Daily Dosing Frequency Research Articles

Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing.

When switching from premixed insulin to insulin degludec/aspart (IDegAsp), IDegAsp usually starts at the same dose as the premixed insulin according to limited clinical experience or at a dose according to clinician discretion. The dose of insulin degludec used in the real world after switching has been poorly investigated. A retrospective analysis was conducted on patients with type 2 diabetes who switched from premixed insulin to IDegAsp from October 2016 to December 2023. Repeated measures analysis of variance was used to compare changes in insulin dose, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) before and after switching. Sixty-six patients with prior low-ratio premixed insulin and 22 with prior mid-ratio premixed insulin were included. Among the low-ratio insulin users, the total daily dose of insulin degludec (IDeg) decreased by 21.43% and 19.05% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). Conversely, among mid-ratio insulin users, the IDeg daily dose increased by 10.71% and 32.14% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). In all patients, HbA1c levels decreased by 0.70%, FBG decreased by 1.00mmol/l, and PBG decreased by 1.61mmol/l after 6months of switching (all p < 0.05); the total daily insulin dose and injection frequency significantly decreased after switching (both p < 0.05); age and disease duration did not affect IDegAsp effects on HbA1c reduction. In the setting of transition to IDegAsp from premixed insulin, the dose of basal insulin in the premixed formulation can be a valuable reference for adjusting insulin degludec dose. IDegAsp is superior to premixed insulin in blood glucose control with reduced total daily dose and injection frequency. IDegAsp could be the best choice for the management of diabetes in elderly patients.

Impact of once-daily versus multiple-daily dosing of gentamicin on the incidence of acute kidney injury in patients treated with synergistic combinations of antibiotics

BackgroundGentamicin is a commonly used antibiotic with synergistic effects that is administered once or multiple times daily. However, the influence of the daily administration frequency on renal function has not yet been identified. This study aimed to investigate the effect of the daily dosing frequency on worsening renal function in patients receiving gentamicin.MethodsThis study included 35 patients undergoing gentamicin treatment who had at least one serum trough level measured and underwent therapeutic drug monitoring (TDM). We evaluated the influence of daily dosing frequency on gentamicin trough concentration and the risk of acute kidney injury (AKI).ResultsCompared to patients who received gentamicin once-daily dosing (n = 22), patients who received multiple-daily dosing (n = 13) had significantly higher initial and minimum trough concentrations after TDM. The proportion of patients with trough concentrations lower than 1.0 µg/mL was significantly higher in the once-daily dosing group at the initial trough concentration, whereas there was no significant difference at the minimum trough concentration after TDM. AKI developed in nine patients; however, there was no significant difference in the incidence of AKI according to the frequency of daily gentamicin dosing. In contrast, a higher minimum trough concentration after TDM was found to be a risk factor for AKI development with an odds ratio of 9.2 (95% confidence intervals; 1.3–65.5).ConclusionA higher trough concentration of gentamicin correlated with a higher incidence of AKI. The risk of developing AKI may be reduced by choosing a once-daily dosing regimen or implementing TDM.

Is compressed colchicine tablet superior to other colchicine preparations in patients with familial Mediterranean fever?

The aim of our study is to evaluate the differences in effectiveness, dosage, and side effect profiles in the use of colchicine preparations and evaluate the superiority of compressed colchicine tablets in familial Mediterranean fever (FMF) patients with resistance or intolerance to coated colchicine tablets. Patients who were diagnosed with FMF according to the Tel Hashomer criteria, aged 18 years and older, and switched from compressed colchicine to coated colchicine tablets in the rheumatology clinic of Gazi University were identified. The daily colchicine dose and FMF attack frequency before and after switching from coated colchicine tablets to compressed colchicine tablets were compared. The study included 43 female (72.9%) and 16 male patients (27.1%), and the mean age was 34.54±8.3 years. The number of attacks per year was significantly reduced after switching to compressed colchicine tablets, and daily colchicine doses were lower after switching to compressed colchicine tablets (1.97±0.23 vs 1.78±0.39 mg, p<0.001). Compressed colchicine tablets were shown to be superior to other colchicine preparations and compressed colchicine tablets to be a useful treatment option before initiating biological agents in patients who were unresponsive to coated colchicine.

Integrated safety summary from Phase 3 clinical trials of IPX203, an extended-release carbidopa-levodopa formulation, in Parkinson disease (P1-11.006)

Integrated safety summary from Phase 3 clinical trials of IPX203, an extended-release carbidopa-levodopa formulation, in Parkinson disease (P1-11.006)

Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial (S32.006)

Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial (S32.006)

Development of Best Evidence Dosing Recommendations for Term and Preterm Neonates (NeoDose Project)

: Many drugs are used off-label in neonates which leads to large variation in prescribed drugs and dosages in neonatal intensive care units (NICUs). The NeoDose project aimed to develop best evidence dosing recommendations (DRs) for term and preterm neonates using a three-step approach: 1) drug selection, 2) establishing consensus-based DRs, and 3) establishing best evidence DRs. Methods: The selection of drugs was based on frequency of prescribing, availability of a neonatal DR in the Dutch Pediatric Formulary, and the labeling status. Clinical need, pharmacological diversity, and Working Group Neonatal Pharmacology (WGNP) preferences were also taken into account, using a consensus-based approach. For the second step, we requested local dosing protocols from all ten Dutch NICUs and established consensus-based DRs within the WGNP, consisting of neonatologists, clinical pharmacologists, hospital pharmacists, and researchers. In the third step, the consensus-based DRs were compared with the available literature, using standardized PubMed searches. Results: Fourteen drugs were selected for which the local dosing protocols were collected. These protocols differed mostly in total daily dose, dosing frequency, and/or route of administration. Strikingly, almost none of the dosing protocols of these 14 drugs distinguished between preterm and term neonates. The working group established consensus-based DRs, which after literature review needed modification in 56%, mainly in terms of a dose increase. Finally, we established 37 best evidence DRs, 22 for preterm and 15 for term neonates, representing 19 indications. Conclusion: This project showed the successful three-step approach for the development of DRs for term and preterm neonates.

Impact of phosphate binders on medication dosing frequency, timing, and number of prescribed pills in hemodialysis patients.

Phosphate binders (PBs) account for a large proportion of the daily pill burden in hemodialysis patients. However, patients do not take them all at once but at several dosing timings. We analyzed the dosing timings of all 322 types of oral drugs prescribed to 533 hemodialysis patients. The median daily dosing frequency for all drugs was 6 (4-7) times/day/patient. Patients prescribed PBs had a markedly higher daily dosing frequency than those not taking PBs (7 [5-8] times/day/patient vs. 4 [3-5] times/day/patient, respectively [p < 0.001]). In addition, the ratio of the number of PB pills to other drugs varied greatly at each dosing timing. Furthermore, it was simulated that the daily dosing frequency could be reduced by approximately two times/day/patient by combining the dosing timings of PBs. Changing PB dosing timings can reduce the daily dosing frequency, which may lead to improved medication adherence.

Time to Rehospitalization for Different Oral Risperidone Dosing Frequencies in Patients With Schizophrenia: A 17-Year Retrospective Cohort Study.

This retrospective cohort study aimed at determining whether the daily administration pattern of risperidone influences time to rehospitalization in patients with schizophrenia. Previous studies have related more frequent dosing to poor medication adherence. This causes suboptimal disease control, which entails shorter times between hospital admissions. We investigated admission records from 1 tertiary psychiatric hospital in Taiwan. Patients were included if they had a main diagnosis of schizophrenia or schizoaffective disorder and were receiving oral risperidone. The enrollment period was July 2001 to December 2016; we observed whether rehospitalization would occur in subsequent periods of 3-month, 6-month, and 1-year follow-ups. There were 1504 patients grouped by daily dosing frequency of oral risperidone. Most patients (95.9%) received 6 mg or less of risperidone per day. After adjustment for covariates, including daily total dosages of risperidone, it showed an independent association that more frequent dosing frequency of risperidone had higher hazard ratios (HRs) of rehospitalizations (in 1-year follow-up: 2 vs 1 dosing a day: HR, 1.566; 3 vs 1 dosing a day: HR, 3.010; 4 vs 1 dosing a day: HR, 4.305) and a significant trend of more possible rehospitalizations (Cochran-Armitage test for trend: P < 0.001) in 3-month, 6-month, and 1-year follow-up. Patients receiving more doses of risperidone per day are more likely to be readmitted within 1 year following last discharge, indicating poorer treatment outcomes for patients who receive more frequent doses.

Potentially Inappropriate Medication Prescribing in Older Adults According to EU(7)-Potentially Inappropriate Medication List: A Nationwide Study in Portugal

BackgroundPortugal has among the highest rates of dependency among older adults in Europe. Older adults with aging-related comorbidities are prone to the use of potentially inappropriate medication (PIM).ObjectiveThe aim of this study was to analyze PIM prescriptions in older Portuguese adults, as well as the change rate of PIM prescriptions over time, and assess the geographical variability between the different regions of mainland Portugal.MethodsUsing a national database, PIM prescriptions were analyzed for older adults (aged 65 years and older) between 2019 and 2021 from 2 perspectives: PIM-defined daily dose (DDD) frequency (%) and DDD per 1000 inhabitants per day (DID).ResultsOverall, mainland Portugal presented a PIM DDD frequency of 9.20%, which was relatively higher in Alentejo and Centro and lower in the North. Alprazolam, fluoxetine, and rivaroxaban were PIM with higher DDD frequency values. Over the years, the DID change rates for these three PIM were –3.80%, –14.86%, and +18.54%, respectively, depending on the geographic region. Alprazolam and fluoxetine were mostly prescribed to older women, whereas rivaroxaban was mostly prescribed to older men.ConclusionsThese results emphasize the need to implement initiatives and interventions to decrease PIM prescriptions in older adults.

61 Adherence to Daily Medication Regimens in Pediatric Asthma: Do Socioeconomic Status and Daily Dose Frequency have an Impact?

Abstract Primary Subject area Respirology Background Children with asthma from lower socioeconomic status (SES), and those with poor adherence to controller medications have worse health outcomes, including higher rates of exacerbations and hospitalizations. Simpler medication regimens could potentially improve medication adherence and asthma control. Objectives We aimed to determine if: (1) medication adherence (proportion of prescribed days covered [PPDC]) and primary non-adherence (PPDC = 0%) varied by SES; and if (2) there was an interaction between SES and daily dose frequency on adherence. Design/Methods This retrospective cohort study included children 2-17 years old followed at the asthma clinic of a large Canadian pediatric hospital between 2011 and 2020. Patients were prescribed one of five medication regimens that included one or more of the following medication classes: inhaled corticosteroids (ICS), long-acting beta-agonists (LABA) and leukotriene receptor antagonists (LTRA). Primary outcome was medication adherence, using the PPDC: the number of days for which a medication was dispensed divided by the number of days for which it was prescribed. For regimens with two different medications, total PPDC was the average of the PPDCs for each medication. The main predictor was SES, measured by the Pampalon’s material deprivation index, a compounded index of income, employment, and education, based on postal codes. It is divided in quintiles, with quintile 1 being the least materially deprived. Comparison of PPDC between quintiles of SES was achieved by a Kruskal-Wallis test. Chi-square testing was used to assess the relationship between the proportion of patients with primary non-adherence (PPDC=0) and quintiles of SES. In the subset of patients who did not have primary non-adherence (n = 462), interaction between SES and daily dose frequency on log transformed PPDC was examined using linear regression models. Results Among 551 patients, mean age was 7.1 years (SD 3.8) (Table1), and there was a similar number of patients in each quintile of SES based on a chi-square goodness of fit test (p=0.61). For the overall sample, mean PPDC was 38.1% (SD 27.6). PPDC was not statistically different between quintiles of SES (p=0.57) (Figure 1). Distribution of primary non-adherence (PPDC = 0) in the cohort was independent of the quintiles of SES (p=0.57). Keeping SES constant, twice-daily dose frequency was associated with a 1.1% decrease in PPDC (p=0.85). The interaction between daily dose frequency and SES was not statistically significant (p=0.66). Conclusion Medication adherence (PPDC) and primary non-adherence (PPDC = 0) did not vary significantly by SES, but twice-daily dose frequency was associated with a small decrease in mean PPDC. Quebec’s mandatory medication insurance could potentially explain the absence of difference in medication adherence across SES quintiles.

Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity.

BackgroundPolymyxin B, as the final treatment against multidrug-resistant Gram-negative bacilli, is widely used in clinical practice. However, little is known about the nephrotoxicity of polymyxin B. The purpose of this study was to elucidate the relationship between polymyxin B nephrotoxicity and daily administration frequency.MethodsSprague–Dawley rats were randomly divided into three groups: 18 mg/kg/q24 h group (Group A, once daily), 9 mg/kg/q12 h group (Group B, twice daily), and normal saline control group (Group C). The rats were injected subcutaneously for 5 consecutive days with the same daily total dose and different frequency of administration. The serum creatinine (SCr) and blood urea nitrogen (BUN) of each group before administration (0 h), and 8 and 24 h after administration, were measured by tail vein blood sampling. On the sixth day, the rats in each group were killed, the left kidney was taken for pathological section observation, and the results of each group were compared.ResultsAfter 96 h of administrated polymyxin B, the total average level of SCr in Group A was 56.98±12.42 μmol/L, that of Group B was 52.02±8.68 μmol/L, and that of Group C was 34.36±5.39 μmol/L. BUN was 9.86±4.58, 10.54±4.08, and 3.55±0.73 mmol/L in Groups A, B, and C, respectively. The daily urinary protein excretion was 5004.45±1333.84 μg in Group A, 4608.04±1444.42 μg in Group B, and 2096.33±215.28 μg in Group C. In addition, according to the observation of pathological slices, compared with Group A, the number of exfoliated and necrotic cells of renal tubules in Group B was higher, and the morphological changes were more serious.ConclusionThe experimental results showed that the renal toxicity in rats treated with a twice-daily subcutaneous dose of polymyxin B was higher than that in rats treated with once-daily dose of polymyxin B.

Student Pharmacists’ Ability to Organize Complex Medication Regimens According to the Universal Medication Schedule

Objective. To assess student pharmacists' ability to impact the administration of complex prescription regimens using the universal medication schedule in a standardized laboratory exercise. Methods. First and third professional year (P1 and P3) student pharmacists at three colleges of pharmacy completed a required activity to simplify and organize a complex medication regimen. Using a medication box, students planned how and when they would advise a patient to take seven fictitious medications over a 24-hour period. Picture documentation of each students' activity was used for data analysis. Descriptive statistics were used to compare P1 and P3 students' performance, and an independent t test was used to assess the frequency of daily dosing. A chi-square analysis was used to compare differences between P1 and P3 students, and analysis of variance was used to compare differences among individual institutions. Results. Of 842 students invited, 459 P1 and 372 P3 students (98.7%) consented to participate. Student pharmacists recommended 5.1 (SD=1.0; Range=3-11) dosing intervals per 24 hours, with 27% of students successfully reducing the regimen to four total intervals. The P3 students were more effective than the P1 students in planning the number of dosing intervals (4.9 vs 5.4 per 24 hours). Conclusion. Student pharmacists may become more effective at organizing complex medication regimens as they proceed through the pharmacy curriculum and gain experience. Student pharmacists can translate what they learned from this exercise to potentially improve patients' self-organized medication regimens.

Do all colchicine preparations have the same effectiveness in patients with familial Mediterranean fever?

Aim Colchicine is the primary treatment for familial Mediterranean fever (FMF). Several colchicine preparations are currently using available globally. This study aimed to describe the demographic, clinical, and genetic features of FMF patients treated with multiple colchicine preparations. Materials and methods The records of patients diagnosed as FMF and followed-up by our pediatric rheumatology department were retrospectively evaluated. Patients that were treated with multiple colchicine preparations were included. Patient demographic, clinical, and laboratory data were obtained from the patient files and the hospital patient database. The daily colchicine dose and FMF attack frequency before and after switching from domestically produced (DP)-coated colchicine tablets to foreign produced (FP)-compressed colchicine tablets were compared. Results The study included 35 pediatric FMF patients (22 males and 13 females) with a mean age of 12.85 ± 4.62 years. Mean age at disease onset was 3.66 ± 2.11 years, versus 5.57 ± 4.28 years at diagnosis. The mean attack frequency before and after treatment with FP-compressed colchicine tablets was 9.50 ± 4.46 and 1.85 ± 1.41/year, respectively (p < .001). The mean attack duration significantly decreased in all the patients treated with FP-compressed colchicine tablets (p < .001). The difference in acute phase reactants during the attack-free periods before and after FP-compressed colchicine tablet treatment was significant (p < .001). Conclusion The present findings show that pediatric FMF patients with ongoing attacks and elevated acute phase reactants during attack-free periods while treated with DP-coated colchicine tablets might benefit from switching to FP-compressed colchicine tablets before initiating biologic treatment. Long-term controlled studies are warranted, so as to obtain better evidence of the benefits of multiple colchicine preparations in pediatric FMF patients.

Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment.

BackgroundEvidence regarding the safety of using proviral HIV-1 DNA genotype (DNA GT) to guide antiretroviral therapy (ART) is limited. We hypothesized that HIV RNA would not increase following ART adjustment guided by DNA GT in a university HIV clinic.MethodsData were obtained from electronic medical records of adult persons living with HIV-1 (PWH) who underwent DNA GT testing and changed ART between October 2014 and November 2017. Logistic regression was used to evaluate the effect of ART switch on HIV RNA over time.ResultsEighty-three PWH had DNA GT performed, 66 (80%) switched ART, and 59 had postswitch follow-up. Data were analyzed pre-/postswitch for these 59 PWH (median age, 54 years; 71% LWH ≥10 years; 46% ≥2 previous regimens; 36% recent low-level viremia; 34% unknown medication history). On DNA GT, 58% had ≥1-class ART resistance, 34% ≥2-class, and 10% 3-class. Median follow-up (range) was 337 (34–647) days. There was no change in probability of HIV RNA ≥50 copies/mL over time (P > .05). At baseline, 76% had HIV RNA <50 vs 88% at last postswitch follow-up (P = .092). Protease inhibitor use decreased from 58% to 24% (P < .001). Average daily pills and dosing frequency decreased from 3.48 to 2.05 (P < .001) and 1.39 to 1.09 (P < .001), respectively; ART cost did not change.ConclusionsDNA GT facilitated changes in ART in a treatment-experienced population without increases in HIV RNA. Decreased pill burden occurred without increased ART cost. Further studies to identify optimal use of DNA GT are needed.

An Evaluation of Risperidone Dosing for Pediatric Delirium in Children Less Than or Equal to 2 Years of Age

Background: Risperidone dosing and safety data are limited in patients ≤2 years of age. Objective: To describe the dosing strategies, safety, and tolerability of risperidone in infants ≤2 years of age. Methods: An institutional review board-approved retrospective study was conducted in a 24-bed pediatric intensive care unit at an academic medical center in patients ≤2 years of age receiving risperidone for the management of ICU delirium. The primary outcome was mean initial daily dose of risperidone. Secondary outcomes included mean daily dose, dosing frequency, treatment duration, and adverse effects. Results: Seventeen patients who received at least 1 dose of risperidone were included in the study. The initial daily dose ranged from 0.1 to 0.25 mg (0.01-0.04 mg/kg), with a mean of 0.17 mg (0.02 mg/kg). Most patients were initiated on once-daily dosing (76.5%) versus twice-daily dosing (17.6%). More than 80% of patients required a dose increase during therapy. Median daily doses of fentanyl, morphine, ketamine, and midazolam were decreased following initiation of risperidone. No adverse events that led to discontinuation of risperidone were reported. Conclusion and Relevance: Risperidone was found to be safe and well tolerated at daily doses of risperidone of 0.1 to 0.25 mg in 1 or 2 doses per day in patients ≤2 years old for the management of ICU delirium. To our knowledge, these results provide the largest cohort describing dosing recommendations specific for risperidone in this age group. Further investigation on the effect of antipsychotic administration on other sedation and analgesic regimens is necessary.

1674-P: Age of Onset Is Associated with Insulin Resistance in Patients with Type 1 Diabetes Mellitus

Objective: Data are limited on insulin resistance (IR) status in patients with type 1 diabetes (T1D). This study aimed to assess the IR status and the effect of onset age on IR in patients with T1D. Methods: Through the Guangdong T1D registry study, we identified adult patients (aged≥18 years) with a diabetes duration≥1 year. Clinical data were collected. A previously established model based on euglycemic-hyperinsulinemic clamp were used to calculate the estimated glucose disposal rate (eGDR) via clinical parameters. Participants were categorized into groups based on age of onset: childhood-onset group (cT1D, age of onset&amp;lt;12 years); adolescent-onset group (pT1D, age of onset 12-17 years); and adult-onset group (aT1D, age at onset ≥18 years). Spearman correlation was used to analyze the correlation between IR and age of onset. ANOVA and Chi square test were used for comparisons of IR status and clinical parameters among the three groups. Results: This analysis included 872 adults with T1D (58.3% female). The mean (SD) eGDR was 8.98 (3.34) mg/kg/min. There was a negative correlation between the level of IR status and the onset age (r=-0.093, p=0.003). The IR status assessed by eGDR decreased alongside an increase in age of onset (p=0.018). Compared with participants with older age of onset, patients in cT1D group had a higher level of A1c, lower proportion of participants with A1c less than 7%, higher daily insulin dose and higher frequency of hypoglycemic events (all p&amp;lt;0.05). Conclusions: Age of onset was significantly and negatively correlated with IR status. Childhood-onset patients with T1D are more likely to benefit from treatment of IR condition. Disclosure D. Yang: None. C. Wang: None. X. Zheng: None. S. Luo: None. Q. Lin: None. J. Yan: None. J. Weng: None.

The Importance of Inhaler Adherence to Prevent COPD Exacerbations.

It has been shown that the better outcomes of chronic obstructive pulmonary disease (COPD) are closely associated with adherence to drug therapy, independent of the treatment administered. The clinical trial Towards a Revolution in COPD Health (TORCH) study clearly showed in a three year follow up that patients with good adherence to their inhaler treatment presented a longer time before the first exacerbation, a lower susceptibility to exacerbation and lower all-cause mortality. The Latin American Study of 24-h Symptoms in Chronic Obstructive Pulmonary Disease (LASSYC), a real-life study, evaluated the self-reported inhaler adherence in COPD patients in seven countries in a cross-sectional non-interventional study and found that approximately 50% of the patients had good adherence, 30% moderate adherence and 20% poor adherence. Adherence to inhaler may be evaluated by the specific inhaler adherence questionnaire, the Test of Adherence to Inhalers (TAI). Several factors may predict the incorrect use of inhalers or adherence in COPD outpatient, including the number of devices and the daily dosing frequency. Ideally, patient education, simplicity of the device operation, the use of just one device for multiple medications and the best adaptation of the patient to the inhaler should guide the physician in prescribing the device.

Freeze-Dried Matrices Based on Polyanion Polymers for Chlorhexidine Local Release in the Buccal and Vaginal Cavities

Chlorhexidine (CLX) is a wide spectrum cationic antimicrobial used for prevention and treatment of infections of buccal and vaginal cavities. To increase the residence time of CLX-based formulations at the application site and consequently reduce the daily dose frequency, new formulations composed of mucoadhesive polymers should be designed. The objective of this work was the development of matrices based on polyanionic polymers, such as sodium alginate, carboxymethylcellulose, xanthan gum and sodium hyaluronate, aimed to prolong the local release of CLX into the buccal or vaginal cavity. Matrices were prepared by freeze-drying and comply with 2 different preparative methods and characterized in terms of resistance to compression, water uptake ability, mucoadhesion, in vitro drug release behavior and antimicrobial activity toward representative pathogens of buccal and vaginal cavities. Results showed that the selection of suitable polymers associated to the adequate preparative method allowed to modulate matrix ability to hydrate, adhere to the mucosa and release the drug as well as to exert antimicrobial activity. In particular, matrix based on sodium hyaluronate was found to be the best performing formulation and could represent a versatile system for local release of CLX with potential application in both buccal and vaginal cavities.

Optimization of feeding quantity and frequency to rear the cyprinid fish Garra rufa (Heckel, 1843)

Garra rufa has a high commercial value, but their rearing methods are still unknown. Aspects like an adequate daily dose and feeding frequency need to be investigated. This work aimed to establish the optimal feed dose per day to obtain satiation and the optimal frequency of feeding to rear a specific size class of G. rufa. A total of 60 fish were distributed by six aquaria containing 10 fish. First, the fish were fed twice per day, by providing a feed dose correspondent to 1% of their body weight and increasing 0.1 g/fish on the following days, until finding feed leftovers on the next morning. Afterwards, the fish went through a 1 month experimental trial to evaluate the optimal feeding frequency. Fish growth was compared between feeding the optimal daily dose distributed in two or three feeding moments per day. The optimal dose that ensured satiation was 0.042 g fish−1 day−1 (3.2% of fish’ body weight). Feeding the fish three times per day promoted higher growth rates, since the fish’ total length was statistically different between feeding frequencies. Statistically significant differences between feeding frequencies were not observed for growth performance parameters. These results contribute to the aquaculture of this target species, allowing fish industry to more efficiently respond to the high demand for G. rufa and, simultaneously, for its preservation in the wild.

Linezolid-based Regimens for Multidrug-resistant Tuberculosis (TB): A Systematic Review to Establish or Revise the Current Recommended Dose for TB Treatment.

Linezolid has been successfully used for treatment of multidrug-resistant tuberculosis (MDR-TB). However, dose- and duration-related toxicity limit its use. Here, our aim was to search relevant pharmacokinetics (PK)/pharmacodynamics (PD) literature to identify the effective PK/PD index and to define the optimal daily dose and dosing frequency of linezolid in MDR-TB regimens. The systematic search resulted in 8 studies that met inclusion criteria. A significant PK variability was observed. Efficacy of linezolid seems to be driven by area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC). Literature is inconclusive about the preferred administration of a daily dose of 600 mg. To prevent development of drug resistance, an AUC/MIC ratio of 100 in the presence of a companion drug at relevant exposure is required. A daily dose of 600 mg seems appropriate to balance between efficacy and toxicity. Being a drug with a very narrow therapeutic window, linezolid treatment may benefit from a more personalized approach, that is, measuring actual MIC values and therapeutic drug monitoring.