Tag: nevin manimala

Br J Psychiatry. 2022 Jun 3:1-11. doi: 10.1192/bjp.2022.77. Online ahead of print.

ABSTRACT

BACKGROUND: Research has shown that 20-30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders.

AIMS: To estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD.

METHOD: We conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16-25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression.

RESULTS: In the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI -2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm.

CONCLUSIONS: ADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.

PMID:35657651 | DOI:10.1192/bjp.2022.77

JAMA Netw Open. 2022 Jun 1;5(6):e2215217. doi: 10.1001/jamanetworkopen.2022.15217.

ABSTRACT

IMPORTANCE: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown.

OBJECTIVE: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant.

DESIGN, SETTING, AND PARTICIPANTS: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population.

INTERVENTIONS: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine.

MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30.

RESULTS: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

PMID:35657627 | DOI:10.1001/jamanetworkopen.2022.15217

JAMA Netw Open. 2022 Jun 1;5(6):e2215425. doi: 10.1001/jamanetworkopen.2022.15425.

ABSTRACT

IMPORTANCE: Drug overdose deaths in the US are currently the highest ever recorded; data collected from public health surveillance sources can help to identify emerging drug use patterns associated with overdose mortality rates, but the time lag in results often limits utility. Urine drug testing (UDT) is one potentially underused source that could augment surveillance efforts through timely data collection.

OBJECTIVE: To evaluate the correlation between real-time UDT results from a proprietary national database and overdose mortality data from the National Vital Statistics System.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study included 500 000 urine specimens submitted for UDT by substance use disorder (SUD) treatment health care practices and collected between January 1, 2013, and December 31, 2020. Real-time UDT data were obtained from the Millennium Health proprietary national database, and overdose mortality data were obtained from the National Vital Statistics System of the Centers for Disease Control and Prevention (CDC WONDER). Specimens were analyzed for specific drugs in 5 categories (cocaine, heroin, methamphetamine, synthetic opioids, and other opioids) using liquid chromatography-tandem mass spectrometry. Participants were adults aged 18 years and older who provided urine specimens at SUD treatment practices.

EXPOSURES: Urine drug testing.

MAIN OUTCOMES AND MEASURES: The primary outcome was the correlation between UDT positivity rates and overdose mortality rates at national, state, and county levels. Univariate and multivariate regression models were also used to evaluate the association between state- and county-level overdose mortality and standardized UDT positivity rates.

RESULTS: Among 500 000 unique patient specimens collected from SUD treatment practices between 2013 and 2020, 288 534 specimens (57.7%) were from men, and the median age of the study population was 34 years (IQR, 17-51 years). On a national level, synthetic opioids and methamphetamine were highly correlated with overdose mortality (Spearman ρ = 0.96 for both). When synthetic opioids were coinvolved, methamphetamine (ρ = 0.98), heroin (ρ = 0.78), cocaine (ρ = 0.94), and other opioids (ρ = 0.83) were also highly correlated with overdose mortality. In the absence of synthetic opioids, all drug categories were highly correlated (ρ = 0.75 for other opioids, 0.81 for heroin, and 0.88 for methamphetamine), with the exception of cocaine (ρ = -0.37). Synthetic opioids (ρ = 0.77) and methamphetamine (ρ = 0.80) had the strongest state-level correlations over time, whereas other opioids had the lowest correlation for both total positivity (ρ = 0.31) and positivity in the absence of synthetic opioids (ρ = 0.23). In Ohio, county-level correlation was strongest for synthetic opioids (ρ = 0.71), followed by heroin (ρ = 0.69) and methamphetamine (ρ = 0.67). At the state level, the multivariate incidence rate ratio (IRR) for synthetic opioids was 1.16 (95% CI, 1.14-1.19; P < .001), and at the county level, the IRR was 1.13 (95% CI, 1.09-1.17; P < .001), suggesting that for every 1-SD increase in the UDT positivity rate, there were 16.2% and 12.8% increases, respectively, in monthly overdose deaths. Both methamphetamine (11.7% increase per 1-SD increase in UDT positivity rate; IRR, 1.12; 95% CI, 1.09-1.14; P < .001) and cocaine (5.1% increase per 1-SD increase in UDT positivity rate; IRR, 1.05; 95% CI, 1.03-1.07; P < .001) also had significant positive associations with mortality rates, but the effect sizes were smaller than that of synthetic opioids (IRR, 1.16).

CONCLUSIONS AND RELEVANCE: In this study, UDT results were highly correlated with mortality rates at national, state, and county levels. These findings suggest that real-time UDT surveillance can help to quickly identify changes in drug use patterns that might inform targeted harm reduction strategies designed to prevent overdose deaths.

PMID:35657623 | DOI:10.1001/jamanetworkopen.2022.15425

Headache. 2022 Jun 3. doi: 10.1111/head.14324. Online ahead of print.

ABSTRACT

OBJECTIVE: This study assesses the concordance in migraine diagnosis between an online, self-administered, Computer-based, Diagnostic Engine (CDE) and semi-structured interview (SSI) by a headache specialist, both using International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria.

BACKGROUND: Delay in accurate diagnosis is a major barrier to headache care. Accurate computer-based algorithms may help reduce the need for SSI-based encounters to arrive at correct ICHD-3 diagnosis.

METHODS: Between March 2018 and August 2019, adult participants were recruited from three academic headache centers and the community via advertising to our cross-sectional study. Participants completed two evaluations: phone interview conducted by headache specialists using the SSI and a web-based expert questionnaire and analytics, CDE. Participants were randomly assigned to either the SSI followed by the web-based questionnaire or the web-based questionnaire followed by the SSI. Participants completed protocols a few minutes apart. The concordance in migraine/probable migraine (M/PM) diagnosis between SSI and CDE was measured using Cohen’s kappa statistics. The diagnostic accuracy of CDE was assessed using the SSI as reference standard.

RESULTS: Of the 276 participants consented, 212 completed both SSI and CDE (study completion rate = 77%; median age = 32 years [interquartile range: 28-40], female:male ratio = 3:1). Concordance in M/PM diagnosis between SSI and CDE was: κ = 0.83 (95% confidence interval [CI]: 0.75-0.91). CDE diagnostic accuracy: sensitivity = 90.1% (118/131), 95% CI: 83.6%-94.6%; specificity = 95.8% (68/71), 95% CI: 88.1%-99.1%. Positive and negative predictive values = 97.0% (95% CI: 91.3%-99.0%) and 86.6% (95% CI: 79.3%-91.5%), respectively, using identified migraine prevalence of 60%. Assuming a general migraine population prevalence of 10%, positive and negative predictive values were 70.3% (95% CI: 43.9%-87.8%) and 98.9% (95% CI: 98.1%-99.3%), respectively.

CONCLUSION: The SSI and CDE have excellent concordance in diagnosing M/PM. Positive CDE helps rule in M/PM, through high specificity and positive likelihood ratio. A negative CDE helps rule out M/PM through high sensitivity and low negative likelihood ratio. CDE that mimics SSI logic is a valid tool for migraine diagnosis.

PMID:35657603 | DOI:10.1111/head.14324

Endocrine. 2022 Jun 3. doi: 10.1007/s12020-022-03097-6. Online ahead of print.

ABSTRACT

INTRODUCTION: The incidence of small, differentiated thyroid cancer (DTC) cases has been increasing in the United States and the world mainly due to incidental detection because of widespread use of diagnostic modalities. While the option of active surveillance instead of surgical resection is getting more popular, there is still an open discussion about the best approach in these cases.

MATERIALS AND METHODS: The National Cancer Database was queried for patients diagnosed with non-metastatic small T1/N0 DTC between 2004 and 2016, who have known surgical status and Charlson comorbidity index of two or less. We evaluated the overall survival (OS) based on the surgery status using Kaplan-Meier estimates and multivariable cox regression analyses.

RESULTS: A total of 98,501 patients with non-metastatic small DTC were included, within which 96,612 (98.1%) were treated with surgery, and 1889 (1.9%) were not treated with surgery or other ablative modalities. We found that patients who were treated with surgery had better OS compared to patients who were not treated with surgery (mean OS 171 months vs 134.1 months, P < 0.001, median OS was not reached). This difference was still statistically significant even after we used propensity score matching for age, gender, race, Charlson-Deyo score, tumor size, and histology. On multivariate analysis, surgery was associated with better OS (HR 0.218; 95% CI: 0.196-0.244; P < 0.001). Same trend was found in subgroup analysis when we split the cohort according to tumor size (<1 and ≥1 cm), histology (follicular, papillary and Hurthle cell carcinoma), and age (<55 years vs ≥55 years).

CONCLUSION: Patients with non-metastatic small DTC who were treated with surgery had significant improvement in OS compared to patients who were not treated with surgery. Notwithstanding the limitations of the current analysis, these results call for caution prior to recommending routine surveillance for all patients with small DTC.

PMID:35657579 | DOI:10.1007/s12020-022-03097-6

Eur J Drug Metab Pharmacokinet. 2022 Jun 3. doi: 10.1007/s13318-022-00776-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: CC-292 is a potent, selective, orally administered small molecule inhibitor of Bruton’s tyrosine kinase (BTK). To support the clinical investigation of CC-292, a randomized, seven-treatment, seven-period, crossover study was conducted to assess the relative bioavailability, pH effect, food effect, and dose-proportionality of two formulated tablets of CC-292.

METHODS: Healthy subjects (n = 24) were enrolled in the study and randomly assigned into different treatment sequences. Blood samples were collected at pre-specified time points to measure the drug concentrations in plasma. Statistical analyses were performed to compare the pharmacokinetics of CC-292 under different conditions.

RESULTS: The relative bioavailability of the newly developed formulation [spray-dried dispersion (SDD)] to the reference formulation (P22) was 1.24. When a single dose of CC-292 SDD tablet was administered under fed conditions, the area under the plasma concentration-time curve from time zero to infinity (AUC_∞) increased by 10.9% and the maximum plasma drug concentration C_max) decreased by 19.4% compared to when CC-292 was administered under fasted conditions. When a single dose of CC-292 SDD tablet was administered after multiple doses of omeprazole, the area under the plasma concentration-time curve from time zero to infinity (AUC_∞) decreased by 36.8% and the maximum plasma drug concentration C_max) decreased by 48.1% compared to when CC-292 was administered alone. Over a dose range of 100-300 mg (SDD formulation), CC-292 exhibited more than dose-proportional increases of drug exposures.

CONCLUSIONS: CC-292 was well tolerated when administered to healthy subjects as single oral doses under all conditions. Food intake had no clinically relevant impact on CC-292 pharmacokinetics compared to fasted conditions. Therefore, CC-292 can be administered with or without food. Co-administration of CC-292 with multiple doses of omeprazole (40 mg) decreased the pharmacokinetic exposure of CC-292. However, the effect was not clinically relevant.

CLINICAL TRIALS REGISTRATION: NCT02433457.

PMID:35657581 | DOI:10.1007/s13318-022-00776-7

J Comput Neurosci. 2022 Jun 3. doi: 10.1007/s10827-022-00820-0. Online ahead of print.

ABSTRACT

The brain is believed to operate in part by making predictions about sensory stimuli and encoding deviations from these predictions in the activity of “prediction error neurons.” This principle defines the widely influential theory of predictive coding. The precise circuitry and plasticity mechanisms through which animals learn to compute and update their predictions are unknown. Homeostatic inhibitory synaptic plasticity is a promising mechanism for training neuronal networks to perform predictive coding. Homeostatic plasticity causes neurons to maintain a steady, baseline firing rate in response to inputs that closely match the inputs on which a network was trained, but firing rates can deviate away from this baseline in response to stimuli that are mismatched from training. We combine computer simulations and mathematical analysis systematically to test the extent to which randomly connected, unstructured networks compute prediction errors after training with homeostatic inhibitory synaptic plasticity. We find that homeostatic plasticity alone is sufficient for computing prediction errors for trivial time-constant stimuli, but not for more realistic time-varying stimuli. We use a mean-field theory of plastic networks to explain our findings and characterize the assumptions under which they apply.

PMID:35657570 | DOI:10.1007/s10827-022-00820-0

Environ Sci Pollut Res Int. 2022 Jun 3. doi: 10.1007/s11356-022-21144-7. Online ahead of print.

ABSTRACT

Childhood overweight and obesity (OWO) has risen dramatically in both developed and developing countries over the past few decades, creating a huge burden of disease. Ambient air pollution and emotional and behavioral problems are important influencing factors of OWO in preschoolers, but few studies have evaluated the impact of air pollution and emotional and behavioral problems on OWO of preschoolers in rural areas and their potential interactions. This study selected 3802 preschool children from 26 kindergartens in 4 rural areas of Anhui Province for a cross-sectional study. A total of 3636 individuals were included in the final analysis. In this study, outdoor air pollutants (PM_2.5 and O₃) were derived from the China Air Pollution Tracking (TAP) data set, matching preschoolers’ external air pollution exposure according to their kindergarten address codes to neighborhoods or administrative villages. OWO were assessed based on WHO Child Growth and Development Standards. Generalized linear model (GLM) and interplot model were used to evaluate the separate effects and potential interactions of air pollutants and emotional and behavioral problems on preschoolers’ OWO. In the separate analysis, we found a significant positive association between air pollution and emotional and behavioral problems and OWO among preschoolers. In the interaction analysis, air pollution could enhance the positive effect of emotional and behavioral problems on OWO in preschoolers. In addition, the effect of air pollution and emotional and behavioral problems on overweight and obesity was stronger in preschoolers aged 5 to 6 years. Finally, we also found a stronger positive association between emotional and behavioral problems among girls, macrosomia, non-left-behind children, and preschoolers without eating problems. This study provided a scientific basis for the control of air pollution and overweight and obesity among preschool children in Anhui Province.

PMID:35657543 | DOI:10.1007/s11356-022-21144-7

Infection. 2022 Jun 3. doi: 10.1007/s15010-022-01852-5. Online ahead of print.

ABSTRACT

PURPOSE: At the beginning of the COVID-19 pandemic, SARS-CoV-2 was often compared to seasonal influenza. We aimed to compare the outcome of hospitalized patients with cancer infected by SARS-CoV-2 or seasonal influenza including intensive care unit admission, mechanical ventilation and in-hospital mortality.

METHODS: We analyzed claims data of patients with a lab-confirmed SARS-CoV-2 or seasonal influenza infection admitted to one of 85 hospitals of a German-wide hospital network between January 2016 and August 2021.

RESULTS: 29,284 patients with COVID-19 and 7442 patients with seasonal influenza were included. Of these, 360 patients with seasonal influenza and 1625 patients with COVID-19 had any kind of cancer. Cancer patients with COVID-19 were more likely to be admitted to the intensive care unit than cancer patients with seasonal influenza (29.4% vs 24.7%; OR 1.31, 95% CI 1.00-1.73 p < .05). No statistical significance was observed in the mechanical ventilation rate for cancer patients with COVID-19 compared to those with seasonal influenza (17.2% vs 13.6% OR 1.34, 95% CI 0.96-1.86 p = .09). 34.9% of cancer patients with COVID-19 and 17.9% with seasonal influenza died (OR 2.45, 95% CI 1.81-3.32 p < .01). Risk factors among cancer patients with COVID-19 or seasonal influenza for in-hospital mortality included the male gender, age, a higher Elixhauser comorbidity index and metastatic cancer.

CONCLUSION: Among cancer patients, SARS-CoV-2 was associated with a higher risk for in-hospital mortality than seasonal influenza. These findings underline the need of protective measurements to prevent an infection with either COVID-19 or seasonal influenza, especially in this high-risk population.

PMID:35657531 | DOI:10.1007/s15010-022-01852-5

Methods Mol Biol. 2022;2526:259-275. doi: 10.1007/978-1-0716-2469-2_19.

ABSTRACT

Cellular redox signaling is triggered by accumulation of various reactive oxygen species (ROS) that integrate with other signaling cascades to enable plants to ultimately respond to (a)biotic stresses. The identification of key regulators underlying redox signaling networks is therefore of high priority. This chapter describes an improved mRNA interactome capture method that allows to systematically detect oxidative stress responsive regulators in the post-transcriptional gene regulation (PTGR) pathway. The protocol includes PSB-D suspension cell culture preparation, setup of oxidative stress conditions, short-term exposure to UV irradiation, cell lysis, pull-down and purification of crosslinked messenger ribonucleoproteins, their mass spectrometric analyses, and identification of proteome by statistical analyses. As result, a comprehensive inventory of the functional oxidative stress responsive RBPome (OxRBPome) is generated, which paves the way toward new insights into PTGR processes in redox signaling.

PMID:35657526 | DOI:10.1007/978-1-0716-2469-2_19