Prevalence of high-risk HPV types and associated genital diseases in women born in 1988/89 or 1983/84 – results of WOLVES, a population-based epidemiological study in Wolfsburg, Germany

BACKGROUND: High-risk human papilloma virus (HR-HPV) infection is associated with the development of cervical cancer. HPV vaccination reduces the risk of developing malignant lesions and is expected to change the dynamics of HPV transmission. Data from non-vaccinated women may provide an important benchmark to allow the impact of HPV vaccination programs to be assessed. This study was designed to prospectively determine the changing dynamics of HR-HPV infection and associated genital diseases in young women, most of whom were non-vaccinated. METHODS: Data from a population-based cohort study, comprising women of two predefined birth cohorts (women born in 1983/84 or 1988/89), were analyzed between 19 October 2009 and 31 December 2010 to determine risk factors for high-risk HPV infection and the association between specific HR-HPV types and atypical Pap smear test results. HPV status was determined by Hybrid Capture 2 (HC2) assay and genotyping. RESULTS: The prevalence of HR-HPV was 22.8% in the 1983/84 cohort (150/659) and 23.7% in the 1988/99 cohort (142/599). Only the number of sexual partners was a significant risk factor for HPV infection (odds ratios 22.687 and 6.124 for more than five versus one partner 84 cohort,/84 and 1988/89 cohorts, respectively) in multivariate analysis. HPV16 positive-women were significantly more likely to have abnormal Pap smears of any degree than HPV16-negative women (22.0% versus 3.61%, p < 0.0001 for the 1983/84 cohort and 9.09% versus 2.52%, p = 0.0482 for the 1988/89 cohort). CIN3 was diagnosed in six women 84 cohort,/84 cohort and two in the 1988/89 cohort. All women with CIN3 tested positive for HC2-HR and all six CIN3 cases 84 cohort,/84 cohort tested positive for HPV16. In the 1988/89 cohort, the rate of HPV16 infection was significantly lower in vaccinated than non-vaccinated women (1.59% versus 8.88%; p = 0.003). CONCLUSIONS: HR-HPV infection was highly prevalent in both cohorts and associated with an increased risk of abnormal Pap smears and biopsy proven CIN2+. HPV16 infection was associated with a high risk of clinically relevant lesions. HPV vaccination significantly decreased the risk of HPV16 infection

Core outcome set measurement for future clinical trials in acute myeloid leukemia: the HARMONY study protocol using a multi-stakeholder consensus-based Delphi process and a final consensus meeting

Abstract: Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has an unacceptably low cure rate. In recent years, a number of new treatment strategies and compounds were developed for the treatment of AML. There were several randomized controlled clinical trials with the objective to improve patients’ management and patients’ outcome in AML. Unfortunately, these trials are not always directly comparable since they do not measure the same outcomes, and currently there are no core outcome sets that can be used to guide outcome selection and harmonization in this disease area. The HARMONY (Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms in Hematology) Alliance is a public-private European network established in 2017 and currently includes 53 partners and 32 associated members from 22 countries. Amongst many other goals of the HARMONY Alliance, Work Package 2 focuses on defining outcomes that are relevant to each hematological malignancy. Accordingly, this pilot study will be performed to define a core outcome set in AML. Methods: The pilot study will use a three-round Delphi survey and a final consensus meeting to define a core outcome set. Participants will be recruited from different stakeholder groups, including patients, clinicians, regulators and members of the European Federation of Pharmaceutical Industries and Associations. At the pre-Delphi stage, a literature research was conducted followed by several semi-structured interviews of clinical public and private key opinion leaders. Subsequently, the preliminary outcome list was discussed in several multi-stakeholder face-to-face meetings. The Delphi survey will reduce the preliminary outcome list to essential core outcomes. After completion of the last Delphi round, a final face-to-face meeting is planned to achieve consensus about the core outcome set in AML. Discussion: As part of the HARMONY Alliance, the pilot Delphi aims to define a core outcome set in AML on the basis of a multi-stakeholder consensus. Such a core outcome set will help to allow consistent comparison of future clinical trials and real-world evidence research and ensures that appropriate outcomes valued by a range of stakeholders are measured within future trials

Incidence of anogenital warts in Germany: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Human papilloma virus (HPV) types 6 and 11 account for 90 percent of anogenital warts (AGW). Assessment of a potential reduction of the incidence of AGW following introduction of HPV vaccines requires population-based incidence rates. The aim of this study was to estimate incidence rates of AGW in Germany, stratified by age, sex, and region. Additionally, the medical practitioner (gynaecologist, dermatologist, urologist etc.) who made the initial diagnosis of AGW was assessed.</p> <p>Methods</p> <p>Retrospective cohort study in a population aged 10 to 79 years in a population-based healthcare insurance database. The database included more than 14 million insurance members from all over Germany during the years 2004-2006. A case of AGW was considered incident if a disease-free period of twelve months preceded the diagnosis. To assess regional variation, analyses were performed by federal state.</p> <p>Results</p> <p>The estimated incidence rate was 169.5/100,000 person-years for the German population aged 10 to 79 years. Most cases occurred in the 15 to 40 years age group. The incidence rate was higher and showed a peak at younger ages in females than in males. The highest incidence rates for both sexes were observed in the city-states Berlin, Hamburg and Bremen. In females, initial diagnosis of AGW was most frequently made by a gynaecologist (71.7%), whereas in males, AGW were most frequently diagnosed by a dermatologist (44.8%) or urologist (25.1%).</p> <p>Conclusions</p> <p>Incidence of AGW in Germany is comparable with findings for other countries. As expected, most cases occurred in the younger age groups. The frequency of diagnoses of AGW differs between sexes and women and men receive treatment by doctors of different specialties.</p

Changes in incidence of anogenital warts diagnoses after the introduction of human papillomavirus vaccination in Germany-an ecologic study.

In a large health insurance database in Germany, incidence of anogenital warts among 15- to 19-year-old females decreased from 316/100,000 person-years in 2007 to 242 in 2008 (23% reduction, P = 0.0001). The decrease started between the first and second quarter of 2007 (human papillomavirus vaccination was introduced in March 2007)

Identification of Incident Uterine Fibroids Using Electronic Medical Record Data

Background: Uterine fibroids are the most common benign tumors of the uterus that are associated with considerable morbidity in women. Diagnosis codes have been used to identify symptomatic fibroid cases, but their accuracy, especially for incident cases, is uncertain. This study assessed the accuracy of diagnosis codes in identifying incident fibroids and developed algorithms to improve incident fibroid case-finding using additional electronic data. Methods: Women aged 18–65 years who received an ICD-9 diagnosis code for uterine fibroid during 2012–2014 were identified from electronic databases at Group Health Cooperative, an integrated health care system in Washington State. Women with a fibroid history or hysterectomy were excluded. Medical records were reviewed on a random sample of 617 women to confirm incident fibroid status. Additional data on demographics, symptoms, treatment, imaging, health care utilization, comorbidities and medication were collected. Classification and regression tree analysis incorporating these additional data were used to develop algorithms to identify incident fibroid. We focused on an algorithm with high sensitivity (ie, maximizing the inclusion of true incident cases) and another with high specificity (ie, avoiding incorrect inclusion of noncases as incident cases). Algorithm performance was assessed by calculating sensitivity, specificity and positive predictive value (PPV) using medical record as gold standard. Results: Among the 617 women, mean age at diagnosis was 48 years. Medical record review confirmed 583 (95%) fibroid cases and 482 incident cases, a 78% PPV for incident cases based on diagnosis codes alone. Incorporating additional electronic data, the algorithm classified 395 incident cases among women with at least 2 pelvic ultrasounds on and prior to diagnosis date. Of these, 344 were correctly classified as incident cases, yielding an 87% PPV. Sensitivity was 71% and specificity 62%. A second algorithm further classified women based on a fibroid code of 218.9 in 2 years after diagnosis and lower body mass index yielded 93% PPV, 53% sensitivity and 85% specificity. Conclusion: Identification of incident uterine fibroids through ICD-9 diagnosis codes alone was good with moderate PPV. Algorithms using additional electronic data improved incident fibroid case finding with higher PPV, and either higher sensitivity or higher specificity to meet different study aims

Incidence, treatment and recurrence of endometriosis in a UK-based population analysis using data from The Health Improvement Network and the Hospital Episode Statistics database

<p><b>Purpose:</b> This retrospective study used medical records from The Health Improvement Network (THIN) and Hospital Episode Statistics (HES) database to evaluate endometriosis (incidence, treatment and need for recurrent invasive procedures) in the general UK population.</p> <p><b>Materials and methods:</b> Women aged 12–54 years between January 2000 and December 2010, with a Read code for endometriosis, were identified in THIN. Cases were validated by manual review of free-text comments in medical records and responses to physician questionnaires. False-negative cases were identified among women with Read codes for hysterectomy or dysmenorrhea. Prescriptions of medical therapies for endometriosis were identified in THIN. Cases of single and recurrent invasive procedures were identified in women with medical records in both THIN and HES.</p> <p><b>Results:</b> Overall, 5087 women had a Read code for endometriosis, corresponding to an incidence of 1.02 (95% confidence interval [CI]: 0.99–1.05) per 1000 person-years. After case validation, the estimate was 1.46 (95% CI: 1.43–1.50) per 1000 person-years. Medical therapy was prescribed to 55.5% of women with endometriosis in the first year after diagnosis. In total, 48.3% of women received invasive treatment during the study period; approximately one-fifth of these women required further invasive treatment, mainly in the 3 years after the index procedure.</p> <p><b>Conclusions:</b> Using Read codes as the only method to identify women with endometriosis underestimates incidence. Over half of women with recorded endometriosis are prescribed medical therapy in the first year after diagnosis. Women with diagnosed endometriosis are at risk of requiring recurrent invasive procedures.</p

Stratification performance of multinomial-based approach on simulated patients.

Illustration of the accuracy of our proposed maximum-likelihood approach based on multinomials to assign the simulated patients to the HDMM components. The metrics of accuracy is the Adjusted Rand Index (ARI), which is able to deal with scenarios where the observed number of components was found different from the expected one. ARI equals to one matches perfect agreement. The upper quadrant reports the result for K = 5 simulated components, while the lower quadrant does it for K = 10 components. The variables αsim and αHDMM respectively indicate when the expected components were uniform-like simulated (αsim = 1) or were low-overlapping (αsim = 1/M). Similarly, scenarios with αHDMM = 1 indicate when the HDMM was set to find poorly disjunct components, whereas αHDMM = 1/M caused the HDMM to estimate highly disjunct components. The boxplots in the plot summarizes the performance across any average number of genomic alterations per simulated patient.</p