Leveraging marginal structural modeling with Cox regression to assess the survival benefit of accepting vs declining kidney allograft offers

Existing studies evaluating the survival benefit of kidney transplantation were unable to incorporate time–updated information on decisions related to each organ offer. We used national registry data, including organ turndown data, to evaluate the survival benefit of accepting vs turning down kidney offers in candidates waitlisted from 2007‐2013. Among candidates who declined their first offer, only 43% ultimately received organ transplantations. Recipients who later underwent organ transplantation after declining their first offer had markedly longer wait times than recipients who accepted their first offer, and 56% received kidney transplants that were of similar or lower quality compared to their initial offer. In marginal structural modeling analyses accounting for time‐updated offer characteristics (including Kidney Donor Profile Index, Public Health System risk status, and pumping), after 3 months posttransplant, there was a significant survival benefit of accepting an offer (adjusted hazard ratio 0.76, 95% confidence interval 0.66‐0.89) that was similar among diabetics, candidates aged >65 years, and candidates living in donor service areas with the longest waitlist times. After carefully accounting for the effect of donor quality, we confirm that the survival benefit of accepting an organ offer is clinically meaningful and persistent beyond 3 months post–kidney transplantation, including high‐risk subgroups of organ transplantation candidates.     

Heme oxygenase/carbon monoxide-biliverdin pathway may be involved in the antinociceptive activity of etoricoxib, a selective COX-2 inhibitor

The aim of this study was to assess the interaction between the heme oxygenase-1/ biliverdin/carbon monoxide (HO-1/BVD/CO) and cyclooxygenase-2 (COX-2) pathways in the writhing test. Mice were pretreated with 0.1, 1 or 10 mg/kg, ip etoricoxib, a selective COX-2 inhibitor, or with one of the following HO-1/BVD/CO pathway modulators: 1, 3 or 9 mg/kg, sc ZnPP IX, a specific HO-1 inhibitor, 0.3, 1 or 3 mg/kg, sc hemin, a substrate of the HO-1/BVD/CO pathway; or 0.00025, 0.025 or 2.5 μmol/kg, sc DMDC, a CO donor. Mice pretreated with etoricoxib or one of the HO-1/BVD/CO pathway modulators received an injection of acetic acid (ip) after 30 and 60 min, respectively. Next, the number of writhes was quantified between 0 and 30 min after stimulus injection. In another series of experiments, ineffective doses of etoricoxib were co-administered with hemin or DMDC and an effective dose of etoricoxib with ZnPP IX, followed by an acetic acid injection. Four hours after the acetic acid injection, levels of bilirubin, which is a product of BVD conversion by the BVD reductase enzyme, in the peritoneal lavage were determined. Hemin or DMDC reduced (p<0.05) the number of writhes, but ZnPP IX potentiated (p<0.05) the effect of acetic acid by increasing (p < 0.05) the number of writhes. The co-administration of etoricoxib with hemin or DMDC reduced (p<0.05) the number of writhes. However, the analgesic effect of etoricoxib was not observed in the presence of ZnPP IX. Pretreatment with ZnPP IX reduced bilirubin levels, but etoricoxib pretreatment significantly increased the bilirubin concentration in peritoneal exudates. The data obtained from these experiments showed that the HO-1/BVD/CO pathway was activated in the acetic acid-induced abdominal writhing model. The analgesic effect of etoricoxib was at least partially dependent on the participation of the HO-1/BVD/CO pathway.     

Genome-wide association scan allowing for epistasis in type 2 diabetes

In the presence of epistasis multilocus association tests of human complex traits can provide powerful methods to detect susceptibility variants. We undertook multilocus analyses in 1924 type 2 diabetes cases and 2938 controls from the Wellcome Trust Case Control Consortium (WTCCC). We performed a two‐dimensional genome‐wide association (GWA) scan using joint two‐locus tests of association including main and epistatic effects in 70,236 markers tagging common variants. We found two‐locus association at 79 SNP‐pairs at a Bonferroni‐corrected P‐value = 0.05 (uncorrected P‐value = 2.14 × 10^?11). The 79 pair‐wise results always contained rs11196205 in TCF7L2 paired with 79 variants including confirmed variants in FTO, TSPAN8, and CDKAL1, which are associated in the absence of epistasis. However, the majority (82%) of the 79 variants did not have compelling single‐locus association signals (P‐value = 5 × 10^?4). Analyses conditional on the single‐locus effects at TCF7L2 established that the joint two‐locus results could be attributed to single‐locus association at TCF7L2 alone. Interaction analyses among the peak 80 regions and among 23 previously established diabetes candidate genes identified five SNP‐pairs with case‐control and case‐only epistatic signals. Our results demonstrate the feasibility of systematic scans in GWA data, but confirm that single‐locus association can underlie and obscure multilocus findings.     

The active search for respiratory symptomatics for the control of tuberculosis in the Potiguara Indigenous Scenario, Paraiba, Brazil

This study sought to analyze the actions of an active search for respiratory symptomatics (RSs) in the control of tuberculosis (TB) in the Potiguara Special Indigenous Sanitary District, Paraiba, Brazil, between May and June 2007. After approval by the Research Ethics Committee, 23 professionals were grouped, including physicians, nurses, nurse technicians and indigenous health agents. The focus group technique was used as an instrument for data collection, based on the discourse analysis technique. Weaknesses of an operational nature that became apparent, related to the organization of local health service for the implementation of routines for diagnosing TB: absence of a systematic routine for searching for RSs, difficulties in organizing the material for bacteriological examination, inadequate approach to patient during sputum collection and inadequate professional training. It is deemed necessary to improve the organization of services for early detection of TB cases in the local indigenous scenario.     

What are the prevalence,characteristics and significance of fetal lateral neck cysts detected in an early anatomical scan?

Purpose

This study evaluated the association of fetal lateral neck cysts (FLNC) with adverse pregnancy outcomes, in relation to specific sonographic characteristics and co-existing findings.

Methods

Pregnancies in which FLNC were detected by a single examiner in early anatomical scans (14–16 weeks) were included. Data regarding the pregnancy and its outcome were retrieved from telephone-based questionnaires, patient charts and from the examiner’s reports.

Results

654 cases of FLNC were detected among 9446 early anatomical scans (6.9%). Complete data regarding 219 pregnancies were available. FLNC were significantly more prevalent in males (65.2%). The prevalence of heart malformations was 3.2% [all were non-isolated cases or with abnormal nuchal translucency (NT) and/or nuchal fold (NF)]. Amniocentesis performed in 165 pregnancies was abnormal in 1.2%. Among 206 children born from this cohort, adverse medical outcomes were reported in 5.3%. The likelihood of adverse pregnancy outcomes was significantly higher in non-isolated cases and in cases with abnormal NT or NF. Sonographic characteristics such as cyst size and bilateral findings were not linked to adverse pregnancy outcomes.

Conclusion

Isolated FLNC are benign findings which do not require additional work up. FLNC with additional sonographic abnormalities are associated with a significantly increased risk for adverse pregnancy outcomes.

     

MSPD Sample Preparation Approach for Reversed-Phase Liquid Chromatographic Analysis of Pesticide Residues in Stem of Coconut Palm

A method was developed using matrix solid-phase dispersion, together with liquid chromatography with ultraviolet diode array detector for determination of carbofuran, difenoconazole, β-cyfluthrin, spirodiclofen and thiophanate-methyl in stem of coconut palm. The best results were obtained using 2.0 g of stem, 1.6 g of Florisil as sorbent and cyclohexane:acetone mixture (4:1). The method was validated using stem samples spiked with pesticides at four concentration levels (0.05–2.0 μg/g). Average recoveries ranged from 70 % to 114.3 %, with relative standard deviations between 1.2 % and 19.2 %. Detection and quantification limits were in the ranges 0.02–0.03 and 0.05–0.1 μg/g, respectively.     

Age-related normogram for antral follicle count in women with polycystic ovary syndrome

Antral follicle count (AFC) has been shown to be a reliable marker for ovarian reserve. The aims of this study were to create an age-related normogram for AFC in infertile women with polycystic ovary syndrome (PCOS) and to compare age-related decline in AFC between infertile women with and without PCOS. A retrospective cohort study was conducted. Of a total of 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were large variations in the AFC between the 10th and 90th percentiles in all age groups. The rate of decline in AFC among women with PCOS was linear, while in those with non-PCOS, it was exponential until 30 years of age, and then became similar to that of PCOS. The rate of follicle loss per year was significantly slower in PCOS women compared with that in non-PCOS women. In both groups, the fastest period of follicle loss was between the ages of 18 and 30. The average follicle loss was 0.8 follicles/year in PCOS women and 1.7 follicles/year in those without PCOS (P < 0.001). This study concludes that age-related decline in AFC among women with PCOS is slower than in those without PCOS.Antral follicle count (AFC) has been shown to be a reliable marker for ovarian reserve. The aims of this study were to create an age-related normogram for AFC in women with polycystic ovary syndrome (PCOS), and to compare age-related decline in AFC between women with and without PCOS. A retrospective cohort study was conducted. All patients underwent a baseline transvaginal ultrasound that was performed on day 2–4 of the menstrual cycle. The total number of antral follicles of 2–9 mm in diameter was recorded. Of total 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were large variations in the AFC between the 10th 90th percentiles in all age groups. The rate of decline in AFC among women with PCOS was linear; while in those with non-PCOS, it was exponential until 30 years of age, and then became similar to that of PCOS. The rate of follicle loss per year was significantly slower in PCOS women compared with that in non-PCOS women. In both groups, the fastest period of follicle loss was between the ages 18–30 years. The average follicle loss was 0.8 follicles/year in PCOS women and 1.7 follicles/year in those without PCOS (P < 0.001). We have concluded that age-related decline in AFC among women with PCOS is slower than in those without PCOS. Further studies are needed to determine if the AFC normogram in women with PCOS could be clinically relevant to select the optimal gonadotrophin dose for ovulation induction.