The effect of different levothyroxine administration regimens on thyroid hormone levels: a systematic review, pairwise, and network meta-analysis.

INTRODUCTION: This systematic review aimed to compare the effect of alternative levothyroxine administration regimens on thyroid hormone levels and patient-reported outcomes (PROs) among adults with hypothyroidism. METHODS: We searched PubMed, Embase, CENTRAL, CINAHL, LILACS, SciELO, Scopus, Web of Science, OpenGrey, ProQuest, ClinicalTrials.gov, and ICTRP from inception to May/2023 for randomized controlled trials (RCTs). We assessed the risk of bias with Cochrane Risk of Bias 2.0 tool. We analyzed TSH levels by pairwise and network meta-analyses (NMA). The FT4 levels and PROs were qualitatively assessed. RESULTS: We included 14 RCTs (906 participants) comparing different regimens, as bedtime vs. before breakfast. A total of 12 RCTs were at high risk of bias. Seven RCTs were included in the TSH meta-analysis, where the mean difference (MD) and 95% confidence interval (CI) were as follows: bedtime vs before breakfast (4 RCTs) 0.69 (-1.67-3.04), I2 = 92%, very low certainty evidence; weekly dose vs before breakfast (2 RCTs) 1.68 (0.94-2.41), I2 = 0%, low certainty evidence; and at breakfast vs before breakfast (1 RCT) 0.65 (-1.11-2.41), very low certainty evidence. The NMA showed no evidence of differences in TSH level with different regimens. CONCLUSION: The evidence is insufficient to determine the most effective levothyroxine administration regimen for hypothyroidism. SYSTEMATIC REVIEW REGISTRATION: PROSPERO - CRD42021279375.

Amoxicillin Administration Regimen and Resistance Mechanisms of Staphylococcus aureus Established in Tissue Cage Infection Model.

Staphylococcus aureus is a zoonotic pathogen that causes various life-threatening diseases. The mechanisms of action of amoxicillin against S. aureus are unclear. Here, we established a rabbit tissue cage infection model to evaluate the relationship between the pharmacokinetic/pharmacodynamic (PK/PD) parameters of amoxicillin and selective enrichment of resistant strains of S. aureus and to elucidate the evolution of its resistance to amoxicillin. S. aureus was injected into the tissue cages at 1010 colony forming units (CFU)/mL. We injected different intramuscular concentrations of amoxicillin at doses of 5, 10, 20, and 30 mg/kg body weight once a day for 5 days and 5, 10, 20, and 30 mg/kg body weight twice a day for 2.5 days. Differences in gene expression between two differentially resistant strains and a sensitive strain were evaluated using Illumina sequencing followed by COG and KEGG analysis. RT-qPCR was carried out to validate the difference in protein translation levels. Our results demonstrated that the emergence of resistant bacteria was dose dependent within a given time interval. In the same dosage group, the appearance of resistant bacteria increased with time. The resistant bacteria showed cumulative growth, and the level of resistance increased over time. The resistant bacteria were completely inhibited when the cumulative percentage of time over a 24-h period that the drug concentration exceeded the mutant prevention concentration (MPC) (%T > MPC) was ≥52%. We also found that mecA and femX in S. aureus played a leading role in the development of resistance to amoxicillin. In conclusion, it provide references for optimizing amoxicillin regimens to treat infections caused by S. aureus.

Prednisolone Effects on Urine Cross-Linked N-Telopeptides of Type I Collagen (Ntx) Diurnal Rhythms in Children.

BACKGROUND: Recently, methods for mimicking endogenous cortisol rhythms hereby potentially reducing the risk of systemic adverse effects of exogenous corticosteroids have been patented. Methods for sensitive detection of adverse effects on bone turnover of various doses, administration routes and regimens of exogenous corticosteroids have been patented. Urine cross-linked Ntelopeptides of Type I collagen (Ntx) have been established as a sensitive bone resorption marker and urine levels of Ntx have been found to exhibit a distinct diurnal rhythm. OBJECTIVE: To assess whether the timing of administration of prednisolone affects the diurnal rhythm of Ntx in urine. METHODS: Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV were studied in an open randomized 2-periods cross-over trial, with a 1-day run in, and two 4-day periods of 5mg prednisolone in the morning and in the evening, respectively, separated by a 3-week washout period. At run in and on the last day of each treatment period, the first sample of urine was collected from 24.00 to 08.00h in the morning of the day of investigation. Thereafter, urine was collected in 4~hour intervals until 24.00 and in another 08.00h interval from 24.00 to 08.00h. RESULTS: Compared to run in and morning prednisolone treatment urine Ntx levels were suppressed from 24.00 to 8.00h during treatment with prednisolone in the evening (P < 0.01 for both comparisons) and no statistically significant circadian rhythm was observed. During morning prednisolone treatment Ntx trough and peak levels occurred from 16.00 to 20.00 and 24.00 to 08.00h, respectively, and the Ntx levels were significantly reduced from 12.00 to 20.00h as compared to run in (P < 0.005) and prednisolone treatment in the evening (P < 0.01). CONCLUSIONS: Depending on the time of administration, prednisolone interferes with diurnal rhythms in urine Ntx.

The timing of administration of exogenous glucocorticoid affects 24hour growth hormone secretion in children.

Exogenous glucocorticoids may suppress linear growth by affecting the diurnal secretory rhythm of GH. OBJECTIVE: To assess whether the timing of exogenous glucocorticoid administration affects GH secretion in children. DESIGN: Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV were studied in an open randomized 2-period cross-over trial, with a 1-day un-in, and two 4-day periods of 5mg prednisolone in the morning or in the evening, respectively, separated by a 3-week washout period. At run-in and on the last day of each treatment period serum was collected every 20min for 24h for assessment of GH. Secondary analyses were serum levels of IGF-I and IGFBP-3 (measured every 8h), and IGFBP-1, insulin, and collagen markers PICP, PINP, ICTP and PIIINP (measured every 2h). RESULTS: Evening prednisolone suppressed 24hour GH secretion (P=0.016), overnight GH secretion (P=0.023) and IGF-I (P=0.024) when compared to morning prednisolone, but not when compared to run-in. Evening prednisolone also increased nocturnal insulin levels as compared to run-in (P=0.010). Irrespective of time of day, prednisolone increased serum collagen markers PICP, PIINP, ICTP and PINP (all P<0.05). CONCLUSIONS: Short-term prednisolone 5mg administered in the morning may alleviate nocturnal GH suppression as compared to evening administration. In analogy, growth rates are less affected by morning as compared to evening administration of exogenous glucocorticoids. In contrast, collagen markers and metabolic indices were not affected by the timing of prednisolone administration.

Clinical considerations on the posology of direct oral anticoagulants. / Consideraciones clínicas sobre la posología de los anticoagulantes orales de acción directa.

The efficacy of dicoumarin anticoagulants has been shown in patients with nonvalvular atrial fibrillation. However, they have drawbacks such as the need to adjust the dosage and the interaction with drugs and food. Direct oral anticoagulants are an effective and safe alternative and have a less complicated clinical management. There is considerable debate on the selection criteria for the posology regimens of direct oral anticoagulants. The differences among them and their administration regimens have raised questions about the clinical, pharmacokinetic and pharmacodynamic selection criteria that support the posology. This review critically analyses the available evidence and its impact on the final selection of the dosage regimen.

The impact of dosing frequency on medication adherence in chronic cardiovascular disease: systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVE: Non-adherence to drug treatment is a major health problem. In Europe, it has been estimated that 9% of cardiovascular events can be attributed to non-adherence. The complexity of dosing regimens is one of the factors identified as contributing to non-adherence. In this systematic review we aimed to assess the impact of dosing frequency on adherence to drug treatment in patients with chronic cardiovascular disease. METHODS: MEDLINE and the Cochrane Library (November 2013) were searched for randomized controlled trials (RCTs) comparing different dosing regimens (once-daily administration vs. two or more daily administrations) and assessing adherence to therapy in patients with chronic cardiovascular disease. Only trials with at least five months of follow-up were included. The results of the studies were pooled through a random effects meta-analysis. Relative risk (RR) and 95% confidence interval (CI) were derived. Statistical heterogeneity was calculated using the I(2) test. RESULTS: Four RCTs (a total of 2557 patients) were included. Dosing regimens with once-daily administration were associated with a significant 56% reduction in risk of non-adherence to drug therapy (RR: 0.44; 95% CI: 0.35-0.54, I(2)=25%). CONCLUSIONS: Few clinical trials have assessed the long-term impact of dosing frequency on medication adherence in chronic cardiovascular disease. The best available evidence suggests that taking medication once daily decreases the risk of non-adherence to treatment by approximately 50%. The impact on clinical outcomes remains to be established.

Cost-Effectiveness Analysis on2Different Administration Regimens for Treatment of Pain in Waist and Back Induced by Osteoporosis / 中国药房

OBJECTIVE:To evaluate the cost-effectiveness of2different administration regimens for treatment for pains in waist and back caused by osteoporosis.METHODS:123patients were randomly divided into2groups,Group A underwent salmon calcitonin nasal spray,Group B received salmon calcitonin intramuscular injection,2different regimens of administration were evaluated using pharmacoeconomic cost-effectiveness analysis.RESULTS:The total costs in Group A and B were1596yuan and2634.66yuan,respectively(P0.05);And the ratios of cost-effectiveness16.8and27.7,respectively.CONCLUSION:Regimen A is preferred to regimen B.