Utilisation of anti-TNF levels in a UK tertiary IBD centre.

OBJECTIVE: To ascertain how anti-tumour necrosis factor (TNF) drug and anti-drug antibody levels testing is used in a 'real-world' setting to optimise inflammatory bowel disease (IBD) treatment. DESIGN: Retrospective cohort study of prospectively collected patient data. SETTING: Tertiary IBD centre in London, UK. PATIENTS: All patients at Guy's and St Thomas' Hospitals on anti-TNF who had levels measured between the start of testing in 2012 and October 2014. INTERVENTIONS: Anti-TNF drug and anti-drug antibody levels as part of routine monitoring. MAIN OUTCOME MEASURES: Indication for measuring levels and changes in management made as a result of the levels. RESULTS: 330 infliximab levels were carried out in 199 patients and 143 adalimumab levels were carried out in 103 patients. Levels were primarily done in those with evidence of loss of response; 37% of infliximab levels and 52% of adalimumab levels. Levels resulted in a change in management in 26% of patients in infliximab group and 25% of patients in adalimumab group; however, this was greater in those with loss of response, 62% and 61% respectively. Anti-drug antibodies were detected in 7% of patients. CONCLUSIONS: Our early experience has demonstrated that measuring anti-TNF drug and anti-drug antibody levels can be useful in the optimisation of IBD management. In an increasing number of patients, particularly those with evidence of loss of response, it allows early decisions to be made regarding changing therapy. It also offers the potential for significant cost-saving by preventing pointless dose escalation in the context of therapeutic levels or when high-level anti-drug antibodies are present.

ERCP cannulation success benchmarking: implications for certification and validation.

OBJECTIVE: Investigate success rates of cannulating a 'virgin' papilla during endoscopic retrograde cholangiopancreatography (ERCP) at a tertiary referral centre; determine reasons for failure and propose learnings for consideration in future revision of success benchmarking. DESIGN: Review of all ERCPs recorded on Endosoft database from 2006 to 2012 (n=1862). Specifically, 'virgin' papillae, defined as those with no evidence of prior surgical intervention, stents in situ or sphincterotomy (n=947). Virgin papillae present the most challenging target for endoscopists. SETTING: Gastroenterology department, St Thomas' Hospital, London. PATIENTS: All patients who underwent an ERCP recorded on Endosoft from 2006 to 2012 (n=1134). A proportion of these patients underwent repeat procedures, all considered virgin provided the aforementioned criteria were met. INTERVENTIONS: None, retrospective audit and benchmarking exercise. MAIN OUTCOME MEASURES: Determine criteria for successful cannulation of a virgin papilla. RESULTS: Overall success of cannulation of a virgin papilla at ERCP was 79.5%, 753 out of a total of 947 virgin papillae cases. Per patient with a virgin papilla, the success rate was 79.7%, 693 out of 869. Eliminating cases with features complicating cannulation increased success rates to 86% and 87%, respectively. Chronic pancreatitis was the single Indication associated with a failed cannulation (OR=3.9, CI 2.1 to 7.1), while biliary stones were significantly associated with a successful cannulation (OR=0.3, CI 0.2 to 0.4). Reasons for failure included patient agitation (OR=27.1, CI 7.9 to 92.7), duodenal stricturing (OR=12.5, CI 5.5 to 28.5), previous anatomy-changing surgery (OR=12.2, CI 3.3 to 45.4), tumour impingement (OR=9.5, CI 4.1 to 22.3) and equipment failure (OR=7.9, CI 1.4=43.5). CONCLUSIONS: The Joint Advisory Group's 80% success rate for completion of therapeutic intent must be viewed in light of published difficulty rating scales, if fair comparisons and standards are to be met. This highlights the need for standardised success criterion for ERCP training and accreditation.

Rural-urban differences in substance use and treatment utilization among prisoners.

Surveys of incarcerated offenders and arrestees consistently report high rates of both alcohol and drug use in this population. This drug-crime connection has highlighted the need to learn more not only about drug treatment effectiveness, but also about drug treatment utilization. While studies have begun to examine drug treatment utilization, most of these studies have been based on urban substance abusers. Little is known about the extent to which urban and rural substance abusers may be different in terms of treatment utilization. This study, therefore, examines differences between urban and rural drug use patterns and treatment utilization among chronic drug abusers to determine whether, and in what ways, rurality may affect substance abuse and treatment seeking. The study examines these issues in a group of chronic drug users who were incarcerated at the time of the study. Findings show significant differences in drug use and treatment utilization of urban and rural offenders. Chronic drug abusers from rural and very rural areas have significantly higher rates of lifetime drug use, as well as higher rates of drug use in the 30 days prior to their current incarceration than chronic drug abusers from urban areas. Nonetheless, being from a very rural area decreased the likelihood of having ever been in treatment after controlling for the number of years using and race. While problem recognition appears to explain much of the effect of very rural residence on treatment utilization for alcohol abuse, the effects of being from a very rural area on seeking treatment for drug abuse remain statistically significant even after controlling for several other variables. The findings point to the importance of providing culturally appropriate education to very rural communities on the benefits of substance abuse treatment and of providing substance abuse treatment within the criminal justice system.

Assessing the differential impact of an hiv prevention intervention: who's putting the message into practice?

Recent data suggest that educational interventions aimed at reducing HIV risk behaviors have shown some success. Nonetheless, HIV risk behaviors are not always reduced by interventions and probably do not reduce risk behavior randomly. That is, the success of interventions may be related to participant characteristics. Identifying participant characteristics related to both intervention completion and reduction in risk behaviors may be useful for further developing explanatory models of health behavior and for targeting and customizing interventions. In this study differences between participants who completed an AIDS educational intervention (N = 741) and those who did not complete the intervention are first examined (N = 652) and then variables related to reducing drug and sexual risk behaviors among those who completed the intervention and follow-up interviews are examined. Results show that the majority of respondents report decreasing five out of six risk behaviors, with the smallest percentage (48.8%) decreasing rates of unprotected sex and the largest percentage (83.4%) decreasing frequency of drug injection. Different variables were found to be related to changes in the various risk behaviors. However, some relatively consistent results emerge. For all risk variables, the frequency of the specific behavior at baseline predicted the amount of change in that behavior, with those having higher levels of risk behaviors reducing their behavior the most. Positive HIV test results significantly decreased three of the four sexual risk behaviors examined, and living in a very rural area was found to be significantly related to three of the six risk behaviors. However, perceived chance of getting AIDS did not significantly reduce any of the risk behaviors. Gender and education level were also not related to changes in any of the risk behaviors. Implications include the importance of developing approaches to retain higher proportions of younger participants, males and homeless in interventions. It is particularly important to develop specific approaches to retain women in interventions. Because very rural participants were more likely to decrease crack use and alcohol or drug use with sex, rural interventions should target these behaviors at the outset of the intervention.

A comparison of non-radioisotopic hybridization assay methods using fluorescent, chemiluminescent and enzyme labeled synthetic oligodeoxyribonucleotide probes.

N4-[N-(6-trifluoroacetylamidocaproyl)-2-aminoethyl]-5'-O-dimethoxy trityl -5-methyl-2'-deoxycytidine-3'-N,N-diisopropyl-methylphosphoramidite++ + has been synthesized. This N4-alkylamino deoxycytidine derivative has been incorporated into oligonucleotide probes during chemical DNA synthesis. Subsequent to deprotection and purification, fluorescent (fluorescein, Texas Red and rhodamine), chemiluminescent (isoluminol), and enzyme (horseradish peroxidase, alkaline phosphatase) labels have been specifically incorporated. Detection limits of the labels and labeled probes were assessed. Also, the detection limits and nonspecific binding of the labeled probes in sandwich hybridization assays were determined. The enzyme modified oligonucleotides were found to be significantly better labeling materials than the fluorescent or chemiluminescent derivatives, providing sensitivities comparable to 32P-labeled probes.

A novel method for the rapid detection of specific nucleotide sequences in crude biological samples without blotting or radioactivity; application to the analysis of hepatitis B virus in human serum.

The detection of a little as 0.2 pg (60,000 molecules) of hepatitis B viral (HBV) DNA in human serum samples in 4 h has been demonstrated using a solution-hybridization and bead-capture method. An amplification method based on chemically crosslinked oligodeoxyribonucleotides was coupled with a horseradish peroxidase-labeling scheme for the ultimate detection of the analyte. Two sets of HBV complementary synthetic oligodeoxyribonucleotide probes containing one of two types of single-stranded (ss) overhangs were employed. These ss overhangs were used to capture the probe-analyte complex onto a bead and subsequently to label it. Detection was achieved with either a chemiluminescent or colorimetric output substrate for the enzyme. Only in the presence of the virus was label specifically bound to the support. The assay was relatively unaffected by either sample composition or by the presence of heterologous nucleic acids.

Base modification and cloning efficiency of oligodeoxyribonucleotides synthesized by the phosphoramidite method: methyl versus cyanoethyl phosphorus protection.

We have found large oligodeoxyribonucleotides (50-120 bases) synthesized with N,N-dialkylmethylphosphoramidites to have considerably lower cloning efficiencies than biological DNA. As evidenced by HPLC analysis, these large fragments contain as much as 30% thymidine conversion to 3-methylthymidine. If cyanoethyl- instead of methyl-phosphorous protection is employed, as anticipated, no thymidine methylation is noted. More importantly, large fragments produced by N,N-diisopropylcyanoethyl-phosphoramidite coupling show cloning efficiencies indistinguishable from biological DNA.

Construction and evaluation of an instrument for the automated synthesis of oligodeoxyribonucleotides.

The details for constructing an easily used and maintained laboratory instrument capable of routine oligodeoxyribonucleotide synthesis are presented. The synthesizer consists of relatively inexpensive, commercially available components and is controlled by an Apple IIe computer. Since reagents are distributed from pressurized reservoirs through a liquid manifold by opening solenoid-activated valves, no pump is required. More than 600 oligomers containing up to 122 bases have been produced with a condensation cycle time of approximately 15 min with apparent coupling yields of 98.5%. A unique bidirectional flow reactor and controlled reagent distribution system provide for rapid mass transfer during solvent and reactant equilibrations and for long-term stability of reagent solutions. Aspects of the system should also find use in other solid-phase synthetic and analytical strategies.