RNA-binding proteins play vital roles in regulating gene expression and cellular physiology in all organisms. Bacterial RNA-binding proteins can regulate transcription termination via attenuation or ...antitermination mechanisms, while others can repress or activate translation initiation by affecting ribosome binding. The RNA targets for these proteins include short repeated sequences, longer single-stranded sequences, RNA secondary or tertiary structure, and a combination of these features. The activity of these proteins can be influenced by binding of metabolites, small RNAs, or other proteins, as well as by phosphorylation events. Some of these proteins regulate specific genes, while others function as global regulators. As the regulatory mechanisms, components, targets, and signaling circuitry surrounding RNA-binding proteins have become better understood, in part through rapid advances provided by systems approaches, a sense of the true nature of biological complexity is becoming apparent, which we attempt to capture for the reader of this review.
The Diabetes Complications Severity Index (DCSI) converts diagnostic codes and laboratory results into a 14-level metric quantifying the long-term effects of diabetes on seven body systems. Adoption ...of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) necessitates translation from ICD-9-CM and creates refinement opportunities.
ICD-9 codes for secondary and primary diabetes plus all five ICD-10 diabetes categories were incorporated into an updated tool. Additional modifications were made to improve the accuracy of severity assignments.
The tools were tested in a Medicare Advantage population.
In the type 2 subpopulation, prevalence steadily declined with increasing score according to the updated DCSI tool, whereas the original tool resulted in an aberrant local prevalence peak at DCSI = 2. In the type 1 subpopulation, score prevalence was greater in type 1 versus type 2 subpopulations (3 versus 0) according to both instruments. Both instruments predicted current-year inpatient admissions risk and near-future mortality, using either purely ICD-9 data or a mix of ICD-9 and ICD-10 data.
While the performance of the tool with purely ICD-10 data has yet to be evaluated, this updated tool makes assessment of diabetes patient severity and complications possible in the interim.
Many biological functions performed by RNAs arise from their in vivo structures. The structure of the same RNA can differ in vitro and in vivo owing in part to the influence of molecules ranging from ...protons to secondary metabolites to proteins. Chemical reagents that modify the Watson-Crick (WC) face of unprotected RNA bases report on the absence of base-pairing and so are of value to determining structures adopted by RNAs. Reagents have thus been sought that can report on the native RNA structures that prevail in living cells. Dimethyl sulfate (DMS) and glyoxal penetrate cell membranes and inform on RNA secondary structure in vivo through modification of adenine (A), cytosine (C), and guanine (G) bases. Uracil (U) bases, however, have thus far eluded characterization in vivo. Herein, we show that the water-soluble carbodiimide 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) is capable of modifying the WC face of U and G in vivo, favoring the former nucleobase by a factor of ∼1.5, and doing so in the eukaryote rice, as well as in the Gram-negative bacterium
While both EDC and glyoxal target Gs, EDC reacts with Gs in their typical neutral state, while glyoxal requires Gs to populate the rare anionic state. EDC may thus be more generally useful; however, comparison of the reactivity of EDC and glyoxal may allow the identification of Gs with perturbed pK
s in vivo and genome-wide. Overall, use of EDC with DMS allows in vivo probing of the base-pairing status of all four RNA bases.
Abstract
Background
Objective tracking of asthma medication use and exposure in real-time and space has not been feasible previously. Exposure assessments have typically been tied to residential ...locations, which ignore exposure within patterns of daily activities.
Methods
We investigated the associations of exposure to multiple air pollutants, derived from nearest air quality monitors, with space-time asthma rescue inhaler use captured by digital sensors, in Jefferson County, Kentucky. A generalized linear mixed model, capable of accounting for repeated measures, over-dispersion and excessive zeros, was used in our analysis. A secondary analysis was done through the random forest machine learning technique.
Results
The 1039 participants enrolled were 63.4% female, 77.3% adult (>18) and 46.8% White. Digital sensors monitored the time and location of over 286 980 asthma rescue medication uses and associated air pollution exposures over 193 697 patient-days, creating a rich spatiotemporal dataset of over 10 905 240 data elements. In the generalized linear mixed model, an interquartile range (IQR) increase in pollutant exposure was associated with a mean rescue medication use increase per person per day of 0.201 95% confidence interval (CI): 0.189-0.214, 0.153 (95% CI: 0.136-0.171), 0.131 (95% CI: 0.115-0.147) and 0.113 (95% CI: 0.097-0.129), for sulphur dioxide (SO2), nitrogen dioxide (NO2), fine particulate matter (PM2.5) and ozone (O3), respectively. Similar effect sizes were identified with the random forest model. Time-lagged exposure effects of 0–3 days were observed.
Conclusions
Daily exposure to multiple pollutants was associated with increases in daily asthma rescue medication use for same day and lagged exposures up to 3 days. Associations were consistent when evaluated with the random forest modelling approach.
Transportation is an important social determinant of health. We conducted a systematic review of the associations on health and health care utilization of interventions aimed at reducing barriers to ...non-emergency transportation and non-medical transportation.
We searched three databases and the gray literature through mid-January 2022. Included studies needed to assess an intervention targeted at non-emergency or non-medical transportation barriers, report missed (or kept) visits, health care utilization, costs, or health outcomes. Data extraction was performed in duplicate and included information about study design, results, and risk of bias. Primary outcomes were frequency of missed appointments, health care utilization, costs, and health outcomes. Synthesis was both narrative and meta-analytic using a random effects model.
Twelve studies met inclusion criteria, three randomized trials, one controlled trial, and eight observational studies. All included studies had some element of risk of bias. Populations studied usually had chronic or serious health conditions or were poor. Interventions included van rides, bus or taxi vouchers, ride-sharing services, and others. Meta-analysis of seven studies (three trials, four observational studies) yielded a pooled estimate of missed appointments = 0.63 (95% confidence interval CI 0.48, 0.83) favoring interventions. Evidence on cost, utilization, and health outcomes were too sparse to support conclusions. Evidence on the effect of non-medical transportation is limited to a single study.
Interventions aimed at non-emergency transportation barriers to access health care are associated with fewer missed appointments; the association with costs, utilization or health outcomes is insufficiently studied to reach conclusions. This review was registered in PROSPERO as ID CRD42020201875.
Chronic obstructive pulmonary disease (COPD) exacerbations account for a substantial proportion of COPD-related costs.
To describe COPD exacerbation patterns and assess the association between ...exacerbation frequency and health care resource utilization (HCRU) and costs in patients with COPD in a Medicare population.
A retrospective cohort study utilizing data from a large US national health plan was conducted including patients with a COPD diagnosis during January 1, 2007 to December 31, 2012, aged 40-89 years and continuously enrolled in a Medicare Advantage Prescription Drug plan. Exacerbation frequency, HCRU, and costs were assessed during a 24-month period following the first COPD diagnosis (follow-up period). Four cohorts were created based on exacerbation frequency (zero, one, two, and ≥three). HCRU and costs were compared among the four cohorts using chi-square tests and analysis of variance, respectively. A trend analysis was performed to assess the association between exacerbation frequency and costs using generalized linear models.
Of the included 52,459 patients, 44.3% had at least one exacerbation; 26.3%, 9.5%, and 8.5% had one, two, and ≥three exacerbations in the 24-month follow-up period, respectively. HCRU was significantly different among cohorts (all P<0.001). In patients with zero, one, two, and ≥three exacerbations, the percentages of patients experiencing all-cause hospitalizations were 49.7%, 66.4%, 69.7%, and 77.8%, respectively, and those experiencing COPD-related hospitalizations were 0%, 40.4%, 48.1%, and 60.5%, respectively. Mean all-cause total costs (medical and pharmacy) were more than twofold greater in patients with ≥three exacerbations compared to patients with zero exacerbations ($27,133 vs $56,033; P<0.001), whereas a greater than sevenfold difference was observed in mean COPD-related total costs ($1,605 vs $12,257; P<0.001).
COPD patients frequently experience exacerbations. Increasing exacerbation frequency is associated with a multiplicative increase in all-cause and COPD-related costs. This underscores the importance of identifying COPD patients at risk of having frequent exacerbations for appropriate disease management.
Abstract Purpose Although the efficacy of canagliflozin has been well established in clinical trials, research regarding its use and impact on outcomes in clinical practice has been limited by the ...availability of data on observations up to and beyond 6 months after the initial use of canagliflozin. The purpose of this study was to evaluate changes in glycemic control after the initiation of canagliflozin use in a managed care population. Methods A retrospective cohort analysis in adults with type 2 diabetes mellitus was conducted using medical and pharmacy claims data and laboratory results from the Humana Research Database. The differences between hemoglobin (Hb) A1c levels pre- and postindex were assessed. Changes from pre- to postindex in the percentages of patients achieving glycemic control (eg, HbA1c <7% or <8%) were evaluated. HbA1c levels were also observed during days 31 to 90, 91 to 180, 181 to 270, and 271 to 360 postindex relative to preindex to assess the durability of HbA1c change over time. Analyses were conducted in the full cohort and in 3 subgroups: (1) HbA1c ≥7% at baseline; (2) age ≥65 years; (3) and Medicare members age ≥65 years and HbA1c ≥7% at baseline. Findings Among the 1562 patients meeting the study criteria, the mean HbA1c values pre- and postindex were 8.6% and 7.9%, respectively ( P < 0.0001); in the subgroup with HbA1c ≥7% at baseline, these values were 8.9% and 8.0%; in the subgroup aged ≥65 years, 8.5% and 7.9%; and in the subgroup aged ≥65 years with HbA1c ≥7% at baseline, 8.8% and 8.1% (all subgroups, P < 0.001). The percentages of patients meeting glycemic-control thresholds (HbA1c <7%, <8%) were significantly greater at postindex in the full study cohort and in all 3 subgroups (all, P < 0.001). Based on longitudinal HbA1c results in the postindex periods, HbA1c reduction appeared durable across 12 months. Implications The findings from this study suggest that treatment with canagliflozin is associated with improved glycemic control, as evidenced by HbA1c reduction and glycemic goal attainment. Even though not all patients had valid HbA1c measurements available in each quarter during the follow-up period, the reductions in mean HbA1c appeared durable across the postindex intervals. The observations from this majority Medicare Advantage with Prescription Drug sample and, more specifically, in the subgroups limited to patients aged ≥65 years are particularly informative for payers and providers managing or caring for patients of this age with diabetes.
The original Charlson Comorbidity Index (CCI) encompassed 19 categories of medical conditions that were identifiable in medical records. Subsequent publications provided scoring algorithms based on
(
...) codes. The recent adoption of
(
) codes in the United States created a need for a new scoring scheme. In addition, a review of existing claims-based scoring systems suggested 3 areas for improvement: the lack of explicit identification of secondary diabetes, the lack of differentiation between HIV infection and AIDS, and insufficient guidance on scoring hierarchy. In addition, addressing the third need raised the issue of disease severity in renal disease.
This initiative aimed to create an expanded and refined
scoring system for CCI, addressing the classification of issues noted above, create a corresponding
system, assess the comparability of
- and
-based scores, and validate the new scoring scheme.
We created
and
code tables for 19 CCI medical conditions. The new scoring scheme was labeled CDMF CCI and was tested using claims-based data for individuals aged ≥65 years who participated in a Humana Medicare Advantage plan during at least 1 of 3 consecutive 12-month periods. Two 12-month periods were during the
era and the third 12-month period was during the
era. Because many individuals were counted in more than one 12-month period, we described the study population as comprising 3 panels. We used regression models to analyze the association between the CCI score and same-year inpatient admissions and near-term (90-day) mortality. Additional testing was done by comparing the mean CCI score or disease prevalence in the 3 subpopulations of people with HIV/AIDS, renal disease, or diabetes. Finally, we calculated area under the receiver operating characteristics (AUC-ROC) curve values by applying the Deyo system and our
and
scoring systems.
The CDMF
and
scoring scheme yielded comparable scores across the 3 panels, and inpatient admissions and mortality rates consistently increased in each panel as the CCI score increased. Comparisons of the performance of the Deyo system and our proposed CDMF
system in the 3 key subpopulations showed that the CDMF
system produced a lower CCI score in the presence of HIV infection without AIDS, achieved similar detection ability of diabetes, and allowed good differentiation between mild-to-moderate and severe renal disease. AUC-ROC values were similar between the CDMF
coding system and the Deyo system.
Our results support the implementation of the CDMF CCI scoring instrument to triage individual patients for disease- and care-management programs. In addition, the CDMF scheme allows for a more precise understanding of chronic disease at a population level, thus allowing health systems and plans to design services and benefits to meet multifactorial clinical needs. Preliminary validation sets the stage for further testing using long-term follow-up data and for the adaptation of this coding scheme to a chart review instrument.
Background
Studies have demonstrated that comorbidities compound the adverse influence of cancer on health-related quality of life (HRQoL). Comorbidities adversely impact adherence to cancer ...treatment. Additionally, adherence to medications for comorbidities is positively associated with HRQoL for various diseases. This study used the Center for Disease Control and Prevention’s Healthy Days measure of HRQoL to explore the association between HRQoL and adherence to comorbidity medication for elderly patients with cancer and at least one comorbid condition.
Methods
We conducted a cross-sectional survey combined with retrospective claims data. Patients with metastatic breast, lung or colorectal cancer were surveyed regarding their HRQoL, comorbidity medication adherence and cancer-related symptoms. Patients reported the number of physical, mental and total unhealthy days in the prior month. The Morisky Medication Adherence 8-point scale was differentiated into moderate/high (> 6) and low (≤ 6) comorbidity medication adherence.
Results
Of the 1847 respondents, the mean age was 69.2 years, most were female (66.8%) and the majority of the sample had Medicare coverage (88.2%). Low comorbidity medication adherence was associated with significantly more total, mental and physical unhealthy days. Low comorbidity medication adherence was associated with the presence of patient-reported cancer-related symptoms. Patients reporting low, as compared to moderate/high, comorbidity medication adherence had 23.4% more unhealthy days in adjusted analysis,
P
= 0.007.
Conclusion
The positive association between low comorbidity medication adherence and the number of unhealthy days suggests that addressing barriers to comorbidity medication adherence during cancer treatment may be an avenue for improving or maintaining HRQoL for older patients with cancer and comorbid conditions.
The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD ...assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs.
The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs.
Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P<0.001 for all). The odds ratio for high vs low symptoms using CAT was 2.51 (P<0.001). Similarly, exacerbation-related costs were 73% higher with each incremental pre-index exacerbation, and over four fold higher for high-vs low-symptom patients using CAT (each P<0.001). The symptoms using mMRC were not statistically significant in either model (P>0.10).
The patient-reported symptoms contribute important information related to future COPD exacerbations and exacerbation-related costs beyond that explained by exacerbation history.
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