Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis.

OBJECTIVE: To meta-analyze clinical efficacy and safety of ketamine compared with other anesthetic agents in the course of electroconvulsive therapy (ECT) in major depressive episode (MDE). METHODS: PubMed/MEDLINE, Cochrane Library, Embase, GoogleScholar, and US and European trial registries were searched from inception through May 23, 2023, with no language limits. We included RCTs with (1) a diagnosis of MDE; (2) ECT intervention with ketamine and/or other anesthetic agents; and (3) measures included: depressive symptoms, cognitive performance, remission or response rates, and serious adverse events. Network meta-analysis (NMA) was performed to compare ketamine and 7 other anesthetic agents. Hedges' g standardized mean differences (SMDs) were used for continuous measures, and relative risks (RRs) were used for other binary outcomes using random-effects models. RESULTS: Twenty-two studies were included in the systematic review. A total of 2322 patients from 17 RCTs were included in the NMA. The overall pooled SMD of ketamine, as compared with propofol as a reference group, was -2.21 (95% confidence interval [CI], -3.79 to -0.64) in depressive symptoms, indicating that ketamine had better antidepressant efficacy than propofol. In a sensitivity analysis, however, ketamine-treated patients had a worse outcome in cognitive performance than propofol-treated patients (SMD, -0.18; 95% CI, -0.28 to -0.09). No other statistically significant differences were found. CONCLUSIONS: Ketamine-assisted ECT is tolerable and may be efficacious in improving depressive symptoms, but a relative adverse impact on cognition may be an important clinical consideration. Anesthetic agents should be considered based on patient profiles and/or preferences to improve effectiveness and safety of ECT use.

Reevaluating the Evidence for Intensive Postoperative Extracolonic Surveillance for Nonmetastatic Colorectal Cancer.

OBJECTIVES: The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful. METHODS: A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy. RESULTS: For all 3 trials, the model predicted a mortality reduction of ≤5% and power of <10%. The FACS recurrence imbalance likely led to a large relative bias (>2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P>.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance-routine computed tomography scans and carcinoembryonic antigen assays-with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients. CONCLUSIONS: Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.

A longitudinal evaluation of family caregivers' willingness to pay for an in-home nonpharmacologic intervention for people living with dementia: results from a randomized trial.

OBJECTIVE: To determine the willingness-to-pay (WTP) of family caregivers to learn care strategies for persons living with dementia (PLwD). DESIGN: Randomized clinical trial. SETTING: Community-dwelling PLwD and their caregivers (dyads) in Maryland and Washington, DC. PARTICIPANTS: 250 dyads. INTERVENTION: Tailored Activity Program (TAP) compared to attention control. TAP provides activities tailored to the PLwD and instructs caregivers in their use. MEASUREMENT: At baseline, 3 and 6 months, caregivers were asked their WTP per session for an 8-session 3-month in-home nonpharmacologic intervention to address behavioral symptoms and functional dependence. RESULTS: At baseline, 3 and 6 months, caregivers assigned to TAP were willing to pay $26.10/session (95%CI:$20.42, $33.00), $28.70 (95%CI:$19.73, $39.30), and $22.79 (95%CI: $16.64, $30.09), respectively; attention control caregivers were willing to pay $37.90/session (95%CI: $27.10, $52.02), $30.92 (95%CI: $23.44, $40.94), $27.44 (95%CI: $20.82, $35.34), respectively. The difference in baseline to 3 and 6 months change in WTP between TAP and the attention control was $9.58 (95%CI: -$5.00, $25.47) and $7.15 (95%CI: -$5.72, $21.81). The difference between TAP and attention control in change in the proportion of caregivers willing to pay something from baseline to 3 and 6 months was -12% (95%CI: -28%, -5%) and -7% (95%CI:-25%, -11%), respectively. The difference in change in WTP, among caregivers willing to pay something, between TAP and attention control from baseline to 3 and 6 months was $17.93 (95%CI: $0.22, $38.30) and $11.81 (95%CI: -$2.57, $28.17). CONCLUSIONS: Family caregivers are willing to pay more for an intervention immediately following participation in a program similar to which they were asked to value.

Efficacy and Safety of Ketamine-assisted Electroconvulsive Therapy in Major Depressive Episode: A Systematic Review and Network Meta-Analysis.

Objective: To meta-analyze clinical efficacy and safety of ketamine compared with other anesthetic agents in the course of electroconvulsive therapy (ECT) in major depressive episode (MDE). Methods: PubMed/MEDLINE, Cochrane Library, Embase, GoogleScholar, and US and European trial registries were searched from inception through May 23, 2023, with no language limits. We included RCTs with (1) a diagnosis of MDE; (2) ECT intervention with ketamine and/or other anesthetic agents; and (3) measures included: depressive symptoms, cognitive performance, remission or response rates, and serious adverse events. Network meta-analysis (NMA) was performed to compare ketamine and 7 other anesthetic agents. Hedges' g standardized mean differences (SMDs) were used for continuous measures, and relative risks (RRs) were used for other binary outcomes using random-effects models. Results: Twenty-two studies were included in the systematic review. A total of 2,322 patients from 17 RCTs were included in the NMA. The overall pooled SMD of ketamine, as compared with a propofol reference group, was -2.21 (95% confidence interval [CI], -3.79 to -0.64) in depressive symptoms, indicating that ketamine had better antidepressant efficacy than propofol. In a sensitivity analysis, however, ketamine-treated patients had a worse outcome in cognitive performance than propofol-treated patients (SMD, -0.18; 95% CI, -0.28 to -0.09). No other statistically significant differences were found. Conclusions: Ketamine-assisted ECT is tolerable and may be efficacious in improving depressive symptoms, but a relative adverse impact on cognition may be an important clinical consideration. Anesthetic agents should be considered based on patient profiles and/or preferences to improve effectiveness and safety of ECT use.

Cost-effectiveness of surveillance with CT colonography after resection of colorectal cancer.

OBJECTIVE: Surveillance following colorectal cancer (CRC) resection uses optical colonoscopy (OC) to detect intraluminal disease and CT to detect extracolonic recurrence. CT colonography (CTC) might be an efficient use of resources in this situation because it allows for intraluminal and extraluminal evaluations with one test. DESIGN: We developed a simulation model to compare lifetime costs and benefits for a cohort of patients with resected CRC. Standard of care involved annual CT for 3 years and OC for years 1, 4 and every 5 years thereafter. For the CTC-based strategy, we replace CT+OC at year 1 with CTC. Patients with lesions greater than 6 mm detected by CTC underwent OC. Detection of an adenoma 10 mm or larger was followed by OC at 1 year, then every 3 years thereafter. Test characteristics and costs for CTC were derived from a clinical study. Medicare costs were used for cancer care costs as well as alternative test costs. We discounted costs and effects at 3% per year. RESULTS: For persons with resected stage III CRC, the standard-of-care strategy was more costly (US$293) and effective (2.6 averted CRC cases and 1.1 averted cancer deaths per 1000) than the CTC-based strategy, with an incremental cost-effectiveness ratio of US$55 500 per quality-adjusted life-year gained. Our analysis was most sensitive to the sensitivity of CTC for detecting polyps 10 mm or larger and assumptions about disease progression. CONCLUSION: In a simulation model, we found that replacing the standard-of-care approach to postdiagnostic surveillance with a CTC-based strategy is not an efficient use of resources in most situations.

Yield and Cost-effectiveness of Computed Tomography Colonography Versus Colonoscopy for Post Colorectal Cancer Surveillance.

Purpose. As part of a clinical trial comparing the utility of computed tomographic colonography (CTC) and optical colonoscopy (OC) for post colorectal cancer resection surveillance, we explored the diagnostic yield and costs of a strategy of CTC followed by OC if a polyp is observed (abbreviated CTC_S), versus OC 1 year following curative bowel resection, using the detection of actionable polyps on OC as the criterion. Methods. Using data from 231 patients who underwent same-day CTC followed by OC, we created a decision tree that outlined the choices and outcomes at 1-year clinical follow-up. Colorectal polyp prevalence, sensitivity, and specificity of CTC were compared with five exemplary studies and meta-analyses. Detection criteria were derived for ≥6 mm or ≥10 mm polyps. OC was the gold standard. Costs were gleaned from cataloging components of the cases at the principal investigator's institution. Analyses included marginal cost of the OC strategy to detect additional actionable polyps and number of polyps missed per 10,000 patients. Results. At our prevalence of 0.156 for ≥6 mm (0.043 ≥10 mm), CTC_S would miss 779 ≥6 mm actionable polyps per 10,000 patients (≥10 mm: 173 per 10,000). Cost to detect an additional ≥6 mm polyp in this cohort is $5,700 (≥10 mm: $28,000). Sensitivity analyses demonstrate that any improvement in performance characteristics would raise the cost of OC to detect more actionable polyps. Similar results were seen using Medicare costs, or when literature values were used for performance characteristics. Conclusion. At an action threshold of ≥6 mm, OC costs at least $5,700 per extra polyp detected relative to CTC_S in patients undergoing surveillance after colorectal cancer surgery, on the order of incremental cost-effectiveness ratios found for other clinical problems involving short-term events.

Cost-effectiveness of enhancing a Quit-and-Win smoking cessation program for college students.

OBJECTIVES: We conducted a cost-effectiveness analysis and model-based cost-utility and cost-benefit analysis of increased dosage (3 vs. 1 consecutive contests) and enhanced content (supplemental smoking-cessation counseling) of the Quit-and-Win contest using data from a randomized control trial enrolling college students in the US. METHODS: For the cost-utility and cost-benefit analyses, we used a microsimulation model of the life course of current and former smokers to translate the distribution of the duration of continuous abstinence among each treatment arm's participants observed at the end of the trial (N = 1217) into expected quality-adjusted life-years (QALYs) and costs and an incremental net monetary benefit (INMB). Missing observations in the trial were classified as smoking. For our reference case, we took a societal perspective and used a 3% discount rate for costs and benefits. A probabilistic sensitivity analysis (PSA) was performed to account for model and trial-estimated parameter uncertainty. We also conducted a cost-effectiveness analysis (cost per additional intermediate cessation) using direct costs of the intervention and two trial-based estimates of intermediate cessation: (a) biochemically verified (BV) 6-month continuous abstinence and (b) BV 30-day point prevalence abstinence at 6 months. RESULTS: Multiple contests resulted in a significantly higher BV 6-month continuous abstinence rate (RD 0.04), at a cost of $1275 per additional quit, and increased the duration of continuous abstinence among quitters. In the long run, multiple contests lead to an average gain of 0.03 QALYs and were cost saving. Incorporating parameter uncertainty into the analyses, the expected INMB was greater than $1000 for any realistic willingness to pay (WTP) for a QALY. CONCLUSIONS: Assuming missing values were smoking, multiple contests appear to dominate a single contest from a societal perspective. Funding agencies seeking to promote population health by funding a Quit-and-Win contest in a university setting should strongly consider offering multiple consecutive contests. Further research is needed to evaluate multiple contests compared to no contest.