Early discharge for patients with exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

BACKGROUND: We have previously reported the use of a hospital based respiratory nurse service (Acute Respiratory Assessment Service, ARAS) to support home treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). A controlled trial was undertaken to compare early discharge with home treatment supported by respiratory nurses with conventional hospital management of patients admitted with exacerbations of COPD. METHODS: Patients with COPD admitted as emergencies were identified the next working day. They were eligible for inclusion in the study if the differential diagnosis included an exacerbation of COPD, but were excluded if other medical conditions or acidotic respiratory failure required inpatient investigation or management. Of 360 patients reviewed, 209 were being assessed for other active medical problems and were excluded, 33 potential participants were already involved in research studies and so were ineligible, and 37 did not wish to participate in the study. Eighty one patients were randomised to receive conventional inpatient care (n=40) or to planned early discharge the next working day (n=41). Those discharged early continued treatment at home under the supervision of specialist respiratory nurses. Outcome measures were readmission, additional hospital days, and deaths within 60 days of initial admission. Process measures included number of visits, duration of follow up by the respiratory nurse, and additional treatment provided to support early discharge. RESULTS: On an intention to treat basis, a policy of early discharge reduced inpatient stay from a mean of 6.1 (range 1-13) days with conventional management to 3.2 (1-16) days with an early discharge policy. Twelve patients (30% conventional management, 29.3% early discharge) were readmitted in each group giving a mean difference in readmission of 0.7% (95% CI of the difference -19.2 to 20.6). In the conventional management group readmitted patients spent a mean of 8.75 additional days in hospital compared with 7.83 days in the early discharge group, giving a mean difference of 0.92 days (95% CI of the difference -6.5 to 8.3). There were two deaths (5%) in the conventional management group and one (2.4%) in the early discharge group, a mean difference of 2.6% (95% CI of the difference -5.7 to 10.8). CONCLUSIONS: Patients with acute exacerbations of COPD uncomplicated by acidotic respiratory failure or other medical problems can be discharged home earlier than is current practice with support by visiting respiratory nurses. No difference was found in the subsequent need for readmission.     

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.     

Hormone replacement therapy with dydrogesterone and 17β-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up

Objective To assess serum lipid and lipoprotein concentrations and oral glucose tolerance in postmenopausal women treated with 17β-oestradiol (2 mg/day) and cyclical dydrogesterone (10 mg/day for 14 days per 28 day cycle).
Design A 24 month prospective study of 29 women acting as their own controls. On-treatment samples were taken during the combined (oestrogen–progestogen) phase of therapy.
Setting Metabolic research unit in London.
Population Postmenopausal women with no previous exposure to hormone replacement therapy attending a menopause clinic in a London hospital.
Methods Fasting serum sampling and oral glucose tolerance testing.
Main outcome measures Serum lipids and lipoprotein concentrations and plasma glucose, insulin and C-peptide responses to an oral glucose load.
Results Restricting the analysis to the 17 women who completed the study, no effect was seen on serum triglyceride concentrations. There was a mean fall of 5.9% (95% CI 1.2 to −13.0) in concentrations of serum total cholesterol, reflecting the balance of a 10.7% fall (95% CI 4.3 to −25.8) in low density lipoprotein cholesterol concentrations and a 16.3% increase (95% CI 7.3 to −25.3) in those of high density lipoproteins. Fasting glucose concentrations and glucose tolerance test responses were unchanged. Fasting insulin concentrations fell substantially (–41.6%, 95% CI −23.4 to −59.8) with falls also being seen in insulin responses to glucose. Fasting C-peptide concentrations increased by 36.2% (95% CI 9.17 to 63.3), with no consistent effect on C-peptide responses to glucose.
Conclusions Dydrogesterone did not appear to oppose the potentially beneficial effects of oestradiol on insulin or either low or high density lipoproteins, making the combination with 17β-oestradiol a potentially useful option for postmenopausal women particularly those at risk of cardiovascular disease or diabetes mellitus.     

Identification of malnutrition in children with cerebral palsy: poor performance of weight-for-height centiles

This study aims to evaluate the use of the United States National Center for Health Statistics (NCHS) weight-for-height centiles (WHC) in screening children with cerebral palsy (CP) for depleted body fat and to identify an alternate screening method. Growth data from 276 children aged from 3 to 12 years with CP were analyzed retrospectively. Height or a proxy for height, mid-upper arm circumference, weight, and skinfold thicknesses were recorded. Mid-upper arm fat area was calculated for each participant. The sensitivities and specificities of WHC and a number of alternative anthropometric screening methods for identifying participants with severely depleted fat stores were determined. WHC <10th centile failed to identify 45% of children with severely depleted fat stores. Triceps skinfold thickness <10th centile identified 96% of malnourished children. WHC standards lack adequate sensitivity for identification of severely depleted fat stores in children with CP. Use of triceps skinfold thickness, using cut-off value of <10th centile for age and sex, is recommended to screen for suboptimal fat stores in children with CP.     

广州、南宁市汽车安全带佩戴状况调查

目的 调查广州、南宁市汽车安全带佩戴情况。方法 采用随机抽样的方法，按照3种不同类型的道路选取观察点，在4个不同时间段对目标车辆进行观察。结果 司机安全带正确佩戴率南宁市（63．8％）高于广州市（49．3％），而不正确佩戴率广州市（22．9％）高于南宁市（8．1％）；乘客安全带佩戴率广州市高于南宁市，包括正确佩戴率和不正确佩戴率；安全带佩戴率受道路类型、时间、性别和车型等的影响，正确佩戴率高速路高于其他道路、白天高于晚上、女性高于男性、小型汽车高于其他车型，不正确佩戴率工作151高于周末。结论 广州市男性出租车司机安全带不正确佩戴率高；两地区周末和晚上佩戴安全带率较低，应加大执法力度；加强宣传教育，提高司乘人员佩戴安全带的意识。     

The HOPA Gene Dodecamer Duplication Is Not a Significant Etiological Factor in Autism

A recent study has suggested that a dodecamer duplication in the HOPA gene in Xq13 may occur in a significant portion of male patients with autism. We have determined the incidence of this duplication in 202 patients from the South Carolina Autism Study. The incidence of the duplication was not significantly different between patients and controls. Three of the female patients inherited the duplication from nonautistic fathers. In addition, there was no systematic skewing of X inactivation in the female patients with the duplication, or in nonautistic mothers and sisters with the duplication. These findings suggest that the dodecamer duplication in the HOPA gene does not play a significant role in the etiology of autism.     

The heart reinnervates after transplantation

Background. Whether cardiac reinnervation occurs after transplantation remains controversial. If reinnervation does occur, how sympathetic and parasympathetic efferent neurons do this remains unknown.

Methods. Power spectral analysis of heart rate variability was assessed for 1 year after cardiac autotransplantation in 9 dogs. After induction of anesthesia 13 months after transplantation, cardiac and intrinsic cardiac neuronal responses elicited by both electrical stimulation of parasympathetic or sympathetic efferent neurons and systemic or local coronary artery administration of nicotine (5 μg/kg), angiotensin II (0.75 μg/kg), and tyramine (1.2 μg/kg) were studied. The transmembrane electrical properties of intrinsic cardiac neurons were studied in vitro. Ventricular tissue catecholamine content, -tubulin expression, and β-adrenergic receptor density and affinity were studied. The presence of axons crossing suture lines was sought histologically.

Results. Nerves were identified crossing suture lines. Electrical or chemical (ie, nicotine or angiotensin II) activation of sympathetic efferent neurons enhanced cardiodynamics, as did tyramine. Stimulating vagal efferent preganglionic axons induced bradycardia in half of the dogs. Functional reinnervation did not correlate with specific power spectra derived from rate variability in the conscious state. Responding to nicotine and angiotensin II in situ, transplanted intrinsic cardiac neurons generated spontaneous activity. These neurons displayed nicotine-dependent synaptic inputs in vitro. Ventricular tissue had normal β-adrenergic receptor affinity and density but reduced catecholamine and -tubulin contents.

Conclusions. The intrinsic cardiac nervous system receives reduced input from extracardiac sympathetic efferent neurons after transplantation and inconsistent input from parasympathetic efferent preganglionic neurons. These heterogeneous neuronal inputs are not reflected in heart rate variability or ventricular β-adrenergic receptor function. Transplanted angiotensin II–sensitive intrinsic cardiac neurons exert greater cardiac control than do nicotine-sensitive ones. The intrinsic cardiac nervous system remodels itself after cardiac transplantation, and this indicates that direct assessment of extracardiac and intrinsic cardiac neuronal behavior is required to fully understand cardiac control after transplantation.     

Heparin octasaccharides inhibit angiogenesis in vivo.

BACKGROUND: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. RESULTS: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing > or =16 saccharide residues were investigated. CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin.     

‘At the moment it is just a couple of eccentrics doing it’: concordance in day‐to‐day practice

Objectives To assess the feasibility and acceptability of concordance in pharmacy practice through examination of communication between customers and pharmacists in two community pharmacies in consultations for over‐the‐counter medicines. Method A qualitative pilot study involving data drawn from six sources: audiotaped training session with all the pharmacists involved, observational field work in the pharmacies, audiotaped consultations with pharmacists and customers, debriefing interviews with pharmacists after the consultation, and semi‐structured interviews with customers a few days after their consultation. Setting Two community pharmacies that concentrate their services on medicine advice and dispensing, one in a deprived inner‐city area, the other in a more affluent suburban area of London. Key findings The pharmacists developed a personal understanding of concordance which informed their practice. Customers reported a high level of satisfaction with services they received from the respective pharmacists. Their accounts of the consultations verified the pharmacists' patient‐centredness in their day‐to‐day practice. Conclusion The implementation of a concordance model was possible through the development of a personalised, patient‐centred model which drew on the model of concordance but was adapted in accordance with both structural constraints as well as the personal style of the pharmacists involved.     

Pharmacist involvement in antimicrobial use at rural community hospitals in four Western states.

PURPOSE: Pharmacist involvement in antimicrobial use at small rural hospitals in four Western states was studied. METHODS: Surveys were mailed in July 2000 to hospitals with a daily patient census of <150 in Idaho, Nevada, Utah, and eastern Washington. RESULTS: Seventy-seven (77%) of 100 hospitals returned completed surveys. Only 5% of the hospitals had onsite pharmacists 24 hours per day. An onsite pharmacist was present for a median of 26 hours per week in hospitals without 24-hour pharmacist coverage (range, 0-116 hr/wk). Many hospitals (71%) had policies for monitoring or controlling antimicrobial use, but only 28% had a system capable of monitoring compliance with such policies. Few hospitals had systems for recommending changes in antimicrobial selection on the basis of susceptibility test results (27%) or for monitoring physician compliance with dosage recommendations by pharmacists (21%). Onsite pharmacist hours were significantly associated with pharmacists being involved in the initial ordering of antibiotics and providing active oversight of antimicrobial use. There was a negative correlation between onsite pharmacist hours and use of third-generation cephalosporins and carbapenems. CONCLUSION: A survey showed that rural hospital pharmacists in four Western states spent relatively little time monitoring and influencing antimicrobial prescribing.