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The diversity of definitions of frequent attendance in the literature hampers comparison of their precision, validity, and associated factors. AimTo examine different definitions of frequent attendance in order to identify the sociodemographic and clinical factors associated with frequent attendance in primary care, according to each definition. Design of studyOne-phase cross-sectional study. SettingSeventy-seven primary care centres in Catalonia, Spain. MethodA total of 3815 primary care patients were interviewed between October 2005 and March 2006. Three definitions of frequent attendance were tested: (1) frequent attenders as the top 25% and the top 10% consulting patients; (2) frequent attenders as the top 25% and the top 10% consulting patients stratified by age and sex; and (3) frequent attenders as the top 25% and the top 10% consulting patients stratified by the presence of physical/mental conditions (patients with only mental disorders, with only chronic physical conditions, with comorbid conditions, and with no condition). Multilevel logistic regressions were used. ResultsThe following factors were systematically related to frequent attender status: being on sick leave, being born outside of Spain, reporting mental health problems as the main reason for consulting, and having arthritis/rheumatism, or bronchitis. Major depression was related to frequent attendance in two of the three definitions. The factor 'GP' was related to frequent attendance when the top decile cut-off point was used. The models with a 10% cut-off point were more discriminative than those with a 25% cut-off point: the area under the receiver operating characteristic curve for models with a 25% cut-off and a 10% cut-off ranged between 0.71 (95% confidence interval [CI] = 0.70 to 0.73) and 0.75 (95% CI = 0.74 to 0.77) and between 0.79 (95% CI = 0.78 to 0.81) and 0.85 (95% CI = 0.83 to 0.86), respectively. ConclusionThe way frequent attendance is defined is of crucial importance. It is recommended that a more discriminative definition of frequent attendance is used (the top 10%).

A 2-month psychoeducational intervention improves the functional status of FM patients to a greater extent than usual care, at least in the short-term. The social desirability bias did not explain the reported outcomes. Trait anxiety was associated with response to treatment.

Eight human plasma preparation protocols were evaluated for their suitability for metabolomic studies by ultra-high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry: organic solvent protein precipitation (PPT) with either methanol or acetonitrile in 2:1 and 3:1 (v/v) ratios with plasma; solid-phase extraction (SPE) using C18 or HybridSPE cartridges; and a combination of PPT and SPE C18 cartridges and microextraction by packed sorbent. A study design in which the order of injection of the samples was not randomized is presented. The analyses were conducted in a BEH C18 column (1.7 μm, 2.1 mm × 100 mm) using a linear gradient from 100% water to 100% methanol, both with 0.1% formic acid, in 21 min. The most reproducible protocol considering both the univariate and the multivariate analysis results was PPT with acetonitrile in a 2:1 (v/v) ratio with plasma, offering a mean coefficient of variation of the area of all the detected features of 0.15 and one of the best clusterings in the principal component analysis plots. On the other hand, the highest number of extracted features was achieved using methanol in a 2:1 (v/v) ratio with plasma as the PPT solvent, closely followed by the same protocol with acetonitrile in a 2:1 (v/v) ratio with plasma, which offered only 1.2% fewer repeatable features. In terms of concentration of remaining protein, protocols based on PPT with acetonitrile provided cleaner extracts than protocols based on PPT with methanol. Finally, pairwise comparison showed that the use of PPT- and SPE-based protocols offers a different coverage of the metabolome.

We present herein the results of microwave promoted N-alkylations of isatin (1) with different alkyl, benzyl and functionalized alkyl halides. Reactions were carried out under different conditions, always employing methodologies compatible with MW assisted chemistry. Generation of isatin anion employing diverse bases and solvents or using the preformed isatin sodium salt was tested. The best results were achieved using K2CO3 or Cs2CO3 and a few drops of N,N-dimethylformamide or N-methyl-2-pyrrolidinone. These reactions present noteworthy advantages over those carried out employing conventional heating.

Thelepamide (1) was characterized during a program to study cytotoxic substances from an unusual source, tidal zone-derived annelid Thelephus crispus. Its structure contains a tetraketide and a tripeptide subunits and it posses striking atom diversity, consisting of 17 carbons and 8 heteroatoms. The relative configurations at four chiral sites were elucidated via ROESY, J-based configurational analysis, and DFT calculations. It was modestly active against leukemia cells (IC50 = 5 μg/mL) and inactive against solid tumor cell lines.

In this study, a selective and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (≤100 μL) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and (13) C6 -fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for (13) C6 -fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25 ng/mL. Intra- and inter-assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5 µg/kg bolus immediately followed by a 90-min infusion of 3 µg/kg/h).

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