Repeated Preoperative Intranasal Administration of Insulin Decreases the Incidence of Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Radical Gastrointestinal Surgery: A Randomized,Placebo-Controlled,Double-Blinded Clinical Study

Study ObjectivesThis study aimed to investigate the effects of repeated preoperative intranasal administration of insulin on the incidence of postoperative delirium (POD) and the levels of serum pro-inflammatory markers in elderly patients undergoing laparoscopic radical gastrointestinal surgery.DesignProspective, randomized, double-blinded, placebo-controlled clinical study.SettingGeneral Hospital of Western Theater Command from August 2019 to December 2019.PatientsNinety elderly patients underwent laparoscopic radical gastrointestinal tumor resections under general anesthesia.InterventionsPatients were randomly divided into a control group (0.5 mL saline administered intranasally) or an insulin group (20 U/0.5 mL insulin administered intranasally) for 2 days prior to surgery, with 45 patients in each group.MeasurementsThe incidence of delirium was measured at postoperative day 1 (T2), day 3 (T3), and day 5 (T4) using the Confusion Assessment Method for the intensive care unit (CAM-ICU). Plasma levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured at T0 (before insulin or saline administration), T1 (at the end of surgery), T2, T3, and T4 by enzyme-linked immunosorbent assay.Main ResultsCompared with the control group, the insulin group demonstrated a decreased POD incidence (12.5% vs. 47.5%, p = 0.001) within 5 days after surgery. The incidence of POD was significantly lower in the Ins group than in the Con group at T2 (12.5% vs. 32.5%, p = 0.032) and at T3 (2.5% vs. 20%, p = 0.034). The incidence of POD decreased in both groups over time and was similar at T4 (0% vs 10%, p = 0.116). Compared with the baseline value at T0, serum TNF-α, IL-6 and IL-1β concentrations increased significantly at T1-4 (p <0.05). Compared with the control group at the same time point, the expression levels of TNF-α, IL-6 and IL-1β in group I at T2 and T3 were significantly reduced (p <0.05). The incidence rates of adverse events were similar in the two groups.ConclusionsRepeated preoperative intranasal administration of insulin prevented the occurrence of delirium after laparoscopic radical gastrointestinal surgery in elderly patients and reduced TNF-α, IL-1β, and IL-6 levels.     

A Randomized Controlled Trial of Relapse Prevention Therapy for First-Episode Psychosis Patients: Outcome at 30-Month Follow-Up

The effectiveness of a novel 7-month psychosocial treatment designed to prevent the second episode of psychosis was evaluated in a randomized controlled trial at 2 specialist first-episode psychosis (FEP) programs. An individual and family cognitive behavior therapy for relapse prevention was compared with specialist FEP care. Forty-one FEP patients were randomized to the relapse prevention therapy (RPT) and 40 to specialist FEP care. Participants were assessed on an array of measures at baseline, 7- (end of therapy), 12-, 18-, 24-, and 30-month follow-up. At 12-month follow-up, the relapse rate was significantly lower in the therapy condition compared with specialized treatment alone (P = .039), and time to relapse was significantly delayed for those in the relapse therapy condition (P = .038); however, such differences were not maintained. Unexpectedly, psychosocial functioning deteriorated over time in the experimental but not in the control group; these differences were no longer statistically significant when between-group differences in medication adherence were included in the model. Further research is required to ascertain if the initial treatment effect of the RPT can be sustained. Further research is needed to investigate if medication adherence contributes to negative outcomes in functioning in FEP patients who have reached remission, or, alternatively, if a component of RPT is detrimental.     

Predicting Medication Nonadherence in Older Adults With Difficult-to-Treat Depression in the IRL-GRey Randomized Controlled Trial

ObjectiveNonadherence to antidepressants interferes with optimal treatment of late-life depression. This analysis examines clinical and treatment factors predicting medication nonadherence in difficult-to-treat late-life depression.MethodsSecondary analysis of data from a clinical trial of antidepressant pharmacotherapy for Major Depressive Disorder in 468 adults aged 60+ years. All participants received venlafaxine XR for 12 weeks. Nonremitters were randomized to augmentation with either aripiprazole or placebo for 12 additional weeks. Medication adherence was assessed 14 times over 24 weeks. The analyses examined sociodemographic, clinical, and treatment factors that may predict antidepressant nonadherence during early (weeks 1–6), late (weeks 7–12), and augmentation (weeks 13-–24) treatment.ResultsPoor cognitive function and early response were predictive of early nonadherence. Poor cognitive function and prior nonadherence were predictive of late nonadherence. Living alone was associated with nonadherence both late and during augmentation treatment.ConclusionFuture studies should consider the role of early response and cognitive function to improve antidepressant adherence, particularly among older adults who live alone.     

Long-Term Effects of Self-Administered Transcranial Direct Current Stimulation in Episodic Migraine Prevention: Results of a Randomized Controlled Trial

BackgroundMigraine is a multifactorial neurovascular disorder, which affects about 12% of the general population. In episodic migraine, the visual cortex revealed abnormal processing, most likely due to decreased preactivation level. Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and might result in an alleviation of migraine occurrence if used repetitively.ObjectiveTo test the hypothesis that self-administered anodal tDCS over the visual cortex significantly decreases the number of monthly migraine days in episodic migraine.Materials and MethodsThe study was single-blind, randomized, and sham-controlled. Inclusion criteria were age 18–80 years and an ICHD-3 diagnosis of episodic migraine. Exclusion criteria were pregnancy, presence of a neurodegenerative disorder, a contraindication against MRI examinations, and less than two migraine days during the 28-day baseline period. Patients in whom the baseline period suggested chronic migraine were excluded. After baseline, participants applied daily either verum (anodal-1 mA to 20 min) or sham tDCS (anodal-1 mA to 30 sec) at Oz (reference Cz electrode) for 28 days. Headache diaries were used to record the number of migraine days at baseline, during the stimulation period, and during four subsequent 28-day periods.ResultsTwenty-eight patients were included; two were excluded after the baseline period because less than two migraine days occurred; three were excluded because their headache diaries suggested the diagnosis of chronic migraine. Twenty-three datasets were taken for further analysis. Compared to sham tDCS (n = 12), verum tDCS (n = 11) resulted in a lower number of migraine days (p = 0.010) across all follow-up periods. We found no significant change in total headache days (p = 0.165), anxiety (p = 0.884), or depression scores (p = 0.535). No serious adverse events occurred; minor side effects were similar in both groups.ConclusionsThis study provides Class II evidence that self-administered anodal tDCS over the visual cortex in episodic migraine results in a significantly lower number of monthly migraine days. However, it has neither an immediate nor a long-term effect.     

A Randomized Controlled Trial of High-Intensity Exercise and Executive Functioning in Cognitively Normal Older Adults

BackgroundThere is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function.MethodsNinety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO₂peak.ResultsFirst, the exercise intervention was found to increase cardiorespiratory fitness (VO₂peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (β = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (β = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants.ConclusionAt the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Generativity.     

Therapeutic Misestimation in Patients with Degenerative Ataxia: Lessons from a Randomized Controlled Trial

Background

The absence of effective treatments may render patients with degenerative cerebellar ataxias susceptible to a placebo response, which could affect the outcome of clinical trials.

Objective

To retrospectively examine expectations of benefit in participants of an ataxia trial and identify determinants of possible therapeutic misestimation.

Methods

Individuals with spinocerebellar ataxia type 3 who participated in a randomized, double-blind, sham-controlled trial received a custom-designed questionnaire about short-term and long-term treatment expectations, allocation preferences, and interpretation of treatment arm assignment based on the presence or absence of clinical improvement. To evaluate whether expectations were specifically related to the application of cerebellar transcranial direct current stimulation (tDCS) or more generally reflect an overly positive attitude of patients with ataxia toward trial participation and results, the last questions involved a hypothetical scenario in which an oral drug was tested against placebo with an aim identical to that of our tDCS study.

Results

All 20 trial participants completed the questionnaire. If allocated to the active treatment arm, 75% of patients expected short-term health benefits and 55% thought they would still have less severe ataxia at 1-year follow-up compared with baseline. After 2 weeks, an average reduction in ataxia severity of 31.5% (standard deviation, 22.2%) was anticipated. Conversely, 65% associated a lack of improvement with probable or definite allocation to the placebo group. High expectations of benefit were neither related to the type of intervention nor to clinical or demographic characteristics.

Conclusion

Therapeutic misestimation is common in patients with degenerative ataxia and requires special attention in future trials. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Alleviated Anxiety Boosts Memory Training Gain in Older Adults with Subjective Memory Complaints: A Randomized Controlled Trial

ObjectiveOlder adults with subjective memory complaints (SMC) have a higher risk of dementia and commonly demonstrate symptoms of depression and anxiety. The study aimed to examine the effect of a memory training program for individuals with SMC, and whether additional group counseling aimed at alleviating depression and anxiety would boost memory training gains.DesignA three-armed, double-blind, randomized controlled trial.Setting and ParticipantsCommunity-dwelling older adults with SMC, age ≥60.MethodsParticipants (n = 124) were randomly assigned to memory training (MT), group counseling (GC), or GC + MT intervention. The GT + MT group received 3 sessions of group counseling followed by a 4-week memory training, while the MT group attended reading and memory training, and the GC group received group counseling and health lectures. Cognitive function and symptoms of depression and anxiety were assessed at baseline, mid-, and post-intervention.ResultsAfter group counseling, the GC + MT and GC groups showed reduced symptoms of anxiety compared to the MT group. Memory training enhanced associative learning in both MT and GC + MT groups compare with the GC group, but the GC + MT group demonstrated a larger memory improvement (Cohen's d = 0.57) than the MT group (Cohen's d = 0.44).Conclusion and ImplicationsGroup counseling decreased symptoms of anxiety, memory training increased associative learning, and the combination of two intervention induced larger memory gain than memory training alone. The results suggest that it may need to integrate treatment for anxiety into memory training for older adults with SMC to achieve better intervention effect.Trial RegistrationChiCTR-IOR-15006165 in the Chinese Clinical Trial Registry.     

Exploring the Efficacy and Moderators of Two Computer-Tailored Physical Activity Interventions for Older Adults: A Randomized Controlled Trial

Background  

Important health benefits can be derived when low-cost (e.g., computer-tailored) physical activity interventions for older adults demonstrate sustained effects.     

The Effects of Remifentanil on Epileptiform Discharges during Intraoperative Electrocorticography in Patients Undergoing Epilepsy Surgery

PURPOSE: High-dose i.v. opioids (e.g., alfentanil, 50 microg/kg bolus) are known to increase the intraoperative reading of epileptiform activity during epilepsy surgery (ES), thereby facilitating localization of the epileptogenic zone (i.e., the site of ictal onset and initial seizure propagation). However, this phenomenon has not been studied with remifentanil (i.e., a novel ultra-short acting opioid). The purpose of the present study was to evaluate the effect of remifentanil on electrocorticography (ECoG) during ES. METHODS: After Institutional Review Board approval, 25 adult patients undergoing elective ECoG-guided anterior temporal corticectomy were enrolled. At the time of ECoG, anesthesia consisted of inhaled isoflurane < or =0.1% (end-tidal) in 50% N2O, and i.v. fentanyl, 2 microg/kg/h and vecuronium. Patients were maintained at normocapnia and normoxia during ECoG. After acquisition of baseline ECoG, bolus remifentanil, 2.5 microg/kg i.v., was administered. The number of epileptiform spikes occurring 5 min before and after this bolus were compared by using a one-sided sign test; p values < or =0.05 were considered statistically significant. RESULTS: When compared with baseline ECoG, bolus i.v. remifentanil significantly increased the frequency of single spikes or repetitive spike bursts in the epileptogenic zone while suppressing activity in surrounding normal brain. CONCLUSIONS: During ES, remifentanil enhanced epileptiform activity during intraoperative ECoG. Such observations facilitate localization of the epileptogenic zone while minimizing resection of nonepileptogenic eloquent brain tissue. Although not specifically evaluated in this study, we speculate that remifentanil's short elimination half-life will facilitate neurologic function testing immediately after ES. Should this be the case, we envision remifentanil has the potential to supplant other opioids (e.g., alfentanil) during ECoG-guided ES.     

Aging and Engaging: A Pilot Randomized Controlled Trial of an Online Conversational Skills Coach for Older Adults

ObjectiveCommunication difficulties negatively impact relationship quality and are associated with social isolation and loneliness in later life. There is a need for accessible communication interventions offered outside specialty mental health settings.DesignPilot randomized controlled trial.SettingAssessments in the laboratory and intervention completed in-home.ParticipantsTwenty adults age 60 and older from the community and a geriatric psychiatry clinic.InterventionA web-based communication coach that provides automated feedback on eye contact, facial expressivity, speaking volume, and negative content (Aging and Engaging Program, AEP), delivered with minimal assistance in the home (eight brief sessions over 4–6 weeks) or control (education and videos on communication).MeasurementsSystem Usability Scale and Social Skills Performance Assessment, an observer-rated assessment of social communication elicited through standardized role-plays.ResultsNinety percent of participants completed all AEP sessions and the System Usability Scale score of 68 was above the cut-off for acceptable usability. Participants randomized to AEP demonstrated statistically and clinically significant improvement in eye contact and facial expressivity.ConclusionThe AEP is acceptable and feasible for older adults with communication difficulties to complete at home and may improve eye contact and facial expressivity, warranting a larger RCT to confirm efficacy and explore potential applications to other populations, including individuals with autism and social anxiety.     

Spinal Cord Stimulation Versus Re-operation in Patients With Failed Back Surgery Syndrome: An International Multicenter Randomized Controlled Trial (EVIDENCE Study)

Objective: This paper presents the protocol of the EVIDENCE study, a multicenter multinational randomized controlled trial to assess the effectiveness and cost‐effectiveness of spinal cord stimulation (SCS) with rechargeable pulse generator versus re‐operation through 36‐month follow‐up in patients with failed back surgery syndrome. Study Design: Study subjects have neuropathic radicular leg pain exceeding or equaling any low back pain and meet specified entry criteria. One‐to‐one randomization is stratified by site and by one or more prior lumbosacral operations. The sample size of 132 subjects may be adjusted to between 100 and 200 subjects using a standard adaptive design statistical method with pre‐defined rules. Crossover treatment is possible. Co‐primary endpoints are proportion of subjects reporting ≥50% leg pain relief without crossover at 6 and at 24 months after SCS screening trial or re‐operation. Insufficient pain relief constitutes failure of randomized treatment, as does crossover. Secondary endpoints include cost‐effectiveness; relief of leg, back, and overall pain; change in disability and quality of life; and rate of crossover. We are collecting data on subject global impression of change, patient satisfaction with treatment, employment status, pain/paresthesia overlap, SCS programming, and adverse events. Discussion: As the first multicenter randomized controlled trial of SCS versus re‐operation and the first to use only rechargeable SCS pulse generators, the EVIDENCE study will provide up‐to‐date evidence on the treatment of failed back surgery syndrome.     

Effects of a Group-Based Aerobic Exercise Program on the Cognitive Functions and Emotions of Substance Use Disorder Patients: a Randomized Controlled Trial

To examine, from behavioral perspectives, the feasibility of applying group-based aerobic exercise as an adjunct to treatment aimed at improving the cognitive functions and emotions of substance use disorder (SUD) patients. Eighty-three male methamphetamine use disorder patients recruited through an isolated detoxification centers (IDCs) were assigned into either an exercise group or control group. The exercise group participated in a group-based aerobic exercise intervention involving moderate-intensity exercises for 3 months. The cognitive functions, emotions, drug cravings, and physical fitness of the patients in both groups were measured at the baseline, 1 months, 2 month, and 3 months time points. After the 3 months intervention, the exercise group exhibited significant improvements in SSRT, HAMA and BDI scores, and physical fitness scores (i.e., BMI, vital capacity, flexibility, and balance) relative to the control group. Furthermore, the exercise group exhibited significantly reduced VAS scores for craving in comparison to the control group after only 2 months of the intervention. The 3 months group-based aerobic exercise program showed beneficial effects for cognitive functions, emotions, cravings, and physical fitness among SUD patients (i.e., methamphetamine use disorder patients), and can thus be considered as a potential therapeutic candidate for addiction rehabilitation.