Patrick Liu

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73u2009119 (95% uncertainty interval [UI], 67u2009949-78u2009241) to 81u2009373 (95% UI, 76u2009814-85u2009770) per 100u2009000, and SBP of 140 mm Hg or higher increased from 17u2009307 (95% UI, 17u2009117-17u2009492) to 20u2009526 (95% UI, 20u2009283-20u2009746) per 100u2009000. The estimated annual death rate per 100u2009000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Comparative immunogenicity assessment: a critical consideration for biosimilar development

An appropriate assessment strategy with validated anti-drug antibody (ADA) assays is critical for comparative evaluation of immunogenicity between a proposed biosimilar and its reference product. The strategy should aim to identify potential differences in immune responses between these products. While an ADA assay employing the proposed biosimilar product as the detecting reagent has been generally recommended for such evaluation, a product-specific assay using the product of interest may be of use as it offers a capability of detecting antibodies against specific epitopes from the respective product. Regardless of assay strategy, the performance of the assay must be fully assessed and method needs to be validated to meet the comparative purpose of immunogenicity assessment.

Vaccine Assistance To Low- And Middle-Income Countries Increased To

In the 2012 Global Vaccine Action Plan, development assistance partners committed to providing sustainable financing for vaccines and expanding vaccination coverage to all children in low- and middle-income countries by 2020. To assess progress toward these goals, the Institute for Health Metrics and Evaluation produced estimates of development assistance for vaccinations. These estimates reveal major increases in the assistance provided since 2000. In 2014,

3.6 Billion In 2014

3.6 billion in development assistance for vaccinations was provided for low- and middle-income countries, up from

A novel method for estimating distributions of body mass index

822 million in 2000. The funding increase was driven predominantly by the establishment of Gavi, the Vaccine Alliance, supported by the Bill & Melinda Gates Foundation and the governments of the United States and United Kingdom. Despite stagnation in total development assistance for health from donors from 2010 onward, development assistance for vaccination has continued to grow.

Differential sensitivity of lipegfilgrastim and pegfilgrastim to neutrophil elastase correlates with differences in clinical pharmacokinetic profile

BackgroundUnderstanding trends in the distribution of body mass index (BMI) is a critical aspect of monitoring the global overweight and obesity epidemic. Conventional population health metrics often only focus on estimating and reporting the mean BMI and the prevalence of overweight and obesity, which do not fully characterize the distribution of BMI. In this study, we propose a novel method which allows for the estimation of the entire distribution.MethodsThe proposed method utilizes the optimization algorithm, L-BFGS-B, to derive the distribution of BMI from three commonly available population health statistics: mean BMI, prevalence of overweight, and prevalence of obesity. We conducted a series of simulations to examine the properties, accuracy, and robustness of the method. We then illustrated the practical application of the method by applying it to the 2011–2012 US National Health and Nutrition Examination Survey (NHANES).ResultsOur method performed satisfactorily across various simulation scenarios yielding empirical (estimated) distributions which aligned closely with the true distributions. Application of the method to the NHANES data also showed a high level of consistency between the empirical and true distributions. In situations where there were considerable outliers, the method was less satisfactory at capturing the extreme values. Nevertheless, it remained accurate at estimating the central tendency and quintiles.ConclusionThe proposed method offers a tool that can efficiently estimate the entire distribution of BMI. The ability to track the distributions of BMI will improve our capacity to capture changes in the severity of overweight and obesity and enable us to better monitor the epidemic.

On the Relative Role of Different Age Groups during Epidemics Associated with Respiratory Syncytial Virus

To assess the basis of the different half‐lives of long‐acting human granulocyte colony‐stimulating factor (G‐CSF) drugs, the effect of neutrophil elastase on lipegfilgrastim and pegfilgrastim was investigated. Sensitivity to human neutrophil elastase (HNE) was evaluated by incubating the drugs with HNE followed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE). Drugs were also incubated with isolated human neutrophils followed by Western blot analysis. Lipegfilgrastim was more resistant to degradation with HNE or neutrophils than pegfilgrastim and appeared more intact on SDS‐PAGE gels and Western blots. Lipegfilgrastim retained more functional activity than pegfilgrastim after incubation with HNE (67% vs ∼9%, respectively) or neutrophils (80% vs ∼4%, respectively) as assessed in an NFS‐60 cell–based [3H]‐thymidine incorporation assay. The binding and affinity of untreated lipegfilgrastim and pegfilgrastim for G‐CSF receptors were evaluated using an NFS‐60 competitive G‐CSF receptor‐binding assay and surface plasmon resonance. Untreated drugs were also evaluated in the functional NFS‐60 thymidine incorporation assay. G‐CSF receptor binding, receptor affinity, and functional activity were comparable between untreated drugs. The results showed a greater resistance to neutrophil elastase degradation and concomitant retention of functional activity of lipegfilgrastim compared with pegfilgrastim, which potentially explains the clinical observations of a longer half‐life of lipegfilgrastim versus pegfilgrastim.

Method establishment for discerned immunogenicity assessment of a recombinant glycoprotein containing nonhuman sialic acid Neu5Gc residues

BackgroundnWhile circulation of respiratory syncytial virus (RSV) results in high rates of hospitalization, particularly among young children and elderly individuals, little is known about the role of different age groups in propagating annual RSV epidemics.nnnMethodsnWe evaluate the roles played by individuals in different age groups during RSV epidemics in the United States between 2001 and 2012, using the previously defined relative risk (RR) statistic estimated from the hospitalization data from the Healthcare Cost and Utilization Project. Transmission modeling was used to examine the robustness of our inference method.nnnResultsnChildren aged 3-4 years and 5-6 years each had the highest RR estimate for 5 of 11 seasons included in this study, with RSV hospitalization rates in infants being generally higher during seasons when children aged 5-6 years had the highest RR estimate. Children aged 2 years had the highest RR estimate during one season. RR estimates in infants and individuals aged ≥11 years were mostly lower than in children aged 1-10 years. Highest RR values aligned with groups for which vaccination had the largest impact on epidemic dynamics in most model simulations.nnnConclusionsnOur estimates suggest the prominent relative roles of children aged ≤10 years (particularly among those aged 3-6 years) in propagating RSV epidemics. These results, combined with further modeling work, should help inform RSV vaccination policies.

Immunogenicity assessment of tbo-filgrastim in cancer patients receiving chemotherapy

AIMnRecombinant glycoprotein produced in nonhuman mammalian cell lines can be modified with the immunogenic nonhuman sialic N-glycolylneuraminic acid (Neu5Gc). We describe here a validated method for detection of antidrug antibodies against both protein and Neu5Gc-containing glycan epitopes.nnnRESULTSnAn electrochemiluminescent method was established with drug conjugates as capture and detection reagents. Rabbit antidrug polyclonal antibodies were used as the positive control for protein moiety-specific antibodies, while chicken anti-Neu5Gc polyclonal antibodies were used as the positive control for antibodies against Neu5Gc glycan epitope. Specificity to Neu5Gc was verified by signal inhibition with bovine γ-globulin that contains Neu5Gc.nnnCONCLUSIONnThe assay illustrated here discerns the immunogenicity of the protein backbone and the sialic acid Neu5Gc glycan moiety of a recombinant protein containing Neu5Gc.

Immunogenicity Assessment of Lipegfilgrastim in Patients with Breast Cancer Receiving Chemotherapy

AIMnThis integrated analysis examined the immunogenicity of tbo-filgrastim and its potential clinical impact in three Phase III randomized studies in patients with breast cancer, lung cancer and non-Hodgkin lymphoma receiving chemotherapy.nnnRESULTSnTreatment-emergent antidrug antibodies (ADA) occurred in 3/213 (1.4%) breast cancer patients, 2/160 (1.3%) lung cancer patients and 1/63 (1.6%) patients with non-Hodgkin lymphoma. None of the treatment-emergent ADA showed cross-reactivity toward native granulocyte-colony stimulating factors or exhibited neutralizing activity against tbo-filgrastim. Among patients with treatment-emergent ADA, there was no treatment-related hypersensitivity or anaphylaxis and no evidence of loss of clinical efficacy.nnnCONCLUSIONnTbo-filgrastim has demonstrated low immunogenicity in cancer patients receiving chemotherapy and ADA response does not impact safety and efficacy in the patients.