Estimated research and development costs of rotavirus vaccines

Diseases like rotavirus afflict both upper- and lower-income countries, but most serious illnesses and deaths occur among the latter. It is a vital public health issue that vaccines for these types of global diseases can recover research and development (R&D) costs from high-priced markets quickly so that manufacturers can offer affordable prices to lower-income nations. Cost recovery depends on how high R&D costs are, and this study attempts to replace high, unverified estimates with lower, more verifiable estimates for two new vaccines, RotaTeq (Merck) and Rotarix (GlaxoSmithKline or GSK), based on detailed searches of public information and follow-up interviews with senior informants. We also offer a new perspective on “cost of capital” as a claim for recovery from public bodies. Our estimates suggest that companies can recover all fixed costs quickly from affluent markets and thus can offer these vaccines to lower-income countries at prices they can afford. Better vaccines are a shared project between companies and public health agencies; greater transparency and consistency in reporting of R&D costs is needed so that fair prices can be established.     

Depressive Symptoms Among HIV Positive Men: Life Stress,Coping, and Social Support1

The significance of life stress, coping, and social support was examined in relation to depressive symptomatology in a sample of 160 asymptomatic and mildly symptomatic HIV-antibody-positive (HIV+) men. The participants (mean age = 32 years) were interviewed about the life stress that they had experienced in the previous 6     

Chronic bronchitis in textile workers

BACKGROUND: Exposure to cotton is known to produce a specific occupational disease known as byssinosis. A large population of textile workers was investigated to determine whether such exposure was also associated with chronic bronchitis once other possible aetiological factors had been accounted for. METHODS: A total of 2991 workers were investigated for the presence of symptoms compatible with chronic bronchitis. An MRC adapted respiratory questionnaire and MRC definition of chronic bronchitis were used for diagnostic labelling. Current and lifetime exposure to dust was estimated by personal and work area sampling, and the use of records of retrospective dust levels previously measured over the preceding 10 years. Airborne endotoxin exposure was measured using a quantitative turbidometric assay. Lung function tests were performed to measure forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A control group of workers exposed to man-made fibre textiles was identified. The comparative prevalence of chronic bronchitis in the two populations was assessed, allowing for sex, age, smoking habit, and ethnic origin. Two case referent studies were also performed; cases of chronic bronchitis were separately matched with controls from the cotton and control populations to determine the effect of the symptomatic state on lung function. RESULTS: After controlling for smoking (pack years), workers in a cotton environment were significantly more likely to suffer from chronic bronchitis and this was most marked in workers over 45 years of age (odds ratio 2.51 (CI 1.3 to 4.9); p < 0.01). Regression analysis of all possible influencing parameters showed that cumulative exposure to cotton dust was significantly associated with chronic bronchitis after the effects of age, sex, smoking, and ethnic group were accounted for (p < 0.0005). In the intra-cotton population case control study a diagnosis of chronic bronchitis was associated with a small decrement in lung function compared with controls: percentage predicted FEV1 in cases 81.4% (95% CI 78.3 to 84.6), controls 86.7% (84.9 to 88.5); FVC in cases 89.9% (95% CI 87.0 to 92.9), controls 94.6% (92.8 to 96.4). After controlling for cumulative past exposure and pack years of smoking the effect of the diagnostic state remained significant for both FEV1 (p < 0.01) and FVC (p < 0.05). CONCLUSIONS: Chronic bronchitis is more prevalent in cotton workers than in those working with man-made fibre and exposure is additive to the effect of smoking. The diagnosis of chronic bronchitis is associated with a small but significant decrement in lung function.


     

Homogeneously staining region in anthracycline-resistant HL-60/AR cells not associated with MDR1 amplification.

Anthracycline-resistant HL-60/AR cells and their drug-sensitive HL-60/S counterparts were characterized by karyotypic analysis and examined for the overexpression of DNA and mRNA sequences coding for P-glycoprotein (Pgp). The HL-60/S cells were karyotypically stable over a 5-year period of study (1986-1991), except for an additional small Giemsa-positive band noted at 7q22 in cultures harvested in 1987, but not in 1986. This change did not affect drug sensitivity. The drug-resistant HL-60/AR cells examined in 1986, 1987, and 1991 demonstrated a very stable karyotype. The most striking feature was a large homogeneously staining region in the long arm of chromosome 7 (7q11.2), and translocation of the remainder of the long arm to another centromere. Other changes in the HL-60/AR cells included inversion in 9q, partial deletion of the short arm of chromosome 10p, addition of material to the p arm of der(16), loss of chromosome 22, and the appearance of a new marker chromosome. Both HL-60/S and the HL-60/AR cells were found not to amplify DNA or mRNA sequences coding for the Pgp. Thus, although the HL-60/AR cells possess the classical multidrug resistance phenotype and demonstrate a homogeneously staining region near the region of the MDR1 gene, their resistance is due to mechanisms other than those coded for by MDR1.     

Clonal chromosomal abnormalities in cutaneous T-cell lymphoma

Chromosome analysis from stimulated and unstimulated lymphocytes of blood, skin, and lymph nodes demonstrated a clonal chromosomal abnormality in eight of 46 patients with cutaneous T-cell lymphoma (CTCL). Nonclonal abnormalities were found in nine other patients. Unstimulated lymph node cultures identified the highest proportion of clonal changes. Clonal changes were found most often in patients with advanced disease, and in patients who tested positive with a monoclonal antibody previously shown to detect the T-cells involved in CTCL. Analysis of the eight abnormal clones and seven others found before or since this consecutive series showed that identifiable changes involving the known sites of T-cell receptor genes on chromosomes #7 and #14 were not usually present. An association between CTCL and chromosome rearrangements of chromosome #10 is suggested both from our cases and those found in the literature. This observation is of interest because this chromosome contains the gene for the interleukin-2 receptor.     

The uptake and costs of guidelines for stroke in a district of southern England.

STUDY OBJECTIVE: To assess the impact of guidelines for stroke management on the utilisation of services by patients and the cost consequences of implementation. DESIGN: Prospective audit. SETTING: District health authority in southern England. PATIENTS: A total of 468 live non-comatose stroke patients registered between November 1991 and May 1993. MAIN OUTCOME MEASURES: A comparison between the three, six month periods for investigations performed and rehabilitation received and their associated costs. RESULTS: The appropriateness of the use of investigations improved over time to between 88 and 92% except for computed tomography (CT) (24%). Younger, more severely impaired patients in a medical bed were more likely to have CT. Overall levels of rehabilitation were low. There was no change in use of physiotherapy (61% to 63%), a significant increase in occupational therapy (26% to 39%) and a non significant change in speech therapy (34% to 25%) over time. Guideline introduction caused a modest 23 Pounds increase in costs per patient in the 2nd six months and 41 Pounds in the 3rd six months but this sum could rise to 430 Pounds per patient if full implementation of the guidelines occurred which is still only around 13% of the costs of nursing care while in hospital. CONCLUSIONS: This 18 month aduit shows only modest changes in practice compared with guidelines, and overall levels of rehabilitation were low. The costs of full implementation seem considerable, but in fact constitute only a small proportion of nursing care costs.     

Telomerase activity in prognostic histopathologic features of melanoma.

BACKGROUND: Telomerase activity (TA) is believed to play a role in the regulation of senescence and to limit the number of cell divisions. The deregulation of telomerase appears to contribute to oncogenesis and the formation of immortal cell lines. As a result, it is believed that it could be used as a prognostic marker in melanoma. METHODS: TA was assayed by the polymerase chain reaction PCR-ELISA-based telomeric repeat amplification protocol (TRAP assay). One hundred and eight samples were distributed in four histological groups: 30 samples from primary cutaneous melanomas, 24 from peritumoural skin sites, 28 from benign melanocytic lesions, and 26 from normal skin sites as a control. RESULTS: TA was different among the four tested groups (Kruskall-Wallis test p<0.001), and increasing values of TA were observed progressing from normal skin to benign and then to malignant lesions. Among melanoma samples, there was a significant association between TA and ulceration (p=0.025), TA and vascular invasion (p=0.018) and TA and mitotic rate (p=0.029) (Mann-Whitney test). A linear regression analysis showed significant associations between the increase of TA with Breslow thickness (p=0.004) and the presence of satellites (p=0.002). CONCLUSIONS: We observed that TA had increased from control skin to peritumoural skin, and then to benign melanocytic lesions and finally to melanoma, suggesting tumour progression. TA showed higher values in the presence of some important histopathologic parameters related to poor prognosis in cutaneous melanoma such as ulceration, vascular invasion, satellites, high rates of mitosis, and in thicker tumours.     

肺栓塞疑似病人咳血的原因

当病人出现咳血、胸膜痛等症状，一般都会诊断为肺栓塞。现在有一种趋势就是为了不耽误病人的治疗，在诊断阶段还没有彻底的检查就开始治疗。通常早期使用肝素来减少可疑为肺栓塞病人的死亡率和发病率。然而，如道其它一些并不常见的咳血的原因也非常重要。