Factors associated with adherence to medications for lowering breast cancer risk between female Medicare beneficiaries in Alabama and nationwide.

PURPOSE: The U.S. Preventive Services Task Force recommends use of selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) for breast cancer (BC) prevention. We examined factors associated with adherence to SERMs/AI treatments among female Medicare beneficiaries in Alabama and those nationwide. METHODS: This retrospective new user cohort study analyzed the 2013-2016 Medicare administrative claims data files (100% Alabama and random 5% national samples). Female Medicare beneficiaries without invasive BC and osteoporosis, continuously enrolled in Medicare Parts A, B, and D for at least 18 months (with a 6-month washout and a 12-month follow-up period) in 2013-2016. Among beneficiaries who initiated (6-month washout) any of the SERMs/AIs (tamoxifen, raloxifene, anastrozole, and exemestane), we examined their 1-year treatment adherence using proportion of days covered (PDC) and operationalized as both continuous (0-1) and dichotomized (≥ 80% as adherent and < 80% as non-adherent) outcomes. Multivariable logistic models were used to identify factors associated with adherence (PDC ≥ 80%) among Alabama and national samples, respectively. RESULTS: A total of 885 women in Alabama and 1,213 women in national sample initiated these SERMs/AI treatments. Among those with ≥ 2 prescriptions (n = 479 in Alabama and n = 870 in national sample), Mean PDC was 0.74 [standard deviation (SD) = 0.30] among Alabamian women, similar to those in the national sample [0.71 (SD = 0.31), p = 0.09]. Use of mammography prior to treatment initiation was associated with higher likelihood of adherence to treatments in both samples. CONCLUSION: Our findings highlight the importance of access to preventive services such as mammography to better adherence to BC preventive treatments among female Medicare beneficiaries.

Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Cancer: A Target Trial Emulation from SEER-Medicare Database.

BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over warfarin in patients with atrial fibrillation (AFib). However, their safety and effectiveness in patients with AFib and cancer are inconclusive. METHODS: We conducted a retrospective cohort study by emulating a target trial. Patients with a record of cancer (breast, prostate, or lung), newly diagnosed with AFib initiated DOACs or warfarin within 3 months after AFib diagnosis from the 2012-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare database were included. We compared the risk of ischemic stroke, major bleeding, and secondary outcomes (venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, and non-critical site bleeding) between patients who initiated DOACs and warfarin. Inverse probability treatment weights and inverse probability censoring weights were used to adjust imbalanced patient and disease characteristics and loss to follow-up between the two groups. Weighted pooled logistic regression were used to estimate treatment effect with hazard ratios (HRs) with 95% confidence interval (95% CIs). RESULTS: The incidence rates of stroke and major bleeding between DOAC and warfarin initiators were 9.97 vs. 9.91 and 7.74 vs. 9.24 cases per 1000 person-years, respectively. In adjusted intention-to-treat analysis, patients initiated DOACs had no statistically significant difference in risk of ischemic stroke (HR = 0.87, 95% CI 0.52-1.44) and major bleeding (HR = 1.14, 95% CI 0.77-1.68) compared to those initiated warfarin. In adjusted per-protocol analysis, there was no statistical difference in risk of ischemic stroke (HR = 1.81, 95% CI 0.75-4.36) and lower risk for major bleeding, but the 95% CI was wide (HR = 0.35, 95% CI 0.12-0.99) among DOAC initiators compared to warfarin initiators. The benefits in secondary outcomes were in favor of DOACs. The findings remained consistent across subgroups and sensitivity analyses. CONCLUSION: DOACs are safe and effective alternatives to warfarin in the management of patients with AFib and cancer.

Benefit and risk of oral anticoagulant initiation strategies in patients with atrial fibrillation and cancer: a target trial emulation using the SEER-Medicare database.

Oral anticoagulants (OACs) are recommended for patients with atrial fibrillation (AFib) having CHA2DS2-VASc score ≥ 2. However, the benefits of OAC initiation in patients with AFib and cancer at different levels of CHA2DS2-VASc is unknown. We included patients with new AFib diagnosis and a record of cancer (breast, prostate, or lung) from the 2012-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare database (n = 39,915). Risks of stroke and bleeding were compared between 5 treatment strategies: (1) initiated OAC when CHA2DS2-VASc ≥ 1 (n = 6008), (2) CHA2DS2-VASc ≥ 2 (n = 8694), (3) CHA2DS2-VASc ≥ 4 (n = 20,286), (4) CHA2DS2-VASc ≥ 6 (n = 30,944), and (5) never initiated OAC (reference group, n = 33,907). Confounders were adjusted using inverse probability weighting through cloning-censoring-weighting approach. Weighted pooled logistic regressions were used to estimate treatment effect [hazard ratios (HRs) and 95% confidence interval (95% CIs)]. We found that only patients who initiated OACs at CHA2DS2-VASc ≥ 6 had lower risk of stroke compared without OAC initiation (HR 0.64, 95% CI 0.54-0.75). All 4 active treatment strategies had reduced risk of bleeding compared to non-initiators, with OAC initiation at CHA2DS2-VASc ≥ 6 being the most beneficial strategy (HR = 0.49, 95% CI 0.44-0.55). In patients with lung cancer or regional/metastatic cancer, OAC initiation at any CHA2DS2-VASc level increased risk of stroke and did not reduce risk of bleeding (except for Regimen 4). In conclusion, among cancer patients with new AFib diagnosis, OAC initiation at higher risk of stroke (CHA2DS2-VASc score ≥ 6) is more beneficial in preventing ischemic stroke and bleeding. Patients with advanced cancer or low life-expectancy may initiate OACs when CHA2DS2-VASc score ≥ 6.

Did the 2021 federal change in the practice guidelines for the administration of buprenorphine for treating opioid use disorder increase buprenorphine prescription dispensing in Medicaid population?

BACKGROUND AND OBJECTIVES: In April 2021, the Department of Health and Human Services released new federal practice guidelines and allowed physicians who wish to treat ≤30 patients with opioid use disorder (OUD) to forego the X-waiver training requirement. METHODS: This observational study compared annual number, dose, and spending of buprenorphine OUD treatments dispensed in the Medicaid population in 2021 versus 2020 using the CMS State Drug Utilization Data (n = 50 states plus D.C.). RESULTS: Compared to 2020, there was a slight decrease (-3.1%) in the annual number of buprenorphine prescriptions dispensed but an increase in total doses (+3.2%) and payment (10.6%) for buprenorphine prescriptions in 2021. DISCUSSION AND CONCLUSIONS: Decrease in number of buprenorphine prescriptions in Medicaid population was observed in 2021. SCIENTIFIC SIGNIFICANCE: Our findings support the hypothesis generation in which the removal of X-waiver training alone is not adequate to increase prescribing and access to OUD treatment buprenorphine.

Nucleic Acid Amplification-Free Digital Detection Method for SARS-CoV-2 RNA Based on Droplet Microfluidics and CRISPR-Cas13a.

Most of the methods currently developed for RNA detection based on CRISPR were combined with nucleic acid amplification. As a result, such methods inevitably led to certain disadvantages such as multiple operations, expensive reagents, and amplification bias. To solve the above problems, we developed a highly sensitive and specific nucleic acid amplification-free digital detection method for SARS-CoV-2 RNA based on droplet microfluidics and CRISPR-Cas13a. In this assay, thousands of monodisperse droplets with a size of 30 µm were generated within 2 min by a negative pressure-driven microfluidic chip. By confining a single target RNA recognition event to an independent droplet, the collateral cleavage products of activated Cas13a could be accumulated in one droplet. By combining the droplet microfluidics and CRISPR-Cas13a, SARS-CoV-2 RNA could be easily detected within 30 min with a detection limit of 470 aM. The performance of this assay was verified by specificity experiments and spiking and recovery experiments with human saliva. Compared with many developed methods for SARS-CoV-2 RNA detection, our method is time- and reagent-saving and easy to operate. Taken together, this digital detection method based on droplet microfluidics and CRISPR-Cas13a provides a promising approach for RNA detection in clinical diagnostics.

Screening for clinically relevant drug-drug interactions between direct oral anticoagulants and antineoplastic agents: a pharmacovigilance approach.

BACKGROUND: Use of direct oral anticoagulants (DOACs) in patients with cancer remains suboptimal due to the concern regarding potential drug-drug interactions (DDIs) with antineoplastic treatments. However, the clinical relevance of these DDIs is unknown. METHODS: We conducted a pharmacovigilance study of adverse event (AE) reports from the US Food and Drug Administration Adverse Event Reporting System from 1/1/2004 to 12/31/2021. AE reports containing DOACs and antineoplastic agents with CYP3A4/P-gp inhibitory or inducing activity suggested by published pharmacokinetic studies were included (n = 36,066). The outcomes of interest were bleeding or stroke, identified by MedDRA dictionary version 25.0. We used disproportionality analyses (DPA), logistic regression models (LR), and Multi-item Gamma-Poisson Shrinker (MGPS) (Empirical Bayes Geometric Means (EBGM) and 90% credible intervals (90% CIs)) algorithms to identify the safety signal of DDIs. RESULTS: The highest bleeding reporting rates for each drug class were the combination of DOACs with neratinib (39.08%, n = 34), tamoxifen (21.22%, n = 104), irinotecan (20.54%, n = 83), and cyclosporine (19.17%, n = 227). The highest rate of stroke was found for prednisolone (2.43%, n = 113). In the primary analysis, no signal of DDIs by the antineoplastic therapeutic class was detected by MGPS, DPA, and LR approaches. By individual antineoplastic drug, DOACs-neratinib was the only signal detected [EBGM (EB05-EB95) = 2.71 (2.03-3.54)]. CONCLUSION: No signal of DDIs between DOACs and antineoplastic agents was detected, except for DOAC-neratinib. Most DDIs between DOACs and antineoplastic agents may not be clinically relevant. The DDIs between DOACs and neratinib should be further examined in future research.

Comparative safety of generic versus brand calcineurin inhibitors in solid organ transplant patients: A systematic review and meta-analysis.

BACKGROUND: Although generic ciclosporin-A (CsA) and tacrolimus (TAC) have been used for the prophylaxis of organ rejection in transplant patients for decades, evidence in their safety profile compared to reference listed drugs (RLDs) in real-world transplant patients remains limited. OBJECTIVES: To compare safety outcomes of generic CsA and TAC with the reference-listed drugs in solid organ transplant patients. METHODS: We systematically searched MEDLINE, International Pharmaceutical Abstracts, PsycINFO, and Cumulative Index of Nursing and Allied Health Literature from inception until March 15, 2022, to select randomized and observational studies comparing safety profiles of generic versus brand CsA and TAC in de novo and/or stable solid organ transplant patients. Primary safety outcomes were changes in serum creatinine (Scr) and glomerular filtration rate (GFR). Secondary outcomes included incidences of infection, hypertension, diabetes, other serious adverse events (AEs), hospitalization, and death. Mean difference (MD) and relative risk (RR) with 95% confidence intervals (CIs) were calculated using random-effects meta-analyses. RESULTS: Of 2612 publications identified, 32 studies met inclusion criteria. Seventeen studies had a moderate risk of bias. Scr was statistically significantly lower in patients using generic CsA compared to brand at 1 month (MD = -0.07; 95% CI: -0.11, -0.04), while there were no statistically significant differences at 4 months, 6 months, and 12 months. No differences were detected in Scr (MD = -0.04; 95% CI: -0.13, 0.04) and estimated GFR (MD = -2.06; 95% CI: -8.89, 4.77) between patients using generic and brand TAC at 6 months. No statistically significant differences between generic CsA and TAC with their RLDs were observed for secondary outcomes. CONCLUSION: Findings support similarity in safety outcomes between generic and brand CsA and TAC in real-world solid organ transplant patients.

Current published evidence on barriers and proposed strategies for genetic testing implementation in health care settings: A scoping review.

BACKGROUND: The slow uptake of genetic testing in routine clinical practice warrants the attention of researchers and practitioners to find effective strategies to facilitate implementation. OBJECTIVES: This study aimed to identify the barriers to and strategies for pharmacogenetic testing implementation in a health care setting from published literature. METHODS: A scoping review was conducted in August 2021 with an expanded literature search using Ovid MEDLINE, Web of Science, International Pharmaceutical Abstract, and Google Scholar to identify studies reporting implementation of pharmacogenetic testing in a health care setting, from a health care system's perspective. Articles were screened using DistillerSR and findings were organized using the 5 major domains of Consolidated Framework for Implementation Research (CFIR). RESULTS: A total of 3536 unique articles were retrieved from the above sources, with only 253 articles retained after title and abstract screening. Upon screening the full texts, 57 articles (representing 46 unique practice sites) were found matching the inclusion criteria. We found that most reported barriers and their associated strategies to the implementation of pharmacogenetic testing surrounded 2 CFIR domains: intervention characteristics and inner settings. Factors relating to cost and reimbursement were described as major barriers in the intervention characteristics. In the same domain, another major barrier was the lack of utility studies to provide evidence for genetic testing uptake. Technical hurdles, such as integrating genetic information to medical records, were identified as an inner settings barrier. Collaborations and lessons from early implementers could be useful strategies to overcome majority of the barriers across different health care settings. Strategies proposed by the included implementation studies to overcome these barriers are summarized and can be used as guidance in future. CONCLUSION: Barriers and strategies identified in this scoping review can provide implementation guidance for practice sites that are interested in implementing genetic testing.

De novo programming: establishment of epigenome in mammalian oocytes†.

Innovations in ultrasensitive and single-cell measurements enable us to study layers of genome regulation in view of cellular and regulatory heterogeneity. Genome-scale mapping allows to evaluate epigenetic features and dynamics in different genomic contexts, including genebodies, CpG islands, imprinting control regions, promoters, partially methylated domains, and repetitive elements. The epigenome of early embryos, fetal germ cells, and sperms has been extensively studied for the past decade, whereas oocytes remain less clear. Emerging evidence now supports the notion that transcription and chromatin accessibility precede de novo DNA methylation in both human and mouse oocytes. Recent studies have also started to chart correlations among different histone modifications and DNA methylation. We discuss the potential mechanistic hierarchy that shapes the oocyte DNA methylome, also providing insights into the convergent and divergent features between humans and mice.

The reference ranges and characteristics of lymphocyte parameters and the correlation between lymphocyte parameters and routine health indicators in adults from China.

BACKGROUND: Assessment of immune function is of key importance in recognition of disease or healthy status, which still faces challenge in clinical practice. We conducted a 10-center study to investigate lymphocyte parameters including the number, phenotype and IFN-γ-producing ability, and routine laboratory indicators by using the standard method. RESULTS: Although the heterogeneity of lymphocyte parameters was widely found, we have established the normal ranges of these parameters by using pooled data which showed no significant difference among centers. Cluster analysis of 35 parameters found 3 interesting clusters which represented different immunological status. Cluster 1 (parameters: IFN-γ+CD4+ T cell percentage and IFN-γ+CD8+ T cell percentage) represented current lymphocyte function, which was associated with indicators such as body mass index and red blood cell; Cluster 2 (parameters: NK cell number and CD45RA+CD4+ T cell percentage) represented potential of lymphocytes, which was associated with indicators such as albumin and high-density lipoprotein. Cluster 3 (parameters: HLA-DR+CD8+ T cell percentage) represented inflammatory status, which was associated with indicators such as low-density lipoprotein, globulin and age. Correlation analysis found that nutritional indicator albumin is significantly positively correlated with lymphocyte potential. Triglyceride and body mass index were positively correlated with current lymphocyte function rather than lymphocyte potential. The loss of CD8+ T cells was extremely pronounced with increasing age and was one of the most important factors to cause immunosenescence, which may be associated with increased glucose. CONCLUSIONS: We have established the normal ranges of lymphocyte parameters in different areas. This study elucidates the key indicators used to reflect the current function or potential of lymphocytes, which may provide a valuable clue for how to keep immunity healthy.

MiR-335 promotes corneal neovascularization by Targeting EGFR.

BACKGROUND: Corneal neovascularization (CRNV) is a severe threat to the vision of people. MicroRNA-335 (miR-335) has the function of facilitating angiogenesis. However, whether miR-335 regulates the progression of CRNV remains unclear. METHODS: The miR-335 expressions in CRNV rats induced by corneal suture and HUVECs induced by b-FGF were detected by quantitative real-time PCR. For the miR-335 function, wound healing and tube formation assays were performed. For the miR-335 mechanism, a dual-luciferase reporter gene assay was conducted. Besides, for the epidermal growth factor receptor (EGFR) function, Cell Counting Kit-8 and wound healing assays were performed. Meanwhile, the rescue assay was used to assess the miR-335/EGFR function in the migration and angiogenesis of b-FGF-treated HUVECs. RESULTS: Functionally, the miR-335 knockdown weakened the migration and angiogenesis of b-FGF-treated HUVECs, while the miR-335 overexpression showed an opposite trend. Mechanistically, miR-335 interacted with EGFR and negatively regulated the expression of EGFR. The rescue assay illustrated that miR-335 regulated the migration and angiogenesis of b-FGF-treated HUVECs through EGFR. CONCLUSIONS: In general, our data confirmed that miR-335 facilitated the process of CRNV by targeting EGFR.

Plateletcrit for predicting prognosis in patients with hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloid.

BACKGROUND: Platelet index was reported to be used as a potential prognostic marker in patients with liver fibrosis. We aimed to explore the association between plateletcrit (PCT) and severity of hepatic sinusoidal obstruction syndrome (HSOS). METHODS: Seventy consecutive patients who diagnosed as HSOS by CT and medical history during January 2017-November 2021 were included. All patients were divided into two groups which confirmed as favorable prognosis and poor prognosis on the basis of Child-Turcotte-Pugh score system. The clinical manifestation and laboratory parameters of two groups were retrospectively selected. PCT was evaluated within two groups, and the diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve. RESULTS: The significant difference between the two groups not only in diarrhea, abdominal pain, abdominal distention, urine volume, and skin ecchymosis (p < 0.005), but also in WBC count, NE count, PLT count, TBIL, and D-Dimer (p < 0.005) were found. The PCT level was significantly higher in HSOS patients with poor prognosis (0.169 ± 0.060) than favorable prognosis patients (0.110 ± 0.047). The area under the receiver operating characteristic curve of RDW in predicting poor prognosis was 0.781, with 67.70% sensitivity and 79.5%specificity. CONCLUSIONS: The PCT level was correlated positively with the poor prognosis in HSOS patients. PCT can be a promising indicator for predicting prognosis in HSOS.

Value of transesophageal echocardiography in device closure of perimembranous ventricular septal defects in children via ultra-minimal trans intercostal incision.

AIMS: To investigate the value of transesophageal echocardiography (TEE) in perimembranous ventricular septal defect (PmVSD) closure via a left parasternal ultra-minimal trans intercostal incision in children. METHODS: From January 2015 to December 2020, 212 children with PmVSDs underwent device occlusion via an ultra-minimal trans intercostal incision. TEE was used throughout the perioperative period, including TEE assessment, TEE-guided localization of the puncture site, and TEE guidance. All patients were followed up using transthoracic echocardiography for more than 6 months. RESULTS: A total of 207 cases were successfully occluded, and the success rate was 97.64%. One hundred forty-five patients had a single orifice, and 62 patients had multiple orifices in the aneurysm of the membranous septum (AMS). During the operation, the surgeon readjusted the device or replaced it with a larger device in 17 cases. After the operation, 19 cases of a slight residual shunt, 13 cases of pericardial effusion, and 4 cases of pleural effusion were noted. All patients returned to normal during the 4-month follow-up period. Mild mitral regurgitation was present in one patient and remained the same during the follow-up period. No other complications were found. CONCLUSIONS: Under TEE guidance, PmVSDs were closed successfully using a concentric occluder via an ultra-minimal trans intercostal incision. TEE, which was used to assess defects and postoperative effect, effectively guide PmVSDs closure, is of great value.

Individuals' preference for financial over social incentives for medication adherence.

BACKGROUND: Patients with chronic conditions continue to face financial and system-related barriers to medication adherence. Pharmacy, provider, and payer-based financial and social incentive-based interventions may reduce these barriers and improve adherence. However, it is unclear how patient demographics and clinical characteristics influence the type of incentives preferred by patients. OBJECTIVES: To examine individuals' preference for financial versus social incentives and to explore the association between patient demographic and clinical characteristics with preferences for financial or social incentives. METHODS: A cross-sectional survey of a nationally representative sample of patients was conducted with Qualtrics panelists (N = 909). U.S. adults taking at least 1 prescription medication for a chronic condition were included. Survey items elicited participants' demographic characteristics, preference for financial or social incentives, self-reported medication adherence, number of prescribed medications, and number of chronic conditions. Bivariate associations between patient characteristics and incentive preferences were tested using t and chi-square tests. Logistic regression was performed to determine patient characteristics associated with participants' preference for incentives. RESULTS: When compared with those who were adherent to medications, individuals who were nonadherent were less likely to prefer financial incentives over social incentives (adjusted odds ratio [OR] 0.55 [95% CI 0.31-0.98]). Patient income, sex, and ethnicity were also associated with preferences for financial incentives. Those earning less than $50,000 per year were less likely to prefer financial incentives compared with social incentives (adjusted OR 0.44 [0.24-0.79]). Females were more likely to prefer financial incentives (adjusted OR 1.98 [1.16-3.37]). Hispanic/Latinos were less likely to prefer financial incentives compared to non-Hispanics/non-Latinos (adjusted OR 0.51 [0.29-0.89]). CONCLUSION: Preferences for medication adherence incentives differed on the basis of adherence status and patients' demographic characteristics. Findings have implications for how incentive-based interventions can be structured to target certain patient groups.

Increasing use of immunization information systems for routine vaccinations in independent community pharmacies: A randomized controlled trial.

BACKGROUND: Only 60% of adults nationwide and just 36.8% of adults in Alabama have immunization data recorded in an Immunization Information System (IIS). The objective of this study, which took place before the coronavirus disease 2019 (COVID-19) pandemic, was to evaluate the impact of an IIS training program on pharmacists' IIS enrollment, participation, awareness, knowledge, intention, and attitudes. METHODS: A randomized controlled trial was conducted in 2019 among Alabama pharmacists (N = 41) practicing in independently owned pharmacies and providing vaccination services but whose pharmacy was not enrolled in Alabama's IIS (Immunization Patient Registry with Integrated Technology [ImmPRINT]). Intervention pharmacists were offered a 2-hour IIS training program, including an online continuing pharmacy education article, demonstration videos, implementation guide, and informational flyer. Control pharmacies received the informational flyer only. Pharmacy-level outcomes, including enrollment and participation, were obtained from ImmPRINT administrative records. Pharmacist-level outcomes, including awareness, knowledge, intention, and attitudes, were self-reported using baseline, 1-month, and 3-month surveys. Two-way mixed analysis of variance, chi-square, and independent t tests were used to analyze differences in outcomes between and within groups. RESULTS: Enrollment in ImmPRINT was significantly greater among intervention pharmacists' pharmacies (P = 0.035). In particular, 59.1% of intervention pharmacies compared with 26.3% of control pharmacies were enrolled in ImmPRINT at 3 months. No statistically significant differences were found between groups in terms of participation in ImmPRINT. Intervention pharmacists' awareness of IIS was significantly greater than control pharmacists (P = 0.028) at 1 month (postintervention). Furthermore, the IIS training program significantly improved intervention pharmacists' knowledge (P = 0.030) and attitudes (P = 0.016) toward IIS over 3 months compared with the control group. CONCLUSIONS: This pharmacist-centered training program focused on practical strategies to integrate IIS into pharmacy workflow. Results show that pharmacists' enrollment, awareness, knowledge, and attitudes significantly improved as a result of this training. As pharmacists become more involved in immunization efforts, particularly in response to COVID-19, awareness of and participation in responsible immunization documentation are critical.

The association of continuity of care and risk of mortality in breast cancer patients with cardiometabolic comorbidities.

OBJECTIVE: The association of continuity of care (COC) among providers and mortality risk for breast cancer patients with comorbidities is not sufficiently studied. DESIGN: A retrospective cohort study using the 2006-2014 Surveillance, Epidemiology and End Results (SEER)-Medicare data. PARTICIPANTS: Newly diagnosed female breast cancer patients (n = 57,578) with comorbidities (hypertension, hyperlipidemia, and/or diabetes). METHODS: All-cause mortality was assessed annually for up to 5 years. COC was estimated using the Bice-Boxerman index, which included: 1) specialty COC capturing continuity of visits to the same provider type (Primary Care Physicians, Oncologists, and Other specialists) and 2) individual COC capturing continuous care to the same provider regardless of provider specialty. Cox proportional hazards models estimated the hazard ratio (HR) of all-cause mortality across quartile of the COC index. RESULTS: Mortality was positively associated with advanced tumor stages and number of comorbidities (p < 0.05). Patients with high specialty COC (4th vs. 1st quartile, HR 1.34, 95%CI 1.29-1.40) had higher risks of mortality compared with those with low specialty COC. However, patients with high individual COC (4th vs. 1st quartile, HR 0.53, 95%CI 0.51-0.54) had lower risks of mortality compared to those with low individual COC. CONCLUSION: Receiving care from fewer providers is associated with lower mortality and from fewer types of provider is associated with higher mortality. The results might be confounded by uncontrolled factors and provoke the need for alternative patient care models that recognize the balance between appropriate subspecialties and minimizing the fragmentation of care within and across subspecialties.

Disparities in all-cause mortality with potentially inappropriate medication use: Analysis of the Reasons for Geographic and Racial Differences in Stroke study.

OBJECTIVES: Health disparities across different socioeconomic subgroups have been reported in previous studies. Mortality with potentially inappropriate medication (PIM) use may be subject to similar disparities. We aimed to assess the association between PIM use and all-cause mortality and the effect of disparity parameters (sex, race, income, education, and location of residence) on this relationship. METHODS: This longitudinal cohort study included 26,399 U.S. adults aged 45 years and older from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, of which 13,475 participants were aged 65 years and older (recruited 2003-2007). PIM use and drug-drug interactions (DDIs) were identified through the 2015 Beers Criteria and a clinically significant DDIs list by the American Family Physicians, respectively. Cox regression was used to assess disparities in mortality with PIM use, iteratively adjusting for disparity parameters and other covariates. The full models included interaction terms between PIM use and other covariates. A similar method was used for the analyses of disparities in mortality with DDIs. RESULTS: Approximately 87% of older adults used at least 1 drug listed in the Beers Criteria, and 3.8% of all participants used 2 or more drugs with DDIs. In the adjusted analysis, an increased risk of mortality was observed among whites with PIM use (hazard ratio [HR] = 1.27 [95% CI 1.10-1.47]). The higher mortality rate was observed among blacks without PIM use (1.34 [1.09-1.65]). Lower income and education were independent predictors for higher mortality. CONCLUSION: Racial differences in all-cause mortality with PIM use were observed. Further research is needed to better understand the contributing factors of such disparities to develop appropriate interventions.

Patient and caregiver opinions about an FDA-developed generic drug educational handout: A pilot cross-sectional survey.

OBJECTIVE: To examine patient and caregiver opinions and "receptivity" regarding generic drug educational material in terms of content, format and design, delivery channel, and level of satisfaction. METHODS: Interviewer-administered surveys were conducted with patients and caregivers who were clients of a regional medication management program or pharmacy services clinic to gather perceptions about generic drugs and input on a generic drug educational handout developed by the U.S. Food and Drug Administration (FDA). Survey questions were developed by the investigators and pretested before use. Data were analyzed using descriptive statistics, and responses to open-ended questions were assessed using qualitative content analysis. Survey psychometrics were examined using exploratory factor analysis (EFA). RESULTS: Of the 100 survey participants, most (93%) had positive perceptions about generic drug safety and effectiveness after reading the handout. Most participants were satisfied or very satisfied with the handout's content (87%) as well as format and design (92%). However, more than 20% of participants were still unsure about the benefits and risks of generic drugs compared with those of brand drugs, and more than 15% were still unsure about which benefits and risks mattered most to them. The participants' preferred source for the handout was a pharmacy (49%) or doctor's office (27%). In an EFA of the survey instrument, 2 factors emerged related to the educational handout's content: (1) generic drug information, a 7-item factor (Cronbach alpha = 0.882); and (2) personal relevance, a 3-item factor (Cronbach alpha = 0.692). CONCLUSION: The findings indicate an overall positive "receptiveness" toward generic drug informational materials from patients and caregivers, which highlights the feasibility and importance of educational outreach programs about generic drugs targeted toward this population. Future studies may focus on more diverse populations and tailor materials to the needs of specific patient and caregiver subgroups and health literacy levels.

COVID-19 pneumonia: CD8+ T and NK cells are decreased in number but compensatory increased in cytotoxic potential.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is posing a huge threat to human health worldwide. We aim to investigate the immune status of CD8+ T and NK cells in COVID-19 patients. METHODS: The count and immune status of lymphocytes were detected by flow cytometry in 32 COVID-19 patients and 18 healthy individuals. RESULTS: As the disease progression in COVID-19 patients, CD8+ T and NK cells were significantly decreased in absolute number but highly activated. After patients' condition improved, the count and immune status of CD8+ T and NK cells restored to some extent. GrA+CD8+ T and perforin+ NK cells had good sensitivity and specificity for assisting diagnosis of COVID-19. CONCLUSIONS: As the disease progression, the declined lymphocytes in COVID-19 patients might lead to compensatory activation of CD8+ T and NK cells. GrA+CD8+ T and perforin+ NK cells might be used as meaningful indicators for assisting diagnosis of COVID-19.

Chalcogenide Photonic Crystals Fabricated by Soft Imprint-Assisted Photodoping of Silver.

This work presents a low-cost, large-scale nanofabrication approach that combines imprint lithography and silver doping (IL-SD) to pattern chalcogenide glass (ChG) films for realizing IR devices. The IL-SD method involves controled photodoping of silver (Ag) atoms into ChG films and selective removing of undoped ChG. For photodoping of Ag, an Ag-coated elastomer stamp is brought in contact with the ChG film and exposed to ultraviolet light, and subsequently, the Ag atoms are photo-dissolved into the ChG film following the nanopatterns on the elastomer stamp. Due to the high wet-etching selectivity of the undoped ChG to Ag-doped one, the ChG film can be precisely patterned with a spatial resolution on the order of a few tens of nanometers. Also, by controling the lateral diffusion of Ag atoms during ultraviolet exposure, it is possible to adjust the size of the final patterns formed in the ChG film. As an application demonstration of the IL-SD process, the As2 S3 -based near-infrared photonic crystals (PhCs) in the wavelength range and flexible midinfrared PhCs are formed, and their optical resonances are investigated. The IL-SD process enables the low-cost fabrication of ChG nanostructures on different substrate materials and gives a great promise to realize various IR devices.