In difficult-to-treat depression (DTD) the outcome metrics historically used to evaluate treatment effectiveness may be suboptimal. Metrics based on remission status and on single end-point (SEP) assessment may be problematic given infrequent symptom remission, temporal instability, and poor durability of benefit in DTD.

Self-report and clinician assessment of depression symptom severity were regularly obtained over a 2-year period in a chronic and highly treatment-resistant registry sample (N = 406) receiving treatment as usual, with or without vagus nerve stimulation. Twenty alternative metrics for characterizing symptomatic improvement were evaluated, contrasting SEP metrics with integrative (INT) metrics that aggregated information over time. Metrics were compared in effect size and discriminating power when contrasting groups that did (N = 153) and did not (N = 253) achieve a threshold level of improvement in end-point quality-of-life (QoL) scores, and in their association with continuous QoL scores.

Metrics based on remission status had smaller effect size and poorer discrimination of the binary QoL outcome and weaker associations with the continuous end-point QoL scores than metrics based on partial response or response. The metrics with the strongest performance characteristics were the SEP measure of percentage change in symptom severity and the INT metric quantifying the proportion of the observation period in partial response or better. Both metrics contributed independent variance when predicting end-point QoL scores.

Revision is needed in the metrics used to quantify symptomatic change in DTD with consideration of INT time-based measures as primary or secondary outcomes. Metrics based on remission status may not be useful.

Innovative shoe insoles, designed to enhance sensory information on the plantar surface of the feet, could help to improve walking in people with Multiple Sclerosis.

To compare the effects of wearing textured versus smooth insoles, on measures of gait, foot sensation and patient-reported outcomes, in people with Multiple Sclerosis.

A prospective, randomised controlled trial was conducted with concealed allocation, assessor blinding and intention-to-treat analysis. Thirty ambulant men and women with multiple sclerosis (MS) (Disease Steps rating 1–4) were randomly allocated to wear textured or smooth insoles for 12 weeks. Self-reported insole wear and falls diaries were completed over the intervention period. Laboratory assessments of spatiotemporal gait patterns, foot sensation and proprioception, and patient-reported outcomes, were performed at Weeks 0 (Baseline 1), 4 (Baseline 2) and 16 (Post-Intervention). The primary outcome was the size of the mediolateral base of support (stride/step width) when walking over even and uneven surfaces. Independent t-tests were performed on change from baseline (average of baseline measures) to post-intervention.

There were no differences in stride width between groups, when walking over the even or uneven surfaces (P ≥ 0.20) at post-intervention. There were no between-group differences for any secondary outcomes including gait (all P values > 0.23), foot sensory function (all P values ≥ 0.08) and patient-reported outcomes (all P values ≥ 0.23).

In our small trial, prolonged wear of textured insoles did not appear to alter walking or foot sensation in people with MS who have limited foot sensory loss. Further investigation is needed to explore optimal insole design.

Australian and New Zealand Clinical Trials Registry (ACTRN12615000421538).

Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse.

This study aims to evaluate whether the Engager intervention improves mental health outcomes following release.

The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3–5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT).

In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI –1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact.

Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

Ketamine, an N-methyl-d-aspartate receptor antagonist, has been “repurposed” as a rapid-acting antidepressant for treatment-resistant depression (TRD). The s-enantiomer of ketamine, “esketamine,” was FDA approved for TRD and depressive symptoms in adults with major depressive disorder with suicidal ideations/behaviors. Intravenous (IV) ketamine, although financially less expensive, is often not covered by insurance and intranasal (IN) esketamine, although covered by insurance can be expensive. There is a paucity of literature on efficacy data comparing subanesthetic IV ketamine and IN esketamine for TRD in a real-world scenario. Thus, we conducted this study comparing the efficacy and the number of treatments required to achieve remission/response with repeated use of subanesthetic IV ketamine/IN esketamine among TRD patients.

This was an observational study where we included adults (≥18 years) with TRD who provided consent and had received up to 6 IV ketamine infusions (0.5 mg/kg, infused over 40 minutes) or up to 8 intranasal (IN) esketamine (56/84 mg) treatments for TRD at the Mayo Clinic Depression Center. Depression symptoms were measured utilizing the self-report 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale before and 24 hours after ketamine/esketamine treatment. Remission and response were defined as QIDS-SR 16 score ≤5 and ≥50% change in QIDS-SR 16, respectively. Continuous variables are reported as means ± SD and categorical variables as counts and percentages. The Wilcoxon rank-sum test was used to compare continuous variables. Chi-square and Fisher’s exact tests were used to compare categorical variables. The number of treatments to remission/response was calculated.

Sixty-three adults with TRD, middle-aged (47.0 ± 12.1 years), predominantly female (65%), of which 76% (n = 48) and 24% (n = 15) received IV ketamine and IN esketamine, respectively. Mean (SE) change in QIDS-SR 16 score was −8.7 ± 0.7 (P < .001), a significant reduction (improvement) from baseline (mean ± SD = 17.6 ± 3.7). Overall remission and response rates were 36.5% and 55.6%, respectively in the acute phase. Response (56.3% vs 53.3%) and remission rates (39.6% vs 26.7%) were similar among patients who received IV ketamine or IN esketamine, respectively (P > .05). The mean number of treatments received to achieve response (2.5 ± 1.6 vs 4.6 ± 2.1) and remission (2.4 ± 1.3 vs 6.3 ± 2.4) were significantly lower among patients who received IV ketamine compared to IN esketamine (P < .005). Most patients tolerated both treatments well.

Intravenous ketamine and intranasal esketamine showed similar response/remission in TRD patients but the number of treatments required to achieve response/remission was significantly lower with IV ketamine compared to IN esketamine. These findings need to be investigated in a randomized control trial comparing these two treatment interventions.

No funding

Schizophrenia-related, health, social, and fiscal consequences are substantial, affecting patients, caregivers, and society. The incidence of health, social, and fiscal outcomes are frequently reported for the overall schizophrenia population, not stratified by remission or relapse status.

This study aimed to assess healthcare resource use, employment status, and housing circumstances for patients with schizophrenia in remission or relapse, compared to the overall schizophrenia population.

The Adelphi Schizophrenia Disease Specific Programme was a point-in-time survey conducted across the USA between July and October 2019. Remission was defined using Clinical Global Impression-Severity (CGI-S) score of 1-3 (stable), with relapse defined as a CGI-S score of 4-7 (unstable). Outcome-specific rate ratios were calculated by dividing the cumulative incidence for those in remission or relapse by the cumulative incidence of the overall schizophrenia population. Ratios greater than 1 indicate a higher probability of the event.

Psychiatrists (n = 124) provided data for 409 patients in remission and 609 patients in relapse. Patients with schizophrenia in remission were more likely to be employed (1.66, 95% confidence interval [1.46-1.90]) and to live with a partner or family (1.08 [1.01-1.17]) compared to the overall schizophrenia population, whereas patients in relapse were more likely to experience hospitalizations in the previous 12 months (1.34 [1.19-1.15]), disability-related unemployment (1.38 [1.25-1.51]), sick leave absences (1.23 [0.66-2.31]), need to support housing (1.39 [1.08-1.79]), and homelessness (1.47 [0.95-2.27]).

Schizophrenia patients in relapse were more likely to experience hospitalizations, unemployment, and have unfavorable housing circumstances compared to the overall schizophrenia population. Identifying patients at risk of relapse may aid physicians in targeting interventional support, thereby reducing the burden of schizophrenia.

Sunovion Pharmaceuticals

Physician-scientists have long been in high demand owing to their role as key drivers of biomedical innovation, but their dwindling prevalence in research and medical communities threatens ongoing progress. As the principal avenue for physician-scientist development, combined MD–PhD training programs and NIH-funded Medical Scientist Training Programs (MSTPs) must address all aspects of career development, including grant writing skills.

The NIH F-series grants – the F30 grant in particular – model the NIH format of federal funding, and are thus ideal opportunities to acquire biomedical research grant preparation experience. Therefore, in this report, we describe a curricular model through which predoctoral MSTP students obtain exposure to – and training for – F-series grant conceptualization, writing, and evaluation.

Since the development of these longitudinal courses, we observed trending improvements in student funding success rates, particularly among original submissions, and perceived benefits among participating students.