Current Issue : July - September Volume : 2013 Issue Number : 3 Articles : 7 Articles
Background: The prevalence of asthma has increased over recent decades and the reasons for this are poorly\r\nunderstood. A sensitive tool that can evaluate potential risk factors for asthma is bronchial hyperresponsiveness\r\n(BHR), a key physiological characteristic of asthma. However, although the minimum clinically important difference\r\nin BHR for an individual is accepted to be around one doubling dose, the minimum important change in a\r\npopulation is not defined. As with surrogate measures of cardiovascular disease risk such as blood pressure and\r\ncholesterol, a change that is not clinically important in an individual may be extremely important in public health\r\nterms.\r\nFindings: To assess the potential impact of a small absolute change in BHR across a population, we modelled the\r\neffect of different changes in BHR on the prevalence rates of moderate and severe BHR in an asthmatic population.\r\nWe calculate that a one half doubling dose increase in BHR increases the prevalence of moderate and severe BHR\r\nby 30%. If this was accompanied by an equivalent increase in the population prevalence of moderate and severe\r\nasthma, this would be highly significant in public health terms.\r\nConclusions: We propose that a one half doubling dose worsening in BHR across a population may represent an\r\nimportant change...
Background: Statins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular\r\ninflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for\r\ncardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery\r\ndisease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more\r\neffective for treating patients with CAD has not been established. The present study compares anti-inflammatory\r\neffects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose\r\nor by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients.\r\nMethods: 46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that\r\nwere not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n = 24) of\r\nrosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n = 22) for 12 weeks. The\r\nprimary endpoint was a change in hs-CRP.\r\nResults: Baseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory\r\nmarkers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the\r\ntwo groups (LDL-C: R10 vs. R2.5/E10: -19.4 �± 14.2 vs. -22.4 �± 14.3 mg/dL). However, high-density lipoprotein cholesterol\r\n(HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6 �± 5.9 vs. 0.0 �± 6.7 mg/dL; p < 0.05).\r\nConclusion: Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in\r\npatients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively\r\nthan R2.5/E10....
Background: Recently research has shown that larviciding can be an effective tool for integrated malaria vector\r\ncontrol. Nevertheless, the uptake of this intervention has been hampered by the need to re-apply larvicides\r\nfrequently. There is a need to explore persistent, environmentally friendly larvicides for malaria vector control to\r\nreduce intervention efforts and costs by reducing the frequency of application. In this study, the efficacy of a 0.5%\r\npyriproxyfen granule (SurmilarvW0.5G, Sumitomo Chemicals) was assessed for the control of Anopheles gambiae\r\nsensu stricto and Anopheles arabiensis, the major malaria vectors in sub-Saharan Africa.\r\nMethods: Doseââ?¬â??response and standardized field tests were implemented following standard procedures of the\r\nWorld Health Organizationââ?¬â?¢s Pesticide Evaluation Scheme to determine: (i) the susceptibility of vectors to this\r\nformulation; (ii) the residual activity and appropriate retreatment schedule for field application; and, (iii) sub-lethal\r\nimpacts on the number and viability of eggs laid by adults after exposure to SumilarvW0.5G during larval\r\ndevelopment.\r\nResults: Anopheles gambiae s.s. and An. arabiensis were highly susceptible to SumilarvW0.5G. Estimated emergence\r\ninhibition (EI) values were very low and similar for both species. The minimum dosage that completely inhibited\r\nadult emergence was between 0.01-0.03 parts per million (ppm) active ingredient (ai). Compared to the untreated\r\ncontrol, an application of 0.018 ppm ai prevented 85% (95% confidence interval (CI) 82%-88%) of adult emergence\r\nover six weeks under standardized field conditions. A fivefold increase in dosage of 0.09 ppm ai prevented 97%\r\n(95% CI 94%-98%) emergence. Significant sub-lethal effects were observed in the standardized field tests. Female\r\nAn. gambiae s.s. that were exposed to 0.018 ppm ai as larvae laid 47% less eggs, and females exposed to 0.09 ppm\r\nai laid 74% less eggs than females that were unexposed to the treatment. Furthermore, 77% of eggs laid by\r\nfemales exposed to 0.018 ppm ai failed to hatch, whilst 98% of eggs laid by females exposed to 0.09 ppm ai did\r\nnot hatch....
Background: Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people\r\naround the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and\r\nincrease the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero\r\nexposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics.\r\nMethods: Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation\r\n(WHO) maximum contaminant level) or 100�µg/L arsenic from gestational day 8 to birth. Birth outcomes and\r\nsomatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect\r\nmeasurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung\r\nmechanics in male and female offspring at two, four, six and eight weeks of age.\r\nResults: In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired\r\nparenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on\r\ngrowth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure\r\nwere recovered by adulthood.\r\nConclusions: Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic\r\ngrowth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in\r\ngrowth and lung development in early life may contribute to the increased susceptibility of developing chronic\r\nrespiratory disease in arsenic exposed human populations...
Background: The FSH starting dose is usually chosen according to women�s age, anamnesis, clinical criteria and\r\nmarkers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a\r\nvery high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a\r\nnomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles.\r\nMethods: This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital.\r\nIVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum\r\nday3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by\r\nbackwards stepwise multiple regression. The variables reaching the statistical significance were then used in the\r\ncalculation for the final predictive model.\r\nResults: A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted\r\nfor 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it\r\npredicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years,\r\nrespectively.\r\nConclusions: The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve,\r\nnamely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily\r\napplicable during the daily clinical practice....
Objective: To determine late toxicity and quality of life (QoL) in patients with localized prostate cancer after highdose\r\nintensity-modulated radiotherapy (IMRT).\r\nPatient and methods: This was a prospective study in patients with localized prostate adenocarcinoma who had\r\nbeen treated by IMRT (76 Gy) between February and November 2006. Physicians scored acute and late toxicity\r\nusing the Common Terminology Criteria for Adverse Events (version 3.0). Patients completed cancer and prostatespecific\r\nQoL questionnaires (EORTC QLQ-C30 and QLQ-PR25) before IMRT (baseline) and at 2, 6, 18 and 54 months.\r\nResult: Data were available for 38 patients (median age, 73 years) (18% low risk; 60% intermediate risk; 32% high\r\nrisk). The incidence of urinary and gastrointestinal toxicity was respectively: immediately post IMRT: 36.8% and 23.7%\r\n(grade 1), 5.3% and 5.3% (grade 2), 2.6% and 0% (grade 3); at 18 months: 23.7% and 10.3% (grade 1), 26.3% and\r\n13.2% (grade 2), 0% and 2.6% (grade 3); at 54 months: 34.2% and 23.7% (grade 1), 5.3% and 15.8% (grade 2), 5.3%\r\nand 0% (grade 3). At 54 months, significant worsening was reported by patients for 11/19 QoL items but the\r\nworsening was clinically relevant (>10 points) for 7 items only: physical, role as well as social functioning, fatigue,\r\npain, dyspnoea and constipation. There was no significant difference between 54-month and baseline QoL scores\r\nfor global health, gastrointestinal symptoms, treatment-related symptoms and sexual function. However, there was\r\nsignificant - but clinically non-relevant (<10 points) - worsening of urinary symptom.\r\nConclusion: High-dose IMRT to the prostate with accurate patient positioning did not induce any clinically relevant\r\nworsening in late urinary and gastrointestinal QoL at 54 months. Impaired physical and role functioning may be\r\nrelated to age and comorbidities...
Purpose: To treat malaria, HIV-infected patients normally receive artemether (80 mg twice daily) concurrently with\r\nantiretroviral therapy and drug-drug interactions can potentially occur. Artemether is a substrate of CYP3A4 and\r\nCYP2B6, antiretrovirals such as efavirenz induce these enzymes and have the potential to reduce artemether\r\npharmacokinetic exposure. The aim of this study was to develop an in vitro in vivo extrapolation (IVIVE) approach to\r\nmodel the interaction between efavirenz and artemether. Artemether dose adjustments were then simulated in\r\norder to predict optimal dosing in co-infected patients and inform future interaction study design.\r\nMethods: In vitro data describing the chemical properties, absorption, distribution, metabolism and elimination of\r\nefavirenz and artemether were obtained from published literature and included in a physiologically based\r\npharmacokinetic model (PBPK) to predict drug disposition simulating virtual clinical trials. Administration of\r\nefavirenz and artemether, alone or in combination, were simulated to mirror previous clinical studies and facilitate\r\nvalidation of the model and realistic interpretation of the simulation. Efavirenz (600 mg once daily) was\r\nadministered to 50 virtual subjects for 14 days. This was followed by concomitant administration of artemether\r\n(80 mg eight hourly) for the first two doses and 80 mg (twice daily) for another two days.\r\nResults: Simulated pharmacokinetics and the drug-drug interaction were in concordance with available clinical\r\ndata. Efavirenz induced first pass metabolism and hepatic clearance, reducing artemether Cmax by 60% and AUC by\r\n80%. Dose increases of artemether, to correct for the interaction, were simulated and a dose of 240 mg was\r\npredicted to be sufficient to overcome the interaction and allow therapeutic plasma concentrations of artemether.\r\nConclusions: The model presented here provides a rational platform to inform the design for a clinical drug\r\ninteraction study that may save time and resource while the optimal dose is determined empirically. Wider\r\napplication of IVIVE could help researchers gain a better understanding of the molecular mechanisms underpinning\r\nvariability in drug disposition....
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