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

A randomised controlled trial comparing standard or intensive management of reduced fetal movements after 36 weeks gestation-a feasibility study

BACKGROUND: Women presenting with reduced fetal movements (RFM) in the third trimester are at increased risk of stillbirth or fetal growth restriction. These outcomes after RFM are related to smaller fetal size on ultrasound scan, oligohydramnios and lower human placental lactogen (hPL) in maternal serum. We performed this study to address whether a randomised controlled trial (RCT) of the management of RFM was feasible with regard to: i) maternal recruitment and retention ii) patient acceptability, iii) adherence to protocol. Additionally, we aimed to confirm the prevalence of poor perinatal outcomes defined as: stillbirth, birthweight <10(th) centile, umbilical arterial pH <7.1 or unexpected admission to the neonatal intensive care unit. METHODS: Women with RFM ≥36 weeks gestation were invited to participate in a RCT comparing standard management (ultrasound scan if indicated, induction of labour (IOL) based on consultant decision) with intensive management (ultrasound scan, maternal serum hPL, IOL if either result was abnormal). Anxiety was assessed by state-trait anxiety index (STAI) before and after investigations for RFM. Rates of protocol compliance and IOL for RFM were calculated. Participant views were assessed by questionnaires. RESULTS: 137 women were approached, 120 (88%) participated, 60 in each group, 2 women in the standard group did not complete the study. 20% of participants had a poor perinatal outcome. All women in the intensive group had ultrasound assessment of fetal size and liquor volume vs. 97% in the standard group. 50% of the intensive group had IOL for abnormal scan or low hPL after RFM vs. 26% of controls (p < 0.01). STAI reduced for all women after investigations, but this reduction was greater in the standard group (p = 0.02). Participants had positive views about their involvement in the study. CONCLUSION: An RCT of management of RFM is feasible with a low rate of attrition. Investigations decrease maternal anxiety. Participants in the intensive group were more likely to have IOL for RFM. Further work is required to determine the likely level of intervention in the standard care arm in multiple centres, to develop additional placental biomarkers and to confirm that the composite outcome is valid. TRIAL REGISTRATION: ISRCTN0794430

Groundwater dependence of riparian woodlands and the disrupting effect of anthropogenically altered streamflow

Riparian ecosystems fundamentally depend on groundwater, especially in dryland regions, yet their water requirements and sources are rarely considered in water resource management decisions. Until recently, technological limitations and data gaps have hindered assessment of groundwater influences on riparian ecosystem health at the spatial and temporal scales relevant to policy and management. Here, we analyze Sentinel-2–derived normalized difference vegetation index (NDVI; n = 5,335,472 observations), field-based groundwater elevation (n = 32,051 observations), and streamflow alteration data for riparian woodland communities (n = 22,153 polygons) over a 5-y period (2015 to 2020) across California. We find that riparian woodlands exhibit a stress response to deeper groundwater, as evidenced by concurrent declines in greenness represented by NDVI. Furthermore, we find greater seasonal coupling of canopy greenness to groundwater for vegetation along streams with natural flow regimes in comparison with anthropogenically altered streams, particularly in the most water-limited regions. These patterns suggest that many riparian woodlands in California are subsidized by water management practices. Riparian woodland communities rely on naturally variable groundwater and streamflow components to sustain key ecological processes, such as recruitment and succession. Altered flow regimes, which stabilize streamflow throughout the year and artificially enhance water supplies to riparian vegetation in the dry season, disrupt the seasonal cycles of abiotic drivers to which these Mediterranean forests are adapted. Consequently, our analysis suggests that many riparian ecosystems have become reliant on anthropogenically altered flow regimes, making them more vulnerable and less resilient to rapid hydrologic change, potentially leading to future riparian forest loss across increasingly stressed dryland regions