英夫利昔治疗克罗恩病的初步研究

背景：近年克罗恩病（CD）的发病率不断升高,生物制剂英夫利昔（IFX）是一种肿瘤坏死因子．d单克隆抗体,可促进CD患者黏膜的愈合。目的：观察IFX治疗CD的疗效。方法：收集2008年7月～2009年6月上海中山医院的16例CD住院患者。根据CDAI评分评估CD严重程度并将患者分为常规治疗组和IFX组．分别予美沙拉秦＋泼尼松以及IFX治疗。治疗8周后,比较两组CDAI评分、WBC、ESR、CRP和ALB水平。结果：11例轻度活动期CD患者接受常规治疗．5例中度活动期患者接受IFX治疗。治疗后．所有患者均取得临床缓解．其中2例伴肛门瘘管的轻度活动期患者经常规治疗无效后改用IFX治疗亦达到临床缓解。两组CDAI评分、ESR和CRP水平均较治疗前明显改善（P〈0．05）;IFX组CDAI评分的降低幅度高于常规治疗组,差异有统计学意义（陛0．019）。结论：IFX对CD的临床缓解优于常规治疗．并可促进常规治疗无效的肛门瘘管患者的愈合。     

Is there a role for inhaled nitric oxide as a rescue therapy in respiratory failure associated with hematologic malignancies?

Inhaled nitric oxide has been demonstrated to improve oxygenation in critically ill patients requiring mechanical ventilation. We therefore performed a retrospective review to determine the outcome of patients with hematological malignancies and acute respiratory failure who received inhaled nitric oxide (INO) in a multidisciplinary intensive care unit of a single tertiary referral medical center.Thirteen patients with hematological malignancies who required endotracheal intubation and mechanical ventilation and received INO for acute respiratory failure between January 1998 and December 2002 were identified. Mean +/- standard deviation (SD) age was 47.6 (+/-13.2) years. The mean +/- SD Acute Physiology and Chronic Health Evaluation (APACHE) III score on the day of ICU admission was 94.1 +/- 33.7 with a mean (SD) predicted probability of ICU death of 42.4% (+/-28.6). Mean APACHE III score on the day of initiating INO was 107.6 (+/-34.4) with a predicted mortality in the intensive care unit of 72.7% (+/-23.3). Mean PaO(2) to FiO(2) (PF) ratios (+/-SD) prior to, and immediately after, the initiation of INO were 62.6 (+/-28.2) and 111 (+/-65.1), respectively (P < 0.001). The median duration of INO therapy was 41.8 h (interquartile range, 6.3-98.2). Patients with hematological malignancies and acute respiratory failure to whom INO was administered had clinical deterioration since ICU admission. Despite a marked initial improvement in arterial oxygen tension, all patients ultimately died in the intensive care unit, 8 of them within 48 h of initiating INO. Therefore, despite initial improvement in oxygenation, we did not observe any survival benefit to INO in this setting.     

The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): results of radiographic analyses after 1 year

OBJECTIVE: Infliximab is effective in improving signs and symptoms of joint/skin involvement, functional status, and quality of life in patients with psoriatic arthritis (PsA). Using IMPACT trial data, we assessed the effect of infliximab (IFX) on structural damage in PsA. METHODS: Patients with active PsA were randomly assigned to receive placebo (PBO/IFX) or infliximab 5 mg/kg (IFX/IFX) at weeks 0, 2, 6, and 14, with the primary endpoint at week 16. The PBO group received infliximab loading doses at weeks 16, 18, and 22. Thereafter, all patients received infliximab 5 mg/kg every 8 weeks through week 50. Hand/feet radiographs were obtained at weeks 0 and 50. Total radiographic scores were determined using the PsA modified van der Heijde-Sharp (vdH-S) score. Projected annual rate of progression was calculated by dividing x ray score by disease duration (years). RESULTS: As reported previously, 65% of infliximab treated patients versus 10% of PBO treated patients achieved an ACR20 response at week 16 (p<0.001). At week 50, 69% of patients achieved an ACR20 response. Radiographs (baseline and week 50) were available for 72/104 patients. At baseline, estimated mean annual rate of progression was 5.8 modified vdH-S points/year. Mean (median) changes from baseline to week 50 in the total modified vdH-S score were -1.95 (-0.50) for PBO/IFX and -1.52 (-0.50) for IFX/IFX patients (p = NS). At week 50, 85% and 84% of patients in the PBO/IFX and IFX/IFX groups had no worsening in the total modified vdH-S score. CONCLUSION: Infliximab inhibits radiographic progression in patients with PsA through week 50.     

Sequential therapy with cefuroxime and cefuroxime-axetil for community-acquired lower respiratory tract infection in the oldest old

BACKGROUND AND AIMS: Community acquired lower respiratory tract infection (CALRTI) is the most common infection requiring hospitalization in the elderly. Sequential antibiotic therapy offers the potential for earlier functional rehabilitation, shorter length of hospital stay and lower costs. We studied the efficacy and safety of an empiric sequential antibiotic therapy with cefuroxime-cefuroxime axetil in elderly patients hospitalized with a CALRTI. METHODS: A prospective, randomized, open-label, in-hospital study of cefuroxime IV 750 mg tid for 10 days (IV group) vs cefuroxime 750 mg IV tid for 3 days, followed by cefuroxime-axetil PO 500 mg bid for 7 days (sequence group), when clinical (symptoms improved and fever disappeared) and/or laboratory response [decrease in C-reactive protein (CRP)] occurred. RESULTS: A total of 142 patients, 71 (mean age: 83.3 (+/-6 SD), M/F ratio: 1.1) in the IV group, and 71 (mean age: 81.5 (+/-7 SD), M/F ratio: 1.5) in the sequence group, were included in the study. Eighty-three (58.4%) presented with radiologically confirmed pneumonia (CAP) and 59 (41.6%) with non-pneumonic LRTI (NPLRTI) (p=ns between study groups). Treatment was considered effective in 84.5% (60/71) of patients in the IV group and 80.3% (57/71) in the sequence group (p=ns). Therapy failed in 15% (21/142) of the study population (p=ns between study groups) and, after day 3 of therapy, 8.45% (6/71) failed in both study groups. By the end of treatment, two patients had died in each study group, and total in-hospital mortality was 8.5% (12/142, p=ns between study groups). The length of hospital stay (LOS) did not differ between the two study groups. CONCLUSIONS: When a favorable clinical or biochemical response occurs on day 3 of IV cefuroxime therapy, further therapy with oral cefuroxime-axetil is as effective and safe as a full course of cefuroxime IV in elderly patients hospitalized with CALRTI. However, LOS was not reduced after sequential antibiotic therapy in this population.     

Long-term outcomes of infliximab treatment and predictors of response in 195 patients with ulcerative colitis: a hospital-based cohort study from Korea

Background: Large-scale studies regarding the long-term efficacy of infliximab (IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are lacking.

Study: We analyzed the long-term outcomes of IFX in 195 Korean UC patients who received scheduled IFX treatments at Asan Medical Center. IFX failure was defined as IFX discontinuation due to colectomy or non-response to IFX, and additionally UC-related hospitalization or a need for rescue corticosteroids during the course of IFX.

Results: Between December 2006 and October 2016, a total of 3101 infusions of IFX were administered to 195 patients over a median period of 21 months. At the end of the follow-up, 86 patients (44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%) patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients, 17.9%) or other reasons such as adverse events or patients’ preferences (15 patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC-related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5 years. In a multivariate regression analysis, cytomegalovirus colitis within 3 months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57; 95% confidence interval 1.04–2.37; p?=?.032).

Conclusions: The long-term efficacy of IFX in a large, real-life cohort of Korean UC patients appears to be comparable to that in previously published Western studies.     

Prognosis of patients with heart failure and obstructive sleep apnea treated with continuous positive airway pressure

BACKGROUND: Therapy with continuous positive airway pressure (CPAP) provides several benefits for patients with heart failure (HF) complicated by obstructive sleep apnea (OSA). However, the effect on the prognosis of such patients remains unknown. Aims: To determine whether CPAP therapy and compliance affects the prognosis of HF patients with OSA. METHODS: We classified 88 patients with HF and moderate-to-severe OSA into a CPAP-treated group (n = 65) and an untreated group (n = 23), and then those treated with CPAP were further subclassified according to CPAP therapy compliance. The frequency of death and hospitalization was analyzed using multivariate analysis. RESULTS: During a mean (+/- SD) period of 25.3 +/- 15.3 months, 44.3% of the patients died or were hospitalized. Multivariate analysis showed that the risk for death and hospitalization was increased in the untreated group (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.07 to 3.68; p = 0.030) and in less compliant CPAP-treated patients (HR, 4.02; 95% CI, 1.33 to 12.2; p = 0.014). CONCLUSION: Therapy with CPAP significantly reduced the risk of death and hospitalization among patients with HF and OSA. However, reduced compliance with CPAP therapy was significantly associated with an increased risk of death and hospitalization.     

Rebamipide enema therapy for left-sided ischemic colitis patients accompanied by ulcers： Open label study

AIM： TO attempt rectal administration of rebamipide in the treatment of ischemic colitis patients with ulcers, and evaluate its effects.
METHODS： We compared 9 ischemic colitis patients （2 men, 7 women） with ulcers treated by bowel rest only from 2000 to 2005 （conventional therapy group）, with 6 patients （2 men, 4 women） treated by rebamipide enema therapy in 2006 （rebamipide enema therapy group） and analyzed the mean duration of fasting and hospitalization, degree of ulcer healing, and decrease in WBC count for the two groups.
RESULTS： The mean duration of fasting and hospitalization were 2.7±1.8 d and 9.2 ±1.5 d in the rebamipide group and 7.9±4.1 d and 17.9±6.8 d in the control group, respectively, and significantly reduced in the rebamipide group （t = -2.915; P = 0.0121 and t = -3.054; P = 0.0092）. As for the degree of ulcer healing at 7 d after admission, the ulcer score was reduced by 3.5±0.5 （points） in the rebamipide group and 2.8±0.5 （points） in the control group （t = 1.975; P = 0.0797）, while the decrease in WBC count was 120.0±55.8 （×10^2μL） in the rebamipide group and 85.9±56.8 （×10^2μL） in the control group （t = 1.006; P = 0.3360）.
CONCLUSION： In left-sided ischemic colitis patients with ulcers, rebamipide enema therapy significantly reduced the duration of fasting and hospitalization, recommending its use as a new and effective therapeutic alternative.     

Factors predicting mortality of patients with lung abscess

BACKGROUND: The rates of morbidity and mortality associated with lung abscess are still significant despite the introduction of antibiotic treatments. The aim of this work was to identify the factors that predict a poor outcome for patients with lung abscess. METHODS: We retrospectively reviewed the records and the roentgenographic files of adult patients with lung abscess who were hospitalized from 1980 to 1996 at the Hadassah University Hospital, in Jerusalem, Israel. RESULTS: The study population comprised 75 patients, and the mean age was 52 years old (range, 12 to 89 years). The mean (+/- SD) hospitalization duration was 25.7+/-21.5 days (range, 5 to 94 days). Fifteen patients (20%) succumbed to the infection. The patients who died had more predisposing factors (+/-SD), such as pneumonia, neoplasm, and altered consciousness, than those who survived, respectively: 2.73+/-1.4 vs 1.9+/-1.3 (p < 0.03). The patients with anemia on admission (hemoglobin levels of < 10 g/dL) had a higher mortality rate than those with higher hemoglobin levels, respectively: 58.3 vs 12.9% (p = 0.0008). A higher mortality rate was also associated with infection by Pseudomonas aeruginosa (83%), Staphylococcus aureus (50%), and Klebsiella pneumoniae (44%). The patients who died had larger abscess volumes (+/-SD) than those who survived (233+/-99 vs 157+/-33 mL), although it did not reach statistical significance. The diameter of the abscess correlated with the hospitalization time (r = 0.5; p < 0.001). CONCLUSION: High rates of morbidity and mortality are associated with lung abscess despite appropriate antibiotic therapy and better supportive care. In patients with several predisposing factors, such as a large abscess size and a right-lower-lobe location, the prognosis was worse. The patients infected with S aureus, K pneumoniae, and particularly P aeruginosa had an ominous prognosis. As the prognosis for lung abscess has not improved sufficiently since the introduction of antibiotics, other modalities should be considered for patients with poor prognostic signs.     

Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn's disease

BACKGROUND: Episodic infliximab (IFX) treatment is associated with the formation of antibodies to IFX (ATIs) in the majority of patients, which can lead to infusion reactions and a shorter duration of response. Concomitant use of immunosuppressives (IS) reduces the risk of ATI formation. AIMS AND METHODS: To investigate which of the IS-that is, methotrexate (MTX) or azathioprine (AZA)-is most effective at reducing the risk of ATI formation, a multicentre cohort of 174 patients with Crohn's disease, treated with IFX in an on-demand schedule, was prospectively studied. Three groups were studied: no IS (n = 59), concomitant MTX (n = 50) and concomitant AZA (n = 65). ATI and IFX concentrations were measured in a blinded manner at Prometheus Laboratories before and 4 weeks after each infusion. RESULTS: ATIs were detected in 55% (96/174) of the patients. The concomitant use of IS therapy (AZA or MTX) was associated with a lower incidence of ATIs (53/115; 46%) compared with patients not taking concomitant IS therapy (43/59; 73%; p<0.001). The incidence of ATIs was not different for the MTX group (44%) compared with the AZA group (48%). Patients not taking IS therapy had lower IFX levels (median 2.42 microg/ml (interquartile range (IQR) 1-10.8), maximum 21 microg/ml) 4 weeks after any follow-up infusion than patients taking concomitant IS therapy (median 6.45 microg/ml (IQR 3-11.6), maximum 21 microg/ml; p = 0.065), but there was no difference between MTX or AZA. In patients who developed significant ATIs >8 microg/ml during follow-up, the IFX levels 4 weeks after the first infusion were retrospectively found to be significantly lower than in patients who did not develop ATIs on follow-up or had inconclusive ATIs. CONCLUSION: Concomitant IS therapy reduces ATI formation associated with IFX treatment and improves the pharmacokinetics of IFX. There is no difference between MTX and AZA in reducing these risks. ATI profoundly influences the pharmacokinetics of IFX. The formation of ATIs >8 microg/ml is associated with lower serum levels of IFX already at 4 weeks after its first administration.     

Alendronate increases lumbar spine bone mineral density in patients with Crohn's disease

BACKGROUND & AIMS: Low bone mineral density (BMD) is a common complication of Crohn's disease and may lead to increased morbidity and mortality because of fractures. We investigated the effect of treatment with the bisphosphonate alendronate on bone mass and markers of bone remodeling in patients with Crohn's disease. METHODS: A 12-month double-blind, randomized, placebo-controlled trial examined the effect of a 10-mg daily dose of alendronate. Thirty-two patients with a bone mass T score of -1 of the hip or lumbar spine were studied. The main outcome measure was the difference in the mean percent change in BMD of the lumbar spine measured by dual-energy x-ray absorptiometry. Secondary outcome measures included changes in BMD of the hip and total body and biochemical markers of bone turnover (S-osteocalcin, urine pyridinoline, and urine deoxypyridinoline excretion). RESULTS: Mean (+/-SEM) BMD of the lumbar spine showed an increase of 4.6% +/- 1.2% in the alendronate group compared with a decrease of 0.9% +/- 1.0% in patients receiving placebo (P < 0.01). BMD of the hip increased by 3.3% +/- 1.5% in the alendronate group compared with a smaller increase of 0.7% +/- 1.1% in the placebo group (P = 0.08). Biochemical markers of bone turnover decreased significantly in the alendronate group (P < 0.001). Alendronate was well tolerated, and there was no difference in adverse events among treatment groups. CONCLUSIONS: Treatment with alendronate, 10 mg daily, significantly increased BMD in patients with Crohn's disease and was safe and well tolerated.     

英夫利西单抗治疗克罗恩病的疗效分析

目的 探讨TNFα单克隆抗体英夫利西(infliximab,IFX)单抗治疗活动性克罗恩病(CD)的疗效与安全性.方法 对传统药物治疗后未能完全缓解、手术治疗后复发或对药物不耐受的CD患者,于0、2、6周时静脉输注IFX(5 mg/kg)诱导缓解治疗,并对第一次输注后14周内的临床疗效,包括疾病活动度、血生化指标及结肠镜表现作出评估.结果 10例患者接受了IFX治疗,其中男8例,女2例,中位年龄31.4岁.5例患者IFX治疗1周后即感症状得到改善,主观症状评分从2.2±0.6降为1.2±0.4(P<0.05);简化CD活动性指数(H-B指数)从6.6±1.6降为2.1±1.0(P<0.05);ESR、C反应蛋白、血清总蛋白及白蛋白也有明显改善;内镜下CD严重度指数也得到明显改善.治疗过程中未观察到输注反应;1例患者在第3次IFX输注后,血ALT及AST暂时性升高;1例患者输注后35周出现严重贫血(三系列均减少).结论 经3次IFX静脉输注方案治疗,本组患者的临床症状及结肠镜下表现可获得较快、较好的改善.IFX长期应用的安全性尚需进一步扩大样本的研究.     

A retrospective analysis of practice patterns in the treatment of methicillin-resistant Staphylococcus aureus skin and soft tissue infections at three Canadian tertiary care centres.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly being encountered and pose an increasing burden to the health care system in Canada. OBJECTIVE: To elucidate and characterize the factors influencing the current MRSA treatment patterns in patients with skin and soft tissue infections (SSTIs) before linezolid became available on the Canadian market. METHODS: A retrospective study collected demographic, treatment and resource use data on patients hospitalized at one of three geographically distinct tertiary care facilities, where MRSA SSTI treatment was initiated with intravenous (IV) vancomycin. Analysis of opportunities for IV-to-oral switch therapy was based on eligibility criteria. RESULTS: Of 89 patients identified over a 43-month period, the mean (+/-SD) durations of anti-infective treatment and hospitalization were 22.4+/-21 days and 28.9+/-20.8 days, respectively. An infected surgical wound was most common, representing 62.9% of infections. The mean duration of vancomycin treatment was 19.5 days and the mean number of 1 g doses received was 29.0+/-32.9. The majority of patients (55.1%) initiated vancomycin therapy a mean of 5.4+/-8.9 days after confirmation of MRSA. Of the 70% of patients meeting criteria for IV-to-oral switch therapy, only 10% received oral treatment. The most common reason cited for not switching was lack of an effective oral alternative. Analysis of switch therapy criteria found that IV treatment continued for a mean of 13 days despite the appropriateness of the oral route. CONCLUSIONS: Considerable variation exists in treatment patterns for MRSA infections. Improvements in the initiation of therapy and the use of IV-to-oral switch therapy may improve care and reduce the duration of hospitalization for MRSA SSTIs.     

Direct hospital costs for patients with inflammatory bowel disease in a Canadian tertiary care university hospital

OBJECTIVE: We set out to determine the direct costs of hospitalizations of patients with Crohn's disease and ulcerative colitis admitted to a university-affiliated tertiary care hospital and to contrast the costs of medical versus surgical inpatient care, Crohn's disease versus ulcerative colitis, and to identify dominant components of inpatient costs. METHODS: We used a patient-specific case costing system at Saint Boniface General Hospital, Winnipeg, Manitoba, for fiscal years 1994 and 1995. We extracted all inpatients whose hospital discharge abstracts included ICD-9-CM codes 555 (Crohn's disease) and 556 (ulcerative colitis) among the top eight discharge diagnoses, and performed a chart review on all cases to ensure that the hospitalization was for inflammatory bowel disease and the diagnoses were accurate. We analyzed cases based on their disease diagnosis, primary mode of therapy associated with the hospitalization (medical vs surgical), and their major diagnosis-related group (DRG). This study evaluated direct patient care costs only and costs are expressed in Canadian dollars. RESULTS: Of 362 hospital admissions, 325 were eligible and of these admissions 275 belonged to the digestive system DRGs. Seventy-one (37%) were admitted more than once during the 2 yr of the study, accounting for 202 (62%) of the total number of admissions. The mean cost per admission of all cases of Crohn's disease was $3,149 (95% confidence interval [CI], $2,665-$3,634) and for ulcerative colitis was $3,726 (95% CI $3,008-$4,445). Surgical therapy cases accounted for 49.8% of all admissions, 57.8% of all hospital days, and 60.5% of all costs. Patients treated surgically had more costly hospitalizations than those treated medically, particularly when analyzing only nontotal parenteral nutrition (TPN) cases. Surgical treatment admissions were significantly more costly for ulcerative colitis digestive DRG admissions than Crohn's disease. The nondigestive DRG admissions were more costly than the digestive DRGs in all categories although this was only statistically different among medically treated Crohn's disease. Patients treated medically were similarly costly whether they had Crohn's disease or ulcerative colitis. There was no significant difference in cost per admission among cases admitted multiple times, compared with those admitted only once. TPN cases accounted for 9.5% of cases but 27.1% of costs. TPN-associated hospitalizations were more costly than non-TPN-use hospitalizations but these costs were primarily driven by duration of stay rather than TPN use itself. For all cases, the top five cost categories in descending order were nursing unit bed-days, drugs and pharmacy, diagnostic lab tests, operating room, and diagnostic imaging and endoscopy. CONCLUSIONS: Using our system we could determine direct costs for inpatients with inflammatory bowel disease and the factors that determined increased costs. Medical therapy admissions were similarly costly between Crohn's disease and ulcerative colitis; however, surgical therapy admissions were costlier among ulcerative colitis patients. Admissions for nondigestive DRGs were more costly than those for digestive DRGs. TPN use identified a sicker group of patients who remained in the hospital longer than nonusers and, not surprisingly, these were the costliest patients.     

Efficacy of infliximab in acute severe ulcerative colitis:A single-centre experience

AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included.Data were extracted from clinical records in order to assess response to IFX therapy.The primary endpoint was colectomy-free survival,and secondary outcomes included glucocorticosteroid-free remission and safety,which was evaluated by recording deaths and adverse events.Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free,both at discharge from their index admission,and during follow-up after an initial response to IFX were compared.RESULTS:Forty-four patients(16 females,mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis.The median duration of follow-up post-first infusion was 396 d(interquartile range = 173-828 d).There were 21(47.7%) patients with < 1 year of follow-up,10(22.7%) with 1 years to 2 years of follow-up,and 13(29.5%) with > 2 years of follow-up post-first infusion of IFX.Overall,35(79.5%) responded to IFX,avoiding colectomy during their index admission,29(65.9%) were colectomyfree at last point of follow-up(median follow-up 396 d),and 25(56.8%) were in glucocorticosteroid-free remission at end of follow-up.There was one death from post-operative sepsis,20 d after a single IFX infusion.Colectomy rates were generally lower among those "bridging" to thiopurine.Of 18 patients "bridged" to thiopurine therapy,17(94.4%) were colectomyfree,and 15(83.3%) were in glucocorticosteroid-free remission at study end.No predictors of response were identified.CONCLUSION:IFX is effective for acute severe ulcerative colitis in real-life clinical practice.Two-thirds of patients avoided colectomy,and more than 50% were in glucocorticosteroid-free remission.     

Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study

BACKGROUND: Treatment with systemic corticosteroids for exacerbations of COPD results in improvement in clinical outcomes. On hospitalization, corticosteroids are generally administered IV. It has not been established whether oral administration is equally effective. We conducted a study to demonstrate that therapy with oral prednisolone was not inferior to therapy with IV prednisolone using a double-blind, double-dummy design. METHODS: Patients hospitalized for an exacerbation of COPD were randomized to receive 5 days of therapy with prednisolone, 60 mg IV or orally. Treatment failure, the primary outcome, was defined as death, admission to the ICU, readmission to the ICU because of COPD, or the intensification of pharmacologic therapy during a 90-day follow-up period. RESULTS: A total of 435 patients were referred for a COPD exacerbation warranting hospitalization; 107 patients were randomized to receive IV therapy, and 103 to receive oral therapy. Overall treatment failure within 90 days was similar, as follows: IV prednisolone, 61.7%; oral prednisolone, 56.3% (one-sided lower bound of the 95% confidence interval [CI], -5.8%). There were also no differences in early (ie, within 2 weeks) treatment failure (17.8% and 18.4%, respectively; one-sided lower bound of the 95% CI, -9.4%), late (ie, after 2 weeks) treatment failure (54.0% and 47.0%, respectively; one-sided lower bound of the 95% CI, -5.6%), and mean (+/- SD) length of hospital stay (11.9 +/- 8.6 and 11.2 +/- 6.7 days, respectively). Over 1 week, clinically relevant improvements were found in spirometry and health-related quality of life, without significant differences between the two treatment groups. CONCLUSION: Therapy with oral prednisolone is not inferior to IV treatment in the first 90 days after starting therapy. We suggest that the oral route is preferable in the treatment of COPD exacerbations. Trial registration: Clinicaltrials.gov Identifier: NCT00311961.     

Safety and efficacy of growth hormone (GH) during extended treatment of adult Japanese patients with GH deficiency (GHD)

OBJECTIVES: To assess the effects of a growth hormone (GH) replacement therapy using a GH dose regimen based on serum insulin-like growth factor (IGF-I) concentrations in Japanese adults with GH deficiency (GHD). DESIGN: In this multicentre, uncontrolled, open-label study, Japanese adults with GHD who had received either GH replacement therapy (GH-GH group, n=35) or placebo (Placebo-GH group, n=36) in a previous randomised, double-blind, placebo-controlled trial were treated with GH replacement therapy for 48 weeks. GH treatment was started at a dose of 0.003 mg/kg/day administered by subcutaneous injection for the first 8 weeks, after which the dose was adjusted to maintain patients' serum IGF-I levels within the reference range adjusted for age and gender. Body composition, serum lipids, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels were measured throughout study. Symptom and quality of life scores were also determined. RESULTS: Lean body mass (LBM) was increased compared with baseline (the end of the preceding double-blind trial) at 24 and 48 weeks, with a mean (+/-SD) increase of 1.3% (+/-4.2%) at week 48 in the GH-GH group (an increase of 6.6% [+/-6.0%] from the start of the preceding double-blind trial) and a larger increase of 4.7% (+/-5.9%) in the Placebo-GH group. Body fat mass (BFM) increased slightly from baseline in the GH-GH group with a mean increase of 2.9+/-10.6% at week 48 (a decrease from the start of the preceding double-blind trial at 48 weeks of 7.8% [+/-15.0%]) but decreased by 6.5% (+/-11.7%) at week 48 in the Placebo-GH group. Serum lipids were unchanged or slightly increased from baseline in the GH-GH group but patients' lipid profiles improved in the Placebo-GH group. In patients who received placebo during the double-blind study, individualised GH therapy in this open-label study increased mean LBM at 48 weeks by 6.2+/-6.8% in patients with CO GHD and by 3.0+/-4.4% in patients with AO GHD. Changes in mean LBM and mean BFM at week 48 were +4.1+/-4.5% and -2.4+/-10.5%, respectively, in females and +5.0+/-6.7% and -8.9+/-11.8%, respectively, in males. In patients who received GH treatment during the double-blind study, overall changes in LBM, BFM and IGF-I SD score after 24 weeks and 48 weeks were small, with no significant differences between subgroups. While the overall incidence of adverse events was broadly similar in the GH-GH and Placebo-GH groups (97% and 89%, respectively), the incidence of treatment-related events was higher in the GH-GH group (83% vs 42% in the Placebo-GH group). Most adverse events in both treatment groups were of mild or moderate severity and not clinically significant. The incidences of oedema and cases of high IGF-I during the IGF-I level-adjusted treatment regimen were lower than those during the preceding fixed dose titration. CONCLUSION: Long-term GH replacement therapy was well tolerated in Japanese adults with GHD. GH treatment maintained the improvements in body composition and lipid profiles in the patients previously treated in the double-blind study (GH-GH group) and improved these parameters in previously untreated patients (Placebo-GH group). Individualised GH administration based on IGF-I levels was well-tolerated and effective.     

Lower respiratory illness in infants and young children with cystic fibrosis

The purpose of our study was to assess the effect on pulmonary function of adding intravenous hydrocortisone to the standard treatment of infants with cystic fibrosis (CF) hospitalized for lower respiratory illnesses (LRI). Twenty CF infants were randomized and received 10 days of hydrocortisone (10 mg/kg/day) or placebo in addition to standard treatment with intravenous antibiotics, chest physiotherapy, and an aerosolized-agonist with cromolyn. Functional residual capacity (FRC) and forced expiratory flows (V′_{max, FRC}) were measured on admission, on Day 10 of hospitalization, and as outpatients 1–2 months following hospital discharge. Pulmonary function values were adjusted for differences in body length and expressed as Z-scores. Upon admission, flows were decreased, and FRC was increased in both groups; there were no differences between the groups. The change in pulmonary function from admission to Day 10 of hospitalization was not different for the two groups. From admission to outpatient follow-up after hospitalization, there was a significant increase in flows for the steroid group, but not for the placebo group. In addition, the direction of change in FRC was significantly different for the two groups; the steroid group had a small decrease in FRC, while the placebo group had a small increase in FRC. These findings suggest that the addition of intravenous hydrocortisone to the standard treatment of CF infants hospitalized for a LRI may produce a greater or a more sustained improvement in lung function following hospitalization. Pediatr. Pulmonol. 1997;24:48–51. © 1997 Wiley-Liss, Inc.     

Optimized timing of using infliximab in perianal fistulizing Crohn's disease

Infliximab(IFX), as a drug of first-line therapy, can alter the natural progression of Crohn's disease(CD), promote mucosal healing and reduce complications,hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission.There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents.Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging.Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.     

住院期间血小板平均体积变化与老年重症肺炎预后的相关性分析

目的 探讨住院期间血小板平均体积(MPV)变化与老年重症肺炎(severe pneumonia,SP)预后的关系.方法 回顾性分析本院于2017年1月至2019年12月收治的158例老年SP病人的临床资料,根据病人出院时MPV与入院时MPV的差值分为MPV未增高组(ΔMPV<0.6 fL)和MPV增高组(ΔMPV≥0....     

Feasibility of an outpatient and home parenteral antibiotic therapy (OHPAT) programme in Tayside, Scotland

Outpatient and home parenteral antibiotic therapy (OHPAT) is under-utilized in the U.K. We performed a feasibility study over a 5-month period in a regional U.K. infection unit. After exclusions, 183 antibiotic treated patients were evaluated. Ninety-five received intravenous (i.v.) therapy, of whom 32 received at least 4 days. Prolonged i.v. therapy was most frequent in soft tissue infections. In these patients, length of stay and duration of i.v. treatment were correlated (r = 0.74, 0.51-0.87). Eighty-three (86%) of patients who received IV therapy judged OHPAT to be an acceptable alternative to hospitalization. Those who did not were older (mean age 64 vs. 46 years, P<0.001) and were less likely to have a carer willing to administer the antibiotic at home (8/28 vs. 117/151, P<0.001). Twenty-five of 32 (79%) patients treated with prolonged parenteral therapy and 27/95 (28%) treated with any length of parenteral therapy met criteria for OHPAT. Thirteen of these were safely and successfully managed as outpatients by ward staff, OHPAT is an acceptable alternative to inpatient therapy in Tayside and may reduce the duration of hospitalization or prevent admission in certain patients.