To compare clinical failure of intravenous vs intravenous with oral step-down antibiotic treatment for Streptococcus and Enterococcus bloodstream infection.

Multicenter, retrospective, cohort study at one academic medical center and eight community hospitals.

Hospitalized adult patients with blood cultures positive for Streptococcus or Enterococcus were included. Patients were excluded if they had complicated infection, had polymicrobial bacteremia, received less than 5 days of therapy, or died before completing therapy.

Patients who completed intravenous therapy were compared with patients who transitioned to oral therapy after 3 to 7 days. The primary endpoint was clinical failure, defined as 90-day all-cause mortality or recurrent bacteremia. The primary analysis excluded patients with unknown outcomes, and the sensitivity analysis treated them as failures.

429 patients were included (intravenous group: n = 225; oral step-down group; n = 204). The intravenous group had more comorbidities and vasopressor use. The intravenous group had a higher risk of clinical failure in the primary analysis (17.5% vs. 8.8%; adjusted OR 2.14 [95% CI, 1.09–4.2]; p = 0.03) while the sensitivity analysis found no difference in clinical failure (adjusted OR 1.1 [95% CI, 0.69–1.74], p = 0.69). The oral step-down group had a mean length of stay of 9.2 days shorter than the intravenous group ([95% CI, 7.5–11.0]; p<0.001).

Oral step-down therapy was not associated with an increased risk of clinical failure compared to a full course of intravenous therapy for uncomplicated Streptococcus and Enterococcus bloodstream infections. Patients with more comorbidities or who required vasopressors were less likely to be switched to oral therapy.

Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.

We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).

Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.

Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

Many factors can impact survey completion rates, including survey length, sensitivity of the topics addressed, and clarity of wording. This study used cognitive interviews (CIs), a methodological tool that can aid in developing and refining elements for multi-faceted assessments, and previous survey response patterns to refine, streamline, and increase response rates of RADx-UP Common Data Elements (CDEs) for survey/questionnaire use.

Ten previously enrolled CO-CREATE study participants were interviewed between May–June 2023. Interviewees identified CDEs that were “confusing, uncomfortable, and/or not applicable,” along with their reasoning. Interview data were analyzed using a rapid qualitative analytic approach, resulting in a summary matrix categorized by language. For further contextualization, CDE response rates were calculated for the 9147 surveys administered during the CO-CREATE study (May 2021–March 2023) and compared against their survey position.

Of the 94 CDEs evaluated in the CIs, 20 (21.3%) were flagged by one or more interviewees. Nine (9.6%) English while fourteen (14.9%) Spanish CDEs were flagged by interviewees, with some overlap. Also, CDE response rates differed according to position in the survey, with lower response rates for questions positioned later in the survey. Following review by the research team and the RADx-UP program, 10 English and 15 Spanish were revised, and seven were removed in both languages in the final survey.

Our findings underscore the importance of integrating community member perspectives to enhance the relevance and clarity of assessment instruments, optimizing the impact of public health research among underrepresented populations.

Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.

To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.

Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.

Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).

These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.