Fieldslater4915

Genomic epidemiology studies of gonorrhea in the United States have primarily focused on national surveillance for antibiotic resistance, and patterns of local transmission between demographic groups of resistant and susceptible strains are unknown.

We analyzed a convenience sample of genome sequences, antibiotic susceptibility, and patient data from 897 gonococcal isolates cultured at the NYC Public Health Laboratory from NYC Department of Health and Mental Hygiene (DOHMH) Sexual Health Clinic (SHC) patients, primarily in 2012-13. We reconstructed the gonococcal phylogeny, defined transmission clusters using a 10 non-recombinant single nucleotide polymorphism threshold, tested for clustering of demographic groups, and placed NYC isolates in a global phylogenetic context.

The NYC gonococcal phylogeny reflected global diversity with isolates from 22/23 of the prevalent global lineages (96%). Isolates clustered on the phylogeny by patient sexual behavior (p&0.001) and race/ethnicity (p&0.001). Mintransmission.

Unwanted weight gain affects some people living with HIV who are prescribed integrase strand transfer inhibitors (INSTI). Mechanisms and risk factors are incompletely understood.

We utilized two cohorts to study pharmacogenetics of weight gain following switch from efavirenz- to INSTI-based regimens. In an observational cohort, we studied weight gain at 48 weeks following switch from efavirenz- to INSTI-based regimens among patients who had been virologically suppressed for at least 2 years at a clinic in the United States. Associations were characterized with CYP2B6 and UGT1A1 genotypes that affect efavirenz and INSTI metabolism, respectively. In a clinical trials cohort, we studied weight gain at 48 weeks among treatment-naïve participants who were randomized to receive efavirenz-containing regimens in AIDS Clinical Trials Group studies A5095, A5142 and A5202 and did not receive INSTIs.

In the observational cohort (N=61), CYP2B6 slow metabolizers had greater weight gain after switch (p=0.01). This was seen following switch to elvitegravir or raltegravir, but not dolutegravir. UGT1A1 genotype was not associated with weight gain. In the clinical trials cohort (N=462), CYP2B6 slow metabolizers had lesser weight gain at week 48 among participants receiving efavirenz with tenofovir disoproxil fumarate (p=0.001) but not those receiving efavirenz with abacavir (p=0.65). Findings were consistent when stratified by race/ethnicity and by sex.

Among patients who switched from efavirenz- to INSTI-based therapy, CYP2B6 genotype was associated with weight gain, possibly reflecting withdrawal of the inhibitory effect of higher efavirenz concentrations on weight gain. The difference by concomitant nucleoside analogue is unexplained.

Among patients who switched from efavirenz- to INSTI-based therapy, CYP2B6 genotype was associated with weight gain, possibly reflecting withdrawal of the inhibitory effect of higher efavirenz concentrations on weight gain. The difference by concomitant nucleoside analogue is unexplained.Cryptococcal antigen (CrAg) detection could direct timely initiation of antifungal therapy. We searched MEDLINE and EMBASE for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on HIV-positive adults with suspected cryptococcal meningitis (CM). With QUADAS-2, we evaluated risk of bias (RoB) of 11 included studies on 3,600 participants and used random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg was 99.8% (88.4 - 100) and 95.2% (88.7 - 98), respectively; of CSF CrAg was 98.8% (96.2 - 99.6) and 99.3% (96.7 - 99.9), respectively. Agreement between CSF CrAg and CSF culture was 97% (96 - 99). In HIV-adults with CM symptoms, serum CrAg-negativity may rule out CM, positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In first episode of CM, CSF CrAg-positivity is diagnostic.

Despite the widespread use of erythropoiesis-stimulating agents (ESAs) to treat anaemia, the risk of adverse outcomes associated with the use of different types of ESAs in non-dialysis chronic kidney disease (CKD) is poorly investigated.

From a pooled cohort of four observational studies, we selected CKD patients receiving short-acting (epoetin α/β; n = 299) or long-acting ESAs (darbepoetin and methoxy polyethylene glycol-epoetin β; n = 403). The primary composite endpoint was end-stage kidney disease (ESKD; dialysis or transplantation) or all-cause death. Multivariable Cox models were used to estimate the relative risk of the primary endpoint between short- and long-acting ESA users.

During follow-up [median 3.6 years (interquartile range 2.1-6.3)], the primary endpoint was registered in 401 patients [166 (72%) in the short-acting ESA group and 235 (58%) in the long-acting ESA group]. In the highest tertile of short-acting ESA dose, the adjusted risk of primary endpoint was 2-fold higher hazard ratio [HR] 2.07 [95% confidence interval (CI) 1.37-3.12] than in the lowest tertile, whereas it did not change across tertiles of dose for long-acting ESA patients. Furthermore, the comparison of ESA type in each tertile of ESA dose disclosed a significant difference only in the highest tertile, where the risk of the primary endpoint was significantly higher in patients receiving short-acting ESAs [HR 1.56 (95% CI 1.09-2.24); P = 0.016]. Results were confirmed when ESA dose was analysed as continuous variable with a significant difference in the primary endpoint between short- and long-acting ESAs for doses >105 IU/kg/week.

Among non-dialysis CKD patients, the use of a short-acting ESA may be associated with an increased risk of ESKD or death versus long-acting ESAs when higher ESA doses are prescribed.

Among non-dialysis CKD patients, the use of a short-acting ESA may be associated with an increased risk of ESKD or death versus long-acting ESAs when higher ESA doses are prescribed.The Philopterus Complex includes several lineages of lice that occur on birds. The complex includes the genera Philopterus (Nitzsch, 1818; Psocodea Philopteridae), Philopteroides (Mey, 2004; Psocodea Philopteridae), and many other lineages that have sometimes been regarded as separate genera. Only a few studies have investigated the phylogeny of this complex, all of which are based on morphological data. Here we evaluate the utility of nuclear and mitochondrial loci for recovering the phylogeny within this group. Sunitinib molecular weight We obtained phylogenetic trees from 39 samples of the Philopterus Complex (Psocodea Philopteridae), using sequences of two nuclear (hyp and TMEDE6) and one mitochondrial (COI) marker. We evaluated trees derived from these genes individually as well as from concatenated sequences. All trees show 20 clearly demarcated taxa (i.e., putative species) divided into five well-supported clades. Percent sequence divergence between putative species (~5-30%) for the COI gene tended to be much higher than those for the nuclear genes (~1-15%), as expected.