[Diagnosis and treatment of scabies by general practitioners: A survey of practices in France]. / Description des pratiques des médecins généralistes dans le diagnostic et la prise en charge de la gale commune.

BACKGROUND: Although there is evidence suggesting an epidemiologic increase of scabies in France, few studies have assessed medical practice in terms of diagnosis and treatment. OBJECTIVES: To describe the management of scabies by general practitioners (GPs). PATIENTS AND METHODS: A questionnaire was addressed to the 524 GPs of the Doubs department in France regarding the management of cases of scabies diagnosed between January and June 2015. RESULTS: The response rate was 57 % (n=299). At least one case of scabies was observed by 89 % of GPs in the previous six months and more than three cases were diagnosed by 59 % of GPs. The main clinical criterion for diagnosis was the specific localization of pruritus (82 %). No diagnostic test was used by 94 % of GPs other than except direct parasitological examination, which was used by 6 %. A systematic examination by a dermatologist was prescribed by 3 % of GPs, by 78 % of them in the case of diagnostic doubt, and not at all by 19 %, even though 66 % of GPs' offices were located under 10 kilometers from a dermatologist's office. Ivermectin (IVM) alone was prescribed by 38 % of GPs, either as a single dose (22 %) or as two repeated doses (16 %). Topical treatment alone was prescribed by 2 % of GPs and the association of IVM and topical treatment was used by 26 %, either as a single dose (19 %) or as two repeated doses (7 %). All household members and any sexual contacts were systematically treated by 77 % of GPs, but 9 % did not prescribe any treatment. Decontamination advice was given by 100 % of GPs. Recurrence of scabies was observed by 25 % of GPs despite systematic treatment (93 %) of patients' close contacts. DISCUSSION: Our study confirms the frequency of scabies in general medicine and the interest of GPs in this evaluation of practice. Our data also demonstrate the heterogeneity of management by GPs and the limitations of/poor compliance with national recommendations on scabies proposed by the Haut conseil de santé publique (Public Health Council) in 2012. CONCLUSION: Our study emphasizes the critical role of GPs in the management of scabies and the need for specific recommendations concerning their practices.

Individual and combined effects of acute and chronic running loads on injury risk in elite Australian footballers.

A model that takes into account the current workload, and the workload the athlete has been prepared for, as an acute:chronic workload ratio has been previously used as a novel way to monitor training load and injury risk. Fifty-nine elite Australian football players from one club participated in this 2-year study. Global Positioning System technology was used to provide information on running workloads of players. An injury was defined as any non-contact "time-loss" injury. One-week (acute), along with 4-week (chronic) workloads were calculated for a range of variables. The size of the acute workload in relation to the chronic workload was calculated as an acute:chronic workload ratio. An acute:chronic workload ratio of >2.0 for total distance during the in-season was associated with a 5 to 8-fold greater injury risk in the current [relative risk (RR) = 8.65, P = 0.001] and subsequent week (RR = 5.49, P = 0.016). Players with a high-speed distance acute:chronic workload ratio of >2.0 were 5-11 times more likely to sustain an injury in the current (RR = 11.62, P = 0.006) and subsequent week (RR = 5.10, P = 0.014). These findings demonstrate that sharp increases in running workload increase the likelihood of injury in both the week the workload is performed, and the subsequent week.

Activity Profiles of Successful and Less-successful Semi-elite Rugby League Teams.

This study investigated whether match intensities during predefined periods differed among successful and less-successful rugby league teams. 4 semi-elite rugby league teams were split into 'high-success' and 'low-success' groups based on their success rates. Movement was recorded using a global positioning system (10 Hz) during 20 rugby league matches. Following the peak ball-in-play time period, the high-success group was able to maintain ball-in-play time that was: (1) 22% greater than the low-success group (P=0.01) and (2) greater than their mean period of match-play (P=0.01). In the peak and mean periods of match play, hit-up forwards from the high-success group covered less total distance (P=0.02; P=0.01), less high-intensity running distance (P=0.01; P=0.01) and were involved in a greater number of collisions (P=0.03; P=0.01) than hit-up forwards from the low-success group. These results demonstrate that greater amounts of high-intensity running and total distance are not related to competitive success in semi-elite rugby league. Rather, competitive success is associated with involvement of hit-up forwards in a greater number of collisions and the ability of high-success teams to maintain a higher ball-in-play time following the peak period. Strength and conditioning programs that: (1) emphasize high-intensity running and neglect to combine these running demands with collisions, and (2) do not offer exposure to match specific ball-in-play time demands, may not provide sufficient physiological preparation for teams to be successful in rugby league.

Effects of skyrin, a receptor-selective glucagon antagonist, in rat and human hepatocytes.

Peptidic glucagon antagonists have been shown to lower blood glucose levels in diabetic models (1-3), but attempts to identify small molecular weight glucagon receptor-binding antagonists have met with little success. Skyrin, a fungal bisanthroquinone, exhibits functional glucagon antagonism by uncoupling the glucagon receptor from adenylate cyclase activation in rat liver membranes (1). We have examined the effects of skyrin on cells transfected with the human glucagon receptor and on isolated rat and human hepatocytes. The skyrin used was isolated from Talaromyces wortmanni American Type Culture Collection 10517. In rat hepatocytes, skyrin (30 micromol/l) inhibited glucagon-stimulated cAMP production (53%) and glucose output (IC50 56 micromol/l). There was no detectable effect on epinephrine or glucagon-like peptide 1 (GLP-1) stimulation of these parameters, which demonstrates skyrin's selective activity. Skyrin was also evaluated in primary cultures of human hepatocytes. Unlike cell lines, which are largely unresponsive to glucagon, primary human hepatocytes exhibited glucagon-dependent cAMP production for 14 days in culture (EC50 10 nmol/l). Skyrin (10 micromol/l) markedly reduced glucagon-stimulated cAMP production (55%) and glycogenolysis (27%) in human hepatocytes. The inhibition of glucagon stimulation was a specific property displayed by skyrin and oxyskyrin but not shared by other bisanthroquinones. Skyrin is the first small molecular weight nonpeptidic agent demonstrated to interfere with the coupling of glucagon to adenylate cyclase independent of binding to the glucagon receptor. The data presented in this study indicate that functional uncoupling of the human glucagon receptor from cAMP production results in metabolic effects that could reduce hepatocyte glucose production and hence alleviate diabetic hyperglycemia.

Hypoglycemic activity of a series of alpha-alkylthio and alpha-alkoxy carboxylic acids related to ciglitazone.

The thiazolidinedione moiety of ciglitazone and its analogues can be replaced by an alpha-alkoxy or alpha-thioether carboxylic acid group. The influence of the nature of the R group, the length of the connector to the aromatic backbone of the molecule, and the stereochemistry have been studied. The most potent compounds have glucose-lowering activity at doses as low as 0.01 mg/kg.

Benzyloxazolidine-2,4-diones as potent hypoglycemic agents.

A series of benzyloxazolidine-2,4-diones, containing oxazole-based side chains, were found to lower blood glucose levels in the genetically obese ob/ob mouse. Incorporation of a benzofuran structural element in these compounds provides greatly enhanced in vivo potency. The syntheses and structure-activity relationships for this series are detailed.

Novel thiazolidine-2,4-diones as potent euglycemic agents.

A new series of thiazolidine-2,4-diones was obtained by replacing the ether function of englitazone with various functional groups, i.e., a ketone, alcohol, or olefin moiety. These compounds lower blood glucose levels in the genetically obese and insulin-resistant ob/ob mouse. Appending an oxazole-based group at the terminus of the chain provided highly potent compounds.

Substituted dihydrobenzopyran and dihydrobenzofuran thiazolidine-2,4-diones as hypoglycemic agents.

A series of dihydrobenzofuran and dihydrobenzopyran thiazolidine-2,4-diones (compounds 3-26) was synthesized from the corresponding aryl aldehydes 1 in two steps. These compounds represent conformationally restricted analogues of the novel hypoglycemic ciglitazone. The series was evaluated by hypoglycemic effects in vitro by measuring stimulation of 2-deoxyglucose uptake in L6 myocytes and stimulation of expression of the glucose transporter protein in 3T3-L1 adipocytes. In vivo hypoglycemic effects were evaluated in the genetically obese ob/ob mouse, and structure-activity relationships are discussed. On the basis of this in vivo potency, we have selected the 2(R)-benzylbenzopyran derivative to be further studied in a clinical setting.

Metabolism of a new thiazolidinedione hypoglycemic agent CP-68,722 in rat: metabolite identification by gas chromatography mass spectrometry.

1. After i.v. administration to rat of CP-68,722, a new thiazolidinedione antidiabetic drug, four metabolites were excreted in bile, as glucuronide conjugates. 2. Incubation of the drug with a rat liver microsomal preparation yielded the four in vivo metabolite aglycones and several additional in vitro metabolites. 3. Seven in vivo-generated metabolites were isolated by h.p.l.c. Each metabolite was converted to stable isotope labelled or non-labelled derivatives. Capillary g.l.c.-mass spectrometric analysis of the derivatives indicated that five metabolites result from hydroxylation and one from oxidation to the chromanone. The sites of metabolism were deduced from the electron ionization spectra. 4. Authentic standards for five metabolites were synthesized. Agreements of mass spectra and chromatographic retention times confirmed the five proposed structures. Two metabolites, detected only in vivo, await structure confirmation.