Treating osteoporosis: economic aspects of bisphosphonate therapy

Each year, fractures associated with osteoporosis place a significant burden on healthcare spending and result in unnecessary morbidity, mortality and reductions in quality of life for individual patients. Several treatments are available that can improve the course of this chronic bone disease, and lead to significant reductions in fractures. Bisphosphonates have proven efficacy, are widely available and currently recommended as the first-line of therapy for osteoporosis in many practice guidelines. In addition to demonstrating clinical benefit, from a health-policy perspective, the economic benefits regarding prevention and treatment must be established. In recent years, several health economic studies have examined the cost-effectiveness and cost-utility of bisphosphonates in various patient groups. This paper reviews a number of these studies regarding the economic benefits of treating osteoporosis with bisphosphonates and considers for whom prevention and/or treatment is most warranted.     

Comparison of allogeneic stem cell transplantation,high-dose cytarabine,and autologous peripheral stem cell transplantation as postremission treatment in patients with de novo acute myelogenous leukemia

BACKGROUND: Postremission therapy is critical in maintaining complete remission (CR) in patients with de novo acute myelogenous leukemia (AML). The aim of this trial was to compare allogeneic stem cell transplantation (SCT), high-dose cytarabine (ara-C; HiDAC), and autologous SCT as postremission therapy in patients with de novo AML. METHODS: One hundred twenty patients age 相似文献   

Mechanisms of relapse in acute leukaemia: involvement of p53 mutated subclones in disease progression in acute lymphoblastic leukaemia

Mutations of the p53 tumour suppressor gene are infrequent at presentation of both acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL), being found in between 5-10% of AML and 2-3% of ALL. Here we have studied the frequency of detection of p53 mutations at relapse of both AML and B-precursor ALL. In those patients with detectable mutations at relapse we investigated whether the mutation was detectable at presentation and was thus an early initiating event or whether it had arisen as a late event associated with relapse. Bone marrow samples from 55 adults and children with relapsed AML (n = 41) or ALL (n = 14) were analysed for p53 gene alterations by direct sequencing of exons 5-9. For samples where a p53 mutation was found at relapse, analysis of presentation samples was carried out by direct sequencing of the exon involved, or by allele-specific polymerase chain reaction (PCR) if the mutation could not be detected using direct sequencing. A p53 mutated gene was found at relapse in seven out of 55 cases. The frequency was higher in relapsed ALL (four out of 14 cases; 28.6%) compared to AML (three out of 41 cases; 7.3%). In five out of the seven cases presentation samples were available to study for the presence of the mutation. In two out of two AML patients the p53 mutation was detectable in the presentation sample by direct sequencing. In three ALL patients analysis of presentation material by direct sequencing showed a small mutant peak in one case, the other two being negative despite the sample analysed containing > 90% blast cells. However in both of these patients, the presence of p53 mutation was confirmed in the presentation sample using allele-specific PCR. In one of these patients the emergence of a subclone at relapse was confirmed by clonality analysis using IgH fingerprinting. Our results confirm that in ALL p53 mutations are present in a proportion of patients at relapse. Furthermore cells carrying the mutation are detectable at presentation in a minor clone suggesting that p53 mutations in ALL may be a mechanism contributing to disease relapse.     

Washing with or without chloramphenicol in the treatment of peritonitis: a prospective, clinical trial

One hundred one suitable patients with peritonitis of diverse origin were randomized into two groups. In each patient in group 1 (50 patients), the abdomen was washed after the appropriate surgical procedure with normal saline solution, and 2 gm chloramphenicol was introduced before abdominal closure; in each patient in group 2 (51 patients), the abdomen was washed as in group 1, but chloramphenicol was not instilled. All patients were given 1 gm chloramphenicol intramuscularly either preoperatively or intraoperatively and 3 gm daily for 3 days. Chloramphenicol was selected on the basis of its activity against aerobic and anaerobic bacteria and its demonstrated stimulating effect on peritoneal macrophages in vitro. All explorations were done through the midline, and the skin and subcutaneous tissues were closed secondarily 3 to 4 days after operation. No drains were used. The two groups were roughly comparable, but results were significantly better for all parameters studied in patients receiving chloramphenicol locally. Blood dyscrasias were not observed. It is suggested that the combination of washing and local antibiotics is superior to washing alone; in addition to its parenteral administration, chloramphenicol is of considerable value if instilled in the area of peritonitis after washing; and besides its bacteriostatic action, chloramphenicol may have a local stimulating effect on peritoneal defenses and may therefore be the drug of choice for local use in generalized peritonitis.     

Biliary calculi fragmentation by a 308 nm excimer laser: a preliminary study

The use of a 308-nm XeCl excimer laser for biliary stone fragmentation is reported. The 130-nsec laser pulses are delivered via UV grade fused silica fibers to the target stones immersed in normal saline solution and placed in direct contact with the fiber. Sixty biliary calculi, 20 cholesterol and 40 pigment, were fragmented in vitro. The energy delivered per unit mass of the stone is kept constant at 50 mJ/mg. The effect of laser repetition rate, energy fluence, and fiber core size on stone fragmentation was studied. Fragmentation thresholds for a variety of biliary calculi of known composition were measured. It was found that higher fragmentation efficiency was obtained with larger fluence, lower repetition rate, and fiber of larger core. Our study indicates that the 308-nm excimer laser may be effective as a laser lithotriptor with low threshold and good efficiency for biliary stone fragmentation.     

Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10.A recombinant mouse strains

Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.     

青少年和成年人无症状阻生智齿干预措施的疗效评价

目的评价在青少年和成人中拔除与保留无症状阻生智齿的效果.方法计算机检索Cochrane口腔健康组资料库(至2004年8月4日),Cochrane中心临床对照试验资料库(CENTRAL),Ovid-MEDLINE(1966～2004年8月4日),PubMed(1966～2004年8月4日)和EMBASE(1974～2004年8月4日).检索无语种限制.同时对主要相关杂志进行手检,并尽力获取正在进行和未发表的研究.纳入比较预防性拔除与保留阻生智齿效果的全部随机对照或临床对照研究.由3位作者分别独立评价所检出文献的相关性、真实性并提取数据,如有不确定性,联系作者以获取关于随机和失访的更多信息.对所有试验均进行了质量评价.结果共纳入3个研究,其中2个已完成的随机对照试验评价了青少年预防性拔除智齿对切牙拥挤的影响,另1个随机对照试验正在进行,但研究者不能提供任何资料,他们准备近期发表文章,如是,其资料将被纳入本评价的更新中.已完成的2个研究结局判断指标不同,不能进行数据合并.结论没有证据支持或反对常规预防性拔除成年人无症状阻生智齿,有一些可靠的证据表明在青少年预防性拔除阻生智齿既不能减少也不能预防切牙拥挤.     

Does Muscle Atrophy and Fatty Infiltration Plateau or Persist in Chronic Spinal Cord Injury?

Atrophy and fatty infiltration of lower extremity muscle after spinal cord injury (SCI) predisposes individuals to metabolic syndrome and related diabetes and cardiovascular disease. The objective of this study was to prospectively measure changes in muscle atrophy and fat content of distal lower extremity muscles and explore related factors in a cohort of adults with chronic SCI and diverse impairments. Muscle cross-sectional area and density were calculated from peripheral quantitative computed tomography scans of the 66% site of the calf from 70 participants with chronic SCI (50 male, mean age 49 years, C2-T12, American Spinal Injury Association Impairment Scale A-D) at study enrollment and annually for 2 years. Mixed-model repeated measures analysis of variance (rANOVA) examined longitudinal changes in muscle area and density, and regression analyses explored factors related to muscle changes using 16 potential correlates selected a priori. A high degree of individual variation in muscle area and density change was observed over 2 years (range: 8.5 to???22.6?cm²; 6.4 to??8.6?mg/cm³). Repeated measures analysis of variance revealed significant reductions in muscle area (estimated mean difference [95% confidence intervals] ?1.76 [?3.29?to ?0.23]) cm², p?=?0.025) and density (?1.04 [?1.94 to??0.14] mg/cm³, p?<?0.024); however, changes in area were not significant with outliers removed. Regression analyses explained a small proportion of the variability in muscle density change; however, none of the preselected variables were significantly related to changes in muscle density after post hoc sensitivity analyses. Lower extremity muscle size and fat content may not reach a “steady-state” after chronic SCI. Progressive atrophy and fatty infiltration of lower extremity muscle may have adverse implications for metabolic syndrome and cardiovascular disease risk and related mortality after chronic SCI.     

Haemostatic profile of full-term, healthy, small for gestational age neonates

Background

Small for Gestational Age (SGA) neonates often appear with haemostatic alterations, principally due to hepatic dysfunction that results from chronic intrauterine hypoxia. Polycythaemia and thrombocytopenia are common findings in this neonatal population.

Study design

We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born full term [gestational age (G.A.) > 37 weeks]. Study population consisted of 188 healthy newborns, 90 of whom were SGA (62 females and 28 males), while the rest were the control group (44 females and 54 males). Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test was used to compare the differences between the values of haemostatic parameters.

Results

Statistical analysis revealed a significant prolongation in PT, INR, elevated levels of tPA (p < 0.015, 0.01 and 0.002 respectively) and a decrease in the values of XII and free protein S (p < 0.045 and 0.007 respectively) in SGA full term neonates. The two groups had similar demographic characteristics (except birth weight), without significant differences in the values of other haemostatic parameters.

Conclusions

Despite of statistically significant differences in PT, INR, values of tPA, XII and free protein S, levels of haemostatic factors range within laboratory references for healthy full term newborns. These findings were not accompanied with clinical manifestations of altered haemostasis.