947 research outputs found

    Mean Field Behavior of Cluster Dynamics

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    The dynamic behavior of cluster algorithms is analyzed in the classical mean field limit. Rigorous analytical results below TcT_c establish that the dynamic exponent has the value zsw=1z_{sw}=1 for the Swendsen-Wang algorithm and zuw=0z_{uw}=0 for the Wolff algorithm. An efficient Monte Carlo implementation is introduced, adapted for using these algorithms for fully connected graphs. Extensive simulations both above and below TcT_c demonstrate scaling and evaluate the finite-size scaling function by means of a rather impressive collapse of the data.Comment: Revtex, 9 pages with 7 figure

    Impact of mass drug administration of azithromycin for trachoma elimination on prevalence and azithromycin resistance of genital Mycoplasma genitalium infection

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    Background Mass drug administration (MDA) of 20 mg/kg (maximum 1 g in adults) azithromycin for ocular Chlamydia trachomatis (CT) infection is a key component of the WHO trachoma elimination strategy. However, this dose may be suboptimal in Mycoplasma genitalium infection and may encourage emergence of antimicrobial resistance (AMR) to azithromycin. Objectives To determine the effect of MDA for trachoma elimination on M. genitalium prevalence, strain type and azithromycin resistance. Methods A secondary analysis of CT-negative vulvovaginal swabs from three outpatient antenatal clinics (Honiara, Solomon Islands) from patients recruited either pre-MDA, or 10 months post-MDA in two cross-sectional surveys was carried out. Swabs were tested for M. genitalium infection using Fast Track Diagnostics Urethritis Plus nucleic acid amplification assay. M. genitalium-positive samples were subsequently tested for azithromycin resistance by sequencing domain V of the 23S rRNA DNA region of M. genitalium and underwent phylogenetic analysis by dual locus sequence typing. Results M. genitalium prevalence was 11.9% (28/236) in women pre-MDA and 10.9% (28/256) 10 months post-MDA (p=0.7467). Self-reported receipt of azithromycin as part of MDA was 49.2% in women recruited post-MDA and 17.9% (5/28) in those who tested M. genitalium positive. Of samples sequenced (21/28 pre-MDA, 22/28 post-MDA), all showed a macrolide susceptible genotype. Strain typing showed that sequence types diverged into two lineages, with a suggestion of strain replacement post-MDA. Conclusion A single round of azithromycin MDA in an island population with high baseline M. genitalium prevalence did not appear to impact on either prevalence or azithromycin resistance, in contrast to reported decreased genital CT prevalence in the same population. This may be due to limitations such as sample size, including CT-negative samples only, and low MDA coverage. Further investigation of the impact of multiple rounds of MDA on M. genitalium azithromycin AMR in antibiotic experienced and naïve populations is warranted

    The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

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    Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

    Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine

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    BACKGROUND: Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. Some nonsteroidal anti-inflammatory drugs (NSAID) have also demonstrated efficacy in treating migraine attacks. There is evidence that the combination of a triptan and a NSAID decreases migraine recurrence in clinical practice. The primary aim of this randomized open label study was to assess the recurrence rates in migraine sufferers acutely treated with rizatriptan (RI) alone vs. rizatriptan plus a COX-2 enzyme inhibitor (rofecoxib, RO) vs. rizatriptan plus a traditional NSAID (tolfenamic acid, TO). We were also interested in comparing the efficacy rates within these three groups. METHODS: We assessed 45 patients from a headache clinic in Rio de Janeiro (35 women and 10 men, ages 18 to 65 years, mean 37 years). Patients with IHS migraine were randomized to one out of 3 groups, where they had to treat 6 consecutive moderate or severe attacks in counterbalanced order. In group 1, patients treated the first two attacks with 10 mg RI, the third and fourth attacks with RI + 50 mg RO and the last attacks with RI + 200 mg of TA. In group 2, we began with RI + TA, followed by RI, and RI + RO. Group 3 treated in the following order: RI + RO, RI + TA, RI alone. The presence of headache, nausea and photophobia at 1, 2 and 4 hours, as well as recurrence and side effects were compared. RESULTS: A total of 33 patients finished the study, treating 184 attacks. The pain-free rates at 1 hour were: RI: 15.5%; RI + RO: 22.6%; RI + TA: 20.3%(NS). Pain-free rates at 2 h were: RI: 37.9%; RI + RO: 62.9%, and RI + TA: 40.6% (p = 0.008 for RI vs. RI + RO; p = 0.007 for RI + RO vs. RI + TA, NS for RI vs RI + TA). At 4 h, pain-free rates were: RI: 69%; RI + RO: 82.3%; RI + TA: 78.1% (NS for all comparisons). The combination of RI + RO was superior to RI and to RI + TA in regard of the absense of nausea and photophobia at 4 hours. Recurrence (after being pain-free at 2 h) was observed in 50% of patients treated with RI, in 15,4% of those treated with RI + RO, and in 7,7% of those treated with RI + TA. CONCLUSIONS: Despite the methodological limitations of this study, the combination of RI and RO revealed a higher response rate at 2 hours. Recurrence was also clearly decreased with both combinations in relation to the use of RI alone. Controlled studies are necessary to provide additional evidence

    Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

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    Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of 20through20 through 800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of 200orless,osteoporosisscreeningfollowedbytreatmentwascostsaving,resultinginlowertotalcoststhannoscreeningaswellasmoreQALYs(10.6additionalqualityadjustedlifedays).Whenassumingalendronatecostsof200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of 400 through 800,screeningandtreatmentresultedingreaterlifetimecoststhannoscreeningbutwashighlycosteffective,withICERsrangingfrom800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from 714 per QALY gained through 13,902perQALYgained.Probabilisticsensitivityanalysesrevealedthatthecosteffectivenessofosteoporosisscreeningfollowedbyalendronatetreatmentwasrobusttojointinputparameterestimatevariationatawillingnesstopaythresholdof13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of 50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

    Benign afebrile cluster convulsions with gastroenteritis: an observational study

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    BACKROUND: The occurrence of afebrile seizures in association with viral gastroenteritis, without dehydration or electrolyte imbalance, is virtually unknown outside Asia. They are reported to have a benign prognosis and not to require specific investigations or therapy. METHODS: We report the occurrence of such afebrile convulsions in association with viral gastroenteritis without dehydration or electrolyte imbalance, over a 3-year period, in a cohort of 14 British children. RESULTS: The children (5 males and 9 females, 10 Caucasians and 4 Asians) were aged 9 to 60 months (median 14.5 months). All 14 had a normal neurological examination and normal serum biochemistry. Twelve children had generalised seizures and 2 had, in addition, absence seizures. The number of seizures per child ranged from 1 to 8. Most convulsions were short with 85.7% of children having the longest seizure not longer than 4 minutes. The longest duration for a seizure was 10 minutes and occurred in 2 children. Convulsions did not recur after the first day in 10 children, 3 children had recurrences the second day and one child on the fourth day. No convulsions recurred after 4 days. Cerebrospinal fluid studies, computed tomography and electroencephalogram (EEG) were performed on two children who had prolonged seizures and the results were normal. No pathogenic bacteria were grown in any of the stools. Enzyme immunoassay detection of Rotavirus in the stools was positive in 7 of the 10 children where it was tested. All 14 children recovered spontaneously within a few days. On long-term follow of up to 31 months (median 16 months), none had further convulsions and all had normal development milestones. CONCLUSIONS: Afebrile seizures in association with viral gastroenteritis do also occur outside Asia. Recognition of this entity should lead to reassurance of the parents. As in previously published series, investigations such as lumbar puncture, neuroimaging and EEG are usually normal and may not be necessary in most cases. Likewise, published data indicate that long-term anticonvulsant therapy is not usually warranted and the prognosis seems to be reassuring

    Bone Loss in Diabetes: Use of Antidiabetic Thiazolidinediones and Secondary Osteoporosis

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    Clinical evidence indicates that bone status is affected in patients with type 2 diabetes mellitus (T2DM). Regardless of normal or even high bone mineral density, T2DM patients have increased risk of fractures. One class of antidiabetic drugs, thiazolidinediones (TZDs), causes bone loss and further increases facture risk, placing TZDs in the category of drugs causing secondary osteoporosis. Risk factors for development of TZD-induced secondary osteoporosis are gender (women), age (elderly), and duration of treatment. TZDs exert their antidiabetic effects by activating peroxisome proliferator-activated receptor-γ (PPAR-γ) nuclear receptor, which controls glucose and fatty acid metabolism. In bone, PPAR-γ controls differentiation of cells of mesenchymal and hematopoietic lineages. PPAR-γ activation with TZDs leads to unbalanced bone remodeling: bone resorption increases and bone formation decreases. Laboratory research evidence points toward a possible separation of unwanted effects of PPAR-γ on bone from its beneficial antidiabetic effects by using selective PPAR-γ modulators. This review also discusses potential pharmacologic means to protect bone from detrimental effects of clinically used TZDs (pioglitazone and rosiglitazone) by using combinational therapy with approved antiosteoporotic drugs, or by using lower doses of TZDs in combination with other antidiabetic therapy. We also suggest a possible orthopedic complication, not yet supported by clinical studies, of delayed fracture healing in T2DM patients on TZD therapy
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