Age- and Lesion-Related Comorbidity Burden Among US Adults With Congenital Heart Disease: A Population-Based Study.

Background As patients with congenital heart disease (CHD) are living longer, understanding the comorbidities they develop as they age is increasingly important. However, there are no published population-based estimates of the comorbidity burden among the US adult patients with CHD. Methods and Results Using the IBM MarketScan commercial claims database from 2010 to 2016, we identified adults aged ≥18 years with CHD and 2 full years of continuous enrollment. These were frequency matched with adults without CHD within categories jointly defined by age, sex, and dates of enrollment in the database. A total of 40 127 patients with CHD met the inclusion criteria (mean [SD] age, 36.8 [14.6] years; and 48.2% were women). Adults with CHD were nearly twice as likely to have any comorbidity than those without CHD (P<0.001). After adjusting for covariates, patients with CHD had a higher prevalence risk ratio for "previously recognized to be common in CHD" (risk ratio, 9.41; 95% CI, 7.99-11.1), "other cardiovascular" (risk ratio, 1.73; 95% CI, 1.66-1.80), and "noncardiovascular" (risk ratio, 1.47; 95% CI, 1.41-1.52) comorbidities. After adjusting for covariates and considering interaction with age, patients with severe CHD had higher risks of previously recognized to be common in CHD and lower risks of other cardiovascular comorbidities than age-stratified patients with nonsevere CHD. For noncardiovascular comorbidities, the risk was higher among patients with severe than nonsevere CHD before, but not after, the age of 40 years. Conclusions Our data underscore the unique clinical needs of adults with CHD compared with their peers. Clinicians caring for CHD may want to use a multidisciplinary approach, including building close collaborations with internists and specialists, to help provide appropriate care for the highly prevalent noncardiovascular comorbidities

Functional Status After Colon Cancer Surgery in Elderly Nursing Home Residents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91352/1/jgs3915.pd

Children and young adults who received tracheostomies or were initiated on long-term ventilation in PICUs

Objectives: To characterize patients who received tracheostomies for airway compromise or were initiated on long-term ventilation for chronic respiratory failure in pediatric intensive care units (PICU), and to examine variation in the incidence of initiation, patient characteristics, and modalities across sites. Design: Retrospective cross-sectional analysis. Settings: Seventy three North American PICUs that participated in the Virtual Pediatric Intensive Care Unit Performance System. Patients: PICU patients admitted between 2009 and 2011. Interventions: None. Measurements and Main Results: Among 115,437 PICU patients, 1.8% received a tracheostomy or were initiated on long-term ventilation; 1034 received a tracheostomy only, 717 were initiated on invasive ventilation (IV), and 381 were initiated on noninvasive ventilation (NIV). Ninety percent had substantial chronic conditions and comorbidities, including more than 50% with moderate or worse cerebral disability upon discharge. Seven percent were initiated after a catastrophic injury/event. Across sites, there was variation in incidence of tracheotomy and initiation of long-term ventilation, ranging 0–4.6%. There also was variation in patient characteristics, time to tracheotomy, number of extubations prior to tracheostomy, and the use of IV versus NIV. Conclusions: While the PICU incidence of initiation of tracheostomies and long-term ventilation was relatively uncommon, it suggests that thousands of children and young adults receive these interventions each year in North American PICUs. The majority of them have conditions and comorbidities that impose on-going care needs, beyond those required by artificial airways and long-term ventilation themselves

Giving formulary and drug cost information to providers and impact on medication cost and use: a longitudinal non-randomized study

BackgroundProviders wish to help patients with prescription costs but often lack drug cost information. We examined whether giving providers formulary and drug cost information was associated with changes in their diabetes patients' drug costs and use. We conducted a longitudinal non-randomized evaluation of the web-based Prescribing Guide ( www.PrescribingGuide.com ), a free resource available to Hawaii's providers since 2006, which summarizes the formularies and copayments of six health plans for drugs to treat 16 common health conditions. All adult primary care physicians in Hawaii were offered the Prescribing Guide, and providers who enrolled received a link to the website and regular hardcopy updates.MethodsWe analyzed prescription claims from a large health plan in Hawaii for 5,883 members with diabetes from 2007 (baseline) to 2009 (follow-up). Patients were linked to 299 "main prescribing" providers, who on average, accounted for >88 % of patients' prescriptions and drug costs. We compared changes in drug costs and use for "study" patients whose main provider enrolled to receive the Prescribing Guide, versus "control" patients whose main provider did not enroll to receive the Prescribing Guide.ResultsIn multivariate analyses controlling for provider specialty and clustering of patients by providers, both patient groups experienced similar increases in number of prescriptions (+3.2 vs. +2.7 increase, p = 0.24), and days supply of medications (+141 vs. +129 increase, p = 0.40) averaged across all drugs. Total and out-of-pocket drug costs also increased for both control and study patients. However, control patients showed higher increases in yearly total drug costs of $208 per patient (+$792 vs. +$584 increase, p = 0.02) and in 30-day supply costs (+$9.40 vs. +$6.08 increase, p = 0.03). Both groups experienced similar changes in yearly out-of-pocket costs (+$41 vs + $31 increase, p = 0.36) and per 30-day supply (-$0.23 vs. -$0.19 decrease, p = 0.996).ConclusionGiving formulary and drug cost information to providers was associated with lower increases in total drug costs but not with lower out-of-pocket costs or greater medication use. Insurers and health information technology businesses should continue to increase providers' access to formulary and drug cost information at the point of care

Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome.

BackgroundThe choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available.ObjectiveTo determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS.DesignDecision-analytic model.Data sourcesPublished literature, Medicare claims, and life tables.Target populationPatients having percutaneous coronary intervention for ACS.Time horizonLifetime.PerspectiveSocietal.InterventionFive strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel.Outcome measuresDirect medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs).Results of base-case analysisThe clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of$35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor).Results of sensitivity analysisStronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor.LimitationNo randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor.ConclusionGenotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings

The universal Glivenko-Cantelli property

Let F be a separable uniformly bounded family of measurable functions on a standard measurable space, and let N_{[]}(F,\epsilon,\mu) be the smallest number of \epsilon-brackets in L^1(\mu) needed to cover F. The following are equivalent: 1. F is a universal Glivenko-Cantelli class. 2. N_{[]}(F,\epsilon,\mu)0 and every probability measure \mu. 3. F is totally bounded in L^1(\mu) for every probability measure \mu. 4. F does not contain a Boolean \sigma-independent sequence. It follows that universal Glivenko-Cantelli classes are uniformity classes for general sequences of almost surely convergent random measures.Comment: 26 page

Correlates of depression among people with diabetes: The Translating Research Into Action for Diabetes (TRIAD) study

Aim The broad objective of this study was to examine multiple dimensions of depression in a large, diverse population of adults with diabetes. Specific aims were to measure the association of depression with: (1) patient characteristics(2) outcomesand (3) diabetes-related quality of care. Methods Cross-sectional analyses were performed using survey and chart data from the Translating Research Into Action for Diabetes (TRIAD) study, including 8790 adults with diabetes, enrolled in 10 managed care health plans in 7 states. Depression was measured using the Patient Health Questionnaire (PHQ-8). Patient characteristics, outcomes and quality of care were measured using validated survey items and chart data. Results Nearly 18% of patients had major depression, with prevalence 2-3 times higher among patients with low socioeconomic status. Pain and limited mobility were strongly associated with depression, controlling for other patient characteristics. Depression was associated with slightly worse glycemic control, but not other intermediate clinical outcomes. Depressed patients received slightly fewer recommended diabetes-related processes of care. Conclusions In a large, diverse cohort of patients with diabetes, depression was most prevalent among patients with low socioeconomic status and those with pain, and was associated with slightly worse glycemic control and quality of care

UV-induced ligand exchange in MHC class I protein crystals

High-throughput structure determination of protein−ligand complexes is central in drug development and structural proteomics. To facilitate such high-throughput structure determination we designed an induced replacement strategy. Crystals of a protein complex bound to a photosensitive ligand are exposed to UV light, inducing the departure of the bound ligand, allowing a new ligand to soak in. We exemplify the approach for a class of protein complexes that is especially recalcitrant to high-throughput strategies: the MHC class I proteins. We developed a UV-sensitive, “conditional”, peptide ligand whose UV-induced cleavage in the crystals leads to the exchange of the low-affinity lytic fragments for full-length peptides introduced in the crystallant solution. This “in crystallo” exchange is monitored by the loss of seleno-methionine anomalous diffraction signal of the conditional peptide compared to the signal of labeled MHC β2m subunit. This method has the potential to facilitate high-throughput crystallography in various protein families

The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding

The validity of the identification and classification of human cancer using antibodies to detect biomarker proteins depends upon antibody specificity. Antibodies that bind to the tumour-suppressor protein p16INK4a are widely used for cancer diagnosis and research. In this study we examined the specificity of four commercially available anti-p16INK4a antibodies in four immunological applications. The antibodies H-156 and JC8 detected the same 16 kDa protein in western blot and immunoprecipitation tests, whereas the antibody F-12 did not detect any protein in western blot analysis or capture a protein that could be recognised by the H-156 antibody. In immunocytochemistry tests, the antibodies JC8 and H-156 detected a predominately cytoplasmic localised antigen, whose signal was depleted in p16INK4a siRNA experiments. F-12, in contrast, detected a predominately nuclear located antigen and there was no noticeable reduction in this signal after siRNA knockdown. Furthermore in immunohistochemistry tests, F-12 generated a different pattern of staining compared to the JC8 and E6H4 antibodies. These results demonstrate that three out of four commercially available p16INK4a antibodies are specific to, and indicate a mainly cytoplasmic localisation for, the p16INK4a protein. The F-12 antibody, which has been widely used in previous studies, gave different results to the other antibodies and did not demonstrate specificity to human p16INK4a. This work emphasizes the importance of the validation of commercial antibodies, aside to the previously reported use, for the full verification of immunoreaction specificity