First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase 3 iLLUMINATE trial

iLLUMINATE is a randomized, open-label phase 3 study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or

ED90 of spinal 2-chloroprocaine 1% in ambulatory knee arthroscopy up to 45 min: a randomized biased-coin- up-and-down sequential allocation trial

BackgroundA short acting spinal anesthetic facilitates smooth flow since quick recovery of motor function will facilitate unassisted ambulation. The aim of this study was to estimate the effective dose (ED90) of intrathecal 2-chloroprocaine 1% in outpatient knee arthroscopy.MethodsTwo cohorts were included in two different hospitals. In cohort I, a randomized biased-coin up-and-down design with 40 patients was used to find the ED90. Four dose-levels of plain 2-chloroprocaine 1% were used: 25, 30, 35 and 40 mg. The identified primary outcome, the ED90, was validated in 50 patients in cohort II with an open label design. Secondary outcomes included time to complete recovery from motor and sensory block with spinal injection as time zero, peak sensory block level, urine retention and time until hospital discharge.ResultsForty patients were included in the final analysis in cohort I. The ED90 was estimated at 27.8 mg, successful spinal anesthesia was obtained in 38 patients (95%). Fifty patients were included in the final analysis in cohort II, 49 patients had successful anesthesia with a fixed round dose of 28 mg. In this Cohort, peak sensory block was T10/T11 (range: (L4–T4)). The median time to full recovery of the motor block was 60 min (45–60) and 90 min (75–105) for the sensory block. The mean time to hospital discharge was 2.9 hours (0.7).ConclusionThe ED90 of 2-chloroprocaine 1% in knee arthroscopy was estimated to be 27.8 mg. In an external population, the ED90 resulted in successful anesthesia in 98% of the patients (95% CI 89% to 100%).Trial registration numberNetherlands Trial Registry (NL6769).

ADHD Prescription Medications and Their Effect on Athletic Performance: A Systematic Review and Meta-analysis

Background Stimulant medications used for the treatment of Attention Deficit-Hyperactivity Disorder (ADHD) are believed to provide a physical advantage in athletics, but several of these medications are not regulated by the World Anti-Doping Association. Given the prevalence of ADHD among the athlete population and concern for abuse of ADHD medications, this review and meta-analysis aimed to evaluate effects of ADHD medications on athletic performance, thereby appraising the validity of claims of performance enhancement. Methods A search of MEDLINE, Embase, CINAHL, and Cochrane Review databases was performed for all randomized controlled trials evaluating athletic performance after ingestion of placebo or ADHD treatment medications from August 2020 through November 2020. All RCTs identified from these search criteria were included for screening, with exclusion of any animal studies. Two reviewers (JB, CK) assessed methodological quality and risk of bias using CONSORT 2010 and Cochrane Collaboration tools. Study results were compiled with corresponding p values for each finding. Effect sizes (Cohen’s D) for athletic performance and physiological changes were aggregated for each study. Studies were further screened for homogeneity that would allow for meta-analysis. Heterogeneity was calculated using I2. Results A total of 13,033 abstracts evaluating amphetamine, methamphetamine, methylphenidate, and bupropion were screened. The final analysis included nine studies, six of which found significant improvement in athletic performance with use of stimulant medications (p < 0.05). Methylphenidate and amphetamine were consistently identified to have a performance effect. Secondary effects identified included significant increase in heart rate, core temperature, and elevation of various serum hormone levels (p < 0.05). Effect size evaluation found seven studies demonstrating small to large effects on physical performance, as well as in categories of cardiometabolic, temperature, hormone, and ratings of perceived exertion, to varying degrees. A meta-analysis was performed on two studies, demonstrating conflicting results. Conclusions Dopaminergic/noradrenergic agonist medications appear to have a positive effect on athletic performance, as well as effects on physiological parameters. Further consideration of medications currently not regulated, i.e. bupropion, is warranted given evidence of athletic performance enhancement. PROSPERO trial registration number: CRD42020211062; 10/29/2020 retrospectively registered.

The Hypothesis of Subliminal Cue Reactivity in Addiction Revisited: An fMRI Study

<b><i>Introduction:</i></b> Exposure to conditioned cues is a common trigger of relapse in addiction. It has been suggested that such cues can activate motivationally relevant neurocircuitry in individuals with substance use disorders even without being consciously perceived. We aimed to see if this could be replicated in a sample with severe amphetamine use disorder and a control group of healthy subjects. <b><i>Methods:</i></b> We used fMRI to test the hypothesis that individuals with amphetamine use disorder, but not healthy controls, exhibit a specific neural reactivity to subliminally presented pictures related to amphetamine use. Twenty-four amphetamine users and 25 healthy controls were recruited and left data of sufficient quality to be included in the final analysis. All subjects were exposed to drug-related and neutral pictures of short duration (13.3 ms), followed by a backward visual mask image. The contrast of interest was drug versus neutral subliminal pictures. <b><i>Results:</i></b> There were no statistically significant differences in BOLD signal between the drug and neutral cues, neither in the limbic regions of primary interest nor in exploratory whole-brain analyses. The same results were found both in amphetamine users and controls. <b><i>Discussion/Conclusion:</i></b> We found no evidence of neural reactivity to subliminally presented drug cues in this sample of subjects with severe amphetamine dependence. These results are discussed in relation to the earlier literature, and the evidence for subliminal drug cue reactivity in substance use disorders is questioned.

Machine Learning Algorithms as a Computer-Assisted Decision Tool for Oral Cancer Prognosis and Management Decisions: A Systematic Review

<b><i>Introduction:</i></b> Despite multiple prognostic indicators described for oral cavity squamous cell carcinoma (OCSCC), its management still continues to be a matter of debate. Machine learning is a subset of artificial intelligence that enables computers to learn from historical data, gather insights, and make predictions about new data using the model learned. Therefore, it can be a potential tool in the field of head and neck cancer. <b><i>Methods:</i></b> We conducted a systematic review. <b><i>Results:</i></b> A total of 81 manuscripts were revised, and 46 studies met the inclusion criteria. Of these, 38 were excluded for the following reasons: use of a classical statistical method (<i>N</i> = 16), nonspecific for OCSCC (<i>N</i> = 15), and not being related to OCSCC survival (<i>N</i> = 7). In total, 8 studies were included in the final analysis. <b><i>Conclusions:</i></b> ML has the potential to significantly advance research in the field of OCSCC. Advantages are related to the use and training of ML models because of their capability to continue training continuously when more data become available. Future ML research will allow us to improve and democratize the application of algorithms to improve the prediction of cancer prognosis and its management worldwide.

A systematic review and meta-analysis of the catastrophic costs incurred by tuberculosis patients

One of the strategies of the World Health Organization End Tuberculosis (TB) was to reduce the catastrophic costs incurred by TB-affected families to 0% by 2020.Catastrophic cost is defined by the total cost related to TB management exceeding 20% of the annual pre-TB household income. This study aimed to estimate the pooled proportion of TB affected households who incurred catastrophic costs. We searched PubMed, SciELO, Scopus, Embase, Google Scholar, ProQuest, SAGE, and Web of Science databases according to Preferred Reporting Items of the Systematic Reviews and Meta-Analysis (PRISMA) guidelines till November 20, 2020. Eligible studies were identified and data on catastrophic costs due to TB were extracted. We performed a meta-analysis to generate the pooled proportion of patients with TB facing catastrophic costs. From 5114 studies identified, 29 articles were included in the final analysis. The pooled proportion of patients faced catastrophic costs was (43%, 95% CI [34–51]). Meta-regression revealed that country, drug sensitivity, and Human immune-deficiency Virus (HIV) co-infection were the main predictors of such costs. Catastrophic costs incurred by drug sensitive, drug resistant, and HIV co-infection were 32%, 81%, and 81%, respectively. The catastrophic costs incurred were lower among active than passive case findings (12% vs. 30%). Half (50%) of TB-affected households faced catastrophic health expenditure at 10% cut-off point. The financial burden of patients seeking TB diagnosis and treatment continues to be a worldwide impediment. Therefore, the End TB approach should rely on socioeconomic support and cost-cutting initiatives.PROSPERO registration: CRD42020221283.

Social Isolation and Associated Factors in Chinese Adults With Epilepsy: A Cross-Sectional Study

Objective: We aimed to determine the prevalence of social isolation and associated factors among adults with epilepsy in northeast China.Methods: A cohort of consecutive patients with epilepsy (PWE) from the First Hospital of Jilin University (Changchun, China) was recruited. Demographic and clinical data for each patient were collected during a face-to-face interview. Social isolation was measured using the Berkman-Syme Social Network Index (SNI), and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Quality of Life in Epilepsy Inventory (QOLIE-31) were also administered. Multivariate logistic regression analyses were used to determine the factors associated with social isolation in PWE.Results: A total of 165 patients were included in the final analysis. The mean SNI score was 2.56 (SD: 1.19), and 35 patients (21.2%) were socially isolated. In multivariate logistic regression analysis, higher depressive symptom levels (OR = 1.15, 95% CI: 1.003–1.318, P = 0.045) and poorer quality of life (OR = 0.967, 95% CI: 0.935–0.999, P = 0.047) emerged as independent factors associated with social isolation in PWE.Conclusion: Social isolation is common and occurs in approximately one-fifth of PWE. Social isolation is significantly associated with depressive symptoms and poor quality of life in PWE. Patients need to be encouraged to actively integrate with others and reduce social isolation, which may help improve their quality of life.

Neutrophil-lymphoycyte-ratio, platelet-lymphocyte-ratio and procalcitonin for early assessment of prognosis in patients undergoing VA-ECMO

The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasing, but mortality remains high. Early assessment of prognosis is challenging and valid markers are lacking. This study aimed to investigate Neutrophil–Lymphocyte Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Procalcitonin (PCT) for early assessment of prognosis in patients undergoing VA-ECMO. This retrospective single-center cohort study included 344 consecutive patients ≥ 18 years who underwent VA-ECMO due to cardiogenic shock. Main exposures were NLR, PLR and PCT measured within 24 h after VA-ECMO initiation. The primary endpoint was all-cause in-hospital mortality. In total, 92 patients were included into final analysis (71.7% male, age 57 ± 14 years). In-hospital mortality rate was 48.9%. Receiver operating characteristics (ROC) curve revealed an area under the curve (AUC) of 0.65 [95% confidence interval (CI) 0.53–0.76] for NLR. The AUCs of PLR and PCT were 0.47 [95%CI 0.35–0.59] and 0.54 [95%CI 0.42–0.66], respectively. Binary logistic regression showed an adjusted odds ratio of 3.32 [95%CI 1.13–9.76] for NLR, 1.0 [95%CI 0.998–1.002] for PLR and 1.02 [95%CI 0.99–1.05] for PCT. NLR is independently associated with in-hospital mortality in patients undergoing VA-ECMO. However, discriminative ability is weak. PLR and PCT seem not to be suitable for this purpose.

Understanding Design Approaches and Evaluation Methods in mHealth applications Targeting Substance Use: Protocol for a Systematic Review (Preprint)

BACKGROUND Substance use and use disorders in the US have had significant and devastating impacts on individuals and communities, and the escalating substance use crisis calls for urgent and innovative solutions to effectively detect and provide interventions for individuals in times of need. Recent mHealth-based approaches offer promising new opportunities to address these issues through ubiquitous devices. However, the design rationale, theoretical framing, and the mechanisms through which users' perspectives and experiences guide the design and deployment of such systems have not been analyzed in any prior systematic reviews. OBJECTIVE In this paper, we systematically review these approaches and applications for their feasibility, efficacy, and usability. Further, we evaluate whether human-centered research principles and techniques guide the design and development of these systems, and examine how the current state-of-art systems apply to real-world contexts. In an effort to gauge the applicability of these systems, we also investigate whether these approaches consider the effects of stigma and the privacy concerns related to collecting data on substance use. Lastly, we examine persistent challenges in the design and large-scale adoption of substance use intervention applications and draw inspiration from other domains of mHealth to suggest actionable reforms into the design and deployment of these applications. METHODS Four databases (PubMed, IEEE, JMIR and ACM DL) were searched over a five-year period (2016 - 2021) for articles evaluating connected mHealth approaches for substance use (alcohol use, marijuana use, opioid use, tobacco use, and substance co-use). Articles that will be included describe an mHealth detection or intervention targeting substance use and provided outcomes data and a discussion of design techniques and user perspectives. Independent evaluation will be conducted by one author, followed by secondary reviewer(s) who will check and validate themes and data. RESULTS This is a protocol for a systematic review, therefore results are not yet available. We are currently in the process of selecting the studies for inclusion in the final analysis. CONCLUSIONS To the best of our knowledge, this is the first systematic review to assess real-world applicability, scalability, and use of human-centered design and evaluation techniques in mHealth approaches targeting substance use. This study is expected to identify gaps in current substance use detection and intervention mHealth technologies and inform and motivate future development of such systems.