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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.

Lyme disease is a rapidly growing illness that remains poorly understood within the medical community. Critical questions about when and why patients respond to treatment or stay ill, what kinds of treatments are effective, and even how to properly diagnose the disease remain largely unanswered. We investigate these questions by applying machine learning techniques to a large scale Lyme disease patient registry, MyLymeData, developed by the nonprofit LymeDisease.org. We apply various machine learning methods in order to measure the effect of individual features in predicting participants&rsquo, answers to the Global Rating of Change (GROC) survey questions that assess the self-reported degree to which their condition improved, worsened, or remained unchanged following antibiotic treatment. We use basic linear regression, support vector machines, neural networks, entropy-based decision tree models, and k-nearest neighbors approaches. We first analyze the general performance of the model and then identify the most important features for predicting participant answers to GROC. After we identify the &ldquo, key&rdquo, features, we separate them from the dataset and demonstrate the effectiveness of these features at identifying GROC. In doing so, we highlight possible directions for future study both mathematically and clinically.

There is considerable uncertainty regarding treatment of Lyme disease patients who do not respond fully to initial short-term antibiotic therapy. Choosing the best treatment approach and duration remains challenging because treatment response among these patients varies: some patients improve with treatment while others do not. A previous study examined treatment response variation in a sample of over 3500 patients enrolled in the MyLymeData patient registry developed by LymeDisease.org (San Ramon, CA, USA). That study used a validated Global Rating of Change (GROC) scale to identify three treatment response subgroups among Lyme disease patients who remained ill: nonresponders, low responders, and high responders. The present study first characterizes the health status, symptom severity, and percentage of treatment response across these three patient subgroups together with a fourth subgroup, patients who identify as well. We then employed machine learning techniques across these subgroups to determine features most closely associated with improved patient outcomes, and we used traditional statistical techniques to examine how these features relate to treatment response of the four groups. High treatment response was most closely associated with (1) the use of antibiotics or a combination of antibiotics and alternative treatments, (2) longer duration of treatment, and (3) oversight by a clinician whose practice focused on the treatment of tick-borne diseases.

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.

Lyme disease caused by the spirochete Borrelia burgdorferi has become a major worldwide epidemic. Recent studies based on Big Data registries show that >300,000 people are diagnosed with Lyme disease each year in the USA, and up to two-thirds of individuals infected with B. burgdorferi will fail conventional 30-year-old antibiotic therapy for Lyme disease. In addition, animal and human evidence suggests that sexual transmission of the Lyme spirochete may occur. Improved companion diagnostic tests for Lyme disease need to be implemented, and novel treatment approaches are urgently needed to combat the epidemic. In particular, therapies based on the principles of precision medicine could be modeled on successful “designer drug” treatment for HIV/AIDS and hepatitis C virus infection featuring targeted protease inhibitors. The use of Big Data registries, companion diagnostics and precision medicine will revolutionize the diagnosis and treatment of Lyme disease., Video abstract

Lyme disease is caused by the bacteria borrelia burgdorferi and is spread primarily through the bite of a tick. There is considerable uncertainty in the medical community regarding the best approach to treating patients with Lyme disease who do not respond fully to short-term antibiotic therapy. These patients have persistent Lyme disease symptoms resulting from lack of treatment, under-treatment, or lack of response to their antibiotic treatment protocol. In the past, treatment trials have used small restrictive samples and relied on average treatment effects as their measure of success and produced conflicting results. To provide individualized care, clinicians need information that reflects their patient population. Today, we have the ability to analyze large data bases, including patient registries, that reflect the broader range of patients more typically seen in clinical practice. This allows us to examine treatment variation within the sample and identify groups of patients that are most responsive to treatment. Using patient-reported outcome data from the MyLymeData online patient registry, we show that sub-group analysis techniques can unmask valuable information that is hidden if averages alone are used. In our analysis, this approach revealed treatment effectiveness for up to a third of patients with Lyme disease. This study is important because it can help open the door to more individualized patient care using patient-centered outcomes and real-world evidence.

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.

This article presents insights into the use of electronic health records (EHRs) by small physician practices participating in a CMS pay-for-performance demonstration. Site visits to four States reveal slow movement toward improved EHR use. Factors facilitating use of EHRs include customization of EHR products and being owned by a larger organization. Factors limiting use of EHRs include system limitations, cost, and lack of strong incentives to improve. Practices in one State were moving more vigorously toward improved EHR use than those in the other States. Many practices also increased use of medical assistants after implementing EHRs.

Lyme disease is a controversial illness, and the existence of chronic Lyme disease induced by persistent infection with the Lyme spirochete, Borrelia burgdorferi, is the subject of continued debate. A recent publication defined the ‘Axis of Evil’ in this controversy as physicians who treat patients with needlessly prolonged courses of antibiotics, ‘specialty laboratories’ that perform ‘inaccurate’ Lyme testing and the internet, which promotes ‘Lyme hysteria’. We examine the ‘Axis of Evil’ components in the context of diagnostic and therapeutic challenges for Lyme disease patients and their physicians, and we present an evidence-based refutation to this misguided view. Despite its virulent nature, the ‘Axis of Evil’ perspective is a useful starting point to resolve the controversy over Lyme disease.

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.

This year’s lucky students, who were awarded delegate places at the 30th Conference and Exhibition, were Lorraine Johnson from Loughborough University;Angela Nicholson and Nicole LeBoeuf from Strathclyde; Helen Barrell from MMU and Sophie Price from UCL. Here are extracts from their reports.

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.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.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.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.

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.

Phillip Baker has taken “Lyme denialism” to new depths (1). According to the Institute of Medicine, there are at least 116 million people living with acute and chronic pain in the United States. According to Baker, not one of those individuals suffers from chronic Lyme disease as a result of persistent infection with the Lyme spirochete, Borrelia burgdorferi. What is the basis for his opinion? Baker claims that “there is no evidence to indicate that chronic Lyme disease is due to a persistent infection” or that “extended antibiotic therapy is beneficial and safe”. This denialist statement about a disease that causes pain and suffering equivalent to that of diabetes or congestive heart failure ignores a growing body of evidence from the peer-reviewed medical literature that contradicts his opinion (2–5). Baker starts by attacking “Lyme-literate” physicians who use a “Lyme disease specialty laboratory” to diagnose tick-borne disease in a manner that is inconsistent with the surveillance case definition established by the Centers for Disease Control and Prevention (CDC). What Baker fails to tell us is that the CDC admits that its surveillance case definition “was developed for national reporting of Lyme disease” and was “not intended to be used in clinical diagnosis” (6). Thus, the diagnostic approach that Baker endorses is inappropriate for diagnosis of Lyme disease. Furthermore, the 46 patented commercial laboratory tests that Baker recommends for Lyme disease diagnosis have a sensitivity of only 46% and appear to yield results that are biased against women (7–9). Consequently, these commercial tests miss more than one-half of the patients with chronic Lyme disease in the United States. In contrast, the maligned “Lyme disease specialty laboratory” uses diagnostic criteria based on evidence from the peerreviewed medical literature (10, 11), and its “genderneutral” testing has a sensitivity and specificity of 90% (12). Clearly, this testing is preferable for the diagnosis of Lyme disease. As for Baker’s pat statement that “there is no evidence to indicate that chronic Lyme disease is due to a persistent infection,” numerous reports of veterinary cases and animal models confirm persistent infection with the Lyme spirochete in gerbils, hamsters, mice, dogs, monkeys, birds, and horses (13– 15). Among these cases, persistent pathology was seen in mice, dogs, and horses after the animals failed short-course treatment for their infection. Furthermore, there are at least 27 reports of persistent symptoms and failure to eradicate B. burgdorferi infection in humans treated with short-course antibiotic therapy for their tick-borne disease (5). Why does Baker deny these reports? He does so because they do not fit his limited view of Lyme disease. Baker also attacks the safety and efficacy of prolonged antibiotic therapy for chronic Lyme disease, stating that “all of the evidence obtained thus far...indicates no significant benefit as well as serious safety problems” with extended antibiotic therapy for these patients. What Baker fails to tell us is that the number of patients in controlled trials of Lyme disease treatment totals a mere 221 highly selected subjects who do not represent the vast majority of patients with chronic Lyme disease (3–5). Further analysis of these studies reveals that they were “of questionable quality”, lacked the power to detect potentially positive treatment effects, and failed to report predefined endpoints (16). Even so, in two of the four controlled trials, a significant benefit was seen in fatigue and cognition with the limited antibiotic regimen that was used, and safety problems were minimal (17, 18). In larger studies of extended antibiotic therapy, the safety of this treatment was shown to be acceptable, and the benefit of extended therapy was significant in terms of cognition, fatigue, and myalgic pain, although it took 6 –12 months of i.v. therapy to achieve this benefit (19, 20). In summary, Baker’s denialist view of the Lyme disease epidemic ignores significant evidence from the peer-reviewed medical literature that contradicts his opinion. It follows that practitioners who subscribe to his narrow view are abandoning the multitude of patients with acute and chronic pain who would benefit from treatment for their persistent spirochetal infection.

Lyme disease is the most common tick-borne illness in the world today. Until recently, the Centers for Disease Control and Prevention (CDC) reported an average of only 30,000 cases of Lyme disease per year in the United States. Three preliminary CDC studies, however, have indicated that the true incidence of Lyme disease may be greater than 300,000 cases and as high as one million cases per year in the United States. A majority of these cases occur in women and children. Based on this new information, Lyme disease should be recognized as a virulent epidemic that is at least six times more common than HIV/AIDS. In response to these alarming statistics, we review the ongoing problems with diagnosis and treatment of Lyme disease. We propose the need for an HIV/AIDS-style “Manhattan project” to combat this serious epidemic that threatens the physical and mental health of millions of people around the world.

An analytical account of the history and aspirations of the Alex Wilson Community Garden in Toronto provides an ideal opportunity to examine the connections between two typically distinct enterprises: ecological restoration and community gardening. These are both important contemporary ecological movements, but are rarely combined in a single project that demonstrates the principles of sustainable land use and community planning. The garden is named in memory of Alex Wilson, a landscape designer, community activist and writer who worked and lived in Toronto, Canada. During his life, Wilson established a community garden which was eventually replaced by conventional urban development. After his death in 1993, friends and colleagues decided to honour his memory by establishing a permanent community garden in his name. The Alex Wilson Community Garden opened to the public in June 1998. The case‐study explores how the garden reflects Wilson's work by linking community gardening and ecological restora...

Lyme disease is the most common tickborne illness in the world today. A recent study describes for the first time an enzyme produced by the spirochetal agent of Lyme disease, Borrelia burgdorferi, that cleaves aggrecan, a proteoglycan found in joints and connective tissue. Discovery of the spirochetal aggrecanase raises many questions about the pathogenesis of Lyme arthritis and lends support to the concept of persistent B. burgdorferi infection in patients with chronic Lyme disease symptoms.

ARTICLE ARTICLE ARTICLE Sir, White et al. describe their ‘real world’ experience with outpatient parenteral antibiotic therapy (OPAT) administered to patients with suspected Lyme borreliosis presumably caused by the spirochete Borrelia burgdorferi .1 The authors focus on the risk of OPAT and the low overall response rate in their heterogeneous group of patients, thereby generating good news and bad news. The good news is that the treatment risk for their patients was similar to the risk considered to be acceptable in OPAT studies of other diseases,2,3 and 86% of patients tolerated OPAT without serious adverse events. The bad news is that by blending their treatment results the authors …

Background We have shown previously that extended intravenous antibiotic therapy is associated with low morbidity and no mortality in patients referred for treatment of neurologic Lyme disease. In this study, we evaluated the benefit of extended intravenous antibiotic therapy in patients with symptoms of neurologic Lyme disease. Methods Patients with significant neurologic symptoms and positive testing for Borrelia burgdorferi were treated with intravenous antibiotics, and biweekly evaluation of symptom severity was performed using a six-level ordinal scale. Four symptoms were selected a priori as primary outcome measures in the study, ie, fatigue, cognition, myalgias, and arthralgias. Patients were placed into five groups according to time on treatment (1–4, 5–8, 9–12, 13–24, and 25–52 weeks), and changes in the primary symptoms as a function of time on treatment were analyzed using a mixed-effects proportional odds model. Results Among 158 patients with more than one follow-up visit who were monitored for up to 1 year, there were on average 6.7 visits per person (median 5, range 2–24). The last follow-up day was on average 96 days after enrollment (median 69, range 7–354 days), corresponding to the length of antibiotic therapy. Each primary symptom was significantly improved at one or more time points during the study. For cognition, fatigue, and myalgias, the greatest improvement occurred in patients on the longest courses of treatment (25–52 weeks) with odds ratios (OR) for improvement of 1.97 (P = 0.02), 2.22 (P < 0.01), and 2.08 (P = 0.01), respectively. In contrast, arthralgias were only significantly improved during the initial 1–4 weeks of therapy (OR: 1.57, P = 0.04), and the beneficial effect of longer treatment did not reach statistical significance for this symptom. Conclusion Prolonged intravenous antibiotic therapy is associated with improved cognition, fatigue, and myalgias in patients referred for treatment of neurologic Lyme disease. Treatment for 25–52 weeks may be necessary to obtain symptomatic improvement in these patients., Video abstract Video

The inversa subtype of autosomal recessive dystrophic epidermolysis bullosa (EBDR-I) is a rare variant characterized by lesions involving primarily the flexural areas of the body. The purpose of this investigation was to characterize the oral manifestations of this unusual dermatologic condition. Ten individuals having EBDR-I were evaluated and compared with an age and sex-matched population of unaffected individuals that served as controls. The diagnosis of EBDR-I was confirmed by skin biopsy that demonstrated tissue separation below the lamina densa and the clinical presentation of blister formation that typically localized to flexural areas. There was clinical variability in the severity and distribution of skin involvement; however, none of the affected individuals demonstrated pronounced digital webbing, severe generalized blistering or growth retardation characteristic of the Hallopeau-Siemens form of EBDR. Oral involvement was seen in all cases with ankyloglossia, loss of tongue papillae and obliteration of the oral vestibule between the lips and gingiva being typical. The oral opening was significantly reduced in older EBDR-I individuals compared with matched controls, confirming that acquired microstomia is a characteristic of EBDR-I. The teeth were not clinically abnormal or malformed and showed no evidence of generalized enamel hypoplasia. Despite this, the prevalence of dental caries in EBDR-I individuals was significantly higher than the control group. The inversa form of EBDR presents with oral findings that are similar but generally milder than those seen in the Hallopeau-Siemens variant of EBDR.

Objective To evaluate the challenges faced by Lyme disease patients in obtaining adequate healthcare. Methods A web-based survey conducted over nine months was analyzed for the study. The survey focused on medical status, access to healthcare, and burden of illness. For inclusion in the study, survey respondents had to reside in the United States, be more than 10 years old, and have clinically diagnosed Lyme disease with chronic symptoms and positive laboratory testing. Results Responses from 2424 patients were included in the study. Half of the respondents reported seeing at least seven physicians before the diagnosis of Lyme disease was made. Nearly half had Lyme disease for more than 10 years and traveled over 50 miles to obtain treatment. Most respondents experienced symptoms lasting six months or more despite receiving at least 21 days of antibiotic treatment. A quarter of respondents had been on public support or received disability benefits due to Lyme disease symptoms, and over half had visited an emergency room at least once as a result of these symptoms. Conclusions Lyme disease patients frequently endure extensive delays in obtaining an initial diagnosis, have poor access to healthcare and suffer a severe burden of illness.

Flawed clinical practice guidelines may compromise patient care. Commercial conflicts of interest on panels that write treatment guidelines are particularly problematic, because panelists may have conflicting agendas that influence guideline recommendations. Historically, there has been no legal remedy for conflicts of interest on guidelines panels. However, in May 2008, the Attorney General of Connecticut concluded a ground-breaking antitrust investigation into the development of Lyme disease treatment guidelines by one of the largest medical societies in the United States, the Infectious Diseases Society of America (IDSA). Although the investigation found significant flaws in the IDSA guidelines development process, the subsequent review of the guidelines mandated by the settlement was compromised by a lack of impartiality at various stages of the IDSA review process. This article will examine the interplay between the recent calls for guidelines reform, the ethical canons of medicine, and due process considerations under antitrust laws as they apply to the formulation of the IDSA Lyme disease treatment guidelines. The article will also discuss pitfalls in the implementation of the IDSA antitrust settlement that should be avoided in the future.

Objective Many worry that the use of specialty tiering for biologic disease-modifying antirheumatic drugs (DMARDs) by Medicare Part D plans imposes a heavy financial burden on beneficiaries with rheumatoid arthritis (RA). To date, no one has examined the cost-sharing structures for biologic DMARDs in Part D plans or the resulting cost burden for patients. Methods We followed 14,929 vulnerable, low-income patients with RA who were enrolled in the Medicare Replacement Drug Demonstration (MRDD) in 2005. As the MRDD population transitioned into Part D in 2006, we examined correlates of Part D enrollment and compared the cost-sharing provisions for biologic DMARDs in the Medicare Advantage and stand-alone plans. We simulated the out-of-pocket costs of beneficiaries under 3 cost-sharing scenarios. Results Eighty-one percent of MRDD beneficiaries with RA enrolled in Part D. Enrollment predictors were female sex (odds ratio [OR] 1.48, 95% confidence interval [95% CI] 1.32–1.67), prior MRDD benefit use (OR 2.29, 95% CI 2.04–2.58), other self-reported drug coverage (OR 1.53, 95% CI 1.36–1.71), and receiving an MRDD subsidy (OR 2.00, 95% CI 1.74–2.30). Compared with stand-alone plans, Medicare Advantage plans had lower deductibles, lower premiums, and fewer prior authorization, step therapy, and quantity limit restrictions. However, ∼75% of all plans used coinsurance as the preferred form of cost sharing. Out-of-pocket costs exceeded $4,000 annually in all cost-sharing scenarios. Conclusion Most MRDD beneficiaries with RA enrolled in Part D. Although plans assume some costs for biologic DMARDs, the majority of costs are shifted to beneficiaries and to Medicare. Such cost shifting may place these medications out of the beneficiary's financial reach and expose Medicare to high financial liability.

Inherited epidermolysis bullosa encompasses a number of diseases, with the common finding of blister formation, after minor mechanical trauma to the skin. In some forms significant, if not eventually fatal, extracutaneous disease activity may occur. In recent years application of newer technologies has contributed substantially to an overall understanding of this collection of inherited diseases. Concurrently, many new phenotypes have been recognized, in part the result of ongoing prospective patient registries in the United States and abroad. Unfortunately, this has resulted in a massive literature that may appear to be confounded by seemingly excessive or arbitrary subdivision of epidermolysis bullosa variants. With these concerns in mind a subcommittee was established by the National Epidermolysis Bullosa Registry to summarize the current literature and to make recommendations as to the best clinical and laboratory criteria for the practical diagnosis and subclassification of patients with inherited epidermolysis bullosa.

Video presentation of the opening keynote address given at the 2007 Greenscapes conference at Brock University (St. Catharines, ON). Lorraine Johnson is the author of numerous books related to environmental issues and gardening, including The New Ontario Naturalized Garden; 100 Easy-to-Grow Native Plants for Canadian Gardens; and The Gardener's Manifesto. In this address Johnson discusses some key ideas relating to the theme of "the garden in the city."

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.

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.

Summary Background The presence in a family of a child or children with epidermolysis bullosa (EB) may have profound psychological implications for other family members. Objectives To assess the impact of the presence of EB in one or more children on the personal relationships between their parents. Methods Standardized questionnaires were used. Results In general, the presence of a child severely affected with EB had profound effects on many aspects of marriage. This included a lack of interest in participating in activities as couples [junctional EB (JEB), 45%; recessive dystrophic EB (RDEB), 25%], a lack of energy to invest in such pursuits (JEB, 82%; RDEB, 50%), limitations in opportunities for sharing nonintimate physical activities (reported by most parents having children with some type of generalized EB), and negatively altered parental sex life (JEB, 55%; RDEB, 39%). This is consistent with the fact that 10%, 64%, 25% and 36% of parents of an affected child with EB simplex (EBS), JEB, dominant dystrophic EB (DDEB) and RDEB, respectively, characterized their relationships as couples as revolving almost exclusively around the day-to-day care of their affected children. The severity of disease in an affected child clearly influenced parental decisions about having more children: 24% and 64% of parents of children with JEB and RDEB, respectively, chose not to have additional children, compared with 26% and 54% of parents with children having EBS or DDEB. This choice was most often pursued via tubal ligation; less often, alternative means of surgical sterilization were chosen. Divorce was common among parents of children with EB (range: 17% in EBS to 31% in JEB) and, with the exception of parents of children with EBS, was usually directly attributed by one or both parents to the profound impact that this disease had exerted on their marriage. Conclusions Physicians caring for children with EB need to give more consideration to the many psychological factors that may contribute to their patients' well being. They may need to assist these children's parents in seeking support and counselling to prevent destruction of the family unit.

Lyme disease is the most common tick-borne disease in the world today. Despite extensive research into the complex nature of Borrelia burgdorferi, the spirochetal agent of Lyme disease, controversy continues over the diagnosis and treatment of this protean illness. This report will focus on two aspects of the treatment of Lyme disease. First, the medical basis for diagnostic and therapeutic uncertainty in Lyme disease, including variability in clinical presentation, shortcomings in laboratory testing procedures, and design defects in therapeutic trials. Second, the standard of care and legal issues that have resulted from the clinical uncertainty of Lyme disease diagnosis and treatment. Specifically, the divergent therapeutic standards for Lyme disease are addressed, and the difficult process of creating treatment guidelines for this complex infection is explored. Consideration by healthcare providers of the medicolegal issues outlined in this review will support a more rational approach to the diagnosis and treatment of Lyme disease and related tick-borne illnesses.

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.

Mitten deformities of the hands and feet occur in nearly every patient with the most severe subtype (Hallopeau-Siemens) of recessive dystrophic epidermolysis bullosa, and in at least 40–50% of all other recessive dystrophic epidermolysis bullosa patients. Smaller numbers of patients with dominant dystrophic, junctional, and simplex types of epidermolysis bullosa are also at risk of this complication. Surgical intervention is commonly performed to correct these deformities, but recurrence and the need for repeated surgery are common. Higher numbers of epidermolysis bullosa patients also develop musculoskeletal contractures in other anatomic sites, further impairing overall function. Lifetable analyses not only better project the cumulative risk of mitten deformities and other contractures but also emphasize the need for early surveillance and intervention, since both of these musculoskeletal complications may occur within the first year of life.

Since its inception in 1986, the NEBR has proved to be an excellent example of how a relatively small allocation of federal research funds for the development of a registry of cases of a single rare disease can have a major impact on the rapid expansion in the depth of knowledge of not only the disease itself but of a number of associated biologic principles, including keratinization and epithelial cell-extracellular matrix interactions. At present, the NEBR is generating extensive clinical, laboratory, and demographic data, both from cross-sectional and longitudinal perspectives, as well as establishing a centralized cell and tissue bank that will serve the scientific community at large as a valuable resource for future basic research on this oftentimes devastating genetic disease.