Category: Nevin Manimala

CJEM. 2021 Apr 10. doi: 10.1007/s43678-021-00119-6. Online ahead of print.

ABSTRACT

BACKGROUND: The recommended rocuronium dose for rapid sequence intubation is 1.0 mg/kg; however, the optimal dose for emergency airway management is not clear. We assessed the relationship between rocuronium dose and first-attempt success among emergency department (ED) patients undergoing rapid sequence intubation.

METHODS: This is a secondary analysis of the National Emergency Airway Registry (NEAR), an observational 25-center registry of ED intubations. Ninety percent recording compliance was required from each site for data inclusion. We included all patients > 14 years of age who received rocuronium for rapid sequence intubation from 1 Jan 2016 to 31 Dec 2018. We compared first-attempt success between encounters using alternative rocuronium doses (< 1.0, 1.0-1.1, 1.2-1.3 and ≥1.4 mg/kg). We performed logistic regressions to control for predictors of difficult airways, indication, pre-intubation hemodynamics, operator, body habitus and device. We also performed subgroup analyses stratified by device (direct vs. video laryngoscopy). We calculated univariate descriptive statistics and odds ratios (OR) from multivariable logistic regressions with cluster-adjusted 95% confidence intervals (CI).

RESULTS: 19,071 encounters were recorded during the 3-year period. Of these, 8,034 utilized rocuronium for rapid sequence intubation. Overall, first attempt success was 88.4% for < 1.0 mg/kg, 88.1% for 1.0-1.1 mg/kg, 89.7% for 1.2-1.3 mg/kg, and 92.2% for ≥1.4 mg/kg. Logistic regression demonstrated that when direct laryngoscopy was used and when compared to the standard dosing range of 1.0-1.1 mg/kg, the adjusted odds of a first attempt success was significantly higher in ≥1.4 mg/kg group at 1.9 (95% CI 1.3-2.7) relative to the other dosing ranges, OR 0.9 (95% CI 0.7-1.2) for < 1.0 mg/kg and OR 1.2 (95% CI 0.9-1.7) for the 1.2-1.3 mg/kg group. First-attempt success was similar across all rocuronium doses among patients utilizing video laryngoscopy. Patients who were hypotensive (SBP < 100 mmHg) prior to intubation had higher first-attempt success 94.9% versus 88.6% when higher doses of rocuronium were used. The rates of all peri-intubation adverse events and desaturation were similar between dosing groups, laryngoscope type utilized and varying pre-intubation hemodynamics.

CONCLUSIONS: Rocuronium dosed ≥1.4 mg/kg was associated with higher first attempt success when using direct laryngoscopy and among patients with pre-intubation hypotension with no increase in adverse events. We recommend further prospective evaluation of the dosing of rocuronium prior to offering definitive clinical guidance.

PMID:33837951 | DOI:10.1007/s43678-021-00119-6

J Am Geriatr Soc. 2021 Apr 10. doi: 10.1111/jgs.17156. Online ahead of print.

ABSTRACT

BACKGROUND: Older patients with acute decompensated heart failure (ADHF) have severely impaired physical function (PF) and quality of life (QOL). However, relationships between impairments in PF and QOL are unknown but are relevant to clinical practice and trial design.

METHODS: We assessed 202 consecutive patients hospitalized with ADHF in the multicenter Rehabilitation Therapy in Older Acute HF Patients (REHAB-HF) Trial. PF measures included Short Physical Performance Battery (SPPB) and 6-min walk distance (6MWD). Disease-specific QOL was assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). General QOL was assessed by the Short Form-12 (SF-12) and EuroQol-5D-5L. PF was evaluated as a predictor of QOL using stepwise regression adjusted for age, sex, race, and New York Heart Association class.

RESULTS: Participants were 72 ± 8 years, 54% women, 55% minority race, 52% with reduced ejection fraction, and body mass index 33 ± 9 kg/m² . Participants had severe impairments in PF (6MWD 185 ± 99 m, SPPB 6.0 ± 2.5 units) and disease-specific QOL (KCCQ Overall Score 41 ± 21 and Physical Score 47 ± 24) and general QOL (SF-12 Physical Score 28 ± 9 and EuroQol Visual Analog Scale 57 ± 23). There were modest, statistically significant correlations between 6MWD and KCCQ Overall, KCCQ Physical Limitation, and SF-12 Physical Scores (r = 0.23, p < 0.001; r = 0.30, p < 0.001; and r = 0.24, p = 0.001, respectively); and between SPPB and KCCQ Physical and SF-12 Physical Scores (r = 0.20, p = 0.004, and r = 0.19, p = 0.007, respectively). Both 6MWD and SPPB were correlated with multiple components of the EuroQol-5D-5L. 6MWD was a significant, weak predictor of KCCQ Overall Score and SF-12 Physical Score (estimate = 0.05 ± 0.01, p < 0.001 and estimate = 0.05 ± 0.02, p = 0.012, respectively). SPPB was a significant, weak predictor of KCCQ Physical Score and SF-12 Physical Score (estimate = 1.37 ± 0.66, p = 0.040 and estimate = 0.54 ± 0.25, p = 0.030, respectively).

CONCLUSION: In older, hospitalized ADHF patients, PF and QOL are both severely impaired but are only modestly related, suggesting that PF and QOL provide complementary information and assessment of both should be considered to fully assess clinically meaningful patient-oriented outcomes.

PMID:33837953 | DOI:10.1111/jgs.17156

J Med Virol. 2021 Apr 10. doi: 10.1002/jmv.27011. Online ahead of print.

ABSTRACT

INTRODUCTION: We have read with great interest the meta-analysis that examined the impact of increased red cell distribution width (RDW) and COVID-19 outcomes, conducted by Lee and colleagues, and recently published in the Journal of Medical Virology. The authors concluded that elevations in RDW were associated with adverse COVID-19 outcomes. However, the impact of elevation of RDW independent of anemia in COVID-19 remains to be clarified.

METHODS: Patients ≥18 years who were diagnosed with COVID-19 at the Mount Sinai Health System between March 1 and April 1, 2020 and had a complete blood count (CBC) at presentation (n=2562) were selected to assess the association between RDW and mortality. Multivariable Cox proportional hazards regression models, stratified by presence of anemia, were performed to assess the independent association of RDW with mechanical ventilation and mortality.

RESULTS: At univariate analysis, elevated RDW was statistically significantly associated with mechanical ventilation (p = 0.0109) and mortality (p < 0.0001). We found that elevated RDW was statistically associated with higher risk of both being placed on a ventilator (HRadj: 1.66, 95% CI: 1.19-2.32) and mortality (HRadj: 1.60, 95% CI: 1.18-2.15) in non-anemic patients, but there was no association in anemic patients. These associations were independent of the effects of age, sex, race, and CCI.

DISCUSSION: In this study, we show that the elevated RDW association with mortality and mechanical ventilation is present exclusively in non-anemic patients. Therefore, we propose that RDW be considered by clinicians, especially in non-anemic patients, when risk-stratifying COVID-19 patients. This article is protected by copyright. All rights reserved.

PMID:33837966 | DOI:10.1002/jmv.27011

Drug Saf. 2021 Apr 10. doi: 10.1007/s40264-021-01063-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Genetic variations of enzymes that affect the pharmacokinetics and hence effects of medications differ between ethnicities, resulting in variation in the risk of adverse drug reactions (ADR) between different populations. Previous work has demonstrated that risk-group considerations can be incorporated into approaches of statistical signal detection. It is unknown whether databases of individual case safety reports (ICSRs) are sensitive to pharmacogenomic differences between populations.

OBJECTIVE: The aim of this study was to explore the sensitivity of a global database of ICSRs to known pharmacogenomic risk variants common in Japan.

METHODS: The data source was VigiBase, the global database of ICSRs, including all reports entered in the version frozen on 5 January 2020. Subgroup disproportionality analysis was used to compare ICSRs of two subgroups, Japan and rest of world (RoW). Reports for UGT1A1-metabolized irinotecan and the CYP2C19-metabolized drugs voriconazole, escitalopram and clopidogrel were selected for comparison between the subgroups based upon known genetic polymorphisms with high prevalence in Japan. Contrast between the subgroups was quantified by IC delta [Formula: see text]), a robust shrinkage observed-to-expected (OE) ratio on a log scale. Harmonic mean p values (HMP) were calculated for each drug to evaluate whether a list of pre-specified ADRs were collectively significantly over- (or under-)reported as hypothesized. Daily drug dosages were calculated for ICSRs with sufficient information, and dose distributions were compared between Japan and RoW and related to differences in regionally approved doses.

RESULTS: The predictions of over-reporting patterns for specific ADRs were observed and confirmed in bootstrap HMP analyses (p = 0.004 for irinotecan and p < 0.001 for each of voriconazole, escitalopram and clopidogrel) and compared with similar drugs with different metabolic pathways. The impact of proactive regulatory action, such as recommended dosing and therapeutic drug monitoring (TDM), was also observable within the global database. For irinotecan and escitalopram, there was evidence of use of lower dosages as recommended in the Japanese labels; for voriconazole, there was evidence of use of TDM with an over-reporting of terms related to drug level measurements and an under-reporting of liver toxicity.

CONCLUSIONS: Pharmaco-ethnic vulnerabilities caused by pharmacogenomic differences between populations may contribute to differences in ADR reporting between countries in a global database of ICSRs. Regional analyses within a global database can inform on the effectiveness of local risk minimization measures and should be leveraged to catalyse the conversion of real-world usage into safer use of drugs in ethnically tailored ways.

PMID:33837924 | DOI:10.1007/s40264-021-01063-1

Int J Lab Hematol. 2021 Apr 9. doi: 10.1111/ijlh.13533. Online ahead of print.

ABSTRACT

INTRODUCTION: Outbreak of corona virus disease in 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Our aim is to document hematological parameters of patients with COVID-19 during initial stage of diagnosis and to identify early hematological indicators of severe infection.

MATERIALS AND METHODS: This retrospective study was conducted at Shifa International Hospital, Pakistan from April to November 2020. Patients hospitalized with COVID-19, diagnosed on RT-PCR and had a complete blood count (CBC) done within 48 hours of diagnosis were included. Data was analyzed using IBM^® SPSS Statistics.

RESULTS: A total of 425 patients were included in this study out of whom 272(64%) were males. The mean age was 55.61 ± 17.84 years. 95 patients (22.4%) had normal blood counts within 48 hours of COVID-19 diagnosis. Cytopenias were seen in 193(45.4%) patients. There were 75(17.6%) mortalities during the study period. Chi-square test showed that thrombocytopenia, lymphopenia and neutrophilic leucocytosis were significantly associated with mortality (P = .037, P < .001, P < .001 respectively) and need for ventilator (P = .009, P < .001, P < .001, respectively). Neutrophilia was also associated with development of Acute Respiratory Distress Syndrome (P < .001). On ROC analysis, Neutrophil-to-Lymphocyte Ratio yielded an area under the curve (AUC) of 0.693 and 0.660 for the outcomes mortality and need for ventilator, respectively. For a subset of 288 patients who had D-dimer levels checked within 48 hours of COVID-19 diagnosis, the AUC for mortality and ventilator need was 0.708 and 0.671, respectively.

CONCLUSION: Hematological indices are vital indicators in the prognosis and risk stratification of COVID-19 during initial stages of disease.

PMID:33837662 | DOI:10.1111/ijlh.13533

Eur J Neurol. 2021 Apr 9. doi: 10.1111/ene.14860. Online ahead of print.

ABSTRACT

BACKGROUND: Mounting evidence supports an association between Guillain-Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, GBSs in the setting of coronavirus disease-2019 (COVID-19) remains poorly characterized, while GBSs prevalence among COVID-19 patients has not been previously systematically evaluated using a meta-analytical approach.

METHODS: We performed a systematic review and meta-analysis of observational cohort and case-series studies reporting on the occurrence, clinical characteristics and outcomes of patients with COVID-19-associated GBSs. A random-effects model was used to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), when comparing to non-COVID-19, contemporary or historical GBSs patients.

RESULTS: We identified 18 eligible studies (11 cohorts, 7 case-series) including a total of 136,746 COVID-19 patients. Among COVID-19 patients, including hospitalized and non-hospitalized cases, the pooled GBSs prevalence was 0.15‰ (95%CI:0-0.49‰; I² =96%). Compared to non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds for demyelinating GBSs subtypes (OR=3.27; 95%CI: 1.32-8.09; I² =0%). In SARS-CoV-2 infected patients, olfactory or concomitant cranial nerve involvement was noted in 41.4% (95%CI:3.5-60.4%; I² =46%) and 42.8% (95%CI:32.8-53%; I² =0%) of the patients, respectively. Clinical outcomes including in-hospital mortality were comparable between COVID-19 GBSs patients and non-infected contemporary or historical GBSs controls.

CONCLUSIONS: GBSs prevalence was estimated at 15 cases per 100,000 SARS-CoV-2 infections. COVID-19 appears to be associated with an increased likelihood of GBSs and with demyelinating GBSs variants in particular.

PMID:33837630 | DOI:10.1111/ene.14860

Int J Clin Pract. 2021 Apr 10:e14196. doi: 10.1111/ijcp.14196. Online ahead of print.

ABSTRACT

BACKGROUND: Tinnitus severity has been exacerbated due to the COVID-19 pandemic and those with tinnitus require additional support. Such support should be informed by patient preferences and needs. The objective of this study was to gather information from individuals with tinnitus living in Europe to inform stakeholders of the (i) support they needed in relation to changes associated with the COVID-19 pandemic, and (ii) suggestions regarding tinnitus care for the future.

METHODS: A cross-sectional mixed methods study design was used using closed and open-ended questions via an online survey. Data was gathered from 710 adults experiencing tinnitus in Western Europe, with the majority living in The Netherlands, Belgium, and Sweden. Data were analysed using qualitative content analysis and descriptive statistics.

RESULTS: Those with tinnitus indicated the following support needs during the pandemic (a) support for tinnitus, (b) support for hearing-related difficulties, (c) social support, and (d) pandemic-related support. Five directions for future tinnitus care were provided, namely (a) need for understanding professional support and access to multidisciplinary experts, (b) greater range of therapies and resources, (c) access to more information about tinnitus, (d) prioritizing tinnitus research, and (e) more support for hearing protection and hearing loss prevention CONCLUSIONS: The findings point to the need for accessible (remote), patient-centred, suitable and evidence-based tinnitus care. Insights from the current study can be used by various stakeholders including clinical practitioners and tinnitus support services to ensure those with tinnitus have access to the help and support required in order to reduce service provision insufficiencies.

PMID:33837639 | DOI:10.1111/ijcp.14196

BJOG. 2021 Apr 9. doi: 10.1111/1471-0528.16719. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the discrepancy between historical and more recent descriptions of the first stage of labour by testing whether the statistical techniques used recently (repeated measures polynomial and interval censored regression) were appropriate for detection of periods of rapid acceleration of cervical dilatation as might occur at the time of transition from a latent to an active phase of labour.

DESIGN AND SETTING: A simulation study using regression techniques.

SAMPLE: We created a simulated dataset for 500,000 labours with clearly defined latent and active phases using the parameters described by Friedman. Additionally, we created a dataset comprising 500,000 labours with a progressively increasing rate of cervical dilatation as described by Zhang et al. METHODS: Repeated-measures polynomial regression was used to create summary labour curves based on simulated cervical examinations. Interval-censored regression was used to create centimetre-by-centimetre estimates of rates of cervical dilatation and their 95^th centiles.

MAIN OUTCOME MEASURES: Labour summary curves and rates of cervical dilatation.

RESULTS: Repeated-measures polynomial regression did not detect the rapid acceleration in cervical dilatation (i.e. ‘acceleration phase’) and over-estimated lengths of labour, especially at smaller cervical dilatations. There was a two-fold overestimation in the mean rate of cervical dilatation from four to six centimetres. Interval-censored regression overestimated median transit-times, at four to five centimetres cervical dilatation or when cervical examinations occurred less than 0.5 to 1.5 hourly.

CONCLUSION: Repeated-measures polynomial regression and interval-censored regression should not be routinely used to define labour progress because they do not accurately reflect the underlying data.

PMID:33837643 | DOI:10.1111/1471-0528.16719

Histopathology. 2021 Apr 10. doi: 10.1111/his.14384. Online ahead of print.

ABSTRACT

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is an uncommon hepatic malignancy with a poor outcome. The 2019 WHO classification modified the definition and discarded the subtypes harboring stem cell features. However, the differences among cHCC-CCA, hepatocellular carcinoma (HCC), HCC with stem cell features (HCCscf) and intrahepatic cholangiocarcinoma (iCCA) remain undetermined. The aim of the study is to investigate the characteristics of cHCC-CCA in comparisons with other primary liver cancers utilizing the updated WHO classification.

METHODS AND RESULTS: We retrospectively analyzed 64 cHCC-CCA and 55 HCCscf patients from Dec2007 to May2018. A propensity score matching was conducted to compare with HCC and iCCA patients. Clinicopathological characteristics, event-free (EFS) and overall survival (OS) were evaluated with multivariate Cox proportional hazard regression. In a median follow-up of 55.9 months, patients with cHCC-CCA had a significantly poor survival as compared with HCCscf and an intermediate survival outcome between HCC and iCCA. HBV infection and high tumor infiltrating lymphocytes (TILs) were associated with a favorable survival in cHCC-CCA. In the multivariate analysis, poor hepatic reserve, absence of HBV infection, stage IV disease and low TILs were significant negative prognostic factors in cHCC-CCA. After pooling with other primary liver cancers, tumor type of cHCC-CCA and iCCA predicted the worse survival results.

CONCLUSION: cHCC-CCA have an intermediate survival between HCC and iCCA and HBV infection and high TILs predict the favorable survival. Our study provides clinical correlations for the new 2019 WHO classification.

PMID:33837585 | DOI:10.1111/his.14384

Trop Med Int Health. 2021 Apr 10. doi: 10.1111/tmi.13587. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the effectiveness of nanopermethrin as a potential new formulation for pest and vector control.

METHODS: Permethrin nanoparticles were prepared by the ionic gelation method and its structure and the formulations were designed using Box-Behnken statistical technique. The effect of independent variables (Chitosan/Permethrin ratio, tripolyphosphate quantity, sonication time) on the properties of nanoparticles was investigated to determine the optimal formulation.

RESULTS: The size of the nanoparticles ranged from 135.27±5.88 to 539.5±24.01nm and the insecticide entrapment efficiency percent (EE%) ranged from 7.72±1.36 to 63.59±3.17%. Anopheles stephensi larvae were then bioassayed with the nanopermethrin and compared with the results of the bioassay with the mother molecule of permethrin using a standard WHO recommended mosquito larval bioassay kit. LC₅₀ with permethrin and nanopermethrin on larvae of An. stephensi were 0.125 and 0.026 ppm showing a 4.8 times difference. The LC₅₀ for permethrin and nanopermethrin on Cx. pipiens were 0.003 and 0.00032 ppm respectively showing a 9.4-fold difference.

CONCLUSION: Nanopermethrin is much more potent than its mother molecule against larvae of An. stephensi and Cx. pipiens.

PMID:33837621 | DOI:10.1111/tmi.13587