Purpose We sought to evaluate the association between childhood socioeconomic status (SES) at two time points and age at menarche in a multiracial sample of U.S. girls. Methods Our study population ...consisted of a cohort of female participants enrolled at birth at the New York site of the Collaborative Perinatal Project, who were born during the period 1959–1963 (n = 262). SES at birth, at age 7, and change between birth and age 7 were measured prospectively through an index score of family income, paternal occupation, and education. Data on age at menarche were collected retrospectively through adult self-report. We used multivariable linear regression to examine the association between SES and age at menarche after adjusting for childhood body mass index (BMI) and other covariates associated with age at menarche. Results After adjustment, SES at age 7 was positively associated with age at menarche (beta: 0.015, 95% confidence interval CI: 0.003–0.024 per unit of SES index). Change in SES was significantly associated with age at menarche; a 20-unit decrease in SES was associated with a 4-month decrease in age at menarche. Conclusions Our results suggest that lower SES at 7 years and reductions in SES in early childhood are both associated with an earlier age at menarche.
Introduction
The public–private ADVANCE collaboration developed and tested a system to generate evidence on vaccine benefits and risks using European electronic healthcare databases. In the safety of ...vaccines, background incidence rates are key to allow proper monitoring and assessment. The goals of this study were to compute age-, sex-, and calendar-year stratified incidence rates of nine autoimmune diseases in seven European healthcare databases from four countries and to assess validity by comparing with published data.
Methods
Event rates were calculated for the following outcomes: acute disseminated encephalomyelitis, Bell’s palsy, Guillain–Barré syndrome, immune thrombocytopenia purpura, Kawasaki disease, optic neuritis, narcolepsy, systemic lupus erythematosus, and transverse myelitis. Cases were identified by diagnosis codes. Participating organizations/databases originated from Denmark, Italy, Spain, and the UK. The source population comprised all persons registered, with at least 1 year of data prior to the study start, or follow-up from birth. Stratified incidence rates were computed per database over the period 2003 to 2014.
Results
Between 2003 and 2014, 148,947 incident cases of nine autoimmune diseases were identified. Crude incidence rates were highest for Bell’s palsy 23.8/100,000 person-years (PYs), 95% confidence interval (CI) 23.6–24.1 and lowest for Kawasaki disease (0.7/100,000 PYs, 95% CI 0.6–0.7). Specific patterns were observed by sex, age, calendar time, and data sources. Rates were comparable with published estimates.
Conclusion
A range of autoimmune events could be identified in the ADVANCE system. Estimation of rates indicated consistency across selected European healthcare databases, as well as consistency with US published data.
Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD).
Taliglucerase Alfa ...Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019.
A total of 106 patients with GD (15.1% children aged < 18 years; 53.8% females) treated with taliglucerase alfa have been enrolled in the Drug Registry, as of January 7, 2019. The median duration of follow-up was 795 days with quartiles (Q1, Q3) of 567 and 994 days. Fifty-three patients (50.0%) were from Israel, 28 (26.4%) were from the United States, and 25 (23.6%) were from Albania. At the time of enrollment, most patients (87.7%) had received prior enzyme replacement therapy (ERT). Thirty-nine of the 106 patients had treatment-emergent adverse events (AEs). Twelve of the 106 patients experienced serious AEs; two patients experienced four treatment-related serious AEs. Four patients died, although none of the deaths was considered to be related to taliglucerase alfa treatment by the treating physicians. Nine patients discontinued from the study, including the four who died. At baseline, patients with prior ERT had a higher mean hemoglobin concentration and platelet counts than treatment-naïve patients, likely reflecting the therapeutic effects of prior treatments. During follow-up, the hemoglobin concentration and platelet counts increased in the treatment-naïve patients and remained relatively constant or increased slightly in patients with prior ERT. Spleen and liver volumes decreased in treatment-naïve patients.
The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa.
Background
There are limited data on the incidence of cardiovascular disease among cancer patients in the pre‐tyrosine kinase inhibitor (TKI) era. Such data are important in order to contextualize ...the incidence of various cardiovascular outcomes among cancer patients enrolled in clinical trials of new agents and for postmarketing surveillance.
Methods
A retrospective cohort study was conducted using data from the Kaiser Permanente Northern California (KPNC) population of cancer patients. The inclusion criterion was a KPNC Cancer Registry diagnosis of any of several selected solid and hematologic tumors between 1997 and 2009 not treated with a TKI. Endpoints were identified using ICD‐9 codes and included acute coronary syndrome, heart failure, stroke, cardiac arrest, hypertension, venous thromboembolism, all‐cause mortality, and cardiovascular mortality. Event rates were calculated according to type of cancer and number of cardiovascular risk factors.
Results
The study included almost 165 000 individuals with a broad variety of tumor types. The parent cohort was 54% female and 35% were ≥70 years old. Cardiovascular risk factors such as diabetes mellitus (14% of patients with solid tumors, 15% of patients with liquid tumors), dyslipidemia (33%, 31%), hypertension (50%, 49%), and smoking (35%, 32%) were common. The most frequent adverse outcomes were incident hypertension (26.8‐61.0 cases per 1000 person‐years, depending on the type of cancer), heart failure (9.4‐78.7), and acute coronary syndrome (2.6‐48.1). These event rates are high compared to what has been reported in prior KPNC cohort studies of patients without cancer. The rates of acute coronary syndrome, heart failure, and ischemic stroke increased with increasing numbers of cardiovascular risk factors.
Conclusions
In a population of patients with cancer not exposed to TKIs, cardiovascular risk factors and outcomes are very common, regardless of cancer type. These data can inform the evaluation of potential excess cardiovascular risks from new interventions.
In a cancer population not exposed to tyrosine kinase inhibitors or bevacizumab, cardiovascular outcomes are common, regardless of cancer type. Cardiovascular events occur more frequently in cancer patients with increasing numbers of cardiovascular risk factors.
Objective: Little is known about the causes of sporadic (noninherited) retinoblastoma. Rates seem to be somewhat higher among
poorer populations in Mexico. Fruits and vegetables are important sources ...of carotenoids and folate. We examined whether decreased
gestational maternal intake of fruits and vegetables may contribute to development of sporadic retinoblastoma.
Methods: At the Instituto Nacional de Pediatria in Mexico City, we conducted a hospital-based case-control study to evaluate
prenatal maternal diet. We examined dietary intake of fruits and vegetables of mothers of 101 children with retinoblastoma
and 172 control children using a dietary recall questionnaire and published food nutrient content tables.
Results: The reported number of mean daily servings of fruits and vegetables was lower among case mothers when compared with
control mothers vegetables: 2.28 in controls, 1.75 in cases ( P < 0.01); fruits: 2.13 in controls, 1.59 in cases ( P = 0.07). Mean daily maternal folate intake from both vegetables and fruits was higher in controls (103 μg) than in cases
(48 μg; P < 0.05). Risk for having a child with retinoblastoma was increased for mothers consuming fewer than 2 daily servings of vegetables
odds ratios (OR), 3.4; 95% confidence interval (95% CI), 2.0-6.0 or with a low intake of folate (OR, 3.9; 95% CI, 2.1, 7.3),
or lutein/zeaxanthin (OR, 2.6; 95% CI, 1.5-4.6) derived from fruits and vegetables.
Conclusions: Decreased intake of vegetables and fruits during pregnancy and the consequent decreased intake of nutrients such
as folate and lutein/zeaxanthin, necessary for DNA methylation, synthesis, and retinal function, may increase risk for having
a child with sporadic retinoblastoma.
Background: Sickle cell disease (SCD) is characterized by recurrent acute vaso-occlusive crises (VOCs), which diminish patient quality-of-life, contribute to end-organ damage and failure, and ...increase mortality. Currently, approved therapies for SCD are only partially effective and do not fully eliminate VOCs. Allogeneic hematopoietic stem cell transplant (HSCT) is the only known curative option for patients with SCD, however, HSCT is available to <20% of patients who have a matched sibling donor and is associated with significant risks, such as graft-versus-host disease. Autologous gene therapies that have the potential to provide a one-time functional cure to patients with SCD are currently in pivotal trials. The primary endpoint for these pivotal studies is the proportion of patients who become VOC-free for ≥12 months after treatment. Absence of VOCs for ≥12 months is expected to predict long-term efficacy. Given this, we evaluated patients with SCD in the national US Medicaid database who underwent allogeneic-HSCT to determine whether VOC-free status at 12 months was predictive of VOC-free status at 18 and 24 months after HSCT. Methods: A cohort of patients with SCD who had a record of allogeneic HSCT with at least 12 months of continuous Medicaid enrollment during 2000-2014 was identified. The date of HSCT was defined as the cohort entry date and the covariate assessment window was the 12 months continuous enrollment period preceding the cohort entry date. A VOC event was identified using ICD-9 diagnosis codes in hospitalization and ER visit claims for Hb-SS disease with crisis, other acute pain crisis, acute chest syndrome, priapism, and splenic sequestration. The cohort was further restricted to patients who had ≥24 months of follow-up after cohort entry to accurately assess VOC outcomes. Diagnosis codes associated with the delivery of healthcare and pharmacy claims were used to identify patient characteristics and outcomes of interest. Primary study outcome was the proportion of patients with no VOCs at 6 months, 12 months, 18 months, and 24 months after allogeneic HSCT. Results: During the study period, 44,685 patients with SCD were identified, out of whom 103 patients had undergone allogeneic HSCT, were enrolled for ≥12 months in the Medicaid program and had ≥24 months of follow-up after HSCT. Mean (SD) age was 10.3 (7.2) years, with 55.3% being male and majority (67%) Black. Patients had an average of 2.7 (SD, 7.9) VOC events during the 12-month period prior to HSCT. The most common (>10%) baseline comorbidities were chronic cardiac disease (42.7%), infections (36.9%), chronic pulmonary disease (31.1%), and acute chest syndrome (12.6%). Among the cohort of 103 patients who had undergone HSCT, 79% (n=81) were VOC-free by 12 months. Furthermore, among patients who were VOC-free at 12 months, 91% (n=74) were VOC-free at 18 months and 90% (n=73) were VOC-free at 24 months. Conclusions: This population-based study provides valuable information regarding long-term VOC-free status among patients with SCD who have undergone allogeneic HSCT in routine clinical care. Our findings suggest that patients with SCD who are VOC-free by 12 months post-HSCT are highly likely to stay VOC-free for longer durations (i.e. 18 and 24 months) after HSCT.
To determine how diabetes technologies, including continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems, impact glycemic metrics, prevalence of severe hypoglycemic events ...(SHEs), and impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes in a real-world setting within the U.S.
In this retrospective, observational study with cross-sectional elements, participants aged ≥18 years were enrolled from the T1D Exchange Registry/online community. Participants completed a one-time online survey describing glycemic metrics, SHEs, and IAH. The primary objective was to determine the proportions of participants who reported achieving glycemic targets (assessed according to self-reported hemoglobin A1c) and had SHEs and/or IAH. We performed additional subgroup analyses focusing on the impact of CGM and insulin delivery modality.
A total of 2,074 individuals with type 1 diabetes were enrolled (mean ± SD age 43.0 ± 15.6 years and duration of type 1 diabetes 26.3 ± 15.3 years). The majority of participants (91.7%) were using CGM, with one-half (50.8%) incorporating AID. Despite high use of diabetes technologies, only 57.7% reported achieving glycemic targets (hemoglobin A1c <7%). SHEs and IAH still occurred, with ∼20% of respondents experiencing at least one SHE within the prior 12 months and 30.7% (95% CI 28.7, 32.7) reporting IAH, regardless of CGM or AID use.
Despite use of advanced diabetes technologies, a high proportion of people with type 1 diabetes do not achieve glycemic targets and continue to experience SHEs and IAH, suggesting an ongoing need for improved treatment strategies.
Introduction
New vaccines are launched based on their benefit–risk (B/R) profile anticipated from clinical development. Proactive post-marketing surveillance is necessary to assess whether the ...vaccination uptake and the B/R profile are as expected and, ultimately, whether further public health or regulatory actions are needed. There are several, typically not integrated, facets of post-marketing vaccine surveillance: the surveillance of vaccination coverage, vaccine safety, effectiveness and impact.
Objective
With this work, we aim to assess the feasibility and added value of using an interactive dashboard as a potential methodology for near real-time monitoring of vaccine coverage and pre-specified health benefits and risks of vaccines.
Methods
We developed a web application with an interactive dashboard for B/R monitoring. The dashboard is demonstrated using simulated electronic healthcare record data mimicking the introduction of rotavirus vaccination in the UK. The interactive dashboard allows end users to select certain parameters, including expected vaccine effectiveness, age groups, and time periods and allows calculation of the incremental net health benefit (INHB) as well as the incremental benefit–risk ratio (IBRR) for different sets of preference weights. We assessed the potential added value of the dashboard by user testing amongst a range of stakeholders experienced in the post-marketing monitoring of vaccines.
Results
The dashboard was successfully implemented and demonstrated. The feedback from the potential end users was generally positive, although reluctance to using composite B/R measures was expressed.
Conclusion
The use of interactive dashboards for B/R monitoring is promising and received support from various stakeholders. In future research, the use of such an interactive dashboard will be further tested with real-life data as opposed to simulated data.
Continuous glucose monitoring (CGM) metrics and self-reported disease characteristics (severe hypoglycemic events SHEs, HbA1c) warrant further description in people with T1D using CGM and pumps, ...including hybrid closed-loop systems (HCLS) . We conducted a one-time online survey of adults with T1D in the T1D Exchange Registry or online communities, where ∼50% of participants contributed up to 1 year of CGM data. Patients were asked about their medical history (SHEs, HbA1c) , while glucose management indicator (GMI) , prolonged hypoglycemic events (<54 mg/dL) , time in and below range (TIR/TBR) , and coefficient of variation (CV) were derived from CGM data. Patients who completed the survey and contributed CGM data (N=926) had a mean age of 42 y and T1D duration of 25 y; 73% were female; 96% were white; 94% had ≥1 year of CGM use. Mean HbA1c was 6.6% (69.0% had HbA1c <7%) . While most patients met consensus glycemic targets (HbA1c, GMI, TIR, TBR, and CV) , with higher proportions observed in those using HCLS pumps than in those using pump + CGM (not HCLS) and MDI + CGM (Table) , patients continued to have significant hypoglycemia based on CGM data and an average of 1.1 SHEs in the prior year. Despite improvements in glycemic control (TIR, TBR, and self-reported HbA1c) with advanced technologies, many patients still cannot achieve clinical targets and experience significant hypoglycemia, highlighting the unmet need for novel T1D treatments.
Disclosure
L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. K.S.M.Chapman: None. D.Finan: None. R.M.Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. J.Liu: None. L.Titievsky: Employee; Intercept Pharmaceuticals, Inc., Pfizer Inc., Vertex Pharmaceuticals Incorporated, Stock/Shareholder; Intercept Pharmaceuticals, Inc., Pfizer Inc., Vertex Pharmaceuticals Incorporated. K.Hagan: Employee; Vertex Pharmaceuticals Incorporated. T.Liu: Employee; Takeda Pharmaceutical Company Limited, Vertex Pharmaceuticals Incorporated, Stock/Shareholder; Seattle Genetics, Inc. K.Chandarana: Employee; Vertex Pharmaceuticals Incorporated. J.L.Gaglia: Advisory Panel; Dompé, Regeneron Pharmaceuticals Inc., Consultant; Vertex Pharmaceuticals Incorporated, Research Support; Avotres Inc., Dompé, Janssen Research & Development, LLC, Provention Bio, Inc., Stock/Shareholder; Vertex Pharmaceuticals Incorporated. W.Wolf: None. J.Bispham: Employee; PPD Inc., T1D Exchange.
Trials of continuous glucose monitors (CGMs) and hybrid closed-loop systems (HCLS) demonstrate improvements in glycemia with reductions in hypoglycemia in T1D, but there is limited real-world data on ...how these technologies impact the prevalence of impaired awareness of hypoglycemia (IAH) , severe hypoglycemic events (SHEs) , and glycemic control. We conducted a one-time online survey of adults with T1D in the T1D Exchange Registry and online communities. Self-reported medical histories (insulin delivery method, HbA1c, IAH, SHEs) and CGM data were collected. 2044 patients (mean age 43 y, mean T1D duration 26 y, 72% female, 95% White) completed the survey. Most reported using CGMs (92%) ; 953 also used HCLS. Mean HbA1c was 6.89%; 41.5% had an HbA1C of ≥7%; 30.7% reported IAH; 19.8% had ≥1 SHE in the prior year; 12.0% had ≥2 SHEs in the prior year; 9.6% had IAH + ≥1 SHE; and 6.6% had IAH + ≥2 SHEs (Table) . Rates of SHEs and IAH + SHEs were lower in CGM users and CGM + HCLS users than in non-CGM users; however, among CGM + HCLS users, 16.6% reported ≥1 SHE, 8.7% ≥2 SHEs, 7.8% IAH + ≥1 SHE, and 4.7% IAH + ≥2 SHEs. Also, 35.6% of CGM + HCLS users had an HbA1C of ≥7%. In a patient cohort with high rates of technology adoption, rates of SHEs and IAH remained high, with a significant proportion of patients not achieving targeted glycemic control, indicating the need for novel T1D treatments.
Disclosure
J. Pettus: Advisory Panel; Lilly, MannKind Corporation, Novo Nordisk, Sanofi. Consultant; Carmot Therapeutics, Inc., Diasome. L. Titievsky: Employee; Intercept Pharmaceuticals, Inc., Pfizer Inc., Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Intercept Pharmaceuticals, Inc., Pfizer Inc., Vertex Pharmaceuticals Incorporated. K. Hagan: Employee; Vertex Pharmaceuticals Incorporated. T. Liu: Employee; Takeda Pharmaceutical Company Limited, Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Seattle Genetics, Inc. K. Chandarana: Employee; Vertex Pharmaceuticals Incorporated. J.L. Gaglia: Advisory Panel; Dompé, Regeneron Pharmaceuticals Inc. Consultant; Vertex Pharmaceuticals Incorporated. Research Support; Avotres Inc., Dompé, Janssen Research & Development, LLC, Provention Bio, Inc. Stock/Shareholder; Vertex Pharmaceuticals Incorporated. W. Wolf: None. J. Bispham: Employee; PPD Inc., T1D Exchange. K.S.M. Chapman: None. D. Finan: None. J. Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated. Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc. Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Lilly Diabetes.
PDF
