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1.
In this prospective cohort of women undergoing infertility treatments, we measured specific-gravity adjusted urinary BPA (SG-BPA) concentrations and used regression models to evaluate the association of BPA with antral follicle count (AFC), day-3 serum follicle stimulating hormone levels (FSH), and ovarian volume (OV). BPA, detected in >80% of women, had a geometric mean (±GSD) of 1.6 ± 2.0, 1.7 ± 2.1, and 1.5 ± 1.8 μg/L for the women contributing to the AFC (n = 154), day-3 FSH (n = 120), and OV (n = 114) analyses, respectively. There was an average decrease in AFC of 12% (95% CI: −23%, −0.6%), 22% (95% CI: −31%, −11%), and 17% (95% CI: −27%, −6%), in the 2nd, 3rd, and 4th SG-BPA quartile compared to the 1st quartile, respectively (p-trend: <0.001). No association of SG-BPA with FSH or OV was observed. Among women from an infertility clinic, higher urinary BPA concentrations were associated with lower AFC, raising concern for possible accelerated follicle loss and reproductive aging. 相似文献
2.
《European neuropsychopharmacology》2014,24(7):1024-1036
Bitopertin is a glycine reuptake inhibitor postulated to improve N-methyl-d-aspartate receptor hypofunction by increasing synaptic glycine concentrations. This randomised, double-blind, placebo- and active-controlled phase II/III trial evaluated the efficacy and safety of bitopertin monotherapy over 4 weeks in patients with acute exacerbation of schizophrenia. Of 301 patients randomised, 299 received placebo (n=80), bitopertin 10 mg (n=80) or 30 mg (n=77), or olanzapine 15 mg (n=62). The primary endpoint, change from baseline in mean Positive and Negative Syndrome Scale (PANSS) total score, showed non-statistically significant improvements with bitopertin 30 mg and olanzapine vs. placebo: bitopertin 10 mg (–11.7; standard error [SE], 1.89; p=0.945), bitopertin 30 mg (–15.3; SE, 1.87; p=0.211), olanzapine (–14.9; SE, 2.13; p=0.295) and placebo (–11.9; SE, 1.90). The PANSS positive subscale score, a secondary endpoint, also showed improvement with bitopertin 30 mg (p=0.030) whereas a trend was observed with olanzapine (p=0.072) vs. placebo. Although not statistically significant, bitopertin 30 mg and olanzapine reduced overall illness severity (Clinical Global Impression–Severity Scale; p=0.098 and p=0.126, respectively). More patients receiving bitopertin 30 mg (51.3%) or olanzapine (52.5%) than placebo (32.9%) were ready for hospital discharge at Week 4 (bitopertin, p=0.014; olanzapine, p=0.024). In summary, this study failed due to lack of statistical separation of either bitopertin or olanzapine (active control) from placebo on the primary endpoint. Of interest, improved positive symptoms and readiness for hospital discharge were associated with both bitopertin and olanzapine treatment. Bitopertin was safe and well tolerated in this study. 相似文献
3.
Low birth weight is associated with exposure to air pollution during pregnancy. The purpose of this study was to evaluate whether null polymorphisms of Glutathione S-transferases (GSTs), specifically GSTM1 and GSTT1 genes in infants or mothers, modify the association between high exposures to household air pollution (HAP) from cooking fires and birth weight. Pregnant women in rural Guatemala were randomized to receive a chimney stove or continue to use open fires for cooking. Newborns were measured within 48 h of birth. 132 mother–infant pairs provided infant genotypes (n = 130) and/or maternal genotypes (n = 116). Maternal null GSTM1 was associated with a 144 g (95% CI, −291, 1) and combined maternal/infant null GSTT1 was associated with a 155 g (95% CI, −303, −8) decrease in birth weight. Although there was a trend toward higher birth weights with increasing number of expressed GST genes, the effect modification by chimney stove use was not demonstrated. 相似文献
4.
Eduard Vieta Stuart Montgomery Ahmad Hatim Sulaiman Rodrigo Cordoba Benedicte Huberlant Lupe Martinez Andreas Schreiner 《European neuropsychopharmacology》2012,22(11):825-835
The efficacy and safety of risperidone long-acting injectable (LAI) for preventing recurrence of mood episodes in patients with bipolar I disorder was evaluated in a randomized, placebo-controlled study. After a 12-week open-label period with risperidone LAI (n=560), patients who did not experience a recurrence entered an 18-month randomized, double-blind period with risperidone LAI (n=132) or placebo (n=135); a third treatment arm (n=131) was randomized to oral olanzapine (10 mg/day) for reference and exploratory comparisons. The primary efficacy endpoint was time to recurrence of any mood episode for risperidone LAI versus placebo in the double-blind period (Kaplan–Meier analysis). Additional efficacy endpoints included Young Mania Rating Scale, Montgomery–Asberg Depression Rating Scale and Clinical Global Impression. During the double-blind period, dosing was fixed at patients' final open-label dose (25 mg, 66% of patients; 37.5 mg, 31%; 50 mg, 4%). The primary outcome demonstrated a median time to mood episode recurrence of 198 day in the placebo arm, whereas the median was not reached in the risperidone LAI arm (p=0.057). Time to recurrence of any mood episode was significantly longer with risperidone LAI versus placebo (log-rank test stratified by region only, p=0.031); the difference was significant for time to recurrence of elevated mood episodes (p=0.005) but not depressive episodes (p=0.655). Significant improvement of manic symptoms and global condition versus placebo were observed for risperidone LAI, with no evidence of worsening of depression. In conclusion, risperidone LAI significantly delayed time to recurrence of elevated mood episodes, with a safety profile consistent with previous studies. 相似文献
5.
Michael S. Bloom Patrick J. Parsons Amy J. Steuerwald Enrique F. Schisterman Richard W. Browne Keewan Kim Gregory A. Coccaro Giulia C. Conti Natasha Narayan Victor Y. Fujimoto 《Reproductive toxicology (Elmsford, N.Y.)》2010,29(3):298-305
Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may threaten human reproductive health. The aim of this study is to generate biologically-plausible hypotheses concerning associations between Hg, Cd, and Pb and in vitro fertilization (IVF) endpoints. For 15 female IVF patients, a multivariable log-binomial model suggests a 75% reduction in the probability for a retrieved oocyte to be in metaphase-II arrest for each μg/dL increase in blood Pb concentration (relative risk (RR) = 0.25, 95% confidence interval (CI) 0.03–2.50, P = 0.240). For 15 male IVF partners, each μg/L increase in urine Cd concentration is associated with an 81% decrease in the probability for oocyte fertilization (RR = 0.19, 95% CI 0.03–1.35, P = 0.097). Because of the magnitude of the effects, these results warrant a comprehensive study with sufficient statistical power to further evaluate these hypotheses. 相似文献
6.
IntroductionWaterpipe smoking has become increasingly popular in adolescents. We examined the association of waterpipe smoking with cigarette smoking susceptibility and nicotine dependence among adolescents in Hong Kong.MethodsWe analyzed the data of School-based Survey on Smoking among Students 2012/13 from a representative sample of 45,857 secondary school students (US grades 7–12) in Hong Kong. Among never cigarette smokers (n = 37,740), we conducted chi-square test to compare cigarette smoking susceptibility by current (past 30-day) waterpipe smoking status, and used multivariate logistic regression to examine the association between current waterpipe smoking and cigarette smoking susceptibility controlling for age, sex, peer cigarette smoking, and living with a cigarette smoker. Then we conducted chi-square test and multivariate logistic regression among current cigarette smokers (n = 1694) to examine the relationship of current waterpipe smoking with two nicotine dependence outcomes, including heavier smoking (≥ 5 cigarettes/day) and first cigarette within 30 min of waking, controlling for demographics and the number of smoking days in the past 30 days.ResultsAmong never cigarette smokers, current waterpipe use was associated with cigarette smoking susceptibility (adjusted odds ratio [AOR] = 3.58, 95% confidence interval [CI]: 1.61–7.97). Of current cigarette smokers, waterpipe use was associated with heavier smoking (AOR = 1.56, 95% CI: 1.00–2.43) and first cigarette within 30 min of waking (AOR = 2.08, 95% CI: 1.35–3.19).ConclusionsSurveillance, prevention, and intervention programs should address waterpipe use in addition to cigarette smoking. Educational programs need to inform youth about the harmful and addictive effects of waterpipe smoking. Public health campaigns deglamourizing waterpipe use may help reduce waterpipe smoking among youth. 相似文献
7.
Jeong-Ah Kwon Jung Eun Lee Wooseong Huh Kyong Ran Peck Yoon-Goo Kim Dae Joong Kim Ha Young Oh 《International journal of antimicrobial agents》2010,35(5):473-477
Colistimethate sodium (CMS) was recently re-introduced into clinical practice as a last resort for the treatment of nosocomial infections caused by multiresistant bacteria. This retrospective cohort study was designed to identify predictors of acute kidney injury (AKI) associated with intravenous (i.v.) CMS treatment. From March 2007 to July 2008, 71 adult patients receiving CMS for ≥72 h were enrolled. AKI was defined using Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) criteria according to serum creatinine. The median total dose of CMS was 54.3 mg/kg (range 27.5–94.5 mg/kg). AKI developed in 38 patients (53.5%). Cox regression analysis based of cumulative CMS dose (mg/kg) identified four independent predictors of AKI: male sex [hazard ratio (HR) = 3.55, 95% confidence interval (CI), 1.47–8.55]; concomitant use of a calcineurin inhibitor (HR = 6.74, 95% CI 2.49–18.24); hypoalbuminaemia (serum albumin level <2.0 g/dL) (HR = 6.29, 95% CI 2.04–19.39); and hyperbilirubinaemia (total bilirubin level >5 mg/dL) (HR = 3.53, 95% CI 1.17–10.71). In conclusion, AKI was a common complication of i.v. CMS treatment. Male sex, concomitant use of calcineurin inhibitors, hypoalbuminaemia and hyperbilirubinaemia were independent predictors of AKI. The effect of AKI on patient outcomes was not determined. 相似文献
8.
IntroductionCigarette use is associated with substance use and mental health problems among youth, but associations are unknown for non-cigarette tobacco product use, as well as the increasingly common poly-tobacco use.MethodsThe current study examined co-occurrence of substance use and mental health problems across tobacco products among 13,617 youth aged 12–17 years from Wave 1 (2013–2014) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. Participants self-reported ever cigarette, e-cigarette, smokeless tobacco, traditional cigar, cigarillo, filtered cigar, hookah, and other tobacco product use; alcohol, marijuana, and other drugs; and lifetime substance use, internalizing and externalizing problems.ResultsIn multivariable regression analyses, use of each tobacco product was associated with substance use, particularly cigarillos and marijuana (AOR = 18.9, 95% CI: 15.3–23.4). Cigarette (AOR = 14.7, 95% CI: 11.8–18.2) and cigarillo (AOR = 8.1, 95% CI: 6.3–10.3) use were strongly associated with substance use problems and tobacco users were more likely to report internalizing (AOR = 1.6, 95% CI: 1.4–1.8) and externalizing (AOR = 1.4, 95% CI: 1.3–1.6) problems. Female tobacco users were more likely to have internalizing problems than male tobacco users. Poly-tobacco users were more likely than exclusive users to use substances (AOR = 3.4, 95% CI: 2.7–4.3) and have mental health (AOR = 1.2, 95% CI: 1.0–1.5) and substance use (AOR = 4.7, 95% CI: 3.4–6.6) problems.ConclusionsRegardless of the tobacco product used, findings reveal high co-occurrence of substance use and mental health problems among youth tobacco users, especially poly-tobacco users. These findings suggest the need to address comorbidities among high risk youth in prevention and treatment settings. 相似文献
9.
The essential element manganese (Mn) might be toxic at excess exposure. We assessed the impact of elevated Mn exposure through drinking water during pregnancy on birth size in a population-based cohort(n = 1695) in rural Bangladesh. Concentrations of water Mn (median = 236 μg/L, range = 7.1–6336; n = 1177) and erythrocyte Mn (median = 30 μg/kg, range = 6.3–114; n = 758) were measured using ICP-MS. In regression analyses, newborns of women in the highest tertile of water Mn (median = 1495 μg/L) were 0.49 cm (0.20 SD) shorter (B = −0.42; 95% CI: −0.77, −0.08) than those in the lowest tertile (56 μg/L). The inverse association was significant in girls and also in boys of mothers with lowest hemoglobin values, likely due to higher absorption of Mn. Manganese concentrations in water and erythrocytes did not correlate, and the associations of the latter with birth size were less obvious. This study suggests that consumption of water with highly elevated Mn levels during pregnancy may impair fetal growth. 相似文献
10.
《Antiviral research》2009,81(3):266-271
Cyanovirin-N (CV-N), a protein derived from Nostoc ellipsosporum, neutralizes influenza virus infectivity by binding to specific high-mannose oligosaccharides (oligomannose-8 and -9) at glycosylation sites on the viral hemagglutinin HA1 subunit. Mouse-adapted viruses lose sensitivity to CV-N due to HA1 mutations that eliminate these glycosylation sites. Recently we created a hybrid (reassortant) influenza A/WSN/33 (H1N1) virus containing the HA gene of A/New Caledonia/20/99 (H1N1) with an Asp225Gly mutation in the HA1, that was lethal to mice yet retained sensitivity to CV-N. We then utilized this model system to test the efficacy of CV-N against influenza. CV-N efficacy was dose-responsive from 0.0625 to 1 mg/kg/day when administered intranasally (i.n.) twice daily for 4 days starting 4 h prior to virus exposure. In a second study, survival benefit was seen with CV-N treatments (0.5 mg/kg/day for 4 days) beginning at −4 or +6 h, but was significantly reduced at +12 h. The early treatment resulted in up to 100% survival and 1000-fold reduction in lung virus titer on day 3 of the infection. In contrast, ribavirin (a positive control—75 mg/kg/day) treatment resulted in 30% survival and 30-fold decrease in lung virus titers. Lung consolidation scores and lung weights were significantly reduced by CV-N and ribavirin treatment on day 6 of the infection. Ferrets infected with a non-animal adapted influenza A/Charlottesville/31/95 (H1N1) virus were treated intranasally with CV-N (50 μg twice daily for 5 days starting 24 h before virus challenge). They exhibited 100-fold lower viral titers in nasal washes than placebos 1 day after treatment, but virus titers were equivalent on days 2–7. CV-N has the potential for prophylaxis and early initiation of treatment of influenza virus infections. 相似文献
11.
IntroductionWaterpipe typically is smoked intermittently over long smoking sessions. Waterpipe is addictive and its users show symptoms of nicotine dependence (ND). This study examined the risk of developing ND symptoms across waterpipe use patterns among Lebanese youth.MethodsWaterpipe use patterns (length of smoking session, smoking a whole waterpipe without sharing, past-30 day use frequency, number of waterpipes smoked) were assessed. Symptoms of ND were assessed using the 10-item Hooked on Nicotine Checklist (HONC; endorsement of ≥ 1 symptom) and the 6 criteria of the International Classification of Diseases-10th revision (ICD-10 ND; presence of ≥ 3 criteria during 12 months).ResultsBoth the proportion of participants endorsing ND symptoms and the average number of endorsed ND symptoms increased with increasing waterpipe use frequency, number of waterpipes smoked, and length of smoking session. The risk of endorsing ≥ 1 HONC symptom increased with increasing number of waterpipes smoked in the past 30-days (≥ 10 vs. < 4 waterpipes; Hazard ratio (HR) = 2.05, 95% CI: 1.52–2.58, p = 0.007), and session length (> 60 min vs. < 30 min; HR = 2.87, 95% CI: 2.83–2.91, p = 0.001). The risk of attaining ICD-10 ND increased with increasing number of waterpipes used in the past 30-days (≥ 10 vs. < 4 waterpipes; HR = 2.56, 95% CI: 1.89–3.22, p = 0.006), and smoking every day/almost every day vs. less than once weekly (HR = 2.86, 95% CI: 2.12–3.60, p = 0.007).ConclusionsIncreasing use frequency, number of waterpipes smoked, and longer smoking sessions were associated with higher risk of ND. The length of smoking session emerged as a novel indicator of ND among waterpipe smokers. 相似文献
12.
Chrisovalantis Papaefthimiou Efthimia Antonopoulou George Theophilidis 《Toxicology in vitro》2009,23(2):272-280
The results of this study have shown that N-acetyl-l-cysteine (NAC), a compound used for protection of tissues or cell cultures against the deleterious effects of various environmental pollutants, has certain unusual effects on the contraction of the spontaneously beating atria of the frog isolated in saline (ex vivo): (1) NAC, 6.0 and 10.0 mM, eliminated, in a concentration-dependent manner, the contractile properties of the atria (force and frequency) within minutes, without affecting its electrical properties; (2) the IC50 of NAC for the force was 5.09 ± 1.01 mM (n = 6) [4.98–5.19 mM, 95% confidence interval (CI)], significantly lower than the IC50 for the frequency, 6.15 ± 1.01 mM, (6.02–6.29 mM, 95% CI), indicating that working atria cells are more sensitive to NAC than autorhythmic cells. The no-observed-effect concentration (NOEC) was 1–2 mM; (3) the pattern of NAC-induced inhibition of electromechanical activity was similar to that of verapamil, an indication that NAC possibly affects L-type voltage-gated calcium channels; (4) NAC at 2 mM protected against cadmium-induced inhibition of atria contraction. The IC50 for cadmium was 17.9 ± 1.1 μM (n = 6) (16.9–19.0 μM, 95% CI), while in the presence of 2 mM NAC, it became 123.3 ± 1.0 μΜ (n = 6) (114.8–132.4 μM, 95% CI). The same concentration of NAC failed to exert any protective effects against rotenone (5 μM)-induced inhibition of atria contraction. The protective effects of NAC are probably due to chelation of cadmium, rather than scavenging of oxidants. 相似文献
13.
Marek Droździk Joanna Stefankiewicz Rafał Kurzawa Wanda Górnik Tomasz Bączkowski Mateusz Kurzawski 《Pharmacological reports : PR》2009,61(4):690-696
Infertility is a common problem affecting one in six couples, and in 30% of infertile couples, the male factor is a major cause due to defective sperm quality. P-glycoprotein (P-gp), a product of the MDR1 (ABCB1) gene, may be a link between genetic and environmental factors contributing to the development of male infertility because pesticides (P-gp substrates) are well established factors of male infertility. The aim of the present study was to examine the effect of the MDR1 gene 3435C>T polymorphism on male infertility. In total, 162 male patients undergoing semen analysis due to initial infertility workup were included in the study. The control group consisted of 191 healthy males with proven fertility. MDR1 3435C>T genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Assessment of MDR1 genotypes among the infertile men showed that 17.9% of subjects were carriers of the CC genotype, 58.0% were CT and 24.1% were TT. Among fertile men, 30.4% of subjects were characterised by the CC genotype, 49.7% were CT and 19.9% were TT. In addition, the frequency of carriers of at least one T allele (i.e., CT and TT genotypes) among infertile and fertile subjects was 82.1% and 69.6%, respectively. The risk of infertility was significantly elevated by two-fold in individuals carrying at least one T allele (CT and TT genotypes: p = 0.009, OR = 2.00, 95% CI: 1.20–3.32). Furthermore, this elevated risk was still found when considering each of the CT and TT genotypes alone (TT genotype: p = 0.027, OR = 2.05, 95% CI: 1.09–3.86; CT genotype: p = 0.013, OR = 1.98, 95% CI: 1.16–3.36). This preliminary report suggests that P-gp may play some role in male infertility, mediating detrimental effects of environmental factors. 相似文献
14.
Massimiliano Fabbiani Simona Di Giambenedetto Enzo Ragazzoni Gabriella D’Ettorre Giustino Parruti Mattia Prosperi Laura Bracciale Roberto Cauda Pierluigi Navarra Andrea De Luca 《Pharmacological research》2011,63(3):249-253
The present study aimed to investigate potential drug interactions between darunavir and raltegravir in patients treated for HIV infection. We enrolled HIV-infected subjects on darunavir-containing regimens that underwent measurement of plasma darunavir trough concentration (12 ± 3 h after dosing). Two groups of patients were compared: those taking darunavir plus a nucleoside/nucleotide backbone (group 1) or a backbone + raltegravir (group 2). Interindividual pharmacokinetic variability was evaluated through the coefficient of variation (CVinter).We obtained 156 plasma samples from 63 patients, of which 44 in group 1 and 19 in group 2. Overall, darunavir geometric mean concentration was 2.90 mg/L (95% CI 2.34–3.60) while ritonavir geometric mean concentration was 0.21 mg/L (95% CI 0.17–0.27). We observed a high inter-individual variability in darunavir (CVinter 59%) and ritonavir (CVinter 103%) plasma levels. Darunavir concentration correlated with concomitant ritonavir levels (r = 0.476, p < 0.001). Patients in group 1 had a higher darunavir geometric mean concentration than those in group 2 [3.44 mg/L (95% CI 2.79–4.23) versus 1.95 mg/L (95% CI 1.19–3.20), p = 0.017]. However, the proportion of subjects with concomitant HIV-RNA <50 copies/mL was higher in group 2 (78.9% versus 47.7%, p = 0.028). In a multivariable model, raltegravir co-administration was independently related to a lower darunavir concentration (mean difference ?0.25 log10 mg/L, 95% CI ?0.46/?0.04, p = 0.020) after adjusting for time from last drug intake and concomitant drugs used.In conclusion, a potential drug interaction between darunavir and raltegravir was observed, although this did not seem virologically significant. For the distinct metabolic pathways of these drugs, its mechanism remains to be determined. 相似文献
15.
《Reproductive toxicology (Elmsford, N.Y.)》2007,23(4):765-773
Exposure to persistent organochlorine pollutants (POPs) may have negative impact on male reproductive function. We, therefore, investigated the association between serum levels of POPs and epididymal and accessory sex gland function. Serum levels of CB-153, p,p′-DDE and seminal markers of epididymal [neutral-α glucosidase (NAG)], prostatic [prostate specific-antigen (PSA)] and zinc, and seminal vesicle function (fructose) were measured from 135 Swedish fishermen and fertile men from Greenland (n = 163), Warsaw, Poland (n = 167) and Kharkiv, Ukraine (n = 158). Multiple linear regression analyses, adjusting for potential confounders, were employed using both continuous and categorized exposure variables. Both exposure and outcome variables were log transformed. Considering the consistency between models with either continuous or categorized CB-153 levels, negative associations with the activity of NAG were found among Greenlandic men (mean difference 7.0 mU/ejaculate, 95% CI 3.0, 34), and in the aggregated cohort (mean difference 4.0 mU/ejaculate, 95% CI −0.2, 8.0). A positive association was observed between CB-153 and PSA as well as zinc among Kharkiv men. In the Swedish cohort, a negative association was found between CB-153 and fructose. In conclusion, the negative effects of POP on sperm motility, observed in the same study population might partly be caused by post-testicular mechanisms, involving a decreased epididymal function. 相似文献
16.
AimsTo assess whether bottles of refill liquids for e-cigarettes were filled true to label, whether their content was constant across two production batches, and whether they contained impurities.MethodsIn 2013, we purchased on the Internet 18 models from 11 brands of e-liquids. We purchased a second sample of the same models 4 months later. We analyzed their content in nicotine, anabasine, propylene glycol, glycerol, ethylene glycol and diethylene glycol, and tested their pH.ResultsThe median difference between the nicotine value on the labels and the nicotine content in the bottles was 0.3 mg/mL (range − 5.4 to + 3.5 mg/mL, i.e. − 8% to + 30%). For 82% of the samples, the actual nicotine content was within 10% of the value on the labels. All models contained glycerol (median 407 mg/mL), and all but three models contained propylene glycol (median 650 mg/mL). For all samples, levels of anabasine, ethylene glycol and diethylene glycol were below our limits of detection. The pH of all the e-liquids was alkaline (median pH = 9.1; range 8.1 to 9.9). The measured content of two batches of the same model varied by a median of 0% across batches for propylene glycol, 1% for glycerol, 0% for pH, and 0.5% for nicotine (range − 15% to + 21%; 5th and 95th percentiles: − 15% and + 10%).ConclusionsThe nicotine content of these e-liquids matched the labels on the bottles, and was relatively constant across production batches. The content of propylene glycol and glycerol was also stable across batches, as was the pH. 相似文献
17.
BackgroundThough direct acting antivirals (DAAs) promise high cure rates, many providers and payers remain concerned about successful treatment for people who use drugs (PWUD), even among those engaged in opioid agonist treatment (OAT). The efficacy of DAAs among PWUD in real-world settings is unclear.MethodsWe conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 (n = 89) at a primary care clinic in the Bronx, NY. Onsite HCV treatment with DAAs was performed by an HCV specialist, with support from a care coordinator funded by the NYC Department of Health. We identified four categories of drug use and drug treatment: (1) no active drug use/not receiving OAT (defined as non-PWUD); (2) no active drug use/receiving OAT; (3) active drug use/not receiving OAT; and (4) active drug use/receiving OAT. The primary outcome was SVR at 12 weeks post-treatment.ResultsOverall SVR rates were 95% (n = 41/43) for non-PWUD and 96% (n = 44/46) for patients actively using drugs and/or receiving OAT [p = 0.95]. There were no differences in SVR rates by drug use or drug treatment category. Compared to non-PWUD, those with no active drug use/receiving OAT had 100% SVR (n = 15/15; p = 1.0), those actively using drugs/not receiving OAT had 90% SVR (n = 9/10; p = 0.47), and those actively using drugs/receiving OAT had 95% SVR (20/21; p = 1.0).ConclusionRegardless of active drug use or OAT, patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates. We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and/or receiving OAT. 相似文献
18.
BackgroundUse of opioid analgesic medicines has doubled globally over the past decade, with a concomitant increase in prevalence of injection of pharmaceutical opioids (PO), including in Australia. This study investigates types of PO injected, methods used to prepare PO for injection and correlates of recent (last 6 months) PO injection among a large national sample of people who inject drugs (PWID).MethodsThe Australian NSP Survey (ANSPS), conducted annually at ∼50 NSP services across Australia, consists of a brief self-administered questionnaire and provision of a capillary dried blood spot for HIV and hepatitis C antibody testing. Data from 2014 were used to conduct univariable and multivariable logistic regression analysis to determine factors independently associated with recent injection of PO.ResultsAmong 1488 ANSPS respondents who were identified as opioid injectors, 57% (n = 848) reported injection of PO in the previous six months. The majority of PO injectors (85%) reported filtering PO prior to injection, although use of efficacious wheel filters was relatively rare (11%). Correlates of POs injection included daily injection (AOR = 1.65, 95% CI 1.31–2.08), receptive sharing of syringes (AOR = 2.00, 95% CI 1.43–2.78), receptive sharing of drug preparation equipment (AOR = 1.55, 95% CI 1.19–2.01), drug overdose in the previous year (AOR = 1.81, 95% CI 1.36–2.42) and residence in inner regional (AOR = 3.27, 95% CI 2.21–5.23) or outer regional/remote (AOR = 5.50, 95% CI 3.42–8.84) areas of Australia.ConclusionPO injection is geographically widespread among Australian PWID and takes place in the context of poly-drug use. People who inject POs are at high risk of overdose, injection related injury and disease and blood borne viral infections. Harm reduction services that target this group, including in non-urban areas, should deliver health education regarding PO-specific overdose risks, the requirement to adequately filter PO before injection and to ensure that both naloxone and specialist pill filters are readily accessible. 相似文献
19.
《European neuropsychopharmacology》2014,24(4):553-563
A randomised placebo-controlled “dose relation study” was conducted in 549 patients who met the criteria for major depressive disorder, to evaluate the efficacy and safety of three doses regimens of agomelatine during 6 weeks: low fixed dosage (10 mg/day, n=133), fixed dosage (25 mg/day, n=138) and a flexible dosage with up-titration in case of insufficient improvement at week 2 (25–50 mg/day, n=137). At last post-baseline assessment, there were significant and incremental placebo-agomelatine differences on mean HAM-D17 total scores in favour of each agomelatine dose regimen (2.46±0.76 points, p=0.001 at 10 mg; 4.71+0.75 points, p<0.0001 at 25 mg and 4.92±0.76 points, p<0.0001 at 25–50 mg) with statistically significant differences between 25 mg and 25–50 mg dose regimens compared to the 10 mg dose. The response rate according to HAM-D17 was significantly higher in patients taking agomelatine than those taking placebo (difference of 16.1% at 10 mg p=0.005; 25.9% and 27.4% respectively at 25 mg and 25–50 mg, p<0.0001). The benefit of agomelatine was demonstrated in the subgroup of severely depressed patients in the 25 mg and 25–50 mg/day regimens. Consistent clinical response according to CGI variables and better social functioning were found in patients receiving agomelatine. All dose regimens of agomelatine were well tolerated and no unexpected adverse event was reported. This study provides evidence of a dose effect for agomelatine between 10 mg and the therapeutic dose regimen of agomelatine 25–50 mg: the efficacy of the higher dose regimens being more efficacious than the lowest (10 mg) daily dose. The data support a definitive statement regarding the utility of 25 mg as the threshold dose for initiating agomelatine in depressed patients. 相似文献
20.
David Coghill Tobias Banaschewski Michel Lecendreux Cesar Soutullo Mats Johnson Alessandro Zuddas Colleen Anderson Richard Civil Nicholas Higgins Andrew Lyne Liza Squires 《European neuropsychopharmacology》2013,23(10):1208-1218
This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6–17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was ?18.6 (95% confidence interval [CI]: ?21.5 to ?15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was ?13.0 (95% CI: ?15.9 to ?10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70–86), 14% (8–21), and 61% (51–70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD. 相似文献