Nevin Manimala

Int J Med Inform. 2021 Sep 21;156:104588. doi: 10.1016/j.ijmedinf.2021.104588. Online ahead of print.

ABSTRACT

BACKGROUND: Electronic health record (EHR) data is commonly used for secondary purposes such as research and clinical decision support. However, reuse of EHR data presents several challenges including but not limited to identifying all diagnoses associated with a patient’s clinical encounter. The purpose of this study was to assess the feasibility of developing a schema to identify and subclassify all structured diagnosis codes for a patient encounter.

METHODS: To develop a subclassification schema we used EHR data from an interhospital transport data repository that contained complete hospital encounter level data. Eight discrete data sources containing structured diagnosis codes were identified. Diagnosis codes were normalized using the Unified Medical Language System and additional EHR data were combined with standardized terminologies to create and validate the subcategories. We then employed random forest to assess the usefulness of the new subcategorized diagnoses to predict post-interhospital transfer mortality by building 2 models, one using standard diagnosis codes, and one using the new subcategorized diagnosis codes.

RESULTS: Six subcategories of diagnoses were identified and validated. The subcategories included: primary or admitting diagnoses (10%), past medical, surgical or social history (9%), problem list (20%), comorbidity (24%), discharge diagnoses (6%), and unmapped diagnoses (31%). The subcategorized model outperformed the standard model, achieving a training AUROC of 0.97 versus 0.95 and testing model AUROC of 0.81 versus 0.46.

DISCUSSION: Our work demonstrates that merging structured diagnosis codes with additional EHR data and secondary data sources provides additional information to understand the role of diagnosis throughout a clinical encounter and improves predictive model performance. Further work is necessary to assess if subcategorizing produces benefits in interpreting the results of prognostic models and/or operationalizing the results in clinical decision support applications.

PMID:34607290 | DOI:10.1016/j.ijmedinf.2021.104588

Eur J Radiol. 2021 Sep 28;144:109978. doi: 10.1016/j.ejrad.2021.109978. Online ahead of print.

ABSTRACT

PURPOSE: The main goal of this systematic review was to assess the technical and clinical success, adverse events (AEs), surgery, and overall mortality proportion after percutaneous catheter drainage (PCD) of two pancreatic lesions.

METHODS: An extant search in online databases including Scopus, PubMed (Medline), Embase (Elsevier), Web of Science, Cochrane library, and Google Scholar, was conducted to recognize all studies that used PCD intervention in the management of pancreatic necrosis (PN) and pancreatic pseudocysts (PP). Random effects meta-analysis was performed, and Cochrane’s Q test and I²statistic were utilized to determine heterogeneity. In addition, meta-regression was used to explore the influence of categorical variables on heterogeneity.

RESULTS: Thirty-two studies (1398 patients) including PN in 26 (1256 cases, 89.8%) studies and PP in 6 (142 cases, 10.2%) studies were identified. Technical success proportion was 100% (95% confidence interval [CI] 100%-100%, I²: 0.0%), clinical success 63% (95% CI 55%-71%, I²: 92.9%), AEs 26% (95% CI 21%-31%, I²: 78%), surgery after PCD intervention 33% (95% CI 25%-40%, I²: 92.4%), and overall mortality was 13% (95% CI 9%-17%, I²: 82.8%). The most common ADs after PCD intervention were development of fistula (106, 42.6%), hemorrhage (44, 17.7%), sepsis (40, 16.1%).

CONCLUSION: A significant clinical success proportion with low AEs, surgery, and overall mortality proportion after PCD intervention was found, although the results should be interpreted with caution due to the high heterogeneity.

PMID:34607289 | DOI:10.1016/j.ejrad.2021.109978

ESMO Open. 2021 Oct 1;6(5):100279. doi: 10.1016/j.esmoop.2021.100279. Online ahead of print.

ABSTRACT

BACKGROUND: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored.

MATERIALS AND METHODS: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR.

RESULTS: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRAS^G12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRAS^G12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRAS^G12C patients tested negative for the presence of p.T790M resistance mutation.

CONCLUSIONS: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRAS^G12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature.

PMID:34607284 | DOI:10.1016/j.esmoop.2021.100279

J Biomech. 2021 Sep 27;129:110769. doi: 10.1016/j.jbiomech.2021.110769. Online ahead of print.

ABSTRACT

Although studies showed that several internal factors affect task-specific stability, the sex-specific effects of fatigue on whole-limb stability during a semi-cycle repetitive pointing task remain unidentified. Synergy and Motor Equivalence concepts in the UCM framework have been developed to explain task-specific stability. The motor equivalence model quantifies the amount of deviation in the space of elemental variables that occurs in two directions; one that preserves the performance variable (good variance), and the other that affects it (bad variance). Synergy index (the difference between good and bad variance divided by the total variance > 0) represent stability in performing a task. Healthy adults (n = 26, 13F; age: 35.3 ± 10.6 yrs.) performed an RPT by moving their dominant arm between a proximal target and a distal target in a standing position until near fatigue (Borg CR10 rating 8/10). Tridimensional kinematics of trunk, upper arm, forearm, and hand segments were captured by high-resolution cameras every minute, and joint angles were extracted according to the ZX’Y″ Euler sequence. Results showed the synergy > 0 for both women and men, reflecting synergies stabilizing the endpoint coordinate in both Non-Fatigue and Fatigue conditions. Statistics (ANOVA) showed a significant Condition * Sex effect (p = 0.01), with higher good (by 0.19 ± 0.1 rad) and bad variances (by 0.15 ± 0.09 rad) in women compared to men after fatigue. Higher good and bad variability, with no change in women’s performance could represent a less stable strategy, leading to the development of risk factors for neck-shoulder disorders.

PMID:34607280 | DOI:10.1016/j.jbiomech.2021.110769

Am J Otolaryngol. 2021 Sep 17;43(1):103214. doi: 10.1016/j.amjoto.2021.103214. Online ahead of print.

ABSTRACT

PURPOSE: Research indicates that most providers give opiates after endoscopic sinonasal surgery. The effectiveness of non-opiate medications after sinonasal surgery is poorly understood and most studies do not assess medication failure. This study compares oral opiate, oral opiate and topical steroid, and oral non-opiate pain control. Patient call-backs are used as a proxy for pain medication failure.

MATERIALS AND METHODS: This study compares three medication regiments after sinonasal surgery for 180 adults with chronic rhinosinusitis. Patients were instructed to take acetaminophen for mild pain. For moderate/severe pain, patients used: 1) oxycodone-acetaminophen, 2) oxycodone-acetaminophen + budesonide nasal rinses, or 3) meloxicam + acetaminophen. Patients were instructed to call clinic if pain was not controlled. Descriptive statistics compared cohorts. Chi-square tests compared call-backs between cohorts. Logistic regression adjusted for baseline differences in covariates, comorbidities, and operative sites.

RESULTS: Cohorts had similar age, sex distribution, disease features, and extent of surgery. The meloxicam cohort had less subjects with pain disorders. The oxycodone cohort had less subjects with diabetes, septoplasty, and turbinate reduction. After adjusting for baseline differences and using oxycodone as the reference group (n = 50), the odds of calling clinic for poorly controlled pain was 0.18 (95% Confidence Interval (CI): 0.05-0.6) in the meloxicam cohort (n = 45) and 0.19 (95% CI:0.07-0.5) in the oxycodone + budesonide rinses cohort (n = 85).

CONCLUSION: In this study, both meloxicam and oxycodone + budesonide rinses were more effective at controlling pain after sinonasal surgery than oxycodone alone.

PMID:34607277 | DOI:10.1016/j.amjoto.2021.103214

Psychoneuroendocrinology. 2021 Aug 14;133:105391. doi: 10.1016/j.psyneuen.2021.105391. Online ahead of print.

ABSTRACT

Salivary cortisol has been the central marker in psychoneuroendocrinological stress research for three decades. Given the technological possibilities to assess data in ecologically valid circumstances, many studies have implemented longitudinal assessments of salivary cortisol in study participants’ everyday life. Such studies bear the potential to understand real-life associations of cortisol with psychological traits, states, and health variables. Furthermore, changes in the neuroendocrine regulation and in cortisol reactivity can be used to evaluate the effects of behavioral interventions in real-life circumstances. While standardized paradigms have been developed to measure cortisol in laboratory settings, there is high heterogeneity in the assessment, statistical processing, and interpretation of everyday life cortisol measures. This methodological tutorial aims at summarizing important knowledge which had been accumulated during the past two decades and which could be used to set up an ambulatory assessment study focusing on salivary cortisol in everyday life. Practical advice for possible strategies at all stages of the research process is outlined in detail. Additionally, an example on how to statistically process cortisol data in a multilevel framework (including syntax) is provided. In these analyses, we investigate within- and between-person research questions regarding the association between stress and cortisol in daily life. Thus, the present work (a) can be used as tutorial for setting up everyday life studies focusing on the assessment of salivary cortisol, and (b) can be useful to avoid inconsistencies in study planning, data assessment and data processing in future studies.

PMID:34607270 | DOI:10.1016/j.psyneuen.2021.105391

Int Immunopharmacol. 2021 Sep 24;101(Pt A):108192. doi: 10.1016/j.intimp.2021.108192. Online ahead of print.

ABSTRACT

The mounting evidence regarding the pathogenesis of COVID-19 indicated that the cytokine storm has an axial role in the severity of this disease, which may lead to thrombotic complications, acute respiratory distress syndrome (ARDS), and myocardial damage, among other consequences. It has recently been demonstrated that statins are known to have anti-viral, anti-inflammatory, anti-thrombotic, and immunomodulatory features; however, their advantage has not been evaluated in COVID-19. This study aimed to investigate the protective effects of lovastatin in intensive care unit (ICU) patients with COVID-19. The case-control study consists of 284 ICU patients, which classified into three groups as follows: 1) the patients who no received lovastatin as a control (92 patients), 2) patients received 20 mg per day lovastatin (99 patients), and 3) patients received 40 mg per day lovastatin (93 patients). Each group’s demographic and clinical parameters, along with CRP, interleukin (IL)-6, IL-8 levels, and mortality rate, were studied in three-time points. The results showed that there was no statistically significant difference between our study groups in terms of age and sex. (P > 0.05). Besides, in patients, receiving lovastatin the CRP, IL-6, IL-8 levels were significantly decreased from T1 to T3 than to the control group. Our results also showed that the use of lovastatin in COVID-19 patients significantly reduced the length of hospitalization in the ICU compared with the control group. In addition, our results showed that the mortality rate in patients receiving lovastatin was lower when compared to the control group; however, this difference was not statistically significant. Since the cytokine storm is a significant factor in the pathology of SARS-CoV-2, our findings highlighted the potential use of lovastatin to mitigate the inflammatory response induced by SARS-CoV-2 infection.

PMID:34607230 | DOI:10.1016/j.intimp.2021.108192

Lung Cancer. 2021 Sep 17;161:180-188. doi: 10.1016/j.lungcan.2021.09.004. Online ahead of print.

ABSTRACT

OBJECTIVES: Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and the programmed death receptor-1 (PD-1) inhibitor nivolumab plus CT have demonstrated encouraging efficacy for treatment of non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated the quadruple combination of veliparib with nivolumab and doublet CT in patients with unresectable advanced/metastatic NSCLC.

MATERIALS AND METHODS: Patients were enrolled into five dosing cohorts: patients received veliparib 120 mg twice daily (BID) combined with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and paclitaxel 200 mg/m² (C/PAC) or veliparib 80/120/200/240 mg BID in combination with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and pemetrexed 500 mg/m² (C/PEM). Primary objective was to identify the recommended phase 2 dose (RP2D) of veliparib + nivolumab + CT. Safety, tolerability, and efficacy of this combination were also assessed.

RESULTS: Twenty-five patients were enrolled: 6 patients received veliparib 120 mg BID + nivolumab + C/PAC and 19 received veliparib (80-240 mg BID) + nivolumab + C/PEM. No dose-limiting toxicities were reported, and the RP2Ds were veliparib 120 mg BID + nivolumab + C/PAC, and veliparib 240 mg BID + nivolumab + C/PEM. The most common any-grade adverse events (AEs) were fatigue (56%), nausea (52%), and anemia (48%). Grade 3/4 AEs included anemia (32%) and neutropenia (24%), and the most frequent serious AE was malignant neoplasm progression (12%). Veliparib exhibited approximately dose proportional kinetics in the dose range 80-240 mg BID combined with nivolumab and C/PEM, with no effects on pemetrexed pharmacokinetics. Overall, the confirmed objective response rate was 40%, and best overall response was 64%.

CONCLUSION: Veliparib combined with nivolumab and platinum doublet CT was tolerated in patients with advanced/metastatic NSCLC, and no evidence of drug-drug interaction was observed. Although preliminary, this quadruple therapy may have promising antitumor activity.

PMID:34607210 | DOI:10.1016/j.lungcan.2021.09.004

J Pharm Biomed Anal. 2021 Sep 21;206:114384. doi: 10.1016/j.jpba.2021.114384. Online ahead of print.

ABSTRACT

The genus Uncaria belongs to the family of Rubiaceae, which contains approximately 34 species. It has been widely used as a traditional Chinese medicine (TCM) in China to treat hypertension, fevers, headaches, gastrointestinal illness, epilepsy, wounds, and ulcers. Uncaria rhynchophylla. (Miq.) Miq. ex Hvail.(URM) and Uncaria hirsuta Havil.(UHH) are mainly used as remedies for hypertension, which both belong to the resource of “Gou-teng” in the Chinese Pharmacopoeia. However, the authentic antihypertensive components of Uncaria still have not been fully elucidated until now. In this work, we firstly explored and compared the vasorelaxation effect of URM and UHH on the isolated rat mesenteric artery ring. Then, the variations of metabolite profiles between URM and UHH samples were investigated by UHPLC/Q-Orbitrap-MS, and 16 different metabolites have been found through multivariate statistical analysis. Further, the potential vasodilative compounds which include corynoxeine, isocorynoxeine, isorhynchophylline, rhynchophylline, hirsuteine and hirsutine were screened through the correlation analysis between metabolites and anti-hypertension activities. And the relaxation effects of the six compounds on the mesenteric artery have verified. The results indicated that metabolomics combined with correlation analysis could be effective strategies to rapid explore the active compounds from TCM.

PMID:34607203 | DOI:10.1016/j.jpba.2021.114384

Clin Neurol Neurosurg. 2021 Sep 17;210:106954. doi: 10.1016/j.clineuro.2021.106954. Online ahead of print.

ABSTRACT

In the present study, we investigated whether Neuroaspis PLP10™, a well-designed intervention, rich in omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) with specific antioxidant vitamins, may exert positive action in the improvement of Parkinson’s disease symptoms and perhaps delay the progression of the disease when used as an adjuvant to the conventional treatment. Forty patients were randomized 1:1 to receive either 20 ml dose, once daily, of control (pure virgin olive oil) or Neuroaspis PLP 10™, a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure gamma (γ)-tocopherol (760 mg), for a total of 30 months in a randomized double-blind, placebo-controlled trial. Participants completed assessments based on the Hoehn and Yahr Staging Scale of Parkinson’s Disease (HY scale) and the Unified Parkinson’s Disease Rating Scale (UPDRS) III. Overall, for this small sample size clinical trial, Neuroaspis PLP10™ supplementation as an adjuvant treatment for 30 months in PD patients significantly delayed disease progression according to UPDRS (p ≤ 0.05) Vs placebo.

PMID:34607196 | DOI:10.1016/j.clineuro.2021.106954