Increase In Number Of Subjects Research Articles

Effects of seafood consumption on mercury exposure in Norwegian pregnant women: A randomized controlled trial

BackgroundSeafood provides nutrients that are important for optimal development of the unborn child. However, seafood is also a source of contaminants including mercury (Hg) and methylmercury (MeHg) that may have adverse effects on neurodevelopment of the fetus. Humans are predominantly exposed to MeHg through seafood consumption, however, levels of MeHg vary considerably between species. ObjectivesInvestigate, in a randomized controlled trial (RCT) during pregnancy, if an increased intake of Atlantic cod (Gadus morhua), a fish species with relatively low levels of MeHg contamination, influences total hair Hg (THHg) concentrations in humans. MethodsPregnant women (n = 137) were enrolled in the RCT “Mommy’s Food” (2016–2017), which was designed to increase iodine status. Participants were randomly assigned to intervention (400 g of cod fillets per week) or control (continued habitual diet) groups for 16 weeks (gestational week 20–36). THHg concentrations were measured at baseline and post-intervention using thermal decomposition, amalgamation, and atomic absorption spectrophotometry (US EPA method 7473). The trial is registered in ClinicalTrials.gov, NCT02610959. ResultsPost-intervention, the intervention group had median (inter-quartile range) THHg concentrations of 554 (392–805) µg/kg, and the control group 485 (341–740) µg/kg (p = 0.186). When adjusting for baseline THHg concentrations, there was a significant difference between the groups in those participants with baseline THHg concentrations below 534 µg/kg. Post-intervention, 8% of the study population exceeded the US EPA reference dose in hair (1,000 µg/kg) (intervention group: n = 6, control group: n = 4). ConclusionTHHg concentrations were generally low in both study groups of pregnant women, despite the relatively high seafood intake. While the intervention with 400 g of cod per week slightly increased THHg concentrations, it did not lead to an increase in number of subjects exceeding the US EPA reference dose; a dose level at which no adverse effects are expected to occur over a period of lifetime exposure.

Dynamics of risk factor prevalence in Ryazan region population (5-year observation)

Aim: To assess 5-year prevalence of certain risk factors (RF) in men and women of Ryazan region. Methods: In 2002 as a part of Russian epidemiological EPOCH study, a representative sample of Ryazan region population was evaluated (2098 subjects, mean age 44.8±18.6 years). Sample generation was made in three steps: consecutive selection of medical institutions, GP districts and flats was made. With a response rate of 83.9% 1760 people were assessed in 2007, 200 died, 223 migrated, 13 withdrawn consent. Dynamics of risk factors prevalence was analysed: hypertension (HT), smoking, alcohol abuse, salt abuse, obesity, low physical activity, diabetes mellitus. Results: HT prevalence did not change over 5 years (36.6±1.1% vs. 39.3±1.2%), in women HT prevalence was higher in both 2002 (38.2% vs. 33.9%, p<0.05) and 2007 (42.1% vs. 34.8%, p<0.001). Smoking prevalence did not significantly change over 5 years (25.1% vs. 23.9%). Maximum smoking prevalence was found in the 30-39 years age group (62.1% of men and 13.8% of women). During 5-years the number of alcohol abusers decreased by 3.1% and amounted to 12.4% in men and 0.6% in women, which is less than in 2002 (15.8% and 1.6%). Prevalence of salt abuse after five years remained the same in both men (45.0% vs. 46.3% in 2002, p=0.62) and women (35.1% vs. 34.7% in 2002, p=0.27). There was a significant increase in number of obese subjects – from 18.8% to 22.6%, p<0.001. Obesity was more typical for women (28.3% vs. 14.0%, p<0.001), whereas it's prevalence increased over 5 years in both women (4.7%, p<0.001) and men (by 2.3%, p=0.068). Over the observation period, portion of subjects with low physical activity increased by 8.8%, p<0.001 (by 14% in men, p<0.001, and by 1.4% in women, p=0.48). Prevalence of diabetes didn't change (4.5% vs. 3.4% in 2002), both in men (3.2% vs. 2.4% in 2002), and in women (4.8% vs. 3.9% in 2002). As five years ago, most of the respondents in the assessed sample have a combination of several risk factors. The number of subjects with two factors increased from 28.4% to 32.2%, p<0.001, with three factors – from 15.6% to 21.3%, p<0.001. The number of subjects with more than 3 risk factors remained the same, and with no or only one factor decreased from 16.0% to 11.8%, p<0.001 and from 29.4% to 24.4%, p<0.001, respectively. Conclusion: A high prevalence of cardiovascular risk factors was revealed in the population of Ryazan region. Over a period from 2002 to 2007 there was a significant increase in number of subjects with obesity (from 18.8% to 22.6%, p<0.001).

Soluble Itraconazole in Tablet Form Using Disordered Drug Delivery Approach: Critical Scale-up Considerations and Bio-equivalence Studies

The present research work explores formulation design, critical scale-up considerations and bio-equivalence studies of soluble itraconazole (ITZ) in a tablet form using disordered drug delivery approach. Disordered system of ITZ with a lower viscosity grade of hydroxypropyl methyl cellulose (Pharmacoat 603) was developed for the first time and extensively characterised at three different stages, namely development of glass system, pellet coating and tablet compression using advanced analytical techniques. Complete molecular embedment of ITZ resulting in amorphisation was observed and found to be sustained until end of the real-time and accelerated stability studies. Developed formulation exhibited comparative in vitro dissolution profile (similarity factor>70) with reference product (Sporanox, Janssen Pharmaceutica) in simulated gastric fluid without enzymes. Formulation was scaled up in three batches (50,000 tablets/batch) with detailed validation of critical process parameters using process capability index method. Critical scale-up considerations like control of residual solvent content, effect of pellet size on dissolution, process variables in pellet coating, compressibility of coated pellets and cushioning effect required for desired compressibility were thoroughly discussed. Bioequivalence study of single dose of test and reference product in seven healthy human volunteers under fed condition exhibited significant bioequivalence with results (AUClast and AUC∞) lying between 90% confidence interval. With increase in number of subjects to 24, a significant effect on pharmacokinetic parameters of both reference as well as developed ITZ tablets was observed.

Abstract 8321: Reduced Estimated Glomerular Filtration Rate Levels to Predict Mortality Depend on Presence of Hypertension or Diabetes

BACKGROUND: The current staging system of chronic kidney disease based on estimated glomerular filtration rate (eGFR) led to a marked increase in number of subjects to target for intervention and better methods for identifying those at high risk of adverse outcomes is needed. Hypertension (HT) and diabetes (DM) are the leading causes of end-stage renal disease and effect of reduced eGFR on mortality may be different among subjects with HT or DM. We examined effect of reduced eGFR on all-cause mortality according to presence or absence of HT and DM. METHODS: We studied 16,461 subjects (mean age 54±13 years, men 26%) who had the annual health examination offered to adult citizens of Moriguchi city, Osaka, Japan in 1997. The new equation for eGFR based on inulin renal clearance for Japanese was applied. The relative risks (RR) were calculated for mortality of each group according to eGFR levels of &lt;30 mL/min/1.73m 2 (group 1), 30-44 mL/min/1.73m 2 (group 2) and 45-59 mL/min/1.73m 2 (group 3), relative to the highest eGFR group (&gt;60 mL/min/1.73m 2 ; group 4), using proportional hazards regression analyses adjusted for age, sex, smoking, drinking, hypercholesterolemia, and history of cardiovascular disease, separately in DM subjects (with DM), HT only subjects (with HT without DM) and control subjects (no HT or DM). RESULTS: Reduced eGFR &lt;60 mL/min/1.73m 2 was observed in 13.5%. During a mean follow-up of 11.0±3.0 years (median 12.2 years), there were 1,208 deaths. In DM subjects, the RRs were significantly higher in group 3 (HR=1.65, 95% CI=1.12 to 2.42), group 2 (HR=2.03, 95% CI=1.04 to 3.97), and group 1 (HR=8.86, 95% CI=4.28 to 18.31), compared to group 4. In HT only subjects, the RRs were significantly higher in group 2 (HR=1.91, 95% CI=1.32 to 2.78) and group 1 (HR=3.42, 95% CI=1.86 to 6.28). In control subjects, the RR was significantly higher only in group 1 (HR=2.98, 95% CI=1.39 to 6.39). (figure). CONCLUSIONS: Reduced eGFR level to predict mortality depended on presence of HT or DM.

Effects of financing smoking cessation outpatient services in Taiwan

Objective: This study assesses the effects of a 2005 increase in funding for smoking cessation services on provider participation, patient utilisation of smoking cessation services and cessation outcome at a...

Brain plasticity, cognitive functioning and the relationship to treatment outcome in patients with tobacco dependence

Tobacco dependence is a complex neurobiological and behavioral phenomenon. Rates of relapse are tremendous. Our clinic offers behaviorally based group therapy in combination with nicotine patches to treat tobacco dependence over a period of six months. In the current study we test, if brain plasticity, as assessed by proton magnetic resonance spectroscopy (MRS) and/or cognitive functioning predict relapse within the initial 6 weeks. We measure N-Acetyl-Aspartate, Choline, Creatin in ventral striatum, anterior cingulate and prefrontal cortex. Cognitive testing includes executive function, memory and attention. 32 subjects and 11 controls have been examined (We expect 40 smokers and 20 controls). Differences were found in metabolic coefficient for Cholin/Creatin in the frontal cortex, responsible for executive function. Differences between smokers and non-smokers in executive functioning were emerging. A test of memory performance was significantly better in non-smokers. As number of relapse was low, increase in number of subjects and period investigated will increase statistical power and likelihood of finding significant predictors.

Dealing with the Proportional Hazards Assumption when Using the Proportional Hazards Model with a Single Independent Variable

In order to examine the proportional hazards assumption implicit in the proportional hazards model, three types of simulations were carried out on two groups of hypothetical survival data. Simulation 1 assumed that the hazard rate for one group was higher than that for the other group but that they were not proportional. Simulation 2 was an example of hazard rates crossing each other. Simulation 3 demonstrated the effect of the extent to which the hazard rates crossed. The test statistic, Z:PH, used for testing the proportional hazards assumption was calculated, along with the logarithm of the hazard ratio with its standard error. Although the increase in number of subjects was found to favor detections of violations of the proportional hazards assumption, cases such as those in Simulation 1 were considered acceptable for clinical use. Cases such as those in Simulation 2 were not suitable for the proportional hazards model. Simulation 3 suggested that cases with a substantial degree of unproportionality could be detected to violate the proportional hazards assumption, even when groups of 100 subjects each were involved in the analysis.