Clinical and economic outcomes in an observational study of COPD maintenance therapies: multivariable regression versus propensity score matching

Melissa H Roberts1, Anand A Dalal21Lovelace Clinic Foundation, (Lovelace Respiratory Research Institute at the time of the study), Albuquerque, NM, 2US Health Outcomes, GlaxoSmithKline, Durham, NC, USAPurpose: To investigate equivalency of results from multivariable regression (MR) and propensity score matching (PSM) models, observational research methods used to mitigate bias stemming from non-randomization (and consequently unbalanced groups at baseline), using, as an example, a large study of chronic obstructive pulmonary disease (COPD) initial maintenance therapy.Methods: Patients were 32,338 health plan members, age ≥40 years, with COPD initially treated with fluticasone propionate/salmeterol combination (FSC), tiotropium (TIO), or ipratropium (IPR) alone or in combination with albuterol. Using MR and PSM methods, the proportion of patients with COPD-related health care utilization, mean costs, odds ratios (ORs), and incidence rate ratios (IRRs) for utilization events were calculated for the 12 months following therapy initiation.Results: Of 12,595 FSC, 9126 TIO, and 10,617 IPR patients meeting MR inclusion criteria, 89.1% (8135) of TIO and 80.2% (8514) of IPR patients were matched to FSC patients for the PSM analysis. Methods produced substantially similar findings for mean cost comparisons, ORs, and IRRs for most utilization events. In contrast to MR, for TIO compared to FSC, PSM did not produce statistically significant ORs for hospitalization or outpatient visit with antibiotic or significant IRRs for hospitalization or outpatient visit with oral corticosteroid. As in the MR analysis, compared to FSC, ORs and IRRs for all other utilization events, as well as mean costs, were less favorable for IPR and TIO.Conclusion: In this example of an observational study of maintenance therapy for COPD, more than 80% of the original treatment groups used in the MR analysis were matched to comparison treatment groups for the PSM analysis. While some sample size was lost in the PSM analysis, results from both methods were similar in direction and statistical significance, suggesting that MR and PSM were equivalent methods for mitigating bias.Keywords: multivariate analysis, outcomes research, propensity score, pulmonary disease, chronic obstructive, statistical bias, statistical model

Testing single aliquot regenerative dose (SAR) protocols for violet stimulated luminescence

Basic assumptions of the single aliquot regenerative dose (SAR) protocol are tested using the violet stimulated luminescence (VSL) signal from quartz. The VSL signal is shown to be reduced to a sufficiently low background level between SAR steps, and the SAR protocol appears to adequately correct for sensitivity changes during measurement. The VSL SAR protocol can recover a large (405 Gy) laboratory beta dose within uncertainties, however the mean value for the dose recovery ratio is commonly 0.8 or less. This poor behaviour is echoed in the measurements of equivalent dose (De) for a sample with an expected De of ∼354 Gy, which underestimates De by 50–70%. Further investigations are required to understand the mechanisms underlying these underestimations in VSL SAR De values

Economic burden of chronic bronchitis in the United States: a retrospective case-control study

Christopher M Blanchette1, Melissa H Roberts1, Hans Petersen1, Anand A Dalal2, Douglas W Mapel31Division of Clinical and Outcomes Research, Lovelace Respiratory Research Institute, Kannapolis, NC, USA; 2US Health Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 3Lovelace Clinic Foundation, Albuquerque, NM, USABackground: Chronic bronchitis (CB) is often misdiagnosed or diagnosed at a later stage of chronic obstructive pulmonary disease (COPD). We examined how this later diagnosis may impact health care costs and utilization during the 12 months prior to and 24 months post initial CB diagnosis.Methods: This retrospective case-control analysis used claims data from a large US database from July 1, 2003 through June 30, 2007. Patients with CB aged 40 years and older were propensity matched (N = 11,674) to patients without evidence of COPD or asthma by demographics, CB diagnosis quarter/year, and comorbidities. Group differences were assessed using Student's t-test and Pearson chi-square test statistics.Results: Six months prediagnosis, CB patients had higher frequencies of any hospitalization (9.6%, 6.7%; P < 0.05), emergency department/urgent care visits (13.3%, 6.7%; P < 0.05), and prescriptions (97.3%, 94.1%; P < 0.05). Six months postdiagnosis, CB patients had 5.6 times more hospitalizations (P < 0.05) and 3.1 times more emergency department/urgent care visits (P < 0.05) compared with controls. Mean total costs (US) for CB patients 12 months prediagnosis were significantly higher than controls (months 12–7: 4212, 3826; P < 0.05; months 6–1: 5289, 4285; P < 0.05). CB patients had higher mean total costs (8919; P < 0.05) 6 months postdiagnosis. Costs remained $2429 higher for CB patients 19–24 months postdiagnosis (P < 0.05).Conclusion: Health care costs and utilization among CB patients are increased both prior to diagnosis and during the 2 years postdiagnosis. This study suggests that not accurately diagnosing CB early has a substantial impact on health care costs, and that the economic burden for CB patients remains elevated even after adjustment for comorbidities associated with COPD.Keywords: chronic bronchitis, burden, economic, chronic obstructive pulmonary diseas

Nitrogen Heterocycles Form Peptide Nucleic Acid Precursors in Complex Prebiotic Mixtures

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth

Geographic Variation in Influenza Vaccination Disparities Between Hispanic and Non-Hispanic White US Nursing Home Residents

BACKGROUND: Disparities in influenza vaccination exist between Hispanic and non-Hispanic White US nursing home (NH) residents, but the geographic areas with the largest disparities remain unknown. We examined how these racial/ethnic disparities differ across states and hospital referral regions (HRRs). METHODS: This retrospective cohort study included >14 million short-stay and long-stay US NH resident-seasons over 7 influenza seasons from October 1, 2011, to March 31, 2018, where residents could contribute to 1 or more seasons. Residents were aged ≥65 years and enrolled in Medicare fee-for-service. We used the Medicare Beneficiary Summary File to ascertain race/ethnicity and Minimum Data Set assessments for influenza vaccination. We calculated age- and sex-standardized percentage point (pp) differences in the proportions vaccinated between non-Hispanic White and Hispanic (any race) resident-seasons. Positive pp differences were considered disparities, where the proportion of non-Hispanic White residents vaccinated was greater than the proportion of Hispanic residents vaccinated. States and HRRs with ≥100 resident-seasons per age–sex stratum per racial/ethnic group were included in analyses. RESULTS: Among 7 442 241 short-stay resident-seasons (94.1% non-Hispanic White, 5.9% Hispanic), the median standardized disparities in influenza vaccination were 4.3 pp (minimum, maximum: 0.3, 19.2; n = 22 states) and 2.8 pp (minimum, maximum: −3.6, 10.3; n = 49 HRRs). Among 6 758 616 long-stay resident-seasons (93.7% non-Hispanic White, 6.5% Hispanic), the median standardized differences were −0.1 pp (minimum, maximum: −4.1, 11.4; n = 18 states) and −1.8 pp (minimum, maximum: −6.5, 7.6; n = 34 HRRs). CONCLUSIONS: Wide geographic variation in influenza vaccination disparities existed across US states and HRRs. Localized interventions targeted toward areas with high disparities may be a more effective strategy to promote health equity than one-size-fits-all national interventions

ICDP workshop on the Deep Drilling in the Turkana Basin Project:Exploring the link between environmental factors and hominin evolution over the past 4 Myr

Scientific drill cores provide unique windows into the processes of the past and present. In the dynamic tectonic, environmental, climatic, and ecological setting that is eastern Africa, records recovered through scientific drilling enable us to look at change through time in unprecedented ways. Cores from the East African Rift System can provide valuable information about the context in which hominins evolved in one of the key regions of hominin evolution over the past 4 Myr. The Deep Drilling in the Turkana Basin (DDTB) project seeks to explore the impact of several types of evolution (tectonic, climatic, biological) on ecosystems and environments. This includes addressing questions regarding the region’s complex and interrelated rifting and magmatic history, as well as understanding processes of sedimentation and associated hydrothermal systems within the East African Rift System. We seek to determine the relative impacts of tectonic and climatic evolution on eastern African ecosystems. We ask, what role (if any) did climate change play in the evolution of hominins? How can our understanding of past environmental change guide our planning for a future shaped by anthropogenic climate change? To organize the scientific community’s goals for deep coring in the Turkana Basin, we hosted a 4-day ICDP supported workshop in Nairobi, Kenya in July 2022. The team focused on how a 4 Myr sedimentary core from the Turkana Basin will uniquely address key scientific research objectives related to basin evolution, paleoclimate, paleoenvironment, and modern resources. Participants also discussed how DDTB could collaborate with community partners in the Turkana Basin, particularly around the themes of access to water and education. The team concluded that collecting the proposed Pliocene to modern record is best accomplished through a 2-phase drilling project with a land-based transect of four cores spanning the interval from 4 Ma to Middle/Late Pleistocene (<0.7 Ma) and a lake-based core targeting the interval from ~1 Ma to present. The second phase, while logistically more challenging due to the lack of drilling infrastructure currently on Lake Turkana, would revolutionize our understanding of a significant interval in the evolution and migration of Homo sapiens for a time period not currently accessible from the Kenyan part of the Turkana Basin. Collectively, the DDTB project will provide exceptional tectonic and climatic data directly associated with one of the world’s richest hominin fossil localities

ICDP workshop on the Deep Drilling in the Turkana Basin Project:Exploring the link between environmental factors and hominin evolution over the past 4 Myr

Scientific drill cores provide unique windows into the processes of the past and present. In the dynamic tectonic, environmental, climatic, and ecological setting that is eastern Africa, records recovered through scientific drilling enable us to look at change through time in unprecedented ways. Cores from the East African Rift System can provide valuable information about the context in which hominins evolved in one of the key regions of hominin evolution over the past 4 Myr. The Deep Drilling in the Turkana Basin (DDTB) project seeks to explore the impact of several types of evolution (tectonic, climatic, biological) on ecosystems and environments. This includes addressing questions regarding the region’s complex and interrelated rifting and magmatic history, as well as understanding processes of sedimentation and associated hydrothermal systems within the East African Rift System. We seek to determine the relative impacts of tectonic and climatic evolution on eastern African ecosystems. We ask, what role (if any) did climate change play in the evolution of hominins? How can our understanding of past environmental change guide our planning for a future shaped by anthropogenic climate change? To organize the scientific community’s goals for deep coring in the Turkana Basin, we hosted a 4-day ICDP supported workshop in Nairobi, Kenya in July 2022. The team focused on how a 4 Myr sedimentary core from the Turkana Basin will uniquely address key scientific research objectives related to basin evolution, paleoclimate, paleoenvironment, and modern resources. Participants also discussed how DDTB could collaborate with community partners in the Turkana Basin, particularly around the themes of access to water and education. The team concluded that collecting the proposed Pliocene to modern record is best accomplished through a 2-phase drilling project with a land-based transect of four cores spanning the interval from 4 Ma to Middle/Late Pleistocene (<0.7 Ma) and a lake-based core targeting the interval from ~1 Ma to present. The second phase, while logistically more challenging due to the lack of drilling infrastructure currently on Lake Turkana, would revolutionize our understanding of a significant interval in the evolution and migration of Homo sapiens for a time period not currently accessible from the Kenyan part of the Turkana Basin. Collectively, the DDTB project will provide exceptional tectonic and climatic data directly associated with one of the world’s richest hominin fossil localities