The advantages of UK Biobank's open-access strategy for health research.

Ready access to health research studies is becoming more important as researchers, and their funders, seek to maximize the opportunities for scientific innovation and health improvements. Large-scale population-based prospective studies are particularly useful for multidisciplinary research into the causes, treatment and prevention of many different diseases. UK Biobank has been established as an open-access resource for public health research, with the intention of making the data as widely available as possible in an equitable and transparent manner. Access to UK Biobank's unique breadth of phenotypic and genetic data has attracted researchers worldwide from across academia and industry. As a consequence, it has enabled scientists to perform world-leading collaborative research. Moreover, open access to an already deeply characterized cohort has encouraged both public and private sector investment in further enhancements to make UK Biobank an unparalleled resource for public health research and an exemplar for the development of open-access approaches for other studies.

Consent for labour epidural analgesia: an observational study in a single institution.

There is a wide range of practice amongst obstetric anaesthetists when obtaining consent for women requesting labour epidural analgesia. This is the first prospective observational study recording the number and types of risks mentioned and whether the risk was quantified. Statements of benefits and alternatives to the procedure were also noted. Fourteen anaesthetists, each consulting a single patient, were recorded during the process of obtaining consent and inserting the epidural. The most commonly mentioned risks (median 7) were headache/dural puncture, failure/difficulty with insertion, nerve damage, bleeding/haematoma and infection/epidural abscess. There was no difference between consultants and trainees, although consultants showed greater variance. It was uncommon for anaesthetists to state a benefit (21%) or mention an alternative option (21%), but there was usually a quantitative statement of risk (71%). Data showed a deviation from the Australian and New Zealand College of Anaesthetists guidelines and these findings may encourage anaesthetists to reflect on their own practice and guide future research.

Communications during epidural catheter placement for labour analgesia.

Evidence suggests that anaesthetists' communication can affect patient experience. There is a lack of guidance for anaesthetists as to the optimal verbal communication to use during insertion of epidurals on the labour ward. We recorded the verbal communication used by 14 anaesthetists during the siting of epidural catheters in women on the labour ward; a classification of the language used was subsequently devised. We found that commands and information statements were the most common types of communication used. Individual anaesthetists differed markedly in their use of positive and negative verbal language. This classification of verbal communication that we produced may be of value in future training and research of verbal communication used by anaesthetists on the labour ward.

A comparison of triage methods for Kenyan women who screen positive for cervical intraepithelial neoplasia by visual inspection of the cervix with acetic acid.

BACKGROUND: Only about one in seven visual inspection with acetic acid (VIA)-positive women has high-grade disease; further confirmatory testing could rule out false positives. OBJECTIVES: To determine if visual inspection with Lugol's iodine (VILI) or visual inspection with acetic acid and magnification (VIAM) can accurately confirm the presence of disease among rural Kenyan women referred to a district hospital because of a VIA-positive result at a primary health facility. METHODS: Referred women received cervical cytology and either VILI and/or VIAM as triage methods. All women were assessed by colposcopy and biopsied, if necessary. RESULTS: Of the 490 VIA-positive subjects referred, 332 (68%) attended the district hospital and received at least one of two triage tests and cervical cytology. The sensitivity and specificity for histologically-confirmed CIN 2 and 3 were 93% (14/15) and 32% (52/161) for VIAM; 100% (3/3) and 77% (49/64) for VILI; and 80% (16/20) and 48% (110/228) for cervical cytology. VILI reduced the number of false-positive screening results by 73%, without missing any true positives. CONCLUSIONS: VILI had comparable sensitivity and significantly higher specificity compared to VIAM and cervical cytology. VILI may be a promising triage test for screen-positive women in low-resource settings; additional research is required.

Report on a cryotherapy service for women with cervical intraepithelial neoplasia in a district hospital in western Kenya.

BACKGROUND: In low-resource settings, cryotherapy can be cost-effective, affordable, and a first-line treatment for cervical intraepithelial neplasia (CIN) of any grade. OBJECTIVES: To report the acceptability, safety and effectiveness of cryotherapy for women with cervical intraepithelial neoplasia (CIN) in Western Kenya. METHODS: Visual inspection with acetic acid (VIA)-positive women and those suspected of having cervical cancer based on an initial evaluation at a primary health facility were referred to the district hospital for colposcopy and additional evaluation using visual inspection with Lugol's iodine (VILI) and/or visual inspection with acetic acid and magnification (VIAM). Cryotherapy was offered immediately to women diagnosed with appropriate CIN lesions based on colposcopy or after waiting for a confirmatory cervical biopsy and a follow up visit occurred one year later. RESULTS: Ninety one 91 women 30 to 39 years of age had CIN appropriate for cryotherapy. Approximately 36% (24/67) were due for their 1 year follow up visit and 20 of 24 (83.3%) attended. Complete data were available for 18 of 20 (90%) and 13 (72.2%) had no sign of CIN. No serious adverse events were reported 1 to 3 months after cryotherapy. All respondents reported that the treatment experience was acceptable. CONCLUSIONS: Cryotherapy was acceptable, safe and effective.

Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid.

We estimate the accuracy of colposcopy and visual inspection with acetic acid (VIA) while minimizing the effects of misclassification bias, and maximizing ascertainment of disease. VIA was performed by experienced physicians on a population-based sample of women aged 30 to 49 years in rural Shanxi province, China. Each woman received VIA, liquid-based cytology (LBC) and hybrid capture 2 (hc2, QIAGEN, Gaithersburg, MD; formerly Digene Corporation). Any woman who tested positive on any test had colposcopy, endocervical curettage (ECC) with directed biopsies as necessary and 4-quadrant random biopsies from normal-appearing areas of the cervix. A standard diagnosis based on colposcopy and directed biopsy, and an expanded diagnosis including ECC and 4-quadrant random biopsy were generated for each woman. In 1,839 women, use of the expanded versus the standard diagnostic criteria increased the prevalence of histologically confirmed high-grade cervical intraepithelial neoplasia and cancer (CIN2+) from 3.2% (59/1,839) to 4.2% (77/1,839) and decreased the sensitivity of VIA for CIN2+ from 69.5% (95% CI: 56.8-79.8) to 58.4% (95% CI: 47.3-68.8%) with little change in specificity of approximately 89%. Compared with the expanded diagnostic criterion, the sensitivity of a visual diagnosis of high-grade CIN or cancer by a colposcopist was 49.4% (95% CI: 38.2-60.5). The use of an expanded diagnostic criterion in this study yielded more conservative estimates of the sensitivity of VIA and colposcopy.

Colposcopists' agreement on cervical biopsy site.

OBJECTIVE: To determine the inter-observer agreement among colposcopists on the most abnormal area of the cervix from which a biopsy would be obtained and whether any attributes predict agreement. MATERIAL AND METHODS: Fifty cervigrams were reviewed and 72 colposcopists from five countries indicated the site to biopsy and whether an ECC should be obtained. Prior to the study, six Canadian colposcopists met to achieve consensus on the most diseased area for biopsy. Consensus was also reached on whether an ECC was indicated. For each cervigram, percent agreement was determined between each study colposcopist and the consensus. Data were analyzed to determine the attributes associated with the consensus response. RESULTS: The percent overall agreement of the colposcopists with the consensus diagnoses had a mean of 0.70 (95% CI, 0.65-0.75). The use of ECC was most common in Canada (15% of cases). The following factors were assessed by multivariate analysis to determine their influence on individual agreement with the consensus recommendation for the site to biopsy: country, duration of practice (less than or greater than 1 year), professional group (nurse, family doctor, pathologist, gynecologist, gynecologic oncologist), expert status (recognized national/international expert vs colposcopist), and gender. No factor was significantly associated. CONCLUSION: This international study was feasible and the level of inter-observer agreement among colposcopists on the location of the most severe lesions in cervical images is good.

Vaginal self sampling versus physician cervical sampling for HPV among younger and older women.

OBJECTIVES: To estimate the agreement between self collected vaginal swabs and physician collected cervical brush samples for detection of oncogenic human papillomavirus infection (HPV) by the hybrid capture 2 (HC-2) test among women younger and older than 50 years, and to assess women's preference for sample collection method based on age. METHODS: Consecutive women aged 15-49 years due for a 1 year visit in a prevalence study of carcinogenic HPV and a new sample of women aged 50 years and older attending their family physicians for cervical screening, in Ontario, Canada, performed vaginal self sampling and underwent physician cervical sampling and cervical cytology. Women completed a self administered questionnaire on demographics and preference for sampling method. RESULTS: Among the 307 women aged 15-49 years, the prevalence of HPV was 20.8% (64/307) and 17.6% (54/307) in the vaginal and cervical specimens, respectively. Among the women aged 50 years and older, prevalence was 9.9% (15/152) and 8.6% (13/152), respectively. Kappa for agreement between sample collection methods was 0.54 for the younger and 0.37 for the older women (both p< 0.001). Nearly half of the women preferred self sampling or had no preference. CONCLUSIONS: There was fair agreement between self collected vaginal and physician collected cervical specimens for detecting carcinogenic HPV in younger and older women. Vaginal sampling for HPV appears to be promising as a primary screening strategy for cervical cancer prevention programmes in low resource settings in developed and developing countries.

Diagnostic accuracy of self collected vaginal specimens for human papillomavirus compared to clinician collected human papillomavirus specimens: a meta-analysis.

BACKGROUND/OBJECTIVES: Providing summary recommendations regarding self collection of vaginal specimens for human papillomavirus (HPV) testing is difficult owing to the wide range of published estimates for the diagnostic accuracy of this approach. To determine summary estimates from analyses of reported findings of the sensitivity, specificity and summary receiver operating characteristic curves (SROC) for self collected vaginal specimens for HPV testing compared to the reference standard, clinician collected HPV specimens. METHODS: Standard search criteria for a diagnostic systematic review were employed. Eligible studies were combined using a random effects model and summary ROC curves were derived for overall and for specific subgroups. RESULTS: Summary measures were determined from 12 studies. Six studies where patients used Dacron or cotton swabs or cytobrushes to obtain samples were pooled and had an overall sensitivity of 0.74 (95% CI 0.61 to 0.84) and specificity of 0.88 (95% CI 0.83 to 0.92), with diagnostic odds ratio of 22.3 and an area under the curve of 0.91. Self specimens using Dacron or cotton swabs or cytobrushes collected by women enrolled at referral clinics had an overall sensitivity of 0.81 (95% CI 0.65 to 0.91) and specificity of 0.90 (95% CI 0.80 to 0.95). Sensitivity and specificity of tampons ranged from 0.67-0.94 and 0.80-0.85 respectively. CONCLUSIONS: Our findings indicate that the combined sensitivity for HPV-DNA is more than 70% when patients use Dacron swabs, cotton swabs, or cytobrushes to obtain their own vaginal specimens for HPV-DNA evaluation. Self collected HPV-DNA swabs may be an appropriate alternative for low resource settings or in patients reluctant to undergo pelvic examinations.

Experience using cryotherapy for treatment of cervical precancerous lesions in low-resource settings.

Cervical cancer can be successfully prevented if timely identification of precancerous lesions is followed by effective treatment. In many developing countries, treatment of precancer is neglected because therapeutic services are unavailable, inaccessible, inappropriate, or inadequately linked to screening services. One of the main focuses of the Alliance for Cervical Cancer Prevention (ACCP) has been to ensure that safe and effective methods of treatment for precancer are both available and accessible to women who need them. Cryotherapy, in use for the past 40 years, is a relatively simple, safe, effective, acceptable, and appropriate outpatient procedure for the treatment of precancer. ACCP studies conducted in more than a dozen developing countries show that cryotherapy for precancer can be performed safely and effectively as an outpatient procedure at all levels of health facilities by trained and competent midlevel providers, thus increasing availability and accessibility to precancer treatment services.

Training for cervical cancer prevention programs in low-resource settings: focus on visual inspection with acetic acid and cryotherapy.

The modern approach to cervical cancer prevention, characterized by use of cytology and multiple visits for diagnosis and treatment, has frequently proven challenging and unworkable in low-resource settings. Because of this, the Alliance for Cervical Cancer Prevention (ACCP) has made it a priority to investigate and assess alternative approaches, particularly the use of visual screening methods, such as visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI), for precancer and cancer detection and the use of cryotherapy as a precancer treatment method. As a result of ACCP experience in providing training to nurses and doctors in these techniques, it is now widely agreed that training should be competency based, combining both didactic and hands-on approaches, and should be done in a clinical setting that resembles the service-delivery conditions at the program site. This article reviews ACCP experiences and perceptions about the essentials of training in visual inspection and cryotherapy and presents some lessons learned with regard to training in these techniques in low-resource settings.

A critical assessment of screening methods for cervical neoplasia.

The objective of cervical cancer screening is to reduce cervical cancer incidence and mortality by detecting and treating precancerous lesions. Conventional cytology is the most widely used cervical cancer screening test. Although cytology has been effective in reducing the incidence of and mortality from cervical cancer in developed countries in both opportunistic and--more dramatically--organized national programs, it has been less successful and largely ineffective in reducing disease burden in low-resource settings where it has been implemented. Liquid-based cytology, testing for infection with oncogenic types of human papillomaviruses, visual inspection with 3-5% acetic acid, magnified visual inspection with acetic acid, and visual inspection with Lugol's iodine have been evaluated as alternative tests. Their test characteristics, and the applications and limitations in screening, are discussed with an emphasis on the work of the Alliance for Cervical Cancer Prevention over the past 5 years.

Correlation between culture testing of swabs and ligase chain reaction of first void urine from patients recently treated for Chlamydia trachomatis.

We assessed the correlation between ligase chain reaction (LCR) on first void urine (FVU) and cultures of urethral and cervical swabs to detect chlamydia during three post-treatment follow up visits for 10 men and 19 women with genital chlamydial infections who had been treated with azithromycin or doxcycline.

Impact of urine collection order on the ability of assays to identify Chlamydia trachomatis infections in men.

BACKGROUND: Noninvasive urine samples have been used to diagnose Chlamydia trachomatis infections, with the assumption that the first-void urine (FVU), defined as the first 20 to 30 ml at any micturition, would be the optimal collection. We compared testing technologies on first, second, and third volumes for diagnosis. GOAL: The goal was to test in nonculture assays three sequential volumes of urine from men also undergoing urethral swabbing for C trachomatis culture specimens. STUDY DESIGN: A total of 237 men attending an STD clinic (C trachomatis prevalence, 11%) collected three containers of urine (each containing 20-30 mL) for testing in four nonculture assays. A urethral swab specimen was tested in cell culture. RESULTS: The numbers of men positive by testing of FVU with nucleic acid amplification (LCx chlamydia), nucleic acid hybridization (PACE 2), enzyme immunoassay (Chlamydiazyme), and a leukocyte esterase dipstick were 26, 7, 14, and 11, respectively; urethral culture identified 6 of the infected men. Comparative testing of all voids from the 26 men positive by the FVU assays demonstrated a reduction of LCx-positives. Non-amplified-test positivity declined precipitously in subsequent voids, approaching zero in the third void. The presence of symptoms and time of last void up to 8 hours had little effect on the number of positives detected by LCx of FVU. CONCLUSION: Amplified testing of FVU was most effective for diagnosing infection in these men.

Confirmation of cervical neoplasia using a hand-held, lighted magnification device.

OBJECTIVES: The objective of this study was to estimate the sensitivity and specificity of visual inspection with acetic acid and magnification (VIAM) using the AviScope device to confirm high-grade cervical intraepithelial neoplasia or carcinoma. METHODS: VIAM was performed on 142 women aged 18-50 years referred to three colposcopy clinics because of abnormal cervical cytology. Each woman then had a colposcopic examination with cervical biopsy when indicated. RESULTS: The AviScope device identified 24 of the 40 women who had CIN 2, 3, or carcinoma, yielding a sensitivity of 60.0% (95% CI 43.4, 74.7). The AviScope correctly identified 60 of 87 women negative for dysplasia or cancer, yielding a specificity of 69.0% (95% CI 58.0, 78.2) compared with colposcopy and cervical histology. CONCLUSION: VIAM using the AviScope device was moderately sensitive and specific for the confirmation of high-grade cervical lesions in women referred with abnormal cervical cytology.

Assessment of the cervix after acetic acid wash: inter-rater agreement using photographs.

OBJECTIVE: To estimate the inter-rater agreement on the assessment of cervical photographs after acetic acid wash, using visual inspection with acetic acid categories. METHODS: Three raters individually assessed 144 photographs as negative, positive, or suspicious for cancer. The inter-rater agreement was analyzed using the unweighted and weighted kappa coefficient. To explore the reasons for concordancy and discordancy, photographs were compared on histologic evidence of cervical intraepithelial neoplasia and on testing for oncogenic types of human papillomavirus. RESULTS: Overall raw agreement among the three raters was 66.7% (96 of 144) with a kappa of 0.57 (95% confidence interval 0.48, 0.66). Pair-wise agreement using unweighted and weighted kappa was moderate to substantial: 0.54-0.60 and 0.56-0.63, respectively. There was concordance on negative in 25.7% (37 of 144) and on positive or suspicious for cancer in 41.0% (59 of 144). Cervical intraepithelial neoplasia II or III was not present on biopsy if photographs were concordant-negative, and the human papillomavirus test was less likely to be positive (relative risk 0.3; 95% confidence interval 0.2, 0.6) in concordant-negatives compared with concordant-positives, including suspicious for cancer. Cervical intraepithelial neoplasia II or III was more common in photographs that were concordant-positive, including suspicious for cancer, compared with discordants (relative risk 3.4, 95% confidence interval 1.5, 7.6). CONCLUSION: Based on photographs of the cervix taken after acetic acid wash, the level of agreement among raters using visual inspection with acetic acid categories was moderate to substantial, consistent with other commonly used tests.

Aseptic precautions for inserting an epidural catheter: a survey of obstetric anaesthetists.

We performed a postal survey of Fellows of the Australian and New Zealand College of Anaesthetists with a special interest in obstetric practice, about their beliefs regarding aseptic precautions for insertion of an epidural catheter in the labour ward. Of the 435 consultant anaesthetists surveyed, 367 responded (84%), revealing a wide variation in practice. It was not thought to be essential practice to remove a watch before washing hands by 51 respondents (14%), to wear a facemask by 105 (29%) or to wear a sterile gown by 45 (12%). Three anaesthetists (1%) did not believe sterile gloves were essential. However, all respondents indicated that an antiseptic skin preparation was essential. Our results raise questions regarding an acceptable standard of aseptic practice for the insertion of an epidural catheter in labour and we propose a minimal standard of essential precautions.

Cost-effectiveness of screening swab or urine specimens for Chlamydia trachomatis from young Canadian women in Ontario.

BACKGROUND: Undetected and untreated Chlamydia trachomatis infections can result in a significant health burden. Diagnostic testing refers to tests performed on patients with symptoms, whereas screening refers to testing specimens in asymptomatic patients. The goal of diagnostic testing and screening programs are early identification of infections to prevent upper tract infection and transmission to other partners. GOAL: To compare the costs and outcomes of alternative diagnostic testing and screening programs for women ages 15 to 24 years in the province of Ontario, Canada. STUDY DESIGN: Using outcome probabilities from the literature and a consensus group, together with the costs from insurance billing, a decision analytic model was constructed to determine the baseline risk of C trachomatis and related sequelae. Seven diagnostic testing and screening programs were compared over a 10-year period. The programs compared included the use of nucleic acid amplification assays collected from urine or endocervical swab specimens. RESULTS: Largely because of lower sensitivity the urine-based testing or screening programs were dominated by the swab-based programs. The move from swab-based testing to a swab-based screening program for high-risk women costs $1873 per case of C trachomatis averted. Expanding the program further to include all women in Ontario between 15 and 24 years of age is considerably more costly at $5990 per case averted. CONCLUSIONS: It is more costly and more effective to screen and treat high-risk women ages 15 to 24 years for C trachomatis than to perform only swab-based diagnostic testing on symptomatic women. Expanding the screening program to include all women ages 15 to 24 years is considerably more expensive and only moderately more effective than screening only high-risk women.

Imiquimod 5% cream is a safe and effective self-applied treatment for anogenital warts--results of an open-label, multicentre Phase IIIB trial.

Our objective was to determine the efficacy and safety of imiquimod 5% cream in the treatment of external genital/perianal warts in an open-label Phase IIIB trial. Patients applied imiquimod 5% cream 3 times per week, for up to 16 weeks. Those who cleared their warts were monitored during a 6-month follow-up period. If their warts recurred, or new warts developed during this time, patients could be re-treated for up to 16 additional weeks. Patients who experienced partial clearance during the initial treatment period entered an extended treatment period of up to an additional 16 weeks. A total of 943 patients from 114 clinic sites in 20 countries participated in this study. Complete clinical clearance was observed in 451/943 (47.8%) patients (intent-to-treat (ITT) analysis) during the initial treatment period, with clearance in an additional 52 (5.5%) patients during the extended treatment period beyond 16 weeks. The overall clearance rate for the combined treatment periods was 53.3%. In a treatment failure analysis, the overall clearance rate was 65.5%; a greater proportion of female patients (75.5%) experienced complete clearance than male patients (56.9%). Low recurrence rates, of 8.8% and 23.0%, were observed at the end of the 3- and 6-month follow-up periods, respectively. The sustained clearance rates (patients who cleared during treatment and remained clear at the end of the follow-up period) after 3 and 6 months were 41.6% and 33.0% (ITT analysis), respectively. Local erythema occurred in 67% of patients. In the majority of patients local skin reactions were of mild to moderate severity. In conclusion, imiquimod 5% cream is an effective self-applied treatment for external genital/perianal warts when applied for up to 16 weeks and is well tolerated for up to 32 weeks.