Acceptability and Utility of a Digital Group Intervention to Prevent Perinatal Depression in Youths via Interactive Maternal Group for Information and Emotional Support (IMAGINE): Pilot Cohort Study.

BACKGROUND: Perinatal depression (depression during pregnancy or the first year postpartum) affects 10%-25% of perinatal individuals, with a higher risk among youths aged <25 years. The Mothers and Babies Course (MB) is an evidence-based intervention for the prevention of perinatal depression, grounded in cognitive behavioral therapy, attachment theory, and psychoeducation. OBJECTIVE: We developed a digital adaptation of MB (Interactive Maternal Group for Information and Emotional Support [IMAGINE]) and evaluated it in a pre-post mixed methods pilot among young perinatal people in the United States. METHODS: IMAGINE was a structured digital group of up to 7 participants, with scheduled MB content and open discussion for 12 weeks, facilitated by a social worker. Scheduled content included asynchronous SMS text messages, graphics, prerecorded videos, mood polls, and optional weekly synchronous video calls. Eligible participants were pregnant or ≤80 days postpartum, aged 16 to 24 years, had access to a smartphone, spoke English, and had a Patient Health Questionnaire score <10. Participants were recruited throughout the United States from August 2020 to January 2021 through paid social media ads, in-person outreach at clinics, and respondent-driven sampling. Participants completed quantitative questionnaires at enrollment and 3 months, and qualitative interviews at 3 months. We determined uptake, acceptability (by Acceptability of Intervention Measure score), and utility (by use of cognitive behavioral therapy skills). We compared depression symptoms (by Patient Health Questionnaire score), social support (by abbreviated Social Support Behavior score), and perceived stress (by Perceived Stress Score) between enrollment and follow-up by paired 2-tailed t test. RESULTS: Among 68 individuals who contacted this study, 22 were screened, 13 were eligible, and 10 enrolled, for an uptake of 76.9%. Furthermore, 4 (40%) participants were pregnant at enrollment. Participants had a median age of 17.9 (IQR 17.4-21.7) years, 6 (67%) identified as Black, 5 (56%) Latinx, and 6 (67%) using Medicaid health insurance. Further, 9 (90%) participants completed follow-up. Among these, the mean acceptability score was 4.3 out of 5 (SD 0.6) and all participants said they would recommend IMAGINE to a friend. Participants reported using a median of 7 of 11 skills (IQR 5-7 skills) at least half the days. We found no significant changes in depression symptoms, perceived stress, or social support. Qualitatively, participants reported one-to-one support from the facilitator, connection with other parents, and regular mood reflection were especially helpful aspects of the intervention. Additionally, participants reported that the intervention normalized their mental health challenges, improved their ability to manage their mood, and increased their openness to mental health care. CONCLUSIONS: This pilot study provides promising evidence of the acceptability and utility of IMAGINE among perinatal youths. Our study's small sample size did not detect changes in clinical outcomes; our findings suggest IMAGINE warrants larger-scale evaluation.

Supreme Court Impacts in Public Health Law: 2022-2023.

In another tumultuous term of the United States Supreme Court in 2022-2023 a series of critical cases implicate instant and forthcoming changes in multiple fronts that collectively shift the national public health law and policy environment.

Midterm Maelstrom: Public Health Legal Impacts of Election 2022.

Among the morass of critical issues impacting the results of the midterm elections in 2022 were core public health issues related to health care access, justice, and reforms. Collectively, voters' communal health and safety concerns dominated outcomes in key races which may shape national, state, and local legal approaches to protecting the public's health in the modern era.

Medicare Drug Pricing Negotiations: Assessing Constitutional Structural Limits.

A series of structural constitutional arguments lodged in multiple cases against Centers for Medicare and Medicaid Services' (CMS) authorities to negotiate prescription drug prices via the 2022 Inflation Reduction Act threaten the legitimacy of CMS program and federal agency powers.

Supreme Court Impacts in Public Health Law: 2021-2022.

In a dynamic term of the United States Supreme Court in 2021-2022 a series of critical cases raise manifold changes and impacts on individual and communal health through 10 key areas ranging from abortions to vaccinations.

Regressive Federalism, Rights Reversals, and the Public's Health.

As the United States emerges from the worst public health threat it has ever experienced, the Supreme Court is poised to reconsider constitutional principles from bygone eras. Judicial proposals to roll back rights under a federalism infrastructure grounded in states' interests threaten the nation's legal fabric at a precarious time. This column explores judicial shifts in 3 key public health contexts - reproductive rights, vaccinations, and national security - and their repercussions.

Quality indicators of psychotropic prescribing to people with dementia in aged psychiatry inpatient units.

OBJECTIVES: To develop indicators of safe psychotropic prescribing practices for people with dementia and to test them in a convenience sample of six aged mental health services in Victoria, Australia. METHOD: The clinical records of 115 acute inpatients were checked by four trained auditors against indicators derived from three Australian health care quality and safety standards or guidelines. Indicators addressed psychotropic medication history taking; the prescribing of regular and 'as needed' psychotropics; the documentation of psychotropic adverse reactions, and discharge medication plans. RESULTS: The most problematic areas concerned the gathering of information about patients' psychotropic prescribing histories at the point of entry to the ward and, later, the handing over on discharge of information concerning newly prescribed treatments and the reasons for ceasing medications, including adverse reactions. There were wide variations between services. CONCLUSION: The indicators, while drawn from current Australian guidelines, were entirely consistent with current prescribing frameworks and provide useful measures of prescribing practice for use in benchmarking and other quality improvement activities.

The Clinical and Service Outcomes of Unilateral and Bilateral ECT Electrode Placements in Australian Aged Psychiatry Services.

OBJECTIVE: The aim of the study was to determine whether depressed aged inpatients treated with brief pulse unilateral electroconvulsive therapy (ECT) differed from those treated with bilateral (bitemporal or bifrontal) ECT with respect to numbers of treatments, length of hospital admission, changes in scores on depression and cognitive scales, and serious adverse effects. METHODS: An audit of routinely collected data regarding 221 acute ECT courses in 7 public aged psychiatry services in Victoria, Australia. RESULTS: Patients given unilateral, bifrontal, and bitemporal treatments were similar with respect to personal, clinical, and treatment characteristics. Most treatments were administered in line with local clinical guidelines and were rated as effective. Psychiatrists preferred unilateral ECT in the first instance with stimulus dosing based on patients' seizure thresholds. Approximately a quarter of unilateral courses were switched later to bitemporal placement, most probably because of insufficient progress. Bilateral treatments were associated with a larger number of treatments, less improvement in scores on mood and cognitive scales, and more refusals to continue treatment than unilateral-only ECT. DISCUSSION: Brief pulse unilateral ECT proved more effective than bitemporal and bifrontal ECT for most aged patients, especially when coupled with stimulus dosing based on seizure threshold.

Determinants of patient screen failures in Phase 1 clinical trials.

OBJECTIVE: Certain eligibility criteria for Phase 1 cancer clinical trials may impede successful patient enrollment onto a study. We evaluated patient-specific or study-specific reasons for screen failures on Phase 1 oncology clinical trials and discuss factors which may inhibit subject enrollment. METHODS: Thirty-eight Phase 1 clinical trials for solid tumors meeting eligibility criteria and opened for enrollment between February 2006 and February 2011 at one oncology Phase 1 program were examined. Categorical reasons for screen failures and patients' demographics were examined and compared to characteristics of patients that successfully enrolled on a Phase 1 trial. RESULTS: There were a total of 583 successful Phase 1 enrollment and dose administration events out of 773 Phase 1 consent events (75.4 % dose success rate). The three most common reasons for screen failure were: out of protocol-specified range for chemistry, development of an interval medical issue that precluded proceeding with study participation, and subject declining participation after signing consent. Living further away from the Phase 1 program and receipt of fewer prior lines of systemic chemotherapy were significantly associated with increased screen failures. CONCLUSION: Screen failures for Phase 1 studies are not uncommon (24.6 %). When a protocol required tumor or host analyte is not required, most screen failures are due to out of protocol-specified range for chemistry or the development of an interval medical issue. Screen failure rates were increased when patients had longer travel distances and fewer prior lines of systemic chemotherapy.

A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors.

PURPOSE: This study was designed to establish the maximum tolerated dose (MTD) and to evaluate tolerability, pharmacokinetics, and antitumor activity of etirinotecan pegol. EXPERIMENTAL DESIGN: Patients with refractory solid malignancies were enrolled and assigned to escalating-dose cohorts. Patients received 1 infusion of etirinotecan pegol weekly 3 times every 4 weeks (w × 3q4w), or every 14 days (q14d), or every 21 days (q21d), with MTD as the primary end point using a standard 3 + 3 design. RESULTS: Seventy-six patients were entered onto 3 dosing schedules (58-245 mg/m(2)). The MTD was 115 mg/m(2) for the w × 3q4w schedule and 145 mg/m(2) for both the q14d and q21d schedules. Most adverse events related to study drug were gastrointestinal disorders and were more frequent at higher doses of etirinotecan pegol. Late onset diarrhea was observed in some patients, the frequency of which generally correlated with dose density. Cholinergic diarrhea commonly seen with irinotecan treatment did not occur in patients treated with etirinotecan pegol. Etirinotecan pegol administration resulted in sustained and controlled systemic exposure to SN-38, which had a mean half-life of approximately 50 days. Overall, the pharmacokinetics of etirinotecan pegol are predictable and do not require complex dosing adjustments. Confirmed partial responses were observed in 8 patients with breast, colon, lung (small and squamous cell), bladder, cervical, and neuroendocrine cancer. CONCLUSION: Etirinotecan pegol showed substantial antitumor activity in patients with various solid tumors and a somewhat different safety profile compared with the irinotecan historical profile. The MTD recommended for phase II clinical trials is 145 mg/m(2) q14d or q21d.

Progression-free Survival Decreases with Each Subsequent Therapy in Patients Presenting for Phase I Clinical Trials.

BACKGROUND: There is often a finite progression-free interval of time between one systemic therapy and the next when treating patients with advanced cancer. While it appears that progression-free survival (PFS) between systemic therapies tends to get shorter for a number of factors, there has not been a formal evaluation of diverse tumor types in an advanced cancer population treated with commercially-available systemic therapies. METHODS: In an attempt to clarify the relationship between PFS between subsequent systemic therapies, we analyzed the records of 165 advanced cancer patients coming to our clinic for consideration for participation in six different phase I clinical trials requiring detailed and extensive past medical treatment history documentation. RESULTS: There were 77 men and 65 women meeting inclusion criteria with a median age at diagnosis of 55.3 years (range 9.4-81.6). The most common cancer types were colorectal (13.9%), other gastrointestinal (11.8%), prostate (11.8%). A median of 3 (range 1-11) systemic therapies were received prior to phase I evaluation. There was a significant decrease in PFS in systemic therapy for advanced disease from treatment 1 to treatment 2 to treatment 3 (p = 0.002), as well as, from treatment 1 through treatment 5 (p < 0.001). CONCLUSIONS: In an advanced cancer population of diverse tumor types, we observe a statistically significant decrease in PFS with each successive standard therapy. Identification of new therapies that reverse this trend of decreasing PFS may lead to improved clinical outcomes.

18-FDG PET/CT assessment of basal cell carcinoma with vismodegib.

The use of 18-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT) in subjects with advanced basal cell carcinoma (BCC) has not been fully explored due to the rarity of disease presentation. This study evaluated PET/CTs from subjects with advanced BCC participating in a phase I dose-escalation clinical trial of vismodegib. Fourteen subjects with BCC were imaged with 18-FDG PET/CT for lesion identification and response categorizing (European Organisation for Research and Treatment for Cancer [EORTC] and PET response criteria in solid tumors [PERCIST] 1.0). Several parameters including metabolic activity of target lesions, site of disease presentation and spread, treatment response, and prognostic significance of metabolic activity following therapy were evaluated. All subjects exhibited at least one hypermetabolic lesion. Most subjects had only four organ systems involved at study enrollment: skin-muscle (93%), lung (57%), lymph nodes (29%), and bone (21%). SUVmax measured across all lesions decreased (median 33%, SD ± 45%) following therapy with metabolic activity normalizing or disappearing in 42% of lesions. No significant difference was observed between EORTC and PERCIST 1.0. Subjects that demonstrated at least a 33% reduction in SUVmax from baseline had a significantly longer progression-free survival (PFS) (median 17 months, 95% confidence interval [CI] ±4 months vs. 9 months, 95% CI ±5 months, P = 0.038) and overall survival (OS) (median 24 months, 95% CI ±4 months vs. 17 months, 95% CI ±13 months, P = 0.019). BCC lesions are hypermetabolic on 18-FDG PET/CT. A decrease in SUVmax was associated with improved PFS and OS. These results further support the incorporation of 18-FDG PET/CT scans in advanced BCC management.

Long-term safety, tolerability, and efficacy of vismodegib in two patients with metastatic basal cell carcinoma and basal cell nevus syndrome.

Tumor responses in advanced basal cell carcinoma (BCC) have been observed in clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism is inhibition Hedgehog Signaling Pathway (HHSP) downstream target genes. HHSP inhibition has been shown to affect stem cells responsible for blood, mammary, and neural development. We report on our experience of treating two patients with advanced BCC participating. These two patients have had no new BCCs develop for at least 2.25 years. Both patients have been receiving ongoing daily treatment with vismodegib for greater than 2.75 years without experiencing any significant side effects. After prolonged continuous daily dosing with a SMO antagonist, we have not observed a significant alteration in hematologic parameters or physical abnormalities of the pectoral regions of two patients with advanced BCC.

Continuation-maintenance electroconvulsive therapy: quality standards in 3 Australian aged psychiatry services.

OBJECTIVE: To check if experienced psychiatrists in Victoria, Australia, observed the standards outlined by the American Psychiatric Association and the Royal College of Psychiatrists regarding the administration and monitoring of continuation-maintenance electroconvulsive therapy (ECT). METHODS: A retrospective chart review of 60 consecutive patients given continuation-maintenance ECT in 3 Victorian public aged psychiatry services. RESULTS: Practice guidelines were often not observed concerning documentation of treatment plans, mental state reviews and patients' and carers' viewpoints. CONCLUSIONS: Continuation-maintenance ECT proved highly effective in this clinical sample. Our audit identifies areas for improvement in clinical practice. It will be helpful to have a simple checklist of treatment plans, rating scale scores, and discussions with patients and carers that clinicians can complete at regular intervals.

The effectiveness of continuation-maintenance ECT in reducing depressed older patients' hospital re-admissions.

BACKGROUND: We report on the outcomes in aged patients with severe, treatment-resistant depression or psychosis who were given ongoing outpatient continuation-maintenance ECT of varying duration to prevent remission and relapse following a successful course of acute ECT. METHODS: A retrospective chart review of 58 consecutive patients of three Australian aged psychiatry services comparing the number and length of psychiatric admissions before and after the start of continuation-maintenance ECT. RESULTS: Four patients had only one treatment and two received over 50 (mean 14.7). Five were still enrolled in a maintenance program two years later. In the two years after continuation-maintenance ECT started, admissions fell by 53% in number and 79% in duration compared with the previous two years. Within the actual treatment period which varied from one patient to another, admissions fell by 90% in number and 97% in duration compared with the same period beforehand. CONCLUSION: A treatment effect cannot be proven but the severity and chronicity of patients' conditions make placebo effects and spontaneous remission unlikely. Randomised, controlled trials are almost impossible in this setting and so carefully conducted reviews and case-control studies are still of value. Our findings suggest that continuation-maintenance ECT is effective in carefully selected patients at high risk of relapse.