Family Perceptions of Newborn Cytomegalovirus Screening: A Qualitative Study

We sought to understand long-term retrospective parental perceptions of the utility of newborn screening in a context where many affected children never develop sequelae but where intensive support services and ongoing healthcare were provided. We conducted focus groups and interviews among parents (N = 41) of children with congenital CMV who had been enrolled in a long-term follow-up study at a large medical college for a mean of 22 years following diagnosis. Groups included parents whose children were: symptomatic at birth; initially asymptomatic but later developed sensorineural hearing loss; and who remained asymptomatic into adulthood. With proper follow-up support, newborn CMV screening was viewed positively by parents, who felt empowered by the knowledge, though parents often felt that they and healthcare providers needed more information on congenital CMV. Parents in all groups valued newborn CMV screening in the long term and believed it should be embedded within a comprehensive follow-up program. Despite initial distress, parents of CMV-positive children felt newborn CMV screening was a net positive. Mandatory or opt-out screening for conditions with variable presentations and treatment outcomes may be valuable in contexts where follow-up and care are readily available

Using theory-based messages to motivate U.S. pregnant women to prevent cytomegalovirus infection: results from formative research

Abstract Background An estimated 1 in 150 infants is born each year with congenital cytomegalovirus (CMV); nearly 1 in 750 suffers permanent disabilities. Congenital CMV is the result of a pregnant woman becoming infected with CMV. Educating pregnant women about CMV is currently the best approach to prevention. Limited research is available on how to effectively communicate with women about CMV. We conducted formative research on fear appeals theory-based messages about CMV and prevention with U.S. women. Fear appeal theories suggest that message recipients will take action if they feel fear. Methods First, we conducted in-depth interviews (N = 32) with women who had young children who tested positive for CMV. Second, we conducted eight focus groups (N = 70) in two phases and two cities (Phase 2: Atlanta, GA; Phase 3: San Diego, CA) with pregnant women and non-pregnant women who had young children. Few participants knew about CMV before the focus groups. Participants reviewed and gave feedback on messages created around fear appeals theory-based communication concepts. The following concepts were tested in one or more of the three phases of research: CMV is severe, CMV is common, CMV is preventable, CMV preventive strategies are similar to other behavior changes women make during pregnancy, CMV preventive strategies can be incorporated in moderation to reduce exposure, and CMV is severe but preventable. Results Participants recommended communicating that CMV is common by using prevalence ratios (e.g., 1 in 150) or comparing CMV to other well-known disabilities. To convey the severity of CMV, participants preferred stories about CMV along with prevention strategies. Participants also welcomed prevention strategies when it included a message about risk reduction. In general, participants said messages were motivating, even if they felt that it could be difficult to make certain behavior changes. Conclusions Findings from this research can contribute to future efforts to educate pregnant women about CMV, especially regarding use of fear appeals-based messages. Pregnant women may face certain challenges to practicing prevention strategies but, overall, are motivated make changes to increase their chances of having a healthy baby

Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD-mutated, relapsed or refractory AML.

This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/refractory (R/R) FLT3-internal tandem duplication (ITD)-mutated acute myeloid leukemia (AML) who previously underwent transplant or 1 second-line salvage therapy. Patients (N = 76) were randomly assigned to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency of at least 10% was defined as FLT3-ITD-mutated disease. Coprimary endpoints were composite complete remission (CRc) rates and incidence of QT interval corrected by Fridericia's formula (QTcF) of more than 480 ms (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both groups, similar to earlier reports with higher quizartinib doses. Incidence of QTcF above 480 ms was 11% and 17%, and QTcF above 500 ms was 5% and 3% in the 30- and 60-mg groups, respectively, which is less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in the 60-mg groups than in the 30-mg group. Dose escalation occurred in 61% and 14% of patients in the 30- and 60-mg groups, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day

Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD-mutated, relapsed or refractory AML.

This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/refractory (R/R) FLT3-internal tandem duplication (ITD)-mutated acute myeloid leukemia (AML) who previously underwent transplant or 1 second-line salvage therapy. Patients (N = 76) were randomly assigned to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency of at least 10% was defined as FLT3-ITD-mutated disease. Coprimary endpoints were composite complete remission (CRc) rates and incidence of QT interval corrected by Fridericia's formula (QTcF) of more than 480 ms (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both groups, similar to earlier reports with higher quizartinib doses. Incidence of QTcF above 480 ms was 11% and 17%, and QTcF above 500 ms was 5% and 3% in the 30- and 60-mg groups, respectively, which is less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in the 60-mg groups than in the 30-mg group. Dose escalation occurred in 61% and 14% of patients in the 30- and 60-mg groups, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day