Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity and mortality and a disproportionate burden on Black communities. Few population-based studies have examined the ...prevalence of comorbidities among persons with SCD. We estimated the prevalence of comorbidities experienced by individuals with SCD enrolled in employer-based health insurance plans in the US over their non-elderly lifetimes (0–64 years of age) with a retrospective cohort design using Truven Health MarketScan commercial claims data from 2007–2018. ICD-9/10 codes were used to identify individuals with SCD using a previously published algorithm. For this cohort, comorbidities associated with SCD were identified across 3 age categories (<18, 18–45, 46–64 years-old), based on the CMS Chronic Comorbidities Warehouse or SCD-specific diagnosis codes, when applicable. The total number of SCD patients available for analysis in each age category was 7,502 (<18 years), 10,183 (18–45 years) and 4,459 (46–64 years). Across all ages, vaso-occlusive pain, infections (non-specific), and fever were the most common comorbidities. Vaso-occlusive pain and infection were the most prevalent conditions for persons age <18- and 18–45-year-olds, while in the 46–54-year-old age group, infection and cardiovascular including pulmonary hypertension were most prevalent. Compared to persons <18 years old, the prevalence of vaso-occlusive pain, fever, and acute chest syndrome claims declined in older populations. The comorbidity burden of SCD is significant across all age groups. SCD patients experience comorbidities of age such as chronic pain, cardio-vascular conditions including pulmonary hypertension and renal disease at far higher rates than the general population. Novel disease modifying therapies in development have the potential to significantly reduce the comorbidity burden of SCD.
Various metrics predicated on Patient Health Questionnaire-9 (PHQ-9) scores denote depression "response" or "remission" over time, but few have been empirically validated. We compare the associations ...of depression response and remission metrics with concomitant clinical improvement in patient-centered outcomes (PCOs).
Secondary analysis of PHQ-9 and PCO data from the treatment arm (n=906) of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial.
We conducted univariate correlations between 9 depression treatment metrics and 4 PCOs. For each PCO, we specified a multivariate linear fixed-effects regression model with penalized LASSO (least absolute shrinkage and selection operator) variable selection that included parameters for each incremental absolute PHQ-9 decrease between 0 and 16 points. Model predictive properties were assessed using a split sample analysis.
There was a notable variation in depression improvement rates across metrics. Each metric was significantly associated with PCOs in univariate analyses. In the multivariate models, the cumulative likelihood of PCO improvement was most improved by absolute PHQ-9 score decreases of 7-9 and 14-16 points. The multivariate models showed greater area under the curve (0.671-0.804) in out-of-sample predictions of PCO changes than the univariate models (0.529-0.649).
Choice of depression response metric impacts observed response and remission rates, though PCOs tend to improve with depression improvement regardless of metric choice. Absolute incremental PHQ-9 score decreases are broadly associated with an increased likelihood of favorable PCO scores. Our findings support a novel PHQ-9 metric defined by an absolute score change of 8 points or greater.
Proteins can form amyloid fibrils that are the cause of various degenerative diseases. In this work, we have investigated the potential of a crown ether, 18-crown-6, to arrest fibrillation in ...lysozyme. Initially, the kinetics of fibrillation were monitored using a Thioflavin T fluorescence assay. This assay revealed that the crown ether suppressed the fibrillation of lysozyme, which was reaffirmed by the absorbance in a Congo red assay. A Nile red fluorescence assay, an ANS binding assay, intrinsic fluorescence studies and steady-state fluorescence anisotropy also provided evidence that fibrillogenesis was inhibited by the crown ether. The formation of amyloid fibrils is characterized by the formation of β-sheet rich structures. Far-UV circular dichroism experiments revealed that the β-sheet content of the protein enhanced upon fibrillation but upon treatment with the crown ether there was a decrease in the total β-sheet content, which again testified the ability of 18-crown-6 to arrest fibrillogenesis. Atomic force microscopy imaging also suggested that the crown ether arrested lysozyme fibrillation. These results can be utilized for developing more effective anti-amyloidogenic agents.
18-crown-6 retarded fibrillogenesis in lysozyme.
U isotope fractionation may serve as an accurate proxy for U(VI) reduction in both modern and ancient environments, if the systematic controls on the magnitude of fractionation (ε) are known. We ...model the effect of U(VI) reduction kinetics on U isotopic fractionation during U(VI) reduction by a novel Shewanella isolate, Shewanella sp. (NR), in batch incubations. The measured ε values range from 0.96 ± 0.16 to 0.36 ± 0.07‰ and are strongly dependent on the U(VI) reduction rate. The ε decreases with increasing reduction rate constants normalized by cell density and initial U(VI). Reactive transport simulations suggest that the rate dependence of ε is due to a two-step process, where diffusive transport of U(VI) from the bulk solution across a boundary layer is followed by enzymatic reduction. Our results imply that the spatial decoupling of bulk U(VI) solution and enzymatic reduction should be taken into account for interpreting U isotope data from the environment.
School and college reopening-closure policies are considered one of the most promising non-pharmaceutical interventions for mitigating infectious diseases. Nonetheless, the effectiveness of these ...policies is still debated, largely due to the lack of empirical evidence on behavior during implementation. We examined U.S. college reopenings' association with changes in human mobility within campuses and in COVID-19 incidence in the counties of the campuses over a twenty-week period around college reopenings in the Fall of 2020. We used an integrative framework, with a difference-in-differences design comparing areas with a college campus, before and after reopening, to areas without a campus and a Bayesian approach to estimate the daily reproductive number (Rt). We found that college reopenings were associated with increased campus mobility, and increased COVID-19 incidence by 4.9 cases per 100,000 (95% confidence interval CI: 2.9-6.9), or a 37% increase relative to the pre-period mean. This reflected our estimate of increased transmission locally after reopening. A greater increase in county COVID-19 incidence resulted from campuses that drew students from counties with high COVID-19 incidence in the weeks before reopening (χ2(2) = 8.9, p = 0.012) and those with a greater share of college students, relative to population (χ2(2) = 98.83, p < 0.001). Even by Fall of 2022, large shares of populations remained unvaccinated, increasing the relevance of understanding non-pharmaceutical decisions over an extended period of a pandemic. Our study sheds light on movement and social mixing patterns during the closure-reopening of colleges during a public health threat, and offers strategic instruments for benefit-cost analyses of school reopening/closure policies.
We provide evidence on the least biased ways to identify causal effects in situations where there are multiple outcomes that all depend on the same endogenous regressor and a reasonable but ...potentially contaminated instrumental variable that is available. Simulations provide suggestive evidence on the complementarity of instrumental variable (IV) and latent factor methods and how this complementarity depends on the number of outcome variables and the degree of contamination in the IV. We apply the causal inference methods to assess the impact of mental illness on work absenteeism and disability, using the National Comorbidity Survey Replication.
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