Nevin Manimala

Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.

ABSTRACT

Disability progression in multiple sclerosis remains resistant to treatment. The absence of a suitable biomarker to allow for phase 2 clinical trials presents a high barrier for drug development. We propose to enable short proof-of-concept trials by increasing statistical power using a deep-learning predictive enrichment strategy. Specifically, a multi-headed multilayer perceptron is used to estimate the conditional average treatment effect (CATE) using baseline clinical and imaging features, and patients predicted to be most responsive are preferentially randomized into a trial. Leveraging data from six randomized clinical trials (n = 3,830), we first pre-trained the model on the subset of relapsing-remitting MS patients (n = 2,520), then fine-tuned it on a subset of primary progressive MS (PPMS) patients (n = 695). In a separate held-out test set of PPMS patients randomized to anti-CD20 antibodies or placebo (n = 297), the average treatment effect was larger for the 50% (HR, 0.492; 95% CI, 0.266-0.912; p = 0.0218) and 30% (HR, 0.361; 95% CI, 0.165-0.79; p = 0.008) predicted to be most responsive, compared to 0.743 (95% CI, 0.482-1.15; p = 0.179) for the entire group. The same model could also identify responders to laquinimod in another held-out test set of PPMS patients (n = 318). Finally, we show that using this model for predictive enrichment results in important increases in power.

PMID:36163349 | DOI:10.1038/s41467-022-33269-x

J Neurointerv Surg. 2022 Sep 26:neurintsurg-2022-019266. doi: 10.1136/jnis-2022-019266. Online ahead of print.

ABSTRACT

BACKGROUND: Successful recanalization after endovascular thrombectomy serves as the primary endpoint in clinical trials and is a crucial predictor of long-term outcomes. Radiographic outcomes for various interventions have been shown to vary based on the type of interpreter, including the site interventionalist compared with an independent reader.

OBJECTIVE: To compare angiographic outcomes in stroke thrombectomy procedures based on the type of reader.

METHODS: A systematic literature search was conducted in Medline, EMBASE, Scopus, and Web-of-Science through February 2022. We included primary studies that reported core laboratory-read and operator angiographic outcomes after mechanical thrombectomy for ischemic stroke. Furthermore, study-defined successful recanalization data were collected.

RESULTS: Eight studies were included with 4797 patients, 51.2% of whom were male. Four thousand, four hundred and thirty-one patients had core readings, and 4211 had operator readings. Study-defined successful recanalization was significantly higher for operator (84%, 3543/4211) examinations than for core laboratory-read (78.4%, 3476/4431) examinations (p<0.001; OR=1.462, 95% CI 1.175 to 1.819). The modified Thrombolysis in Cerebral Infarction (mTICI) scale score of ≥2 b was higher for operator (85%, 3341/3929) examinations than for core laboratory-read (78.6%, 3107/3952) examinations (p<0.001; OR=1.349, 95% CI 1.071 to 1.701). mTICI 3 was significantly higher for operator (54.6%, 1000/1832) examinations than for core laboratory-read (39.9%, 731/1832) examinations (p<0.001; OR=1.823, 95% CI 1.598 to 2.081).

CONCLUSION: Operator angiographic reads are statistically significantly higher than core laboratory-read readings following stroke thrombectomy, especially for complete recanalization. These differences should be considered when interpreting reports of angiographic outcomes after thrombectomy.

PMID:36163347 | DOI:10.1136/jnis-2022-019266

Heart Lung Circ. 2022 Sep 23:S1443-9506(22)01089-7. doi: 10.1016/j.hlc.2022.08.016. Online ahead of print.

ABSTRACT

OBJECTIVE: Data regarding optimal electrode positioning for direct current cardioversion (DCCV) of atrial fibrillation (AF) has been inconsistent. This meta-analysis was conducted to systematically compare the efficacy of anteroposterior (AP) versus anterolateral (AL) electrode placement for DCCV of AF.

METHODS: Electronic databases were searched for randomised controlled trials (RCTs) comparing AP versus AL electrode positioning in patients undergoing DCCV for AF. Primary endpoints were first-shock success and overall DCCV success. Subgroup analysis was performed by defibrillator waveform (monophasic versus biphasic). Meta-regression analyses were performed to assess for significant moderators.

RESULTS: Twelve (12) RCTs, including a total of 2,046 patients, met inclusion criteria. Neither first-shock success (relative risk [RR] 0.92; 95% CI 0.79-1.07; p=0.28) nor overall DCCV success (RR 1.01; 95% CI 0.96-1.05; p=0.78) were significantly different with AP versus AL electrode positioning. The mean number of shocks (mean difference [MD] 0.3, 95% CI -0.4 to 0.9), energy level of first successful shock (MD 3 joules; 95% CI -20 to 27) and cumulative energy delivered (MD 39 joules; 95% CI -168 to 246) were similar in AP versus AL arms. In subgroup analysis of six RCTs using biphasic defibrillators, improvement in first-shock success (RR 0.85; 95% CI 0.69-1.03; p=0.10) and overall DCCV success (RR 0.97; 95% CI 0.93-1.01; p=0.09) with AL electrode positioning did not reach statistical significance. Meta-regression analyses identified older age, higher body mass index, and longer AF duration as significant moderators favouring AL electrode positioning.

CONCLUSIONS: Pooled analysis of randomised data overall does not show a significant difference in efficacy between AP versus AL electrode positioning. Meta-regression and subgroup analyses suggest that, in contemporary practice with use of biphasic defibrillators, there may be a subset of AF patients in whom AL electrode positioning improves efficacy of DCCV.

PMID:36163316 | DOI:10.1016/j.hlc.2022.08.016

Nat Genet. 2022 Sep 26. doi: 10.1038/s41588-022-01171-3. Online ahead of print.

ABSTRACT

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.

PMID:36163277 | DOI:10.1038/s41588-022-01171-3

BMC Pharmacol Toxicol. 2022 Sep 26;23(1):72. doi: 10.1186/s40360-022-00614-1.

ABSTRACT

BACKGROUND: Mushroom poisoning can cause gastrointestinal, renal, and hepatic symptoms and even death. This descriptive study examined the demographic, clinical, and laboratory findings of patients with fungal poisoning, a type of fungus causing the poisoning, and the incidence and mortality rates of fungal poisoning in Kermanshah province, western Iran, from 2014 to 2018.

METHODS: The medical records of 193 patients with mushroom poisoning from 2014 to 2018 were evaluated. The liver and kidney function tests, electrolytes, abdominal and pelvic ultrasound, chest x-ray, coagulation tests, and coagulation factors (fibrinogen, prothrombin) were assessed. Data were collected from the medical records of patients admitted to the Poisoning Center of Imam Khomeini Hospital in Kermanshah, Iran using a researcher-made checklist. Data were analyzed by SPSS (version 16) using descriptive statistics, including mean, standard deviation, and frequency distribution tables. Trend analysis for proportion was done by chi-square statistics in STATA-14 software (ptrend command).

RESULTS: Of cases, ‌51.3% were male, 92.6% were city dwellers, 38.3% were aged 21-40 years, and 92.5% were poisoned during the spring. The fungus that caused poisoning was Amanita virosa. The gastrointestinal, nervous, and visual systems were the most common systems involved. The most common gastrointestinal symptoms included nausea and vomiting (72.0%) and abdominal pain (71.0%). Vertigo (11.9%) and headache (9.3%) were the most common neurological symptoms. The most common visual manifestation was blurred vision (7.8%). Of cases, 23.7% had metabolic acidosis. The increased alkaline phosphatase level was the most common liver disorder in 98.7% of the cases. Increased blood urea nitrogen and creatinine levels were also reported in 21.0% and 17.7% of the cases, respectively. The serum lactic dehydrogenase and creatine phosphokinase levels also increased in 99.3% and 30.2% of the patients, respectively. The mortality rate was 1.6% (n = 3).

CONCLUSION: The fungal poisoning diagnosis should always be considered in young patients referred to the emergency department with gastrointestinal complaints, a history of consuming wild self-picked mushrooms, and high liver and kidney test values. Since most fungal poisonings occur in the spring, it is necessary to inform the community of the dangers of consuming self-picked wild mushrooms, especially in this season.

PMID:36163273 | DOI:10.1186/s40360-022-00614-1

Virol J. 2022 Sep 26;19(1):153. doi: 10.1186/s12985-022-01881-4.

ABSTRACT

BACKGROUND: JC polyomavirus (JCPyV) is known to induce solid tumors such as astrocytomas, glioblastomas, and neuroblastomas in experimental animals, and recent studies have shown that the virus may be correlated with carcinogenesis. This study aimed to evaluate the impact of JCPyV on the progression of papillary thyroid cancer (PTC).

METHODS: A total of 1057 samples, including 645 paraffin-embedded PTC biopsy samples (PEBS) and 412 fresh biopsy samples (FBS), and 1057 adjacent non-cancerous samples were evaluated for the presence of JCPyV DNA and RNA.

RESULTS: We observed that 10.8% (114/1057) samples, including 17.5% (72/412) FBS and 6.5% (42/645) PEBS were positive for the JCPyV DNA. Among the JCPyV-positive samples, the mean JCPyV copy number was lower in patients with PEBS (0.3 × 10^-4 ± 0.1 × 10^-4 copies/cell) compared to FBS (1.8 × 10^-1 ± 0.4 × 10^-1 copies/cell) and non-PTC normal samples (0.2 × 10^-5 ± 0.01 × 10^-5 copies/cell), with a statistically significant difference (P < 0.001). The LT-Ag RNA expression was lower in PEBS than in FBS, while no VP1 gene transcript expression was found.

CONCLUSIONS: Although our results confirmed the presence of JCPyV in some Iranian patients with PTC, more research is needed to verify these results.

PMID:36163265 | DOI:10.1186/s12985-022-01881-4

Sci Rep. 2022 Sep 26;12(1):16057. doi: 10.1038/s41598-022-20421-2.

ABSTRACT

Independent coffee shops are the alternative workplaces for people working remotely from traditional offices but are not concerned about their indoor air quality (IAQ). This study aimed to rank the environmental factors in affecting the IAQ by Random Forests (RFs) models. The indoor environments and human activities of participated independent coffee shops were observed and recorded for 3 consecutive days including weekdays and weekend during the business hours. The multi-sized particulate matter (PM), particle-bound polycyclic aromatic hydrocarbons (p-PAHs), total volatile organic compounds (TVOCs), CO, CO₂, temperature and relative humidity were monitored. RFs models ranked the environmental factors. More than 20% of the 15-min average concentrations of PM₁₀, PM_2.5, and CO₂ exceeded the World Health Organization guidelines. Occupant density affected TVOCs, p-PAHs and CO₂ concentrations directly. Tobacco smoking dominated PM₁₀, PM_2.5, TVOCs and p-PAHs concentrations mostly. CO concentration was affected by roasting bean first and tobacco smoking secondly. The non-linear relationships between temperature and these pollutants illustrated the relative low concentrations happened at temperature between 22 and 24 °C. Tobacco smoking, roasting beans and occupant density are the observable activities to alert the IAQ change. Decreasing CO₂ and optimizing the room temperature could also be the surrogate parameters to assure the IAQ.

PMID:36163251 | DOI:10.1038/s41598-022-20421-2

Sci Rep. 2022 Sep 26;12(1):16041. doi: 10.1038/s41598-022-20302-8.

ABSTRACT

There is a lack of information on the epidemiology of acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in developing countries. This research presents incidence and mortality rates of stroke patients based on hospital admission and discharge status in one of the Central Asian countries by analysis of large-scale healthcare data. The registry data of 177,947 patients admitted to the hospital with the diagnosis of stroke between 2014 and 2019 were extracted from the National Electronic Health System of Kazakhstan. We provide descriptive statistics and analyze the association of socio-demographic and medical characteristics such as comorbidities and surgical treatments. Among all stroke patients, the incidence rate based on hospital admission of AIS was significantly higher compared to SAH and ICH patients. In 5 year follow-up period, AIS patients had a better outcome than SAH and ICH patients (64.7, 63.1 and 57.3% respectively). The hazard ratio (HR) after the trepanation and decompression surgery was 2.3 and 1.48 for AIS and SAH patients; however, it was protective for ICH (HR = 0.87). The investigation evaluated an increase in the all-cause mortality rates based on the discharge status of stroke patients, while the incidence rate decreased over time.

PMID:36163245 | DOI:10.1038/s41598-022-20302-8

Transl Psychiatry. 2022 Sep 26;12(1):410. doi: 10.1038/s41398-022-02181-9.

ABSTRACT

Adverse effects of psychological stress on physical and mental health, especially in older age, are well documented. How perceived stress relates to the epigenetic clock measure, DNA methylation age acceleration (DNAmAA), is less well understood and existing studies reported inconsistent results. DNAmAA was estimated from five epigenetic clocks (7-CpG, Horvath’s, Hannum’s, PhenoAge and GrimAge DNAmAA). Cohen’s Perceived Stress Scale (PSS) was used as marker of psychological stress. We analyzed data from 1,100 Berlin Aging Study II (BASE-II) participants assessed as part of the GendAge study (mean age = 75.6 years, SD = 3.8 years, 52.1% women). In a first step, we replicated well-established associations of perceived stress with morbidity, frailty, and symptoms of depression in the BASE-II cohort studied here. In a second step, we did not find any statistically significant association of perceived stress with any of the five epigenetic clocks in multiple linear regression analyses that adjusted for covariates. Although the body of literature suggests an association between higher DNAmAA and stress or trauma during early childhood, the current study found no evidence for an association of perception of stress with DNAmAA in older people. We discuss possible reasons for the lack of associations and highlight directions for future research.

PMID:36163242 | DOI:10.1038/s41398-022-02181-9

J Med Imaging Radiat Sci. 2022 Sep 23:S1939-8654(22)00354-X. doi: 10.1016/j.jmir.2022.09.002. Online ahead of print.

ABSTRACT

INTRODUCTION: Vertigo has been reported by operators and patients during magnetic resonance imaging (MRI) examinations and found to increase in severity as the strength of the scanner magnet increases. This study examined a cohort of MRI radiographers’ awareness of MRI-induced vertigo and their perspectives on post-MRI care.

METHODS: This cross-sectional study used a web-based survey distributed to 110 radiographers. The 18-item survey included questions to elicit demographic information, MRI radiographers’ awareness of MRI-induced vertigo, and their perspectives on the post-MRI care that should be provided to patients. Responses were collected between June 2021 and January 2022. The collected data were analyzed using SPSS, version 27.

RESULTS: A total of 110 MRI radiographers completed the survey. Participants were predominantly male (64.5 %) and working in public practice (91.8 %). Almost all the radiographers were aware of MRI-induced vertigo. About two-thirds of participants knew patients needed assistance off the couch. Nearly all participants knew patients should be asked about their experience with MRI-induced vertigo after their procedures. There were statistically significant associations between the size of magnetic field strength used by the participants and their appreciation of the needed support for patients post-MRI examinations (p= 0.012).

CONCLUSION: This study provides the first insight into Saudi Arabian MRI radiographers’ awareness and perceptions of MRI-induced vertigo. Radiographers were largely aware of MRI-induced vertigo and the supportive care they were supposed to provide their patients.

IMPLICATIONS FOR PRACTICE: The current study points to a need for training to expand awareness levels of MRI-induced vertigo among a few Saudi MRI radiographers.

PMID:36163238 | DOI:10.1016/j.jmir.2022.09.002