利奈唑胺对肾功能不全G~+感染患者血小板减少的相关性研究

目的:分析利奈唑胺对肾功能不全G+患者血小板减少的关系。方法:回顾性分析92例应用利奈唑胺治疗的革兰阳性球菌感染患者的临床资料,根据是否伴有肾功能不全分为肾功能不全组(33例),正常组(59例),检测用药前、用药后血小板计数,观察停药后血小板计数恢复正常时间及不良反应发生情况。结果:肾功能不全组治疗后血小板计数显著低于治疗前及正常组(P0.01),正常组治疗前、后血小板计数比较无统计学意义(P0.05);肾功能不全组血小板减少发生率高于正常组(P0.05);停药后正常组血小板恢复正常时间短于肾功能不全组(P0.01);肾功能不全组血红蛋白下降率高于正常组(P0.05),其余不良反应发生率比较差异无统计学意义(P0.05)。结论:感染患者肾功能可影响利奈唑胺所致血小板减少发生率,肾功能不全患者在应用利奈唑胺时应定期监测血小板计数。     

Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis

Background

Treatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances.

Objective

To systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis.

Methods

We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy.

Results

Twenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38–82.83 %, I² = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82–92.38 %, I² = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p < 0.0001) between dose comparisons. The incidence of neuropathy and other adverse events leading to permanent discontinuation of linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively).

Conclusion

Available evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and neuropathy. Additionally, highly powered randomized controlled trials including participants from endemic regions are urgently needed to better inform the magnitude and significance of Linezolid treatment effect in MDR and XDR TB patients.

     

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts

Background

Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100?×?10⁹/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100?×?10⁹/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100?×?10⁹/L are reported.

Methods

Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability.

Results

By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75?×?10⁹/L. Seven patients experienced platelet count increases ≥15?×?10⁹/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia.

Conclusions

Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts.

Trial registration

ClinicalTrials.gov:NCT01348490.

     

利福平导致严重血小板减少1例

利福平主要用于结核病的治疗,能引起血小板减少等不良反应。本病例使用利福平后出现严重血小板减少,血小板下降至4×10⁹/L,立即停用利福平并输注血小板后血小板恢复正常。因此,在利福平使用过程中应密切观察病情,监测血常规、肝肾功能等,及时发现不良反应,必要时立即停药,并对血小板明显下降者(<30×10⁹/L)给予补充血小板等治疗。对明确由利福平引起血小板减少者,治疗时应不再使用该药,以避免药物不良事件的发生。     

Decreased Platelet Count in Patients Receiving Continuous Veno-Venous Hemofiltration: A Single-Center Retrospective Study

Background

A decreased platelet count may occur and portend a worse outcome in patients receiving continuous renal replacement therapy (CRRT). We aim to investigate the incidence of decreased platelet count and related risk factors in patients receiving CRRT.

Methods

In this retrospective study, we screened all patients receiving continuous veno-venous hemofiltration (CVVH) at Jinling Hospital between November 2008 and October 2012. The patients were included who received uninterrupted CVVH for more than 72 h and had records of blood test for 4 consecutive days after ruling out pre-existing conditions that may affect the platelet count. Platelet counts before and during CVVH, illness severity, CVVH settings, and outcomes were analyzed.

Results

The study included 125 patients. During the 3-day CVVH, 44.8% and 16% patients had a mild decline (20–49.9%) and severe decline (≥50%) in the platelet count,respectively; 37.6% and 16.0% patients had mild thrombocytopenia (platelet count 50.1–100×10⁹/L) and severe thrombocytopenia (platelet count ≤50×10⁹/L), respectively. Patients with a severe decline in the platelet count had a significantly lower survival rate than patients without a severe decline in the platelet count (35.0% versus 59.0%, P = 0.012), while patients with severe thrombocytopenia had a survival rate similar to those without severe thrombocytopenia (45.0% versus 57.1%, P = 0.308). Female gender, older age, and longer course of the disease were independent risk factors for a severe decline in the platelet count.

Conclusions

A decline in the platelet count and thrombocytopenia are quite common in patients receiving CVVH. The severity of the decline in the platelet count rather than the absolute count during CVVH may be associated with hospital mortality. Knowing the risk factors for a severe decline in the platelet count may allow physicians to prevent such an outcome.     

Platelet and neutrophil responses to Gram positive pathogens in patients with bacteremic infection

Background

Many Gram-positive pathogens aggregate and activate platelets in vitro and this has been proposed to contribute to virulence. Platelets can also form complexes with neutrophils but little is however known about platelet and platelet-neutrophil responses in bacterial infection.

Methodology/Principal Findings

We added isolates of Gram-positive bacteria from 38 patients with a bacteremic infection to blood drawn from the same patient. Aggregometry and flow cytometry were used to assess platelet aggregation and to quantify activation of platelets, neutrophils, and platelet-neutrophils complexes (PNCs) induced by the bacteria. Fifteen healthy persons served as controls. Most isolates of Staphylococcus aureus, beta hemolytic streptococci, and Enterococcus faecalis induced aggregation of platelets from their respective hosts, whereas pneumococci failed to do so. S. aureus isolates induced platelet aggregation more rapidly in patients than in controls, whereas platelet activation by S. aureus was lower in patients than in controls. PNCs were more abundant in baseline samples from patients than in healthy controls and most bacterial isolates induced additional PNC formation and neutrophil activation.

Conclusion/Significance

We have demonstrated for the first time that bacteria isolated from patients with Gram-positive bacteremia can induce platelet activation and aggregation, PNC formation, and neutrophil activation in the same infected host. This underlines the significance of these interactions during infection, which could be a target for future therapies in sepsis.     

Platelet function and ageing

There are clear age-related changes in platelet count and function, driven by changes in hematopoietic tissue, the composition of the blood and vascular health. Platelet count remains relatively stable during middle age (25–60 years old) but falls in older people. The effect of age on platelet function is slightly less clear. The longstanding view is that platelet reactivity increases with age in an almost linear fashion. There are, however, serious limitations to the data supporting this dogma. We can conclude that platelet function increases during middle age, but little evidence exists on the changes in platelet responsiveness in old age (>75 years old). This change in platelet function is driven by differential mRNA and microRNA expression, an increase in oxidative stress and changes in platelet receptors. These age-related changes in platelets are particularly pertinent given that thrombotic disease and use of anti-platelet drugs is much more prevalent in the elderly population, yet the majority of platelet research is carried out in young to middle-aged (20–50 years old) human volunteers and young mice (2–6 months old). We know relatively little about exactly how platelets from people over 75 years old differ from those of middle-aged subjects, and we know even less about the mechanisms that drive these changes. Addressing these gaps in our knowledge will provide substantial understanding in how cell signalling changes during ageing and will enable the development of more precise anti-platelet therapies.     

In vitro activity of linezolid and eperezolid, two novel oxazolidinone antimicrobial agents, against anaerobic bacteria

Linezolid (formerly U-100766) and eperezolid (formerly U-100592) are novel oxazolidinone antimicrobial agents that are active against multi-drug-resistant staphylococci, streptococci, enterococci, corynebacteria, and mycobacteria. Preliminary studies also demonstrated that the compounds inhibited some test strains of anaerobic bacteria. Therefore, we extended the in vitro evaluation of these agents to include a total of 54 different anaerobic species. Minimal inhibitory concentration (MIC) values were determined using a standard agar dilution method for 143 anaerobic bacterial isolates. Eperezolid and linezolid demonstrated potent activity against the anaerobic Gram-positive organisms with most MIC values in the range of 0.25-4 microg/mL. Viridans streptococci demonstrated MICs of 1-2 microg/mL; Peptostreptococcus species and Propionibacterium species were inhibited by 相似文献   

Treatment of orthopedic infections caused by resistant staphylococci

During 1999-2005 we treated 15 patients with linezolid for relevant infections of locomotion apparatus (7 cases with endoprosthesis infection, 5x osteomyelitis and 3x another infection). With the exception of one case the antibiotic therapy was always combined with appropriate surgical intervention. Average period of linezolid administration was 26 d; linezolid was applied from the beginning intravenously on average for 10 d, and then orally for 16 d (average). There were no undesirable effects in the file. Success rate reached 86.6%. MRSA strains were proved by standard methods: growth on Mueller-Hinton agar with increased concentration of NaCl and 2 mg/L of oxacilline, and measuring inhibitory zones around cephoxitine disk. The sensitivity to other antibiotics was specified by disk-diffusion test; that to linezolid was verified by E-test. Linezolid represents a medical reserve for the treatment of multiresistant Gram-positive infections or for emergencies, when allergy onset, high toxicity risk, intolerance, etc. do not allow to use other, in vitro effective, antibiotics.     

Combined prednisone and levothyroxine improve treatment of severe thrombocytopenia in hepatitis B with compensatory cirrhosis accompanied by subclinical and overt hypothyroidism

The aim of the present study was to investigate the relationship between hypothyroidism and thrombocytopenia in hepatitis B-related compensatory liver cirrhosis and to determine whether treatment with levothyroxine and prednisone is superior in a multicenter, open-label, observational study in China. In total, 125 consecutive hepatitis B-related compensated liver cirrhosis patients with severe thrombocytopenia accompanied by hypothyroidism were included. The patients were divided into four groups according to treatment strategy: a control group (n=29), a prednisone group (n=25), a levothyroxine group (n=32) and a prednisone plus levothyroxine group (n=39). Severe thrombocytopenia was more prevalent in hepatitis B-associated compensatory liver cirrhosis patients with hypothyroidism than in euthyroid patients (29.6% vs. 14.7%, P<0.05). Combination treatment with prednisone and levothyroxine decreased the risk of bleeding and improved platelet recovery compared to control treatment and treatment with either prednisone or levothyroxine alone. The platelet count before therapy, serum thyroid stimulating hormone and combination treatment with prednisone and levothyroxine were associated with bleeding events. Therefore, the present study suggests that hypothyroidism is associated with severe thrombocytopenia in hepatitis B-associated compensatory liver cirrhosis. Treatment with prednisone plus levothyroxine may present a novel approach in these patients.     

Age and rest–activity rhythm as predictors of survival in patients with newly diagnosed lung cancer

Disruption of the rest–activity rhythm in patients with lung cancer can accelerate cancer progression and affect survival. Rest–activity rhythm changes with age. Therefore, we investigated the effects of rest–activity rhythm and age on patients’ survival. A total of 84 patients with lung cancer were recruited, then separated into two groups; younger patients aged under 65 years or elderly patients aged 65 and over. The dichotomy index (I < O) was used to estimate the rest–activity rhythm measured through the actigraphy motion detector. Cox proportional hazards models were adopted to investigate the effects of different variables on the patients’ survival. After adjusting for confounding, the risk of earlier mortality in the younger patients with disrupted I < O were 2.52 (95%CI = 1.09–5.82) times higher than that in the younger patients with robust I < O (p = 0.03), the risk of earlier mortality in the elderly patients with disrupted I < O was 4.08 (95%CI = 1.91–8.68) times higher than that in the elderly patients with robust I < O (p < 0.001). Therefore, age and I < O influence the survival period of patients with lung cancer. Moreover, disrupted I < O has a substantial influence on elderly patients. In conclusion, aging and disrupted rest–activity rhythm negatively and jointly influenced the survival period of the patients with lung cancer and significantly increased their death risk.     

The Efficacy and Safety of Linezolid and Glycopeptides in the Treatment of Staphylococcus aureus Infections

To assess the effectiveness and safety of linezolid in comparison with glycopeptides (vancomycin and teicoplanin) for the treatment of Staphylococcus aureus infections, we conducted a meta-analysis of relevant randomized controlled trials. A thorough search of Pubmed and other databases was performed. Thirteen trials on 3863 clinically assessed patients were included. Linezolid was slightly more effective than glycopeptides in the intent-to-treat population (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.10), was more effective in clinically assessed patients (OR 95% CI: 1.38, 1.17–1.64) and in all microbiologically assessed patients (OR 95% CI: 1.38, 1.15–1.65). Linezolid was associated with better treatment in skin and soft-tissue infections (SSTIs) patients (OR 95% CI: 1.61, 1.22–2.12), but not in bacteraemia (OR 95% CI: 1.24, 0.78–1.97) or pneumonia (OR 95% CI: 1.25, 0.97–1.60) patients. No difference of mortality between linezolid and glycopeptides was seen in the pooled trials (OR 95% CI: 0.98, 0.83–1.15). While linezolid was associated with more haematological (OR 95% CI: 2.23, 1.07–4.65) and gastrointestinal events (OR 95% CI: 2.34, 1.53–3.59), a significantly fewer events of skin adverse effects (OR 95% CI: 0.27, 0.16–0.46) and nephrotoxicity (OR 95% CI: 0.45, 0.28–0.72) were recorded in linezolid. Based on the analysis of the pooled data of randomized control trials, linezolid should be a better choice for treatment of patients with S. aureus infections, especially in SSTIs patients than glycopeptides. However, when physicians choose to use linezolid, risk of haematological and gastrointestinal events should be taken into account according to the characteristics of the specific patient populations.     

Thrombocytopenia in liver cirrhosis complicated by variceal haemorrhage: lack of increase in platelet count after spleno renal distal shunt

10 patients with liver cirrhosis (LC) and previous variceal bleeding have been studied. Platelet count was markedly depressed. Giant platelet percentage (MTI) was significantly increased, reflecting bone marrow compensatory hyperactivity. Platelet associated IgG (PAIgG) was elevated. Such elevation, however, was inconstant and did not correlate with platelet count. Beta-thromboglobulin was markedly increased when referred to circulating platelet number, but its level did not accurately reflect platelet activation, because of decreased liver cell function. Platelet Factor 4 was always zero, thus confirming that high values of this protein represent only a laboratory artifact, due to platelet activation in vitro. 5 patients underwent spleno renal distal shunt, which transiently improved hypersplenism only in one case. Despite this, MTI became perfectly normal in all patients, suggesting a decrease in the thrombopoietic stimulus. PAIgG dramatically fell in the two patients with the highest pre-operative values. Since thrombocytopenia persisted, the non-specific nature of PAIgG in LC seems to be further supported.     

血小板生成素与白介素-11治疗胃癌术后辅助化疗后血小板减少症时效及安全性的比较

目的:比较血小板生成素与白介素-11治疗胃癌患者术后化疗血小板减少症的时效和安全性。方法:术后辅助化疗出现血小板计数低于75×109/L的进展期胃癌患者68例,将其分为TPO组与IL-11组,分别为35例和33例。分别皮下注射rhTPO 15000U,每日1次;rhIL-11 1.5 mg,每日1次,当血小板计数125×109/L或比用药前上升50×109/L,即停止给药,疗程最长为14天。每3天抽取外周静脉血2 m L,通过全自动血液分析仪测定血小板计数,密切观察出现的不良反应并记录。比较两组患者不同临床病理资料、血小板计数、血小板计数升至75×109/L和125×109/L的时程、药物不良反应。结果:两组患者年龄、性别、化疗方案、血小板最低值出现的化疗周期及临床病理分期的比较均没有统计学差异(P值均0.05)。TPO组与IL-11组血小板动态值的比较,第9天出现显著差异(P=0.032)。TPO组与IL-11组血小板计数恢复至75×109/L和125×109/L所需的时间,有显著差异(P=0.041,P=0.013)。TPO组中,有3例(8.6%)患者发生不良反应,IL-11组中,有13例(39.4%)患者发生不良反应,TPO组患者出现的不良反应少且较轻微(P=0.006)。结论:rhTPO治疗胃癌患者术后化疗血小板减少症时效快,安全性好。     

Use of mean platelet volume improves detection of platelet disorders

Classification of platelet disorders has been based on the platelet count. Addition of a second variable, mean platelet volume (MPV), to the routine blood count allows classification of patients into 9 categories: high, low, or normal MPV, and high, low or normal platelet count. We studied 1,244 adult inpatients. 1,134 had both platelet values normal. 11 patients had high MPV and low platelet count: all had hyperdestructive causes. 15 patients had high MPV and normal platelet count: 12 had heterozygous thalassemia, and three had iron deficiency. Seven patients had high MPV and high platelet count: causes included myeloproliferative disorders, inflammation, iron deficiency, and splenectomy, 25 patients had high platelet counts and normal MPV: the causes were inflammation, infection, sickle cell anemia, iron deficiency, or chronic myelogenous leukemia. 52 patients had an MPV that was inappropriately low for the platelet count (high, normal, or low). All had sepsis, splenomegaly, aplastic anemia, chronic renal failure, or a disease being treated with myelosuppressive drugs. High MPV thus appears correlated with myeloproliferative disease or thalassemia; and low MPV, with cytotoxic drugs or marrow hypoplasia. Addition of MPV to the platelet count allows subtler disorders to be detected (when the platelet count is normal), and allows distinction of the cause of thrombocytopenia.     

Efficacy of Various Combined Blood Purification Techniques for Treating Patients with Non-viral Acute Liver Failure

We sought to study the clinical efficacy of various combined blood purification techniques in patients with non-viral acute liver failure complicated by multiple organ dysfunction syndrome (MODS). For this purpose, 19 patients diagnosed of mid- or late-stage liver failure with MODS score-4 were randomly divided into 3 treatment groups of PE+HP+CVVHDF, PE+CVVHDF, and HP+CVVHDF, respectively. Pre- and post-treatment heart rate (HR), mean arterial pressure (MAP), arterial blood gases (pH, PaO₂, and PaCO₂), hepatic function, platelet count, and blood coagulation were determined. The data show significant improvement in HR, MAP, PaO₂/FiO₂, total bilirubin (TBIL), and alanine aminotransferase (ALT) levels after treatment (P < 0.05). TBIL decreased more significantly after treatment in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.01). Significant improvement in prothrombin time and albumin was observed only in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.05). The decrease of TBIL and improvement of PaO₂/FiO₂ ratio were more pronounced in PE+HP+CVVHDF than in HP+CVVHDF group (P < 0.05). To conclude, liver function was relatively improved by all the three combined blood purification techniques used; however, PE+HP+CVVHDF approach was found more efficient in the removal of toxic metabolites, especially bilirubin. The data suggest that the combined blood purification techniques used were effective and involved minor side effects.     

Role of interleukin-17 in a murine community-associated methicillin-resistant Staphylococcus aureus pneumonia model

Interleukin (IL)-17 is a key member of the Th17 cytokines and has been reported to be involved in the pathomechanisms underlying various diseases, including infectious diseases. Infections with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) have garnered worldwide attention, and the representative USA300 strain is known to cause pneumonia in healthy people, which can be lethal. However, little is known about the role of IL-17 in CA-MRSA pneumonia. In this study, we investigated the role of IL-17 in a CA-MRSA pneumonia animal model. Mortality was higher and occurred at an earlier stage of infection in the IL-17A-knockout mice than in the wild-type (P < 0.01) and IL-17A/F-knockout mice (P < 0.05); however, no significant difference in the intrapulmonary bacterial counts was observed among the three groups of mice. Moreover, the IL-17A-knockout group showed significantly higher levels of IL-17F and granulocyte-colony stimulating factor (G-CSF) and a significantly higher neutrophil count in the bronchoalveolar lavage fluid than the other groups. These results confirmed that G-CSF expression significantly increased, and significant neutrophilic inflammation occurred under conditions of IL-17A deficiency in the murine CA-MRSA pneumonia model.     

Immunologic findings,thrombocytopenia and disease activity in lupus nephritis.

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis.     

Linezolid for the treatment of nosocomial infections after cardiac surgery]

Clinical and bacteriological efficacy of linezolid in the treatment of cardiosurgical patients with various localization nosocomial infections due to problem grampositive cocci was estimated. The group included 10 patients: children at the age 3 months to 12 years (n = 3) and adults at the age of 17 to 65 years (n = 7) with infectious complications such as infectious endocarditis (n = 4), pneumonia (n = 2), wound infection (n = 3) and sepsis (n = 1). All the patients isolated MR staphylococci. The use of glycopeptides was not possible in 6 patients because of vancomycin intolerance (n = 1), renal insufficiency (n = 1) and failure of the previous vancomycin therapy (n = 4). To all the patients linezolid was administered per os (tablets or suspension) or intravenously (infusion solution) in doses of 600 mg twice a day (1200 mg a day) for the adults and 10 mg/kg body weight every 12 hours (20 mg/kg body weight a day) for the children. Linezolid monotherapy was applied to 2 patients. 8 patients were treated with linezolid in combination with some other antibiotics. By the clinical findings the positive dynamics confirmed by thermometry and hemograms was observed in 8 patients beginning from the 4th day of the linezolid use. Eradication of MR staphylococci from the blood, sputum and wounds was stated in all 10 patients. No toxic or adverse reactions were noted. It was concluded that linezolid is an optimal alternative to vancomycin especially when the use of the latter is not possible. No nephrotoxic effects of linezolid provided its recommendation as a drug of choice in the treatment of patients with renal disturbances, including polyorganic insufficiency.     

A non-interventional study of extended-release methylphenidate in the routine treatment of adolescents with ADHD: effectiveness, safety and adherence to treatment

This multi-centre, open-label, non-interventional study evaluates effectiveness, safety and adherence to treatment of a specific extended-release methylphenidate with a 50 % immediate and a 50 % extended-release component (Medikinet^® retard) in the clinical routine treatment of 381 adolescents with ADHD and a mean age of 14.0 ± 1.9 years. ADHD and associated psychiatric symptoms, medication status and dosage frequency, treatment adherence and adverse events were assessed at baseline and after a median treatment length with Medikinet^® retard of 70 days. Primary outcome criterion was the change of ADHD symptom severity from baseline to endpoint according to the ADHD–KGE (German: ADHS–Klinische Gesamteinschätzung) change score. At baseline, 4.2 % of the patients were treatment naïve, 92.7 % had previously received different methylphenidate formulations and 3.1 % had received atomoxetine or amphetamine. During the study, patients received a mean daily dose of 35.7 ± 15.1 mg Medikinet^® retard. At endpoint, in 78 % of patients, the total ADHD symptom severity was reduced, in 20.4 %, it remained unchanged and in 1.6 %, it was worsened. The mean ADHD–KGE total ADHD symptom score was reduced from 1.8 ± 0.7 (moderate) at baseline to 0.8 ± 0.5 (mild; p < 0.001) at endpoint; the mean ADHD–KGE total-associated symptom score was reduced from 1.9 ± 0.7 (moderate) at baseline to 1.0 ± 0.6 (mild; p < 0.0001) at endpoint. After the medication switch from previous methylphenidate formulation to Medikinet^® retard, multiple dosing with ≥3 daily medication intakes was reduced from 12.9 % at baseline to 3.1 % at endpoint (p < 0.001). Adherence to treatment was improved in 37 % of patients. Most frequent adverse events were loss of appetite and gastrointestinal problems. The findings suggest that pharmacologically treated adolescents with ADHD and insufficient symptom reduction and/or treatment adherence benefit from switching to Medikinet^® retard and that it is well tolerated when given in clinical routine care.