Background . Initially the course of the 2009 swine flu pandemic was uncertain and impossible to predict with any confidence. An effective prospective data resource exists in the United Kingdom (UK) that could have been utilized to describe the scope and extent of the swine flu outbreak as it unfolded. We describe the 2009 swine flu outbreak in the UK as recorded daily by general practitioners and the potential use of this database for real-time tracking of flu outbreaks. Methods . Using the General Practice Research Database, a real-time general practice, electronic database, we estimated influenza incidence from July 1998 to September 2009 according to age, region, and calendar time. Results . From 1998 to2008, influenza outbreaks regularly occurred yearly from October to March, but did not typically occur from April to September until the swine flu outbreak began in April 2009. The weekly incidence rose gradually, peaking at the end of July, and the outbreak had largely dissipated by early September. Conclusions . The UK swine flu outbreak, recorded in real time by a large group of general practitioners, was mild and limited in time. Simultaneous online access seemed feasible and could have provided additional clinical-based evidence at an early planning stage of the outbreak.

Study Objective. To estimate the rate of suicide in patients taking montelukast.Design. Population-based cohort studyData Source. United Kingdom General Practice Research Database.Patients. A total of 23,500 patients who had received at least one prescription for montelukast in the cumulative data from February 1998-March 2007.Measurements and Main Results. Rate of suicide was to be calculated as number of suicides divided by person-time at risk. Person-time of montelukast exposure was accrued for each patient as a cumulative duration of all prescriptions. The 23,500 patients had received 252,593 prescriptions for montelukast, representing 21,050 person-years at risk for suicide. We then sought to identify all cases that had a computer-recorded diagnosis of suicide; however, no cases of suicide were found in patients exposed to montelukast during our time frame.Conclusion. The risk of suicide attributable to montelukast, if present at all, is extremely low in users.

Postprandial triglyceride-rich lipoproteins (TRL) exert proatherogentic effects at the arterial wall, including lipid deposition. Following consumption of a mixed meal (1,200 kcal), plasma-mediated cellular free cholesterol (FC) efflux, lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP) activities were determined in subjects (n = 12) displaying type IIB hyperlipidemia and compared with those in a normolipidemic control group (n = 14). The relative capacity of plasma to induce FC efflux from Fu5AH cells via the SR-BI receptor was significantly increased 4 It postprandially (+23%; P < 0.005) in the type IIB group, whereas it remained unchanged for postprandial plasma from normolipidemic subjects. LCAT activity was significantly elevated 2 It postprandially in both the IIB and control groups, (+46% and +36%, respectively; P < 0.005 vs. respective baseline value). In type IIB subjects, total cholesteryl ester (CE) mass transfer from HDL to total TRL [chylomicrons (CMs) + VLDL-1 + VLDL-2 + IDL] increased progressively from 15 +/- 2 mug CE/h/ml at baseline to 28 +/- 2 mug CE transferred/h/ml (+87%; P = 0.0004) at 4 h postprandially. CE transfer to CMs and VLDL,1 was preferentially stimulated (2.6-fold and 2.3-fold respectively) at 4 h in IIB subjects and occurred concomitantly, with elevation in mass and particle number of both CMs (2.3-fold) and VLDL-1 (1.3-fold). Furthermore, in type IIB subjects, CETP-mediated total CE flux over the 8 It postprandial period from HDL to potentially atherogenic TRL was significantly enhanced, and notably to VLDL-1 (32-fold elevation; P < 0.005), relative to control subjects. Such CE transfer flux was reflected in a significant postprandial increase in CE-TG ratio in both CMs and VLDL-1 in type IIB plasmas. In conclusion, HDL-CE is preferentially targeted to VLDL-1 via the action of CETP during alimentary lipemia, thereby favoring formation and accumulation of atherogenic CE-rich remnant particles.

Type IIB hyperlipidemia is associated with premature vascular disease, an atherogenic lipoprotein phenotype characterised by elevated levels of triglyceride-rich VLDL and small dense LDL, together with subnormal levels of HDL. The dose-dependent and independent effects of a potent HMGCoA reductase inhibitor, Atorvastatin, at daily doses of 10 and 40 mg, were evaluated on triglyceride-rich lipoprotein subclasses (VLDL-1, VLDL-2 and IDL), on the major LDL subclasses (light LDL, LDL-1+LDL-2, D: 1.019-1.029 g/ml; intermediate LDL, LDL-3, D: 1.029-1.039 g/ml and small dense LDL, LDL-4+LDL+5, D: 1.039-1.063 g/ml), on CETP-mediated cholesteryl ester transfer from HDL to apoB-containing lipoproteins, on phospholipid transfer protein activity and on plasma-mediated cellular cholesterol efflux in patients (n=10) displaying type IIB hyperlipidemia. Plasma concentrations of triglyceride-rich lipoprotein subclasses (TRL: VLDL-1, Sf 60-400; VLDL-2, Sf 20-60 and IDL, Sf 12-20) and of LDL (D: 1.019-1.063 g/ml) were markedly diminished after 6 weeks of statin treatment at 10 mg per day (-31 and -36%, respectively; P<0.002) and by 42 and 51%, respectively at the 40 mg per day dose. Increasing doses of atorvastatin progressively normalised both the quantitative and qualitative features of the LDL subclass profile, in which dense LDL predominated at baseline. Indeed, dense LDL levels were reduced by up to 57% at the 40-mg dose, leading to a shift in the peak of the density profile towards larger, buoyant LDL particles typical of normolipidemic subjects. In addition, marked reduction in numbers of apoB100-containing particle acceptors led to a 30% decrease (P<0.02) in CETP-mediated CE transfer from HDL. Finally, a significant dose-dependent statin-mediated elevation (+15% at 10 mg; P=0.0003 and +35% at 40 mg; P<0.0001 compared to baseline) in the capacity of plasma from type IIB subjects to mediate free cholesterol efflux from Fu5AH hepatoma cells was observed. Moreover, atorvastatin (40 mg per day) significantly increased plasma apoAI levels (+24%; P<0.05), thereby suggesting that this statin enhances production of apoAI and with it, formation of nascent pre-beta HDL particles. Plasma PLTP activity was not affected by either dose of atorvastatin. We conclude that increasing the dose of atorvastatin leads to dose-dependent, preferential and progressive reduction in particle numbers of atherogenic VLDL-2, IDL and dense LDL, and concomitantly, to enhanced cellular cholesterol efflux in type IIB dyslipidemia, thereby diminishing the atherosclerotic burden in subjects characterised by high cardiovascular risk.

The effect of atorvastatin, at 10 mg or 40 mg for 6 wk, on lipid and lipoprotein metabolism during the postprandial phase in subjects (n = 11) displaying type IIB hyperlipidemia was evaluated. The postprandial increment in area under the curve above baseline concentrations in type IIB subjects was significantly decreased by atorvastatin for plasma triglyceride (A10: -42% and A40: -55%, P < 0.01), chylomicrons (CMs) (A10: -24% and A40: -40%, P < 0.03) and VLDL-1 (A10: -54% and A40: -52%, P < 0.02). Before atorvastatin therapy, postprandial cholesteryl ester (CE) transfer from high-density lipoprotein (HDL) to CMs (2.5-fold; P < 0.005), very low-density lipoprotein (VLDL)-1 (1.8-fold; P < 0.005), VLDL-2 (1.4-fold; P < 0.05), and intermediate-density lipoproteins (1.4-fold; P < 0.05) were significantly increased 4 h postprandially. Following statin treatment, the postprandial transfer of CE from HDL to triglyceride-rich lipoproteins (TRLs) at the 4-h time point was significantly reduced at 10 mg/d (-26%; P < 0.05) and at 40 mg/d (-24%; P < 0.05), compared with that before treatment. Such postprandial increase in CE transferred from HDLs to TRLs arose exclusively from accelerated CE transfer from HDLs to CMs (2.5-fold; P < 0.005). In conclusion, atorvastatin attenuates the abnormal intravascular remodeling of postprandial TRL particles via marked reduction in CE transfer in type IIB hyperlipidemia and diminishes the postprandial formation and accumulation of CMs and VLDL-1.