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Smoking during pregnancy is a leading preventable cause of poor pregnancy outcomes. Financial incentives interventions yield quit rates of approximately 30% during pregnancy, versus ~4% in traditional smoking cessation programs. This pilot study assessed the feasibility of translating an efficacious University of Vermont research-based intervention into a rural community setting delivered by the Vermont Department of Health. Pregnant women using tobacco products were recruited from the Women, Infants and Children program and Rutland Women's Healthcare. Women were provided in-person tobacco cessation counseling during regularly scheduled meetings and received gift cards throughout pregnancy and 3 months postpartum contingent upon biochemically verified smoking abstinence. Cessation counseling and abstinence monitoring began with high frequency (three visits per week), tapering through postpartum to biweekly visits. Gift card values began at $15, increasing by $5 for consecutive negative samples, to $40 maximum. Participants completed three surveys (enrollment, 4-6 weeks postpartum, 6-12 months postpartum) assessing smoking habits, and barriers and facilitators of treatment engagement and success. From 2018 to 2020, we enrolled 20 pregnant women, of whom six self-reported quitting tobacco at some point during the intervention. At study completion, three reported sustained abstinence. Results suggest that it is feasible to translate a research-based smoking cessation program into a community setting. This article discusses the challenges faced and the lessons learned when implementing research in a rural community setting, recruiting and retaining participants, and adapting protocols during the Covid-19 pandemic.

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Eliglustat is a first-line oral therapy for adults with Gaucher disease type 1 (GD1) with extensive, intermediate, or poor CYP2D6-metabolizer phenotypes (90% of patients). We report real-world outcomes after 2 years of eliglustat therapy in the International Collaborative Gaucher Group Gaucher Registry (NCT00358943). As of January 2019, baseline and 2-year data (±1 year) were available for 231 eliglustat-treated GD1 patients: 19 treatment-naïve (zero splenectomized) and 212 ERT patients who switched to eliglustat (36 splenectomized). Most patients (89%) were from the United States, where eliglustat was first approved. In treatment-naïve patients, mean hemoglobin increased from 12.4 to 13.4 g/dL (P = .004, n = 18), mean platelet count increased from 113 to 156 × 109 /L (P < .001, n = 17); mean spleen volume decreased from 7.4 to 3.5 multiples of normal (MN) (P = .02, n = 7); mean liver volume remained normal (n = 7), and median spine Z-score was unchanged (-1.3 to -1.2, n = 6). In non-splenectomized switch patients, mean hemoglobin remained stable/non-anemic (n = 167); mean platelet count remained stable/normal (n = 165); mean spleen volume decreased from 3.3 to 2.8 MN (P < .001, n = 64); mean liver volume remained normal (n = 63), and median lumbar spine Z-score improved from -0.7 to -0.4 (P = .014, n = 68). In splenectomized switch patients, mean hemoglobin remained stable/non-anemic (n = 31); mean platelet count increased from 297 to 324 × 109 /L (non-significant, n = 29); mean liver volume remained normal (n = 13); median spine Z-score improved from -0.8 to -0.6 (non-significant, n = 11). Median chitotriosidase decreased in all groups (P < .01 for all). These real-world results are consistent with eliglustat clinical trial results demonstrating long-term benefit in treatment-naïve patients and stability in ERT switch patients.

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BACKGROUND: Eliglustat is a first-line oral treatment for adults with Gaucher disease type 1 who have an extensive, intermediate or poor CYP2D6 metabolizer phenotype (> 90% of patients). Whereas enzyme replacement therapy for Gaucher disease has been widely used for more than two decades, eliglustat has only been in commercial use since 2014. Clinicians and patients want to better understand which adverse events are most commonly associated with eliglustat, as well as their severity, frequency, and duration. METHODS: This pooled analysis of treatment-emergent adverse events combines data from four completed eliglustat clinical trials involving 393 Gaucher disease type 1 patients. It represents 1400 patient-years of eliglustat exposure and a mean treatment duration of 3.6 years (maximum: 9.3 years). RESULTS: Eighty-one percent of patients remained in their respective trial until commercial availability of eliglustat (US patients only) or until trial completion. Nine patients (2.3%) withdrew from their respective trial due to one or more adverse events reported as eliglustat treatment-related; all but one of these events were mild or moderate. Overall, 97% of adverse events were mild or moderate and 86% were reported by the investigator as unrelated to eliglustat treatment. The overall rate of adverse events decreased over time and did not increase with increasing eliglustat dose. We evaluated frequency, duration, and severity of 14 adverse event terms reported at least once as treatment-related in 2% or more of all patients: dyspepsia (5.9%), headache (5.3%), abdominal pain upper (5.1%), dizziness (5.1%), diarrhea (4.6%), nausea (4.6%), arthralgia (3.6%), constipation (3.3%), abdominal pain (2.8%), gastroesophageal reflux disease (2.8%), fatigue (2.8%), palpitations (2.8%), abdominal distension (2.5%), and gastritis (2.3%). For abdominal pain upper, diarrhea, nausea, abdominal pain, and headache events, median duration was less than 14 days. All 14 adverse event terms, except for arthralgia and headache, were reported only once per patient in more than 70% of patients experiencing the event. CONCLUSIONS: This final pooled analysis of treatment-emergent adverse events reinforces the favorable safety profile of eliglustat. The majority of the most frequently reported treatment-related adverse events were mild or moderate, transient, and occurred only once per patient.

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Eliglustat, an oral substrate reduction therapy, is a first-line therapy for adults with Gaucher disease type 1 and a compatible CYP2D6 metabolizer phenotype. Clinicians have requested more information about frequency, timing, and duration of adverse events associated with eliglustat. Adverse event data as of January 31, 2013 for all patients who received at least one dose of eliglustat were pooled from four eliglustat clinical trials (393 patients representing 535 patient-years of exposure). The following 10 adverse events noted in the eliglustat US Prescribing Information (USPI) and EU Summary of Product Characteristics (SmPC) were evaluated with regard to frequency, drug-relatedness, severity, seriousness, duration, and timing of onset: headache, arthralgia, diarrhea, nausea, fatigue, flatulence, abdominal pain, upper abdominal pain, back pain, and extremity pain. Of 393 patients, 334 experienced one or more adverse events. Most patients (92%) continued taking eliglustat; 3% withdrew from a trial due to an adverse event. Among the 10 adverse events evaluated, none was reported as serious and none resulted in discontinuing treatment; most were mild or moderate, reported only once, and not considered eliglustat-related. The majority of adverse events noted in the eliglustat USPI and SmPC were non-serious, occasional, non-severe, and did not lead to drug discontinuation.

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Gaucher disease type 1 is an autosomal recessive disorder caused by deficient activity of the lysosomal enzyme acid ß-glucosidase resulting in accumulation of glucosylceramide and clinical manifestations of anemia, thrombocytopenia, hepatosplenomegaly, and skeletal disease. The historic standard of care is intravenous recombinant enzyme therapy with imiglucerase. Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 who have a compatible CYP2D6-metabolizer phenotype (≈ 95% of patients). The 12-month ENCORE trial (NCT00943111) found eliglustat non-inferior to imiglucerase in maintaining stability in adult Gaucher patients previously stabilized after ≥ 3 years of enzyme therapy (imiglucerase or velaglucerase alfa). This post-hoc analysis examined safety and efficacy in the 30 ENCORE patients who were receiving velaglucerase alfa at study entry and were randomized to eliglustat (n = 22) or imiglucerase (n = 8). Efficacy and safety in velaglucerase alfa-transitioned patients were consistent with the full ENCORE trial population; 90% of patients switched to eliglustat and 88% of patients switched to imiglucerase met the composite endpoint (stable hemoglobin concentration, platelet count, spleen volume, and liver volume). Clinical stability was maintained for 12 months in Gaucher disease type 1 patients in the ENCORE trial who switched from velaglucerase alfa to either eliglustat or imiglucerase.

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Eliglustat is a recently approved oral therapy in the United States and Europe for adults with Gaucher disease type 1 who are CYP2D6 extensive, intermediate, or poor metabolizers (> 90% of patients) that has been shown to decrease spleen and liver volume and increase hemoglobin concentrations and platelet counts in untreated adults with Gaucher disease type 1 and maintain these parameters in patients previously stabilized on enzyme replacement therapy. In a post-hoc analysis, we compared the results of eliglustat treatment in treatment-naïve patients in two clinical studies with the results of imiglucerase treatment among a cohort of treatment-naïve patients with comparable baseline hematologic and visceral parameters in the International Collaborative Gaucher Group Gaucher Registry. Organ volumes and hematologic parameters improved from baseline in both treatment groups, with a time course and degree of improvement in eliglustat-treated patients similar to imiglucerase-treated patients.

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BACKGROUND/PURPOSE: Mucopolysaccharidosis I (MPS I) is a rare lysosomal storage disorder caused by deficiency of α-L-iduronidase, which results in progressive multisystemic disease. Patients with MPS I often require multiple common and uncommon surgeries and are at risk for surgical and anesthetic complications because of respiratory and cardiac disease. Surgery often precedes diagnosis; thus, surgeons and anesthesiologists may be unaware of potential risks. METHODS: We analyzed data from the MPS I Registry, a voluntary observational database, for deaths occurring within 1 month of a surgical procedure among the 932 patients enrolled as of July 2010. RESULTS: Among the 196 deceased patients, 186 reported 1 surgery or more, and 32 had 1 surgery or more within 1 month of death, including 20 who had 1 surgery or more within 10 days of death. Surgeries before death included hernia repair, central line placement, spinal surgery, tracheostomy, and ventriculo-peritoneal shunt. Most patients (28/32) had severe MPS I (Hurler), and 20 of 32 patients (all Hurler) died at 3 years or younger. In 6 of 32 patients, surgery was directly noted in the cause of death, including 4 patients with an attenuated form of MPS I. CONCLUSIONS: Patients with mucopolysaccharidosis have a high postoperative mortality because of underlying respiratory and cardiac diseases.

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UNLABELLED: Our objective was to assess how the diagnosis and treatment of mucopolysaccharidosis I (MPS I) have changed over time. We used data from 891 patients in the MPS I Registry, an international observational database, to analyze ages at symptom onset, diagnosis, treatment initiation, and treatment allocation (hematopoietic stem cell transplantation, enzyme replacement therapy with laronidase, both, or neither) over time for all disease phenotypes (Hurler, Hurler-Scheie, and Scheie syndromes). The interval between diagnosis and treatment has become shorter since laronidase became available in 2003 (gap during 2006-2009: Hurler--0.2 year, Hurler-Scheie--0.5 year, Scheie--1.4 years). However, the age at diagnosis has not decreased for any MPS I phenotype over time, and the interval between symptom onset and treatment initiation remains substantial for both Hurler-Scheie and Scheie patients (gap during 2006-2009, 2.42 and 6.71 years, respectively). Among transplanted patients, an increasing proportion received hematopoietic stem cells from cord blood (34 out of 64 patients by 2009) and was also treated with laronidase (42 out of 45 patients by 2009). CONCLUSIONS: Despite the availability of laronidase since 2003, the diagnosis of MPS I is still substantially delayed for patients with Hurler-Scheie and Scheie phenotypes, which can lead to a sub-optimal treatment outcome. Increased awareness of MPS I signs and symptoms by primary care providers and pediatric subspecialists is crucial to initiate early treatment and to improve the quality of life of MPS I patients.

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The mucopolysaccharidoses (MPSs) often present a diagnostic challenge, particularly for patients who have more slowly progressive disease phenotypes, as early disease manifestations can be subtle or non-specific. However, certain types of bone and joint involvement should always prompt consideration of an MPS diagnosis, such as early joint involvement without classic inflammatory features or erosive bone lesions, claw hand, spinal deformities or dysostosis multiplex. All such patients should be referred to a geneticist or metabolic specialist for diagnostic evaluation. The earlier the diagnosis is made, the better the potential outcome of treatment. Each type of MPS is associated both with deficient activity of a specific lysosomal enzyme that degrades specific glycosaminoglycans (GAGs) and with abnormalities in urinary GAG excretion. MPS patients usually excrete excess GAG in urine and/or have different relative proportions of types of GAG in urine as compared with age-matched normal subjects. Although urinary GAG analyses (both quantitative and qualitative) can suggest the most likely type of MPS, diagnosis must be confirmed by enzyme assay. Multiple assays may be necessary to identify the disease subtype. Correct identification of the MPS type is essential to guide treatment and management decisions.

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OBJECTIVE: To clarify the extent and chronology of surgical burden in relation to symptom onset and diagnosis in patients with mucopolysaccharidosis I (MPS I) as reported in the MPS I Registry, an international observational database. STUDY DESIGN: Analysis of surgical data from 544 patients enrolled in the MPS I Registry. Among all patients with at least 1 reported surgery, the number and frequency of procedures, and age at procedure, diagnosis, and symptom onset were collected overall, by patient, and by reported phenotype (Hurler, Hurler-Scheie, Scheie). RESULTS: Overall and by phenotype, approximately 75% of patients in the MPS I Registry reported at least 1 surgery. The most common were myringotomies and related procedures, hernia repair, adenoidectomy/tonsillectomy, and carpal-tunnel release. Median age at first surgery was <5 years. A median of 3 to 4 surgeries was reported per patient. By age 1.5, 4, and 10 years, respectively, 22%, 44%, and 54% of patients reported > or = 2 surgeries. At least 1 surgery preceded diagnosis in 36%, 46%, and 63% of patients with Hurler, Hurler-Scheie, and Scheie, respectively. CONCLUSIONS: Pediatricians and pediatric surgeons need to be aware of the surgical burden of MPS I and be alert to its presenting signs and symptoms in children scheduled for surgery.

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Given the increasing incidence of chronic diseases across the world, the search for more effective strategies to prevent and manage them is essential. The use of the Chronic Care Model (CCM) has assisted healthcare teams to demonstrate effective, relevant solutions to this growing challenge. However, the current CCM is geared to clinically oriented systems, and is difficult to use for prevention and health promotion practitioners. To better integrate aspects of prevention and health promotion into the CCM, an enhanced version called the Expanded Chronic Care Model is introduced. This new model includes elements of the population health promotion field so that broadly based prevention efforts, recognition of the social determinants of health, and enhanced community participation can also be part of the work of health system teams as they work with chronic disease issues.

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