Tag: nevin manimala

Drug Saf. 2021 Aug 10. doi: 10.1007/s40264-021-01091-x. Online ahead of print.

ABSTRACT

INTRODUCTION: The safety profile of remdesivir, conditionally approved for COVID-19, was limited at its 2020 introduction. Adverse drug reactions (ADRs) for medicines are collected in VigiBase, the WHO Global Database of Individual Case Safety Reports (ICSRs).

OBJECTIVE: This study aimed to provide a descriptive analysis of COVID-19 ICSR data focusing on remdesivir, including a disproportionality analysis (DA) of ADRs.

METHODS: A dedicated algorithm enabled retrieval of all COVID-19 treatment-specific ICSRs. A severity algorithm based on co-reported medicines and symptoms enabled selection of tocilizumab with its well established safety profile as comparator for remdesivir. Descriptive statistics were used for general ICSR demographics for all COVID-19-specific medicines, remdesivir and tocilizumab individually and furthermore to present treatment patterns of medicines co-reported with remdesivir. A COVID-19 indication-focused DA was deployed to minimize confounding from underlying polysymptomatic disease.

RESULTS: 14,574 COVID-19-related ICSRs were entered into VigiBase during 2020. Remdesivir was the most common medicine reported. Of 4944 remdesivir ICSRs, where tocilizumab was not co-reported, 93% described remdesivir as the sole suspect medicine. Sixty percent of ICSRs concerned males, median age was 63 years and the majority originated from the Americas (72%). In 1089 (21%) of remdesivir ICSRs, data indicated severe/critical disease. Co-reported medicines peaked during the first 3 days of remdesivir treatment. The DA for the established tocilizumab and the new remdesivir were mainly in line with the safety profiles for both medicines but suggested new safety concerns. The most reported ADRs for remdesivir represented liver dysfunction, kidney injury, death and bradycardia.

CONCLUSION: Global COVID-19-related ADR reporting proved useful in providing information on ADRs as well as on treatment patterns in this patient group. Indication-focused disproportionality analysis, together with the use of a comparator with a known safety profile, proved effective in identifying known safety information and suggested new safety concerns for remdesivir.

PMID:34374967 | DOI:10.1007/s40264-021-01091-x

J Assist Reprod Genet. 2021 Aug 10. doi: 10.1007/s10815-021-02260-8. Online ahead of print.

ABSTRACT

PURPOSE: To examine associations between objectively measured sleep duration and sleep timing with odds of completion of an in vitro fertilization (IVF) cycle.

METHODS: This prospective cohort study enrolled 48 women undergoing IVF at a large tertiary medical center between 2015 and 2017. Sleep was assessed by wrist-worn actigraphy, 1-2 weeks prior to initiation of the IVF cycle. Reproductive and IVF cycle data and demographic and health information were obtained from medical charts. Sleep duration, midpoint, and bedtime were examined in relation to IVF cycle completion using logistic regression models, adjusted for age and anti-Müllerian hormone levels. A sub-analysis excluded women who worked non-day shifts to control for circadian misalignment.

RESULTS: The median age of all participants was 33 years, with 29% of women >35 years. Ten women had an IVF cycle cancelation prior to embryo transfer. These women had shorter sleep duration, more nocturnal awakenings, lower sleep efficiency, and later sleep timing relative to those who completed their cycle. Longer sleep duration was associated with lower odds of uncompleted IVF cycle (OR = 0.88; 95%CI 0.78, 1.00, per 20-min increment of increased sleep duration). Women with later sleep midpoint and later bedtime had higher odds of uncompleted cycle relative to those with earlier midpoint and earlier bedtime; OR = 1.24; 95%CI 1.09, 1.40 and OR = 1.33; 95%CI 1.17, 1.53 respectively, for 20-min increments. These results were independent of age, anti-Müllerian hormone levels, or sleep duration, and remained significant after exclusion of shift-working women.

CONCLUSIONS: Shorter sleep duration and later sleep timing increase the odds of uncompleted cycles prior to embryo transfer.

PMID:34374922 | DOI:10.1007/s10815-021-02260-8

Infect Dis Ther. 2021 Aug 10. doi: 10.1007/s40121-021-00516-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Tigecycline is a potential alternative to trimethoprim-sulfamethoxazole in treating Stenotrophomonas maltophilia infections due to its potent in vitro antimicrobial activity. Clinical evidence regarding the use of tigecycline in the treatment of S. maltophilia infections is scarce. In this study, we assessed the efficacy of tigecycline treating ventilator-associated pneumonia (VAP) due to S. maltophilia in comparison with fluoroquinolones.

METHODS: This is a multicenter retrospective cohort study of patients admitted between January 2017 and December 2020 with the diagnosis of VAP caused by S. maltophilia receiving either tigecycline or fluoroquinolones as the definitive therapy ≥ 48 h. Clinical outcomes including 28-day mortality, clinical cure and microbiological cure were analyzed.

RESULTS: Of 82 patients with S. maltophilia VAP included, 46 received tigecycline, and 36 received fluoroquinolones; 70.7% of patients had polymicrobial pneumonia, and the appropriate empiric therapy was applied to only 14.6% of patients. The overall 28-day mortality was 39%. Compared with patients receiving fluoroquinolones, tigecycline therapy resulted in worse clinical cure (32.6% vs. 63.9%, p = 0.009) and microbiological cure (28.6% vs. 59.1%, p = 0.045), while there was no statistical difference between 28-day mortality (47.8% vs. 27.8%, p = 0.105) in the two groups. Similar results were also shown in the inverse probability of treatment weighted univariable regression model and multivariable regression model.

CONCLUSIONS: The standard dose of tigecycline therapy was associated with a lower clinical and microbiological cure rate but not associated with an increased 28-day mortality in patients with S. maltophilia VAP compared with fluoroquinolones. Considering the unfavorable clinical outcomes, we therefore recommend against using the standard dose of tigecycline in treating S. maltophilia VAP unless new clinical evidence emerges.

PMID:34374953 | DOI:10.1007/s40121-021-00516-5

Lasers Med Sci. 2021 Aug 10. doi: 10.1007/s10103-021-03395-x. Online ahead of print.

ABSTRACT

The purpose of this study is to analyze the influence of InGaAlP diode laser (660 nm) with or without an odontogenic medium (OM) in the functional activity of OD-21 cells. Undifferentiated OD-21 pulp cells were cultivated with or without OM and divided into four groups (n = 5): nonirradiated control (C -), nonirradiated + OM (C +), irradiated (L -), and irradiated + OM (L +). Laser application was performed in two sessions of a 24-h interval with an irradiance of 11.3 mW/cm2, energy density of 1 J/cm², and total cumulative energy/well of 4.6 J. Cell proliferation, VEGF-164 expression, mineralization, and expression of Alp, Runx2, and Dmp1 genes, as well as immunolocalization of RUNX2 and MEPE proteins, were evaluated. Data were analyzed by statistical tests (α = 0.05). All studied groups showed a similar increase in cell proliferation with or without OM. After 7 and 10 days, a significatively higher concentration of VEGF-164 in L – group when compared to C – group was observed. A significant increase in mineralized nodules in the L + was noted when compared to C + in the same conditions. Photobiomodulation upregulated significantly Runx2 and Dmp1 expression after 10 days in L – and after 7 days in L + , with downregulation of Dmp1 after 10 days in L + group. Immunolocalization of RUNX2 and MEPE was expressive after 7 days of culture in the cytoplasm adjacent to the nucleus with a decrease after 10 days, regardless of the presence of OM. Photobiomodulation enhances metabolism associated with angiogenesis, gene expression, and mineralization regardless of the odontogenic medium in OD-21 cells.

PMID:34374881 | DOI:10.1007/s10103-021-03395-x

MAGMA. 2021 Aug 10. doi: 10.1007/s10334-021-00952-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Diffusion kurtosis imaging (DKI) has been proven to provide additional value for assessing many central nervous system diseases compared with conventional diffusion tensor imaging (DTI); however, whether it has the same value in peripheral nerve injury is unclear. This study aimed to investigate the performance of DKI, DTI, and electromyography (EMG) in evaluating peripheral nerve crush injury (PNCI) in rabbits.

MATERIALS AND METHODS: A total of 27 New Zealand white rabbits were selected to establish a PNCI model. Longitudinal DTI, DKI, and EMG were evaluated before surgery and 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks after surgery. At each time point, two rabbits were randomly selected for pathological examination.

RESULTS: The results showed that fractional anisotropy (FA) derived from both DKI and DTI demonstrated a significant difference between injured and control nerves at all time points (all P < 0.005) mean kurtosis of the injured nerve was lower than that on the control side after 2-8 weeks (all P < 0.05). No statistically significant difference was found in radial kurtosis, axial kurtosis, and apparent diffusion coefficient at almost every time point. The difference in compound muscle action potential (CMAP) of the bilateral gastrocnemius at each time point was statistically significant (all P < 0.001).

CONCLUSIONS: CMAP was a sensitive and reliable method to assess acute PNCI without being affected by perineural edema. DKI may not be superior to DTI in evaluating peripheral nerves, DTI with a shorter scanning time was preferred as an effective choice for evaluating acute peripheral nerve traumatic injury.

PMID:34374905 | DOI:10.1007/s10334-021-00952-x

Pediatr Radiol. 2021 Aug 10. doi: 10.1007/s00247-021-05145-1. Online ahead of print.

ABSTRACT

BACKGROUND: Renal artery stenosis is an important cause of hypertension in children, accounting for 5-10% of cases. When suspected, noninvasive imaging options include ultrasound (US), computed tomography (CT) angiography and magnetic resonance (MR) angiography. However, digital subtraction angiography (DSA) remains the gold standard.

OBJECTIVE: To investigate the accuracy and inter-reader reliability of CT angiography in children with suspected renal artery stenosis.

MATERIALS AND METHODS: This is a retrospective study of patients suspected of having renal artery stenosis evaluated by both CT angiography and DSA between 2008 and 2019 at a tertiary pediatric hospital. Only children who underwent CT angiography within 6 months before DSA were included. CT angiography studies were individually reviewed by two pediatric radiologists, blinded to clinical data, other studies and each other’s evaluation, to determine the presence of stenosis at the main renal artery and 2nd- and 3rd-order branches. The sensitivity, specificity and accuracy were calculated using DSA as the reference. The effective radiation dose for CT angiography and DSA was also calculated. Kappa statistics were used to assess inter-reader agreement.

RESULTS: Seventy-four renal units were evaluated (18 girls, 19 boys). The patients’ median age was 8 years (range: 1-21 years). Overall, CT angiography was effective in detecting renal artery stenosis with a sensitivity of 85.7%, specificity of 91.5% and accuracy of 88.9%. There was moderate inter-reader agreement at the main renal artery level (k=0.73) and almost perfect inter-reader agreement at the 2nd/3rd order (k=0.98). However, the sensitivity at the 2nd- and 3rd-order level was lower (14.3%). CT angiography provided excellent negative predictive value for evaluating renal artery stenosis at the main renal artery level (90.1%) and at the 2nd- or 3rd-order branches (82.7%). The median effective dose of CT angiography studies was 2.2 mSv (range: 0.6-6.3) while the effective dose of DSA was 13.7 mSv.

CONCLUSION: CT angiography has high sensitivity and specificity at the main renal artery level with a lower radiation dose than previously assumed. Therefore, it can be used as a diagnostic tool in patients with low to medium risk of renal artery stenosis, and as a screening and treatment planning tool in patients at high risk.

PMID:34374838 | DOI:10.1007/s00247-021-05145-1

J Patient Rep Outcomes. 2021 Aug 10;5(1):70. doi: 10.1186/s41687-021-00320-2.

ABSTRACT

BACKGROUND: Hypoparathyroidism (HP) is a rare endocrine disorder characterized by absent or inappropriately low levels of circulating parathyroid hormone with associated significant physical and cognitive symptoms. This study evaluated the psychometric properties of the Hypoparathyroidism Patient Experience Scales (HPES), which were developed as disease-specific, patient-reported outcome (PRO) measures to assess the symptoms and impacts associated with HP in adults.

METHODS: Data from a non-interventional, observational study (N = 300) and a Phase 2 clinical trial (N = 59) were used in the psychometric evaluation. Observational and trial assessments included: an online validation battery (baseline or screening) and retest (approximately 2 weeks after baseline or screening). In the trial, the primary efficacy endpoint was assessed at week 4 through re-administration of the HPES and validation battery subset. The observational study’s larger sample size allowed for evaluation of the HPES descriptive properties, scoring algorithm, test-retest reliability, and construct validity. The trial data examined responsiveness, meaningful within-patient change estimates, and treatment impact on HPES scores.

RESULTS: Demographic and self-reported medical characteristics results were similar across the 2 studies. Factor analysis confirmed domains in the HPES-Symptom (n = 2) and HPES-Impact (n = 4). For both measures, total and domain scores demonstrated acceptable reliability and validity for both the observational and trial samples. Internal consistency evidence was strong. Test-retest reliability estimates generally approached the recommended 0.70 threshold. The construct validity correlations with other PRO measures were mainly as hypothesized, thus supporting the HPES scores and constructs. Mean scores for both measures also differed as anticipated and significantly across known-groups, thus providing evidence for the scores discriminating between meaningful groups. Trial results supported both HPES total and domain scores’ ability to detect change. The difference in mean total and domain scores for both measures demonstrated statistically significant improvements for TransCon PTH compared to placebo treated subjects despite the small sample and a short 4-week duration on fixed, non-optimized doses.

CONCLUSIONS: The HPES were found to be conceptually sound with adequate evidence supporting their reliability and validity. Incorporation of the HPES into clinical and research settings will help to further elucidate and assess the patient experience of living with HP and identify treatment differences.

PMID:34374868 | DOI:10.1186/s41687-021-00320-2

Heart Vessels. 2021 Aug 10. doi: 10.1007/s00380-021-01891-2. Online ahead of print.

ABSTRACT

Red cell distribution width (RDW) is reportedly associated with cardiovascular events, including atrial fibrillation (AF). We investigated whether the RDW values were associated with the outcomes of catheter ablation for AF. This retrospective multicenter study included 501 patients with AF (239 paroxysmal AF cases, 196 persistent AF cases, and 66 long-standing persistent AF cases) who underwent initial AF ablation between March 2017 and May 2018. The RDW values were evaluated before and at 1-3 months after the procedure. The patients were stratified based on the recurrence of AF within 1 year after the index procedure with a blanking period of 3 months into recurrence group (107 patients, 21.4%) and no-recurrence group (394 patients, 78.6%). There were no significant differences in preoperative RDW values between the groups (p = 0.37). The RDW value did not change significantly after the ablation in the recurrence group (13.55-13.60%, p = 0.37), although it decreased significantly in the no-recurrence group (13.64-13.37%, p < 0.001). Multivariate Cox proportional hazards regression analyses revealed that a postoperative change in RDW (ΔRDW) was independently associated with AF recurrence (hazard ratio 2.00, 95% confidence interval 1.42-2.76, p < 0.001). Receiver operating characteristic curve analysis revealed that a ΔRDW cut-off value of – 0.1% provided a c-statistic of 0.65 for predicting AF recurrence. Decrease in RDW during the blanking period after ablation independently predicted the 1-year success of AF ablation.

PMID:34374825 | DOI:10.1007/s00380-021-01891-2

Eur Radiol. 2021 Aug 10. doi: 10.1007/s00330-021-08015-4. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine reproducible MRI parameters predictive of molecular subtype and risk stratification in glioma and develop a structured reporting system.

METHODS: All study patients were initially diagnosed with glioma, 141 from the Cancer Genome Atlas and 131 from our tertiary institution, as training and validation sets, respectively. Images were analyzed by three neuroradiologists with 1-7 years of experience. MRI features including contrast enhancement pattern, necrosis, margin, edema, T2/FLAIR mismatch, internal cyst, and cerebral blood volume higher than normal cortex were reported using a structured reporting system. The pathology was stratified into five risk types: (1) oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, 1p19q co-deleted; (2) diffuse astrocytoma, IDH-mutant, grade II-III; (3) glioblastoma, IDH-mutant, grade IV; (4) diffuse astrocytoma, IDH-wild, grade II-III; and (5) glioblastoma, IDH-wild, grade IV. Significant predictors were selected using multivariate logistic regression, and diagnostic performance was tested using a validation set.

RESULTS: Reproducible imaging parameters exhibiting > 50% agreement across readers included the presence of necrosis, T2/FLAIR mismatch, internal cyst, and predominant contrast enhancement. In the validation set, prediction of risk type 5 exhibited the highest diagnostic performance with AUCs of 0.92 (reader 1) and 0.93 (reader 2) with predominant enhancement, followed by risk type 2 with AUCs of 0.95 and 0.95 with T2/FLAIR mismatch sign and no necrosis, and risk type 1 with AUCs of 0.84 and 0.83 with internal cyst or necrosis. Risk types 3 and 4 were difficult to visually predict.

CONCLUSIONS: Imaging parameters with high reproducibility enabling prediction of IDH-wild-type glioblastoma, IDH-mutant/1p19q co-deletion oligodendroglioma, and IDH-mutant diffuse astrocytoma were identified.

KEY POINTS: • Reproducible MRI parameters for determining molecular subtypes of glioma included the presence of necrosis, T2/FLAIR mismatch, internal cyst, and predominant contrast enhancement. • IDH-wild type glioblastoma, IDH-mutant/1p19q co-deletion oligodendroglioma, and IDH-mutant low-grade astrocytoma were identified using MRI parameters with high inter-reader reproducibility. • Identification of IDH-wild type low-grade glioma and IDH-mutant glioblastoma was difficult by visual analysis.

PMID:34374800 | DOI:10.1007/s00330-021-08015-4

JAMA Netw Open. 2021 Aug 2;4(8):e2120176. doi: 10.1001/jamanetworkopen.2021.20176.

ABSTRACT

IMPORTANCE: Administration of epinephrine has been found to be associated with an increased chance of survival after out-of-hospital cardiac arrest (OHCA), but the optimal timing of administration has not been fully investigated.

OBJECTIVE: To ascertain whether there is an association between timing of epinephrine administration and patient outcomes after OHCA.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adults 18 years or older with OHCA treated by emergency medical services (EMS) personnel from April 1, 2011, to June 30, 2015. Initial cardiac rhythm was stratified as either initially shockable (ventricular defibrillation or pulseless ventricular tachycardia) or nonshockable (pulseless electrical activity or asystole). Eligible individuals were identified from among publicly available, deidentified patient-level data from the Resuscitation Outcomes Consortium Cardiac Epidemiologic Registry, a prospective registry of adults with EMS-treated, nontraumatic OHCA with 10 sites in North America. Data analysis was conducted from May 2019 to April 2021.

EXPOSURES: Interval between advanced life support (ALS)-trained EMS personnel arrival at the scene and the first prehospital intravenous or intraosseous administration of epinephrine.

MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge. In each cohort of initial cardiac rhythms, patients who received epinephrine at any period (minutes) after EMS arrival at the scene were matched with patients who were at risk of receiving epinephrine within the same period using time-dependent propensity scores calculated from patient demographic characteristics, arrest characteristics, and EMS interventions.

RESULTS: Of 41 079 eligible individuals (median [interquartile range] age, 67 [55-79] years), 26 579 (64.7%) were men. A total of 10 088 individuals (24.6%) initially had shockable cardiac rhythms, and 30 991 (75.4%) had nonshockable rhythms. Those who received epinephrine included 8223 patients (81.5%) with shockable cardiac rhythms and 27 901 (90.0%) with nonshockable rhythms. In the shockable cardiac rhythm cohort, the risk ratio (RR) for receipt of epinephrine with survival to hospital discharge was highest between 0 and 5 minutes after EMS arrival (1.12; 95% CI, 0.99-1.26) across the categorized timing of the administration of epinephrine by 5-minute intervals after EMS arrival; however, that finding was not statistically significant. Treating the timing of epinephrine administration as a continuous variable, the RR for survival to hospital discharge decreased 5.5% (95% CI, 3.4%-7.5%; P < .001 for the interaction between epinephrine administration and time to matching) per minute after EMS arrival. In the nonshockable cardiac rhythm cohort, the RR for the association of receipt of epinephrine with survival to hospital discharge was the highest between 0 and 5 minutes (1.28; 95% CI, 0.95-1.72), although not statistically significant, and decreased 4.4% (95% CI, 0.8%-7.9%; P for interaction = .02) per minute after EMS arrival.

CONCLUSIONS AND RELEVANCE: Among adults with OHCA, survival to hospital discharge differed across the timing of epinephrine administration and decreased with delayed administration for both shockable and nonshockable rhythms.

PMID:34374770 | DOI:10.1001/jamanetworkopen.2021.20176