Network Meta-analysis and Economic Evaluation of Neurostimulation Interventions for Chronic Non-surgical Refractory back Pain.

OBJECTIVES: Different types of spinal cord stimulation (SCS) have now been evaluated for the management of chronic non-surgical refractory back pain (NSRBP). A direct comparison between the different types of SCS or between closed-loop SCS with conventional medical management (CMM) for patients with NSRBP has not been previously conducted, and therefore, their relative effectiveness and cost-effectiveness remain unknown. The aim of this study was to perform a systematic review, network meta-analysis (NMA) and economic evaluation of closed-loop SCS compared with fixed-output SCS and CMM for patients with NSRBP. METHODS: Databases were searched to 8th September 2023. Randomised controlled trials of SCS for NSRBP were included. Results of studies were combined using fixed-effect NMA models. A cost-utility analysis was performed from the perspective of the UK National Health Service with results reported as incremental cost per quality-adjusted life-year (QALY). RESULTS: Closed-loop SCS resulted in statistically and clinically significant reductions in pain intensity (mean difference [MD] 32.72 [95% CrI 15.69-49.78]) and improvements in secondary outcomes compared to fixed-output SCS at 6-months follow-up. Compared to CMM, both closed-loop and fixed-output SCS result in statistically and clinically significant reductions in pain intensity (closed-loop SCS vs. CMM MD 101.58 [95% CrI 83.73-119.48]; fixed-output SCS versus CMM MD 68.86 [95% CrI 63.43-74.31]) and improvements in secondary outcomes. Cost-utility analysis shows that closed-loop SCS dominates fixed-output SCS and CMM, and fixed-output SCS also dominates CMM. DISCUSSION: Current evidence shows that closed-loop and fixed-output SCS provide more benefits and are cost-saving compared to CMM for patients with NSRBP.

Neurophysiological outcomes that sustained clinically significant improvements over 3 years of physiologic ECAP-controlled closed-loop spinal cord stimulation for the treatment of chronic pain.

INTRODUCTION: A novel, spinal cord stimulation (SCS) system with a physiologic closed-loop (CL) feedback mechanism controlled by evoked compound action potentials (ECAPs) enables the optimization of physiologic neural dose and the accuracy of the stimulation, not possible with any other commercially available SCS systems. The report of objective spinal cord measurements is essential to increase the transparency and reproducibility of SCS therapy. Here, we report a cohort of the EVOKE double-blind randomized controlled trial treated with CL-SCS for 36 months to evaluate the ECAP dose and accuracy that sustained the durability of clinical improvements. METHODS: 41 patients randomized to CL-SCS remained in their treatment allocation and were followed up through 36 months. Objective neurophysiological data, including measures of spinal cord activation, were analyzed. Pain relief was assessed by determining the proportion of patients with ≥50% and ≥80% reduction in overall back and leg pain. RESULTS: The performance of the feedback loop resulted in high-dose accuracy by keeping the elicited ECAP within 4µV of the target ECAP set on the system across all timepoints. Percent time stimulating above the ECAP threshold was >98%, and the ECAP dose was ≥19.3µV. Most patients obtained ≥50% reduction (83%) and ≥80% reduction (59%) in overall back and leg pain with a sustained response observed in the rates between 3-month and 36-month follow-up (p=0.083 and p=0.405, respectively). CONCLUSION: The results suggest that a physiological adherence to supra-ECAP threshold therapy that generates pain inhibition provided by ECAP-controlled CL-SCS leads to durable improvements in pain intensity with no evidence of loss of therapeutic effect through 36-month follow-up.

Controversies of COVID-19 vaccine promotion: lessons of three randomised survey experiments from Hungary.

OBJECTIVES: This study aimed to investigate vaccine promotion messages, examine the heterogeneous effects of these messages and provide experimental evidence to help evaluate the efficiency of COVID-19 vaccine promotion campaigns in Hungary. STUDY DESIGN: This study presents the results of three randomised survey experiments that were embedded in cross-sectional, representative, public opinion studies of Hungarian adults based on in-person interviews. Simple randomisation and blinding were applied to assign participants into the control group (no message) or treatment groups (vaccine promotion messages). METHODS: The first experiment (March 2021) aimed to test vaccination promotion messages from politicians (N = 331) and medical experts (N = 342) by comparing experimental groups' trust in vaccines and conspiratorial beliefs with the control group (N = 327). The second experiment (September 2022) tested the impact of two communication strategies ([1] highlighting the safety and effectiveness of vaccines, N = 104; and [2] highlighting the wide variety of vaccines available, N = 110) on increasing vaccine uptake among those who were still unvaccinated (control group, N = 89). The third experiment (September 2022) tested one message aiming to increase COVID-19 booster uptake among those who received only the first round of vaccination (N = 172; control group, N = 169). The outcome variable in the second and third experiments was intent to get vaccinated. Robust regressions, logit models, Mann-Whitney U-tests and model-based recursive partitioning were run. The inference criteria (p < 0.05) was set in pre-registration of the experiments. RESULTS: All treatment effects were insignificant, but exploratory research found significant conditional treatment effects. Exposure to vaccine promotion by medical professionals was associated with a higher level of trust in Russian and Chinese COVID-19 vaccines in older age cohorts (weighted robust regressions, 50-59 years old, Russian vaccine: +0.769, interaction term [i.t.] p = 0.010; Chinese vaccine: +0.326, i.t. p = 0.044; and ≥60 years old, Russian vaccine +0.183, i.t. p = 0.040; Chinese vaccine +0.559, i.t. p = 0.010) and with a lower level of trust in these vaccines among younger adults (<30 years old, Russian vaccine: -1.236, i.t. p = 0.023; Chinese vaccine: -1.281, i.t. p = 0.022). Receiving a vaccine promotion message from politicians led to a higher level of trust in Chinese vaccines among the oldest respondents (≥60 years: +0.634, i.t. p = 0.035). CONCLUSIONS: Short-term persuasion attempts that aimed to convince respondents about COVID-19 vaccination were ineffective. Booster hesitancy, similar to primary vaccine hesitancy, was resistant to vaccine promotion messages. Significant conditional effects suggest that COVID-19 vaccine promotion by medical experts and politicians may have had adverse effects for some demographic groups in Hungary.

On uniform stability and numerical simulations of complex valued neural networks involving generalized Caputo fractional order.

The dynamics and existence results of generalized Caputo fractional derivatives have been studied by several authors. Uniform stability and equilibrium in fractional-order neural networks with generalized Caputo derivatives in real-valued settings, however, have not been extensively studied. In contrast to earlier studies, we first investigate the uniform stability and equilibrium results for complex-valued neural networks within the framework of a generalized Caputo fractional derivative. We investigate the intermittent behavior of complex-valued neural networks in generalized Caputo fractional-order contexts. Numerical results are supplied to demonstrate the viability and accuracy of the presented results. At the end of the article, a few open questions are posed.

PLM-GAN: A Large-Scale Protein Loop Modeling Using pix2pix GAN.

Revealing the tertiary structure of proteins holds huge significance as it unveils their vital properties and functions. These intricate three-dimensional configurations comprise diverse interactions including ionic, hydrophobic, and disulfide forces. In certain instances, these structures exhibit missing regions, necessitating the reconstruction of specific segments, thereby resulting in challenges in protein design, which encompasses loop modeling, circular permutation, and interface prediction. To address this problem, we present two pioneering models: pix2pix generative adversarial network (GAN) and PLM-GAN. The pix2pix GAN model is adept at generating and inpainting distance matrices of protein structures, whereas the PLM-GAN model incorporates residual blocks into the U-Net network of the GAN, building upon the foundation of the pix2pix GAN model. To bolster the models' performance, we introduce a novel loss function named the "missing to real regions loss" (LMTR) within the GAN framework. Additionally, we introduce a distinctive approach of pairing two different distance matrices: one representing the native protein structure and the other representing the same structure with a missing region that undergoes changes in each successive epoch. Moreover, we extend the reconstruction of missing regions, encompassing up to 30 amino acids and increase the protein length by 128 amino acids. The evaluation of our pix2pix GAN and PLM-GAN models on a random selection of natural proteins (4ZCB, 3FJB, and 2REZ) demonstrated promising experimental results. Our models constitute significant contributions to addressing intricate challenges in protein structure design. These contributions hold immense potential to propel advancements in protein-protein interactions, drug design, and further innovations in protein engineering. Data, code, trained models, examples, and measurements are available on https://github.com/mena01/PLM-GAN-A-Large-Scale-Protein-Loop-Modeling-Using-pix2pix-GAN_.

Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial.

INTRODUCTION: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. METHODS: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. RESULTS: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p<0.001 at all time points). CONCLUSION: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. TRIAL REGISTRATION NUMBER: NCT02924129.

Kratom use and mental health: A systematic literature review and case example.

OBJECTIVE: This review aims to synthesize and critically evaluate the existing literature on kratom use and its possible association with induction of psychotic and manic symptoms, in order to identify potential areas for future research that would improve our understanding of the risks of kratom consumption. METHODS: An electronic search was performed using five major databases: including PubMed, Scopus, Google Scholar, Web of Science, and PsycINFO. keywords such as kratom, Mitragyna speciosa, mania, psychosis, bipolar disorder, schizophrenia, schizoaffective, case report, and case series. The retrieved articles on initial search were screened based on predefined inclusion and exclusion criteria for this study, and then data synthesis was performed to analyze relevant information from the included studies. RESULTS: Six prior papers were found using (1 case series and 5 case reports). These included 10 cases, involving kratom use association with mania and psychosis. The ages of patients ranged from 28 to 55 years mean age was 38, and (SD 13.74), the majority were males (8 out of 11). Patients had durations of kratom use ranging from 2 wk to 15 years. Significant association was found between kratom use and the worsening of psychotic and manic symptoms in individuals with psychiatric conditions. CONCLUSIONS: Our research highlights the possibility of worsening preexisting psychiatric conditions in the context of kratom use. This study emphasizes the need for clinical evaluation of patients for kratom use. Additional research is required to gain a deeper understanding of the potential mental health implications of kratom use, especially among vulnerable populations.

Vitamin D levels among adult psychiatric inpatients and the association with psychosis.

BACKGROUND: The association between low vitamin D levels and mental illness has been described in earlier research. The aim of our study was to examine the association between vitamin D levels with psychotic symptoms among hospitalized patients. METHODS: A total of 1,456 patient records from an academic psychiatric hospital were examined. Vitamin D levels were classified as normal (>30 ng/mL); insufficient (20 to 30 ng/mL); and deficient (<20 ng/mL). We then analyzed the association among vitamin D groups and symptoms of psychosis. RESULTS: The average vitamin D level in our sample was 23.59 ng/mL, with 76.2% of patients presenting with vitamin D levels <30 ng/mL. There was a significant association between vitamin D levels <20 ng/mL and symptoms of psychosis (P < .05). African American patients had lower mean vitamin D levels than White patients (15.6 ± 0.2 ng/mL vs 25.8 ± 0.4 ng/mL, P < .001). There was no sex difference in vitamin D levels (females: 23.3 ± 11.5 ng/mL; males: 23.9 ± 11.0 ng/mL). CONCLUSIONS: Patients with vitamin D levels <30 ng/mL were 1.5 times more likely to have symptoms of psychosis. Patients who were African American, Hispanic, Asian, or biracial had lower vitamin D levels than patients who were White. Multivariate analysis found that after adjusting for age, sex, and race, the association between vitamin D and psychosis was not statistically significant. Possible explanations could include the known tendency to overdiagnose psychosis among individuals who are African American, referral bias, subgroup effect, or an epiphenomenon.

Spherical densities and potentials in exactly solvable model molecules.

A recently initiated variant of density functional theory utilizes a set of spherically symmetric densities instead of the density. The exact functionals are unknown in the new theory akin to the standard density functional theory. In order to test approximate functionals exactly solvable models are introduced. A harmonic molecular ion, the analogue to the hydrogen molecule ion and a harmonic two-electron molecule showing analogy to the hydrogen molecule are proposed. It has been found that the wave function and the density can be given analytically. The exact spherical densities and the effective potentials of the Euler equations also have analytical form. It has been shown that the models can be easily extended to several "nuclei."

Multidisciplinary management of acute cholecystitis during the COVID-19 pandemic.

The coronavirus disease 2019 pandemic had a major impact on most medical services. Our aim was to assess the outcome of acute cholecystitis during the nationwide lockdown period. All patients admitted to our emergency department for AC were analysed. Patient characteristics, performance status, AC severity, treatment modality and outcome of AC were assessed during the lockdown period (Period II: 1 April 2020-30 November 2021) and compared to a historical control period (Period I: 1 May 2017-31 December 2018). AC admissions increased by 72.8% in Period II. Patients were younger (70 vs. 74 years, p = 0.017) and greater in number in the CCI 1 group (20.4% vs. 11.2%, p = 0.043) in Period II. The unplanned readmission rate (6.3 vs. 0%, p = 0.004) and the gallbladder perforation (GP) rate was higher (18.0 vs. 7.3%, p = 0.006) in Period II. Percutaneous transhepatic gallbladder drainage (PTGBD) was more frequent (24.1 vs. 12.8%, p = 0.012) in Period II. In addition to a drop in patient age and CCI, a significant rise in the prevalence of acute cholecystitis, GP and unplanned readmissions was observed during the nationwide lockdown due to the COVID-19 pandemic. PTGBD was more frequent during this period, whereas successful conservative treatment was less frequent.

Psychometric validation of the Reported and Intended Behaviour Scale (RIBS) in Hungary with a particular focus on 'Don't know' responses and further scoring recommendations.

AIMS: Reported and Intended Behaviour Scale (RIBS) was designed to measure mental health stigma-related behaviors in the general public. We aimed to examine its psychometric properties and validate the scale in a Hungarian non-clinical community sample. The secondary aim of this study was to assess the appropriateness of the current scoring recommendations of 'Don't know' responses being coded as neutral, which had never been investigated before. In addition, we provide an overview of the results of already existing studies on the scale. METHODS: Hungarian participants completed the RIBS within this cross-sectional online survey study and were considered non-clinical individuals based on a cut-off point of the Global Severity Index T score of 63 on the Symptom Checklist-90-Revised. Confirmatory factor analysis, reliability measures, and comparative analyses were performed. RESULTS: Of the n = 5,701, n = 5,141 participants were included in the analysis. The mean age was 27.8 ± 11.1 years, and 89.2% (n = 4,587) of the sample were female. The unidimensional structure was supported by good model fit indices (RMSEA = 0.031, CFI = 0.999, TLI = 0.996, and WRMR = 0.006). Internal consistency of the RIBS and its test-retest reliability with a 5-month follow-up period were found to be good (Cronbach's alpha = 0.88 and ICC = 0.838). We found statistically significant differences between the total scores when the 'Don't know' responders were excluded from the sample or when they were coded as neutral as recommended by the scale authors (16 (IQR:13-18) vs. 15 (IQR:13-18) p < 0.0001). There were also statistically significant differences between 'Neither agree nor disagree' and 'Don't know' participants in several aspects of lived experiences of mental health problems. CONCLUSIONS: The RIBS demonstrated good psychometric properties and can be transferred to the Hungarian context. It will be a valuable tool in assessing stigmatizing behavior and testing the efficacy of antistigma programs. Our results suggest that 'Neither agree nor disagree' and 'Don't know' responses bear different meanings, and coding should account for this.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

INTRODUCTION: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group. CONCLUSION: This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS. TRIAL REGISTRATION NUMBER: NCT02924129.

Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-Month results of a randomized controlled trial.

AIMS: To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN). METHODS: The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment. In total, 142 patients with a 10 kHz SCS system were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. Assessments included pain intensity, health-related quality of life (HRQoL), sleep, and neurological function. Investigators assessed neurological function via sensory, reflex, and motor tests. They identified a clinically meaningful improvement relative to the baseline assessment if there was a significant persistent improvement in neurological function that impacted the participant's well-being and was attributable to a neurological finding. RESULTS: At 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing ≥50% pain relief. Participants had significantly improved HRQoL and sleep, and 65.7% demonstrated clinically meaningful neurological improvement. Five (3.2%) SCS systems were explanted due to infection. CONCLUSIONS: Over 24 months, 10 kHz SCS provided durable pain relief and significant improvements in HRQoL and sleep. Furthermore, the majority of participants demonstrated neurological improvement. These long-term data support 10 kHz SCS as a safe and highly effective therapy for PDN. TRIAL REGISTRATION: ClincalTrials.gov Identifier, NCT03228420.

Posttraumatic stress disorder comorbidity in patients undergoing ECT for major depressive disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is not recognized as an indication for electroconvulsive therapy (ECT). However, research indicates promise for this treatment modality. To elucidate the effects of ECT for treating PTSD, prospective research is needed. The first step in assessing the feasibility of such research is to determine if many patients being treated with ECT have comorbid PTSD. This study examined the PTSD comorbidity rates and compared demographic data among patients with major depressive disorder (MDD) who were treated with ECT vs patients with MDD who were not treated with ECT. METHODS: Data from patients with MDD were obtained from the Nationwide Inpatient Sample. RESULTS: Approximately 10% of patients undergoing ECT for MDD also had PTSD. The difference in comorbidity of PTSD in those treated with ECT vs those not treated with ECT was approximately 1%. CONCLUSIONS: Prospective naturalistic studies that examine the response of PTSD to ECT are feasible because a sizable number of patients with PTSD are receiving ECT.

Electroconvulsive therapy in individuals with dementia/major NCD presenting with behavioral symptoms: a systematic review.

OBJECTIVE: This study aims to systematically review the literature on using electroconvulsive therapy (ECT) in patients with dementia/major NCD (Neuro cognitive disorder) presenting with behavioral symptoms. DESIGN: We conducted a PRISMA-guided systematic review of the literature. We searched five major databases, including PubMed, Medline, Embase, Cochrane, and registry (ClinicalTrials.gov), collaborating with "ECT" and "dementia/major NCD" as our search terms. MEASUREMENTS: Out of 445 published papers and four clinical trials, only 43 papers and three clinical trials met the criteria. There were 22 case reports, 14 case series, 4 retrospective chart reviews, 1 retrospective case-control study, 1 randomized controlled trial, and 2 ongoing trials. We evaluated existing evidence for using ECT in dementia/major NCD patients with depressive symptoms, agitation and aggression, psychotic symptoms, catatonia, Lewy body dementia/major NCD, manic symptoms, and a combination of these symptoms. SETTINGS: The studies were conducted in the in-patient setting. PARTICIPANTS: Seven hundred and ninety total patients over the age of 60 years were added. RESULTS: All reviewed studies reported symptomatic benefits in treating behavioral symptoms in individuals with dementia/major NCD. While transient confusion, short-term memory loss, and cognitive impairment were common side effects, most studies found no serious side effects from ECT use. CONCLUSION: Current evidence from a systematic review of 46 studies indicates that ECT benefits specific individuals with dementia/major NCD and behavioral symptoms, but sometimes adverse events may limit its use in these vulnerable individuals.

Electroconvulsive therapy plus lithium is associated with less cognitive impairment and drug-induced delirium in bipolar depression compared to unipolar depression.

BACKGROUND: Although major depressive disorder (MDD) and bipolar depression can present with similar symptoms, biological differences exist. One difference is the possible variance in adverse effects associated with treatment. This study examined the association of cognitive impairment and delirium in patients treated with electroconvulsive therapy (ECT) plus lithium for MDD or bipolar depression. METHODS: The Nationwide Inpatient Sample included 210 adults receiving ECT plus lithium. Descriptive statistics and a Chi-square test were used to evaluate the differences between mild cognitive impairment and drug-induced delirium for those with MDD or bipolar depression. We calculated the odds ratio (OR) for drug-induced delirium in inpatients with MDD (compared to inpatients with bipolar depression) using a binomial logistic regression model. RESULTS: Mild cognitive impairment was observed in 9.1% of patients with MDD (n = 110), compared to 0 in bipolar depression (n = 100) (P = .002). Drug-induced delirium was more prevalent in MDD (OR 1.19; 95% CI, 1.11 to 1.30). CONCLUSIONS: ECT plus lithium is associated with less cognitive impairment and drug-induced delirium in bipolar depression compared to MDD. This study may also support biological differences between the 2 types of depression.

Size distribution and relationship of airborne SARS-CoV-2 RNA to indoor aerosol in hospital ward environments.

Aerosol particles proved to play a key role in airborne transmission of SARS-CoV-2 viruses. Therefore, their size-fractionated collection and analysis is invaluable. However, aerosol sampling in COVID departments is not straightforward, especially in the sub-500-nm size range. In this study, particle number concentrations were measured with high temporal resolution using an optical particle counter, and several 8 h daytime sample sets were collected simultaneously on gelatin filters with cascade impactors in two different hospital wards during both alpha and delta variants of concern periods. Due to the large number (152) of size-fractionated samples, SARS-CoV-2 RNA copies could be statistically analyzed over a wide range of aerosol particle diameters (70-10 µm). Our results revealed that SARS-CoV-2 RNA is most likely to exist in particles with 0.5-4 µm aerodynamic diameter, but also in ultrafine particles. Correlation analysis of particulate matter (PM) and RNA copies highlighted the importance of indoor medical activity. It was found that the daily maximum increment of PM mass concentration correlated the most with the number concentration of SARS-CoV-2 RNA in the corresponding size fractions. Our results suggest that particle resuspension from surrounding surfaces is an important source of SARS-CoV-2 RNA present in the air of hospital rooms.

Cognitive impairment in REM-sleep behaviour disorder and individuals at risk of Parkinson's disease.

BACKGROUND: Mild cognitive impairment (MCI) is commonly present at the time of Parkinson's Disease (PD) diagnosis, but its prevalence amongst individuals at increased risk of PD is unclear. METHODS: Cognition was assessed using the Montreal Cognitive Assessment (MoCA) in 208 participants in the PREDICT-PD study, and 25 participants with REM-sleep behaviour disorder (RBD). Prevalence of MCI level I was determined in all participants, and level II MCI in the RBD sub-group. RESULTS: Total MoCA scores were worse in the higher risk than the lower risk group defined as those below the 15th percentile of risk (p = 0.009), and in the RBD group compared to all healthy participants (p < 0.001). The prevalence of MCI level I was 12.8% in the lower-risk, 21.9% in the higher-risk (within the highest 15th percentile) and 64% in RBD participants; 66% of RBD participants had MCI level II with multi-domain MCI, but particularly attention and memory deficits. CONCLUSIONS: Cognitive impairment is increased in different groups at higher risk of PD, particularly in the subgroup formally diagnosed with RBD.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis.

OBJECTIVE: Spinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. MATERIALS AND METHODS: The EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. RESULTS: The mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved "good sleep quality" scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. "Normative" sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. CONCLUSIONS: ECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. CLINICAL TRAIL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02924129.