HPV vaccination leads to decrease of anogenital warts and precancerous lesions of the cervix uteri in young women with low vaccination rates: a retrospective cohort analysis.

BACKGROUND: Although the human papillomavirus (HPV) vaccine has been recommended in Germany for girls since 2007, no organised vaccination programme was introduced and HPV vaccine coverage remains low. We investigated the HPV vaccination rates from 2008 to 2018 and the effects of HPV vaccination on anogenital warts and precancerous lesions in young women in Bavaria, Germany, a state with low vaccination rates. METHODS: Retrospective analyses of claims data from the Bavarian Association of Statutory Health Insurance Physicians (KVB) on females born between 1990 and 2009 (9 to 28 years old in 2018) were conducted to calculate vaccination rates by birth cohort, proportion of vaccine types administered and incidence of anogenital warts and precancerous lesions of the cervix uteri. 942 841 Bavarian females 9 to 28 years old with available information on HPV vaccination were included to calculate vaccination rates. For the outcome analyses, data from 433 346 females 19 to 28 years old were analysed. Hazard ratios (HR) were computed from univariable and multivariable Cox regression models comparing vaccinated and unvaccinated women, considering type of vaccine used and contraceptive prescription. RESULTS: 40·9% of 18-year-olds and only 13·3% of 12-year-olds were fully vaccinated in 2018 in Bavaria. Gardasil® and Gardasil9® were most commonly administered. Vaccinated compared to unvaccinated women had a lower incidence of anogenital warts and cervical lesions, however only small differences were detected between fully and partially vaccinated women. Fully vaccinated women had a 63% (HR 0·37 (95% confidence interval (CI) 0·34 to 0·40) and 23% (HR 0·77, 95%CI 0·71 to 0·84) lower risk of anogenital warts and cervical lesions, respectively. Women who were prescribed contraceptives prior to vaccination had a 49% higher risk of developing anogenital warts (HR 1·49, 95%CI 1·25 to 1·79) or cervical lesions (HR 1·49, 95%CI 1·27 to 1·75) compared to vaccinated women without contraceptive prescription. CONCLUSIONS: The evaluation of the effects of HPV vaccination in Bavaria showed a promising decline of anogenital warts and precancerous lesions in vaccinated young women. However, an increase in vaccination rates is necessary to achieve a greater population impact in preventing HPV-related diseases.

Incidence of post-COVID syndrome and associated symptoms in outpatient care in Bavaria, Germany: a retrospective cohort study using routinely collected claims data.

OBJECTIVES: To estimate the treatment incidence of post-COVID syndrome (postinfectious sequelae present at least 12 weeks following infection) in the context of ambulatory care in Bavaria, Germany, and to establish whether related diagnoses occur more frequently than in patients with no known history of COVID-19. DESIGN: Retrospective cohort analysis of routinely collected claims data. SETTING: Ambulatory care in Bavaria, Germany, observed from January 2020 to March 2022 (data accessed May 2022). PARTICIPANTS: 391 990 patients with confirmed COVID-19 diagnosis, 62 659 patients with other respiratory infection and a control group of 659 579 patients with no confirmed or suspected diagnosis of COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome is diagnosis of post-COVID syndrome documented in ambulatory care. Secondary outcomes are: chronic fatigue syndrome, psychological disorder, fatigue, mild cognitive impairment, disturbances of taste and smell, dyspnoea, pulmonary embolism and myalgia. RESULTS: Among all patients with confirmed COVID-19, 14.2% (95% CI 14.0% to 14.5%) received a diagnosis of a post-COVID syndrome, and 6.7% (95% CI 6.5% to 6.9%) received the diagnosis in at least two quarterly periods during a 2-year follow-up. Compared with patients with other respiratory infections and with controls, patients with COVID-19 more frequently received a variety of diagnoses including chronic fatigue syndrome (1.6% vs 0.6% and 0.3%, respectively), fatigue (13.3% vs 9.2% and 6.0%), dyspnoea (9.9% vs 5.1% and 3.2%) and disturbances of taste and smell (3.2% vs 1.2% and 0.5%). The treatment incidence of post-COVID syndrome was highest among adults aged 40-59 (19.0%) and lowest among children aged below 12 years (2.6%). CONCLUSIONS: Our results demonstrate a moderately high incidence of post-COVID syndrome 2 years after COVID-19 diagnosis. There is an urgent need to find efficient and effective solutions to help patients with dyspnoea, fatigue, cognitive impairment and loss of smell. Guidelines and treatment algorithms, including referral criteria, and occupational and physical therapy, require prompt and coherent implementation.

Ambulatory specialist costs and morbidity of coordinated and uncoordinated patients before and after abolition of copayment: A cohort analysis.

To strengthen the coordinating function of general practitioners (GPs) in the German healthcare system, a copayment of €10 was introduced in 2004. Due to a perceived lack of efficacy and a high administrative burden, it was abolished in 2012. The present cohort study investigates characteristics and differences of GP-coordinated and uncoordinated patients in Bavaria, Germany, concerning morbidity and ambulatory specialist costs and whether these differences have changed after the abolition of the copayment. We performed a retrospective routine data analysis, using claims data of the Bavarian Association of the Statutory Health Insurance Physicians during the period 2011-2012 (with copayment) and 2013-2016 (without copayment), covering 24 quarters. Coordinated care was defined as specialist contact only with referral. Multinomial regression modelling, including inverse probability of treatment weighting, was used for the cohort analysis of 500 000 randomly selected patients. Longitudinal regression models were calculated for cost estimation. Coordination of care decreased substantially after the abolition of the copayment, accompanied by increasing proportions of patients with chronic and mental diseases in the uncoordinated group, and a corresponding decrease in the coordinated group. In the presence of the copayment, uncoordinated patients had €21.78 higher specialist costs than coordinated patients, increasing to €24.94 after its abolition. The results indicate that patients incur higher healthcare costs for specialist ambulatory care when their care is uncoordinated. This effect slightly increased after abolition of the copayment. Beyond that, the abolition of the copayment led to a substantial reduction in primary care coordination, particularly affecting vulnerable patients. Therefore, coordination of care in the ambulatory setting should be strengthened.

Prescribers' compliance with summary of product characteristics of dabigatran, rivaroxaban and apixaban-A European comparative drug utilization study.

Despite a tremendous increase of direct oral anticoagulants (DOACs) prescriptions in recent years, only few data is available analysing prescribers' adherence to Summary of Product Characteristics (SmPC). We aimed to assess adherence to registered indications, contraindications, special warnings/precautions, and potential drug-drug interactions for three DOAC compounds (dabigatran, rivaroxaban, and apixaban) in six databases of five European countries (The Netherlands, United Kingdom, Spain, Denmark, and Germany). We included adult patients (≥18 years) initiating DOACs between 2008 and 2015. For several SmPC items, broad definitions were used due to ambiguous SmPC terms or lacking data in some databases. Within the study period, a DOAC was initiated in 407 576 patients (rivaroxaban: 240 985 (59.1%), dabigatran: 95 303 (23.4%), and apixaban: 71 288 (17.5%)). In 2015, non-valvular atrial fibrillation was the most common indication (>60% in most databases). For the whole study period, a substantial variation between the databases was found regarding the proportion of patients with at least one contraindication (inter-database range [IDR]: 8.2%-55.7%), with at least one special warning/precaution (IDR: 35.8%-75.2%) and with at least one potential drug-drug interaction (IDR: 22.4%-54.1%). In 2015, the most frequent contraindication was "malignant neoplasm" (IDR: 0.7%-21.3%) whereas the most frequent special warning/precaution was "prescribing to the elderly" (≥75 years; IDR: 25.0%-66.4%). The most common single compound class interaction was "concomitant use of non-steroidal anti-inflammatory drugs" (IDR: 3.0%-25.3%). Contraindications, special warnings/precautions, and potential drug-drug interactions were present in a relevant number of new DOAC users. Due to broad definitions used for some SmPC terms, overall proportions for contraindications are prone to overestimation. However, for unambiguous SmPC terms documented in the databases sufficiently, the respective estimates can be considered valid. Differences between databases might be related to "true" differences in prescription behaviour, but could also be partially due to differences in database characteristics.

Differences in treatment and monitoring of chronic myeloid leukemia with regard to age, but not sex: Results from a population-based study.

There are established guidelines for treatment and monitoring of chronic myeloid leukemia (CML) but little is known about routine care. Data on ICD-10 codes as well as prescribed medications were available for 10.5 million patients in the statutory health insurance system in Bavaria for the years 2010 to 2016. Also, data on the molecular and cytogenetic monitoring were integrated. A total of 1714 adult patients with CML were observed. Only 50.8% received more than 67.5 daily doses per quarter year (target: 91.5) while 18.2% did not receive any tyrosine kinase inhibitor (TKI). The median number of daily doses was at least 80 doses per quarter year for all age groups in men, but decreased to 62 doses in elderly women. With this exception, no differences between men and women were observed. The percentage of patients without any TKI increased with age. The median number of molecular examinations was 3.54 independent of age and sex. Even in a highly developed country, still a considerable number of patients with CML seem to not receive adequate treatment, whereas molecular monitoring can be considered satisfactory.

Improved survival boosts the prevalence of chronic myeloid leukemia: predictions from a population-based study.

PURPOSE: Due to prolonged survival, there will be many more chronic myeloid leukemia (CML) patients alive in the future. The aims of this work were to estimate the current prevalence of CML by using routine data and to project future patient numbers in Germany. METHODS: Data were available for about 10.5 million people in the statutory health insurance system in Bavaria for the years 2008-2013. Survival rates were adapted from two recent publications. RESULTS: The mean estimated age-standardized (Old European Standard Population) incidence rates per 100,000 inhabitants were 1.300 and 1.768 for women and men. Based on the population data, we estimated a total number of about 9000 CML patients in Germany for 2012. We expect the number of CML patients to increase further until at least 2040-2050 with a maximum of more than 20,000 CML patients as the most probable scenario. CONCLUSIONS: Using a restrictive definition for case patients, we do not think that there is much overestimation. As a consequence of this considerable increase of the prevalence of CML the burden for the health care system will increase with respect to costs and medical care needed. The procedure presented here allows to estimate the expected number of CML patients in other countries, too.