Higher Maintenance Dose Research Articles

Different onset patterns of monthly paliperidone palmitate in hospitalised patient diagnosed with schizophrenia

AimsPaliperidone palmitate long-acting injectable (PPLAI) initially requires two loading doses of 150 and 100 mg on days 1 and 8 (± 4 days) intramuscularly. In clinical practice, different PPLAI initiation patterns have been observed. The aim of this study is to describe different PPLAI onset patterns in hospitalised patients diagnosed with schizophrenia.MethodA naturalistic, transversal, retrospective, descriptive study was carried out. Patients were recruited in the adult inpatient unit of Hospital Universitario Jiménez Díaz (Madrid, Spain) from November 2012 to February 2021. During this period, a total of 357 patients were treated with PPLAI, 172 of them were diagnosed with schizophrenia and, among these, 24 received an atypical onset pattern during hospitalization. Different PPLAI onset patterns, PPLAI dose at discharge and number of days hospitalised were analysed. This study followed the Declaration of Helsinki principles and was approved by the Local Ethics Committee. All participants gave written informed consent.ResultThe sample presents 24 patients (17 men, 7 women) that represents 6.72% of a global sample, with an average age of 40.21 years (men 35.59 years vs. women 51.43 years). In this study, different PPLAI onset patterns were described: those receiving 150-150 mg represent 25% of the sample (n = 6), as do those receiving 100-75 mg, also representing 25% of the sample (n = 6). The rest of the onset patterns were: 150-75 mg (20.83%, n = 5), 100-100 mg (12.5%, n = 3), 150-75 mg (4.16%, n = 1), 100-50 mg (4.16%, n = 1), 75-100 mg (4.16%, n = 1), and 75-75 mg (4.16%, n = 1). The average hospital stay is 17.88 days. The PPLAI maintenance dose at discharge was 104.17 mg/month. The group of patients who received two doses of 150 mg (150-150 mg) had an average length of stay of 27.67 days compared to the rest of the patients who had an average length of stay of 15.12 days, this difference being statistically significant (p = 0.010). The 150-150 mg group was discharged with a mean maintenance dose of 141.67 mg versus the other patients who needed a mean maintenance dose of 91.18 mg, which was also statistically significant (p = 0.001).ConclusionThe most used pattern of atypical onset of PPLAI in this sample is 150-150 mg and 100-75 mg. Patients treated with 150-150 mg loading pattern are hospitalized for a longer period and needed higher maintenance dose at discharge. Further studies are needed.

Comparison of Efficacy of Two Different Dose Regimens of Intravenous Dexmedetomidne for Awake Transnasal Fibreoptic Intubation

Background and Objectives: Nasal Fibreoptic intubation (NFI) is the recommended technique in patients with difficult airway like facial defects, limited mouth-opening and cervical instability but it requires the patient to be awake. The usage of an ideal sedative agent and stabilizing the intubating condition was essential for this. In this study we compare efficacy of different doses of dexmedetomidine for conscious sedation facilitating NFI. Materials and Methods: This is a prospective, blinded-randomized-trial to correlate the effectiveness of different loading and maintenance doses of dexmedetomidine during NFI on 60 patients, 30 in each group, aged between 20 and 60 years with ASA grade I or II enrolled for elective surgery. All patients received 2 mg Midazolam as premedication before transferring to operating room. Group A patients received Dexmedetomidine 1 mcg/kg I.V bolus slowly over 10 minutes then 0.8 mcg/kg/h as maintenance throughout the procedure. Group B patients received Dexmedetomidine 0.8 mcg/kg I.V. as bolus and 0.2 mcg/kg/h as maintenance dose. Primary outcomes were assessment of sedation level and comfort of each patient by Total Comfort Scale (TCS). The difference in quantitative measures was done using student ‘t’ test and difference in proportions by ‘Chi’ square test. P<0.05 was considered statistically significant. Results: With respect to comfort scores and optimal conditions during NFI, Group A people showed significantly lower scores when compared to Group B. Conclusion: Dexmedetomidine with loading 1μg/kg and higher maintenance dose 0.8μg/ kg/h were better for NFI with better patient tolerance, patient comfort, patient satisfaction, good sedation and preserved upper airway with spontaneous breathing. Key words: Comfort scale; Dexmedetomidine; Fibreoptic intubation.

Sequential tirofiban infusions combined with endovascular treatment may improve outcomes in acute ischemic stroke - a meta-analysis.

In this meta-analysis, we explored whether tirofiban could safely improve outcomes when combined with endovascular therapy in acute ischemic stroke with large vessel occlusion. We searched the PubMed, EMBASE, Web of Science, and The Cochrane Library databases from January 2000 to October 2019 for relevant RCTs/non-RCTs. A total of 13 trials involving 2584 patients, of whom 893 (34.5%) received tirofiban, were ultimately included in the meta-analysis. The results suggested that tirofiban improved patient independence at 90 days (51.2% vs 42.4%; OR 1.26; p =0.02) without increasing the risk of symptomatic intracranial hemorrhage (OR 1.01; p =0.96) or mortality (OR 0.86; p =0.09). There was no association between the use of tirofiban and recanalization rate (OR 1.35; p =0.11). Subgroup analysis showed that a loading dose followed by maintenance doses, but not a single dose, of tirofiban increased favorable 90-day functional outcomes (OR 1.49; p =0.0008). Moreover, low maintenance doses may be more effective than high maintenance doses (OR 1.41; p =0.02). These results suggest that adjunctive tirofiban treatment administered as a loading dose followed by low-dose maintenance may improve functional outcomes of endovascular therapy in acute ischemic stroke.

Risk Factors for Bleeding and Clinical Ineffectiveness Associated With Clopidogrel Therapy: A Comprehensive Meta-Analysis.

Although clopidogrel is a frequently used antiplatelet medication to treat and prevent atherothrombotic disease, clinicians must balance its clinical effectiveness with the potential side effect of bleeding. However, many previous studies have evaluated beneficial and adverse factors separately. The objective of our study was to perform a comprehensive meta‐analysis of studies of clopidogrel’s clinical effectiveness and/or risk of bleeding in order to identify and assess all reported risk factors, thus helping clinicians to balance patient safety with drug efficacy. We analyzed randomized controlled trials (RCTs) of maintenance use in four stages: search for relevant primary articles; abstract and full article screening; quality assessment and data extraction; and synthesis and data analysis. Screening of 7,109 articles yielded 52 RCTs that met the inclusion criteria. Twenty‐seven risk factors were identified. “Definite risk factors” were defined as those with aggregated odds ratios (ORs) > 1 and confidence intervals (CIs) > 1 if analyzed in more than one study. Definite risk factors for major bleeding were concomitant aspirin use (OR 2.83, 95% CI 2.04–3.94) and long duration of clopidogrel therapy (> 6 months) (OR 1.74, 95% CI 1.21–2.50). Dual antiplatelet therapy, extended clopidogrel therapy, and high maintenance dose (150 mg/day) of clopidogrel were definite risk factors for any bleeding. Reduced renal function, both mild and severe, was the only definite risk factor for clinical ineffectiveness. These findings can help clinicians predict the risks and effectiveness of clopidogrel use for their patients and be used in clinical decision support tools.

Myasthenia gravis: MuSK MG, late-onset MG and ocular MG.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction which affects all striated muscles, resulting in fluctuating weakness. Approaching MG as a disease with subgroups having different clinical, serological and genetic features is crucial in predicting the progression and planning treatment. Three relatively less frequently seen subtypes of MG are the subject of this review: MG with anti-MuSK antibodies (MuSK MG), non-thymomatous late-onset MG (LOMG), and ocular MG (OMG). In addition to reviewing the literature, mainly from a clinical point of view, our experience in each of the subgroups, based on close to 600 patients seen over a 10 year period, is related. MuSK MG is a severe disease with predominant bulbar involvement. It is more common in women and in early-onset patients. With the use of high dose corticosteroids, azathioprine and more recently rituximab, outcome is favorable, though the patients usually require higher maintenance doses of immunosuppressives. LOMG with onset ≥ 50 years of age is more common in men and ocular onset is common. Frequency of anti-AChR and anti-titin antibodies are high. Although it can be severe in some patients, response to treatment is usually very good. OMG is reported to be more frequent in men in whom the disease has a later onset. Anti-AChR antibodies are present in about half of the patients. Generalization is less likely when symptoms remain confined to ocular muscles for 2 years. Low dose corticosteroids are usually sufficient. Thyroid disease is the most common autoimmune disease accompanying all three subgroups.

Controversies in Ocular Myasthenia Gravis.

Myasthenia gravis (MG) with symptoms limited to eye muscles [ocular MG (OMG)] is a rare disease. OMG incidence varies according to ethnicity and age of onset. In recent years, both an increase in incidence rate, particularly in the elderly, and a lower risk for secondary generalization may have contributed to the growing disease prevalence in Western countries. OMG should be considered in patients with painless ptosis and extrinsic ophthalmoparesis. Though asymmetric muscle involvement and symptom fluctuations are typical, in some cases, OMG can mimic isolated cranial nerve paresis, internuclear ophthalmoplegia, and conjugate gaze palsy. Diagnostic confirmation can be challenging in patients negative for anti-acetylcholine receptor and anti-muscle-specific tyrosine kinase antibodies on standard radioimmunoassay. Early treatment is aimed at relieving symptoms and at preventing disease progression to generalized MG. Despite the absence of high-level evidence, there is general agreement on the efficacy of steroids at low to moderate dosage; immunosuppressants are considered when steroid high maintenance doses are required. The role of thymectomy in non-thymoma patients is controversial. Prolonged exposure to immunosuppressive therapy has a negative impact on the health-related quality of life in a proportion of these patients. OMG is currently excluded from most of the treatments recently developed in generalized MG.

PREGNANCY AFTER IVF IN A PATIENT WITH SHERESHEVSKY-TURNER SYNDROME (clinical case)

Shereshevsky-Turner Syndrome (SJT) is caused by full or partial X-monosomy, presented in all or part of the cells of the body. For Shereshevsky-Turner syndrome, pronounced hormonal disorders are characteristic - these are primary ovarian, somatotropic, thyrotropic insufficiency, as well as defects of the cardiovascular and urinary systems. With the advent of ART, pregnancy has become more accessible for this category of patients, most often with a donor egg. In the available literature, it was not possible to find the exact information on the selection of progestogen support, duration of appointment, and term of withdrawal; therefore, the clinical case is presented below. In this case, we left high maintenance doses of progesterone, not only due to the use of ART, but also due to concomitant extragenital pathology, which leads to a decrease in all functions of the placenta, including endocrine.

Evaluation and Development of Vancomycin Dosing Schemes to Meet New AUC/MIC Targets in Intermittent Hemodialysis Using Monte Carlo Simulation Techniques.

Published vancomycin dosing recommendations for patients receiving maintenance hemodialysis were not designed to meet newly recommended 24-hour area under the curve/minimum inhibitory concentration (AUC24h /MIC) pharmacokinetic/pharmacodynamic targets. The aims of this study were to predict pharmacokinetic/pharmacodynamic target attainment rates with a commonly used vancomycin regimen and to design a new dosing scheme incorporating therapeutic drug monitoring (TDM) to maximize target attainment in patients receiving vancomycin and hemodialysis with high- or low-flux hemodialyzers. Vancomycin pharmacokinetic- and dialysis-specific parameters were incorporated into Monte Carlo simulations (MCS). A commonly used vancomycin regimen was modeled to determine its likelihood of attaining AUC24h /MIC targets for 1 week of thrice-weekly hemodialysis treatments. MCS was then used to develop optimal initial vancomycin dosing for patients receiving intradialytic or postdialytic vancomycin administration with either high- or low-flux hemodialyzers. Finally, a new MCS model incorporating TDM was built to further optimize the probability of pharmacokinetic/pharmacodynamic target attainment. Traditional vancomycin dosing methods are unlikely to meet AUC24h /MIC targets. Vancomycin doses necessary to attain AUC24h /MIC targets are significantly influenced by hemodialyzer permeability and whether vancomycin is administered intradialytically or after hemodialysis. Depending on dialyzer type and whether vancomycin is administered during or after hemodialysis, loading doses of 25 to 35mg/kg followed by maintenance doses of 7.5 to 15mg/kg are necessary to reach minimum AUC24h /MIC targets in 90% of virtual patients. For a 3-day interdialytic period, a 30% higher maintenance dose is required to maintain target attainment. Dosing based on a single vancomycin serum concentration obtained prior to the second dialysis session greatly enhances the probability of target attainment.

Caffeine citrate maintenance doses effect on extubation and apnea postventilation in preterm infants.

Caffeine citrate is used to prevent apnea in premature infants and help in extubation of invasive ventilation, but the optimal dose remains undetermined. Neonates born at less than 30 weeks gestation who had received invasive ventilation for at least 48 hours and a loading dose of 20 mg/kg caffeine citrate were randomly assigned into high (10 mg/kg daily) or low (5 mg/kg daily) maintenance dose groups. The drug was discontinued if no apnea occurred for 7 consecutive days. A total of 111 infants were assigned into the high (54) or low (57) dose groups. Extubation failure (16.7% vs 36.8%), age of extubation (8.2 ± 2.1 vs 10.7 ± 2.3 day), duration of invasive ventilation (7.2 ± 2.1 vs 8.5 ± 2.4 day), duration of ventilation before extubation (8.0 ± 1.8 vs 10.1 ± 1.9 day), and number of days of apnea (1.8 ± 1.3 vs 3.2 ± 1.1 day) were significantly lower in the high dose group than the low dose group. Difference in time until failure (6.7 ± 1.7d vs 7.0 ± 1.9d) and duration of nasal continuous positive airway pressure(7.8 ± 1.8 vs 8.0 ± 2.2 day) were not significant. Furthermore, no significant differences in the incidence of tachycardia (9.3% vs 12.3%), abdominal distension (16.7% vs 12.3%), feeding intolerance (3.7% vs 5.3%), or irritability (7.4% vs 5.3%) were observed between groups. A higher maintenance dose of caffeine citrate reduced the incidence of extubation failure and apnea of prematurity without increasing the occurrence of adverse reactions.

Antimicrobial Therapy in Septic Shock Is Conservative During Resuscitation and Maintenance Phases

Background: Maximal dosing of early antimicrobials with high loading and maintenance doses may optimize pharmacokinetic parameters to achieve and maintain therapeutic concentrations at the site of infection in septic shock. Little is known about the current practice of early antimicrobial dosing in septic shock. Objective: To characterize early antimicrobial dosing in patients in the resuscitation phase of septic shock. Methods: This retrospective cohort study included patients admitted to the medical intensive care unit (ICU) with septic shock. The primary outcome was the percentage of early antibiotic orders that were maximal or conservative during the resuscitation (0 to 48 hours) phase based on predefined dosing criteria. The secondary outcomes were the correlations of different dosing strategies on hospital length of stay (LOS), ICU LOS, and hospital mortality. Results: This study evaluated 161 patients and 692 antibiotic orders; 504 (72.8%) of the orders during the resuscitation phase were conservative. There were no differences in mortality (odds ratio = 0.66; 95% confidence interval = 0.35-1.25; P = .20), hospital LOS (median = 20 [interquartile range (IQR) = 10-34] vs 19 [IQR = 11-32] days; P = .93), or ICU LOS (median = 8 [IQR = 5-16] vs 9 [IQR = 5-15] days; P = .63) between maximal and conservative dosing groups, respectively, in the resuscitation phase. Limitations of this study included the use of institution-specific antimicrobial dosing guidelines and its retrospective nature. Conclusions: Early antibiotic dosing is conservative for a majority of patients in septic shock. Future studies are needed to evaluate the impact of dosing strategy on patient-centered outcomes in septic shock.

Experience with Selexipag to Treat Pulmonary Arterial Hypertension

Aim To present an own experience in using a medication selexipag in patients with pulmonary arterial hypertension (PAH) included into the V. A. Almazov National Medical Research Center registry and participating in the GRIPHON and GRIPHON OL clinical studies.Material and methods 26 patients with PAH were included into this study since 2010: 20 patients with idiopathic PAH, 4 patients with PAH associated with systemic scleroderma, and 2 patients with corrected congenital heart defects. At the time of randomization, 19 patients had been receiving therapy with phosphodiesterase type 5 inhibitors for at least one month. Among the patients treated with selexipag (n=14), 4 patients reached a high individual maintenance dose (1200-1600 µg b.i.d.), 4 patients reached a medium dose (600-1000 µg b.i.d.), and 6 patients reached a low dose (200-400 µg b.i.d.).Results The selexipag therapy exerted a positive effect on secondary endpoints, specifically, on changes in the functional class of pulmonary hypertension, serum concentration of NT-proBNP, and physical working capacity of patients. Adverse events associated with the selexipag treatment, which resulted in termination of study participation, were observed in one patient.Conclusion To achieve the main goal of drug therapy, low risk of death with selexipag it is critical to observe the titration schedule and to aim at reaching the highest individual maintenance dose.

Comparison between prasugrel and clopidogrel used as antiplatelet medication for endovascular treatment of unruptured intracranial aneurysms. A meta-analysis

Background Clopidogrel is routinely used to decrease ischemic complications during neurointerventional procedures. However, the efficacy may be limited by the antiplatelet resistance. Purpose To analyze the efficacy of prasugrel (PS) compared to clopidogrel (CP) in the cerebrovascular field. Data sources A systematic search of two large databases was performed for studies published from 2000 to 2018. Study selection According to PRISMA guidelines, we included studies reporting treatment-related outcomes of patients undergoing neurointerventional procedures under PS, and studies comparing PS and CP. Data analysis Random-effects meta-analysis was used to pool the following: overall rate of complications, ischemic and hemorrhagic events, influence of the dose of PS. Data synthesis Including 7 studies, 682 and 672 unruptured intracranial aneurysms were treated under PS (cases) and CP (controls), respectively. Low-dose (20 mg/5 mg) (loading and maintenance doses) of PS compared with the standard dose of CP (300 mg/75 mg) showed a significant reduction of the complication rate (OR = 0.36, 95% CI = 0.17–74, P = 0.006, I2 = 0%). Overall, ischemic complication rate was significantly higher among the CP group (40/672 = 6%, 95% CI = 3%–13%, I2 = 83% vs 16/682 = 2%, 95% CI = 1%–5%, I2 = 73%, P = 0.03). Low and high loading doses of PS were associated with 0.6% (5/535, 95% CI = 0.1%–1.6%, I2 = 0%) and 9.3% (13/147, 95% CI = 0.2%–18%, I2 = 60%) of intra-periprocedural hemorrhages, respectively (P = 0.001), whereas low and high maintenance doses of PS were associated with 0% (0/433) and 0.9% (2/249, 95% CI = 0.3%–2%, I2 = 0%) of delayed hemorrhagic events, respectively (P = 0.001). Limitations Retrospective series and heterogeneous endovascular treatments. Conclusions In our study, low-dose of prasugrel, compared with clopidogrel premedication, is associated with an effective reduction of the ischemic events with an acceptable rate of hemorrhagic complications.

P3671Selexipag dosing and titration in the first 500 patients enrolled in SPHERE (SelexiPag: tHe UsErs dRug rEgistry)

Abstract Introduction SPHERE is an ongoing US-based, multicentre, prospective, registry collecting data on use of the oral selective IP prostacyclin receptor agonist selexipag in real-world settings. Here, we report selexipag dosing and titration in the first 500 patients. Methods SPHERE, initiated in November 2016, will enrol 800 patients newly initiated on or already treated with selexipag at enrolment who have a documented titration regimen. Patients are followed for up to 18 months. Patients were considered “newly initiated” on selexipag if they were enrolled in SPHERE ≤60 days after starting selexipag and were considered “previously initiated” if they enrolled >60 days after starting selexipag. The highest dose is the maximum dose reached during up-titration within 6 months since initiation. Selexipag “maintenance dose” is defined as the first dose received for ≥14 days without interruption or change; “titration speed” is defined as the highest dose reached within the first 6 months after initiation divided by the time (in weeks) to reach it. Results The data cut-off for this analysis was December 20, 2018. Most patients had Group 1 pulmonary hypertension (PH) (95.4%), which was primarily idiopathic (49.6%) or connective tissue disease associated (26.0%). At selexipag initiation 49.8% of patients had functional class III symptoms. At the time of selexipag initiation, 19.2% of patients were on PH therapy containing a prostacyclin pathway agent (PPA) (8.5% with a parenteral PPA). The median maintenance dose of selexipag was 1200 μg BID (IQR: 800–1600 μg BID) and the median time to reach it was 8.1 wks (IQR: 5.3–11.0 wks). Low (≤400 μg BID), medium (600–1000 μg BID), and high (≥1200 μg BID) maintenance doses were attained by 15.1%, 30.8%, and 49.5% of patients, respectively (and in 23.2%, 31.2%, and 36.2%, respectively, in GRIPHON). The median titration speed was 175 μg BID/wk (IQR: 110.5–195.3 μg BID/wk), slower than the protocol-outlined 200 μg BID/wk in GRIPHON. In SPHERE, most patients titrated at speeds <200 μg BID/wk, regardless of whether they were newly (175 μg BID/wk; IQR 118.6, 195.3) or previously (175 μg BID/wk; IQR 109.8, 195.3) initiated. As expected, more patients discontinued due to adverse events in the newly (29.0%) versus previously (14.1%) initiated groups. The most common adverse events leading to selexipag discontinuation were worsening pulmonary hypertension (2.2%), headache (2.0%), myalgia (1.4%), and nausea (1.0%). Conclusion The median maintenance selexipag dose in SPHERE was 1200 μg BID. While the median titration speed was 175 μg BID/wk, there was marked variation and the vast majority of patients titrated slower than 200 μg BID/wk. No new safety signals were observed. Acknowledgement/Funding Actelion Pharmaceuticals US, Inc.

A Modeling Framework to Characterize Cytokine Release upon T‐Cell–Engaging Bispecific Antibody Treatment: Methodology and Opportunities

T‐cell–engaging bispecific antibodies (T‐BsAbs) are an important class of antibody therapeutics in immuno‐oncology. T‐BsAbs simultaneously bind to CD3 on T cells and a tumor‐associated antigen on tumor cells, activate T cells, and redirect T cells’ cytotoxicity against tumor cells. Cytokine release syndrome (CRS), a common dose‐limiting adverse event for T‐BsAbs, is associated with T‐cell activation. A “priming” dose strategy (i.e., a lower initial dose followed by a higher maintenance dose) has been implemented in the clinic to mitigate CRS and to achieve efficacious doses with T‐BsAbs. So far, the selection of the optimal priming dosing regimen is largely empirical. A “fit‐for‐purpose” semimechanistic pharmacokinetic/pharmacodynamic model was developed to characterize the cytokine release profiles upon T‐BsAb treatment, including the priming effect observed with repeated dosing. This model can be utilized to simulate cytokine profiles following various dosing regimens and may assist the design of clinical dosing strategies for T‐BsAbs programs.

Clinical effect and safety of different maintenance doses of caffeine citrate in treatment of apnea in very low birth weight preterm infants: a prospective randomized controlled trial

To study the clinical effect and safety of different maintenance doses of caffeine citrate in the treatment of apnea in very low birth weight preterm infants. A total of 78 very low birth weight preterm infants with primary apnea were enrolled who were admitted from January 2016 to January 2018. They were randomly divided into high-dose caffeine group with 38 children and low-dose caffeine group with 40 children. Both groups received a loading dose of 20 mg/kg caffeine citrate, and 24 hours later, the children in the high-dose caffeine group were given a maintenance dose of 10 mg/kg, and those in the low-dose caffeine group were given a maintenance dose of 5 mg/kg. The two groups were compared in terms of response rate and incidence rate of adverse events. The high-dose caffeine group had a significantly higher response rate than the low-dose caffeine group (71% vs 48%; P<0.05). Compared with the low-dose caffeine group, the high-dose caffeine group had significantly shorter duration of apnea and time of caffeine treatment (P<0.05). There were no significant differences between the two groups in length of hospital stay and incidence rates of tachycardia, feeding intolerance, bronchopulmonary dysplasia, necrotizing enterocolitis, and intracranial hemorrhage (P>0.05). There was no significant difference in the mortality rate between the two groups (P>0.05). Higher maintenance dose of caffeine citrate has a better clinical effect than lower maintenance dose of caffeine citrate in the treatment of apnea in very low birth weight preterm infants, without increasing the incidence rates of adverse drug reactions and serious complications in preterm infants.

P686 Neither high infliximab maintenance doses nor high trough levels trigger skin side effects of the drug: a prospective cross-sectional study

P686 Neither high infliximab maintenance doses nor high trough levels trigger skin side effects of the drug: a prospective cross-sectional study

Efficacy and Safety of Different Maintenance Doses of Caffeine Citrate for Treatment of Apnea in Premature Infants: A Systematic Review and Meta-Analysis.

Background Caffeine is widely used for the treatment of neonatal apnea, but there is no agreement on the optimum maintenance dose for preterm infants. Objective The aims of this meta-analysis were to compare the efficacy and safety of high versus low maintenance doses of caffeine citrate for the treatment of apnea in premature infants. Methods Literature searches were conducted using PubMed, Cochrane Library, OVID, Embase, Web of Science, Chinese Biomedical Literature, Weipu Journal, Wanfang, and CNKI databases up to September 2018. Only randomized controlled trials (RCTs) of caffeine citrate for apnea treatment in premature infants were included. Trials were divided into those testing high maintenance doses (10−20 mg/kg daily) and low maintenance doses (5−10 mg/kg daily) for comparison. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Results Among the 345 studies initially identified, thirteen RCTs involving 1515 patients were included. Compared to the low-dose group, the high-dose group exhibited greater effective treatment rate (RR: 1.37, 95%CI: 1.18 to 1.60, P<0.0001) and success rate for ventilator removal (RR: 1.74, 95%CI: 1.04 to 2.90, P=0.03), but higher incidence of tachycardia (RR: 2.02, 5%CI: 1.30 to 3.12, P=0.002). The high-dose group also demonstrated lower extubation failure rate (RR: 0.5, 95%CI: 0.35 to 0.71, P=0.0001), frequency of apnea (WMD: -1.55, 95%CI: -2.72 to -0.39, P=0.009), apnea duration (WMD: -4.85, 95%CI: -8.29 to -1.40, P=0.006), and incidence of bronchopulmonary dysplasia (RR: 0.79, 95%CI: 0.68 to 0.91, P=0.002). There were no significant group differences in other adverse events including in-hospital death (P>0.05). Conclusions Higher maintenance doses of caffeine citrate appear more effective and safer than low maintenance doses for treatment of premature apnea, despite a higher incidence of tachycardia.

Risk factors for irreversible organ damages in peri- and postmenopausal women with systemic lupus erythematosus

Objective: to identify irreversible organ damages and factors influencing their development and to compare existing musculoskeletal injuries with the activity of systemic lupus erythematosus (SLE).Patients and methods. The investigation enrolled 197 peri- and postmenopausal female outpatients (mean age, 50.94±9.1 years) with SLE, who were followed up at Clinical Rheumatology Hospital Twenty-Five, Saint Petersburg. The mean disease duration was 9.7±7.5 years. Cytostatic and glucocorticoid (GC) treatment regimens and dosages in the examinees were analyzed on the basis of their primary medical records. The investigators assessed the current disease activity by the SLE Disease Activity Index (SLEDAI-2K) and the Lupus Low Disease Activity State (LLDAS) and irreversible organ damages by the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (DI).Results and discussion. 93.4% of the patients continued to receive GS therapy at the time of inclusion in the study. The median GS maintenance dose was 12.5 mg/day. Almost half of the patients (n=86/43.7%) were in menopause (its mean duration was 12.8±7.1 years). Half of the examinees were noted to have remission (n=36/18.3%) or low SLE activity (n=92/46.7%) according to the SLEDAI-2K. Fifty-seven (28.9%) patients met all 5 LLDAS criteria; at the same time other 96 (48.7%) patients met 4 out of the 5 criteria, the 5th criterion being a high GC maintenance dose. High DI scores of ≥4 were found in two thirds (n=131/66.5%) of the examinees. Musculoskeletal system injuries ranked first among other disorders: osteoporosis (OP) and muscle weakness were detected in 76 (38.6%) and 69 (35.0%) patients, respectively. Regression analysis involving all statistically significant factors showed that the degree of damage was influenced by age (p=0.013215), total GS dose (p=0.000047), and previous therapy with cyclophosphamide (p=0.041505).Conclusion. The contribution of GS therapy to irreversible damage accrual is obvious in peri- and postmenopausal women with SLE. Timely dose adjustment or complete withdrawal of GS during remission in SLE is one of the key factors that substantially reduce the risk of progression of irreversible organ damages due to the prevention of OP and osteoporotic fractures in these patients.

Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia.

Magnesium sulfate is the standard therapy for prevention and treatment of eclampsia. Two standard dosing regimens require either continuous intravenous infusion or frequent, large‐volume intramuscular injections, which may preclude patients from receiving optimal care. This project sought to identify alternative, potentially more convenient, but similarly effective dosing regimens that could be used in restrictive clinical settings. A 2‐compartment population pharmacokinetic (PK) model was developed to characterize serial PK data from 92 pregnant women with preeclampsia who received magnesium sulfate. Body weight and serum creatinine concentration had a significant impact on magnesium PK. The final PK model was used to simulate magnesium concentration profiles for the 2 standard regimens and several simplified alternative dosing regimens. The simulations suggest that intravenous regimens with loading doses of 8 g over 60 minutes followed by 2 g/h for 10 hours and 12 g over 120 minutes followed by 2 g/h for 8 hours (same total dose as the standard intravenous regimen but shorter treatment duration) would result in magnesium concentrations below the toxic range. For the intramuscular regimens, higher maintenance doses given less frequently (4 g intravenously + 10‐g intramuscular loading doses with maintenance doses of 8 g every 6 hours or 10 g every 8 hours for 24 hours) or removal of the intravenous loading dose (eg, 10 g intramusculary every 8 hours for 24 hours) may be reasonable alternatives. In addition, individualized dose adjustments based on body weight and serum creatinine were proposed for the standard regimens.

Efficacy of agglutination test in diagnosis of motile Aeromonas septicemia in Nile tilapia (Oreochromis niloticus)

The time-course of the neuromuscular effects of vecuronium (n = 25) and atracurium (n = 25) has been compared at three different levels of maintenance dose in anaesthetized patients. Following intubation with vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1, surgical muscle relaxation was maintained by using increments of equipotent maintenance doses equivalent to 0.5, 1.0 and 1.5 x ED95 for each drug. Repeat doses were administered each time the twitch height, depressed by the previous dose, returned to 25% of its control value. The apparent increase in the duration of action, i.e. the difference between the duration of the last and the first maintenance dose, did not reach statistical significance and approximated 3 +/- 2, 6 +/- 4, 11 +/- 5 and 3 +/- 2, 8 +/- 13, 5 +/- 7 min following the low, medium and high maintenance doses of vecuronium and atracurium, respectively.