%, 70.0%, and 78.7% by ages 35, 45, and 55, respectively. MM arose in RDEB-HS, with a cumulative risk of 2.5% by age 12. BCCs arose almost exclusively in the most severe EB simplex subtype (Dowling-Meara) (cumulative risk = 43.6% by age 55). LIMITATIONS: Mutational analyses were performed on only a minority of enrollees in the National EB Registry, preventing evaluation of the possible influence of specific genotypes on the risk of developing or dying from cutaneous SCCs. CONCLUSIONS: SCC is the most serious complication of EB within adults, especially those with RDEB-HS. By mid-adulthood, nearly all will have had at least one SCC, and nearly 80% will have died of metastatic SCC despite aggressive surgical resection. When compared with SCCs arising within the normal population, the remarkably high risk of occurrence of and then death from SCCs among RDEB patients suggests likely differences in pathogenesis. Additional studies of EB-derived tumors and SCC cell lines may not only provide new insights into the mechanisms of carcinogenesis but also means whereby these particular tumors may be prevented or more effectively treated.

Cause-specific risks of childhood death in inherited epidermolysis bullosa.

OBJECTIVE: To determine the cause-specific risks of death in children with epidermolysis bullosa (EB). STUDY DESIGN: Data were collected throughout the continental United States between 1986 and 2002 by the National EB Registry. The study design is cross-sectional (n = 3280), containing within it a nested randomly sampled longitudinal subcohort (n = 450). RESULTS: The risk of death during infancy and childhood was greatest in junctional EB (JEB), with cumulative and conditional risks of 40% to 44.7% by age 1 in both JEB subtypes, rising to 61.8% in children with JEB, Herlitz subtype and 48.2% in those with JEB, non-Herlitz subtype (JEB-nH) by age 15. In decreasing order, sepsis, failure to thrive, and respiratory failure were the major causes of death in children with JEB, plateauing by age 2 to 6. A small minority of children with epidermolysis bullosa simplex, Dowling-Meara subtype was at risk for death by age 1 (cumulative risk, 2.8%), with sepsis and respiratory failure accounting for cumulative risks of 1.9% and 0.9%. Only a minority of children with recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens subtype was at risk of death (cumulative risk = 8% by age 15). Renal failure also rarely accounted for death in children with JEB-nH. CONCLUSIONS: Infants and children with inherited EB, particularly those with JEB, are at significant risk of death as a result of disease complications.

Gastrointestinal complications of inherited epidermolysis bullosa: cumulative experience of the National Epidermolysis Bullosa Registry.

BACKGROUND: Portions of the gastrointestinal (GI) tract may be severely involved in patients with inherited epidermolysis bullosa (EB). Evidence-based data are lacking as to the frequency and time of onset of these complications. PATIENTS AND METHODS: Cross-sectional and longitudinal data were analyzed on 3,280 and 450 patients with EB, respectively, who were followed from 1986-2002 as part of the National EB Registry, an epidemiological study that attempted to identify, enroll, and collect data on every EB patient residing within the continental United States. Frequencies of abnormalities arising within the esophagus, stomach, small and large intestines, rectum, and anus were determined for each major EB subtype. Cumulative risks were similarly calculated for esophageal stenoses or strictures, and for severe growth retardation. RESULTS: Esophageal strictures and growth retardation were commonly seen among the more severe EB subtypes, most notably Hallopeau-Siemens recessive dystrophic EB, and occurred as early as within the first year of life. EB subtype-specific differences were also observed in the frequency of occurrence of other GI complications. DISCUSSION: A variety of GI complications arise in patients with inherited EB, varying across the major EB subtypes in their relative severity, frequency, and time of onset. CONCLUSIONS: Data generated by the National EB Registry should provide a sound basis whereby evidence-based strategies can be implemented for more effective surveillance and treatment of specific GI complications.

Tracheolaryngeal complications of inherited epidermolysis bullosa: cumulative experience of the national epidermolysis bullosa registry.

OBJECTIVES/HYPOTHESIS: To accurately determine the frequency with which complications arise in the ears, noses, and throats of patients with inherited epidermolysis bullosa (EB) as well as the cumulative risk of tracheolaryngeal stenosis or stricture. STUDY DESIGN: Cross-sectional study (3,280 patients) with a nested, randomly sampled longitudinal subcohort (n=450), representing data collection, stratified by major EB subtype, of the National EB Registry, an epidemiologic project focused on enrolling all EB patients within the continental United States from 1986 to 2002, to permit generalization of findings to the entire American EB population. METHODS: Systematic epidemiologic case finding and data collection were performed throughout the continental United States, followed by subclassification of patients by EB subtype. ENT complications were quantified via contingency tables (as frequencies) and lifetable analyses. Frequencies of surgical procedures were also determined. RESULTS: The most important clinical ENT complication in inherited EB was tracheolaryngeal stenosis or stricture, arising during early childhood and primarily within infants and children with junctional EB (JEB) (cumulative risk of 39.8% and 12.8% in Herlitz and non-Herlitz JEB, respectively, by ages 6 and 9). Other uncommon complications included chronic otitis media, chronic otitis externa, and hearing loss. CONCLUSIONS: Given the potential risk for sudden airway occlusion and death, meticulous surveillance by a pediatric otolaryngologist is a critical part of the overall management of infants and children with EB, especially those with JEB and two rare subtypes of generalized EB simplex. Elective tracheostomy should be considered in EB infants and children with evidence of airway embarrassment.

Genitourinary complications of inherited epidermolysis bullosa: experience of the national epidermylosis bullosa registry and review of the literature.

PURPOSE: We determined the frequency with which 6 genitourinary tract complications (urethral meatal stenosis, urinary retention, bladder hypertrophy, hydronephrosis secondary to ureteral strictures, pyelonephritis and cystitis) occur in inherited epidermolysis bullosa (EB) in the American EB population. MATERIALS AND METHODS: Up to 16 years of longitudinal followup was done in 3,280 consecutively enrolled patients in the National EB Registry, a National Institutes of Health funded epidemiological study covering the entire continental United States. Data were stratified by major EB type and subtype. Frequencies of occurrence were determined for each of 6 genitourinary tract variables and stratified into 10 mutually exclusive, major EB subtypes. RESULTS: Urinary tract complications occurred in a minority of patients across all major EB subtypes with the highest frequency seen in Herlitz junctional EB (JEB-H). Urethral meatus stenosis was the most common complication, occurring in 11.6% and 8.0% of patients with JEB-H and Hallopeau-Siemens recessive dystrophic EB (RDEB), respectively. Urinary retention, hydronephrosis and bladder hypertrophy occurred in 9.3%, 7.0% and 4.6% of JEB-H cases, respectively. In contrast, pyelonephritis and cystitis were most often seen in the setting of generalized EB simplex (Koebner variant) and inversa RDEB. CONCLUSIONS: The urinary tract may be involved in any subtype of inherited EB, although these complications usually arise in patients with the most severe subtypes of junctional and recessive dystrophic disease. Chronic surveillance for the presence of genitourinary tract disease activity is warranted, especially in patients with JEB and RDEB, given the potential for longterm kidney injury if untreated.

Inherited epidermolysis bullosa and the risk of death from renal disease: experience of the National Epidermolysis Bullosa Registry.

BACKGROUND: Isolated case reports and limited clinical series suggested that renal failure may occur in some patients with inherited epidermolysis bullosa (EB). Reported causes have included poststreptococcal glomerulonephritis, secondary amyloidosis, and chronic mechanical obstruction. To date, no data exist that permit an accurate estimation of the risk for death from renal failure in patients with this disease. METHODS: Life table analyses were performed using 16 years of data from the National EB Registry, a federally funded longitudinal epidemiological study encompassing the entire continental United States. Data were stratified so that cumulative and conditional risks for death from renal failure could be estimated. Renal failure as cause of death was identified by death certificates and verified from hospital records and interviews with the patients' immediate families. RESULTS: The cumulative risk for death from renal failure among patients with Hallopeau-Siemens recessive dystrophic EB (RDEB-HS) was 12.3% by age 35 years. In addition, deaths from renal failure also were reported rarely in patients with other subtypes of generalized RDEB and in junctional EB (JEB). CONCLUSION: Renal failure is an important cause of death among adults with RDEB-HS, surpassed only by death from metastatic squamous cell carcinoma. It also rarely may occur in the setting of JEB and other subtypes of generalized RDEB. Given our data, medical surveillance for early renal involvement should become part of the routine evaluation of all adults with RDEB and JEB.

Eye involvement in inherited epidermolysis bullosa: experience of the National Epidermolysis Bullosa Registry.

PURPOSE: To determine the frequency of ocular manifestations in inherited epidermolysis bullosa (EB) within the continental United States and to define the estimated cumulative risks of developing nonscarring (blisters or erosions) and scarring corneal manifestations within each major EB subtype over time. DESIGN: Observational (cross-sectional and longitudinal). METHODS: Up to 16 years of longitudinal follow-up was conducted on 3,280 consecutively enrolled patients in the National EB Registry, an epidemiologic study funded by the National Institutes of Health. Data were stratified by major EB type and subtype. Frequencies of occurrence were determined for eight variables (corneal erosions or blistering; corneal scarring; symblepharons; blepharitis; ectropions; lacrimal duct obstruction; impaired vision; blindness) by contingency tables, and cumulative risks were generated by life table analysis technique. RESULTS: The most common ocular manifestations were corneal erosions and blisters. Frequencies mirrored relative severity of skin disease, with 74.10% of all patients with recessive dystrophic EB, Hallopeau-Siemens (RDEB-HS) and 47.50% of all patients with junctional EB, Herlitz (JEB-H) experiencing at least one episode. Lower frequencies were noted for corneal scarring. Symblepharons and ectropions were most commonly seen in inversa RDEB and JEB-H, respectively. Blindness was reported in 6.47% of RDEB-HS patients. The cumulative risks of nonscarring and scarring corneal lesions in JEB-H at age 5 are 83.18% and 27.08% and at age 25 are 83.18% and 72.22%. With time, the cumulative risk of each in RDEB-HS approached that reported in JEB-H patients. CONCLUSION: Ocular disease activity, particularly corneal, is common in some EB subtypes. Careful ophthalmologic examination should become an integral part of the management of all patients with inherited EB.

Chemoprevention of squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: results of a phase 1 trial of systemic isotretinoin.

BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) are at high risk of developing squamous cell carcinoma on or after midadolescence, and most patients die of metastatic squamous cell carcinoma within 5 years of diagnosis of their first squamous cell carcinoma. OBJECTIVE: We sought to determine whether isotretinoin can be safely administered to patients with RDEB as a possible chemopreventive agent. METHODS: A total of 20 patients with RDEB aged 15 years or older were treated daily for 8 months with isotretinoin (with a targeted dosage of 0.5 mg/kg/d). RESULTS: No unusual adverse reactions were noted in this patient population. Several patients experienced reduced blistering at lower doses and increased mechanical fragility at maintenance dosage. CONCLUSIONS: Isotretinoin, at least up to a dosage of 0.5 mg/kg/d, may be safely used in patients with RDEB. Although increased fragility may occur, patients tolerated this drug well and were receptive to its long-term use for possible chemoprevention of cancer. Whether such an effect will occur is yet to be proven.

Relative extent of skin involvement in inherited epidermolysis bullosa (EB): composite regional anatomic diagrams based on the findings of the National EB Registry, 1986 to 2002.

BACKGROUND: Inherited epidermolysis bullosa (EB) encompasses 4 major types and at least 23 clinically distinctive phenotypes. Although considerable variability in cutaneous disease activity is known to exist within each, severity and anatomic distribution of skin lesions remain the major criteria used for subclassification. OBJECTIVE: We sought to generate accurate anatomic "density" diagrams depicting the relative extent and location of skin lesions within each major EB subtype. METHODS: Diagrams were created for each major EB type, on the basis of medical history and physical examination findings obtained from 1986 to 2002 from 3280 consecutive enrollees in the National EB Registry. RESULTS: An anatomic diagram was created for each of the major EB subtypes, representing a prototypic composite photograph of cutaneous disease activity. CONCLUSIONS: Marked variability exists in the extent of skin involvement within each major EB subtype. The use of these diagrams, generated from the world's largest cohort of patients with EB, should assist the clinician in more accurately subclassifying newly encountered patients.