A Systematic Review of Epidemiology and Outcomes Associated with Local Surgical and Intersphincteric Ligation Procedures for Complex Cryptoglandular Fistulas.

INTRODUCTION: This systematic literature review (SLR) assessed incidence/prevalence of cryptoglandular fistulas (CCF) and outcomes associated with local surgical and intersphincteric ligation procedures for CCFs. METHODS: Two trained reviewers searched PubMed and Embase for observational studies evaluating the incidence/prevalence of cryptoglandular fistula and clinical outcomes of treatments for CCF after local surgical and intersphincteric ligation procedures for CCF. RESULTS: In total 148 studies met a priori eligibility criteria for all cryptoglandular fistulas and all intervention types. Of those, two assessed incidence/prevalence of cryptoglandular fistulas. Eighteen reported clinical outcomes of surgeries of interest in CCF and were published in the past 5 years. Prevalence was reported as 1.35/10,000 non-Crohn's patients, and 52.6% of non-IBD patients were found to progress from anorectal abscess to fistula over 12 months. Primary healing rates ranged from 57.1% to 100%; recurrence occurred in a range of 4.9-60.7% and failure in 2.8-18.0% of patients. Limited published evidence suggests postoperative fecal incontinence and long-term postoperative pain were rare. Several of the studies were limited by single-center design with small sample sizes and short follow-up durations. DISCUSSION: This SLR summarizes outcomes from specific surgical procedures for the treatment of CCF. Healing rates vary according to procedure and clinical factors. Differences in study design, outcome definition, and length of follow-up prevent direct comparison. Overall, published studies offer a wide range of findings with respect to recurrence. Postsurgical incontinence and long-term postoperative pain were rare in the included studies, but more research is needed to confirm rates of these conditions following CCF treatments. CONCLUSION: Published studies on the epidemiology of CCF are rare and limited. Outcomes of local surgical and intersphincteric ligation procedures show differing success and failure rates, and more research is needed to compare outcomes across various procedures. (PROSPERO; registration number CRD42020177732).

A systematic review of epidemiology and outcomes of Crohn's disease-related enterocutaneous fistulas.

BACKGROUND: Enterocutaneous fistulas (ECF) are rare sequelae of Crohn's disease (CD) that occur either postoperatively or spontaneously. ECFs are associated with high morbidity and mortality. This systematic literature review assesses the disease burden of CD-related ECF and identifies knowledge gaps around incidence/prevalence, treatment patterns, clinical outcomes, healthcare resource utilization (HCRU), and patient-reported outcomes (PROs). METHODS: English language articles published in PubMed and Embase in the past 10 years that provided data and insight into the disease burden of CD-related ECF (PROSPERO Registration number: CRD42020177732) were identified. Prespecified search and eligibility criteria guided the identification of studies by two reviewers who also assessed risk of bias. RESULTS: In total, 582 records were identified; 316 full-text articles were assessed. Of those, eight studies met a priori eligibility criteria and underwent synthesis for this review. Limited epidemiologic data estimated a prevalence of 3265 persons with ECF in the USA in 2017. Clinical response to interventions varied, with closure of ECF achieved in 10% to 62.5% of patients and recurrence reported in 0% to 50% of patients. Very little information on HCRU is available, and no studies of PROs in this specific population were identified. CONCLUSION: The frequency, natural history, and outcomes of ECF are poorly described in the literature. The limited number of studies included in this review suggest a high treatment burden and risk of substantial complications. More robust, population-based research is needed to better understand the epidemiology, natural history, and overall disease burden of this rare and debilitating complication of CD.

A systematic review of the patient burden of Crohn's disease-related rectovaginal and anovaginal fistulas.

BACKGROUND: Crohn's disease (CD)-related rectovaginal fistulas (RVFs) and anovaginal fistulas (AVFs) are rare, debilitating conditions that present a substantial disease and treatment burden for women. This systematic literature review (SLR) assessed the burden of Crohn's-related RVF and AVF, summarizing evidence from observational studies and highlighting knowledge gaps. METHODS: This SLR identified articles in PubMed and Embase that provide data and insight into the patient experience and disease burden of Crohn's-related RVF and AVF. Two trained reviewers used pre-specified eligibility criteria to identify studies for inclusion and evaluate risk of bias using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. RESULTS: Of the 582 records identified, 316 full-text articles were assessed, and 16 studies met a priori eligibility criteria and were included. Few epidemiology studies were identified, with one study estimating the prevalence of RVF to be 2.3% in females with Crohn's disease. Seven of 12 treatment pattern studies reported that patients had or required additional procedures before and/or after the intervention of interest, demonstrating a substantial treatment burden. Seven of 11 studies assessing clinical outcomes reported fistula healing rates between 50 and 75%, with varying estimates based on population and intervention. CONCLUSIONS: This SLR reports the high disease and treatment burden of Crohn's-related RVF and AVF and identifies multiple evidence gaps in this field. The literature lacks robust, generalizable data, and demonstrates a compelling need for substantial, novel research into these rare and debilitating sequelae of CD. Registration The PROSPERO registration number for the protocol for this systematic literature review is CRD42020177732.

Qualitative measures that assess functional disability and quality of life in ALS.

BACKGROUND: Selection of appropriate trial endpoints and outcome measures is particularly important in rare disease and rapidly progressing disease such as amyotrophic lateral sclerosis (ALS) where the challenges to conducting clinical trials, are substantial: patient and disease heterogeneity, limited understanding of exact disease pathophysiology, and lack of robust and available biomarkers. To address these challenges in ALS, the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised version (ALSFRS-R) was developed and has become a key primary endpoint in ALS clinical trials to assess functional disability and disease progression, often replacing survival as a primary outcome. However, increased understanding of the ALS disease journey and improvements in assistive technology for ALS patients have exposed issues with the ALSFRS-R, including non-linearity, multidimensionality and floor and ceiling effects that could challenge its continued utility as a primary outcome measure in ALS clinical trials. Recently, other qualitative scale measures of functioning disability have been developed to help address these issues. With this in mind, we conducted a literature search aimed at identifying both established and promising new measures for potential use in clinical trials. METHODS: We searched PubMed, Google, Google Scholar, and the reference sections of key studies to identify papers that discussed qualitative measures of functional status for potential use in ALS studies. We also searched clinicaltrials.gov to identify functional status and health-related quality of life (HRQoL) measures that have been used in ALS interventional studies. RESULTS: In addition to the ALSFRS-R, we identified several newer qualitative scales including ALSFRS-EX, ALS-MITOS, CNS-BFS, DALS-15, MND-DS, and ROADS. Strengths and limitations of each measure were identified and discussed, along with their potential to act as a primary or secondary outcome to assess patient functional status in ALS clinical trials. CONCLUSION: This paper serves as a reference guide for researchers deciding which qualitative measures to use as endpoints in their ALS clinical trials to assess functional status. This paper also discusses the importance of including ALS HRQoL and ALS cognitive screens in future clinical trials to assess the value of a new ALS therapy more comprehensively.

A Descriptive Review of Global Real World Evidence Efforts to Advance Drug Discovery and Clinical Development in Amyotrophic Lateral Sclerosis.

Understanding patient clinical progression is a key gateway to planning effective clinical trials and ultimately enabling bringing treatments to patients in need. In a rare disease like amyotrophic lateral sclerosis (ALS), studies of disease natural history critically depend on collaboration between clinical centers, regions, and countries to enable creation of platforms to allow patients, caregivers, clinicians, and researchers to come together and more fully understand the condition. Rare disease registries and collaborative platforms such as those developed in ALS collect real-world data (RWD) in standardized formats, including clinical and biological specimen data used to evaluate risk factors and natural history of disease, treatment patterns and clinical (ClinROs) and patient- reported outcomes (PROs) and validate novel endpoints. Importantly, these data support the development of new therapeutics by supporting the evaluation of feasibility and design of clinical trials and offer valuable information on real-world disease trajectory and outcomes outside of the clinical trial setting for comparative purposes. RWD may help to accelerate therapy development by identifying and validating outcome measures and disease subpopulations. RWD can also make potential contributions to the evaluation of the safety and effectiveness of new indications for approved products and to satisfy post-approval regulatory and market access requirements. There is a lack of amalgamated information on available registries, databases, and other sources of real-world data on ALS; thus, a global review of all available resources was warranted. This targeted review identifies and describes ALS registries, biobanks and collaborative research networks that are collecting and synthesizing RWD for the purposes of increasing patient awareness and advancing scientific knowledge with the hope of expediting future development of new therapies.

Ticagrelor Removal by CytoSorb® in Patients Requiring Emergent or Urgent Cardiac Surgery: A UK-Based Cost-Utility Analysis.

BACKGROUND: Acute coronary syndrome patients receiving dual antiplatelet therapy who need emergent or urgent cardiac surgery are at high risk of major bleeding, which can impair postoperative outcomes. CytoSorb®, a blood purification technology based on adsorbent polymer, has been demonstrated to remove ticagrelor from blood during on-pump cardiac surgery. OBJECTIVE: The aim of this study was to evaluate the cost utility of intraoperative removal of ticagrelor using CytoSorb versus usual care among patients requiring emergent or urgent cardiac surgery in the UK. METHODS: A de novo decision analytic model, based on current treatment pathways, was developed to estimate the short- and long-term costs and outcomes. Results from randomised clinical trials and national standard sources such as National Health Service (NHS) reference costs were used to inform the model. Costs were estimated from the NHS and Personal Social Services perspective. Deterministic and probabilistic sensitivity analyses (PSAs) explored the uncertainty surrounding the input parameters. RESULTS: In emergent cardiac surgery, intraoperative removal of ticagrelor using CytoSorb was less costly (£12,933 vs. £16,874) and more effective (0.06201vs. 0.06091 quality-adjusted life-years) than cardiac surgery without physiologic clearance of ticagrelor over a 30-day time horizon. For urgent cardiac surgery, the use of CytoSorb was less costly than any of the three comparators-delaying surgery for natural washout without adjunctive therapy, adjunctive therapy with short-acting antiplatelet agents, or adjunctive therapy with low-molecular-weight heparin. Results from the PSAs showed that CytoSorb has a high probability of being cost saving (99% in emergent cardiac surgery and 53-77% in urgent cardiac surgery, depending on the comparators). Cost savings derive from fewer transfusions of blood products and re-thoracotomies, and shorter stay in the hospital/intensive care unit. CONCLUSIONS: The implementation of CytoSorb as an intraoperative intervention for patients receiving ticagrelor undergoing emergent or urgent cardiac surgery is a cost-saving strategy, yielding improvement in perioperative and postoperative outcomes and decreased health resource use.

Spinal Muscular Atrophy (SMA) Subtype Concordance in Siblings: Findings From the Cure SMA Cohort.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous survival of motor neuron 1 (SMN1) gene disruption. Despite a genetic etiology, little is known about subtype concordance among siblings. OBJECTIVE: To investigate subtype concordance among siblings with SMA. METHODS: Cure SMA maintains a database of newly diagnosed patients with SMA, which was utilized for this research. RESULTS: Among 303 sibships identified between 1996 and 2016, 84.8% were subtype concordant. Of concordant sibships, subtype distribution was as follows: Type I, 54.5%; Type II, 31.9%; Type III, 13.2%; Type IV, 0.4%. Subtype and concordance/discordance association was significant (Fisher's exact test; p < 0.0001). Among discordant sibships (chi-square test, p < 0.0001), Types II/III (52.2%) and Types I/II (28.3%) were the most common pairs. No association was found between sibling sex and concordance. Our findings show that most siblings with SMA shared the same subtype concordance (most commonly Type I). CONCLUSIONS: These data are valuable for understanding familial occurrence of SMA subtypes, enabling better individual treatment and management planning in view of new treatment options and newborn screening initiatives.

An overview of the Cure SMA membership database: Highlights of key demographic and clinical characteristics of SMA members.

BACKGROUND: The Cure SMA database is one of the largest patient reported databases for people affected with SMA. OBJECTIVE: The purpose of this study was to examine a subset of affected SMA persons with types I, II, and III from a patient reported database. METHODS: Individuals with SMA were selected from the database using a date of first contact to Cure SMA between 2010 and 2016. Data analyzed included age at diagnosis, number of weeks from SMA diagnosis to contacting Cure SMA, and geographic distribution of individuals. RESULTS: A total of 1,966 individuals with SMA were included in the analysis. Of these individuals, 51.9% had type I, 32.3% had type II, and 15.8% had type III. The average age of diagnosis for type I patients was 5.2 months, 22.1 months for type II, and 97.8 months for type III. From published incidence, about 59.0% of affected individuals in the US are registered in the Cure SMA database. CONCLUSIONS: The Cure SMA database is a unique and robust source of patient reported data that informs on the burden of illness and supports the development of new therapeutic modalities.

Epidemiology of hyperhidrosis in 2 population-based health care databases.

BACKGROUND: Population-based and clinical case reports of hyperhidrosis (HH) provide prevalence estimates that vary widely across reported studies because of differences in case ascertainment. OBJECTIVE: In this study, we specify diagnostic, symptom, and prescription codes for HH to estimate incidence and prevalence for the United Kingdom and the United States. METHODS: Data from UK and US health care databases were analyzed to ascertain HH cases and estimate incidence and prevalence from health care records during calendar years 2011 through 2013. RESULTS: On the basis of 2013 data for the United States and United Kingdom, between 1.0% and 1.6% of these populations have health care records indicating diagnosis or treatment of HH. Women accounted for approximately 60% of incident and prevalent cases in both databases. LIMITATIONS: Because the case ascertainment methods rely on available data for those seeking health care, we may have underestimated the number of HH cases in both countries. CONCLUSIONS: The findings represent a plausible estimate for incidence and prevalence of HH among persons seeking medical care for excessive sweating. Improved practices for identifying HH in clinical settings may increase the sensitivity and specificity of future studies and improve characterization and quantification of the population burden of this significant disease.

Phenome-wide association study using research participants' self-reported data provides insight into the Th17 and IL-17 pathway.

A phenome-wide association study of variants in genes in the Th17 and IL-17 pathway was performed using self-reported phenotypes and genetic data from 521,000 research participants of 23andMe. Results replicated known associations with similar effect sizes for autoimmune traits illustrating self-reported traits can be a surrogate for clinically assessed conditions. Novel associations controlling for a false discovery rate of 5% included the association of the variant encoding p.Ile684Ser in TYK2 with increased risk of tonsillectomy, strep throat occurrences and teen acne, the variant encoding p.Arg381Gln in IL23R with a decrease in dandruff frequency, the variant encoding p.Asp10Asn in TRAF3IP2 with risk of male-pattern balding, and the RORC regulatory variant (rs4845604) with protection from allergies. This approach enabled rapid assessment of association with a wide variety of traits and investigation of traits with limited reported associations to overlay meaningful phenotypic context on the range of conditions being considered for drugs targeting this pathway.

Indirect estimation of the prevalence of spinal muscular atrophy Type I, II, and III in the United States.

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive, devastating disease and a leading inherited cause of infant mortality. The limited population-based literature is confined to small regional studies. Estimates of prevalence are needed to characterize the burden of SMA and to understand trends in prevalence by disease type as new treatments become available. The reported estimates of SMA genotype prevalence at birth consistently range from 8.5-10.3 per 100,000 live births, with a mid-range estimate of 9.4 per 100,000. Among infants born with an SMA genotype, it is reported that ~58% will develop SMA Type I, 29% will develop Type II, and 13% will develop Type III, respectively. RESULTS: Using evidence from peer-reviewed literature for SMA birth prevalence, age at symptom onset, and SMA type-specific survival, and incorporating United States vital statistics, we constructed life tables to estimate prevalence for SMA Types I, II, and III in the United States. We estimated the number of prevalent cases in the US to be 8526, 9429, and 10,333 based on a birth prevalence of 8.5, 9.4, and 10.3, respectively (the lower, midpoint, and upper ends of the reported range). Assuming the midpoint of 9.4 and US-reported survival, the type-specific population prevalence estimates were 1610 for SMA Type I, 3944 for SMA Type II, and 3875 for SMA Type III. Evidence-based estimates of the number of people living with SMA in the United States in the published literature were previously unavailable. CONCLUSIONS: In the absence of a survey or other means to directly estimate prevalence in the US population, estimates can be calculated indirectly using a life table.

Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review.

Spinal muscular atrophy linked to chromosome 5q (SMA) is a recessive, progressive, neuromuscular disorder caused by bi-allelic mutations in the SMN1 gene, resulting in motor neuron degeneration and variable presentation in relation to onset and severity. A prevalence of approximately 1-2 per 100,000 persons and incidence around 1 in 10,000 live births have been estimated with SMA type I accounting for around 60% of all cases. Since SMA is a relatively rare condition, studies of its prevalence and incidence are challenging. Most published studies are outdated and therefore rely on clinical rather than genetic diagnosis. Furthermore they are performed in small cohorts in small geographical regions and only study European populations. In addition, the heterogeneity of the condition can lead to delays and difficulties in diagnosing the condition, especially outside of specialist clinics, and contributes to the challenges in understanding the epidemiology of the disease. The frequency of unaffected, heterozygous carriers of the SMN1 mutations appears to be higher among Caucasian and Asian populations compared to the Black (Sub-Saharan African ancestry) population. However, carrier frequencies cannot directly be translated into incidence and prevalence, as very severe (death in utero) and very mild (symptom free in adults) phenotypes carrying bi-allelic SMN1 mutations exist, and their frequency is unknown. More robust epidemiological data on SMA covering larger populations based on accurate genetic diagnosis or newborn screening would be helpful to support planning of clinical studies, provision of care and therapies and evaluation of outcomes.

A multi-source approach to determine SMA incidence and research ready population.

In spinal muscular atrophy (SMA), degeneration of motor neurons causes progressive muscular weakness, which is caused by homozygous deletion of the SMN1 gene. Available epidemiological data on SMA are scarce, often outdated, and limited to relatively small regions or populations. Combining data from different sources including genetic laboratories and patient registries may provide better insight of the disease epidemiology. To investigate the incidence of genetically confirmed SMA, and the number of patients who are able and approachable to participate in new clinical trials and observational research, we used both genetic laboratories, the TREAT-NMD Global SMA Patient Registry and the Care and Trial Sites Registry (CTSR). In Europe, 4653 patients were genetically diagnosed by the genetic laboratories in the 5-year period 2011 to 2015, with 992 diagnosed in 2015 alone. The data provide an estimated incidence of SMA in Europe of 1 in 3900-16,000 live births. Patient numbers in the national patient registries and CTSR were considerably lower. By far, most patients registered in the national patient registries and the CTSR live in Europe and are reported to have SMA type II. Considerable differences between countries in patient participation in the registries were observed. Our findings indicate that not all patients with SMA are accessed by specialist healthcare services and these patients may not have access to research opportunities and optimal care.

Exploring Methods to Measure the Prevalence of Ménière's Disease in the US Clinformatics™ Database, 2010-2012.

Recent studies on the epidemiology of the inner-ear disorder Ménière's disease (MD) use disparate methods for sample selection, case identification and length of observation. Prevalence estimates vary geographically from 17 to 513 cases per 100,000 people. We explored the impact of case detection strategies and observation periods in estimating the prevalence of MD in the USA, using data from a large insurance claims database. Using case detection strategies of ≥1, ≥2 and ≥3 ICD-9 claim codes for MD within a 1-year period, the 2012 prevalence estimates were 66, 27 and 14 cases per 100,000 people, respectively. For ≥1, ≥2 and ≥3 insurance claims within a 3-year observation period, the prevalence estimates were 200, 104 and 66 cases per 100,000 people, respectively. Estimates based on a single claim are likely to overestimate prevalence; this conclusion is aligned with the American Academy of Otolaryngology-Head and Neck Foundation criteria requiring ≥2 definitive episodes for a definite diagnosis, and it has implications for future epidemiologic research. We believe estimates for ≥2 claims may be a more conservative estimate of the prevalence of MD, and multiyear estimates may be needed to allow for adequate follow-up time.

Collecting Biospecimens From an Internet-Based Prospective Cohort Study of Inflammatory Bowel Disease (CCFA Partners): A Feasibility Study.

BACKGROUND: The Internet has successfully been used for patient-oriented survey research. Internet-based translational research may also be possible. OBJECTIVE: Our aim was to study the feasibility of collecting biospecimens from CCFA Partners, an Internet-based inflammatory bowel disease (IBD) cohort. METHODS: From August 20, 2013, to January 4, 2014, we randomly sampled 412 participants, plus 179 from a prior validation study, and invited them to contribute a biospecimen. Participants were randomized to type (blood, saliva), incentive (none, US $20, or US $50), and collection method for blood. The first 82 contributors were also invited to contribute stool. We used descriptive statistics and t tests for comparisons. RESULTS: Of the 591 participants, 239 (40.4%) indicated interest and 171 (28.9%) contributed a biospecimen. Validation study participants were more likely to contribute than randomly selected participants (44% versus 23%, P<.001). The return rate for saliva was higher than blood collected by mobile phlebotomist and at doctors' offices (38%, 31%, and 17% respectively, P<.001). For saliva, incentives were associated with higher return rates (43-44% versus 26%, P=.04); 61% contributed stool. Fourteen IBD-associated single nucleotide polymorphisms were genotyped, and risk allele frequencies were comparable to other large IBD populations. Bacterial DNA was successfully extracted from stool samples and was of sufficient quality to permit quantitative polymerase chain reaction for total bacteria. CONCLUSIONS: Participants are willing to contribute and it is feasible to collect biospecimens from an Internet-based IBD cohort. Home saliva kits yielded the highest return rate, though mobile phlebotomy was also effective. All samples were sufficient for genetic testing. These data support the feasibility of developing a centralized collection of biospecimens from this cohort to facilitate IBD translational studies.

Enrollment factors and bias of disease prevalence estimates in administrative claims data.

PURPOSE: Considerations for using administrative claims data in research have not been well-described. To increase awareness of how enrollment factors and insurance benefit use may contribute to prevalence estimates, we evaluated how differences in operational definitions of the cohort impact observed estimates. METHODS: We conducted a cross-sectional study estimating the prevalence of five gastrointestinal conditions using MarketScan claims data for 73.1 million enrollees. We extracted data obtained from 2009 to 2012 to identify cohorts meeting various enrollment, prescription drug benefit, or health care utilization characteristics. Next, we identified patients meeting the case definition for each of the diseases of interest. We compared the estimates obtained to evaluate the influence of enrollment period, drug benefit, and insurance usage. RESULTS: As the criteria for inclusion in the cohort became increasingly restrictive the estimated prevalence increased, as much as 45% to 77% depending on the disease condition and the definition for inclusion. Requiring use of the insurance benefit and a longer period of enrollment had the greatest influence on the estimates observed. CONCLUSIONS: Individuals meeting case definition were more likely to meet the more stringent definition for inclusion in the study cohort. This may be considered a form of selection bias, where overly restrictive inclusion criteria definitions may result in selection of a source population that may no longer represent the population from which cases arose.

Prevalence of chronic narcotic use among children with inflammatory bowel disease.

BACKGROUND & AIMS: Narcotic analgesics are not recommended for long-term management of pain for patients with inflammatory bowel disease (IBD), particularly pediatric patients. We compared chronic use of narcotics among children with IBD and the general population and investigated factors associated with narcotic use in the pediatric IBD population. METHODS: This cross-sectional study included children (younger than 18 years old) with continuous enrollment in a large administrative claims database from 2010 through 2011 (n = 4,911,286). Children with IBD were identified through diagnosis codes and dispensation of IBD medication (n = 4344); they were matched for age, sex, and region with 5 children without IBD (n = 21,720). Chronic narcotic use was defined as ≥3 dispensements of narcotics. We estimated prevalence odds ratios (PORs) and 95% confidence intervals (CIs), comparing narcotic use on the basis of IBD status and evaluating variables associated with narcotic use by patients with IBD by using conditional and unconditional logistic regression. RESULTS: The prevalence of chronic narcotic use was 5.6% among children with IBD vs 2.3% in the general population (POR, 2.6; 95% CI, 2.2-3.0). Compared with the general population, POR for chronic narcotic use was significantly higher for pediatric IBD patients with psychological impairment (POR, 6.8; 95% CI, 4.3-10.6) than those without (POR, 2.3; 95% CI, 1.9-2.7). Older age, increased healthcare utilization, fracture, and psychological impairment were strongly associated with chronic use of narcotics among children with IBD. CONCLUSIONS: Chronic narcotic use is common in pediatric IBD patients, particularly among those with anxiety and depression. Increased awareness of psychological comorbidity, screening, and treatment may reduce symptoms that lead to narcotic use and its complications.

Perceptions of patients with inflammatory bowel diseases on biobanking.

BACKGROUND: Little is known about beliefs, understanding, and perceptions of biobanking among patients with inflammatory bowel diseases. We aimed to further understand perceptions of biobanking in the inflammatory bowel disease community. METHODS: Subjects were recruited to participate in a 1:1 telephone interview on their perceptions of the risks and benefits of contributing specimens for research. These interviews informed a survey instrument evaluating perceptions of biobanking within Crohn's and Colitis Foundation of America Partners cohort. We used descriptive statistics to summarize participant responses, and bivariate statistics to compare willingness to participate in biobanking by disease and demographic factors. RESULTS: A total of 26 interviews were conducted. Various themes emerged from the interviews and aided in the development of the survey instrument. Concerns focused on storage, loss of confidentiality, outside uses, and life insurance discrimination. A total of 1007 individuals completed the survey. Overall, 397 (39.4%) reported that they would definitely donate samples, 568 (56.4%) would probably donate, 36 (3.6%) probably not, and 6 (0.6%) would definitely not donate. No significant differences in willingness to donate samples were seen for Crohn's disease versus ulcerative colitis (P = 0.25) or for remission versus active disease (P = 0.14). For sample-type preference, 956 (89.6%) would donate blood, 997 (93.5%) saliva, and 822 (77.1%) stool. CONCLUSIONS: Majorities of patients with inflammatory bowel disease demonstrated willingness to donate specimens for biobanking, albeit with concerns. Addressing these concerns will enhance participation and engagement and create greater alignment between the desires of research participants and the governance structure and operating policies of biobanks.

Validation of an internet-based cohort of inflammatory bowel disease (CCFA partners).

BACKGROUND: As traditional methods have become increasingly difficult, the Internet offers a mechanism for conducting survey research quickly and efficiently. However, the validity of this research depends on the ability of respondents to accurately report health status. We used a large Internet-based inflammatory bowel disease (IBD) cohort to validate self-reported IBD against physician reports. METHODS: Between June 22, 2012, and April 01, 2013, all participants of CCFA Partners (n = 6681) were invited to participate, and 450 were selected by random stratified sampling. We sent physicians a survey to confirm IBD diagnosis and characteristics. We used descriptive statistics to compare data. RESULTS: A total of 4423 participants (66%) indicated interest. Of 450 selected, 261 (58%) consented, and physician reports were obtained for 184 (71%). Physicians confirmed IBD status in 178 (97%) and type in 171 (97% of confirmed). The matching between patient and physician reports for Crohn's disease (CD) was 82% for disease location, 89% for the presence of perianal disease, and 46% for disease behavior. For ulcerative colitis (UC), disease location matched 54% of the time. Physician reports confirmed the status of ever having bowel surgery for 97% of CD and 94% for UC and confirmed current pouch or ostomy in 84% of CD and 81% of UC. CONCLUSIONS: Self-reported IBD in CCFA Partners is highly accurate, and participants are willing to release medical records for research. Self-reported phenotypic characteristics were less valid. The validity of IBD diagnoses among the participants of CCFA Partners supports the use of this cohort for patient-centered outcome research.

Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort of commercially insured individuals diagnosed with Crohn's disease in the United States.

BACKGROUND AND AIMS: Thiopurines, including 6-mercaptopurine (6-MP) and azathioprine (AZA), are the mainstay of maintenance therapy for Crohn's disease (CD). However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy. METHODS: Using the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001-2008 (n=3,657). We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan-Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the "noncontinuers," we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation. RESULTS: The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ≤18 years) and individuals with no prior anti-tumor necrosis factor (TNF) use were more likely to continue 6-MP/AZA, while those dispensed more (>4) outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39%) and 105 (4%) individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF. CONCLUSION: Most patients initiating 6-MP/AZA monotherapy did not continue beyond 1 year. In contrast to trial evidence showing 1-year remission rates of 40%-80%, this study observed a lower effectiveness of 6-MP/AZA treatment, possibly due to differences in disease severity, patient demographics, comorbidity, adherence, and health care utilization.