Development of an LC-MS/MS method for the quantitation of 55 compounds prescribed in combined cardiovascular therapy

This paper reports an LC-MS/MS method with positive electrospray ionization for the screening of commonly prescribed cardiovascular drugs in human plasma, including compounds with antihypertensive (57), antidiabetic (12), hypolipemiant (5), anticoagulant (2) and platelet anti-aggregation (2) effects. Sample treatment consisted of a simple protein precipitation with MeOH/0.1 M ZnSO₄ (4:1, v/v) solution after the addition of internal standard, followed by evaporation and reconstitution. Analytes separation was performed on a Polar-RP column (150 m x 2 mm, 4 μm) using a gradient elution of 15 min. The MS system was operated in MRM mode, monitoring one quantitation and one confirmation transition for each analyte. The recovery of the protein precipitation step ranged from 50 to 70% for most of the compounds, while some were considerably affected by matrix effects. Since several analytes fulfilled the linearity, accuracy and precision values required by the ICH guidelines, the method proved to be suitable for their quantitative analysis. The limits of quantitation varied from 0.38 to 9.1 μg/L and the limits of detection from 0.12 to 5.34 μg/L. The method showed to be suitable for the detection of plasma samples of patients under cardiovascular treatment with the studied drugs, and for 55 compounds reliable quantitative results could be obtained.

[Endoscopic decompression of the ulnar nerve in the cubital tunnel syndrome: about 55 patients]

Sulcus ulnaris syndrome is the second most common neurocompression syndrome in the upper limb after carpal tunnel syndrome. Its severity can be appreciated by the Dellon Classification. We present our experience and results after endoscopic decompression.

A refined TALDICE-1a age scale from 55 to 112 ka before present for the Talos Dome ice core based on high-resolution methane measurements

A precise synchronization of different climate records is indispensable for a correct dynamical interpretation of paleoclimatic data. A chronology for the TALDICE ice core from the Ross Sea sector of East Antarctica has recently been presented based on methane synchronization with Greenland and the EDC ice cores and δ18Oice synchronization with EDC in the bottom part (TALDICE-1). Using new high-resolution methane data obtained with a continuous flow analysis technique, we present a refined age scale for the age interval from 55–112 thousand years (ka) before present, where TALDICE is synchronized with EDC. New and more precise tie points reduce the uncertainties of the age scale from up to 1900 yr in TALDICE-1 to below 1100 yr over most of the refined interval and shift the Talos Dome dating to significantly younger ages during the onset of Marine Isotope Stage 3. Thus, discussions of climate dynamics at sub-millennial time scales are now possible back to 110 ka, in particular during the inception of the last ice age. Calcium data of EDC and TALDICE are compared to show the impact of the refinement to the synchronization of the two ice cores not only for the gas but also for the ice age scale.

Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial

OBJECTIVE: To determine the impact of a community based Helicobacter pylori screening and eradication programme on the incidence of dyspepsia, resource use, and quality of life, including a cost consequences analysis. DESIGN: H pylori screening programme followed by randomised placebo controlled trial of eradication. SETTING: Seven general practices in southwest England. PARTICIPANTS: 10,537 unselected people aged 20-59 years were screened for H pylori infection (13C urea breath test); 1558 of the 1636 participants who tested positive were randomised to H pylori eradication treatment or placebo, and 1539 (99%) were followed up for two years. INTERVENTION: Ranitidine bismuth citrate 400 mg and clarithromycin 500 mg twice daily for two weeks or placebo. MAIN OUTCOME MEASURES: Primary care consultation rates for dyspepsia (defined as epigastric pain) two years after randomisation, with secondary outcomes of dyspepsia symptoms, resource use, NHS costs, and quality of life. RESULTS: In the eradication group, 35% fewer participants consulted for dyspepsia over two years compared with the placebo group (55/787 v 78/771; odds ratio 0.65, 95% confidence interval 0.46 to 0.94; P = 0.021; number needed to treat 30) and 29% fewer participants had regular symptoms (odds ratio 0.71, 0.56 to 0.90; P = 0.05). NHS costs were 84.70 pounds sterling (74.90 pounds sterling to 93.91 pounds sterling) greater per participant in the eradication group over two years, of which 83.40 pounds sterling (146 dollars; 121 euro) was the cost of eradication treatment. No difference in quality of life existed between the two groups. CONCLUSIONS: Community screening and eradication of H pylori is feasible in the general population and led to significant reductions in the number of people who consulted for dyspepsia and had symptoms two years after treatment. These benefits have to be balanced against the costs of eradication treatment, so a targeted eradication strategy in dyspeptic patients may be preferable.

Partner notification of chlamydia infection in primary care: randomised controlled trial and analysis of resource use

OBJECTIVE: To evaluate the effectiveness of a practice nurse led strategy to improve the notification and treatment of partners of people with chlamydia infection. DESIGN: Randomised controlled trial. SETTING: 27 general practices in the Bristol and Birmingham areas. PARTICIPANTS: 140 men and women with chlamydia (index cases) diagnosed by screening of a home collected urine sample or vulval swab specimen. INTERVENTIONS: Partner notification at the general practice immediately after diagnosis by trained practice nurses, with telephone follow up by a health adviser; or referral to a specialist health adviser at a genitourinary medicine clinic. MAIN OUTCOME MEASURES: Primary outcome was the proportion of index cases with at least one treated sexual partner. Specified secondary outcomes included the number of sexual contacts elicited during a sexual history, positive test result for chlamydia six weeks after treatment, and the cost of each strategy in 2003 sterling prices. RESULTS: 65.3% (47/72) of participants receiving practice nurse led partner notification had at least one partner treated compared with 52.9% (39/68) of those referred to a genitourinary medicine clinic (risk difference 12.4%, 95% confidence interval -1.8% to 26.5%). Of 68 participants referred to the clinic, 21 (31%) did not attend. The costs per index case were 32.55 pounds sterling for the practice nurse led strategy and 32.62 pounds sterling for the specialist referral strategy. CONCLUSION: Practice based partner notification by trained nurses with telephone follow up by health advisers is at least as effective as referral to a specialist health adviser at a genitourinary medicine clinic, and costs the same. Trial registration Clinical trials: NCT00112255.

Amplified bioproductivity during Transition IV (332 000-342 000 yr ago): evidence from the geochemical record of Lake El'gygytgyn

Abstract. To date, terrestrial archives of long-term climatic change within the Arctic have widely been restricted to ice cores from Greenland and, more recently, sediments from Lake El’gygytgyn in northeast Arctic Russia. Sediments from this lake contain a paleoclimate record of glacialinterglacial cycles during the last three million years. Lowresolution studies at this lake have suggested that changes observed during Transition IV (the transition from marine isotope stage (MIS) 10 to MIS 9) are of greater amplitude than any observed since. In this study, geochemical parameters are used to infer past climatic conditions thus providing the first high-resolution analyses of Transition IV from a terrestrial Arctic setting. These results demonstrate that a significant shift in climate was subsequently followed by a rapid increase in biogenic silica (BSi) production. Following this sharp increase, bioproductivity remained high, but variable, for over a thousand years. This study reveals differences in the timing and magnitude of change within the ratio of silica to titanium (Si/Ti) and BSi records that would not be apparent in lower resolution studies. This has significant implications for the increasingly common use of Si/Ti data as an alternative to traditional BSi measurements.

Adalimumab in recalcitrant severe psoriasis associated with atopic dermatitis

Tumor necrosis factor-α inhibitors may induce various cutaneous side effects including eczematous-like lesions. The management of such side effects can be challenging. Herein, we report a case of a 55-year-old man who had a flare-up and subsequent improvement of atopic dermatitis during treatment of severe psoriasis with adalimumab.

Comparison of a Novel Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent: Results of the Randomized BIOFLOW-II Trial.

BACKGROUND Biodegradable polymers for release of antiproliferative drugs from drug-eluting stents aim to improve vascular healing. We assessed noninferiority of a novel ultrathin strut drug-eluting stent releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) compared with the durable polymer Xience Prime everolimus-eluting stent (X-EES) in terms of the primary end point in-stent late lumen loss at 9 months. METHODS AND RESULTS A total of 452 patients were randomly assigned 2:1 to treatment with O-SES (298 patients, 332 lesions) or X-EES (154 patients, 173 lesions) in a multicenter, noninferiority trial. The primary end point was in-stent late loss at 9 months. O-SES was noninferior to X-EES for the primary end point (0.10±0.32 versus 0.11±0.29 mm; difference=0.00063 mm; 95% confidence interval, -0.06 to 0.07; Pnoninferiority<0.0001). Clinical outcome showed similar rates of target-lesion failure at 1 year (O-SES 6.5% versus X-EES 8.0%; hazard ratio=0.82; 95% confidence interval, 0.40-1.68; log-rank test: P=0.58) without cases of stent thrombosis. A subgroup of patients (n=55) underwent serial optical coherence tomography at 9 months, which demonstrated similar neointimal thickness among lesions allocated to O-SES and X-EES (0.10±0.04 mm versus 0.11±0.04 mm; -0.01 [-0.04, -0.01]; P=0.37). Another subgroup of patients (n=56) underwent serial intravascular ultrasound at baseline and 9 months indicating a potential difference in neointimal area at follow-up (O-SES, 0.16±0.33 mm(2) versus X-EES, 0.43±0.56 mm(2); P=0.04). CONCLUSIONS Compared with durable polymer X-EES, novel biodegradable polymer-based O-SES was found noninferior for the primary end point in-stent late lumen loss at 9 months. Clinical event rates were comparable without cases of stent thrombosis throughout 1 year of follow-up. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01356888.