Levofloxacin in the treatment of community-acquired pneumonia

Levofloxacin is a fluoroquinolone that has a broad spectrum of activity against several causative bacterial pathogens of community-acquired pneumonia (CAP). The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP are well established. Furthermore, a high-dose (750 mg), short-course (5 days) of once-daily levofloxacin has been approved for use in the USA in the treatment of CAP, acute bacterial sinusitis, acute pyelonephritis and complicated urinary tract infections. Levofloxacin can be used as a monotherapy in patients with CAP, however, levofloxacin combination therapy with anti-pseudomonal β-lactam (or aminoglycoside) should be considered if Pseudomonas aeruginosa is the causative pathogen of the respiratory infection. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent antibacterial activity, decreases the potential for drug resistance and has better patient compliance. Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation and the patients can switch between these formulations, which results in more options with respect to the therapeutic regimens. Furthermore, levofloxacin is generally well tolerated, has good tissue penetration and adequate concentrations can be maintained at the site of infections.     

Removal of oral secretion prior to position change can reduce the incidence of ventilator‐associated pneumonia for adult ICU patients: a clinical controlled trial study

Aim. The purpose of this study was to explore the effect of oral secretion on aspiration and reducing ventilator‐associated pneumonia. Background. Ventilator‐associated pneumonia is a serious hospital‐acquired infection with reported incidence rate of 12·2% and mortality rate of 29·3%. Oral secretion is purported as a media which brings the oropharyngeal pathogens down to the respiratory track. Methods. Two‐group comparison study design was adopted. Subjects were recruited from an adult general intensive care unit of a medical centre in Taipei city. Patients in the study group received suction of oral secretion before each positional care, in contrast with patients in the control group who received routine care. Results. Ventilator‐associated pneumonia was found in 24 of 159 (15·1%) patients in the control group and in five of 102 (4·9%) patients in the study group with a reduction of risk ratio of 0·32 (95% CI 0·11–0·92). Eight of the 24 ventilator‐associated pneumonia patients died in the control group; however, none of those ventilator‐associated pneumonia patients died in the study group. The increased chance of survival was 1·50 (95% CI 1·13–1·99). The length of stay in ICU and duration of mechanical ventilation were reduced in the study group. In consideration of cost, the cost of tubes used to remove oral secretion is much less than the one used to do continuous subglottal suction. Conclusion. Removal of oral secretion is effective in reducing the incidence of ventilator‐associated pneumonia with minimum cost intervention. Relevance to Clinical Practice. This study provides evidence that removal of oral secretion prior to position change is cost effective to reduce the incidence of ventilator‐associated pneumonia. As such intervention is an easy task, routine removal of oral secretion is recommended as the standard of daily nursing care of patients on ventilator.     

Effect of polymerized-type I collagen in knee osteoarthritis. II. In vivo study

Background Polymerized‐Type I Collagen (Polymerized‐Collagen) is an anti‐inflammatory and a tissue regenerator biodrug. The aim of the study was to evaluate the efficacy and safety of intra‐articular injections of Polymerized‐Collagen in patients with knee osteoarthritis (OA). Methods and design Patients (n = 53) were treated with 12 intra‐articular injections of 2 mL of Polymerized‐Collagen (n = 27) or 2 mL of placebo (n = 26) during 6 months. Follow up period was 6 months. The primary endpoints included Western Ontario and McMaster University Osteoarthritis Index, Lequesne index, and pain intensity on a visual analogue scale (VAS). Secondary outcomes were patient global score, investigator global score and drug evaluation. Clinical improvement was determined if the decrease in pain exceeds 20 mm on a VAS and patients achieved at least 20% of improvement from baseline. Urinary levels of C‐terminal crosslinking telopeptide of collagen type II (CTXII) and serum high‐sensitivity C‐reactive protein (hsCRP) were determined by enzyme immunoassays. Statistical analysis was performed by intention to treat. Results Polymerized‐Collagen was safe and well tolerated. Patients had a statistically significant improvement (P < 0·05) from baseline vs. Polymerized‐Collagen and vs. placebo at 6 months in: Lequesne Index (13·1 ± 0·5 vs. 7·1 ± 0·7 vs. 9·6 ± 0·8; P = 0·027), WOMAC (9·0 ± 0·5 vs. 4·0 ± 0·6 vs. 5·80 ± 0·8; P = 0·032), patient VAS (60·0 ± 2·6 vs. 20·6 ± 2·4 vs. 36·1 ± 4·5; P = 0·003), physician VAS (49·8 ± 1·9 vs. 16·8 ± 2·9 vs. 29·8 ± 2·9; P = 0·002), patient global score (1·08 ± 0·1 vs. 2·7 ± 0·1 vs. 1·9 ± 0·2; P = 0·028) and analgesic usage (30·1 ± 9·4 vs. 11·0 ± 3·4 vs. 17·9 ± 4·9; P = 0·001). This improvement was persistent during the follow up. A threefold increase in CTXII was determined in placebo group. No differences were found on hs CRP and incidence of adverse events between groups. Conclusion Polymerized‐Collagen is safe and effective in the treatment of knee OA.     

The effect of enhanced external counterpulsation on C-reactive protein and flow-mediated dilation in porcine model of hypercholesterolaemia

Background: Lipid disorder causes vascular endothelial cell damage and contributes to the early development of dyslipidaemia‐induced atherosclerosis. In vivo and in vitro, it has been found that increasing shear stress can improve endothelial function. Clinically, enhanced external counterpulsation (EECP) plays important roles in the treatment of coronary artery disease by promoting arterial shear stress. The present study aims to evaluate the effect of EECP on vascular endothelial function in porcine hypercholesterolaemic model. Methods: Twenty‐six hypercholesterolaemic pigs were equally divided into EECP group (HC‐EECP group) and control group (HC group). Shear stress of a right forearm superficial artery was measured during EECP in comparison with the basal physiological status in the HC‐EECP group. Endothelial‐dependent flow‐mediated vasodilation (FMD) was applied to assess endothelial function. Serum high‐sensitivity C‐reactive protein (hs‐CRP) levels were measured at indicated time points. Results: Endothelial shear stress was increased significantly during EECP treatment (P<0·001). Compared to HC group, hs‐CRP decreased significantly by EECP at 18‐ and 36‐h, respectively (P<0·05). FMD was improved significantly by EECP compared to that of HC group at 18 h (11·09 ± 5·63%) and at 36 h (11·42 ± 2·75%) post‐EECP, P<0·05. Meanwhile, in animals of HC group, FMD was decreased from baseline 7·76 ± 3·70% to 6·75 ± 3·57% at 18 h and 5·07 ± 1·97% at 36 h, P<0·05. Conclusion: Long‐term EECP can improve endothelial function partially by an increased endothelial shear stress in hypercholesterolaemic porcine model. This implies that long‐term EECP can be used as a complementary therapeutic strategy to prevent atherosclerosis in hypercholesterolaemic patients.     

Conventional treatment after myocardial infarction in routine clinical practice results in regression of left common carotid intima‐media thickness

This study aimed to evaluate the effect of standard medical treatment on the progression of atherosclerosis after a myocardial infarction, in an ordinary clinical setting, by measuring the right and left common carotid intima‐media thickness (IMT). The first investigation took place 3–12 months after the index event; the second took place 3·3–8·2 years after the first. In both investigations, the right and left carotid arteries of 102 patients were examined with an ultrasound duplex scanner. Common carotid IMT and calculated cross‐sectional intima‐media area (cIMa) were measured on both sides. More than 90% of the patients were treated with aspirin, beta‐blockers and statins. In the first investigation, IMT and cIMa were significantly greater on the left side compared to the right (IMT: 0·83 ± 0·22 and 0·74 ± 0·18 mm, P<0·001; cIMa: 18·2 ± 5·2 and 16·3 ± 5·1 mm², P<0·001). In the second investigation, IMT on the left side was significantly reduced compared to the first investigation (0·79 ± 0·22 and 0·83 ± 0·22 mm, P<0·05) with a corresponding tendency towards a decrease in cIMa on the same side. In our study, conventional medical treatment after a myocardial infarction in ordinary clinical routines resulted in regression of the common carotid IMT on the left side. The significant side difference in IMT emphasizes the importance of where and how the carotid IMT is measured in studies using this surrogate end point.     

Serum sialic acid changes in type 2 diabetic patients on metformin or rosiglitazone treatment

What is known and objective: Serum sialic acid is a recently investigated potential risk‐marker for cardiovascular complications. There is a known association between sialic acid and cardiovascular complications in diabetes mellitus. We aimed to investigate the effect of antidiabetic drugs on the serum concentration of sialic acid. Methods: We investigated the effect of metformin and rosiglitazone on the concentration of sialic acid in 120 type 2 diabetic patients, divided into a group (n = 60) receiving metformin and a group (n = 60) receiving rosiglitazone treatment. Results: Serum sialic acid was significantly higher in patients on rosiglitazone (66·90 ±8·80 mg/dL vs. 57·6 ± 8·46 mg/dL, P <0·01) and metformin (61·95 ± 10·49 mg/dL vs. 57·6 ±8·46mg/dL, P < 0·04) when compared with control subjects. In addition, rosiglitazone‐treated patients showed a significant increase in cardiovascular risk factors, notably total cholesterol (246·45 ± 20·2 mg/dL vs. 170·6 ± 15·1 mg/dL, P =0·01), triglyceride (178 ± 9·20 mg/dL vs. 149·35 ±6·31 mg/dL, P < 0·04) and glycohemoglobin (HbA1‐c) concentration (8·17 ± 1·43% vs. 4·38 ±0·96%, P < 0·02) compared with normal control subjects. The patients on metformin also showed significantly higher levels of serum glucose (133·7 ± 9·63 mg/dL vs. 88·35 ± 6·31 mg/dL, P <0·04) and glycohemoglobin (HbA1‐c) (8·23 ±1·75% vs. 4·38 ± 0·96%, P < 0·02) when compared with control subjects. Comparison of the two groups of patients revealed a significantly higher serum sialic acid (66·90 ± 8·80 mg/dL vs. 61·95 ±10·49 mg/dL, P < 0·05), total cholesterol (246·45 ±20·2 mg/dL vs. 192 ± 14·23 mg/dL, P <0·02) and triglyceride (178 ± 9·20 mg/dL vs. 158 ± 14·51mg/dL, P < 0·05) concentrations in the rosiglitazone‐treated patients. What is new and conclusions: This study suggests significantly higher levels of serum sialic acid and other cardiovascular risk factors in rosiglitazone‐treated patients than in metformin‐treated patients. The lower sialic acid concentration may explain a better metformin antidiabetic effect than with rosiglitazone.     

Effect of levofloxacin on lithium – a pharmacokinetic study in rabbits

The aim of this study was to evaluate potential drug–drug interaction between lithium and levofloxacin. The study was conducted on New Zealand white rabbits with three groups having two subgroups each (n = 12). The first group compared the pharmacokinetic (Pk) parameters of lithium when lithium was given as a single dose (56 mg/kg) and when lithium was co‐administered with levofloxacin (35 mg/kg). The second group compared the Pk parameters of lithium when lithium was given for 6 days alone and when levofloxacin was given on the sixth day after lithium steady‐state levels were achieved. The third group compared the Pk parameters of lithium when lithium was given alone for 8 days and levofloxacin was given on days 6, 7, and 8 along with lithium. Apart from this, creatinine levels were also measured to detect nephrotoxicity effects because of this co‐administration. It was found that there was increase in lithium levels in all three groups. The increase was significant when a single dose of levofloxacin was administered with steady‐state level of lithium (C_max of lithium: 2.54 ± 0.15 vs 2.79 ± 0.12 mm , P < 0.001 and AUC_0‐α of lithium: 24.36 ± 3.68 vs 31.88 ± 4.83 mmol/mL h, P < 0.001). The increase in lithium levels was also significant when levofloxacin was coprescribed for 3 days after lithium steady‐state levels were achieved (C_max increased from 2.72 ± 0.29 to 3.96 ± 0.29 mm , P < 0.001 and AUC_0‐α increased from 27.1 ± 4.96 to 42.64 ± 4.94 mmol/mL h). Levofloxacin increases lithium levels when they are co‐administered, and this interaction might be clinically significant as they may be coprescribed.     

Maintained cerebral metabolic ratio during exercise in patients with β‐adrenergic blockade

Background: Decreased cerebral metabolic ratio (CMR) [molar uptake of O₂ versus molar uptake of (glucose + ½ lactate)] during exercise is attenuated by intravenous administration of the non‐selective β‐adrenergic receptor antagonist propranolol. We evaluated to what extent cirrhotic patients in oral treatment with propranolol are able to mobilize brain non‐oxidative carbohydrate metabolism. Methods: Incremental cycle ergometry to exhaustion (86 ± 4·2 W; mean ± SD) was performed in eight cirrhotic patients instrumented with a catheter in the brachial artery and one retrograde in the right internal jugular vein. Healthy subjects form the control group. Results: In β‐blocked cirrhotic patients arterial lactate increased from 1·5 ± 0·3 to 5·1 ± 0·8 mM (P<0·05) and the arterial–jugular venous difference (a–v diff) from ?0·01 ± 0·03 to 0·30 ± 0·05 mM (P<0·05) at rest and during exercise, respectively. During exercise the glucose a–v diff of 0·46 ± 0·06 mM remained at a level similar to rest (0·54 ± 0·03 mM) and at exhaustion the CMR was not significantly changed (5·8 ± 1·1 versus 6·0 ± 0·6). In controls, CMR decreased from 5·6 ± 0·9 at rest to 3·4 ± 0·7 (P<0·05) during maximal exercise and at a lactate level comparable to that achieved by the patients it was 3·8 ± 0·4. Conclusion: During exhaustive exercise in cirrhotic patients the CMR is maintained and a significant cerebral uptake of lactate is demonstrated. The data suggest that oral treatment with a non‐selective β‐adrenergic receptor antagonist attenuates cerebral non‐oxidative metabolism.     

A prospective comparison of nursing- and healthcare-associated pneumonia (NHCAP) with community-acquired pneumonia (CAP)

Nursing- and healthcare-associated pneumonia (NHCAP) has been proposed by the Japanese Respiratory Society as a new category of pneumonia considering the characteristics of the Japanese medical care environment. It is necessary to ascertain the epidemiology and clinical outcomes of NHCAP. A prospective study was conducted of patients with pneumonia who were hospitalized at our hospital from August 2011 to July 2012. We compared 192 cases of NHCAP with 114 cases of community-acquired pneumonia (CAP). Compared with CAP, NHCAP had a higher disease severity, higher 30-day mortality rate (10.9 vs. 3.5 %, P = 0.022), and longer length of hospital stay (median, 12 vs. 8 days, P < 0.001). Streptococcus pneumoniae was the most frequent causative pathogen in both NHCAP and CAP (33.9 vs. 34.8 %, P = 0.896). The incidence of atypical pathogens in NHCAP was low (1.7 %). Multidrug-resistant (MDR) pathogens were isolated more frequently in NHCAP than in CAP, but there was no significant difference (11.0 vs. 4.5 %, P = 0.135). Among 192 NHCAP patients, 122 (63.5 %) were aspiration pneumonia. Aspiration pneumonia was associated with poor outcomes and was considered a major characteristic of NHCAP. Our study suggested that many patients with NHCAP do not need broad-spectrum antibiotic therapy targeting MDR pathogens. Excess mortality in NHCAP patients is the result of patient backgrounds or disease severity rather than the presence of MDR pathogens.     

Assessment of a training programme for the prevention of ventilator‐associated pneumonia

Background: Ventilator‐associated pneumonia (VAP) is the most frequent nosocomial infection in intensive care units (ICUs). Most published studies have analysed nurses' theoretical knowledge about a specific procedure; however, the transfer of this knowledge to the practice has received little attention. Aim: To assess the impact of training session on nurses' knowledge regarding VAP, compliance with VAP preventive measures, VAP incidence and determining whether nursing workload affects compliance. Method: A prospective, quasiexperimental, pre‐ and post‐study of the nursing team in a 16‐bed medical/surgical ICU. Pre‐intervention phase: a questionnaire to assess nurses' knowledge of VAP prevention measures, direct observation and review of clinical records to assess compliance. Intervention phase: eight training sessions for nurses. The post‐intervention phase mirrored the pre‐intervention phase. Findings: Nurses answered more questions correctly on the post‐intervention questionnaire than on the pre‐intervention (17·87 ± 2·69 versus 15·91 ± 2·68, p = 0·002). Compliance with the following measures was better during the post‐intervention period (p = 0·001): use of the smallest possible nasogastric tube, controlled aspiration of subglottic secretions and endotracheal tube cuff pressure, use of oral chlorhexidine and recording the endotracheal tube fixation number. VAP incidence remained unchanged throughout the study. However, a trend towards lower incidence of late (>4 days after intubation) VAP was observed (4·6 versus 3·1 episodes/1000 ventilation days, p = 0·37). Conclusion: The programme improved both knowledge of and compliance with VAP preventive measures, although improved knowledge did not always result in improved compliance.     

Osteocalcin metabolism in the pulmonary circulation

The aim of this study was to evaluate the role of the pulmonary vessel endothelium in the removal of circulating osteocalcin, by measuring the osteocalcin levels in serum from pulmonary and radial artery blood from 39 patients undergoing aorto‐coronary bypass. Because of the discrepancies between methods of measurement, two methods were used. Significant differences were observed in group A (n = 18), tested with heterologous radioimmunoassay (2·85 ± 0·67 μg l^?1 in the pulmonary versus 2·69 ± 0·67 μg l^?1 in the radial artery serum, P<0·001) and in group B (n = 21), tested with a two‐site immunoradiometric assay (5·22 ± 1·46 versus 4·93 ± 1·36 μg l^?1, P<0·01). The percentage differences were –5·54 ± 4·76% (P<0·001) in group A and –4·99 ± 8·13% (P<0·01) in group B; the comparison between the percentage differences was not significant. These different osteocalcin concentrations between the two vascular compartments were considered a marker of osteocalcin degradation. Therefore, the study seems to demonstrate that, as well as kidney, liver and bone, the lung is a relevant site of osteocalcin catabolism. The proteolytic activity of pulmonary vessel endothelium seems to involve about 5% of the circulating peptide.     

Insulin treatment increases skeletal muscle fibre area in patients with diabetes mellitus type 2

The effects of insulin treatment on skeletal muscle characteristics were studied in 18 patients (62 ± 11 years) with poorly controlled diabetes mellitus type 2 (mean duration 7·5 ± 6 years). Skeletal muscle biopsy samples were taken from the lateral portion of the quadriceps muscle before and after a period of insulin treatment of 40 ± 14 days. Enzyme activities (phosphofructokinase, 3‐hydroxyacyl‐CoA dehydrogenase, citrate synthase, lactate dehydrogenase and creatine kinase) and myoglobin content were assessed. In a subgroup of 11 patients (60 ± 11 years), skeletal muscle fibre type composition (type I, IIA, IIB and IIC) and fibre type cross‐sectional area were also analysed. Following insulin treatment there were 32 and 38% increases, respectively, in the cross‐sectional areas of type IIA and IIB fast‐twitch fibres (P<0·02). The fibre type distribution did not change. The myoglobin content in muscle decreased by 20% (P<0·01). Of the enzymes tested, the 3‐hydroxyacyl‐CoA dehydrogenase activity decreased by 10% (P<0·04). Serum glucose, HbA1_C and serum triglyceride levels decreased (P<0·001) and body weight and arm muscle circumference increased (P<0·02). In conclusion, insulin treatment of patients with poorly controlled non‐insulin‐dependent diabetes mellitus increased the fast‐twitch fibre area, reduced myoglobin levels and decreased muscle enzyme activity related to fatty acid oxidation.     

Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects

Background To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat‐derived factor retinol‐binding protein‐4 (RBP‐4) in HIV‐infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Materials and methods Fourteen HIV‐positive, HAART‐naïve subjects were compared with 10 HIV‐negative healthy controls and reassessed after a 1‐year treatment with HAART. Plasma visfatin and RBP‐4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X‐ray absorptiometry (DXA). Homeostasis model assessment (HOMA‐IR) was assessed using insulin and glucose levels. Results Visfatin and RBP‐4 levels in HIV‐positive subjects were comparable with those of HIV‐negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6·9‐fold and 7·1‐fold increase of visfatin and RBP‐4 levels (+54·0 ± 9·7 ng mL^?1, P < 0·0001 and +95·3 ± 31·7 ng mL^?1, P < 0·01), respectively. Leptin (?2·7 ± 1·6 ng mL^?1, P = 0·054) was unchanged and adiponectin (?2·8 ± 0·7 µg mL^?1, P < 0·01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP‐4 (r = 0·78, P = 0·001), fat‐free mass (FFM, r = 0·75, P < 0·05) and change of HOMA‐IR (r = 0·64, P < 0·05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Conclusions Treatment with HAART induced a pronounced increase of plasma visfatin and RBP‐4 as well as a decrease of adiponectin in HIV‐infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.     

The exercise heart rate profile in master athletes compared to healthy controls

Endurance exercise protects the heart via effects on autonomic control of heart rate (HR); however, its effects on HR indices in healthy middle‐aged men are unclear. This study compared HR profiles, including resting HR, increase in HR during exercise and HR recovery after exercise, in middle‐aged athletes and controls. Fifty endurance‐trained athletes and 50 controls (all male; mean age, 48·7 ± 5·8 years) performed an incremental symptom‐limited exercise treadmill test. The electrocardiographic findings and HR profiles were evaluated. Maximal O₂ uptake (52·6 ± 7·0 versus 34·8 ± 4·5 ml kg^?1 min^?1; P<0·001) and the metabolic equivalent of task (15·4 ± 1·6 versus 12·2 ± 1·5; P<0·001) were significantly higher in athletes than in controls. Resting HR was significantly lower in athletes than in controls (62·8 ± 6·7 versus 74·0 ± 10·4 beats per minute (bpm), respectively; P<0·001). Athletes showed a greater increase in HR during exercise than controls (110·1 ± 11·0 versus 88·1 ± 15·4 bpm; P<0·001); however, there was no significant between‐group difference in HR recovery at 1 min after cessation of exercise (22·9 ± 5·6 versus 21·3 ± 6·7 bpm; P = 0·20). Additionally, athletes showed a lower incidence of premature ventricular contractions (PVCs) during exercise (0·0% versus 24·0%; P<0·001). Healthy middle‐aged men participating in regular endurance exercise showed more favourable exercise HR profiles and a lower incidence of PVCs during exercise than sedentary men. These results reflect the beneficial effect of endurance training on autonomic control of the heart.     

左氧氟沙星750mg注射液5日短程疗法治疗社区获得性肺炎的多中心临床研究

目的：比较左氧氟沙星750 mg注射液5 d短程疗法与500 mg注射液7-14 d常规疗法治疗社区获得性肺炎（CAP）疗效和安全性差异。方法本临床试验为随机对照、开放、非劣效性多中心临床试验。CAP患者被随机分配到左氧氟沙星750 mg组治疗5 d或500 mg组治疗7-14 d ,两组均接受静脉给药治疗,观察其临床表现、实验室检查、影像学改变及微生物学检查等,比较两组安全性和疗效差异。结果10个研究中心共入选病例241例。其中全分析集（FAS ）223例,包括750 mg组111例,500 mg组112例。符合方案分析集（PPS）211例,包括750 mg组107例,500 mg组104例。安全性分析集（SS）241例,包括750 mg组121例,500 mg组120例。FAS 750 mg组疗程中位数为5．0 d ,500 mg组疗程中位数为9．0 d。750 mg组总剂量中位数为3750 mg ,500 mg组总剂量中位数为4500 mg。FAS第4次随访750 mg组有效率为86．2％,500 mg组有效率为84．7％,两组综合疗效评价相比为非劣效。FAS 750 mg组可进行微生物疗效评价者共40例,获病原菌41株,500 mg组可行微生物疗效评价者共49例,获病原菌51株,两组细菌清除率均为100％。另外,750 mg组和500 mg组的非典型病原体的临床有效率均为100％。对750 mg组安全性观察结果显示,临床不良反应最常见为注射部位瘙痒、疼痛和充血等,其次为失眠、恶心、皮疹等。较常见的实验室指标异常为中性粒细胞比率降低、白细胞总数降低、ALT升高、AST升高等。以上不良反应多属轻微,患者可耐受,与500 mg组相比,因药物中止试验和不良反应发生率差异无统计学意义,提示两组安全性相仿。结论左氧氟沙星750 mg注射液5 d短程疗法治疗CAP与左氧氟沙星500 mg注射液7-14 d常规疗程相比,其临床和微生物疗效相仿,不良反应发生率相仿,均较轻微,患者耐受性好。     

Reduced preload elicits increased LV twist in healthy humans: an echocardiographic speckle-tracking study during lower body negative pressure

Background: In normal left ventricles (LV), counterclockwise rotation (CCR) and net twist angle (NTA) have shown important roles during ejection. We investigated the effect of reduced preload by lower body negative pressure (LBNP) on CCR and NTA. Methods and Results: Twelve healthy men were examined at rest, LBNP ?20 and ?40 mmHg. By two‐dimensional speckle‐tracking imaging, we measured rotation at four short‐axis levels: basal, papillary, sub‐papillary and apical. LV NTA was calculated as apex‐to‐base difference in rotation. Additionally, regional end‐diastolic (EDA) and end‐systolic area (ESA) were measured and regional area fraction (RAF) calculated [(EDA‐ESA)/EDA] × 100). From rest to LBNP ?40 mmHg, rotation at basal and papillary levels was unchanged. At sub‐papillary level, rotation increased from 3·2 ± 3·6 to 5·8 ± 4·7° (P<0·05), while apical rotation increased from 9·3 ± 3·4 to 12·8 ± 4·7° (P<0·05). Correspondingly, LV NTA increased for each load reduction by 1·6 ± 1·8° (P<0·05) and 4·2 ± 2·3° (P<0·05). RAF increased at sub‐papillary and apical levels from 57·6 ± 3·7 to 64·7 ± 8·8% and from 63·4 ± 8·8 to 74·8 ± 10·1%, respectively (P<0·05). From rest to LBNP ?40 mmHg, changes in rotation and RAF correlated significantly at sub‐papillary and apical levels (r = 0·94, P<0·01, and r = 0·63, P<0·05, respectively). Conclusions: Preload reduction in normal LV elicits increased systolic CCR and regional area fraction at sub‐papillary and apical levels as well as net twist angle. These findings might be of physiological importance to minimize reduction in stroke volume and maintain arterial blood pressure.     

Clinical implementation of systematic medication reconciliation and review as part of the Lund Integrated Medicines Management model – impact on all‐cause emergency department revisits

What is known and objective: Interventions involving medication reconciliation and review by clinical pharmacists can reduce drug‐related problems and improve therapeutic outcomes. The objective of this study was to examine the impact of routine admission medication reconciliation and inpatient medication review on emergency department (ED) revisits after discharge. Secondary outcomes included the combined rate of post‐discharge hospital revisits or death. Methods: This prospective, controlled study included all patients hospitalized in three internal medicine wards in a university hospital, between 1 January 2006 and 31 May 2008. Medication reconciliation on admission and inpatient medication review, conducted by clinical pharmacists in a multiprofessional team, were implemented in these wards at different times during 2007 and 2008 (intervention periods). A discharge medication reconciliation was undertaken in all the study wards, during both control and intervention periods. Patients were included in the intervention group (n = 1216) if they attended a ward with medication reconciliation and review, whether they had received the intervention or not. Control patients (n = 2758) attended the wards before implementation of the intervention. Results and Discussion: No impact of medication reconciliation and reviews on ED revisits [hazard ratio (HR), 0·95; 95% confidence interval (CI), 0·86–1·04]or event‐free survival (HR, 0·96; 95% CI, 0·88–1·04) was demonstrated. In the intervention group, 594 patients (48·8%) visited the ED, compared with 1416 (51·3%) control patients. In total, 716 intervention (58·9%) and 1688 (61·2%) control patients experienced any event (ED visit, hospitalization or death). Because the time to a subsequent ED visit was longer for the control as well as the intervention groups in 2007 than in 2006 (P < 0·05), we re‐examined this cohort of patients; the proportion of patients revisiting the ED was similar in both groups in 2007 (P = 0·608). What is new and conclusion: Routine implementation of medication reconciliation and reviews on admission and during the hospital stay did not appear to have any impact on ED revisits, re‐hospitalizations or mortality over 6‐month follow‐up.     

Improvement of glycaemic control by nateglinide decreases systolic blood pressure in drug-naive patients with type 2 diabetes

Background It has been speculated that oral hypoglycaemic agents that block K‐ATP channels could potentially increase blood pressure by blocking such channels in vascular myocytes. No information about this issue exists regarding nateglinide. Design A multicentre, double‐blind, placebo‐controlled, randomized trial was conducted in 109 drug‐naive 30‐ to 75‐year‐old patients with type 2 diabetes and < 5 years of diabetes diagnosis, who are not taking antihypertensive drugs. These patients were assigned to receive placebo or fixed doses of nateglinide (120 mg before each main meal: breakfast, lunch and dinner) and evaluated at weeks 0 and 12 for (i) body mass index and blood pressure; (ii) standard laboratory tests, including haemoglobin A1c (HbA1c) and fasting plasma glucose; and (iii) incremental area under the curve for glucose and C‐peptide after a standardized liquid breakfast challenge, homeostasis model assessment (HOMA)‐B% (as surrogate of β‐cell activity) and HOMA‐S% (as surrogate of insulin sensitivity). Results At the end of the follow‐up period, patients in the nateglinide group (n = 55), compared to patients in the placebo group (n = 54), showed lower values of HbA1c (6·7 ± 0·6 vs. 7·2 ± 0·7%, respectively; P < 0·001), fasting plasma glucose (7·9 ± 2·1 vs. 8·5 ± 2·0 mmol L^?1; P = 0·023) and systolic blood pressure (125·3 ± 15·4 vs. 129·3 ± 18·7 mmHg; P = 0·015), and higher values of HOMA‐B%[75·7 (51·8–99·4) vs. 57·7 (42·2–83·4); P = 0·033]. A positive correlation was found between changes in HbA1c and systolic blood pressure in the nateglinide group (r = 0·355, P = 0·011). Conclusions In drug‐naive patients with type 2 diabetes, the improvement in glycaemic control with nateglinide is associated with a decrease in systolic blood pressure.     

Utilization of antithrombotic therapy for stroke prevention in atrial fibrillation: a cross‐sectional baseline analysis in general practice

What is known and objective: Antithrombotics for stroke prevention in atrial fibrillation (AF) are reportedly underutilised. Since the burden of care lies within general practice, attention must be paid to identifying and addressing practice gaps in this setting. The objective of this study was to determine the contemporary utilisation of antithrombotic therapy for stroke prevention in AF within Australian general practice (GP). Methods: Data pertaining to AF patients’ (aged ≥65 years) were collected from GP surgeries in New South Wales, Australia, using purpose‐designed data collection forms; extracted data comprised patients’ medical histories, current pharmacotherapy, and relevant characteristics. Results and Discussion: Data pertaining to 393 patients (mean age 78·0 ± 7·0 years) were reviewed. Overall, most (98·5%) patients received antithrombotic therapy. Among the 387 patients using antithrombotics, most (94·1%) received mono‐therapy. “Warfarin ± antiplatelet” was most frequently used (81·7%); 77·5% used “warfarin” as a monotherapy, followed by “dabigatran ± clopidogrel” (11·6%), “aspirin” (5·9%) and “clopidogrel” alone (0·8%). High stroke risk and low bleeding risk were associated with increased use of “warfarin ± antiplatelet” therapy. Older patients (≥80 years) were more likely to receive ‘nil therapy’ (P = 0·04), and less likely to receive dual and triple antithrombotic therapy. Conclusion: We found an encouraging improvement compared to previous studies in the utilisation of antithrombotic therapy for stroke prevention in AF within general practice. Warfarin is now utilised as the mainstay therapy, followed by aspirin, although the novel oral anticoagulants are entering the spectrum of therapies used. Consideration needs to be given to the potential impact of the newer agents and their scope of use.