Global Ring Study to Investigate the Comparability of Total Assay Performance of Commercial Claudin 18 Antibodies for Evaluation in Gastric Cancer.

Claudin 18.2 (CLDN18.2), the dominant isoform of CLDN18 in gastric tissues, is a highly specific tight junction protein of the gastric mucosa with variably retained expressions in gastric and gastroesophageal junction cancers. Additionally, CLDN18.2-targeted treatment with zolbetuximab, in combination with chemotherapy, has recently been assessed in 2 phase-III studies of patients with HER2-negative, locally advanced, unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma. These trials used the investigational VENTANA CLDN18 (43-14A) RxDx immunohistochemistry (IHC) assay on the Ventana BenchMark platform to identify patients eligible for CLDN18.2-targeted treatment. We report the findings of a global ring study evaluating the analytical comparability of concordance of the results of 3 CLDN18 antibodies (Ventana, LSBio, and Novus) stained on 3 IHC-staining platforms (Ventana, Dako, and Leica). A tissue microarray (TMA), comprising 15 gastric cancer cases, was stained by 27 laboratories across 11 countries. Each laboratory stained the TMAs using at least 2 of the 3 evaluated CLDN18 antibodies. Stained TMAs were assessed and scored using an agreed IHC-scoring algorithm, and the results were collated for statistical analysis. The data confirmed a high level of concordance for the VENTANA CLDN18 (43-14A; Ventana platform only) and LSBio antibodies on both the Dako and Leica platforms, with accuracy, precision, sensitivity, and specificity rates all reaching a minimum acceptable ≥85% threshold and good-to-excellent levels of concordance as measured by Cohen's kappa coefficient. The Novus antibody showed the highest level of variability against the reference central laboratory results for the same antibody/platform combinations. It also failed to meet the threshold for accuracy and sensitivity when used on either the Dako or Leica platform. These results demonstrated the reliability of IHC testing for CLDN18 expression in gastric tumor samples when using commercially available platforms with an appropriate methodology and primary antibody selection.

An evaluation study of the Becton-Dickinson ProbeTec Qx (BDQx) Trichomonas vaginalis trichomoniasis molecular diagnostic test in two large, urban STD services.

OBJECTIVES: The BASHH guidelines recommend molecular tests to aid diagnosis of Trichomonas vaginalis (TV) infection; however many clinics continue to use relatively insensitive techniques (pH, wet-prep microscopy (WPM) and culture). Our objectives were to establish a laboratory pathway for TV testing with the Becton-Dickinson Qx (BDQx) molecular assay, to determine TV prevalence and to identify variables associated with TV detection. METHODS: A prospective study of 901 women attending two urban sexual health services for STI testing was conducted. Women were offered TV BDQx testing in addition to standard of care. Data collected were demographics, symptoms, results of near-patient tests and BDQx results for TV, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). Women with any positive TV result were treated and followed up for test of cure (TOC). RESULTS: 901 women had a TV BDQx test. 472 (53%) were white, 143 (16%) black and 499 (55%) were symptomatic. Infections detected by BDQx were: 11 TV (1.2%), three GC (0.3%) and 44 CT (4.9%). Of the 11 BDQx-detected TV infections, 8 (73%) were in patients of black ethnicity. Of these, four of seven cases (57%) were WPM-positive. All patients received treatment and nine of nine (100%) were BDQx-negative at TOC. In univariate analysis, only black ethnicity was associated with likelihood of a positive TV BDQx result (relative risk (RR) 10.2 (95% CI 2.15 to 48.4)). CONCLUSIONS: The use of the BDQ enhanced detection of TV in asymptomatic and symptomatic populations. Cost-effective implementation of the test will rely on further work to reliably detect demographic and clinical variables that predict positivity.

ALK Immunohistochemistry in NSCLC: Discordant Staining Can Impact Patient Treatment Regimen.

INTRODUCTION: Diagnostic immunohistochemistry (IHC) is increasingly accepted as a screening method for anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements in NSCLC. We have sought to establish an ongoing robust external quality assessment process to gauge quality of anaplastic lymphoma kinase (ALK) IHC, which can have an impact on interpretation of patient samples. METHODS: Unstained tissue and cell line samples were distributed on a quarterly basis to participating laboratories from 30 countries. Participants stained the slide using their routine diagnostic ALK IHC method and returned the slide along with their in-house control and methodology details. Slides were assessed by a team of pathologists and scientists. RESULTS: Overall, there was a mean pass rate of 83% (range 71%-98%), with 38 variations in staining protocol. Methods included the following: the Roche D5F3 assay (65% of users, pass rate 93%); Novocastra 5A4 (15% of users, pass rate 65%); Cell Signaling Technology D5F3 (7% of users, pass rate 91%), and Dako ALK1 (5% of users, pass rate 50%). Choice of methodology directly affected final interpretation of distributed ALK-positive and ALK-negative NSCLC cases, which were correctly identified by 89% and 88% of participants, respectively. Antibody detection method was a contributing factor in false-negative staining results. The choice of laboratory controls was found to be unsuitable, and as such, in-house control recommendations are also provided. CONCLUSIONS: ALK IHC is a robust screening technique, but there is concern that some diagnostic laboratories are using inadequate staining methods, which has a direct impact on final interpretation. External assessment helps provide laboratories with continued confidence in their ALK IHC testing.

Sexually transmitted infections in children as a marker of child sexual abuse and direction of future research.

PURPOSE OF REVIEW: This review considers recent evidence on sexually transmitted infections (STIs) as a marker of child sexual abuse (CSA), when diagnosed after the neonatal period. It also aims to identify if there are specific areas where additional research is required. RECENT FINDINGS: An evidence-based systematic review using strict inclusion criteria shows that CSA is a major cause of STIs in children. In children 12 years and below, 36-83% of Neisseria gonorrhoeae and 75-94% of Chlamydia trachomatis infections are due to CSA; for children 14 years and younger, 31-58% of anogenital warts are due to CSA. In child genital sampling, genital human papillomavirus (HPV) types were more common in those considered abused (13.7%) than nonabused (1.3%). HPV typing of genital warts in children were all of genital type 6. Subsequent research, into N. gonorrhoeae, C. trachomatis, Trichomonas vaginalis and syphilis in children including ophthalmic infection, found that 13 of 15 cases were confirmed/likely due to CSA. Recent data indicate that bacterial vaginosis and Mycoplasma genitalium are related to sexual activity in adults but did not assess children. SUMMARY: STIs in children under 13-14 years may indicate CSA. Genital HPV types are associated with CSA. Research is required of sufficient standard to contribute to the evidence base.

Uptake of the HPV vaccination programme in England: a cross-sectional survey of young women attending sexual health services.

OBJECTIVES: The U.K. human papilloma virus (HPV) vaccination programme requires 80% uptake to have a significant impact on cervical cancer rates. Uptake in the first three years of the programme was 66%. We report the results of a cross-sectional survey of young women attending sexual health services (SHS) in England, reviewing HPV vaccination uptake and prevalence of HPV-related risk factors. METHODS: An anonymous questionnaire surveyed women aged 13-19 attending 19 hospital-based and 13 community-based SHS across England, March-August 2011. Data were analysed using multiple logistic regression. RESULTS: 2247 questionnaires were completed. Compared with national data, respondents had higher smoking rates (48% vs. 14% of 15 year olds), coitarche under-16 (52% vs. 38%), previous sexually transmitted infections (STIs) (25% vs. 4%) and a higher proportion not in education, employment or training (NEETs) (8% vs. 2% of 16 year olds). Seventy-four per cent had been offered the vaccination, with significantly lower offer rates in London, non-white ethnicities, 17-19 year olds, NEETs, smokers and those with previous STIs (all p<0.05 in multivariate analysis). Sixty-five per cent of those offered, completed, with significantly lower completion rates in London, non-white ethnicities, 17-19 year olds, NEETs, smokers and those with previous STIs (all p<0.05 in multivariate analysis). Overall completion rate was 47%. CONCLUSIONS: We observed lower vaccination offer and completion rates and higher prevalence of HPV-related risk factors compared with national data. The highest risk individuals were the least likely to have been offered or to have completed the course. This survey highlights an opportunity for primary prevention by routinely offering the HPV vaccine to eligible women attending SHS.

Targeting those in need: baseline data from the first English National Health Service (NHS) health trainer service.

As part of a wider strategy to reduce health inequalities, England's National Health Service has introduced health trainers (HTs) to facilitate healthier behaviour among disadvantaged groups. This study reports baseline data from the first English HT service: assessing whether the HTs reached socially disadvantaged clients engaging in unhealthy behaviours and describing client belief characteristics relevant to the delivery of the service. Data from 864 clients show that the service reached disadvantaged groups and that those groups were engaging in risky health behaviours. Self-efficacy about changing behaviour was not strong and clients were unlikely to have made explicit behaviour-change plans prior to attending the service. Implications for HT services around targeting those most in need and supporting psychological triggers for change are discussed.

Meta-analysis of experimental data concerning antimicrobial resistance gene transfer rates during conjugation.

This paper presents the results of a meta-analysis of published transfer rates of antimicrobial resistance genes. A total of 34 papers were identified, of which 28 contained rates estimated in relation to either donor or recipient bacterial counts. The published rates ranged from 10(-2) to 10(-9). Generalized linear modeling was conducted to identify the factors influencing this variation. Highly significant associations between transfer frequency and both the donor (P = 1.2 x 10(-4)) and recipient (P = 1.0 x 10(-5)) genera were found. Also significant was whether the donor and recipient strains were of the same genus (P = 0.023) and the nature of the genetic element (P = 0.0019). The type of experiment, in vivo or in vitro, approached statistical significance (P = 0.12). Parameter estimates from a general linear model were used to estimate the probability of transfer of antimicrobial resistance genes to potential pathogens in the intestine following oral ingestion. The mean logarithms of these probabilities are in the range of [-7.0, -3.1]. These probability distributions are suitable for use in the quantitative assessment of the risk of transfer of antimicrobial resistance genes to the intestinal flora of humans and animals.

Use of comparative data for integrated cancer services.

BACKGROUND: Comparative data are an important resource for management of integrated care. In 2001, the English Department of Health created 34 cancer networks, broadly serving populations of half to three million people, to coordinate cancer services across providers. We have investigated how national and regional routine data are used by the cancer network management teams. METHODS: Telephone interviews using a standardised semi-structured questionnaire were conducted with 68 participants in 29 cancer network teams. Replies were analysed both quantitatively and qualitatively. RESULTS: While most network teams had a formal information strategy, data were used ad hoc more than regularly, and were not thought to be as influential in network decision making as other sources of information. Data collection was more prominent in information strategies than data use. Perceptions of data usefulness were mixed and there were worries over data quality, relevance, and potential misuse. Participants were receptive to the idea of a new limited dataset collating comparative data from currently available routine data sources. Few network structural factors were associated with data use, perceptions of current data, or receptivity to a new dataset. CONCLUSION: Comparative data are underused for managing integrated cancer services in England. Managers would welcome more comparative data, but also desired data to be relevant, quality assured and contextualised, and for the teams to be better resourced for data use.

The use and perceptions of routine health data: a qualitative study of four cancer network teams in England.

Health service managers have been criticized for placing more emphasis on the collection of data than on their use for the improvement of care. The present study examined how routine aggregate data on cancer services are perceived by management teams and how such data are used to inform strategic decision-making and planning. Semi-structured interviews were conducted with 19 members of four cancer network teams in England. The interviews were transcribed and thematically analysed independently by two researchers. Respondents said that routine aggregate data were not highly prioritized as an information resource, although their use had produced some beneficial impacts, such as reduced waiting times. Limited use of aggregate data appeared to relate to problems of accessibility, lack of resources to turn the data into meaningful information and service improving action, and poor data quality and relevance. These factors apparently lead to inability or reluctance to use routine data to monitor and improve cancer services at the network level. Data-user concerns should be addressed to facilitate greater use of available routine data.

Subtypes of Cryptosporidium parvum in humans and disease risk.

The 2 main species of Cryptosporidium that infect humans are Cryptosporidium hominis and C. parvum. Here, multilocus fragment analysis of 3 microsatellite loci (ML1, ML2, and gp60) was used to subtype strains from sporadic cases of cryptosporidiosis in Wales and northwest England. Of 72 strains of C. parvum, 63 were typeable at all 3 loci, forming 31 subtypes. These strains formed 3 broad clusters, representing 74.6%, 20.6%, and 4.8% of typeable strains. Of 118 C. hominis strains, 106 were typeable at all 3 loci, forming 9 subtypes; however, 90% belonged to the same subtype. Analysis with epidemiologic data found an association between strains from case-patients who reported contact with farm animals and individual C. parvum microsatellite alleles. The strongest association was with ML1; all strains from case-patients that reported farm animal contact had the same allele (ML1-242). Microsatellite typing of C. parvum provides valuable additional information on the epidemiology of this pathogen.

Constructing an integrated model of the antecedents of adolescent smoking.

OBJECTIVE: Reviews have called for integrative, theoretically informed models of the 'hundreds of associations' (Miller & Slap, 1989, p. 131) between psychosocial measures and adolescent smoking (e. g. Tyas & Pederson, 1998). Such a model was tested. METHOD: A prospective, classroom-based survey measuring previously identified correlates of smoking allowed comparison of the strength of relationships between antecedents and smoking status six months later. The prospective sample included 225 13 to 14-year-olds. Measures of behaviour-specific cognitions derived from the Theory of Planned Behaviour (TPB)-as well as personality, self-esteem, parental support and parental control, sociodemographic factors, and descriptive norms-were included. Relationships between antecedents were explored using path analyses. RESULTS: High initial rates of smoking were observed. Of the variance in smoking six months later, 56% was explained by seven direct predictors: intention, perceived ease of smoking, estimated number of friends smoking, percentage of older brothers smoking, self-esteem, extraversion and car access. DISCUSSION: Results emphasize the importance of behaviour-specific cognitions specified by the TPB but suggest that other factors, including extraversion and self-esteem, need to be included in models of the antecedents of smoking. The findings also imply that some antecedents, such as parental support, may indirectly influence adolescent smoking through their effect on other variables.

The clinical effectiveness of healing touch.

OBJECTIVES: (1) to determine the clinical effectiveness of Healing Touch (HT) on variables assumed to be related to health enhancement; (2) to determine whether practitioner training level moderates treatment effectiveness. DESIGN: Mixed-method repeated measures design with quasi-experimental and naturalistic approaches, paired with nomothetic and idiographic analyses. SETTING/LOCATION: Practitioner's offices or client's home. SUBJECTS: Twenty-two (22) clients who had never experienced HT. INTERVENTIONS: Three treatment conditions: no treatment (NT), HT only (standard HT care), and HT+ (Standard HT care plus music plus guided imagery). OUTCOME MEASURES: Secretory immunoglobulin A (sIgA) concentrations in saliva, self-reports of stress levels, client perceptions of health enhancement, and qualitative questionnaires about individual effects. RESULTS: Clients of practitioners with more training experienced statistically significant positive sIgA change over the HT treatment series, while clients of practitioners with less experience did not. Clients reported a statistically significant reduction of stress level after both HT conditions. Perceived enhancement of health was reported by 13 of 22 clients (59%). Themes of relaxation, connection, and enhanced awareness were identified in the qualitative analysis of the HT experience. Pain relief was reported by 6 of 11 clients (55%) experiencing pain. CONCLUSIONS: The data support the clinical effectiveness of HT in health enhancement, specifically for raising sIgA concentrations, lowering stress perceptions and relieving pain. The evidence indicates that positive responses were not exclusively as a result of placebo, that is, client beliefs, expectations, and behaviors regarding HT.