Abstract Aims To explore epidemiological trends in Type 2 diabetes mellitus (T2D) in the US between 2007 and 2012 using a large US claims database, with a particular focus on demographics, ...prevalence, newly-diagnosed cases, and comorbidities. Methods Truven Health MarketScan® Databases were used to identify patients with claims evidence of T2D in the years 2007 and 2012. Newly-diagnosed T2D was characterized by an absence of any T2D claims or related drug claims for 6 months preceding the index claim. Demographic and comorbidity characteristics of the prevalent and new-onset T2D groups were compared and analyzed descriptively for trends over time. Results The overall prevalence of T2D remained stable from 2007 (1.24 million cases/15.07 million enrolled; 8.2%) to 2012 (2.04 million cases/24.52 million enrolled; 8.3%), while the percentage of newly-diagnosed cases fell dramatically from 2007 (152,252 cases; 1.1%) to 2012 (147,011 cases; 0.65%). The mean age of patients with prevalent T2D was similar in 2007 (60.6 y) and 2012 (60.0 y), while the mean age of newly-diagnosed T2D patients decreased by 3 years from 2007 (57.7 y) to 2012 (54.8 y). Hypertension and hyperlipidemia were the most common comorbidities, evident in 50-75% of T2D patients, and increased markedly from 2007 to 2012 in both prevalent and new-onset T2D populations. Cardiovascular disease decreased slightly in prevalent (-0.9%) and new-onset (-2.8%) cases. Conclusions This large US health claims database analysis suggests stabilization in prevalence and declining incidence of T2D over a recent 5-year period, a downward shift in age at T2D diagnosis, but increases in several comorbidities.
Electrodiagnosis is routinely integrated into clinical neurophysiology practice for peripheral nerve disease diagnoses, such as neuropathy, demyelinating disorders, nerve entrapment/impingement, ...plexopathy, or radiculopathy. Measured with conventional surface electrodes, the propagation of peripheral nerve action potentials along a nerve is the result of ionic current flow which, according to Ampere's Law, generates a small magnetic field that is also detected as an "action current" by magnetometers, such as superconducting quantum interference device (SQUID) Magnetoencephalography (MEG) systems. Optically pumped magnetometers (OPMs) are an emerging class of quantum magnetic sensors with a demonstrated sensitivity at the 1 fT/√Hz level, capable of cortical action current detection. But OPMs were ostensibly constrained to low bandwidth therefore precluding their use in peripheral nerve electrodiagnosis. With careful OPM bandwidth characterization, we hypothesized OPMs may also detect compound action current signatures consistent with both Sensory Nerve Action Potential (SNAP) and the Hoffmann Reflex (H-Reflex). In as much, our work confirms OPMs enabled with expanded bandwidth can detect the magnetic signature of both the SNAP and H-Reflex. Taken together, OPMs now show potential as an emerging electrodiagnostic tool.
The National Aeronautics and Space Administration Soil Moisture Active Passive (SMAP) mission has been validating its soil moisture (SM) products since the start of data production on March 31, 2015. ...Prior to launch, the mission defined a set of criteria for core validation sites (CVS) that enable the testing of the key mission SM accuracy requirement (unbiased root-mean-square error <0.04 m 3 /m 3 ). The validation approach also includes other ("sparse network") in situ SM measurements, satellite SM products, model-based SM products, and field experiments. Over the past six years, the SMAP SM products have been analyzed with respect to these reference data, and the analysis approaches themselves have been scrutinized in an effort to best understand the products' performance. Validation of the most recent SMAP Level 2 and 3 SM retrieval products (R17000) shows that the L -band (1.4 GHz) radiometer-based SM record continues to meet mission requirements. The products are generally consistent with SM retrievals from the European Space Agency Soil Moisture Ocean Salinity mission, although there are differences in some regions. The high-resolution (3-km) SM retrieval product, generated by combining Copernicus Sentinel-1 data with SMAP observations, performs within expectations. Currently, however, there is limited availability of 3-km CVS data to support extensive validation at this spatial scale. The most recent (version 5) SMAP Level 4 SM data assimilation product providing surface and root-zone SM with complete spatio-temporal coverage at 9-km resolution also meets performance requirements. The SMAP SM validation program will continue throughout the mission life; future plans include expanding it to forested and high-latitude regions.
Background
ACU193 is a humanized IgG2 subclass monoclonal antibody targeting soluble amyloid‐beta oligomers (sAβOs). Growing evidence supports the view that sAβOs may be the most toxic and pathogenic ...form of Aβ relative to Aβ monomers and amyloid plaques and are one of the primary drivers of Alzheimer’s disease (AD) neurodegeneration. Thus, blocking the toxicity of sAβOs with ACU193 is a promising approach for treating AD.
Method
INTERCEPT‐AD is a phase 1 randomized, placebo‐controlled, single‐ and multiple‐ ascending dose (SAD/MAD) study of the safety, tolerability, and pharmacokinetics (PK) of intravenous ACU193 in participants with early AD, i.e., mild cognitive impairment or mild dementia due to AD. Key inclusion criteria are 55‐90 years of age, confirmation of amyloid pathology with a PET scan, MMSE score of 18‐30, and CDR‐Global score (CDR‐GS) of 0.5 or 1.0. The MAD portion of the study includes three administrations of ACU193 at doses of 10, 25, or 60 mg/kg. In addition to standard safety measures, MRI is assessed periodically. Cerebrospinal fluid is collected to assess PK and evidence of target engagement. The study also includes exploratory measures such as standard cognitive and functional assessments, a computerized cognitive test battery, measures of cerebral blood flow via arterial spin labeling on MRI, and various plasma biomarkers.
Result
Sixty‐five participants from 17 U.S. study sites were randomized to INTERCEPT‐AD, with 53% female and baseline age of 72.1 ± 7.8 years (mean ± SD). The baseline MMSE was 24.2 ± 3.6, CDR‐GS was 0.64 ± 0.27, and CDR‐Sum of Boxes was 3.5 ± 1.8. In addition to baseline characteristics, the presentation will provide topline safety results, frequency of amyloid‐related imaging abnormalities (ARIA), PK assessments, and evidence of target engagement. Some exploratory measures including cognitive and functional assessments, computerized cognitive testing, and endpoint florbetapir PET results will also be presented.
Conclusion
We will present topline results, along with key baseline demographic, clinical, and cognitive characteristics of participants in the INTERCEPT‐AD trial. The data generated from this trial will guide further development of ACU193 in a subsequent trial to test the novel mechanism of action of ACU193 in the treatment of early AD.
Abstract Purpose Documenting diabetes treatment patterns and associated costs over time is an important step in gauging the medical and economic impact of current treatment guidelines in a real-world ...setting. This study was designed to assess changes in medication treatment patterns, health care costs, and comorbidities over a 6-year period after a new diagnosis of type 2 diabetes mellitus (T2DM). This analysis is the first of its kind to observe, over time, a single US cohort of patients newly diagnosed with T2DM. Methods This study was a longitudinal assessment of changes in medical services and comorbidities for a single cohort (N = 35,017) of adults newly diagnosed with T2DM in 2006 using claims data from Truven Health Analytics MarketScan® databases. Prevalence of diabetes-related comorbidities and utilization/costs of inpatient/outpatient services and medications were analyzed annually for the index (diagnosis) year (Y1) through year 6 (Y6) postindex. Costs were adjusted to 2012 dollars. Findings From Y1 to Y6, increased prevalence was noted for several T2DM-associated comorbidities: cerebrovascular disease (13%–21%), peripheral vascular disease (3%–10%), nephropathy (3%–13%), and retinopathy (4%–14%). All-cause costs of inpatient and outpatient services and medications were analyzed for the index year (Y1) through Y6 postindex (adjusted to 2012 dollars). Total health care utilization costs (services plus drugs) increased by 33.3% from Y1 ($329.8 million) to Y6 ($439.5 million). Inpatient costs across the entire cohort increased 19.3% from Y1 ($49.8 million; $1421/patient) to Y6 ($59.4 million; $1695/patient) but increased 46.6% among utilizers, despite a decline in inpatient utilizers (7.3% to 5.9% of patients). The percentage of outpatient services utilizers remained stable (Y1, 98.2%; Y6, 97.2%), but total visits increased by 9.1%. Costs of outpatient services increased by 32.5%, from $145 million (Y1) to $192 million (Y6). Total drug costs increased from $101.5 million (Y1) to $114.7 million (Y6) but accounted for a smaller percentage of all health care costs in Y6 versus Y1 (26.1% vs 30.7%). Antidiabetes drugs accounted for a small percentage of overall costs in both Y1 (3.6%) and Y6 (5.3%). Implications Overall, we found evidence of increasing comorbidities paralleled by large increases in costs for medical services but less for prescriptions. These findings confirm a need for aggressive diabetes management to slow disease progression and minimize comorbidity and economic burdens of the disease.
Abstract Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central ...nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual’s distinct endophenotype.
We conducted an adaptive design single‐center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra‐short‐term perioperative pangenotypic direct acting ...antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)‐nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R−). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12‐week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype GT1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% 3/10; Group 2A:13% 2/15; Group 2B:4% 1/25). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first‐line DAA therapy; and two after retreatment with second‐line DAA). At a median follow‐up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4‐day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval CI: 1.8%‐20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R − transplants.
This single‐center, open‐label clinical kidney transplant trial provides early evidence that it might be feasible to use ultra‐short direct‐acting antiviral drug preoperative prophylaxis to prevent hepatitis C transmission from infected donors to uninfected recipients, though emergence of resistant viral strains in some patients might pose a problem. Terrault and Sher’s editorial is on page 627.
Variant-containing mRNA vaccines for COVID-19 to broaden protection against SARS-CoV-2 variants are recommended based on findings in adults. We report interim safety and immunogenicity of an omicron ...BA.1 variant-containing (mRNA-1273.214) primary vaccination series and booster dose in paediatric populations.
This open-label, two-part, non-randomised phase 3 trial enrolled participants aged 6 months to 5 years at 24 US study sites. Eligible participants were generally healthy or had stable chronic conditions, without known SARS-CoV-2 infection in the previous 90 days. Individuals who were acutely ill or febrile 1 day before or at the screening visit or those who previously received other COVID-19 vaccines (except mRNA-1273 for part 2) were excluded. In part 1, SARS-CoV-2-vaccine-naive participants received two-dose mRNA-1273.214 (25 μg; omicron BA.1 and ancestral Wuhan-Hu-1 mRNA) primary series. In part 2, participants who previously completed the two-dose mRNA-1273 (25 μg) primary series in KidCOVE (NCT04796896) received a mRNA-1273.214 (10 μg) booster dose. Primary study outcomes were safety and reactogenicity of the mRNA-1273.214 primary series (part 1) or booster dose (part 2) as well as the inferred effectiveness of mRNA-1273.214 based on immune responses against ancestral SARS-CoV-2 (D614G) and omicron BA.1 variant at 28 days post-primary series (part 1) or post-booster dose (part 2). The safety set included participants who received at least one dose of the study vaccine; the immunogenicity set included those who provided immunogenicity samples. Interim safety and immunogenicity are summarised in this analysis as of the data cutoff date (Dec 5, 2022). This trial is registered with ClinicalTrials.gov, NCT05436834.
Between June 21, 2022, and Dec 5, 2022, 179 participants received one or more doses of mRNA-1273.214 primary series (part 1) and 539 received a mRNA-1273.214 booster dose (part 2). The safety profile within 28 days after either dose of the mRNA-1273.214 primary series and the booster dose was consistent with that of the mRNA-1273 primary series in this age group, with no new safety concerns or vaccine-related serious adverse events observed. At 28 days after primary series dose 2 and the booster dose, both mRNA-1273.214 primary series (day 57, including all participants with or without evidence of prior SARS-CoV-2 infection at baseline) and booster (day 29, including participants without evidence of prior SARS-CoV-2 infection at baseline) elicited responses that were superior against omicron-BA.1 (geometric mean ratio part 1: 25·4 95% CI 20·1–32·1 and part 2: 12·5 11·0–14·3) and non-inferior against D614G (part 1: 0·8 0·7–1·0 and part 2: 3·1 2·8–3·5), compared with neutralising antibody responses induced by the mRNA-1273 primary series (in a historical comparator group).
mRNA-1273.214 was immunogenic against BA.1 and D614G in children aged 6 months to 5 years, with a comparable safety profile to mRNA-1273, when given as a two-dose primary series or a booster dose. These results are aligned with the US Centers for Disease Control and Prevention recommendations for the use of variant-containing vaccines for continued protection against the emerging variants of SARS-CoV-2.
Moderna.
ObjectiveThis study evaluated relationships between glycaemic control, body mass index (BMI), comorbidities and pharmacological treatment in patients with type 2 diabetes mellitus (T2D).Research ...design and methodsThis was a retrospective, cross-sectional analysis of Quintiles electronic medical records research data (study period 1 October 2013–30 September 2014). Eligibility included age ≥18 years, T2D diagnosis, and at least one available BMI measurement.ResultsThe study included 626 386 patients (mean age, 63.8 year; 51.3% female; 78.5% white; 62.6%, BMI ≥30 kg/m2). A1c data were available for 414 266 patients. The proportion of patients with good glycaemic control (A1c ≤6.5) decreased as BMI category increased, ranging from 40.1% of patients with BMI <30% to 30.1% of patients with BMI ≥40. The proportions of patients with poor glycaemic control (A1c >8% and A1c ≥9%) increased with increasing BMI category. Oral antidiabetic drugs (OAD) were the most frequently used (54.4% of patients with A1c values). Among patients using insulin-based therapy, 50% had an A1c ≥8% and 29% had an A1c ≥9% regardless of concomitant OAD or glucagon-like peptide 1 receptor agonist use. Among patients using three or more OADs, 34.3% and 16.1% had A1c values ≥8% and ≥9%, respectively. There was no common trend observed for changes in the proportion of patients with T2D-related comorbidities according to BMI category. The most notable trend was a 7.6% net increase in the percentage of patients with hypertension from BMI <30 to BMI ≥40.ConclusionsThis large dataset provides evidence that roughly one out of four patients with T2D is not well controlled, and the prevalence of poor glycaemic control increases as BMI increases.
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