scholarly journals Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259400
Author(s):  
Katsuhito Nagai ◽  
Yoshikazu Ryuno ◽  
Yoshihito Iwanami ◽  
Sachiko Omotani ◽  
Shuhei Fukuno ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Oral Administration ◽  
Pharmacokinetic Interaction ◽  
Limited Information ◽  
Nutrition Management ◽  
Pharmacokinetic Profiles ◽  
Significant Difference ◽  
Semi Solid ◽  
Enteral Nutrients

Background The use of enteral nutrients plays a highly important role in accurate nutrition management, but limited information is currently available on the cautionary points of semi-solid enteral nutrients. Aim In this study, we examined whether the pharmacokinetic profiles of sodium valproate (SVA), levetiracetam (LEV), and carbamazepine (CBZ) are affected by altering the dosing time of RACOL®-NF Semi Solid for Enteral Use (RASS), a prescribed semi-solid formula. We also investigated whether the pharmacokinetic interaction observed in this study can be avoided by staggered dosing of the chemical drug and semi-solid enteral nutrient. Methods The plasma concentration of SVA, LEV and CBZ after oral administration was measured by LC-MS/MS method. Results There was no difference in pharmacokinetic characteristics of SVA and LEV when the dosing time of RASS was altered. On the other hand, the plasma concentration of CBZ after oral administration at all sampling points decreased with the extension of the dosing time of RASS, which was consistent with the Cmax and AUC. However, no significant difference was observed in the pharmacokinetic profiles or parameters of CBZ between the short-term and long-term RASS dosing groups by prolonging the administered interval of CBZ and RASS for 2 hr. Conclusion We concluded that the pharmacokinetic profiles of CBZ, but not SVA and LEV, after its oral administration are affected by the dosing time of RASS, but staggered administration of CBZ and RASS prevented their interaction.

Correction: surgery and long-term medication (September 24, p 73)

1984 ◽  
Vol 22 (25) ◽  
pp. 100-100
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Oral Dose ◽  
Oral Administration ◽  
Oral Drug ◽  
Once Daily ◽  
Muscle Necrosis ◽  
Correction Surgery ◽  
Slow Absorption

Phenytoin: Our statement that the slow absorption of intramuscular phenytoin did not matter when substituting for the oral drug postoperatively was incorrect. Changing from oral to intramuscular administration risks a fall in plasma concentration because of the slow absorption from muscle. Changing back to oral administration would then risk toxicity as the drug was slowly released from muscle. Restarting with a smaller oral dose can prevent this. However, intramuscular phenytoin can cause muscle necrosis. These disadvantages of intramuscular phenytoin are not mentioned in the data sheet, but should be. Slow intravenous injection (50 mg or less/minute) once daily is a better alternative, but requires monitoring of the pulse, blood pressure and respiration.

Improvement Of Curvilinear Diagrams Of Concrete Deformation

2019 ◽  
pp. 99-104
Keyword(s):  
Reinforced Concrete ◽  
Peak Load ◽  
Experimental Studies ◽  
Concrete Structures ◽  
Deformation Model ◽  
Reinforced Concrete Structures ◽  
Significant Difference ◽  
Deformation Diagrams

Problems when calculating reinforced concrete structures based on the concrete deformation under compression diagram, which is presented both in Russian and foreign regulatory documents on the design of concrete and reinforced concrete structures are considered. The correctness of their compliance for all classes of concrete remains very approximate, especially a significant difference occurs when using Euronorm due to the different shape and sizes of the samples. At present, there are no methodical recommendations for determining the ultimate relative deformations of concrete under axial compression and the construction of curvilinear deformation diagrams, which leads to limited experimental data and, as a result, does not make it possible to enter more detailed ultimate strain values into domestic standards. The results of experimental studies to determine the ultimate relative deformations of concrete under compression for different classes of concrete, which allowed to make analytical dependences for the evaluation of the ultimate relative deformations and description of curvilinear deformation diagrams, are presented. The article discusses various options for using the deformation model to assess the stress-strain state of the structure, it is concluded that it is necessary to use not only the finite values of the ultimate deformations, but also their intermediate values. This requires reliable diagrams "s–e” for all classes of concrete. The difficulties of measuring deformations in concrete subjected to peak load, corresponding to the prismatic strength, as well as main cracks that appeared under conditions of long-term step loading are highlighted. Variants of more accurate measurements are proposed. Development and implementation of the new standard GOST "Concretes. Methods for determination of complete diagrams" on the basis of the developed method for obtaining complete diagrams of concrete deformation under compression for the evaluation of ultimate deformability of concrete under compression are necessary.

Percutaneous glycerol rhizotomy for trigeminal neuralgia in patients with multiple sclerosis: a long-term retrospective cohort study

2020 ◽  
Vol 132 (5) ◽  
pp. 1405-1413 ◽  
Author(s):  
Michael D. Staudt ◽  
Holger Joswig ◽  
Gwynedd E. Pickett ◽  
Keith W. MacDougall ◽  
Andrew G. Parrent
Keyword(s):  
Multiple Sclerosis ◽  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Retrospective Chart Review ◽  
Medication Usage ◽  
Free Response ◽  
Free Survival ◽  
Time To Recurrence ◽  
Significant Difference

OBJECTIVEThe prevalence of trigeminal neuralgia (TN) in patients with multiple sclerosis (MS-TN) is higher than in the general population (idiopathic TN [ITN]). Glycerol rhizotomy (GR) is a percutaneous lesioning surgery commonly performed for the treatment of medically refractory TN. While treatment for acute pain relief is excellent, long-term pain relief is poorer. The object of this study was to assess the efficacy of percutaneous retrogasserian GR for the treatment of MS-TN versus ITN.METHODSA retrospective chart review was performed, identifying 219 patients who had undergone 401 GR procedures from 1983 to 2018 at a single academic institution. All patients were diagnosed with medically refractory MS-TN (182 procedures) or ITN (219 procedures). The primary outcome measures of interest were immediate pain relief and time to pain recurrence following initial and repeat GR procedures. Secondary outcomes included medication usage and presence of periprocedural hypesthesia.RESULTSThe initial pain-free response rate was similar between groups (p = 0.726): MS-TN initial GR 89.6%; MS-TN repeat GR 91.9%; ITN initial GR 89.6%; ITN repeat GR 87.0%. The median time to recurrence after initial GR was similar between MS-TN (2.7 ± 1.3 years) and ITN (2.1 ± 0.6 years) patients (p = 0.87). However, there was a statistically significant difference in the time to recurrence after repeat GR between MS-TN (2.3 ± 0.5 years) and ITN patients (1.2 ± 0.2 years; p < 0.05). The presence of periprocedural hypesthesia was highly predictive of pain-free survival (p < 0.01).CONCLUSIONSPatients with MS-TN achieve meaningful pain relief following GR, with an efficacy comparable to that following GR in patients with ITN. Initial and subsequent GR procedures are equally efficacious.

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

scholarly journals A206 EVOLUTION OF PEDIATRIC AUTOIMMUNE CHOLANGITIS AND PRIMARY SCLEROSING CHOLANGITIS INTO ADULTHOOD

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 234-236
Author(s):  
P Willems ◽  
J Hercun ◽  
C Vincent ◽  
F Alvarez
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Response To Treatment ◽  
Similar Proportion ◽  
Autoimmune Cholangitis ◽  
Significant Difference ◽  
One Year ◽  
Liver Tests

Abstract Background The natural history of primary sclerosing cholangitis (PSC) in children seems to differ from PSC in adults. However, studies on this matter have been limited by short follow-up periods and inconsistent classification of patients with autoimmune cholangitis (AIC) (or overlap syndrome). Consequently, it remains unclear if long-term outcomes are affected by the clinical phenotype. Aims The aims of this is study are to describe the long-term evolution of PSC and AIC in a pediatric cohort with extension of follow-up into adulthood and to evaluate the influence of phenotype on clinical outcomes. Methods This is a retrospective study of patients with AIC or PSC followed at CHU-Sainte-Justine, a pediatric referral center in Montreal. All charts between January 1998 and December 2019 were reviewed. Patients were classified as either AIC (duct disease on cholangiography with histological features of autoimmune hepatitis) or PSC (large or small duct disease on cholangiography and/or histology). Extension of follow-up after the age of 18 was done for patients followed at the Centre hospitalier de l’Université de Montréal. Clinical features at diagnosis, response to treatment at one year and liver-related outcomes were compared. Results 40 patients (27 PSC and 13 AIC) were followed for a median time of 71 months (range 2 to 347), with 52.5% followed into adulthood. 70% (28/40) had associated inflammatory bowel disease (IBD) (78% PSC vs 54% AIC; p=0.15). A similar proportion of patients had biopsy-proven significant fibrosis at diagnosis (45% PSC vs 67% AIC; p=0.23). Baseline liver tests were similar in both groups. At diagnosis, all patients were treated with ursodeoxycholic acid. Significantly more patients with AIC (77% AIC vs 30 % PSC; p=0.005) were initially treated with immunosuppressive drugs, without a significant difference in the use of Anti-TNF agents (0% AIC vs 15% PSC; p= 0.12). At one year, 55% (15/27) of patients in the PSC group had normal liver tests versus only 15% (2/13) in the AIC group (p=0.02). During follow-up, more liver-related events (cholangitis, liver transplant and cirrhosis) were reported in the AIC group (HR=3.7 (95% CI: 1.4–10), p=0.01). Abnormal liver tests at one year were a strong predictor of liver-related events during follow-up (HR=8.9(95% CI: 1.2–67.4), p=0.03), while having IBD was not (HR=0.48 (95% CI: 0.15–1.5), p=0.22). 5 patients required liver transplantation with no difference between both groups (8% CAI vs 15% CSP; p=0.53). Conclusions Pediatric patients with AIC and PSC show, at onset, similar stage of liver disease with comparable clinical and biochemical characteristics. However, patients with AIC receive more often immunosuppressive therapy and treatment response is less frequent. AIC is associated with more liver-related events and abnormal liver tests at one year are predictor of bad outcomes. Funding Agencies None

scholarly journals 1005 Antibiotic-Impregnated Calcium Sulfate Beads Are Not Effective in the Primary Prevention of Infection in Open Femur and Tibia Fractures

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
A Fung ◽  
A Ward ◽  
K Patel ◽  
M Krkovic
Keyword(s):  
Primary Prevention ◽  
Infection Rate ◽  
Calcium Sulfate ◽  
Acute Infection ◽  
Open Fractures ◽  
Prevention Of Infection ◽  
Significant Difference ◽  
Tibia Fractures ◽  
Systemic Antibiotics

Abstract Introduction Infection is a major complication of open fractures. Antibiotic-impregnated calcium sulfate (AICS) beads are widely used as an adjuvant to systemic antibiotics. Whilst their efficacy in the secondary prevention of infection is established, we present the first retrospective study evaluating AICS beads in the primary prevention of infection in open fractures. Method 214 open femur and tibia fractures in 207 patients were reviewed over a seven-year period. 148 fractures received only systemic antibiotic prophylaxis. 66 fractures also received AICS beads. The occurrence of acute infection (wound infection and acute osteomyelitis) was recorded, as well as that of long-term complications (chronic osteomyelitis, non-union and death). Results Fractures that received AICS with systemic antibiotics had an overall acute infection rate of 42% (28/66), compared to 43% (63/148) in fractures that received only systemic antibiotics (p &gt; 0.05). There was no significant difference in infection rate even when fractures were stratified by Gustilo-Anderson grade. There was also no significant difference in the rate of long-term complications. Conclusions Our results indicate that the adjuvant use of AICS beads is not effective for the primary prevention of acute infection or long-term complications in open leg fractures. Further research is needed to elucidate the factors influencing the outcomes of AICS use.

scholarly journals Long-Term Mortality after Histoplasma Infection in People with HIV

2021 ◽  
Vol 7 (5) ◽  
pp. 369
Author(s):  
Joseph Cherabie ◽  
Patrick Mazi ◽  
Adriana M. Rauseo ◽  
Chapelle Ayres ◽  
Lindsey Larson ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Modern Art ◽  
Private Insurance ◽  
Early Mortality ◽  
Late Mortality ◽  
Significant Difference ◽  
Common Opportunistic Infection ◽  
Long Term Survivors ◽  
Long Term Mortality

Histoplasmosis is a common opportunistic infection in people with HIV (PWH); however, no study has looked at factors associated with the long-term mortality of histoplasmosis in PWH. We conducted a single-center retrospective study on the long-term mortality of PWH diagnosed with histoplasmosis between 2002 and 2017. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death < 90 days), late mortality (death ≥ 90 days), and long-term survivors. Patients diagnosed during or after 2008 were considered part of the modern antiretroviral therapy (ART) era. Insurance type (private vs. public) was a surrogate indicator of socioeconomic status. Out of 54 PWH infected with histoplasmosis, overall mortality was 37%; 14.8% early mortality and 22.2% late mortality. There was no statistically significant difference in survival based on the availability of modern ART (p = 0.60). Insurance status reached statistical significance with 38% of survivors having private insurance versus only 8% having private insurance in the late mortality group (p = 0.05). High mortality persists despite the advent of modern ART, implicating a contribution from social determinants of health, such as private insurance. Larger studies are needed to elucidate the role of these factors in the mortality of PWH.

scholarly journals Is It Definitely Clear That Long-Term Survival after Breast Cancer Surgery Is Not Affected by Anaesthetics?

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3390
Author(s):  
Mats Enlund
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Retrospective Studies ◽  
Breast Cancer Surgery ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Long Term Survival ◽  
Significant Difference ◽  
One Year

Retrospective studies indicate that cancer survival may be affected by the anaesthetic technique. Propofol seems to be a better choice than volatile anaesthetics, such as sevoflurane. The first two retrospective studies suggested better long-term survival with propofol, but not for breast cancer. Subsequent retrospective studies from Asia indicated the same. When data from seven Swedish hospitals were analysed, including 6305 breast cancer patients, different analyses gave different results, from a non-significant difference in survival to a remarkably large difference in favour of propofol, an illustration of the innate weakness in the retrospective design. The largest randomised clinical trial, registered on clinicaltrial.gov, with survival as an outcome is the Cancer and Anesthesia study. Patients are here randomised to propofol or sevoflurane. The inclusion of patients with breast cancer was completed in autumn 2017. Delayed by the pandemic, one-year survival data for the cohort were presented in November 2020. Due to the extremely good short-term survival for breast cancer, one-year survival is of less interest for this disease. As the inclusions took almost five years, there was also a trend to observe. Unsurprisingly, no difference was found in one-year survival between the two groups, and the trend indicated no difference either.

scholarly journals Intracameral Bevacizumab Versus Sub-Tenon’s Mitomycin C as Adjuncts to Trabeculectomy: 3-Year Results of a Prospective Randomized Study

2021 ◽  
Vol 10 (10) ◽  
pp. 2054
Author(s):  
Gerasimos Kopsinis ◽  
Dimitrios Tsoukanas ◽  
Dimitra Kopsini ◽  
Theodoros Filippopoulos
Keyword(s):  
Mitomycin C ◽  
Primary Outcome ◽  
Randomized Study ◽  
Primary Outcome Measure ◽  
Complication Rates ◽  
Filtration Surgery ◽  
Significant Difference ◽  
Exfoliative Glaucoma

Conjunctival wound healing determines success after filtration surgery and the quest for better antifibrotic agents remains active. This study compares intracameral bevacizumab to sub-Tenon’s mitomycin C (MMC) in trabeculectomy. Primary open-angle or exfoliative glaucoma patients were randomized to either bevacizumab (n = 50 eyes) or MMC (n = 50 eyes). The primary outcome measure was complete success, defined as Intraocular Pressure (IOP) > 5 mmHg and ≤ 21 mmHg with a minimum 20% reduction from baseline without medications. Average IOP and glaucoma medications decreased significantly in both groups at all follow-up points compared to baseline (p < 0.001), without significant difference between groups at 3 years (IOP: bevacizumab group from 29 ± 9.4 to 15 ± 3.4 mmHg, MMC group from 28.3 ± 8.7 to 15.4 ± 3.8 mmHg, p = 0.60; Medications: bevacizumab group from 3.5 ± 0.9 to 0.5 ± 1, MMC group from 3.6 ± 0.7 to 0.6 ± 1.1, p = 0.70). Complete success, although similar between groups at 3 years (66% vs. 64%), was significantly higher for bevacizumab at months 6 and 12 (96% vs. 82%, p = 0.03; 88% vs. 72%, p = 0.04, respectively) with fewer patients requiring medications at months 6, 9 and 12 (4% vs. 18%, p = 0.03; 6% vs. 20%, p = 0.04; 8% vs. 24%, p = 0.03, respectively). Complication rates were similar between groups. In conclusion, intracameral bevacizumab appears to provide similar long-term efficacy and safety results as sub-Tenon’s MMC after trabeculectomy.

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