Daily Maintenance Dose Research Articles

Food Sublingual Immunotherapy: Safety and Simplicity of a Real Food Updosing Protocol

BACKGROUNDSublingual immunotherapy (SLIT) using food extracts is safe and effective in desensitizing food allergy patients yet not often used in clinical practice. OBJECTIVESWe propose a cost-effective, expedited SLIT protocol using real food. METHODSFood allergy patients 5-50 years, median 11, initiated food SLIT in a single clinic setting. The daily maintenance dose was 4-11 mg protein in 0.1-0.5 ml volume, depending on the food. Some foods were available in liquid form at the local grocery (milk, egg white liquid, and cashew/walnut/sunflower/hazelnut milk), while others were prepared in the office using flour and 50% glycerin saline (peanut/sesame/wheat). The first cohort of 20 patients began dosing at a 1:1,000 dilution, the next 30 patients at 1:100 dilution. An exercise challenge was performed in a subset of patients on maintenance dosing to evaluate the need for a pre- or post-dose rest period. RESULTSThe 1:1,000 and 1:100 cohorts both completed day one without adverse reactions beyond itchy mouth. There were no systemic reactions requiring epinephrine throughout the study period and 88% reached their maintenance dose. Skin testing of 6-months-old peanut flour solution was not diminished from fresh solution and similar to food extract. Exercise challenge tests in 12 patients were negative. CONCLUSIONSAllergen extract food SLIT as used in published trials has limitations of cost and multiple office visits. Inexpensive real food, at the same or slightly higher protein dose, was well tolerated in 4 updose visits, a minimum of a week apart. Unlike food oral immunotherapy, a pre- or post-dose rest period may not be necessary.

Study on Risk Factors and Receiver Operator Characteristic Curve of Iatrogenic Withdrawal Syndrome in Pediatric Intensive Care Units: A Retrospective Study

Introduction: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. Methods: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. Results: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610–0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. Conclusion: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice.

Does lower dose pilocarpine have a role in radiation-induced xerostomia in the modern radiotherapy era? A single-center experience based on patient-reported outcome measures

PurposeThis study aims to investigate the efficacy of lower dose pilocarpine in alleviating late dry mouth symptoms in head and neck cancer patients received radiotherapy.MethodsEighteen head and neck cancer patients experiencing persistent dry mouth were enrolled in this study. All participants started pilocarpine treatment a median of 6 months post-radiotherapy. Initially, patients received pilocarpine at 5 mg/day, with a gradual increase to the recommended dose of 15 mg/day. A Patient-Reported Outcome Measurement (PROMs) questionnaire assessed symptoms’ severity related to hyposalivation.ResultsAll patients reported symptomatic dry mouth above grade 2 before starting the medication. Pilocarpine treatment continued based on patients’ self-assessment, with a median duration of 12 months (range, 3–36 months). The median daily maintenance dose was 10 mg (range, 5 to 20 mg). Total PROMs scores significantly decreased following medication, from 13 points (range 7–18 points) to 7 points (range 4–13 points) (p = 0.001). Significant improvements were observed in questions related to dry mouth (p < 0.001), water intake during eating (p = 0.01), carrying water (p = 0.01), taste (p < 0.001), and water intake during speech (p < 0.001). Initial and maintenance doses of pilocarpine were lower, and the duration of pilocarpine usage was shorter in patients treated with intensity-modulated radiation therapy compared to conformal radiotherapy (12 months vs. 25 months, p = 0.04).ConclusionPilocarpine may be considered at doses lower for late-term dry mouth. With modern radiotherapy techniques effectively preserving the parotid gland, short-term use may be recommended in these patients. Future studies may enhance the development of a more robust patient selection criteria model.

Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

Defined Daily Dose (DDD): An Essential Metric in the Antimicrobial Stewardship Programmes (AMSPs) in the Healthcare Sector

Antimicrobial stewardship programmes (AMSPs) decrease antimicrobial resistance, optimize usage of antimicrobials, and enhance patient outcomes. The Anatomical Therapeutic Chemical (ATC) is the foundation of the World Health Organization (WHO) global methodology, which groups the pharmacologically active substances of antimicrobials according to their therapeutic, pharmacological, and chemical characteristics and the organ or system on which they work. Since varied unit doses of daily administration of antimicrobials are prescribed, it is best to utilize a standard approach to measure antimicrobial intake. The Defined Daily Dose (DDD) is awarded to active ingredients with an active ingredient code currently in effect. It is the anticipated average daily maintenance dose of an antimicrobial drug or substances used for their primary indication in adults. The ATC/DDD approach was created to enhance patient care by tracking antimicrobial usage and conducting research. Healthcare facilities would benefit immensely from establishing an antimicrobial stewardship programme, and more research is required to determine the baseline of antimicrobial consumption in the country.

Optimizing anidulafungin exposure across a wide adult body size range.

Echinocandins like anidulafungin are first-line therapies for candidemia and invasive candidiasis, but their dosing may be suboptimal in obese patients. Our objective was to quantify anidulafungin exposure in a cohort of adults across a wide body size range to test if body size affects anidulafungin pharmacokinetics (PK). We enrolled 20 adults between the ages of 18 and 80 years, with an equal distribution of patients above and below a body mass index of 30 kg/m2. A single 100-mg dose of anidulafungin was administered, followed by intensive sampling over 72 h. Population PK analysis was used to identify and compare covariates of anidulafungin PK parameters. Monte Carlo simulations were performed to compute the probability of target attainment (PTA) based on alternative dosing regimens. Participants (45% males) had a median (range) age of 45 (21-78) years and a median (range) weight of 82.7 (42.4-208.3) kg. The observed median (range) of AUC0-∞ was 106.4 (51.9, 138.4) mg∙h/L. Lean body weight (LBW) and adjusted body weight (AdjBW) were more influential than weight as covariates of anidulafungin PK parameters. The conventional 100 mg daily maintenance is predicted to have a PTA below 90% in adults with an LBW > 55 kg or an AdjBW > 75 kg. A daily maintenance dose of 150-200 mg is predicted in these heavier adults. Anidulafungin AUC0-∞ declines with increasing body size. A higher maintenance dose will increase the PTA compared to the current approach in obese patients.

Clinical Pharmacokinetics of Ponesimod, a Selective S1P1 Receptor Modulator, in the Treatment of Multiple Sclerosis.

Ponesimod, a selective, rapidly reversible, and orally active, sphingosine-1 phosphate receptor (S1P) modulator, is indicated for the treatment of relapsing-remitting multiple sclerosis (RRMS). The clinical pharmacokinetics (PK) and pharmacodynamics (PD) of ponesimod was studied in 16 phase I, one phase II, and one phase III clinical studies. Ponesimod population PK was characterized by an open two-compartment disposition model with a terminal half-life of 33h (accumulation factor of 2- to 2.6-fold), and fast and almost complete oral absorption (absolute oral bioavailability: 84%), reaching peak plasma and blood concentrations within 2-4h. Ponesimod is highly metabolized, and the parent compound along with its two major (non-clinically active) metabolites are mainly excreted in the feces (recovery: 57.3-79.6%) and to a lesser extent in the urine (recovery: 10.3-18.4%). Additionally, the population PKPD model characterized the ponesimod effects on heart rate: a transient, dose-dependent decrease in heart rate in the first days of dosing, that is mitigated by administering the first doses of ponesimod treatment using a gradual up-titration schedule, before reaching the daily maintenance dose of 20mg. This selected maintenance dose has been shown to be superior in reducing annualized relapse rate (ARR) when compared with teriflunomide in a pivotal phase III study. Furthermore, a dose-dependent reduction of peripheral lymphocyte counts that is sustained with continued daily oral dosing of ponesimod and is rapidly (4-7days) reversible upon drug discontinuation has been characterized with an indirect response model.

Fecal microbial transplantation as a novel therapeutic for autism spectrum disorders: a review of the current literature

BackgroundAutism spectrum disorders (ASDs) are complex neurobiological conditions with poor long-term outcomes and limited treatment options. The microbiota–gut–brain axis indicates a pathway by which the gut microbiota links to ASDs. Fecal microbial transplantation (FMT), whereby the gut microbiota is replaced with that of a healthy individual, shows promise for the treatment of neurobiological conditions. This review examines the current evidence for the use of FMT as a therapeutic for ASD.DiscussionASDs and their associated gastrointestinal symptoms are improved with FMT, potentially due to the engraftment of features of a healthy gut. Longer treatment regimens that include daily maintenance doses appear to be the most effective long-term therapeutic option, with benefits persisting 2 years post-intervention. Evidence is mixed regarding the use of preparatory treatments. Considering the sex bias in ASD research, small sample sizes and the lack of placebo control arms, randomized controlled trials would be of benefit to the evidence base regarding the use of FMT as a therapeutic option for ASD.ConclusionFMT is a promising new therapeutic for ASD, but the evidence base is in its infancy.

Predictors of Achievement of Response With Cenobamate: Post-hoc Subset Analysis From a Phase 3, Open-Label Safety Study (S44.006)

Predictors of Achievement of Response With Cenobamate: Post-hoc Subset Analysis From a Phase 3, Open-Label Safety Study (S44.006)

Predictors of Sustainability of Response With Cenobamate: Post-hoc Subset Analysis of a Phase 3, Open-Label, Study (P14-1.005)

Predictors of Sustainability of Response With Cenobamate: Post-hoc Subset Analysis of a Phase 3, Open-Label, Study (P14-1.005)

Comparison of 300 mg versus 600 mg daily maintenance doses of aspirin treatment after desensitization in N-ERD: A three-year multicentre experience

Background: Aspirin treatment after desensitization (ATAD) is effective in preventing nasal polyps recurrence as well as respiratory symptoms in patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory diseases (N-ERD). However, there is no consensus on effective daily maintenance doses in ATAD. Therefore, we aimed to compare the effects of two different maintenance doses of aspirin on clinical outcomes for 1-3 years of ATAD. Methods: This was a retrospective, multicenter study that involved four tertiary centers. The maintenance doses of daily aspirin were 300 mg in one center and 600 mg in the remaining three. The data of patients who were on ATAD for 1-3 years were included. Study outcomes (nasal surgeries, sinusitis, asthma attacks, hospitalization, oral corticosteroid use, and medication uses) were assessed in a standardized way and recorded from case files. Results: The study initially included 125 subjects, 38 and 87 were receiving 300 and 600 mg daily aspirin for ATAD, respectively. Number of nasal polyp surgeries decreased after 1 -3 years compared with before ATAD in both groups (group 1, baseline: 0.44 ± 0.07 versus first year: 0.08 ± 0.05; p < 0.001 and baseline: 0.44 ± 0.07 versus 3rd year: 0.01 ± 0.01; p < 0.001; and group 2, baseline 0.42 ± 0.03 versus first year: 0.02 ± 0.02; p < 0.001 and baseline: 0.42 ± 0.03 versus 3rd year: 0.07 ± 0.03; p < 0.001). Conclusion: Given the comparable effects of 300 mg and 600 mg aspirin daily as maintenance treatment of ATAD on both asthma and sinonasal outcomes in N-ERD, our results suggest using 300 mg of aspirin daily in ATAD owing to its better safety profile.

Long-term response to immunotherapy in patients with hypertrophic pachymeningitis.

In this study, we aimed to clarify the relationship between initial treatment response, prednisolone (PSL) dosage, clinical type, and recurrence in patients with hypertrophic pachymeningitis (HP). The study cohort comprised eight patients with HP who had been admitted to our hospital from April 2015 to June 2020. Diagnostic criteria for HP included neurological abnormalities and dural thickening on magnetic resonance gadolinium-enhanced T1-weighted images. Relevant characteristics of the eight study patients are as follows. There were two men and six women. The average age at onset was 58.3 (range: 29-79) years. Three of them had myeloperoxidase-antineutrophil cytoplasmic antibody-related vasculitis, one immunoglobulin G4-related disease, and one ulcerative colitis. The remaining three patients had idiopathic HP. The average maximum dosage of PSL was 0.79mg/kg/day, and the average daily maintenance dosage 0.18mg/kg/day. Three patients needed additional immunosuppressive drugs. Both idiopathic and secondary HP initially responded well to PSL, with improvement in activities of daily living. Six patients had some sequelae related to cranial nerve involvement. No relapses occurred while the patients were taking moderate doses of PSL; however, all patients with idiopathic HP had recurrences when their PSL dosage was reduced. Patients with idiopathic HP and HP associated with immune disorders respond to steroids and immunosuppressive drugs and recover well. However, there is a high rate of relapse after reduction of PSL dosage, mainly in those with idiopathic HP.

Reduction in anti-seizure medications use in pediatric patients with pharmacoresistant epilepsy submitted to surgical treatment.

We aimed to analyze the potential for postoperative (PO) medication suspension and reduction, emphasizing passive withdrawal. Retrospective study of patients under 18years old submitted to surgical treatment for pharmacoresistant epilepsy and classified as Engel I during the first year of PO follow-up. Therapeutic management was evaluated through discontinuation or reduction of medications, both in terms of the number of ASM prescribed and in daily maintenance dosages in mg/kg. ASM withdrawal started in the first year PO and occurred in 1.2% of cases, with a significant yearly reduction in the number of ASM during follow-up (p < 0.001). A comparison of the most commonly used ASM in daily mg/kg between the preoperative period (preop) and PO showed a reduction of ASM maintenance dosages during PO. Even though recurrence of seizures was observed 5years after surgery, 125 patients (85%) were still classified as Engel I, albeit a higher number of ASM per patient was observed. Most patients showed no changes in cognitive and adaptive behavior evaluation between preop and PO, even in those who were able to reduce ASM. Significant reduction observed both in the number and daily maintenance dosages of ASM following each year of PO may be an indirect measure of the effectiveness of epilepsy surgery.

Daily oral vitamin D3 without concomitant therapy in the management of psoriasis: A case series

• Vitamin D3 and resistance and subsequent deficiency play an important role in the pathogenesis of psoriasis. • A high daily dose of vitamin D3 is a safe therapeutic option in managing psoriasis. • Vitamin D3 therapy offers complete remission of psoriasis without any adverse events. • The results of this case series warrants robust clinical trials. Evidence suggests vitamin D3 resistance with gene polymorphisms related to its metabolism to have a potential role in the patho-prognosis of psoriasis. We report 6 cases of psoriasis treated with daily oral Vitamin D3 (25 hydroxy cholecalciferol) in doses ranging from 30,000 IU to 60,000 IU over a period of 2 to 6 months and then followed by lower daily maintenance dose. The dose of vitamin D3 was adjusted based on the drop in the level of parathyroid hormone as the ionized calcium levels were also periodically monitored to prevent hypercalcemia. Complete control of psoriasis was observed within a span of 2–6 months, which was measured by Psoriasis Area and Severity Index (PASI) and a symptom Visual analog scale. Our observations suggest that supervised, daily oral higher than usual Vitamin D3 can be given safely as an effective therapeutic modality for treating psoriasis.

STEROID RESISTANCE AND ANNEXIN A1 LEVEL IN PATIENTS WITH ACANTHOLYTIC PEMPHIGUS

Systemic glucocorticosteroids due to their powerful anti-inflammatory and immunosuppressive properties are widely used in the treatment of severe chronic autoimmune diseases. Systemic glucocorticosteroids are the basic therapy for acantholytic pemphigus that must be taken continually. Therapy regimens of systemic glucocorticosteroids in acantholytic pemphigus depend on the sensitivity of patients to hormonal drugs. Recently, there have been observed an increasing number of patients with acantholytic pemphigus who have reduced sensitivity to systemic glucocorticosteroids. The scientific literature describes theories of the development of steroid resistance; they are diverse and still insufficiently studied. Therefore, further investigation of new pathogenetic links of steroid resistance, including the presence of annexin A1 (annexin A1, ANXA1, lipocortin-1) in patients with acantholytic pemphigus receiving long-term therapy with systemic glucocorticosteroids, in relation to the dose of hormonal drugs and the course of the disease, is extremely relevant and timely. The aim: to determine the level of annexin A1 in patients with acantholytic pemphigus during treatment depending on the dose of systemic glucocorticosteroids and steroid sensitivity. Materials and methods: 33 patients with acantholytic pemphigus were under observation at the Department of Dermatology, Institute of Dermatology and Venereology of the National Academy of Medical Sciences of Ukraine, Kharkiv. The level of ANXA1 in blood serum was studied by enzyme-linked immunosorbent assay (ELISA). The study was conducted in patients with acantholytic pemphigus before treatment, at the beginning of treatment and over the course of maintenance therapy, taking into account the daily dose of systemic glucocorticosteroids. Evaluation of sensitivity to systemic glucocorticosteroids in patients with acantholytic pemphigus was assessed by a specially developed 12-point scale of the index of resistance to systemic glucocorticosteroids. Discussion. According to the results of the study, a significant increase in the level of ANXA1 was observed in patients with acantholytic pemphigus at the beginning of therapy and under the maintenance therapy with systemic glucocorticosteroids. In untreated patients, ANXA1 levels were equal to those in the control group. This is confirmed by the theory of glucocorticosteroid sensitivity of this mediator. An increase in ANXA1 level at the beginning of therapy with systemic glucocorticosteroids was determined: in steroid-sensitive group at an average daily dose of 45.63±5.49 mg, the level of ANXA1 was on average 0.82±0.09 ng/mL; in steroid-resistant group, with an average daily dose of systemic glucocorticosteroids of 59.57±7.94 mg/d, ANXA1 was 1.18±0.13 ng/mL. With a decrease in the daily dose of systemic glucocorticosteroids to 17.25±4.14 mg/d, the ANXA1 level in patients of steroid-sensitive group had the values of the control group 0.46±0.11 ng/mL and 0.48±0.05 ng/mL, respectively, while in patients of steroid-resistant group the ANXA1 level was 0.68±011 ng/mL at an average daily dose of corticosteroids of 27.23±2.94 mg/d. Conclusion. ANXA1 level depends on the dose of systemic glucocorticosteroids. All patients who did not receive systemic glucocorticosteroids had the level of ANXA1 equal to the control group. All patients with acantholytic pemphigus at the beginning of therapy had a significant increase in ANXA1 levels and their decrease when a maintenance dose was reached. The average daily maintenance dose of systemic glucocorticosteroids is 1.57 times higher in the group of steroid-resistant patients.

Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU

Vitamin D as an immunomodulator has not been studied in patients with severe COVID-19. This study aimed to estimate the efficacy of vitamin D3 supplementation on cellular immunity and inflammatory markers in patients with COVID-19 admitted to the intensive care unit (ICU). A single-center, double-blind, randomized, placebo-controlled pilot trial was conducted (N = 110). Patients were randomly assigned to receive a weekly oral dose of 60,000 IU of vitamin D3 followed by daily maintenance doses of 5000 IU (n = 55) or placebo (n = 55). Primary outcomes were lymphocyte counts, natural killer (NK) and natural killer T (NKT) cell counts, neutrophil-to-lymphocyte ratio (NLR), and serum levels of inflammatory markers on 7th day of treatment. On day 7, patients in the vitamin D3 group displayed significantly higher NK and NKT cell counts and NLR than those in the placebo group did. The mortality rate (37% vs 50%, P = 0.16), need for mechanical ventilation (63% vs 69%, P = 0.58), incidence of nosocomial infection (60% vs 41%, P = 0.05) did not significantly differ between groups. Vitamin D3 supplementation, compared with placebo, significantly increased lymphocyte counts, but did not translate into reduced mortality in ICU.Trial Registration: ClinicalTrials.gov Identifier: NCT05092698.

Performance Measurement for Opioid Use Disorder Medication Treatment and Care Retention.

Performance Measurement for Opioid Use Disorder Medication Treatment and Care Retention.

Evaluation of Levetiracetam Dosing Strategies for Seizure Prophylaxis Following Traumatic Brain Injury.

Although levetiracetam has been increasingly used as an alternative to phenytoin for early posttraumatic seizure prophylaxis following traumatic brain injury (TBI), an optimal dosing strategy has not been elucidated. The objective of this study is to determine whether different dosing strategies of levetiracetam are associated with the incidence of early posttraumatic seizures when used as prophylaxis following TBI. This retrospective single-center cohort study included admitted patients ≥ 18years of age with a diagnosis of TBI and receiving levetiracetam for early posttraumatic seizure prophylaxis between July 1, 2013, and September 1, 2019. The primary outcome of this study was to evaluate three different dosing strategies of levetiracetam (≤ 1000mg/day, 1500mg/day, and ≥ 2000mg/day) and associated rates of early posttraumatic seizures. Secondary outcomes were to summarize absolute total daily maintenance doses of levetiracetam among patients who experienced early posttraumatic seizures compared with those who did not, to determine the impact of three different dosing strategies on hospital length of stay and in-hospital mortality, and to assess patient-specific variables on the occurrence of posttraumatic seizures. Overlap propensity score weighting was used to address the potential for confounding. Of the 1287 patients who received levetiracetam for early posttraumatic seizure prophylaxis during the study time frame, 866 patients met eligibility criteria and were included in the study cohort (289 patients in the ≤ 1000mg/day group, 137 patients in the 1500mg/day group, and 440 patients in the ≥ 2000mg/day group). After weighting, the cumulative incidence of early posttraumatic seizure was 2.9% in the ≤ 1000mg/day group, 8.8% in the 1500mg/day group, and 9% in the ≥ 2000mg/day group. The 1500mg/day and ≥ 2000mg/day levetiracetam groups had a 209% and 216% increase in the subdistribution hazard of early posttraumatic seizures compared with the ≤ 1000mg/day levetiracetam group, respectively, but these differences were not statistically significant. In conclusion, the results of this study demonstrate no statistically significant difference in the cumulative incidence of early posttraumatic seizures within 7days of TBI between three different levetiracetam dosing strategies. After weighting, the ≤ 1000mg/day levetiracetam group had the lowest rates of early posttraumatic seizures, death without seizure, and in-hospital mortality.

Impact of VKORC1, CYP2C9, CYP1A2, UGT1A1, and GGCX polymorphisms on warfarin maintenance dose: Exploring a new algorithm in South Chinese patients accept mechanical heart valve replacement.

Background:Warfarin is the most recommended oral anticoagulant after artificial mechanical valve replacement therapy. However, the narrow therapeutic window and varying safety and efficacy in individuals make dose determination difficult. It may cause adverse events such as hemorrhage or thromboembolism. Therefore, advanced algorithms are urgently required for the use of warfarin.Objective:To establish a warfarin dose model for patients after prosthetic mechanical valve replacement in southern China in combination with clinical and genetic variables, and to improve the accuracy and ideal prediction percentage of the model.Methods:Clinical data of 476 patients were tracked and recorded in detail. The gene polymorphisms of VKORC1 (rs9923231, rs9934438, rs7196161, and rs7294), CYP2C9 (rs1057910), CYP1A2 (rs2069514), GGCX (rs699664), and UGT1A1 (rs887829) were determined using Sanger sequencing. Multiple linear regressions were used to analyze the gene polymorphisms and the contribution of clinical data variables; the variables that caused multicollinearity were screened stepwise and excluded to establish an algorithm model for predicting the daily maintenance dose of warfarin. The ideal predicted percentage was used to test clinical effectiveness.Results:A total of 395 patients were included. Univariate linear regression analysis suggested that CYP1A2 (rs2069514) and UGT1A1 (rs887829) were not associated with the daily maintenance dose of warfarin. The new algorithm model established based on multiple linear regression was as follows: Y = 1.081 − 0.011 (age) + 1.532 (body surface area)-0.807 (rs9923231 AA) + 1.788 (rs9923231 GG) + 0.530 (rs1057910 AA)-1.061 (rs1057910 AG)-0.321 (rs699664 AA). The model accounted for 61.7% of individualized medication differences, with an ideal prediction percentage of 69%.Conclusion:GGCX (rs699664) may be a potential predictor of warfarin dose, and our newly established model is expected to guide the individualized use of warfarin in clinical practice in southern China.

Long-Term Growth in Children and Young People with Autoimmune Liver Disease Treated with Daily Steroids.

We aimed to evaluate long-term growth in children and young people with autoimmune liver disease (AILD) treated with daily steroids. This is a retrospective observational cohort study of patients diagnosed between 1992 and 2004 before the age of 16 years. Growth measurements (height, weight and body mass index (BMI)) converted to z-scores were recorded, at diagnosis, 1 and 5 years after commencing treatment and at age 18 years and analyzed together with demographics, disease and treatment related characteristics. Seventy-four patients (35 female) were started on treatment at median age of 12.85 (Inter quartile range (IQR) 9.44, 14.14) years for median duration of 12.07 (IQR 8.68, 13.97) years. At all time-points, the mean z-scores for weight, height and BMI were within the normal range, indicating normal nutritional status. There was no difference in change in z-score for weight, height and BMI from diagnosis until age 18 years when comparing gender (male vs female), ethnicity (Caucasian vs non-Caucasian), diagnosis (AIH vs ASC) and presence of IBD (n = 23). Change in z-score was lower for height and weight for the < 12 years group compared to the ≥12 years age group ( P < 0.05 and P < 0.05, respectively). In addition, change in height z-score correlated positively with age at start of steroid treatment (r = 0.321, P < 0.05) and negatively with duration of steroid treatment (r = -0.321, P < 0.05). Growth of patients with AILD on a daily maintenance dose of steroids remains stable and within normal range during long-term follow up. Small, daily doses are effective in maintaining disease control and minimize the need for high-dose steroid pulses during relapses.