Rapid cancer diagnosis for patients with vague symptoms: a cost-effectiveness study.

BACKGROUND: A pilot rapid diagnosis centre (RDC) allows GPs within targeted clusters to refer adults with vague and/or non-specific symptoms suspicious of cancer, who do not meet criteria for referral under an urgent suspected cancer (USC) pathway, to a multidisciplinary RDC clinic where they are seen within 1 week. AIM: To explore the cost-effectiveness of the RDC compared with standard clinical practice. DESIGN AND SETTING: Cost-effectiveness modelling using routine data from Neath Port Talbot Hospital, Wales. METHOD: Discrete-event simulation modelled a cohort of 1000 patients from referral to radiological diagnosis based on routine RDC and hospital data. Control patients were those referred to a USC pathway but then downgraded. Published sources provided estimates of patient quality of life (QoL) and pre-diagnosis anxiety. The model calculates time to diagnosis, costs, and quality-adjusted life years (QALYs), and estimates the probability of the RDC being a cost-effective strategy. RESULTS: The RDC reduces mean time to diagnosis from 84.2 days in usual care to 5.9 days if a diagnosis is made at clinic, or 40.8 days if further investigations are booked during RDC. RDC provision is the superior strategy (that is, less costly and more effective) compared with standard clinical practice when run near or at full capacity. However, it is not cost-effective if capacity utilisation drops below 80%. CONCLUSION: An RDC for patients presenting with vague or non-specific symptoms suspicious of cancer in primary care reduces time to diagnosis and provides excellent value for money if run at ≥80% capacity.

High throughput quantitative analysis of the ß-lyase sulfur mustard metabolite, 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] in urine via high performance liquid chromatography tandem mass spectrometry.

Sulfur Mustard (HD) has a 100year history of use as a chemical warfare agent and recent events in the Middle East are causing it to once again be a potential concern. We report a new high-throughput method for the determination of HD exposure by the analysis of the ß-lyase metabolite 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE) in human urine. This method features a hydrogen peroxide (H2O2) oxidative conversion of the ß-lyase metabolites to SBMSE, followed by sample extraction and concentration using solid phase extraction in 96-well plate format. Subsequent high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analysis gave linear quantitation over a calibration range of 0.1-100ng/mL, with a method detection limit of 0.03ng/mL. Liquid chromatographic separation was achieved using a hydrophilic interaction liquid chromatography (HILIC) column with an analyte retention time of 0.9min and method time of 1.5min (cycle time=2.0min). Users of this method could prepare and analyze approximately 650 samples in 24h which would be important for an emergency response.

The effect of HMPA on the reactivity of epoxides, aziridines, and alkyl halides with organolithium reagents.

A kinetic study of the effect of added HMPA cosolvent on the reaction of 2-lithio-1,3-dithiane (1), bis(phenylthio)methyllithium (2), and bis(3,5-bistrifluoromethylphenylthio)methyllithium (3) with methyloxirane (propylene oxide), N-tosyl-2-methylaziridine, and the several alkyl halides (BuCl, BuBr, BuI, allyl chloride) was carried out. Widely varied rate effects of HMPA on these SN2 substitutions were observed, ranging from >108 rate increases for 1 and butyl chloride to >103 rate decreases for 3 and methyloxirane. These reactions appear to go through separated ion pair intermediates, so a key effect is the ease of ion pair separation of the lithium reagent (3 > 2 > 1). Because 3 is already almost fully separated in THF, HMPA has no effect on the rate of halide substitution, but a large reduction is observed with the epoxide as substrate, a consequence of strong lithium assistance to the ring opening which is suppressed when excess HMPA is present. When ion pair separation is difficult (1), modest rate increases (104) are seen for epoxide opening, but very large increases are seen for aziridine (106) and alkyl halide reactions (108), for which lithium assistance is much less important. Reagent 2 shows more complicated behavior in reaction with the epoxide: 1-2 equiv of HMPA causes a small rate increase, while larger amounts cause a large rate decrease. Here the rate-accelerating effects of SIP formation are more nearly balanced with the rate-retarding effects of suppression of lithium catalysis.