A randomised controlled trial to measure the effect of chest pain unit care upon anxiety,depression, and health-related quality of life [ISRCTN85078221]

Background  

The chest pain unit (CPU) has been developed to provide a rapid and accurate diagnostic assessment for patients attending hospital with acute, undifferentiated chest pain. We aimed to measure the effect of CPU assessment upon psychological symptoms and health-related quality of life.     

Impact of the introduction of fee for service payments on types of minor surgical procedures undertaken by general practitioners: observational study

The 1990 general practitioners (GPs) contract introduced item of service payment for minor surgery, payable for six categories of procedure. Early review showed no substitution of cheaper procedures for more expensive treatments. Detailed payment data from six Health Authorities for the period 1993-2000 show an 11 per cent increase in claims, largely accounted for by the rise in cautery, incorporating cryotherapy. Cryotherapy is no more effective at treating warts than cheap commercially available products, but is quite profitable for GPs. This is yet another example of item of service payment distorting treatment priorities. The new GP contract, and the initiative to develop GPs with special interests in dermatology and minor surgery, will allow primary care trusts to develop minor surgery undertaken by appropriately skilled and experienced GPs, and which reflects the needs of the population.     

Effects of data limitations when modeling fatal occupational injury rates

BACKGROUND: Occupational fatal injury rate studies are often based upon uncertain and variable data. The numerator in rate calculations is often obtained from surveillance systems that can understate the true number of deaths. Worker-years, the denominator in many occupational rate calculations, are frequently estimated from sources that exhibit different amounts of variability. METHODS: Effects of these data limitations on analyses of trends in occupational fatal injuries were studied using computer simulation. Fatality counts were generated assuming an undercount. Employment estimates were produced using two different strategies, reflecting either frequent but variable measurements or infrequent, precise estimates with interpolated estimates for intervening years. Poisson regression models were fit to the generated data. A range of empirically motivated fatality rate and employment parameters were studied. RESULTS: Undercounting fatalities resulted in biased estimation of the intercept in the Poisson regression model. Relative bias in the trend estimate was near zero for most situations, but increased when a change in fatality undercounting over time was present. Biases for both the intercept and trend were larger when small employment populations were present. Denominator options resulted in similar rate and trend estimates, except where the interpolated method did not capture true trends in employment. CONCLUSIONS: Data quality issues such as consistency of conditions throughout the study period and the size of population being studied affect the size of the bias in parameter estimation.     

Polyacetal-diethylstilboestrol: a polymeric drug designed for pH-triggered activation

Those polymer anticancer-drug conjugates currently undergoing clinical evaluation have a tripartite structure; a water-soluble polymer, an anticancer agent and a pendant linker. To simplify the construct it would be attractive to develop anticancer polymer therapeutics that contain the bioactive agent as an integral part of the polymer backbone. The aim of this study was to utilise the reaction between a divinyl ethers and diols, to synthesise polyacetals incorporating a drug with bis-hydroxyl functionality into the polymer backbone. Degradation of the polymer backbone in the acidic environment of the lysosome or the extracellular fluid of some tumours would then trigger drug release eliminating the need for a biodegradable linker. A tert-polymerisation approach was used to incorporate non-steroidal oestrogen diethylstilboestrol (DES) into the mainchain of water-soluble polyacetals synthesised using as co-monomer PEG of Mw 2900 or 3400 g/mol. When PEG2900 was used the resultant polymer had a Mw of 18,900 g/mol, a Mw/Mn of 1.9 and a DES loading 4.3 wt.%. With PEG3400 the polymer Mw was 43,000 g/mol, Mw/Mn=1.8 and it had a DES loading 4.7 wt.%. 1H-NMR confirmed the presence of two distinct sets of acetal peaks, which correspond to the two possible mainchain acetals; from PEG at 1.25-1.3(d) and 4.7-4.8(q) ppm and from DES at 1.55-1.6(d) and 5.4-5.5(q) ppm. These were consistent with the acetal signals observed for the non-water-soluble co-polymer DES: tri(ethylene glycol) divinyl ether (TEGDVE) (1 : 2, Mw=6859 g/mol, Mw/Mn=1.3). When evaluated in vitro, the DES-polyacetal displayed greater cytotoxicity than DES against human and murine tumour cell lines (IC50=48 and 420 microg/ml against MCF-7 human breast cancer cells and IC50=97 and 560 microg/ml against B16F10 murine melanoma cells, respectively). These polymers showed no significant haemolysis at concentrations up to 20 mg/ml confirming suitability for further in vivo evaluation. An enhanced rate of hydrolytic degradation of the polymer backbone was seen at pH 5.5, (65% trans-DES released in 96 h), compared to pH 7.4 (4% trans-DES released in 96 h). These bioresponsive DES-polyacetals tert-polymers are the first water-soluble anticancer polymeric drugs designed for acidic pH-triggered release of a drug incorporated into the polymer mainchain. Their in vitro characteristics suggest further in vivo evaluation is warranted.     

Relation of family history of prostate cancer to perceived vulnerability and screening behavior

Men with a positive family history of prostate cancer are known to be at increased risk for the disease; however, relatively little is known about their risk perceptions or screening behavior. To address these issues, the current study examined the relationship of family history of prostate cancer to perceived vulnerability of developing prostate cancer and prostate cancer screening practices. Participants were 83 men with a positive family history of prostate cancer and 83 men with a negative family history of prostate cancer. As predicted, men with a positive family history reported greater (p< or =0.05) perceived vulnerability of developing prostate cancer and stronger intentions to undergo screening (p< or =0.05). They also reported greater past performance of prostate-specific antigen screening and were more likely to request information about prostate cancer (p< or =0.05). Additional analyses indicated that perceived vulnerability mediated the relation between family history and intentions to undergo prostate cancer screening. Findings confirm the increased likelihood of men with a positive family history to undergo prostate cancer screening and suggest that heightened concerns about developing the disease are an important motivating factor.     

Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2

Angiopoietin-2 (Ang2) exhibits broad expression in the remodeling vasculature of human tumors but very limited expression in normal tissues, making it an attractive candidate target for antiangiogenic cancer therapy. To investigate the functional consequences of blocking Ang2 activity, we generated antibodies and peptide-Fc fusion proteins that potently and selectively neutralize the interaction between Ang2 and its receptor, Tie2. Systemic treatment of tumor-bearing mice with these Ang2-blocking agents resulted in tumor stasis, followed by elimination of all measurable tumor in a subset of animals. These effects were accompanied by reduced endothelial cell proliferation, consistent with an antiangiogenic therapeutic mechanism. Anti-Ang2 therapy also prevented VEGF-stimulated neovascularization in a rat corneal model of angiogenesis. These results imply that specific Ang2 inhibition may represent an effective antiangiogenic strategy for treating patients with solid tumors.     

Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program

A combined analysis of genome scans was performed for adult height in the NHLBI Family Blood Pressure Program. Height data were available on 6752 individuals. Linkage analysis was performed first separately for each of the eight ethnic groups in the four networks using the variance component method. To increase the power to detect the common genetic components affecting height for all the individuals, a linkage analysis was performed subsequently for the combined data set by pooling the average allele-sharing IBD () for all groups. By combining the data, we replicated evidence for a QTL influencing adult height on chromosome 7 (7q31) (LOD=2.46), which has been reported in two previous studies. Suggestive linkage (LOD>1) was found in another six regions in our combined analysis. Evidence for linkage for two of these regions (2p12, 20p11) has also been reported previously.