Safety of extended treatment with anakinra in patients with rheumatoid arthritis

OBJECTIVE: To determine the safety profile of anakinra after extended exposure in a diverse clinical trial population of patients with rheumatoid arthritis. METHODS: A six month, randomised, double blind phase comparing anakinra (100 mg/day) with placebo was followed by open label anakinra treatment for up to three years in patients with rheumatoid arthritis. Concomitant non-steroidal anti-inflammatory drugs, corticosteroids, and other disease modifying antirheumatic drugs were permitted. RESULTS: In all 1346 patients with rheumatoid arthritis received anakinra for up to three years. Patients had varying levels of disease severity, concomitant drug use, and comorbid conditions. Cumulative, exposure adjusted event (EAE) rates for all adverse events (AEs), serious AEs, and deaths were similar during each year of anakinra treatment; the overall rate (0 to 3 years) was similar to that observed for controls during the blinded phase. The most frequent AEs were injection site reactions (122.26 events/100 patient-years), rheumatoid arthritis progression (67.80 events/100 patient-years), and upper respiratory infections (26.09 events/100 patient-years). The EAE rate of serious infections was higher for patients treated with anakinra for 0 to 3 years (5.37 events/100 patient-years) than for controls during the blinded phase (1.65 events/100 patient-years). However, if the patient was not receiving corticosteroid treatment at baseline, the serious infection rate was substantially lower (2.87 event/100 patient-years). The overall incidence of malignancies was consistent with expected rates reported by SEER. Neutralising antibodies developed in 25 patients, but appeared to be transient in 12; neutralising antibody status did not appear related to occurrence of malignancies or serious infections. There were no clinically significant trends in laboratory data related to anakinra. CONCLUSION: Anakinra is safe and well tolerated for up to three years of continuous use in a diverse population of patients with rheumatoid arthritis.     

Toxicity profiles of traditional disease modifying antirheumatic drugs for rheumatoid arthritis

BACKGROUND: The progression of rheumatoid arthritis (RA) can be retarded or halted by disease modifying antirheumatic drugs (DMARDs). Next to inefficacy, toxicity limits their use. OBJECTIVE: To explore the toxicity profiles of DMARDs in daily life. PATIENTS AND METHODS: Five hundred and ninety three patients with RA charts (>2300 patient years of treatment) were reviewed at two rheumatology outpatient clinics. All recorded data on toxicity and reasons for stopping treatment were collected. RESULTS: Adverse events were common reasons for treatment discontinuation (42% of treatments). In 70% they were subjectively reported at the clinical visit, while substantial laboratory abnormalities were seen relatively rarely (9% of treatments: abnormal liver function tests in 5%; haematological abnormalities in 3%; impaired renal function in 1%). No single case of retinopathy from antimalarial drugs (that is, an incidence of <0.3 events/1000 patient years) was found, although eye examinations by the specialists were abnormal 30 times per 1000 patient years, mostly revealing keratopathy. Most commonly reported symptoms per 1000 patient years were nausea (54 events), abdominal pain (37 events), and rashes (34 events). Adverse events were more likely to occur with increasing number of consecutive DMARD courses. CONCLUSION: The first DMARD course in a patient seems to be safer than the consecutive ones. In addition, the incidence of adverse events (AEs) seems to be similar for high and low dose treatment. Data are also provided on types and incidence of AEs that are consistent with previous studies in other countries and different settings.     

Incidence of thromboembolic complications in patients with atrial fibrillation or mechanical heart valves with a subtherapeutic international normalized ratio: a prospective multicenter cohort study

Subtherapeutic international normalized ratio (INR) is frequently encountered in clinical practice, and patients with high-risk atrial fibrillation (AF) and with mechanical heart valve (MHV) with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events (TE). However, there are no prospective data evaluating this risk. Consecutive patients with a history of stable anticoagulation, but with a subtherapeutic INR, were prospectively included. Data on use and dose of low-molecular weight heparin (LMWH) bridging therapy were collected. The incidence of objectively confirmed TE and of major bleeding events within 90 days after the index INR was assessed. Five hundred and one patients with INR value 0.5-1 INR units below the lower limit of the patient-specific target INR were included in the study (280 with MHV and 221 with AF and CHADS2 score ≥3). LMWH was prescribed for 64 patients (12.8%). During follow-up, seven patients had a TE (1.40%; 95% confidence interval 0.68, 2.86%; 5.58 events for 100 patients year). All the events occurred within 14 days after the index INR. When we consider only patients who did not receive bridging therapy, the incidence of TE was 1.14% (5 of 437 patients; 95% confidence interval 0.49, 2.64%; 4.58 events for 100 patients year). There were no major bleeding events. The risk of TE in this population was not negligible. Given the frequent observation of subtherapeutic INR levels when monitoring vitamin K antagonists, this finding warrants additional investigation to improve the management of these patients.     

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis

OBJECTIVE: To assess the safety of adalimumab in global clinical trials and postmarketing surveillance among patients with rheumatoid arthritis (RA). METHODS: Safety data for adalimumab treated patients from randomised controlled trials, open label extensions, and two phase IIIb open label trials were analysed. In addition, postmarketing spontaneous reports of adverse events in the United States were collected following Food and Drug Administration approval of adalimumab on 31 December 2002. RESULTS: As of 15 April 2005, the RA clinical trial safety database analysed covered 10,050 patients, representing 12,506 patient-years (PYs) of adalimumab exposure. The rate of serious infections, 5.1/100 PYs, was comparable to that reported on 31 August 2002 (4.9/100 PYs), and to published reports of RA populations naive to anti-tumour necrosis factor (TNF) therapy. Following implementation of tuberculosis (TB) screening in clinical trials, the rate of TB decreased. There were 34 cases of TB as of this analysis (0.27/100 PYs). The standardised incidence ratio for lymphoma was 3.19 (95% CI 1.78 to 5.26), consistent with the observed increased incidence in the general RA population. As of 30 June 2005, there were an estimated 78 522 PYs of exposure to adalimumab in the US postmarketing period. Seventeen TB cases were spontaneously reported (0.02/100 PYs) from the US. Rates of other postmarketing events of interest, such as congestive heart failure, systemic lupus erythematosus, opportunistic infections, blood dyscrasias, lymphomas, and demyelinating disease, support observations from clinical trials. CONCLUSION: Analyses of these data demonstrate that long term adalimumab treatment is generally safe and well tolerated in patients with RA.     

Results of European post-marketing surveillance of bosentan in pulmonary hypertension.

After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were na?ve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-na?ve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.     

Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control

OBJECTIVES: To determine burden and risk factors for tuberculosis (TB) in an antiretroviral treatment (ART) programme and its impact on ART outcomes. DESIGN: Prospective cohort study. METHODS: Prevalent TB was assessed at baseline and incident TB was ascertained prospectively over 3 years among 944 patients accessing a community-based ART programme in South Africa. RESULTS: At enrollment, median CD4 cell count was 96 cells/microl and 52% of patients had a previous history of TB. Prevalent TB (current antituberculosis treatment or active TB) was present in 25% and was strongly associated with advanced immunodeficiency. During 782 person-years of ART, 81 cases of TB were diagnosed. The incidence was 22.1/100 person-years during the first 3 months of ART and decreased to an average of 4.5/100 person-years during the second and third years. In multivariate analysis, risk of incident TB during follow-up was only associated with the current absolute CD4 cell count at that time point; an increase of 100 cells/mul was associated with a 25% lower risk (P = 0.007). Although prevalent and incident TB were associated with greater than two-fold increased mortality risk, they did not compromise immunological and virological outcomes among survivors at 48 weeks. CONCLUSIONS: Late initiation of ART was associated with a major burden of TB in this ART programme. TB reduced survival but did not impair immunovirological outcomes. Reductions in TB incidence during ART were dependent on CD4 cell count; however, after 3 years of treatment, rates were still 5- to 10-fold higher than among non-HIV-infected people. Earlier initiation of ART may reduce this burden of TB.     

Comparison of cardiovascular thrombotic events in patients with osteoarthritis treated with rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, and nabumetone).

Aspirin, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and specific cyclooxygenase-2 (COX-2) inhibitors each have distinctive effects on COX-1-mediated thromboxane biosynthesis, the major determinant of platelet aggregation. It is unclear whether these effects are associated with differences in thrombogenic risks. To compare the risk for thrombotic cardiovascular events among patients receiving rofecoxib, nonselective NSAIDs, and placebo, cardiovascular safety was assessed in 5,435 participants in 8 phase IIB/III osteoarthritis trials. The median treatment exposure was 31/2 months. The primary end point assessed was the risk of any arterial or venous thrombotic cardiovascular adverse event (AE). A second analysis assessed differences in the Anti-Platelet Trialists' Collaboration (APTC) events, a cluster end point that consists of the combined incidence of (1) cardiovascular, hemorrhagic, and unknown death; (2) myocardial infarction; and (3) cerebrovascular accident. Similar rates of thrombotic cardiovascular AEs were reported with rofecoxib, placebo, and comparator nonselective NSAIDs (ibuprofen, diclofenac, or nabumetone). In trials that compared rofecoxib with NSAIDs, the incidence of thrombotic cardiovascular AEs was 1.93/100 patient-years in the rofecoxib treatment group compared with 2.27/100 patient-years in the combined nonselective NSAID group. In trials that compared rofecoxib with placebo, the incidence of thrombotic cardiovascular AEs was 2.71/100 patient-years in the rofecoxib group compared with 2.57/100 patient-years in the placebo group. Consistent with the risks of cardiovascular AEs, similar rates of APTC events were reported with rofecoxib, placebo, and comparator nonselective NSAIDs. Thus, in the rofecoxib osteoarthritis development program, there was no difference between rofecoxib, comparator nonselective NSAIDs, and placebo in the risks of cardiovascular thrombotic events.     

The risk of cardiovascular events in Japanese hypertensive patients with hypercholesterolemia: sub-analysis of the Japan Lipid Intervention Trial (J-LIT) Study, a large-scale observational cohort study.

Coronary events and stroke are leading causes of death in Japan. However, the effects of hypertension on the risk of coronary events and stroke have not been well established in Japanese hypercholesterolemic patients. This study aimed to determine the relationship between the risk of coronary events or stroke and blood pressure and cholesterol levels during low-dose simvastatin treatment using data from the Japan Lipid Intervention Trial (J-LIT) study (a large scale nationwide cohort study). In the present study, 47,294 hypercholesterolemic patients were treated with open-labeled simvastatin (5 to 10 mg/day) for 6 years by a large number of physicians in a clinical setting. The adjusted incidence rates of coronary events in males and females were 8.9 and 2.3 and those of stroke were 17.6 and 11.3/1000 patients during the 6-year period, respectively. The incidence rate of stroke was higher than that of coronary events in both males and females. An obvious sex difference was observed in terms of the incidence of coronary events. The risk of coronary events, stroke, and total cardiovascular events were increased, with elevations in blood pressure observed in patients treated for hypercholesterolemia. The risk of total cardiovascular events in the groups exhibiting less lipid control increased, with lower blood pressure levels than those of the well-controlled group. For patients with hypercholesterolemia and hypertension, blood pressure should be strictly controlled in order to prevent both coronary events and stroke, and the serum total cholesterol levels should be maintained at low levels as well.     

Increasing incidence of childhood Graves' disease in Hong Kong: a follow-up study

OBJECTIVE: Childhood Graves' disease has been reported to be rare but preliminary epidemiological data on its incidence appeared to be high in Hong Kong Chinese children. The aim of this study is to determine the incidence of childhood Graves' disease in Hong Kong and to analyse whether there is an increasing trend of the incidence. PATIENTS AND DESIGN: We established a registry of childhood Graves' disease at our centre to collect cases from four districts in Hong Kong. The diagnosis of Graves' disease was based on clinical features, diffused enlargement of thyroid gland, raised free thyroxine or triiodothyronine levels, suppressed TSH levels, and the presence of thyroid receptor antibodies. Confirmed cases of Graves' disease who resided in any of the four districts were used to calculate the incidence for the study period between 1989 and 1998. RESULTS: One hundred and eighteen Chinese children under 15 years of age had a confirmed diagnosis of Graves' disease during the study period from January 1989 to December 1998. There were 11 boys and 107 girls giving a male to female ratio of 1 : 9.7. The overall incidence rates were 3.2/100 000/year and 6.5/100 000/year for the two periods 1989-93 and 1994-98, respectively. The incidence rates for girls have increased significantly (P < 0.001) from 3.8/100 000/year in 1989 to 14.1/100 000/year in 1998. The current incidence of childhood Graves' disease in our population is about eight times that reported in Danish children. CONCLUSIONS: This study confirms the high incidence of childhood Graves' disease in Hong Kong and documents an increasing trend for girls. Further studies are required to reveal possible genetic or environmental factors responsible for such epidemiology in Hong Kong Chinese children.     

Are the Twelve Steps more acceptable to drug users than to drinkers? A comparison of experiences of and attitudes to Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) among 200 substance misusers attending inpatient detoxification.

The present study is a cross-sectional interview-based investigation comparing experiences of and attitudes towards Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) in a sample of 200 patients attending inpatient substance misuse detoxification services. Two hundred consecutive admissions were recruited; 100 each from one drug and one alcohol in-patient treatment service in which attendance at AA/NA was a voluntary adjunct to a generic treatment programme. Although there were no differences in the history of AA/NA attendance, the drug users (who were on average younger) reported significantly more positive attitudes towards AA/NA, more willingness to attend during their in-patient treatment and greater intention to attend following completion of their detoxification. In particular, despite no differences in spiritual/religious orientation, the drug users reported more positive views of the Twelve Steps. As AA/NA remain popular and accessible forms of substance misuse support, it is critical that we develop a clearer understanding of their impact and of the scope for their integration with generic forms of substance misuse treatment.     

Compliance and satisfaction with a comprehensive falls intervention programme

IntroductionFalls intervention programs can reduce falls risk, but the programs often include comprehensive diagnostic and therapeutic procedures that might be too strenuous for frail old persons.PurposeThe aim of this study was to explore old people's perception and satisfaction with a comprehensive falls intervention programme. The study was planned to assess self-perceived benefit and not objective benefit as, for example, reduction in falls.Materials and methodsOne hundred and sixty geriatric patients who had been through a comprehensive falls prevention program were contacted by telephone and asked to participate in an interview in order to explore their satisfaction and compliance with the program.ResultsFifty-nine patients were lost to follow-up. One hundred and one patients participated in the interview. Only one patient found the examination programme too comprehensive. Generally patients complied well with advice on physical training, when it was offered as part of hospital treatment (100% compliance) or offered in the municipality (73% compliance). The amount and intensity of training offered was perceived as satisfactory by 65%, whereas 27% wished more training than they were offered. Benefit of training was reported by 82% of patients trained in hospital or municipal facilities, whereas 74% reported benefit of a home-based programme. Only 4,2% perceived the training programme as too strenuous. To attend training, 71% reported the need for transport assistance.Discussion and conclusionFrail geriatric patients perceive benefit from, comply and are overall satisfied with a comprehensive falls examination and intervention program. Non-compliance may be due to simple technical barriers like lack of transport facilities. To attend training, the majority needs assistance with transport.     

Recurrence of angina pectoris after percutaneous coronary intervention is reduced by statins in Japanese patients

Background

Statins have been reported to reduce cardiovascular events in patients with coronary artery disease (CAD). Percutaneous coronary intervention (PCI) is commonly used to relieve ischemic symptoms in patients with CAD. However, there is little information on the effect of statins on cardiovascular events after PCI, even in the era of coronary stent implantation.

Methods

A total of 1019 patients with acute or chronic CAD and modest total cholesterol levels (180–240 mg/dl) were enrolled and randomly assigned to treatment with or without statins. We evaluated the effect of any available statin on the incidence of cardiovascular events after PCI. The primary endpoint was a composite of cardiovascular death, nonfatal acute myocardial infarction (MI), recurrent angina pectoris requiring emergency rehospitalization (rAP), heart failure, and stroke.

Results

Indications for PCI were stable angina in 54%, ST-elevation MI in 41% and non-ST-elevation MI/unstable angina pectoris in 5%. After 2 years of statin treatment, low-density lipoprotein cholesterol (LDL-C) decreased from 133 to 96 mg/dl. Stents were implanted in 84% of all cases. The primary endpoint event rate was 9.5% in the statin group and 14.7% in the non-statin group (p = 0.0292). Of all primary endpoint events, only rAP was significantly suppressed by statins (p = 0.0027). In rAP patients, coronary angiography revealed that statins suppressed restenosis but not new lesions.

Conclusions

For Japanese CAD patients treated with PCI and stent implantation, statin therapy reduced the incidence of recurrent cardiovascular events, particularly rAP. Discretionary statin treatment to achieve LDL-C levels <100 mg/dl effectively reduced restenosis causing rAP.     

2011年中国在校学生肺结核疫情分析

目的 研究2011年中国在校学生肺结核报告发病率及疫情特征。方法采用数据挖掘方法,由国家疾病监测信息报告管理系统获得全人群、学生肺结核报告发病例数数据,根据中国统计年鉴统计在校学生人数,两者结合共同计算全人群、学生肺结核报告发病率。由结核病管理信息系统获取全人群、学生登记肺结核患者人口学特征、诊断分类及预后数据。由国家突发公共卫生事件管理信息系统获取结核病突发事件报告信息。采用上述数据对比分析在校学生肺结核疫情特征。结果2011年全人群肺结核报告发病率为71.09/10万(953 275/1 340 909 996),在校学生肺结核报告发病率为20.16/10万(41 608/206 339 584)。山东省在校学生肺结核报告发病率最低,为10.54/10万（1508/14 300 995）,西藏的在校学生肺结核报告发病率最高,为66.24/10万（350/528 389）。2011年登记学生患者的涂阳比率为30.59%（12 193/39 853）,低于全人群患者涂阳比率的46.82%(423 830/905 344),差异有统计学意义（χ²＝3542.85,P<0.01）。学生初治涂阳患者2个月末痰菌转阴率（97.37%,11 310/11 616）及治愈率（95.56%,11 278/11 802）均高于全人群患者（93.83%,353 729/377 005;93.98%,353 238/375 859）,差异均有统计学意义（χ²值分别为247.70和50.79,P值均<0.01）。 结论 2011年中国在校学生肺结核报告发病率约为全人群报告发病率的1/3,学生登记涂阳肺结核患者比率低,而学生初治涂阳患者治愈率较高,学校结核病控制仍需进一步加强。     

The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease

The acute chest syndrome (ACS), a pneumonia-like illness in sickle cell patients, is one of the most frequent causes of their morbidity and hospitalizations. Repeated ACS events may predict the development of chronic lung disease. ACS is reported as a frequent cause of death in these patients. We examine here the incidence and risk factors of ACS in 3,751 patients with sickle cell disease who were observed prospectively for at least 2 years (19,867 patient-years [pt-yrs]) as part of a multicenter national study group. The ACS, defined by a new pulmonary infiltrate on x-ray, occurred at least once in 1,085 patients (2,100 events). ACS incidence was higher in patients with homozygous sickle cell disease (SS; 12.8/100 pt-yrs) and in patients with sickle cell-beta(0) -thalassemic (9.4/100 pt-yrs), and lower in patients with hemoglobin (Hb) SC disease (5.2/100 pt-yrs) and patients with sickle cell-beta(+) thalassemia (3.9/100 pt-yrs). alpha-Thalassemia did not affect the rate of ACS incidence in SS patients. Within each Hb type the incidence was strongly but inversely related to age, being highest in children 2 to 4 years of age (25.3/100 pt-yrs in SS) and decreasing gradually to its lowest value in adults (8.8/100 pt-yrs in SS). In SS children (< 10 years of age), we documented an age-related within- person reduction in ACS attack rates. Adults with a higher ACS rate had a higher rate of mortality (from all causes) than those with low ACS rates. This increased rate of mortality might also have contributed to the decline in ACS rate with age. In multivariate analysis, other factors affecting incidence in SS patients were degree of anemia (lower ACS rates in patients with lower steady-state Hb levels) and fetal Hb (lower rates in patients with high fetal Hb). There was also a positive association between ACS rate and steady-state leukocyte count. The relationship of ACS rate to higher steady-state Hb levels in SS patients is unexplained but might be caused by increased blood viscosity.     

Short-term safety and pharmacodynamics of amdoxovir in HIV-infected patients

OBJECTIVES: To evaluate the pharmacodynamics and safety of escalating doses of amdoxovir (DAPD) monotherapy administered to treatment-naive and experienced HIV-1-infected patients over 15 days. DESIGN: Ninety patients with plasma HIV-1 RNA levels between 5000 and 250,000 copies/ml were randomized to DAPD 25, 100, 200, 300 or 500 mg twice daily or 600 mg once daily monotherapy [antiretroviral therapy (ART)-naive and ART-experienced] or to add DAPD 300 or 500 mg twice daily to existing ART. After 15 days of dosing, patients were followed for an additional 7 days. METHODS: Antiviral activity was compared between treatment arms using log10 HIV-1 RNA based on average area under the curve minus baseline to day 15. Safety and tolerability was analyzed by incidence of grade 1 to 4 clinical and laboratory adverse events. RESULTS: In ART-naive patients receiving short-term DAPD monotherapy, a median reduction in plasma HIV-1 RNA of 1.5 log10 copies/ml at the highest doses was observed. In ART-experienced patients, the reduction in viral load observed at each dose was less than that observed in treatment-naive patients (reduction of 0.7 log10 at 500 mg twice daily). The incidence of adverse events was similar across groups with the majority of adverse events reported as mild or moderate in severity. Steady-state plasma concentrations of DAPD and dioxolane guanosine followed linear kinetics. CONCLUSIONS: DAPD was well tolerated and produced antiviral activity in treatment-naive and in some treatment-experienced patients. In ART-experienced patients, the antiviral activity was significant in those with no thymidine-analogue mutations and higher baseline CD4+ cell counts.     

A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia

Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony- stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of > or = 1.5 x 10(9)/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events.     

Surveillance for Barrett's oesophagus: results from a programme in Northern Ireland

BACKGROUND: The reported incidence of adenocarcinoma in patients with Barrett's oesophagus in surveillance programmes varies widely. Great Britain has one of the highest incidence rates of this cancer in the world, but there are no data from Ireland reporting its incidence in patients with Barrett's oesophagus undergoing surveillance. We carried out a study of all such patients at a large District General Hospital in Northern Ireland. METHODS: A retrospective review of all patients with Barrett's oesophagus from January 1986 to March 2004 at Altnagelvin Area Hospital, Derry, Northern Ireland was performed. Barrett's oesophagus was defined as specialized intestinal metaplasia present in the tubular oesophagus. RESULTS: A total of 277 patients had Barrett's oesophagus. Twenty-one patients had adenocarcinoma and two patients had high-grade dysplasia at initial endoscopy and were excluded. Of the remaining 254 patients, 178 were entered into the surveillance programme (127 men, 51 women). The average follow-up period was 3.4 years, resulting in 613 patient-years of follow-up. Three patients developed adenocarcinoma, an incidence of 1/204 patient-years of follow-up. Two of the three patients had early-stage (T1 or T2) cancers detected and are alive and well. A total of 429 surveillance endoscopies were performed, and a marked year-on-year increase in the workload generated as a result of the surveillance programme was observed. CONCLUSIONS: The incidence of adenocarcinoma in patients in Northern Ireland was similar to the incidence reported by other large institutions. Clinical benefit is suggested but is not certain from these data, because of biases that affect surveillance programmes. Large multicentre studies are required to determine whether surveillance is beneficial.     

沙库巴曲缬沙坦在低收缩压心力衰竭患者中的临床研究

目的 探究沙库巴曲缬沙坦在低收缩压（90~100） mmHg心力衰竭患者中的耐受剂量、治疗效果和安全性。 方法 选取2018年12月~2019年12月就诊于空军军医大学西京医院心内科的心衰患者116例,患者收缩压（90~100）mmHg,随机分为对照组和试验组。对照组在基础治疗上加用缬沙坦,起始剂量20 mg,1次/d;试验组在基础治疗上加用沙库巴曲缬沙坦,起始剂量25 mg,2次/d;接受过ACEI或ARB治疗的患者需停药36 h进行药物洗脱,两组患者治疗开始后每周电话随访血压情况,密切检测不良反应,治疗6个月后评估相关指标。 结果 治疗6个月后,沙库巴曲缬沙坦显著改善患者NYHA心功能分级、左室射血分数（LVEF）、N末端B型利钠肽原(NT-proBNP)、6分钟步行距离(6MWD)、明尼苏达心衰量表评分（MHFQL）等指标（均P<0.05）,且改善程度优于对照组（均P<0.05）。两组心血管不良事件和药物相关不良事件发生率无统计学差异。 结论 收缩压（90~100）mmHg的心衰患者持续接受沙库巴曲缬沙坦滴定治疗能够显著改善心脏功能和生活质量,且改善程度优于缬沙坦。     

Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT (treating to new targets) study.

OBJECTIVE: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. BACKGROUND: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. METHODS: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. RESULTS: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. CONCLUSIONS: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).