A mixed-methods study of multi-level factors influencing mammography overuse among an older ethnically diverse screening population: implications for de-implementation

Background There is growing concern that routine mammography screening is overused among older women. Successful and equitable de-implementation of mammography will require a multi-level understanding of the factors contributing to mammography overuse. Methods This explanatory, sequential, mixed-methods study collected survey data (n= 52, 73.1% Hispanic, 73.1% Spanish-speaking) from women ≥70 years of age at the time of screening mammography, followed by semi-structured interviews with a subset of older women completing the survey (n=19, 63.2% Hispanic, 63.2% Spanish-speaking) and providers (n=5, 4 primary care, 1 obstetrics and gynecology) to better understand multi-level factors influencing mammography overuse and inform potential de-implementation strategies. We conducted a descriptive analysis of survey data and content analysis of qualitative interview data. Survey and interview data were examined separately, compared, integrated, and organized according to Norton and Chambers Continuum of Factors Influencing De-Implementation Process. Results Survey findings show that 87.2% of older women believe it is important to plan for an annual mammogram, 80.8% received a provider recommendation, and 78.9% received a reminder in the last 12 months to schedule a mammogram. Per interviews with older women, the majority were unaware of or did not perceive to have experienced overuse and intended to continue mammography screening. Findings from interviews with older women and providers suggest that there are multiple opportunities for older women to obtain a mammogram. Per provider interviews, almost all reported that reducing overuse was not viewed as a priority by the system or other providers. Providers also discussed that variation in mammography screening practices across providers, fear of malpractice, and monetary incentives may contribute to overscreening. Providers identified potential strategies to reduce overscreening including patient and provider education around harms of screening, leveraging the electronic health record to identify women who may receive less health benefit from screening, customizing system-generated reminder letters, and organizing workgroups to develop standard processes of care around mammography screening. Conclusions Multi-level factors contributing to mammography overuse are dynamic, interconnected, and reinforced. To ensure equitable de-implementation, there is a need for more refined and empirical testing of theories, models, and frameworks for de-implementation with a strong patient-level component that considers the interplay between multilevel factors and the larger care delivery process

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

Proteins of the bromodomain and extra-terminal (BET) family are epigenetics "readers" and promising therapeutic targets for cancer and other human diseases. We describe herein a structure-guided design of [1,4]oxazepines as a new class of BET inhibitors and our subsequent design, synthesis, and evaluation of proteolysis-targeting chimeric (PROTAC) small-molecule BET degraders. Our efforts have led to the discovery of extremely potent BET degraders, exemplified by QCA570, which effectively induces degradation of BET proteins and inhibits cell growth in human acute leukemia cell lines even at low picomolar concentrations. QCA570 achieves complete and durable tumor regression in leukemia xenograft models in mice at well-tolerated dose-schedules. QCA570 is the most potent and efficacious BET degrader reported to date.http://deepblue.lib.umich.edu/bitstream/2027.42/192135/2/qin-et-al-2018-discovery-of-qca570-as-an-exceptionally-potent-and-efficacious-proteolysis-targeting-chimera-(protac).pdfPublished versio

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

Proteins of the bromodomain and extra-terminal (BET) family are epigenetics “readers” and promising therapeutic targets for cancer and other human diseases. We describe herein a structure-guided design of [1,4]­oxazepines as a new class of BET inhibitors and our subsequent design, synthesis, and evaluation of proteolysis-targeting chimeric (PROTAC) small-molecule BET degraders. Our efforts have led to the discovery of extremely potent BET degraders, exemplified by QCA570, which effectively induces degradation of BET proteins and inhibits cell growth in human acute leukemia cell lines even at low picomolar concentrations. QCA570 achieves complete and durable tumor regression in leukemia xenograft models in mice at well-tolerated dose-schedules. QCA570 is the most potent and efficacious BET degrader reported to date

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

Proteins of the bromodomain and extra-terminal (BET) family are epigenetics “readers” and promising therapeutic targets for cancer and other human diseases. We describe herein a structure-guided design of [1,4]­oxazepines as a new class of BET inhibitors and our subsequent design, synthesis, and evaluation of proteolysis-targeting chimeric (PROTAC) small-molecule BET degraders. Our efforts have led to the discovery of extremely potent BET degraders, exemplified by QCA570, which effectively induces degradation of BET proteins and inhibits cell growth in human acute leukemia cell lines even at low picomolar concentrations. QCA570 achieves complete and durable tumor regression in leukemia xenograft models in mice at well-tolerated dose-schedules. QCA570 is the most potent and efficacious BET degrader reported to date

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

Proteins of the bromodomain and extra-terminal (BET) family are epigenetics “readers” and promising therapeutic targets for cancer and other human diseases. We describe herein a structure-guided design of [1,4]­oxazepines as a new class of BET inhibitors and our subsequent design, synthesis, and evaluation of proteolysis-targeting chimeric (PROTAC) small-molecule BET degraders. Our efforts have led to the discovery of extremely potent BET degraders, exemplified by QCA570, which effectively induces degradation of BET proteins and inhibits cell growth in human acute leukemia cell lines even at low picomolar concentrations. QCA570 achieves complete and durable tumor regression in leukemia xenograft models in mice at well-tolerated dose-schedules. QCA570 is the most potent and efficacious BET degrader reported to date

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

Proteins of the bromodomain and extra-terminal (BET) family are epigenetics “readers” and promising therapeutic targets for cancer and other human diseases. We describe herein a structure-guided design of [1,4]­oxazepines as a new class of BET inhibitors and our subsequent design, synthesis, and evaluation of proteolysis-targeting chimeric (PROTAC) small-molecule BET degraders. Our efforts have led to the discovery of extremely potent BET degraders, exemplified by QCA570, which effectively induces degradation of BET proteins and inhibits cell growth in human acute leukemia cell lines even at low picomolar concentrations. QCA570 achieves complete and durable tumor regression in leukemia xenograft models in mice at well-tolerated dose-schedules. QCA570 is the most potent and efficacious BET degrader reported to date