Efficiency and patient experience with propofol vs conventional sedation: A prospective study

AIM: To determine whether anaesthesiologistadministered sedation with propofol(AAP) or endoscopist-administered conscious sedation(EAC) with fentanyl/midazolam shortens colonoscopy duration/total room time. METHODS: This is a prospective, non-randomized, comparative study that enrolled patients greater than 18 years of age undergoing colonoscopy in a single Canadian academic outpatient endoscopy unit over a three-month consecutive period. Colonoscopies in this unit are performed both with AAP and EAC. Patient demographics, procedure-related data and adverse events were documented. Additionally, the level of procedure difficulty, and whether a staff endoscopist, trainee with assistance, or independent trainee, performed the procedure were documented. A validated modified 4-question, 5-point Likert scale telephone survey was used to assess patient satisfaction with colonoscopy. The telephone patient satisfaction survey was conducted 24-72 h following the procedure.RESULTS: Two hundred and thirty patients were enrolled during the study period with 126 patients in the AAP group and 104 patients in the EAC group. Mean procedure time was 18.3 ± 10.1 min in the AAP group and 14.7 ± 7.1 min in the EAC group(P = 0.002). Mean total room time was 36.8 ± 13.7 with AAP and 30.1 ± 11 min with EAC(P 0.001). Multivariate analysis revealed the use of AAP(P = 0.002), resident participation(P 0.001), diagnostic interventions(P = 0.033), therapeutic interventions(P 0.001), lower body mass index(P = 0.008) and American Society of Anaesthesiologist class(P = 0.016), to be predictors of longer total room time. Patient age and gender were not significant predictors. After excluding cases in which trainees were involved, there was no significant difference in procedure time between the two groups(P = 0.941), however total room time was still prolonged in the AAP group(P = 0.019). The amount of pain experienced was lower with AAP(P = 0.02), with a trend toward overall higher patient satisfaction(P = 0.074). There were 2 sedation-related adverse events, both in the AAP group involving a patient with aspiration requiring hospitalization and a patient with hypoxia managed with bronchodilators.CONCLUSION: EAC results in reduced total room time compared to AAP. Resident participation doubles procedure time regardless of sedation type.     

Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76

Mutations in the Plasmodium falciparum genes pfcrt and pfmdr1 are selected by amodiaquine treatment in Africa. To examine the importance of these mutations in amodiaquine-treated Asian parasites, we determined pre- and posttreatment genotypes for amodiaquine treatment failures from a clinical trial in Afghanistan. The pfcrt codon 72 to 76 haplotype SVMNT was present in all samples tested, both before and after treatment. Amodiaquine did not clearly select for any pfmdr1 genotype, but a novel mutation, pfmdr1 N86F, was detected in four samples. We provide in vivo data to support the in vitro correlation between pfcrt SVMNT and increased resistance to the metabolite of amodiaquine.Amodiaquine (AQ), a 4-aminoquinoline related to chloroquine (CQ), has been used commonly as a monotherapy and now as a partner drug in artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated Plasmodium falciparum malaria. In many countries, predominantly in Africa, the in vivo efficacy of AQ was found to be good even in the face of increasing CQ resistance (12). However, reports of AQ resistance have come from South America, Asia, and East Africa (7, 8, 10).Mutations in the P. falciparum chloroquine resistance transporter gene (pfcrt) and multidrug resistance gene 1 (pfmdr1) have been associated with clinical resistance to both CQ and AQ (13). The presence of the pfcrt codon 72 to 76 haplotype SVMNT (Ser-Val-Met-Asn-Thr) correlates with high-level resistance to the AQ metabolite desethylamodiaquine (DEAQ) in in vitro tests (14) and has been detected with a high prevalence in parasite populations from Brazil, Papua New Guinea, Laos, Iran, and India (9, 18). Clinical trials in East Africa have also demonstrated high levels of in vivo resistance to AQ; in those studies, the parasites carried pfcrt codon 72 to 76 haplotype CVIET, and pfmdr1 polymorphisms 86Y, 184Y, and 1246Y were found to be selected after AQ treatment failure (5, 6, 11).A clinical trial performed in Nangahar Province, East Afghanistan, in 2002 and 2003 to explore possible replacement treatments for CQ showed very poor efficacies of both CQ and AQ monotherapy (adequate clinical and parasitological responses were seen in 11% and 9% of cases, respectively, by day 42) (4). Our aim in this study was to evaluate pre- and posttreatment samples from patients treated with AQ for pfcrt and pfmdr1 mutations and to determine which, if any, polymorphisms are associated with AQ treatment failure in Afghanistan.     

Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity

Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly linked loci at 4q26-4q28 (MRT17), 6q12-q15 (MRT18), 18p11 (MRT19), 16p12-q12 (MRT20), 11p15 (MRT21), 11p13-q14 (MRT23), 6p12 (MRT24), 12q13-q15 (MRT25), 14q11-q12 (MRT26), 15q23-q26 (MRT27), and 6q26-q27 (MRT28), respectively. Loci ranged between 1.2 and 45.6 Mb in length. One family showed linkage to chromosome 8q24.3, and we identified a mutation in TRAPPC9. Our study further highlights the extreme heterogeneity of NS-ARID, and suggests that no major disease gene is to be expected, at least in this study group. Systematic analysis of large numbers of affected families, as presented here, will help discovering the genetic causes of ID.     

Imipenem Resistance in Klebsiella pneumoniae Is Associated to the Combination of Plasmid-Mediated CMY-4 AmpC β-Lactamase and Loss of an Outer Membrane Protein

This study was conducted to identify the molecular mechanisms of imipenem resistance in a Klebsiella pneumoniae (Kp16137) isolate recovered in August 2008 at the University Hospital Sahloul, Sousse, Tunisia. The strain was identified with the API 20E system; antibiotic-containing disks were used for detection of antibiotic susceptibility by a disk diffusion assay. We investigated the presence of β-lactamases by PCR, using specific primers for bla(TEM), bla(SHV), bla(CTX-M), bla(OXA), bla(CMY), bla(ACC), bla(FOX), bla(IMP), bla(KPC), bla(VIM), and by sequencing. Extraction of plasmid DNA from Kp16137 and the transconjugant was performed by the method of Kado. Southern transfer was performed on nylon. The membrane was hybridized with a specific probe for the bla(CMY-2) gene. Outer membrane proteins were isolated and were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis on 12% polyacrylamide gel. K. pneumoniae Kp16137 was resistant to all available β-lactams, including third generation cephalosporins and carbapenems. The screening of β-lactamases showed the presence of three β-lactamases: TEM-1, SHV-61, and CMY-4. The CMY-4 β-lactamase was located on an 80-kb plasmid. An analysis of the outer membrane proteins of this isolate revealed that it lacked a porin of 42?kDa. The loss of this outer membrane protein band correlated with imipenem resistance in this strain. In K. pneumoniae 16137, synthesis of a plasmid-mediated β-lactamase: AmpC CMY-4, together with alteration in permeability led to resistance to all available β-lactams and carbapenems.     

The Importance of 4th Generation HIV Testing in an Urban Emergency Department

Early Acute Human Immunodeficiency Virus Infection (eAHI) diagnosis, via 4th generation testing methodology, presents an opportunity for earlier detection and immediate linkage to care for infected persons. We report on two patients with high-risk behaviors for HIV infection, presenting with atypical symptoms of eAHI in an urban Emergency Department (ED). This case report should raise the index of suspicion for HIV among ED physicians as well as underscore the importance of reducing HIV transmission through earlier detection. Universal screening of patients aged 13–64, incorporating new HIV diagnostic algorithms, is recommended by the Centers for Disease Control and Prevention (CDC). By employing the 4th generation HIV testing methodology, we can potentially diagnose HIV infection earlier compared to older testing methodologies. Currently, 3rd generation HIV testing is used to detect the presence of HIV antibodies, generally through an enzyme-linked immunosorbent assay (ELISA). However, detection of HIV antibodies can take anywhere from 3 to 12 weeks, depending on the individual and testing modality used. This newer diagnostic paradigm enables earlier identification of newly infected individuals. Early HIV detection allows for linkage to care and the administration of effective treatment modalities shortly thereafter. As HIV transmission is highest during its initial acquisition, early detection and linkage to care has been shown to be an efficient method to decrease transmission through subsequent changes in behaviors of those infected.     

Cloning the shared components of complex DNA resources

The complex and repetitive nature of mammalian genomes limitsthe ability of conventional molecular techniques to recoversequences of interest. Here we describe a rapid and simple procedurefor the direct cloning of sequences which are coincident betweenDNA mixtures of whole genome complexity. The system, calledend ligation coincident sequence cloning (EL-CSC), can enrichcoincident DNA by greater than 10⁶-fold and overcomes problemsassociated with repetitive elements. Applying EL-CSC to variouspaired DNA resources enables the facile cloning of both genomicmarkers and novel genes. To demonstrate the power of the methodwe have 1) selectively purified single copy sequences from acomplete genome, and II) isolated gene fragments from 260 kbof cloned genomic DNA.     

Histopathological and histochemical effects of Naja haje venom on kidney tissue of mice

Naja haje venom in a lethal dose caused focal tubular degenerative lesions with intact glomeruli. The tubular basement membrane was intact. The brush border of the proximal convoluted tubules was only destroyed in the markedly degenerated tubules. The activity of both alkaline phosphatase and succinic dehydrogenase enzymes was decreased. Vacuolization and shading of the epithelial lining of the cells of Henle's loop and the distal convoluted tubules was observed. Cases were found in the collecting tubules. Minimal tubular damage with normal enzymatic activity followed the injection of a single sublethal dose of the venom. Multiple sublethal doses caused mainly glomerular changes with almost normal tubules. Hypertrophy of the cells of the parietal layer of Bowman's capsule appeared. The cells acquired as a PAS positive free border similar to that of the proximal convoluted tubules. The thickened empty rings of basement membrane were suggestive of endothelial damage. Distortion of some of the glomeruli with obliteration of the capsular space at certain points was observed. The cells of the proximal convoluted tubules showed double nuclei and prominent nucleoli with normal enzymatic activity of both succinic dehydrogenase and alkaline phosphatase.     

The Experiences of Minors Seeking Asylum in the United States: A Modified Consensual Qualitative Research Analysis

Minors fleeing violence in their countries of origin constitute a significant portion of asylum seekers in the United States. Medical and mental health professionals provide continuity care services and offer pro bono forensic evaluations for this population to document evidence of human rights abuses and torture. The present study included a retrospective, qualitative chart review of deidentified personal declarations and clinician medico–legal affidavits associated with 36 asylum seekers under 21 years of age. Data were analyzed through a modified consensual qualified research (CQR-M) approach to identify patterns in these individuals’ reports of persecution and assess health outcomes. Among the cases studied, violence by organized criminal groups (47.2%), family-based violence (44.4%), and gender-based violence (44.4%) were the most commonly cited reasons minors sought asylum. Evaluators documented a wide range of psychological sequelae: 80.5% of minors presented with clinically significant symptoms associated with trauma- and stressor-related disorders, depression, and/or anxiety at the time of their applications for asylum. Of note, almost three-quarters of the minors reported current enrollment in school and two-thirds reported factors related to adaptive functioning. Despite reported exposure to premigratory and migratory trauma, postmigratory stressors, and psychological sequelae related to their experiences of violence, these young asylum seekers exhibited signs of resilience and a range of health-promoting strengths.