Initial Dose Research Articles

Apomorphine titration with and without anti-emetic pretreatment in patients with Parkinson’s disease experiencing OFF episodes: A modified Delphi panel

IntroductionIn the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed. MethodsThis modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment. During Round 1, a panel of 9 US movement disorder specialists rated the appropriateness of prescribing apomorphine therapy with and without antiemetic pretreatment across 192 patient scenarios and were able to review their scores in relation to other scores. During the Round 2, consensus was defined for each scenario as either strong (>75 % agreement) or moderate (66 % agreement). ResultsThere was strong consensus on 118 of 192 scenario’s (97 as appropriate and 21 as inappropriate), moderate consensus on 29 scenarios, some agreement on 32 scenarios, and lack of agreement on 13 scenarios. In the absence of an antiemetic, there was strong consensus that titration schedules should be flexible and based on dose response. However, the group only reached moderate consensus on the speed of titration, highlighting the need for more systematic information on this area. In the presence of an antiemetic, panelists considered usual initial dosing and flexible titration to be appropriate in most scenarios except for when the patient is already experiencing dopaminergic adverse events. ConclusionsExperts generally reached consensus that apomorphine can usually be prescribed without antiemetic pretreatment. Recommendations described here reflect the areas of greatest agreement among a panel of experts based on current available evidence.

Machine Learning Approach in Dosage Individualization of Isoniazid for Tuberculosis.

Isoniazid is a first-line antituberculosis agent with high variability, which would profit from individualized dosing. Concentrations of isoniazid at 2 h (C2h), as an indicator of safety and efficacy, are important for optimizing therapy. The objective of this study was to establish machine learning (ML) models to predict the C2h, that can be used for establishing an individualized dosing regimen in clinical practice. Published population pharmacokinetic (PopPK) models for adults were searched based on PubMed and ultimately four reliable models were selected for simulating individual C2h datasets under different conditions (demographics, genotype, ethnicity, etc.). Machine learning models were trained on simulated C2h obtained from the four PopPK models. Five different algorithms were used for ML model building to predict C2h. Real-world data were used for predictive performance evaluations. Virtual trials were used to compare ML-optimized doses with PopPK model-optimized doses. Categorical boosting (CatBoost) exhibited the highest prediction ability. Target C2h can be predicted using the ML model combined with the dosing regimen and three covariates (N-acetyltransferase 2 [NAT2] genotypes, weight and race [Asians and Africans]). Real-world data validation results showed that the ML model can achieve an overall prediction accuracy of 93.4%. Using the final ML model, the mean absolute prediction error value decreased by 45.7% relative to the average of PopPK models. Using the ML-optimized dosing regimen, the probability of target attainment increased by 43.7% relative to the PopPK model-optimized dosing regimens. Machine learning models were developed with great predictive performance, which can be used to determine the individualized initial dose of isoniazid in adult patients.

Effectiveness of ceftazidime/avibactam as a continuous infusion in critically ill patients with OXA-48-producing Klebsiella pneumoniae infection

Introduction. Ceftazidime/avibactam, a novel beta-lactam antibiotic, demonstrates time-dependent bacterial killing; thus, new reports advocate its administration as a continuous infusion, as opposed to bolus or prolonged infusion application. Methods. Critically ill COVID-19 patients (n=10) superinfected with OXA-48-producing Klebsiella pneumoniae susceptible to ceftazidime/avibactam were treated with ceftazidime/avibactam as a continuous infusion for an average of 10 days. The treatment regimen included an initial loading dose, followed by a continuous infusion of ceftazidime/avibactam. These patients were immunocompromised because of severe COVID-19, treatment with corticosteroids, and some solid organ transplant recipients (n=2), all with high disease severity scores. Discussion. Considering the published literature to this date, this is the one of first reports describing the real-life results of using a continuous infusion of ceftazidime/avibactam in the treatment of OXA-48-producing K. pneumoniae superinfection in critically ill COVID-19 patients. Microbiological effectiveness of treatment, evidenced by negativization of microbiological samples, was achieved in eight cases (80%) overall, but in patients with sepsis and urinary tract infection, the cure rate was 100%. Conclusion. The reasons for the low treatment success rates in pneumonia caused by OXA-48-producing K. pneumoniae could be explained by the concurrent severe COVID-19 pneumonia.

Alternative production of fucoxanthin and PUFAs using Chlorochromonas danica and Hibberdia magna, unicellular chrysophytes with different trophic modes

Ochrophyte microalgae attract attention from the applied phycology perspective, due to their ability to grow rapidly, engage variable trophic modes, and simultaneously produce high-value compounds such as xanthophyll carotenoids and polyunsaturated fatty acids. Unlike more often considered marine diatoms and haptophytes, unicellular chrysophytes may represent a reasonable freshwater alternative. In this work, we introduced two representatives: Chlorochromonas danica (Ochromonadales) and Hibberdia magna (Hibberdiales). We compared their ability to produce target compounds in mixotrophic and photoautotrophic modes, respectively. Both organisms had a similar temperature optima (18–22 °C), but light demands were much higher in the photoautotrophic H. magna. This work is the first report of fucoxanthin content and productivity by C. danica, showing that the presence of light enhanced the content of fucoxanthin 4.5-fold compared with darkness. For fucoxanthin productivity in the mixotrophic batch cultured C. danica, the optimal initial glucose dose was 10 g L−1. Culture medium supplemented with mineral nutrients resulted in an increase in biomass and fucoxanthin productivity of C. danica achieving the highest biomass productivity of 0.81 ± 0.06 g L−1 d−1. H. magna accumulated a maximum of 4.54 ± 0.04 mg g−1 DW of fucoxanthin, which was slightly more than the maximum value for C. danica of 3.99 ± 0.19 mg g−1 DW. However, due to the lower biomass productivity of H. magna, the maximal fucoxanthin productivities reached very similar values of 1.15 ± 0.05 and 1.16 ± 0.01 mg L d−1 in C. danica and H. magna, respectively. Both organisms had a relatively high fatty acid content, accounting for 17 % and 19 % of DW in C. danica and H. magna, respectively. H. magna had a higher level of polyunsaturated fatty acids, which were more diverse, longer, and more unsaturated. The potential for utilization of selected chrysophytes as producers in a multi-target biorefinery is discussed.

TIRZEPATIDE: Trending ‘Weight loss’ Drug– Potential Influence in Tackling Obesity Epidemic

Obesity is a chronic disease that is associated with severe complications. A lifestyle involving an increased appetite and reduced energy expenditure promotes weight gain. A better understanding of the endocrine regulation of appetite has led to the development of newer medications for the treatment of obesity. Among these medications is an incretin-based drug named tirzepatide. Many studies have been conducted in obese, insulin-resistant, and lipid-diet-fed mice to evaluate the effect of tirzepatide and its combination of GIP and GLP-1 agonism demonstrated higher anorectic activity by increasing satiety and satiation, decreasing liking for high-fat diets and decreasing sweet taste reference as compared to the effects of semaglutide. Adverse effects of mild gastrointestinal events and decreased appetite were reported with tirzepatide (which reduced after some time) than with placebo. In phase 3 SURPASS clinical trial optimized dose escalation scheme was adopted to improve gastrointestinal tolerability with an initial low dose of tirzepatide. The results of the SURPASS-1 trial showed significant improvement in glycemic control and durable bodyweight reductions with all the doses (3 doses) of tirzepatide compared to placebo in type 2 diabetic patients along with diet and exercise. Weight loss occurred regardless of whether participants reported any gastrointestinal adverse events and did not elevate over the period.

RETOUR DEXPERIENCE CLINIQUE SUR TROIS ANS DE PRESCRIPTION DE LA FLUOXETINE EN PEDOPSYCHIATRIE UNIVERSITAIRE

Objectives: Our work has three objectives: To analyze our prescribing practices for fluoxetine in the light of international recommendations, to evaluate the tolerance and effectiveness of this molecule in children and adolescent and to identify the rules for proper use in this age group. Patients and method: We conducted a cross-sectional and descriptive clinical study spanning a period of 3 years, from January 2021 to January 2024, concerning children and adolescents aged between 8 and 17 years old who had been diagnosed with major depressive disorder, persistent depression, and/or anxiety disorders, or bulimia and placed on fluoxetine for a minimum follow-up period of 4 months and a maximum of 18 months. Results: The prescription of fluoxetine concerned 76 patients out of 660 patients with mood and anxiety disorder out of a total of 2215 patients. Major depressive disorder is the most common child psychiatric diagnosis (90%), anxiety disorders are present in 10%. Fluoxetine is prescribed as first-line treatment with psychotherapy in 40% of cases. Indicated as second-line treatment in 60% of patients due to an insufficient response or non-response to psychotherapy. No pre-therapeutic assessment is carried out. Fluoxetine is prescribed as monotherapy at an initial dose of 20 mg/day taken in the morning for an average duration of 9 months for depressive disorders and 12 to 18 months for anxiety disorders. Consented cessation of treatment is gradual. We report good therapeutic compliance and good tolerance with an average effectiveness time of 10 days. Mainly two side effects are described: headache and nervousness. We report one case of manic conversion in a 14years old girl. Discussion: The prescription of psychotropic medications in children and adolescents can only be considered as part of multimodal care, generally as second-line treatment when the adequate therapeutic response is not achieved or sometimes as first-line treatment when the clinical case is immediately severe or with there is an impact on the child and/or those around him. Only fluoxetine has label use in children aged over 8 years for moderate to severe depressive episodes. Fluoxetine is supported by the greatest results of evidence for its effectiveness and superiority compared to other SSRIs in this indication. Fluoxetine is also indicated in juvenile anxiety disorders and obsessive-compulsive disorder. Conclusion: In the case of mood and anxiety disorders in children, notably depression, fluoxetine is the choice molecule with the best tolerance-effectiveness ratio.

PRACTICAL RECOMMENDATION FOR CALIBRATION OF RADIATION SOURCES USED FOR CONTACT RADIOTHERAPY

Relevance: This paper presents two methods for calibrating ionizing radiation sources in brachytherapy. The first method involves measuring the radiation activity using a well chamber, while the second method involves measuring the air kerma using an ionization chamber. Additionally, the application and measurement method of radiochromic film is demonstrated. The relevance of the above calibration methods of the ionizing radiation source in brachytherapy is explained by the need to ensure high accuracy and reliability of treatment. All calibration methods provide a multilevel approach to quality control and safety of brachytherapy. Combining an ionization chamber, air kerma power measurement, and radiochromic film allows for high dosimetry accuracy, which is critical for successfully treating patients and minimizing side effects. The study aimed to analyze primary calibration methods and their applicability in medical institutions. Methods: The data from the radiation source provided by the manufacturer is compared with the measurements obtained using the method proposed in the article. Radiochromic film was exposed to radiation to assess the initial dose distribution in the phantom. This scientific research was carried out within the framework of the PCF scientific program “Metrological support of dosimetric measurements in contact radiation therapy,” IRN BR12967832. Results: It has been established that the measurement accuracy is approximately 1.2% at a 95% confidence interval. The activity of the radiation source and the field distribution around it were measured using methods recommended by the IAEA. Conclusion: In our case, the difference between the data measured by these two methods is 1.2%. Using the third method, which involves radiochromic film, it has been established that the radiation source distribution matches the treatment plan. The user has the right to choose any of the calibration methods mentioned above for the eye, taking into account the technical capabilities of their medical facility.

Certolizumab Pegol for the Treatment of Plaque Psoriasis in Routine Clinical Practice: One-Year Results from the CIMREAL Study.

Certolizumab pegol (CZP) is an anti-tumor necrosis factor alpha (TNFα) approved for the treatment of moderate to severe plaque psoriasis (PSO). However, data on its real-world use is currently limited. The objective of this study was to describe the 1-year real-world effectiveness of CZP, its impact on health-related quality of life (HRQoL), and safety outcomes in patients with moderate to severe PSO in multi-country settings. CIMREAL, a prospective, noninterventional study, was conducted across Europe and Canada from August 2019 to December 2022. Patients were followed for 1-year, receivingCZP 400mg initial doses at weeks 0, 2, and 4, followed byCZP 200mg every 2weeks (Q2W) or CZP 400mg Q2W maintenance dosing. Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety was also evaluated. Overall, 399 patients with moderate to severe PSO were included. Of these, 93.7% (374/399) and 77.9% (311/399) completed months 3 and 12, respectively. Mean age (± standard deviation) was 42.9 ± 13.5yearsand body mass index was 28.5 ± 6.8kg/m2, with the majority of patients being female (68.2%). At 12months, CZP showed substantial effectiveness, achieving PASI 75 and PASI 90 response rates (≥ 75% and ≥ 90% improvement from baseline, respectively) of 77% and 56.5%, respectively. Patients with PASI score of ≤ 3 and ≤ 2 experienced improvement from 3months (49.8% and 41.1%, respectively) to 12months (82.0% and 75.3%, respectively). HRQoL considerably improved, with mean DLQI scores decreasing from 12.4 to 2.3 after 12months of treatment, and the proportion of patients with DLQI 0/1 increased from 28.6% at 3months to 59.4% at 12months. The 1-year probability of persistence was approximately 85%. Overall, 30.6% of the patients experienced any adverse events and 9.3% had serious adverse events. In routine clinical practice, CZP exhibited consistent effectiveness, positively impacting both skin psoriasis activity and HRQoL. The 1-year persistence of CZP was high, and no new safety signals were identified. ClinicalTrials.gov Identifier: NCT04053881 https://www. gov/study/NCT04053881 .

Vaccination for communicable endemic diseases: optimal allocation of initial and booster vaccine doses.

For some communicable endemic diseases (e.g., influenza, COVID-19), vaccination is an effective means of preventing the spread of infection and reducing mortality, but must be augmented over time with vaccine booster doses. We consider the problem of optimally allocating a limited supply of vaccines over time between different subgroups of a population and between initial versus booster vaccine doses, allowing for multiple booster doses. We first consider an SIS model with interacting population groups and four different objectives: those of minimizing cumulative infections, deaths, life years lost, or quality-adjusted life years lost due to death. We solve the problem sequentially: for each time period, we approximate the system dynamics using Taylor series expansions, and reduce the problem to a piecewise linear convex optimization problem for which we derive intuitive closed-form solutions. We then extend the analysis to the case of an SEIS model. In both cases vaccines are allocated to groups based on their priority order until the vaccine supply is exhausted. Numerical simulations show that our analytical solutions achieve results that are close to optimal with objective function values significantly better than would be obtained using simple allocation rules such as allocation proportional to population group size. In addition to being accurate and interpretable, the solutions are easy to implement in practice. Interpretable models are particularly important in public health decision making.

Trimethoprim-sulfamethoxazole dosing and outcomes of pulmonary nocardiosis.

Nocardia often causes pulmonary infection among those with chronic pulmonary disease or immunocompromising conditions. Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as first-line treatment, though little data exists regarding outcomes of different dosing regimens. We performed a multicenter retrospective cohort study of adult patients with non-disseminated pulmonary nocardiosis initially treated with TMP-SMX monotherapy. Patients' initial TMP-SMX dosing was categorized as high- (> 10mg/kg/day), intermediate- (5-10mg/kg/day) or low-dose (< 5mg/kg/day). Outcomes included one-year mortality, post-treatment recurrence, and dose adjustment or early discontinuation of TMP-SMX. SMX serum concentrations and their effect on management were also assessed. Inverse probability of treatment weighting was applied to Cox regression analyses. Ninety-one patients were included with 24 (26.4%), 37 (40.7%), and 30 (33.0%) treated with high-, intermediate-, and low-dose TMP-SMX, respectively. Patients who initially received low-dose (HR 0.07, 95% CI 0.01-0.68) and intermediate-dose TMP-SMX (HR 0.27, 95% CI 0.07-1.04) had lower risk of one-year mortality than the high-dose group. Risk of recurrence was similar between groups. Nineteen patients had peak SMX serum concentrations measured which resulted in 7 (36.8%) dose changes and was not associated with one-year mortality or recurrence. However, 66.7% of the high-dose group required TMP-SMX dose adjustment/discontinuation compared to 24.3% of the intermediate-dose and 26.7% of the low-dose groups (p = 0.001). Low- and intermediate-dose TMP-SMX for non-disseminated pulmonary nocardiosis were not associated with poor outcomes compared to high-dose therapy, which had a higher rate of dose adjustment/early discontinuation. Historically used high-dose TMP-SMX may not be necessary for management of isolated pulmonary nocardiosis.

Heparin-Induced Thrombocytopenia (HIT) in the Direct Oral Anticoagulants (DOAC) Era

Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role and outcome of direct oral anticoagulants (DOACs) for the management of HIT. After institutional review board (IRB) approval, a retrospective review was performed identifying all patients with positive HIT serotonin-release assays between 2020 and 2022 at two hospitals. The demographic and clinical variables were collected as follows: initial anticoagulant, dosing and indication, interval before onset of HIT, thrombotic complications, platelet nadir and recovery, direct thrombin inhibitor (DTI) and DOAC usage, and clinical outcomes. 15 patients were included in the study. 8 underwent a vascular procedure, 3 had cardiac surgery, 1 patient had both and was included in both groups, and 5 patients had either noncardiac, nonvascular surgery, or no surgery. 14 patients received unfractionated heparin (93% with therapeutic dosing), and 1 received prophylactic enoxaparin prior to diagnosis of HIT. The average time to diagnosis of HIT was 10.77days after initial anticoagulation. In-hospital mortality was 27%, related to Covid-19 infection (3/4) and intracranial hemorrhage (1/4). 40% developed thrombosis (67% venous, 33% arterial) after the diagnosis of HIT. 8/11 survivors were discharged on a DOAC. With DOAC therapy, platelet counts rebounded to an average of 265K (±104.6K) within an average of 2.3days and 364K (±273.9K) within 30days after initiation of a DOAC. No recurrent thrombosis occurred after DOAC administration and only one patient had persistent thrombocytopenia within 30days. Mortality and thrombosis (arterial and venous) are common complications in patients diagnosed with HIT. In patients who survive to discharge, DOACs are the most common discharge antithrombotic agent, with low rates of recurrent thrombosis and thrombocytopenia.

Impact of Vancomycin trough levels monitoring on uncomplicated methilcillin-resistant Staphylococcus aureus bacteremia in chronic kidney disease on hemodialysis, retrospective cohort

BackgroundCKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels.MethodsThis is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes.ResultsThe main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2).ConclusionsWe conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.

Prediction of Warfarin Dosage Based on Genotype (VKORC1) – 1639 G&gt;A – rs9923231 In South Indian Populations

Background: Venous thromboembolism (VTE), characterized by thrombus formation in veins, ranks as the third most prevalent vascular disease globally after myocardial infarction (MI) and stroke. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common clinical manifestations of VTE, with potentially fatal consequences. In this study, the mean daily warfarin dose using VKORC1 (-1639 G&gt;A) rs9923231 genotyping will be established in order to categorize warfarin treatment into high, moderate, and low-dose groups within the South Indian population. Methods and Materials: A cohort of 192 patients was enrolled, and genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: In our study sample, the A allele frequency was 23.9%, and the AA genotype frequency was 12.5%. The mean daily doses required by AA homozygous (1.54 ± 1.05 mg/day) and GA heterozygous (2.93 ± 2.03 mg/day) genotype carriers were considerably lower to attain the optimal international normalized ratio (INR) than those of GG genotype carriers (4.07 ± 1.75 mg/day), with a p-value of 0.866. Conclusion: Our findings strongly advocate for incorporating VKORC1 polymorphism analysis in South Indian patients with DVT to guide the initial warfarin dosage genetically.

The modified pomegranate peel as an economical and highly effective adsorbent for malachite green dye removal from wastewater

This research investigated the ability of acid-modified pomegranate peel to remove malachite green (MG) dye from aqueous solutions. Pomegranate peel, an abundant agricultural byproduct, was modified using hydrochloric acid to enhance its adsorption capacity. The effects of parameters like particle size, pH, initial MG concentration, contact time, temperature and adsorbent dosage on the dye removal efficiency were studied. Under optimized conditions of pH 8, 40 min contact time, 25°C temperature and 0.01 g/ml adsorbent dose with 5 mg/L MG solution, about 96.8 % dye removal was achieved. Kinetic data fitted well to the pseudo-second order model, indicating chemisorption with electrostatic interactions governing the adsorption. Equilibrium data were best described by the Temkin isotherm model, suggesting a heterogeneous binding energy distribution. Thermodynamic calculations revealed the exothermic and spontaneous nature of MG adsorption. FTIR analysis confirmed introduction of functional groups like carboxyl, amine and alkyl groups on the adsorbent surface after acid modification, enabling interactions with dye cations. SEM images displayed increased surface roughness and porosity for the modified biosorbent relative to the raw form. The acid-modified pomegranate peel proved to be an economical, eco-friendly and effective adsorbent for removing the hazardous cationic dye MG from wastewater. The findings support agricultural waste valorization for environmental remediation applications.

Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease

BackgroundSebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3–5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials.MethodsWe recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed.ResultsAnalyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective.Conclusion5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the ‘trough’ periods before the next dosing, even with this intensive regimen.

Comparison of Changes in Rso2 in Midazolam and Propofol Sedation Post Craniotomy in the Icu of H. Adam Malik Hospital

Introduction: Cerebral oxygen saturation reflects tissue perfusion in the cerebrum. Decreases in cerebral oxygen saturation are linked to longer hospital stays and cognitive impairment. Midazolam and propofol can decrease cerebral blood flow through decreasing the cerebral oxygen metabolic rate. The purpose of this research is to analyze the comparison of changes in cerebral oxygen saturation after midazolam and propofol administration in post-craniotomy patients in the ICU of Haji Adam Malik General Hospital Medan. Subject and Method: This is a randomized control trial study. Patients were divided into, Midazolam group, that given an initial dose of 0.05 mg/kg followed by a maintenance dose of 0.02-0.10 mg/kg/hour and Propofol group that given sedation with a dose of 0.3-3mg/kg/hour, with the target of the 2 groups being a Richmond Agitation-Sedation Scale (RASS) value of 0 to -2. Data analysis using unpaired T test. Results: The results for cerebral regional oxygen saturation and RASS between groups showed significant differences in right and left value (p &lt; 0.001), but there was no significant difference in RASS (p&gt;0.05) between each group at each measurement time. The results of the analysis of cerebral regional oxygen saturation and RASS between times, there was no significant difference in right and left value (p&gt;0.05), but there was a significant difference in RASS (p&lt;0.001) at each measurement time. Based on the results of the analysis carried out, it is known that there is no statistically significant difference in changes in cerebral regional oxygen saturation both right and left in changes in RASS because it is found that all data have p&gt;0.05. Conclusion: There is no change in right and left for cerebral regional oxygen saturation after administration of propofol and midazolam groups with RASS value 0 to -2 in post-craniotomy patients in the ICU of Haji Adam Malik General Hospital Medan

A Trajectory of Long-Term Antipsychotic Medication Dosage in Inpatients with Severe Behavioral and Psychological Symptoms of Dementia: A Retrospective Study.

While antipsychotics are often prescribed for behavioral and psychological symptoms of dementia (BPSD), typically on an off-label basis, these medications have serious adverse effects. This study investigated the long-term use of antipsychotics among inpatients with dementia displaying severe BPSD, focusing on how prescriptions change over time. Medical charts at Kusakabe Memorial Hospital were retrospectively reviewed from October 2012 to September 2021. The study included patients diagnosed with dementia, admitted for BPSD, and were continuing antipsychotics at 3 months of their admission. Antipsychotic dosages were categorized as high (≥300 mg/d), medium (100-300 mg/d), and low (<100 mg/d) based on chlorpromazine equivalents and tracked until 15 months during hospitalization. Binary logistic regression was used to identify factors associated with dosage reductions between months 3 and 6. This study involved 188 patients, with an average age of 81.2 years, 67% of whom were diagnosed with Alzheimer&apos;s dementia. At 3 months, 15.4% were taking high, 44.1% on medium, and 40.4% on low dosages of antipsychotics. The highest average dosage was observed at 3 months, with a subsequent decrease over time. By the 12th month, 20-30% of patients in all dosage categories had stopped their antipsychotic medication. Significant factors for dosage reduction included higher initial doses (OR 1.003, 95%Cl: 1.001-1.006, P=0.01) and male gender (OR 2.481, 95%Cl: 1.251-4.918, P=0.009). A trajectory of antipsychotic dosage in inpatients with severe BPSD has rarely been reported. This research emphasizes the need for personalized strategies in managing long-term pharmacotherapy for this vulnerable group of patients.

Standard Versus Rapid Inpatient Methadone Titration for Pregnant Patients With Opioid Use Disorder: A Retrospective Cohort Study.

Our study evaluated if rapid inpatient titration of methadone for pregnant patients with opioid use disorder (OUD) improved outcomes without increasing the risk for overdose. This is a retrospective cohort study of pregnant patients admitted for inpatient methadone titration from January 2020 to June 2022. Outcomes were compared between standard versus rapid titration protocols. Standard titration involved an initial methadone dose with additional doses every 6 hours if clinical opiate withdrawal score (COWS) is >9. Rapid titration involved an initial methadone dose with additional doses every 4 hours if COWS is >9. The primary outcome was time required to achieve stable dose. Secondary outcomes included elopement prior to achieving stable dose, methadone-related readmission, opioid overdose, and final dose. There were 97 patients in the standard titration (STP) and 97 patients in the rapid titration (RTP) groups. Demographic characteristics and substance use history did not differ between the 2 groups. Time to stable dose did not differ between the 2 groups (RTP, 5.0 days ±4.0; STP, 4.0 days ±3.0; P = 0.08). Patients in the rapid titration group were less likely to elope from the hospital prior to stabilization (RTP 23.0% vs STP 37.9%, P = 0.03) and had fewer methadone-related readmissions (P < 0.001). One patient (1.0%) in the RTP group required naloxone treatment while inpatient for concern for overdose, while none did in the STP group (P = 0.32). There was no difference in median final stable dose between the 2 groups (P = 0.07). Rapid titration of methadone for pregnant patients with OUD was associated with decreased medical elopement and methadone-related readmission, without increasing the risk for overdose.

An asymptotic description of a basic FcRn-regulated clearance mechanism and its implications for PBPK modelling of large antibodies.

A basic FcRn-regulated clearance mechanism is investigated using the method of matched asymptotic expansions. The broader aim of the work is to obtain further insight on the mechanism, thereby providing theoretical support for future pharmacologically-based pharmacokinetic modelling efforts. The corresponding governing equations are first non-dimensionalised and the order of magnitudes of the model parameters are assessed based on their values reported in the literature. Under the assumption of high FcRn-binding affinity, analytical approximations are derived that are valid over the characteristic phases of the problem. Additionally, relatively simple equations relating clearance and AUC to physiological model parameters are derived, which are valid over the longest characteristic time scale of the problem. For lower to moderate doses clearance is effectively linear, whereas for higher doses it is nonlinear. It is shown that for all doses sufficiently high the leading-order approximation for the IgG concentration in plasma, over the longest characteristic time scale, is independent of the initial dose. This is because IgG that is in 'excess' of FcRn is eliminated over a time scale much shorter than that of the terminal phase. In conclusion, analytical approximations of the basic FcRn mechanism have been derived using matched asymptotic expansions, leading to a simple equation relating clearance to FcRn binding affinity, the ratio of degradation and FcRn concentration, and the volumes of the system.

Biotransformation of ferulic acid into vanillyl alcohol and vanillic acid employing thermophilic bacterium Caldimonas thermodepolymerans

Caldimonas thermodepolymerans, a Gram-negative, moderately thermophilic bacterium, exhibits a remarkable biotechnological potential. Given the presence of genes in its genome dedicated to the metabolization of ferulic acid (FA), this study aimed to explore the bacterium's capability for biotransforming FA into high-value metabolites. The results unequivocally demonstrate the bacterium's proficiency in the efficient and rapid conversion of FA into vanillyl alcohol (VOH) and vanillic acid (VA). By manipulating key cultivation parameters, such as adjusting initial FA doses and varying cultivation periods, the product profile can be tailored. Higher initial doses and shorter cultivation periods favor the production of VOH, while lower FA doses and extended cultivation periods lead to the predominant formation of VA. Furthermore, the process can be operated in a repeated-batch scenario. This underscores the potential of C. thermodepolymerans for industrial biotransformation of FA, presenting a promising avenue for leveraging its capabilities in practical applications.