The bacterial colonization in tunneled cuffed dialysis catheter and its effects on residual renal function in incident hemodialysis patients

Background

The bacterial colonization of hemodialysis catheter occurs frequently and reaches to the catheter-related bloodstream infections (CRBSIs). We hypothesized bacterial colonization promotes inflammation and that might be associated with renal outcome. The aim of this study was to investigate the colonization status for tunneled cuffed dialysis catheter (TCC) and the factors for contributing to the catheter colonization and explore whether bacterial colonization would be related with declining of residual renal function (RRF).

Methods

115 patients who received TCC removal operation and underwent catheter tip culture from January 2005 to June 2014 were enrolled. The follow-up data such as urine output (UO), time to anuria and patients’ survival were collected from the patients or their family members by telephone in June, 2014.

Results

There were nineteen patients (16.5 %, 19/115) with positive tip culture (colonization group). In the analysis of demographic and biochemical parameters, there were no significant differences between both groups. Fifty of all the subjects responded to the telephone survey and ten patients (20.0 %, 10/50) belonged to colonization group. The monthly decreasing rate of UO was significantly more rapid in colonization group (p = 0.001). The survival analysis showed that colonization group had worse estimated anuria-free survival than non-colonization group (p < 0.001). In multivariate cox regression, bacterial colonization of TCC was an independent factor influencing the loss of RRF (HR 4.29, 95 % CI: 1.905–9.683, p ≤ 0.001).

Conclusions

Bacterial colonization of TCC was associated with rapid loss of RRF.

     

Rectal administration of artemisinin derivatives for the treatment of malaria

Context  Rectal administration of artemisinin derivatives is a potentially lifesaving emergency treatment of severe malaria. Many different preparations are marketed in tropical countries, but their pharmacokinetic disposition and clinical efficacy may vary. Objective  To review the pharmacokinetics, efficacy, and safety of rectally administered artesunate, artemisinin, dihydroartemisinin, and artemether. Data Sources  We searched the MEDLINE, EMBASE, Cochrane Database of Clinical Reviews, Global Health, Web of Science, and CINAHL computerized databases up to December 2006, along with reviewing unpublished data from conference proceedings, pharmaceutical companies, and regulatory applications. Studies in languages other than English were translated. Study Selection  Studies were included involving rectal administration of an artemisinin derivative to healthy volunteers or patients with measurement of plasma drug concentrations or rates of initial parasite clearance. Both single-arm and comparative trials were included. Data Extraction  Forty-five studies were identified, of which 39 eligible studies were included in the review. Primary efficacy outcome measures included parasite density as a percentage of baseline at 12 and 24 hours following the first dose. Pharmacokinetic variables included maximum plasma concentration (C_max), time to C_max (T_max), and area under the plasma concentration–time curve. Weighted means were calculated from available data. Data Synthesis  Thirty-two studies provided valid clinical efficacy data: 19 of artesunate, 10 of artemisinin, 2 of dihydroartemisinin, and 1 of artemether. All demonstrated prompt parasite clearance, with evidence of a dose-dependent effect for artesunate. Mortality rates in severe malaria (weighted means, 0%-13%) were consistent with those expected. Eight studies compared rectal artemisinin with conventional parenteral treatment (quinine, artemether, or artesunate) for severe malaria. Despite similar clinical outcomes, rectal artemisinin derivatives initiated parasite clearance more rapidly than parenteral treatment (percentage of baseline at 12 hours, 27% vs 56%, respectively). Eighteen pharmacokinetic studies were identified, including 13 of artesunate. There was marked interindividual variability in most pharmacokinetic variables, but artesunate achieved an earlier T_max and higher C_max and area under the plasma concentration–time curve than other artemisinin derivatives. Conclusions  Available rectal preparations of artemisinin derivatives differ in their pharmacokinetic disposition. Most available evidence pertains to artesunate and artemisinin. Despite marked interindividual variability in bioavailability, rectal preparations appear to have acceptable therapeutic efficacy, including in severe illness.      

Therapeutic roles of intracavernosal papaverine

Intracavernosal self-injection of smooth muscle relaxants, primarily papaverine admixed with phentolamine, have been used to treat impotence in over 300 patients. The program is effective in a large fraction of this group. Selection of patients, adjustment of dose, methods for monitoring, clinical efficacy, and complications are discussed.     

Factors relating to readmission of term and near-term neonates in the first two weeks of life. Early Discharge Survey Group of the Health Professional Advisory Board of the Greater New York Chapter of the March of Dimes

AIMS: A multisite study of term and near term infants readmitted in the first two weeks of life to 9 New York City area hospitals in 1995 was conducted to evaluate factors related to readmission, including length of newborn stay. RESULTS: Of the 30,884 infants born at the 9 study hospitals 391 newborns were readmitted. The major admission diagnoses were infection, 40.7%, hyperbilirubinemia, 39.1%, and feeding and/or gastrointestinal problems, 10.5%. In the first week, 65.1% of readmissions were for hyperbilirubinemia and 19.1% were for infection or suspected sepsis. In the second week, 67.8% of readmissions were for infection and 7.6% were for hyperbilirubinemia. Hyperbilirubinemia was the most frequent diagnosis for White and Asian infants, while infection was most frequent for African-American and Hispanic infants. Age at readmission was younger and the interval from discharge was shorter for infants with hyperbilirubinemia. Abnormalities which should have precluded early discharge included feeding difficulties, cyanotic congenital heart defects, hemolytic disease of the newborn, early jaundice or early high bilirubin levels. CONCLUSION: Attention to identification of infants at risk and programs such as lactation counseling and universal screening for bilirubin (with appropriate interpretation) prior to discharge could have reduced the necessity for readmission regardless of the newborn length of stay.     

Lead poisoning associated with illicit opium use

Lead poisoning is an uncommon and challenging diagnosis to make. In 2018, The Victorian Department of Health issued a health warning following four cases of lead poisoning associated with illicit opium use in Melbourne, Australia. We present these cases to highlight clinical features and the relevant investigations leading to diagnosis. All cases occurred in recent immigrants to Australia, who had access to non‐traditional sources of opioids. Health care professionals should consider lead poisoning in patients with appropriate symptoms and a history of illicit opium use.     

Ataxia telangiectasia-mutated protein and DNA-dependent protein kinase have complementary V(D)J recombination functions

Antigen receptor variable region exons are assembled during lymphocyte development from variable (V), diversity (D), and joining (J) gene segments. Each germ-line gene segment is flanked by recombination signal sequences (RSs). Recombination-activating gene endonuclease initiates V(D)J recombination by cleaving a pair of gene segments at their junction with flanking RSs to generate covalently sealed (hairpinned) coding ends (CEs) and blunt 5'-phosphorylated RS ends (SEs). Subsequently, nonhomologous end joining (NHEJ) opens, processes, and fuses CEs to form coding joins (CJs) and precisely joins SEs to form signal joins (SJs). DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activates Artemis endonuclease to open and process hairpinned CEs before their fusion into CJs by other NHEJ factors. Although DNA-PKcs is absolutely required for CJs, SJs are formed to variable degrees and with variable fidelity in different DNA-PKcs-deficient cell types. Thus, other factors may compensate for DNA-PKcs function in SJ formation. DNA-PKcs and the ataxia telangiectasia-mutated (ATM) kinase are members of the same family, and they share common substrates in the DNA damage response. Although ATM deficiency compromises chromosomal V(D)J CJ formation, it has no reported role in SJ formation in normal cells. Here, we report that DNA-PKcs and ATM have redundant functions in SJ formation. Thus, combined DNA-PKcs and ATM deficiency during V(D)J recombination leads to accumulation of unjoined SEs and lack of SJ fidelity. Moreover, treatment of DNA-PKcs- or ATM-deficient cells, respectively, with specific kinase inhibitors for ATM or DNA-PKcs recapitulates SJ defects, indicating that the overlapping V(D)J recombination functions of ATM and DNA-PKcs are mediated through their kinase activities.     

Characterization of treatment failure in efficacy trials of drugs against Plasmodium vivax by genotyping neutral and drug resistance-associated markers

Plasmodium vivax intervention trials customarily report uncorrected treatment failure rates. Application of recrudescence-reinfection genotyping and drug resistance single-nucleotide polymorphism typing to a 4-arm comparative efficacy trial illustrated that molecular approaches can assist in understanding the relative contributions of true drug resistance (recurrent with same genotype) and new infections to treatment failure. The PCR-corrected adequate clinical and parasitologic response may constitute an informative secondary endpoint in future P. vivax drug trials.     

Caregivers' acceptance of using artesunate suppositories for treating childhood malaria in Papua New Guinea

Community-based interventions using artemisinin-derived suppositories may potentially reduce malaria-related childhood mortality. However, their sociocultural acceptability is unknown in Papua New Guinea and a formal examination of caregiver's attitudes to rectal administration was needed to inform effective deployment strategies. Caregivers (n = 131) of children with uncomplicated malaria were questioned on their prior experience with, and attitudes to, rectal administration and then offered artesunate suppositories as treatment of their child. The 29% who refused this alternative were further questioned to determine their reasons for this refusal. Lack of spousal approval and fear of side effects were the most common reasons for refusal. Sixty-six percent of caregivers agreed to self-administer suppositories, which were perceived as effective (99%), safe (96%), and fast-acting (91%), but problematic to administer to a struggling child (56%). Shame, embarrassment, and hygiene were not significant concerns. Acceptability of rectal administration should be relatively high in Papua New Guinea. However, deployment must be accompanied by health education that addresses the practical aspects of administration, is appropriate for the illiterate, and is directed at fathers as well as mothers.