Nevin Manimala

JAMA Netw Open. 2022 Nov 1;5(11):e2243848. doi: 10.1001/jamanetworkopen.2022.43848.

ABSTRACT

IMPORTANCE: Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements.

OBJECTIVE: To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention.

DATA SOURCES: A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered.

STUDY SELECTION: Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders.

DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model.

MAIN OUTCOMES AND MEASURES: Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g).

RESULTS: Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q1 = 5.47; I2 = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes.

CONCLUSIONS AND RELEVANCE: Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief.

PMID:36441553 | DOI:10.1001/jamanetworkopen.2022.43848

JAMA Netw Open. 2022 Nov 1;5(11):e2243883. doi: 10.1001/jamanetworkopen.2022.43883.

ABSTRACT

IMPORTANCE: Gathering data on socioeconomic status (SES) is a prerequisite for health programs that aim to improve equity. There is a lack of evidence on which approaches offer the best combination of reliability, cost, and acceptability.

OBJECTIVE: To compare the performance of different approaches to gathering data on SES in community health programs.

DATA SOURCES: A search of the Cochrane Library, MEDLINE, Embase, Global Health, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and OpenGrey from 1999 to June 29, 2021, was conducted, with no language limits. Google Scholar was also searched and the reference lists of included articles were checked to identify further studies. The search was performed on June 29, 2021.

STUDY SELECTION: Any empirical study design was eligible if it compared 2 or more modalities to elicit SES data from the following 3 categories: in-person, voice call, or automated telephone-based systems.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. They also assessed the risk of bias using Cochrane tools and assessed the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. Findings were synthesized thematically without meta-analysis.

MAIN OUTCOMES AND MEASURES: Response rate, equivalence, time, costs, and acceptability to patients and health care professionals.

RESULTS: The searches returned 3943 records. The 11 included studies reported data on 14 036 individuals from 7 countries, collecting data on 11 socioeconomic domains using 2 or more of the following modes: in-person surveys, computer-assisted telephone interviews (CATIs), and 2 types of automated data collection: interactive voice response calls (IVRs) and web surveys. Response rates were greater than 80% for all modes except IVRs. Equivalence was high across all modes (Cohen κ > 0.5). There were insufficient data to make robust time and cost comparisons. Patients reported high levels of acceptability providing data via IVRs, web surveys, and CATIs.

CONCLUSIONS AND RELEVANCE: Selecting an appropriate and cost-effective modality to elicit SES data is an important first step toward advancing equitable effective service coverage. This systematic review did not identify evidence that remote and automated data collection modes differed from human-led and in-person approaches in terms of reliability, cost, or acceptability.

PMID:36441550 | DOI:10.1001/jamanetworkopen.2022.43883

J Exp Anal Behav. 2022 Nov 28. doi: 10.1002/jeab.810. Online ahead of print.

ABSTRACT

A recent social discounting study showed that individuals share personal information in a similar way to money, suggesting that personal information has quantifiable properties for individuals. This is important because many online scams, such as phishing, target sharing different forms of personal information. However, no previous study has tested whether different forms of personal information are shared more or less than others. The current study used a modified social discounting task to test whether there were differences in the amount of personal information shared across four different forms: identification, financial, health, and security information. A between-participant experiment enrolling 100 college-aged participants showed that individuals had a significantly higher discounting rate for health information compared to three other forms of personal information, suggesting that health information was shared more for the participants. There were no statistically significant discounting rate differences between the other three forms of personal information. The results demonstrate that the social discounting task is a viable way to assess differential sharing for personal information. Future research should examine why health information is shared less than other forms of personal information, and whether this increases risk for falling prey to phishing scams targeting different forms of personal information.

PMID:36441508 | DOI:10.1002/jeab.810

Rheumatol Ther. 2022 Nov 27. doi: 10.1007/s40744-022-00506-0. Online ahead of print.

ABSTRACT

A 2021 study described the development and validation of a blood-based precision medicine test called the molecular signature response classifier (MSRC) that uses 23 features to identify rheumatoid arthritis (RA) patients who are likely nonresponders to tumor necrosis factor-α inhibitor (TNFi) therapy. Both the gene expression features and clinical components (sex, body mass index, patient global assessment, and anti-cyclic citrullinated protein) included in the MSRC were statistically significant contributors to MSRC results. In response to continued inquiries on this topic, we write this letter to provide additional insights into the contribution of clinical components to the MSRC on the Network-004 validation cohort.

PMID:36441482 | DOI:10.1007/s40744-022-00506-0

Forensic Sci Med Pathol. 2022 Nov 28. doi: 10.1007/s12024-022-00560-8. Online ahead of print.

ABSTRACT

This paper presents the results of a study on the applicability of cerebrospinal fluid (CSF) collected from the spinal canal in the post-mortem determination of ethyl alcohol. The present study reviewed data of autopsy cases (n = 45), in which ethyl alcohol was detected in CSF using gas chromatography with a flame ionization detector (HS-GC-FID), to investigate ethyl alcohol concentrations in CSF, compared with blood. As a result of statistical analysis of the obtained data, a high positive correlation was found between blood ethanol concentration and cerebrospinal fluid collected from the spinal canal ethanol concentration. The Pearson correlation coefficient was statistically highly significant (p < 0.001) (r = 0.9503). The data obtained allowed us to conclude that cerebrospinal fluid collected from the spinal canal can be collected during an autopsy as an alternative biological specimen to assess the ethanol content. Cerebrospinal fluid collected from the spinal canal can corroborate and lend credibility to the results obtained for blood and, in special cases, when blood is drawn from putrefied bodies and may even be a superior specimen to blood for assessing ethyl alcohol intoxication status.

PMID:36441476 | DOI:10.1007/s12024-022-00560-8

J Epidemiol Glob Health. 2022 Nov 28. doi: 10.1007/s44197-022-00077-x. Online ahead of print.

ABSTRACT

BACKGROUND: In Benin, some riders of two-wheeled vehicles still do not wear helmets, the main protection against head injuries in road accidents. The objective of this study is to describe the characteristics of two-wheeled users, and to determine the factors influencing helmet use among this group.

METHODS: This is a prospective cross-sectional study of 977 two-wheeled road accident victims from a cohort. Proportions or means were calculated for the different variables. Statistical comparisons were made to test the association with helmet use. Logistic regression modelling was performed to identify factors associated with helmet use.

RESULTS: Among all subjects, 81.1% [CI_95% (78.5; 83.4)] wore a helmet. Factors explaining helmet use were female gender (OR = 2.8 [1.3-6.1]), purpose of trip (OR = 1.7 [1.1-2.6]), possession of health insurance (OR = 3.7 [1.3-10, 5]), having been driving for 15-20 years (OR = 2.6 [1.4-4.7]) or more than 20 years (OR = 3.4 [2.0-5.8]), good road conditions (OR = 3.1 [2.0-4.8]), and good visibility (OR = 1.9 [1.3-3.1]).

CONCLUSION: The factors influencing helmet use are gender, reason for travel, length of time as a driver, possession of health insurance, conditions, and visibility of the road on which the subject are driving. These factors are related to experience and appropriation of the notion of risk, but also related to the environment. To increase helmet use among two-wheelers, helmet awareness should take into account the individual factors found in this study. Enforcement actions should be strengthened, and the quality of the roads improved.

PMID:36441473 | DOI:10.1007/s44197-022-00077-x

Eur J Drug Metab Pharmacokinet. 2022 Nov 28. doi: 10.1007/s13318-022-00806-4. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The Extended Clearance Classification System (ECCS) was established to facilitate the timely anticipation of clearance rate determination according to the physicochemical characteristics of a given compound and in vitro passive membrane permeability. Unfortunately, distinguishing between renal and hepatic uptake clearance mechanisms using ECCS class 3B is not possible. We determined the effects of plasma protein binding (PPB) on major hepatic organic anion transporting polypeptide (OATP) and renal organic anion transporter (OAT) substrates. A modified ECCS could predict when renal or hepatic uptake mechanisms were the main clearance rate determinants (accounting for ≥ 70% of total clearance).

METHODS: A dataset of 66 human OATP and 41 OAT substrates was analyzed to determine the effect of PPB. A total of 63 acidic and zwitterionic, and high-molecular-weight (MW > 400 Da) compounds, including 50 drugs in ECCS classes 1B and 3B, were reanalyzed considering their PPB.

RESULTS: Statistical analyses revealed that hepatic uptake transporter (OATP1B1 and OATP1B3) substrates possess a high PPB rate of ≥ 90%, whereas OAT1 and/or OAT3 substrates possess low PPB rates of < 90%. By analyzing the 63 drugs on the basis of their PPB, the active hepatic uptakes of acids and zwitterions were determined to be the main clearance mechanisms, with PPB ≥ 90%, whereas renally eliminated drugs exhibited limited PPB (< 90%).

CONCLUSIONS: Therefore, PPB is an effective parameter for defining clearance rate determination for acidic and zwitterionic drugs with high MWs. Using PPB as an additional parameter in ECCS, clearance mechanisms for class 1B and 3B compounds can be predicted, and OATP and OAT substrates may be readily distinguished.

PMID:36441468 | DOI:10.1007/s13318-022-00806-4

Methods Mol Biol. 2023;2595:225-237. doi: 10.1007/978-1-0716-2823-2_16.

ABSTRACT

The bioinformatics analysis of miRNA is a complicated task with multiple operations and steps involved from processing of raw sequence data to finally identifying accurate microRNAs associated with the phenotypes of interest. A complete analysis process demands a high level of technical expertise in programming, statistics, and data management. The goal of this chapter is to reduce the burden of technical expertise and provide readers the opportunity to understand crucial steps involved in the analysis of miRNA sequencing data.In this chapter, we describe methods and tools employed in processing of miRNA reads, quality control, alignment, quantification, and differential expression analysis.

PMID:36441466 | DOI:10.1007/978-1-0716-2823-2_16

Mol Divers. 2022 Nov 28. doi: 10.1007/s11030-022-10574-7. Online ahead of print.

ABSTRACT

Cytochrome P450-1B1 is a majorly overexpressed drug-metabolizing enzyme in tumors and is responsible for inactivation and subsequent resistance to a variety of anti-cancer drugs, i.e., docetaxel, tamoxifen, and cisplatin. In the present study, a 3D quantitative structure-activity relationship (3D-QSAR) model has been constructed for the identification, design, and optimization of novel CYP1B1 inhibitors. The model has been built using a set of 148 selective CYP1B1 inhibitors. The developed model was evaluated based on certain statistical parameters including q² and r² which showed the acceptable predictive and descriptive capability of the generated model. The developed 3D-QSAR model assisted in understanding the key molecular fields which were firmly related to the selective CYP1B1 inhibition. A theoretic approach for the generation of new lead compounds with optimized CYP1B1 receptor affinity has been performed utilizing bioisosteric replacement analysis. These generated molecules were subjected to a developed 3D-QSAR model to predict the inhibitory activity potentials. Furthermore, these compounds were scrutinized through the activity atlas model, molecular docking, electrostatic complementarity, molecular dynamics, and waterswap analysis. The final hits might act as selective CYP1B1 inhibitors which could address the issue of resistance. This 3D-QSAR includes several chemically diverse selective CYP1B1 receptor ligands and well accounts for the individual ligand’s inhibition affinities. These features of the developed 3D-QSAR model will ensure future prospective applications of the model to speed up the identification of new potent and selective CYP1B1 receptor ligands.

PMID:36441444 | DOI:10.1007/s11030-022-10574-7

Oral Radiol. 2022 Nov 28. doi: 10.1007/s11282-022-00665-4. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the possible risk factors for mastoid cellulitis after treatment in patients with oral cancer.

METHODS: Patients with oral cancer who underwent preoperative and postoperative contrast-enhanced computed tomography (CECT) between January 2017 and March 2020 were retrospectively evaluated. Using an image reporting system, cases with reports containing the keyword “mastoid cellulitis” were registered in the mastoid cellulitis group. Fifty patients with oral cancer who did not develop mastoid cellulitis were randomly selected as the control group. Information concerning age, sex, location, and histopathological type of the primary tumor, presence or absence of cervical lymph node metastasis, and treatment methods were obtained from the hospital’s electronic medical records to investigate the association between these factors and the occurrence of mastoid cellulitis.

RESULTS: Statistically significant differences were observed in the following factors: age (p = 0.004), primary tumor site (p < 0.001), histopathological type (p = 0.032), radiotherapy (p < 0.001), and chemotherapy (p < 0.001). Logistic regression analysis revealed that maxillary tumors (p < 0.001), histopathological type (p = 0.047), and radiotherapy (p = 0.0301) were significantly associated with the occurrence of mastoid cellulitis.

CONCLUSIONS: In oral cancer, the risk of postoperative mastoid cellulitis was higher in patients with a maxillary tumor, histopathology other than squamous cell carcinoma, and history of radiotherapy.

PMID:36441420 | DOI:10.1007/s11282-022-00665-4