Intensive Blood Pressure Control After Endovascular Thrombectomy for Acute Ischemic Stroke: a Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Optimal clinical outcome with successful recanalization from endovascular thrombectomy (EVT) requires optimal blood pressure (BP) management. We aimed to evaluate the efficacy and safety of the intensive BP target (< 140 mm Hg) versus the standard BP target (< 180 mm Hg) after EVT for acute ischemic stroke. METHODS: We conducted a systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 7th, 2023. We used the fixed-effect model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42023463206. RESULTS: We included four RCTs with 1559 patients. There was no difference between intensive BP and standard BP targets regarding the National Institutes of Health Stroke Scale (NIHSS) change after 24 h [MD: 0.44 with 95% CI (0.0, 0.87), P = 0.05]. However, the intensive BP target was significantly associated with a decreased risk of excellent neurological recovery (mRS ≤ 1) [RR: 0.87 with 95% CI (0.76, 0.99), P = 0.03], functional independence (mRS ≤ 2) [RR: 0.81 with 95% CI (0.73, 0.90), P = 0.0001] and independent ambulation (mRS ≤ 3) [RR: 0.85 with 95% CI (0.79, 0.92), P < 0.0001]. CONCLUSIONS: An intensive BP target after EVT is associated with worse neurological recovery and significantly decreased rates of functional independence and independent ambulation compared to the standard BP target. Therefore, the intensive BP target should be avoided after EVT for acute ischemic stroke.

Improved Quantification of MicroPET/CT Imaging Using CT-derived Scaling Factors.

Purpose: Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BPND) in rodent PET studies. Procedures: PET and CT scans were acquired on 5 female and 5 male CD-1 mice with PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5). In the proposed PET/CT (PTCT) approach, the tracer-specific standard volume was dimension-customized to each animal using the scaling factors from CT-to-standard CT coregistration to simplify PET-to-standard PET coregistration (i.e., 3 CT- and 6 PET-derived parameters). For comparison, conventional PET-based coregistration was performed with 9 (PT9) or 12 (PT12) parameters. PET frames were transferred to the standard space by the three approaches (PTCT, PT9, and PT12) to obtain regional time-activity curves (TACs) and BPND in 14 standard volumes of interest (VOIs). Lastly, CT images of the animals were transferred to the standard space by CT-based parameters from PTCT and with the scaling factors replaced with those from PET-based PT9 to evaluate agreement of the skull to the standard CT. Results: The PET-based approaches showed various degrees of underestimations of scaling factors in the posterior-anterior-direction compared to PTCT, which resulted in negatively proportional overestimation of radioactivity in the cerebellum (reference region) up to 20%, and proportional, more prominent underestimation of BPND in target regions down to -50%. The skulls of individual animals agreed with the standard skull for scaling factors from PTCT but not for the scaling factors from PT9, which suggested inaccuracy of the latter. Conclusions: The results indicated that conventional PET-based coregistration approaches could yield biased estimates of BPND due to erroneous estimates of brain dimensions when applied to tracers for which the cerebellum serves as reference region. The proposed PTCT provides evidence of a quantitative improvement over PET-based approaches for brain studies using micro-PET/CT scanners.

Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Istaroxime, an intravenous inotropic agent with a dual mechanism-increasing both cardiomyocyte contractility and relaxation-is a novel treatment for acute heart failure (AHF), the leading cause of morbidity and mortality in heart failure. We conducted a systematic review and meta-analysis that synthesized randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane until 24 April 2023. We used a fixed-effect or random-effect model-according to heterogeneity-to pool dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD), with a 95% confidence interval (CI). We included three RCTs with a total of 300 patients. Istaroxime was significantly associated with an increased left ventricular ejection fraction (mL) (MD: 1.06, 95% CI: 0.29, 1.82; p = 0.007), stroke volume index (MD: 3.04, 95% CI: 2.41, 3.67; p = 0.00001), and cardiac index (L/min/m2) (MD: 0.18, 95% CI: 0.11, 025; p = 0.00001). Also, istaroxime was significantly associated with a decreased E/A ratio (MD: -0.39, 95% CI: -0.58, -0.19; p = 0.0001) and pulmonary artery systolic pressure (mmHg) (MD: 2.30, 95% CI: 3.20, 1.40; p = 0.00001). Istaroxime was significantly associated with increased systolic blood pressure (mmHg) (MD: 5.32, 95% CI: 2.28, 8.37; p = 0.0006) and decreased heart rate (bpm) (MD: -3.05, 95% CI: -5.27, -0.82; p = 0.007). Since istaroxime improved hemodynamic and echocardiographic parameters, it constitutes a promising strategy for AHF management. However, the current literature is limited to a small number of RCTs, warranting further large-scale phase III trials before clinical endorsement.

A Deep Learning Approach for Automatic and Objective Grading of the Motor Impairment Severity in Parkinson's Disease for Use in Tele-Assessments.

Wearable sensors provide a tool for at-home monitoring of motor impairment progression in neurological conditions such as Parkinson's disease (PD). This study examined the ability of deep learning approaches to grade the motor impairment severity in a modified version of the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) using low-cost wearable sensors. We hypothesized that expanding training datasets with motion data from healthy older adults (HOAs) and initializing classifiers with weights learned from unsupervised pre-training would lead to an improvement in performance when classifying lower vs. higher motor impairment relative to a baseline deep learning model (XceptionTime). This study evaluated the change in classification performance after using expanded training datasets with HOAs and transferring weights from unsupervised pre-training compared to a baseline deep learning model (XceptionTime) using both upper extremity (finger tapping, hand movements, and pronation-supination movements of the hands) and lower extremity (toe tapping and leg agility) tasks consistent with the MDS-UPDRS. Overall, we found a 12.2% improvement in accuracy after expanding the training dataset and pre-training using max-vote inference on hand movement tasks. Moreover, we found that the classification performance improves for every task except toe tapping after the addition of HOA training data. These findings suggest that learning from HOA motion data can implicitly improve the representations of PD motion data for the purposes of motor impairment classification. Further, our results suggest that unsupervised pre-training can improve the performance of motor impairment classifiers without any additional annotated PD data, which may provide a viable solution for a widely deployable telemedicine solution.

Corrigendum to "Feasibility of virtual low-cost quantitative continuous measurement of movements in the extremities of people with Parkinson's disease" [MethodsX 11 (2023) 102230].

[This corrects the article DOI: 10.1016/j.mex.2023.102230.].

Dataset of quality assurance measurements of rhythmic movements.

A low-cost quantitative structured office measurement of movements in the extremities of people with Parkinson's disease [1,2] was performed on participants with Parkinson's disease and multiple system atrophy as well as age- and sex-matched healthy participants with typical development. Participants underwent twelve videotaped procedures rated by a trained examiner while connected to four accelerometers [1,2] generating a trace of the three location dimensions expressed as spreadsheets [3,4]. The signals of the five repetitive motion items (3.4 Finger tapping, 3.5 Hand movements, 3.6 Pronation-supination movements of hands, 3.7 Toe tapping, and 3.8 Leg agility) [1] underwent processing to fast Fourier [5] and amor and bump continuous wavelet transforms [6], [7], [8], [9], [10], [11], [12], [13]. Images of the signals and their transforms [4], [5], [6] of the five repetitive tasks of each participant were randomly expressed as panels on an electronic framework for rating by 35 trained examiners who did not know the source of the original output [14]. The team of international raters completed ratings of the signals and their transforms independently using criteria like the scoring systems for live assessments of movements in human participants [1,2]. The raters scored signals and transforms for deficits in the sustained performance of rhythmic movements (interruptions, slowing, and amplitude decrements) often observed in people with Parkinson's disease [15], [16], [17], [18], [19], [20]. Raters were first presented the images of the signals and transforms of a man with multiple system atrophy as a test and a retest in a different random order. After the raters completed the assessments of the man with multiple system atrophy, they were presented random test and retest panels of the images of signals and transforms of ten participants with Parkinson's disease who completed a single rating session. After the raters completed the assessments of the participants with Parkinson's disease who completed one set of ratings, they were presented random test and retest panels of the images of signals and transforms of (A) ten participants with Parkinson's disease and (B) eight age- and sex-match healthy participants with typical development who completed two rating session separated by a month or more [15], [16], [17], [18], [19], [20]. The data provide a framework for further analysis of the acquired information. Additionally, the data provide a template for the construction of electronic frameworks for the remote analysis by trained raters of signals and transforms of rhythmic processes to verify that the systems are operating smoothly without interruptions or changes in frequency and amplitude. Thus, the data provide the foundations to construct electronic frameworks for the virtual quality assurance of a vast spectrum of rhythmic processes. The dataset is a suitable template for solving unsupervised and supervised machine learning algorithms. Readers may utilize this procedure to assure the quality of rhythmic processes by confirming the absence of deviations in rate and rhythm. Thus, this procedure provides the means to confirm the quality of the vast spectrum of rhythmic processes.

Contact Force-Guided versus Contact Force-Blinded Cavo-Tricuspid Isthmus Ablation for Atrial Flutter: A Systematic Review and Meta-Analysis.

Contact force (CF) is a novel approach developed to increase the safety and efficacy of catheter ablation. However, the value of CF-sensing technology for atrial flutter (AFL) cavo-tricuspid isthmus ablation (CTIA) is inconclusive. To generate a comprehensive assessment of optimal extant data on CF for AFL, we synthesized randomized controlled trials (RCTs) and observational studies from Web of Science, SCOPUS, EMBASE, PubMed, and Cochrane until 29 November 2022, using the odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with a corresponding 95% confidence interval (CI). Two RCTs and three observational studies with a total of 376 patients were included in our analysis. CF-guided ablation was associated with (A) a higher rate of AFL recurrence (OR: 2.26 with 95% CI [1.05, 4.87]) and total CF (MD: 2.71 with 95% CI [1.28, 4.13]); (B) no effect on total procedure duration (MD: -2.88 with 95% CI [-7.48, 1.72]), fluoroscopy duration (MD: -0.96 with 95% CI [-2.24, 0.31]), and bidirectional isthmus block (BDIB) (OR: 1.50 with 95% CI [0.72, 3.11]); and (C) decreased radiofrequency (RF) duration (MD: -1.40 with 95% CI [-2.39, -0.41]). We conclude that although CF-guided CTIA was associated with increased AFL recurrence and total CF and reduced RF duration, it did not affect total procedure duration, fluoroscopy duration, or BDIB. Thus, CF-guided CTIA may not be the optimal intervention for AFL. These findings indicate the need for (A) providers to balance the benefits and risks of CF when utilizing precision medicine to develop treatment plans for individuals with AFL and (B) clinical trials investigating CF-guided catheter ablation for AFL to provide definitive evidence of optimal CF-sensing technology.

Feasibility of virtual low-cost quantitative continuous measurement of movements in the extremities of people with Parkinson's disease.

A low-cost quantitative continuous measurement of movements in the extremities of people with Parkinson's disease, a structured motor assessment administered by a trained examiner to a patient physically present in the same room, utilizes sensors to generate output to facilitate the evaluation of the patient. However, motor assessments with the patient and the examiner in the same room may not be feasible due to distances between the patient and the examiner and the risk of transmission of infections between the patient and the examiner. Therefore, we propose a protocol for the remote assessment by examiners in different locations of both (A) videos of patients recorded during in-person motor assessments and (B) live virtual assessments of patients in different locations from examiners. The proposed procedure provides a framework for providers, investigators, and patients in vastly diverse locations to conduct optimal motor assessments required to develop treatment plans utilizing precision medicine tailored to the specific needs of each individual patient. The proposed protocol generates the foundation for providers to remotely perform structured motor assessments necessary for optimal diagnosis and treatment of people with Parkinson's disease and related conditions.

Research Trends of Vitamin D Metabolism Gene Polymorphisms Based on a Bibliometric Investigation.

Vitamin D requires activation to show its pharmacological effect. While most studies investigate the association between vitamin D and disease, only a few focus on the impact of vitamin D metabolism gene polymorphisms (vitDMGPs). This bibliometric study aims to provide an overview of current publications on vitDMGPs (CYP27B1, CYP24A1, CYP2R1, CYP27A1, CYP2R1, DHCR7/NADSYN1), compare them across countries, affiliations, and journals, and inspect keywords, co-citations, and citation bursts to identify trends in this research field. CiteSpace© (version 6.1.R3, Chaomei Chen), Bibliometrix© (R version 4.1.3 library, K-Synth Srl, University of Naples Federico II, Naples, Italy), VOSviewer© (version 1.6.1, Nees Jan van Eck and Ludo Waltman, Leiden University, Leiden, Netherlands) and Microsoft® Excel 365 (Microsoft, Redmond, Washington, USA) classified and summarized Web of Science articles from 1998 to November 2022. We analyzed 2496 articles and built a timeline of co-citations and a bibliometric keywords co-occurrence map. The annual growth rate of vitDMGPs publications was 18.68%, and their relative research interest and published papers were increasing. The United States of America leads vitDMGPs research. The University of California System attained the highest quality of vitDMGPs research, followed by the American National Institutes of Health and Harvard University. The three productive journals on vitDMGPs papers are J. Steroid. Biochem. Mol. Biol., PLOS ONE, and J. Clin. Endocrinol. Metab. We highlighted that the vitDMGPs domain is relatively new, and many novel research opportunities are available, especially those related to studying single nucleotide polymorphisms or markers in a specific gene in the vitamin D metabolism cycle and their association with disease. Genome-wide association studies, genetic variants of vitDMGPs, and vitamin D and its role in cancer risk were the most popular studies. CYP24A1 and CYB27A1 were the most-studied genes in vitDMGPs. Insulin was the longest-trending studied hormone associated with vitDMGPs. Trending topics in this field relate to bile acid metabolism, transcriptome and gene expression, biomarkers, single nucleotide polymorphism, and fibroblast growth factor 23. We also expect an increase in original research papers investigating the association between vitDMGPs and coronavirus disease 2019, hypercalcemia, Smith-Lemli-Opitz syndrome, 27-hydroxycholesterol, and mendelian randomization. These findings will provide the foundations for innovations in the diagnosis and treatment of a vast spectrum of conditions.

The Efficacy and Safety of Direct Oral Anticoagulants versus Standard of Care in Patients without an Indication of Anti-Coagulants after Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials.

Transcatheter aortic valve replacement (TAVR) is now considered the mainstay of aortic stenosis management; however, the optimal antithrombotic therapy in patent without indications for an oral anticoagulant (OAC) is yet to be identified. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of direct oral anticoagulant (DOAC) treatment versus the standard of care in patients without indications of OACs after TAVR. We synthesized randomized controlled trials (RCTs) from Web of Science, SCOPUS, EMBASE, PubMed, and Cochrane until 18 August 2022. We used the risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022357027. Three RCTs with 2922 patients were identified. DOACs were significantly associated with higher incidence of all-cause mortality (RR: 1.68 with 95% CI [1.22, 2.30], p = 0.001), mortality due to non-cardiovascular causes (RR: 2.34 with 95% CI [1.36, 4.02], p = 0.002), and the composite outcome of death, myocardial infarction, or stroke (RR: 1.41 with 95% CI [1.13, 1.76], p = 0.002). However, DOACs were associated with decreased incidence of reduced leaflet motion (RLM) (RR: 0.19 with 95% CI [0.09, 0.41], p = 0.0001) and hypoattenuated leaflet thickening (HALT) (RR: 0.50 with 95% CI [0.36, 0.70], p = 0.0001). DOACs were effective to reduce RLM and HALT; however, the clinical effect of this is still controversial. DOACs were associated with worse efficacy and safety outcomes, including all-cause mortality. Further RCTs investigating the optimal antithrombotic regimen after TAVR.

Efficacy and Safety of Polaprezinc-Based Therapy versus the Standard Triple Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Helicobacter pylori (H. pylori) is the most prevalent etiology of gastritis worldwide. H. pylori management depends mainly on antibiotics, especially the triple therapy formed of clarithromycin, amoxicillin, and proton pump inhibitors. Lately, many antibiotic-resistant strains have emerged, leading to a decrease in the eradication rates of H. pylori. Polaprezinc (PZN), a mucosal protective zinc-L-carnosine complex, may be a non-antibiotic agent to treat H. pylori without the risk of resistance. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of a PZN-based regimen for the eradication of H. pylori. This study used a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, PubMed, and Google Scholar until 25 July 2022. We used the odds ratio (OR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022349231. We included 3 trials with a total of 396 participants who were randomized to either PZN plus triple therapy (n = 199) or triple therapy alone (control) (n = 197). Pooled OR found a statistical difference favoring the PZN arm in the intention to treat and per protocol H. pylori eradication rates (OR: 2.01 with 95% CI [1.27, 3.21], p = 0.003) and (OR: 2.65 with 95% CI [1.55, 4.54], p = 0.0004), respectively. We found no statistical difference between the two groups regarding the total adverse events (OR: 1.06 with 95% CI [0.55, 2.06], p = 0.85). PZN, when added to the triple therapy, yielded a better effect concerning the eradication rates of H. pylori with no difference in adverse event rates, and thus can be considered a valuable adjuvant for the management of H. pylori. However, the evidence is still scarce, and larger trials are needed to confirm or refute our findings.

The Effect of Vitamin D Supplementation on the Severity of Symptoms and the Quality of Life in Irritable Bowel Syndrome Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Irritable bowel syndrome (IBS), a gastrointestinal disorder affecting 7-12% of the population, is characterized by abdominal pain, bloating, and alternating bowel patterns. Data on risk and protective influences have yielded conflicting evidence on the effects of alternative interventions, such as vitamin D. This review focuses on the effects of vitamin D on IBS. A systematic review and meta-analysis considered all articles published until 4 April 2022. The search for randomized controlled trials assessing vitamin D efficacy in IBS with outcomes, primary (Irritable Bowel Severity Scoring System (IBS-SSS)) and secondary (IBS quality of life (IBS-QoL) and serum level of calcifediol (25(OH)D)), was performed on six databases, Google Scholar, Web of Science, SCOPUS, EMBASE, PubMed (MEDLINE), and Cochrane Central Register of Controlled Trials. We included six trials with 616 patients. The pooled analysis found no difference between vitamin D and placebo in improving IBS-SSS (MD: -45.82 with 95% CI [-93.62, 1.98], p = 0.06). However, the pooled analysis favored vitamin D over placebo in improving the IBS-Qol (MD: 6.19 with 95% CI [0.35, 12.03], p = 0.04) and serum 25(OH)D (MD: 25.2 with 95% CI [18.41, 31.98], p = 0.00001). Therefore, further clinical trials are required to reach clinically applicable and generalizable findings.

Reply to Aljabali et al. Comment on "Abbas et al. The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Medicina 2022, 58, 213".

We appreciate Ahmed Sami Aljabali and his colleagues for their interest and comments [...].

Classification of extremity movements by visual observation of signals and their transforms.

A low-cost quantitative continuous measurement of movements utilizes accelerometers to generate signal outputs to precisely record the positions of extremities during the performance of movements. This procedure can readily be accomplished with inexpensive materials constructed indivisuals throughout the world. The proposed protocol provides the framework for trained raters to assess the signal outputs by visual observation to generate objective measurements like the measurements of the actual movements. Expert raters can then remotely give quantitative suggestions for providers in underserved regions to utilize precision medicine to develop optimal treatment plans tailored to the specific needs of each individual. The proposed protocol lays the foundations for experts located in tertiary centers to provide optimal assessments of signal outputs generated remotely in underserved regions. This protocol provides the means to address gaps in current research including the dearth of objective measurements of movements utilizing automatic intelligence and machine learning to accurately and precisely analyze movement assessments. Future research will include the development of robotic tools to perform assessments and analyses of the movements of human beings to enhance the conduct of movement evaluations of people with Parkinson's disease and related conditions to apply precision medicine for optimal diagnostic and therapeutic interventions.

Fragile X Mental Retardation Protein and Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Men with Fragile X Syndrome: A Pilot Study.

Multiple lines of evidence suggest that a deficiency of Fragile X Mental Retardation Protein (FMRP) mediates dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) in the pathogenesis of fragile X syndrome (FXS), the most commonly known single-gene cause of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Nevertheless, animal and human studies regarding the link between FMRP and mGluR5 expression provide inconsistent or conflicting findings about the nature of those relationships. Since multiple clinical trials of glutamatergic agents in humans with FXS did not demonstrate the amelioration of the behavioral phenotype observed in animal models of FXS, we sought measure if mGluR5 expression is increased in men with FXS to form the basis for improved clinical trials. Unexpectedly marked reductions in mGluR5 expression were observed in cortical and subcortical regions in men with FXS. Reduced mGluR5 expression throughout the living brains of men with FXS provides a clue to examine FMRP and mGluR5 expression in FXS. In order to develop the findings of our previous study and to strengthen the objective tools for future clinical trials of glutamatergic agents in FXS, we sought to assess the possible value of measuring both FMRP levels and mGluR5 expression in men with FXS. We aimed to show the value of measurement of FMRP levels and mGluR5 expression for the diagnosis and treatment of individuals with FXS and related conditions. We administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a specific mGluR5 radioligand for quantitative measurements of the density and the distribution of mGluR5s, to six men with the full mutation (FM) of FXS and to one man with allele size mosaicism for FXS (FXS-M). Utilizing the seven cortical and subcortical regions affected in neurodegenerative disorders as indicator variables, adjusted linear regression of mGluR5 expression and FMRP showed that mGluR5 expression was significantly reduced in the occipital cortex and the thalamus relative to baseline (anterior cingulate cortex) if FMRP levels are held constant (F(7,47) = 6.84, p < 0.001).These findings indicate the usefulness of cerebral mGluR5 expression measured by PET with [18F]FPEB and FMRP values in men with FXS and related conditions for assessments in community facilities within a hundred-mile radius of a production center with a cyclotron. These initial results of this pilot study advance our previous study regarding the measurement of mGluR5 expression by combining both FMRP levels and mGluR5 expression as tools for meaningful clinical trials of glutamatergic agents for men with FXS. We confirm the feasibility of this protocol as a valuable tool to measure FMRP levels and mGluR5 expression in clinical trials of individuals with FXS and related conditions and to provide the foundations to apply precision medicine to tailor treatment plans to the specific needs of individuals with FXS and related conditions.

The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disease that leads to progressive proximal muscle weakness and muscle atrophy. To assess the beneficial and adverse effects of nusinersen, a promising intervention for SMA, we conducted a systematic search and meta-analysis of the published randomized control trials (RCTs) of nusinersen for SMA. Materials and methods: Utilizing the Preferred Reporting for Systematic Review and Meta-Analysis (PRISMA), we searched PubMed, Scopus, Web of Science, Cochrane Central, and Clinicaltrials.gov from inception to 22 July 2021. Results: Three RCTs satisfying the inclusion and exclusion criteria covered 274 patients: 178 patients in the nusinersen group. Our results show a significant risk difference (RD) in the motor milestone response (RD: 0.51; 95% CI: 0.39, 0.62; p < 0.00001) and improvement in the HINE-2 score (RD: 0.26; 95% CI: 0.12, 0.40; p < 0.0003) in the nusinersen group compared to the control group. Moreover, a significant decrease in the risk ratio (RR) for severe adverse events (RR: 0.72; 95% CI: 0.57, 0.92; p = 0.007) and any adverse event leading to treatment discontinuation (RR: 0.40; 95% CI: 0.22, 0.74; p = 0.004) was observed. An insignificant result was found for any adverse effects (RR: 0.93; 95% CI: 0.97, 1.01; p = 0.14) and for serious adverse effects (RR: 0.81; 95% CI: 0.60, 1.07; p = 0.14). Conclusions: This review provides evidence that nusinersen treatment was effective in treatment for infants with SMA and was associated with fewer severe adverse events; however, more RCTs are needed to establish evidence.

The role of lumateperone in the treatment of schizophrenia.

Schizophrenia is a devastating mental disorder resulting in marked morbidity and mortality despite the optimal use of all currently available interventions. For this reason, the release of lumateperone (CaptylaR), also known as ITI-007, an orally administered, atypical antipsychotic provided a welcome novel tool for clinicians to utilize precision medicine to tailor an optimal treatment plan to the specific needs of each person with schizophrenia. To generate a foundation for clinicians to assess the risks and benefits of lumateperone in relation to other interventions for schizophrenia, we conducted a search of items for 'ITI-007' and 'lumateperone' on PubMed, ScienceDirect, Web of Science, Google Scholar, and www.clinicaltrials.gov. We present a critical evaluation of the limited information about lumateperone for schizophrenia, its use approved by the US Food and Drug Administration. Lumateperone merits consideration for patients with treatment-resistant schizophrenia and for patients with schizophrenia who are vulnerable to developing metabolic dysfunction and movement disorders. On the other hand, lumateperone should not be used for (a) women who are pregnant or breastfeeding, children, adolescents, and elderly patients with dementia-related psychosis, (b) patients who are at risk for cerebrovascular diseases, (c) patients who use inducers and moderate or strong inhibitors of the cytochrome P450-3A4 (CYP3A4) isozyme, and (d) patients who use alcohol and other sedating agents. Clinical trials from multiple centers without financial conflicts of interest to market lumateperone are needed to directly compare and contrast lumateperone and other antipsychotic agents to generate trustworthy evidence to be assessed objectively by clinicians treating patients with schizophrenia. Future investigations will provide the foundations to identify the evidence for comprehensive evaluations of the role of lumateperone in the treatment of people with schizophrenia and other conditions.

Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Idiopathic Autism Spectrum Disorder and Fragile X Syndrome: A Pilot Study.

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR5 expression provide conflicting findings about the nature of dysregulation of cerebral mGluR5 pathways in subtypes of ASD. The demonstration of reduced mGluR5 expression throughout the living brains of men with fragile X syndrome (FXS), the most common known single-gene cause of ASD, provides a clue to examine mGluR5 expression in ASD. We aimed to (A) compare and contrast mGluR5 expression in idiopathic autism spectrum disorder (IASD), FXS, and typical development (TD) and (B) show the value of positron emission tomography (PET) for the application of precision medicine for the diagnosis and treatment of individuals with IASD, FXS, and related conditions. Two teams of investigators independently administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a novel, specific mGluR5 PET ligand to quantitatively measure the density and the distribution of mGluR5s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR5 expression was significantly increased in the cortical regions of participants with IASD and significantly reduced in all regions of men with FXS. These results suggest the feasibility of this protocol as a valuable tool to measure mGluR5 expression in clinical trials of individuals with IASD and FXS and related conditions.

Dataset of quantitative structured office measurements of movements in the extremities.

A low-cost quantitative structured office measurement of movements in the extremities of people with Parkinson's disease [1,2] was performed on people with Parkinson's disease, multiple system atrophy, and age-matched healthy volunteers. Participants underwent twelve videotaped procedures rated by a trained examiner while connected to four accelerometers [1,2] generating a trace of the three location dimensions expressed as spreadsheets [3,4]. The signals of the five repetitive motion items [1,2] underwent processing to fast Fourier [5] and continuous wavelet transforms [6]. The dataset [7] includes the coding form with scores of the live ratings [1,2], the raw files [3], the converted spreadsheets [4], and the fast Fourier [5] and continuous wavelet transforms [6]. All files are unfiltered. The data also provide findings suitable to compare and contrast with data obtained by investigators applying the same procedure to other populations. Since this is an inexpensive procedure to quantitatively measure motions in Parkinson's disease and other movement disorders, this will be a valuable resource to colleagues, particularly in underdeveloped regions with limited budgets. The dataset will serve as a template for other investigations to develop novel techniques to facilitate the diagnosis, monitoring, and treatment of Parkinson's disease, other movement disorders, and other nervous and mental conditions. The procedure will provide the basis to obtain objective quantitative measurements of participants in clinical trials of new agents.