Andexanet alfa after 4-factor PCC administration for intracranial hemorrhage: a case series

Journal of Thrombosis and Thrombolysis - The ongoing controversy regarding optimal reversal agent for factor Xa-inhibitors is mainly due to lack of comparative data of andexanet alfa (AA) to...     

Collaborating toward equity in Pennsylvania: The Age-Friendly Care,PA project

Objective

To collaboratively implement the age-friendly health systems framework, known as the 4Ms: What Matters, Medication, Mentation, and Mobility, at The Primary Health Network (PHN), a federally qualified health center.

Data Sources

Data were collected from PHN electronic medical records (EMRs) for individuals over age 65 from December 30, 2019 to December 24, 2021 and from Project ECHO© attendance and evaluation surveys.

Study Design

The telementoring educational program, Project ECHO©, was used to engage PHN health care professionals working in rural areas of Pennsylvania to incorporate the 4Ms into their practice starting with the annual wellness visit (AWV). Project ECHO© was launched at three primary care sites. After 18 months, it was then disseminated to an additional 18 sites creating pilot and comparison groups. Outcomes included codesigned patient process metrics using EMR data and project ECHO© participant data.

Data Collection Methods

EMR data were generated by system reports created by PHN's quality assurance program manager. Project ECHO© data were collected and managed using REDCap electronic data capture tools. Outcomes were aggregated, analyzed for trends over time, and compared between groups.

Principal Findings

All nine process outcomes increased from baseline to follow-up at the three initial sites, ranging from 4% to 43% g. At year two, the three initial sites had higher rates on AWVs (pilot 24%, comparison 12%; p < 0.0001), Advance Care Planning (New on file, pilot 8%, comparison 2%; Discussed with patient, pilot 18%, comparison 13%; Patient declined, pilot 0%, comparison 0%; p = 0.0001), Dementia Screening (pilot 24%, comparison 12%; p < 0.0001), Fall Risk Management (pilot 43%, comparison 10%; p < 0.0001), and Mobility Goal (pilot 19%, comparison 9%; p < 0.0001); and lower rates on High-Risk Medication Elimination (pilot 54%, comparison, 63%, p < 0.02).

Conclusions

Access to high-quality geriatric care for rural older adults can be improved by increasing health care professionals' knowledge of the 4Ms, beginning with its incorporation into the AWV.     

Intermediate-term outcomes of combined phacoemulsification and Aurolab aqueous drainage implant in eyes with refractory glaucoma and coexistent cataract

International Ophthalmology - To investigate the efficacy and safety of non-valved Aurolab aqueous drainage implant (AADI) surgery combined with phacoemulsification in eyes with refractory glaucoma...     

Effects of state reinsurance programs on health insurance exchange premiums and insurer participation

Objective

The aim of the study was to estimate the effect of the state-based reinsurance programs through the section 1332 State Innovation Waivers on health insurance marketplace premiums and insurer participation.

Data Source

2015 to 2022 Robert Wood Johnson Foundation Health Insurance Exchange Compare Datasets.

Study Design

An event study difference-in-differences (DD) model separately for each year of implementation and a synthetic control method (SCM) are used to estimate year-by-year effects following program implementation.

Data Collection/Extraction Methods

Not applicable.

Principal Findings

Reinsurance programs were associated with a decline in premiums in the first year of implementation by 10%–13%, 5%–19%, and 11%–17% for bronze, silver, and gold plans (p < 0.05). There is a trend of sustained declines especially for states that implemented their programs in 2019 and 2020. The SCM analyses suggest some effect heterogeneity across states but also premium declines across most states. There is no evidence that reinsurance programs affected insurer participation.

Conclusion

State-based reinsurance programs have the potential to improve the affordability of health insurance coverage. However, reinsurance programs do not appear to have had an effect on insurer participation, highlighting the need for policy makers to consider complementary strategies to encourage insurer participation.     

4′‐Bromo‐resveratrol,a dual Sirtuin‐1 and Sirtuin‐3 inhibitor,inhibits melanoma cell growth through mitochondrial metabolic reprogramming

Sirtuin‐1 and ‐3 (SIRT1 and SIRT3) are important nicotinamide adenine dinucleotide (NAD⁺)‐dependent deacetylases known to regulate a variety of cellular functions. Studies have shown that SIRT1 and SIRT3 were overexpressed in human melanoma cells and tissues and their inhibition resulted in a significant antiproliferative response in human melanoma cells and antitumor response in a mouse xenograft model of melanoma. In this study, we determined the antiproliferative efficacy of a newly identified dual small molecule inhibitor of SIRT1 and SIRT3, 4′‐bromo‐resveratrol (4′‐BR), in human melanoma cell lines (G361, SK‐MEL‐28, and SK‐MEL‐2). Our data demonstrate that 4′‐BR treatment of melanoma cells resulted in (a) decrease in proliferation and clonogenic survival; (b) induction of apoptosis accompanied by a decrease in procaspase‐3, procaspase‐8, and increase in the cleavage of caspase‐3 and poly (ADP‐ribose) polymerase (PARP); (c) marked downregulation of proliferating cell nuclear antigen (PCNA); and (d) inhibition of melanoma cell migration. Further, 4′‐BR caused a G0/G1 phase arrest of melanoma cells that was accompanied by an increase in WAF‐1/P21 and decrease in Cyclin D1/Cyclin‐dependent kinase 6 protein levels. Furthermore, we found that 4′‐BR causes a decrease in lactate production, glucose uptake, and NAD⁺/NADH ratio. These responses were accompanied by downregulation in lactate dehydrogenase A and glucose transporter 1 in melanoma cells. Collectively, our data suggest that dual inhibition of SIRT1 and SIRT3 using 4′‐BR imparted antiproliferative effects in melanoma cells through a metabolic reprogramming and affecting the cell cycle and apoptosis signaling. Therefore, concomitant pharmacological inhibition of SIRT1 and SIRT3 needs further investigation for melanoma management.     

Defining breakthrough invasive fungal infection–Position paper of the mycoses study group education and research consortium and the European Confederation of Medical Mycology

Breakthrough invasive fungal infections (IFIs) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG‐ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed and circulated to all members of the two organisations for comment and suggestions. The authors addressed comments received and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non‐response to treatment. Relapsed IFI occurs after treatment and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.